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Interleukin-6 increases rat metalloproteinase-13 gene expression through Janus kinase-2-mediated inhibition of serine/threonine phosphatase-2A. Interleukin-6 (IL-6) increases metalloproteinase-13 (MMP-13) gene expression by increasing phosphorylated c-Jun and by inhibiting serine/threonine phosphatase-2A (PP2A) activity. We investigated the mechanisms by which IL-6 induces c-Jun phosphorylation and PP2A inactivation in Rat-1 fibroblasts. We show that IL-6 increased MMP-13 mRNA, phosphorylated c-Jun, and activator protein 1 (AP1) binding activity without increasing c-Jun-N-terminal kinase (JNK) activity. These effects did not seem to be mediated by ERK, p38 MAP kinase, phosphatidylinositol-3-kinase, calmoduline-dependent protein kinase, protein kinase C (PKC) or protein kinase A since inhibition with specific inhibitors did not abrogate these effects. IL-6 increases PP2A catalytic subunit tyrosine phosphorylation. Inhibition of the tyrosine kinase Jak2, with the specific inhibitor AG490, abrogated this effect. Likewise, this Jak2 inhibitor blocked the effects of IL-6 on c-Jun phosphorylation, AP1 binding activity and metalloproteinase-13 gene expression. We conclude that IL-6 increases MMP-13 gene expression by activation of Jak2, resulting in tyrosine phosphorylation of the catalytic subunit of PP2A, which in turn decreases PP2A activity and prolongs c-Jun phosphorylation.

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Early in the course, MRI studies are usually normal; later, the MRI reveals cerebellar atrophy.Brainstem dysfunction, upgoing toes, or a mild neuropathy may occur.The examination usually shows downbeating nystagmus and, rarely, opsoclonus.618 days or weeks later, patients develop dysarthria, gait and limb ataxia, and variable dysphagia.Encephalitis with glycine receptor (GlyR) antibodies has been described in adults with progressive encephalomyelitis with rigidity and myoclonus (PERM) and stiff-person spectrum of symptoms (with or without GAD antibodies). The disorder usually occurs without tumor association, although some patients have lung cancer, thymoma, or Hodgkin’s lymphoma. Encephalitis with dipeptidyl-peptidase-like protein-6 (or DPPX) antibodies results in symptoms of CNS hyperexcitability including agitation, hallucinations, paranoid delusions, tremor, myoclonus, nystagmus, seizures, and sometimes hyperekplexia. Some patients develop progressive encephalomyelitis with rigidity and myoclonus. Diarrhea, other gastrointestinal symptoms, and substantial loss of weight often suggest the presence of an underlying tumor, but no tumor association has been identified. The disorder responds to immunotherapy. This disorder is often preceded by a prodrome that may include dizziness, oscillopsia, blurry or double vision, nausea, and vomiting. A few FIGURE 122-4 Pathologic findings in anti–N-methyl-D-aspartate (NMDA) receptor encephalitis. Infiltrates of plasma cells (brown cells; stained for CD138) in the meninges and brain of a patient (A); the inset is a magnification of some plasma cells. (B) Neurons and neuronal processes in the teratoma of a patient (brown cells; stained with MAP2); these neurons express NMDA receptors (not shown). (From E Martinez-Hernandez et al: Neurology 77:589, 2011, with permission.) 618 days or weeks later, patients develop dysarthria, gait and limb ataxia, and variable dysphagia. The examination usually shows downbeating nystagmus and, rarely, opsoclonus. Brainstem dysfunction, upgoing toes, or a mild neuropathy may occur. Early in the course, MRI studies are usually normal; later, the MRI reveals cerebellar atrophy.The tumors more frequently involved are SCLC, cancer of the breast and ovary, and Hodgkin’s lymphoma.Anti-Yo antibodies in patients with breast and gynecologic cancers and anti-Tr antibodies in patients with Hodgkin’s lymphoma are the two immune responses typically associated with prominent or pure cerebellar degeneration.

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It is unclear, however, if these changes represent primary defects or are secondary to an inherent lack of motivation.These deficits correlate with reduced cognitive activation activity in functional MRI.Detailed neuropsychologic testing has disclosed deficits in attention and abnormalities of the P300 waves (cortical “event-related” potentials).Equally compelling is the finding that young individuals having 2 or more relatives with the disease, and therefore being at risk for developing schizophrenia, have certain volumetric brain changes detected by imaging studies (Lawrie et al). In unaffected relatives, the left hippocampal–amygdaloid region was smaller than in healthy people, but slightly larger than in affected relatives. In an attempt to organize the imaging findings, Murray and coworkers raised the possibility that there are 2 types of this disease: one with ventricular enlargement and a negative family history and the other with normal ventricles and a positive family history. In the first group of sporadic, “acquired” schizophrenia, environmental factors, such as birth injury, and EEG abnormalities (see in the following text) were considered to be more frequent. In summarizing the many cerebral changes observed in schizophrenic patients, Harrison concluded that several are quite consistent. These include mild enlargement of the lateral and third ventricles; decreased cortical volume, perhaps disproportionate in the temporal lobe; microscopically, diminution in size of cortical and hippocampal neurons; a diminished number of neurons in the dorsal thalamus; and a notable absence of gliosis. EEG data, for the most part not useful, were alluded to earlier. Detailed neuropsychologic testing has disclosed deficits in attention and abnormalities of the P300 waves (cortical “event-related” potentials). These deficits correlate with reduced cognitive activation activity in functional MRI. It is unclear, however, if these changes represent primary defects or are secondary to an inherent lack of motivation.Weinberger and colleagues (1986) and Liddle and Barnes have reported a decrease in blood flow in the prefrontal areas during cognitive tasks.Friston and associates found consistent abnormalities in the left parahippocampal region in all forms of chronic schizophrenia.

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ATP binding brings together the two ATPase domains, and ATP hydrolysis leads to their dissociation (Figure 11–16).Helix movement opens and closes passageways through which Ca2+ enters from the cytosol and binds to the two centrally located Ca2+ binding sites. The two Ca2+ then exit into the SR lumen and are replaced by two H+, which are transported in the opposite direction. The Ca2+-dependent phosphorylation and H+-dependent dephosphorylation of aspartic acid are universally conserved steps in the reaction cycle of all P-type pumps: they cause the conformational transitions to occur in an orderly manner, enabling the proteins to do useful work. (Adapted from C. Toyoshima et al., Nature 432:361–368, 2004 and J.V. Møller et al., Q. Rev. Biophys. 43:501– 566, 2010.) Figure 11–15 The function of the Na+-K+ pump. This P-type ATPase actively pumps Na+ out of and K+ into a cell against their electrochemical gradients. It is structurally closely related to the Ca2+ ATPase but differs in its selectivity for ions: for every molecule of ATP hydrolyzed by the pump, three Na+ are pumped out and two K+ are pumped in. As in the Ca2+ pump, an aspartate is phosphorylated and dephosphorylated during the pumping cycle (Movie 11.4). ABC Transporters Constitute the Largest Family of Membrane Transport Proteins The last type of transport ATPase that we discuss is the family of the ABC transporters, so named because each member contains two highly conserved ATPase domains, or ATP-Binding “Cassettes,” on the cytosolic side of the membrane. ATP binding brings together the two ATPase domains, and ATP hydrolysis leads to their dissociation (Figure 11–16).In this way, ABC transporters harvest the energy released upon ATP binding and hydrolysis to drive transport of solutes across the bilayer.The transport is directional toward inside or toward outside, depending on the particular conformational change in the solute binding site that is linked to ATP hydrolysis (see Figure 11–16).

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Thomas Frodl, a neurobiology researcher at Trinity College Dublin, found that depressive episodes may result in neuroplastic changes to the brain.Untreated depression bathes the brain in the stress hormone cortisol, and long-term exposure to cortisol can cause the brain's prefrontal cortex to waste.On the one hand, is it right to put patients on a drug that may be making their brains behave in an abnormal fashion, especially when there is no definitive evidence of chemical imbalance in the first place? On the other hand, is it right to do nothing in the face of severe suffering? ## Does Depression Damage the Brain? Helen Mayberg, a neurologist and leading depression researcher at Emory University, reported in 2013 that psychotherapy, specifically cognitive behavior therapy, is just as effective, statistically, as antidepressants are in reversing depression. But what about those patients who are too sick to tolerate the rigors of reflection? Beyond that, just because we have not found a chemical imbalance in the brains of mental patients does not mean there isn't something terribly askew in those brains, something that antidepressants could be treating, albeit in indirect or not entirely detectable ways. Perhaps, for those with a depressive disorder, raising the amount of serotonin available in the synaptic cleft triggers the DNA to make a new protein, and this altered gene expression allows a patient to recover. Suppose we do nothing for the depressive except watch and wait for him to recover. The trouble is that myriad researchers and practitioners have suggested that depression is at least as toxic to the brain as the drugs we use to treat it. Untreated depression bathes the brain in the stress hormone cortisol, and long-term exposure to cortisol can cause the brain's prefrontal cortex to waste. Thomas Frodl, a neurobiology researcher at Trinity College Dublin, found that depressive episodes may result in neuroplastic changes to the brain."Compared with controls," he observed, "patients showed significantly more decline in gray matter density."In other words, contra Whitaker, untreated depression may cause brain damage too.Furthermore, other research shows that the more episodes of depression a person has, the more vulnerable he or she is to future relapse.

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There have been major advances in non-surgical periodontal treatment for chronic periodontal disease. Our state-of-the-art ultrasonic scalers have been designed by a periodontist for maximum effectiveness on root surfaces. Antibiotic gels, which are placed below the gum line, reduce the need for periodontal surgery, and with the latest innovations like the dental endoscope (camera) which can be placed below the gum line, your needs for surgical treatment can be reduced. We take every opportunity to help you control your periodontal disease problem non-surgically and then reevaluate to determine the effectiveness of the treatment. We are committed to providing the best possible dental care for your child in a friendly, anxiety-free environment. Our staff is comfortable and trained on all phases of children’s dental care, including cleanings, fillings, fluoride treatments, sealants and we have techniques specifically designed for children. Our team will regularly evaluate your child’s dental needs to provide the highest level of prevention and treatment. An extraction is performed when a tooth becomes impacted because it is prevented from growing into its normal position in the mouth by gum tissue, bone or other teeth. Extracting other teeth may also be required prior to straightening or if the teeth cannot be restored because they are badly decayed or broken. Contact Campbell Dental Group directly at (520) 322-0600 for your next dental appointment.

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Have complications been prevented?2.Has the client's fluid and electrolyte balance been maintained?Evaluation 1.Provide postsurgical care—adrenalectomy or medullectomy 4.Allow time to verbalize concerns to decrease nervousness and tremors 11.Administer apresoline for hypertensive crisis 10.Administer adrenergic-blocking medications 9.Limit activity 8.Pounding headache, weakness, visual disturbances during hypertensive episodes 7. Pain 8. Urinary vanillylmandelic acid (VMA) test 1. 24-hour urine for VMA—breakdown product of catecholamine metabolism 2. Normal results: 1–5 mg, positive for tumor if significantly higher 3. Foods affecting VMA excretion excluded 3 days before test 1. Coffee 2. Tea 3. Bananas 4. Vanilla 5. Chocolate 4. All drugs discontinued during test 5. Urine collected on ice or refrigerated with preservative 9. Clonidine suppression test—conidine levels not decreased 2. Diagnose 1. Definition—hypersecretion of catecholamines (epinephrine and norepinephrine) activate fight-or-flight response due to secreting tumors of the adrenal medulla; tumor can also occur anywhere, from neck to pelvis, along course of sympathetic nerve chain 2. Potential nursing diagnoses 1. Deficient knowledge 2. Decreased cardiac output/ineffective tissue perfusion 3. Plan/Implementation 1. Avoid physical and emotional stress 2. Monitor blood pressure in lying and sitting positions 3. Frequent bathing, but avoid chilling 4. Administer analgesics for pain, sedatives and tranquilizers for rest and relaxation 5. Increase caloric, vitamin, and mineral intake due to increased metabolic demand 6. Avoid coffee, tea, cola, and foods containing tyramine 7. Limit activity 8. Administer adrenergic-blocking medications 9. Administer apresoline for hypertensive crisis 10. Allow time to verbalize concerns to decrease nervousness and tremors 11. Provide postsurgical care—adrenalectomy or medullectomy 4. Evaluation 1. Has the client's fluid and electrolyte balance been maintained? 2. Have complications been prevented?Assessment 1.Change in skin color—cyanosis or reddish color 2.Weakness, weight loss 3.Risk factors 1.Smoking tobacco 2.Passive tobacco smoke 3.Occupational exposure 4.Air pollution, coal, gas, asbestos exposure 5.Genetic abnormalities—alpha 1 antitrypsin deficiency 4.Use of accessory muscles of breathing, dyspnea 5.

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Early decomposition may be evidenced.This condition may be caused by gasses accumulating in the cavities, and it may be necessary to reaspirate and reinject the cavities._Odor_.In addition to aspirating the cavities, it may be necessary to open and dry the mouth and reset the mouth.It needs immediate correction.This condition is caused by a buildup of gases in the abdominal and thoracic cavities.They should be properly sealed with a trocar button or superglue. 9. Are tracheotomy and colostomy openings closed? A purse string suture can be used to close these openings. They should be packed with a cautery chemical and cotton. The tracheotomy can also be filled with some incision seal powder. These openings should be covered with glue and cotton after the suturing is completed. 10. Are incisions sutured? Sutures should be tight and not seeping. If leakage is present the sutures should be removed and the incision resutured. These 10 items represent the type of evaluation necessary during the third and final stage of embalming analysis. Table 10–3 is by no means complete but serves to illustrate some of the variables considered by the embalmer in choosing treatments to achieve good sanitation, preservation, and restoration of the body. TABLE 10–3. EMBALMING TECHNIQUE VARIABLES #### **POST-EMBALMING MONITORING** During the time the embalmed body is in the custody of the funeral establishment, it is necessary to daily monitor the body to note any adverse changes (Table 10–4). Several examples of these changes are as follows: TABLE 10–4. BODY CONDITIONS AND EMBALMING TREATMENTS _Dehydration_. It is possible that dehydration can be caused by: (1) embalming chemicals within the body, (2) gravitation of tissue fluids from the face and neck, or (3) environmental loss of moisture due to air conditioning or heating. The results of dehydration can be a darkening of the skin, a "sunken" look to the face, as well as wrinkled and separated lips and eyelids. _Purge_. This condition is caused by a buildup of gases in the abdominal and thoracic cavities. It needs immediate correction. In addition to aspirating the cavities, it may be necessary to open and dry the mouth and reset the mouth. _Odor_. This condition may be caused by gasses accumulating in the cavities, and it may be necessary to reaspirate and reinject the cavities. Early decomposition may be evidenced.Odors may be temporarily covered by the use of plastic garments and absorbent embalming powders._Leakage_.The source of leakage may be edema or possibly an embalming incision that was not sutured.The source needs to be identified and the soiled garments removed, dried, or replaced.Plastic garments may be necessary to contain or control any further problems._Softening of visible tissues_.

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Patients with MHE report a decrease in the quality of their sleep and in their physical and mental HRQoL.Psychological status and a patient's mood can affect the course of a disease and treatment response, and depression affects social functioning, physical abilities, and health status.Cirrhotic patients suffer not only from liver disease itself, but also from decreased quality of life in the form of poor work performance and an increased risk of accidents. Therefore, there is a need for extensive social attention and research on public social support systems and economic support for cirrhotic patients. ## Effects of treatment on he and health-related quality of life Although many studies have aimed at improving HE, relatively few studies have aimed at a significant improvement in the HRQoL of patients with HE.Prasad et al.first investigated the effect of treatment-related improvements in cognitive function on HRQoL. Patients with MHE treated with lactulose for 3 months showed a significant improvement in their HRQoL on several SIP subscores, particularly in emotional behavior, mobility, sleep/rest, and recreation and pastimes. In an 8-week study of rifaximin therapy in patients with MHE, the patients showed significantly improved scores in both neuro-psychometric performance and the SIP.Another study reported that rifaximin therapy to prevent a recurrence in patients with HE favorably affected HRQoL as measured by CLDQ scores.

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Can you explain what a kidney stone is? NIH Article Template:Nephrology Template:WH Template:WS af:Niersteen ar:حصوة كلوية ca:Litiasi renal da:Nyresten de:Nierenstein hy:Միզաքարային հիվանդություններ id:Batu ginjal ia:Calculo renal he:אבנים בכליות lt:Inkstų akmenligė hu:Vesekövesség nl:Niersteen no:Nyrestein qu:Wasa ruru rumi fi:Virtsakivitauti sv:Njursten yi:ניר שטיין Template:WikiDoc Sources

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5 mL (= 1 medicine measure) contains 12,1 mg of dihydrocodeine bitartrate, and as preservatives 0,1% m/v methyl paraben and 0,02% m/v propyl paraben. Paracodin syrup is particularly suitable for children. All types of cough and cough irritation, particularly in inflammation of the respiratory tract. Paracodin is therefore specially indicated in the following conditions: Bronchitis, whooping cough, tracheitis, pharyngitis, laryngitis, as well as in cough associated with emphysema and pulmonary tuberculosis. Conditions associated with impaired respiratory function; long term administration in chronic constipation. Adults 5 - 10 mL (1 - 2 medicine measures) up to 3 times a day. Paracodin may lead to constipation, especially in small children. Diabetics are reminded that 5 mL of Paracodin syrup contains about 1 g of glucose equivalent. As with all other drugs acting on the central nervous system the consumption of alcohol should be avoided under Paracodin therapy. Paracodin may impair the speed of patient's reaction (eg. in traffic), particularly when administered in high doses. In accordance with present views on the use of drugs in pregnant women, prescription of Paracodin should be considered carefully during the first 3 months of pregnancy. Drowsiness: retention of urine and faeces may occur which should be treated symptomatically according to the severity of the clinical picture. A clear slightly yellowish solution. Glass bottles containing 100 mL and 200 mL of syrup. Store in a cool (below 30°C), dry place. Keep out of reach of children.

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This likely resulted from LBBB which was induced with a similar coupled APC delivered at a shorter drive cycle length (450 msec) which blocked in the bypass tract.The H-V is unchanged.An APC is delivered which demonstrates marked preexcitation ova fasciculoventricular pathway.Atrial stimulation is present during an Isuprel infusion.Thus, because it is not directly responsible for arrhythmias, this form of preexcitation does not require treatment. FIGURE 10-143 _Recordings of a fasciculoventricular bypass tract during sinus and junctional rhythms._ Leads I, II, V1, and V6 are shown with intracardiac recordings from the HRA, HBE, and RVA. Preexcitation (note delta wave) is present with an identical, short H-V interval (30 msec) during both sinus and junctional rhythm. This is diagnostic of a fasciculoventricular bypass tract. FIGURE 10-144 _His bundle pacing in a patient with a fasciculoventricular pathway A 12 lead ECG is shown._ The first complex is sinus. His bundle pacing is initiated with a stimulus to V and QRS identical to the H-V and QRS in sinus. This is diagnostic of a fasciculoventricular pathway. FIGURE 10-145 _Loss of preexcitation over a fasciculoventricular bypass tract during pacing-induced A-V nodal Wenckebach._ The tracing is organized with leads 1, aVF, and V1 with multiple His bundle leads (HBE), HRA, 4 CS leads, and an EGM from the RVA. During atrial pacing at a cycle length of 500 msec results in A-V nodal Wenckebach. Preexcitation is lost with A-V nodal block. This is characteristic of a fasciculoventricular bypass tract. See text for discussion. (From Ganz LI, Elson JJ, Chenarides JG. Preexcitation in a child with syncope: where is the connection? _J Cardiovasc Electrophysiol_ 1998;9:892–895.) FIGURE 10-146 _Change in preexcitation over a fasciculoventricular pathway with an APD producing LBB conduction delay or block._ Leads II and V1 are shown with recordings from the HRA, HBE, CS, and RVA. Atrial stimulation is present during an Isuprel infusion. An APC is delivered which demonstrates marked preexcitation ova fasciculoventricular pathway. The H-V is unchanged. This likely resulted from LBBB which was induced with a similar coupled APC delivered at a shorter drive cycle length (450 msec) which blocked in the bypass tract.10-145.During atrial pacing (S1-S1) at a cycle length of 400 msec an atrial extrastimulus (S2) is delivered at a coupling interval of 290 msec.During the pacing drive (S1) preexcitation is present with an H-V interval of 20 msec.Following S2, block in the fasciculoventricular bypass tract occurs, which is associated with a prolongation of the H-V interval to 45 msec.See text for discussion.

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Combination of physical activity, nutrition, or other metabolic factors and vaccine response. A number of lifestyle factors that reduce cancer risk in the primary prevention setting may be potential new targets for use in combination with cancer vaccines. This review discusses the modulation of energy balance (physical activity, calorie restriction, and obesity prevention), and the supplementation with natural and synthetic analogs of vitamins A and E, as potential interventions for use in combination with cancer vaccines. Additionally, the pharmacologic manipulation of nutrient metabolism in the tumor microenvironment (e.g., arachidonic acid, arginine, tryptophan, and glucose metabolism) is discussed. This review includes a brief overview of the role of each agent in primary cancer prevention; outlines the effects of these agents on immune function, specifically adaptive and/or anti-tumor immune mechanisms, when known; and discusses the potential use of these interventions in combination with therapeutic cancer vaccines. Modulation of energy balance through exercise and strategies targeting nutrient metabolism in the tumor microenvironment represent the most promising interventions to partner with therapeutic cancer vaccines. Additionally, the use of vitamin E succinate and the retinoid X receptor-directed rexinoids in combination with cancer vaccines offer promise. In summary, a number of energy balance- and nutrition-related interventions are viable candidates for further study in combination with cancer vaccines.

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Cholesteryl-conjugated phosphorothioate oligodeoxynucleotides modulate CYP2B1 expression in vivo. 5' cholesteryl-conjugated phosphorothioate oligodeoxynucleotides with sequence complementary to the rat CYP2B1 mRNA were evaluated in adult male Sprague-Dawley rats for their pharmacokinetic properties, toxicity, and ability to modulate CYP2B1 expression in vivo. Following intraperitoneal administration of 35S-labelled oligodeoxynucleotides, volume of distribution for the phosphorothioate was 0.33 l/kg while the 5' cholesteryl-conjugate oligodeoxynucleotide was 0.12 l/kg. The elimination half-life was 23.2 and 55.4 hrs for cholesteryl-modified and unmodified oligodeoxynucleotides, respectively. Cholesteryl-conjugate oligodeoxynucleotide toxicity was detected at a dose of 1.0 mg/kg and consisted primarily of midzonal liver cell enlargement and increased total RNA. Hexobarbital sleep times, a measure of CYP2B1 enzyme activity in vivo, increased from 21.9 minutes in saline-treated animals to 29.5 minutes in cholesterol oligodeoxynucleotide-treated animals. A significant decrease in liver microsomal pentoxyresorufin O-dealkylase enzyme activity, a CYP2B1/2 specific assay, was observed but not a change in p-nitrophenol hydroxylase activity, a specific CYP2E1 assay. These data indicate that in vivo modulation of the CYP2B1 gene can be accomplished with synthetic phosphorothioate oligodeoxynucleotides in a sequence-specific manner. Further, cholesteryl conjugation to the 5' end of the oligodeoxynucleotide enhanced potency despite lesser bioavailability.

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The test progresses such that the correct solution is initially stimulus color.The subject is told whether the sorting choice is correct or incorrect.The subject's task is to sort the stack of cards into piles in front of the stimulus cards.The participant sees four cards bearing designs that differ in color, form, and number of elements.50.4).Findings pointing to a significant genetic contribution come from family, twin, and adoption studies. Evidence for environmental factors derives from studies of prenatal intrauterine environment, neonatal obstetric complications, and postnatal brain insults. Currently, it remains an open question whether these environmental factors play a necessary role in the neurodevelopmental abnormalities responsible for psychotic brain disorders or whether their role is additive or interactive with genetic contributions. People with schizophrenia are more likely than others to have schizophrenic relatives. The most compelling evidence is the 50% concordance rate for monozygotic twins relative to 15% concordance for dizygotic twins. Neuroimaging studies of discordant monozygotic twins consistently indicate more prominent structural brain abnormalities in the ill twin. More importantly, a neuroimaging study demonstrated that schizophrenia is associated with dysfunction of a prefrontal-limbic network (Weinberger, Berman, Suddath, & Torrey, 1992). In this study, monozygotic twins discordant for schizophrenia underwent PET blood flow scans while they performed a task known to activate the dorsolateral prefrontal cortex in normal subjects. This assessment, known as the Wisconsin Card Sorting Task (WCST), measures abstract problem solving requiring attention and working memory (see Fig. 50.4). The participant sees four cards bearing designs that differ in color, form, and number of elements. The subject's task is to sort the stack of cards into piles in front of the stimulus cards. The subject is told whether the sorting choice is correct or incorrect. The test progresses such that the correct solution is initially stimulus color.In a final phase the correct solution again changes unexpectedly, now to the number of elements.Shifting response strategies is difficult for patients with frontal lobe dysfunction.Among affected schizophrenic twins, prefrontal activation correlates strongly with both left and right hippocampal volumes; a relationship that is not observed in their unaffected twins.

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Dysbiosis (also called dysbacteriosis) is characterized as a disruption to the microbiota homeostasis caused by an imbalance in the microflora, changes in their functional composition and metabolic activities, or a shift in their local distribution. It is a term for a microbial imbalance or maladaptation on or inside the body, such as an impaired microbiota. For example, a part of the human microbiota, such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract, particularly during small intestinal bacterial overgrowth (SIBO) or small intestinal fungal overgrowth (SIFO). Typical microbial colonies found on or in the body are normally benign or beneficial. These beneficial and appropriately sized microbial colonies carry out a series of helpful and necessary functions, such as aiding in digestion. They also help protect the body from the penetration of pathogenic microbes. These beneficial microbial colonies compete with each other for space and resources. Causes Dysbiosis may be caused by such diverse things as antibiotic or mold exposure, or alcohol misuse. Many of these things can lead to interruptions in the human body like the oral cavity and gut flora which has been linked to a variety of diseases such as IBD, ulcerative colitis, allergies and more. Gut Bacteria in the human gut’s intestines are the most diverse in the human body and play a vital role in human health. The consumer’s dietary habits can be one of the most influential factors on the gut’s microbiota. Diets high in carbohydrates and refined sugars are common links to dysbiosis in the gut, whereas foods rich in fruits, vegetables, and fish oils are considered more favorable to the gut due to their anti-inflammatory properties. Many diseases, such as IBD, Type 2 Diabetes, Crohn's, and even allergies, are suggested to be due, in part, to an alteration in the microbiome of the gut. Oral Dysbiosis can be sectioned into different compartments of the human body. The oral cavity is no exception. What enters the mouth is one of the first exposures to microbes involved in this process and can also lead to other microbial disturbances such as in the gut and intestines. Hygiene and nutritional variation are imperative in preventing oral diseases such as gingivitis, tooth decay, cavities, etc., which are linked to the interrupted microbial community in the oral cavity. Oral pathogens can trigger dysbiotic functions throughout multiple microbiota compartments of the body and alter systemic processes, such as immunological or digestion interruptions. Smoking, drinking, oral intercourse, salivary glands, and age are all considered links to sources that can lead to oral dysbiosis. Skin The use of minocycline in acne vulgaris has been associated with skin and gut dysbiosis. Antibiotics Dysbiosis can occur during many stages of life and can be triggered by many different sources, antibiotics, for example, being a significant contributor to disruptions in microbiotas. Antibiotic usage during young childhood development can lead to adverse gut issues (dysbiosis) in adulthood. The gut microbiome is altered from antibiotics and is linked to future gut disease, i.e., IBD, ulcerative colitis, obesity, etc. The intestinal immune system is directly influenced by the gut microbiome and can be hard to recover if damaged through antibiotics. Effects Gut dysbiosis has been linked to the “pathogenesis of both intestinal and extra-intestinal disorders." Intestinal disorders include IBD, IBS, and coeliac disease, and extra-intestinal conditions include allergies, asthma, metabolic syndrome, cardiovascular disease, and obesity. Dysbiosis has played a role in autoimmune diseases, allergies, and metabolic disorders. Gut dysbiosis can also be a factor in neurodegenerative and cerebrovascular diseases due to the link between age-related dysbiosis and neurological decline by inflammation being the common factor for a wide variety of age-related pathologies. By correcting the dysbiosis in elderly patients, it may be possible to prevent the development of neurodegenerative diseases. Dysbiosis may contribute to the cause or development of neurological conditions, including “autism, pain, depression, anxiety, and stroke.” Dysbiosis contributing to neurological conditions is due to interactions with the gut-brain axis allowing the gut microbiome to influence neural development, cognition, and behavior. There has also been evidence that the gut microbiota composition can be altered due to changes in behavior, and changing the microbiome can also cause depressive-like behaviors. When this balance is disturbed, these colonies exhibit a decreased ability to check each other's growth, which can then lead to overgrowth of one or more of the disturbed colonies which may further damage some of the other smaller beneficial ones in a vicious cycle. As more beneficial colonies are damaged, making the imbalance more pronounced, more overgrowth issues occur because the damaged colonies are less able to check the growth of the overgrowing ones. If this goes unchecked long enough, a pervasive and chronic imbalance between colonies will set in, which ultimately minimizes the beneficial nature of these colonies as a whole. Microbial colonies also excrete many different types of waste byproducts. Using different waste removal mechanisms, under normal circumstances the body effectively manages these byproducts with little or no trouble. Unfortunately, oversized and inappropriately large colonies, due to their increased numbers, excrete increased amounts of these byproducts. As the amount of microbial byproducts increases, the higher waste byproducts levels can overburden the body's waste removal mechanisms. It is the combination of these two negative outcomes that causes many of the negative health symptoms observed when dysbiosis is present. A human’s microbiome can change because of inflammatory processes, such as cell-mediated inflammation and host-mediated inflammation, or a ‘driver’ bacteria causing/aggravating inflammation. This change allows the microbial community to become more susceptible to pathogens. Once the pathogens are established successfully, they contribute to dysbiosis and produce genotoxins and other potential cancer-causing microbial metabolites. The evolution of pathogens is another possible effect of dysbiosis, contributing to a potential increase in cancer risk. Gut dysbiosis can affect the cardiovascular system “via signaling molecules and bioactive metabolites. This could cause diseases through neuro-entero-endocrine hormones that can lead to heart failure and other conditions such as chronic kidney disease, hypertension, obesity, and diabetes. Associated illnesses Cross-regulation occurs between the host and the gut microbiota in healthy people, resulting in a homeostatic equilibrium of bacteria that keeps the gastrointestinal tract healthy and free of potentially pathogenic bacteria. There are three significant categories of dysbiosis: loss of beneficial organisms, excessive growth of potentially harmful microorganisms, and loss of overall microbial diversity. Disruptions in the microbiome can allow outside factors or even pathogenic members of the microbiome to take hold in the gut environment. Dysbiosis has been reported to be associated with illnesses, such as multiple chemical sensitivity, periodontal disease, inflammatory bowel disease, chronic fatigue syndrome, obesity, cancer, bacterial vaginosis, and colitis. IBD There is no mono-associated cause of IBD; the three major pathogens that have been associated with IBD are Mycobacterium avium paratuberculosis (MAP), adherent-invasive escherichia coli (AIEC), and clostridium difficile. There is no evidence that these pathogens are the culprit of IBD. Rather than the “one-microbe-one disease” hypothesis, it is thought that IBD is caused by an imbalance of commensal microflora associated with more complex interactions between the host and the entire intestinal microbiota. Obesity Obesity is a metabolic condition in which the body retains an unhealthy amount of fat. The prevalence of obesity in the United States is increasing, with about 93.3 million adults and 14.4 million children recorded in 2015-2016, according to the Center for Disease Control and Prevention. Similar to IBD, a specific microbiota appears to be linked to the development of obesity. There is a notable reduction in microbial diversity in obese individuals. Research in humans and animals shows an association of obesity with altered ratios between Bacteroidetes and Firmicutes; as Bacteriodetes decreases, Firmicutes increases. This ratio has been linked to body weight and fat accumulation, indicating that obese people have a higher disproportionate ratio of these bacteria. Diabetes Mellitus Diabetes mellitus (DM) is a carbohydrate metabolism disorder characterized by insufficient insulin output or utilization, which is needed for the body to turn sugars and starches into energy. The prevalence of DM in the United States is about 29.1 million, with about 1.7 million new diagnoses annually. The two forms of diabetes are Type 1 and Type 2. Type 1 DM is also known as Insulin-Dependent Diabetes Mellitus (IDDM). Type 1 diabetes is an autoimmune condition that affects the beta cells in the pancreas, causing insulin production to be impaired. It is most often diagnosed in children and young adults. Type 2 diabetes mellitus, also known as Non-Insulin-Dependent Diabetes Mellitus (NIDDM), is a type of diabetes that affects adults and is characterized by insulin resistance, which occurs when tissue sensitivity insulin is reduced, causing the body to ignore the insulin released. Research has shown dysbiosis of the intestinal microbiota may contribute to both forms of diabetes. Dysbiosis related to type 1 DM is characterized by a decline in mucin-degrading bacteria, such as Bifidobacteria, Lactobacillus, and Prevotella, and an increase in Bacteroidetes and Clostridium. Cancer Sustained periods of dysbiosis lead to extended amounts of stress and inflammation in the gut microbiome, which can in turn promote the production of carcinogenic metabolites. Intestinal dysbiosis has been associated with colorectal cancer (CRC). According to the American Cancer Society, colorectal cancer is the third most common cancer and the second leading cause of cancer death in the United States. In CRC patients, a general dysbiosis pattern has been discovered, including a decrease in butyrate-producing bacteria and an increase in the proportion of several potentially pathogenic bacteria. Clostridioides difficile C. difficile is an opportunistic bacteria that commonly infects patients following a disruption in the microbiome, such as treatment with antibiotics. Infection can lead to several different symptoms including watery diarrhea, fever, loss of appetite, nausea, and abdominal pain. Severe or chronic infections of C. difficile can lead to inflammation of the colon, a condition known as colitis. Periodontitis Periodontitis is an oral infection that can damage the bones supporting teeth and lead to tooth loss. One of the major risk factors for periodontitis is the disruption of the oral microbiome such that there is an accumulation of pathogenic bacteria. Studies show that the oral microbiota changes as periodontitis progress, shifting from gram-positive aerobes to gram-negative anaerobes. Oral dysbiosis is likely to evolve, shifting the symbiotic host-microbe relationship to a pathogenic one. During this time, the host's oral health deteriorates, eventually leading to clinical disease. Acne vulgaris The use of minocycline in acne vulgaris has been associated with skin and gut dysbiosis. Treatments Antibiotics Because of the complex interactions in the microbiome, not much data exists on the efficacy of using antibiotics to treat dysbiosis. However, the broad-spectrum antibiotic rifaximin has been shown to have a favorable response in several of the ailments associated with dysbiosis, including irritable bowel syndrome. While most antibiotics alter the gut microbiota for the duration of the treatment, some cause long-lasting changes. However, repeated exposure to antibiotics can also cause the opposite of the intended effect and destabilize the gut microbiome, resulting in promoting “outgrowth of antibiotic-resistant pathogenic bacteria” (see antibiotic misuse) thus aggravating gut dysbiosis. Fecal microbiota transplant (FMT) Fecal Microbiota Transplantation (FMT) is an experimental treatment that has resolved 80-90 percent of dysbiosis-related infections caused by recurrent C. difficile infections that do not respond to antibiotics in randomized, controlled clinical trials. A patient's colon is transplanted during FMT with a fecal preparation from a carefully screened, healthy stool donor. FMT is thought to work by repopulating the patient's microbiome with various microorganisms that compete with C. difficile for space. FMTs use the same line of reasoning as probiotics; to recreate a healthy balance of microbiota in the microbiome by inserting beneficial microbes into the environment. FMT accomplishes this by taking a donation of fecal matter from a healthy individual, diluted, strained and introduced to a diseased patient. FMTs are currently used to treat patients with Clostridium difficile infections, who have proved resistant to other therapies.; however, this is considered an investigational therapy at present with risks that have not been fully defined. Because the process is not sterile and contaminations can pass from donor to patient, there is a push to isolate key microbiota and culture them independently. Probiotics The World Health Organization defines probiotics as "live microorganisms, which when administered in adequate amounts, confer a health benefit on the host". The benefit of using probiotics to treat dysbiosis related diseases lies in its ability to treat the underlying cause of said diseases. Some benefits include their ability to suppress inflammation in the microbiome and disrupt colonization by pathogens. Excessive use of antibiotics, IBD, obesity, diabetes, cardiovascular disease, and many more ailments are related to interruptions in the microbiome(dysbiosis), especially in the human gut. Probiotics can promote healthier microbial function by introducing or reintroducing helpful bacteria to strengthen the weaknesses presented in a dysbiotic microbiome. It is essential to recognize that such circumstances are beneficial bacteria that occur more frequently than harmful ones. Probiotics can be utilized in aiding existing conditions and preventing such diseases by instituting antiinflammatory properties and improving immune cell function. The human gut contains a wide diversity of bacteria and can easily be disrupted through diet, medicinal usage, diseases, and many others. Probiotics have proven influential in returning the intestinal microbiota to homeostatic balance and improve intestinal health. Probiotics contain anti-inflammatory properties that assist in the prevention and treatment of intestinal diseases due to microbial dysbiosis. More research is needed to understand better the many benefits probiotics can offer for multiple forms of dysbiosis. See also Gut flora Human microbiome List of bacterial vaginosis microbiota Microbiome Notes and references External links Intestinal dysbiosis Symptoms and signs

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Patients who had cholestatic jaundice during pregnancy may develop it while taking birth control pills.Fluid retention may occur.**H. OTHER DISORDERS—**Depression may occur or be worsened with oral contraceptive use.Progestin-only pills, levonorgestrel implants, and DMPA are alternatives with no adverse effects on milk quality.Oral contraceptives have been associated with the development of benign hepatocellular adenomas and peliosis hepatis (blood-filled cavities) (but not focal nodular hyperplasia or hepatocellular carcinoma); hepatocellular adenomas may rarely cause rupture of the liver, hemorrhage, and death. The risk of hepatocellular adenoma increases with higher dosage, longer duration of use, and older age. **E. HYPERTENSION—**Oral contraceptives may cause hypertension in some women; the risk is increased with longer duration of use and older age. Women in whom hypertension develops while using oral contraceptives should use other non-estrogen–containing contraceptive methods. However, with regular blood pressure monitoring, nonsmoking women with well-controlled mild hypertension may use oral contraceptives. **F. HEADACHE—**Migraine or other vascular headaches may occur or worsen with pill use. If severe or frequent headaches develop while using this method, it should be discontinued. Women with migraine headaches _with an aura_ should not use oral contraceptives. **G. LACTATION—**Combined oral contraceptives can impair the quantity and quality of breast milk. While it is preferable to avoid the use of combination oral contraceptives during lactation, the effects on milk quality are small and are not associated with developmental abnormalities in infants. Combination oral contraceptives should be started no earlier than 6 weeks postpartum to allow for establishment of lactation. Progestin-only pills, levonorgestrel implants, and DMPA are alternatives with no adverse effects on milk quality. **H. OTHER DISORDERS—**Depression may occur or be worsened with oral contraceptive use. Fluid retention may occur. Patients who had cholestatic jaundice during pregnancy may develop it while taking birth control pills.In addition, obesity is a risk factor for thromboembolic complications.It is important that obese women are not denied effective contraception as a result of concerns about complications or efficacy of oral contraceptives.Alternatives, including progestin only injections, implants, or intrauterine devices, should be considered as first options instead of oral contraceptives.**6.

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Pyogenic liver abscesses also occur as a result of impaired biliary drain-age, subacute bacterial endocarditis, infected indwelling cath-eters, dental work, or the direct extension of infections such as diverticulitis or Crohn’s disease into the liver.Due to the high level of retic-uloendothelial cells in the liver, nonviral infections are unusual.Pyogenic Liver AbscessesPyogenic liver abscesses are the most common liver abscesses seen in the United States. They may be single or multiple and are more frequently found in the right lobe of the liver.65 The abscess cavities are variable in size and, when multiple, may coalesce to give a honeycomb appearance. Approximately 40% of abscesses are monomicrobial, an additional 40% are polymicrobial, and 20% are culture-negative. The most com-mon infecting agents are gram-negative bacteria. Escherichia coli is found in two thirds of cases, and other common organ-isms include Streptococcus faecalis, Klebsiella, and Proteus vulgaris. Anaerobic organisms such as Bacteroides fragilis also are seen frequently. In patients with endocarditis and infected indwelling catheters, Staphylococcus and Streptococcus species are more commonly found.In the past, pyogenic liver abscesses often resulted from infections of the intestinal tract such as acute appendicitis and diverticulitis, which then spread to the liver via the portal circu-lation. With improved imaging modalities and earlier diagnosis of these intra-abdominal infections, this particular etiology of pyogenic liver abscesses has become less common. Pyogenic liver abscesses also occur as a result of impaired biliary drain-age, subacute bacterial endocarditis, infected indwelling cath-eters, dental work, or the direct extension of infections such as diverticulitis or Crohn’s disease into the liver.Jaundice occurs in up to one-third of affected patients.A thorough history and physical examination are usually helpful in identifying the underlying cause of the liver abscess.Leuko-cytosis, an elevated sedimentation rate, and an elevated AP level are the most common laboratory findings.Significant abnor-malities in the results of the remaining liver function tests are unusual.

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Apoptosis accompanied by up-regulation of TNF-alpha death pathway genes in the brain of Niemann-Pick type C disease. Niemann-Pick disease type C (NP-C) is an autosomal recessive neurovisceral storage disease with neurodegeneration caused by mutations in either the NPC-1 or NPC-2 gene. The murine ortholog of NPC-1 is mutated in BALB/c npc(nih) and this mutant mouse shows equally conspicuous neurodegeneration and loss of neurons. However, the molecular mechanisms causing neurodegeneration in NP-C remain elusive. Here, we report the presence of apoptotic cells detected by both TUNEL staining and electron microscopy in the cerebrum and cerebellum of human patients and the mouse model. Moreover, we found that with progression of the disease process leading to neuronal cell death, an up-regulation of genes involved in the TNF-alpha death pathway caspase-8, FADD, TNFRp55, TRADD, and RIP-by an RNA protection assay. Furthermore, RT-PCR showed that TNF-alpha mRNA expression level also increased up to 30-50-fold in the cerebellum of 7- and 9-week-old NP-C mice compared with wild-type mice. Elevated expression of TNF-alpha was detected in both neurons and astrocytes with TNF-alpha-expressing astrocytes distributed in the affected brain regions. Collectively, our results suggest that the cell death in the brain of NP-C disease occurs through apoptosis and it is mediated by the TNF receptor superfamily pathway.

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If deep venous thrombosis is not detected, they should be considered for a pulmonary angiogram.If deep venous thrombosis is detected, they should be anticoagulated.Patients with equivocal ventilation-perfusion findings should be evaluated as described above for deep venous thrombosis in their legs.Patients with mismatched segmental perfusion defects have a pulmonary embolus.The most common cancers associated with thromboembolic episodes include lung, pancreatic, gastrointestinal, breast, ovarian, and genitourinary cancers; lymphomas; and brain tumors. Patients with cancer who undergo surgical procedures requiring general anesthesia have a 20–30% risk of deep venous thrombosis. Diagnosis The diagnosis of deep venous thrombosis in patients with cancer is made by impedance plethysmography or bilateral compression ultrasonography of the leg veins. Patients with a noncompressible venous segment have deep venous thrombosis. If compression ultrasonography is normal and there is a high clinical suspicion for deep venous thrombosis, venography should be done to look for a luminal filling defect. Elevation of D-dimer is not as predictive of deep venous thrombosis in patients with cancer as it is in patients without cancer; elevations are seen in people over age 65 years without concomitant evidence of thrombosis, probably as a consequence of increased thrombin deposition and turnover in aging. Patients with symptoms and signs suggesting a pulmonary embolism should be evaluated with a chest radiograph, electrocardiogram, arterial blood gas analysis, and ventilation-perfusion scan. Patients with mismatched segmental perfusion defects have a pulmonary embolus. Patients with equivocal ventilation-perfusion findings should be evaluated as described above for deep venous thrombosis in their legs. If deep venous thrombosis is detected, they should be anticoagulated. If deep venous thrombosis is not detected, they should be considered for a pulmonary angiogram.In light of the many possible primary sites, diagnostic testing in asymptomatic patients is wasteful.However, if the clot is refractory to standard treatment or is in an unusual site or if the thrombophlebitis is migratory or recurrent, efforts to find an underlying cancer are indicated.

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Osteoporosis Management: Drug vs. Vitamin Therapy? OSTEOCLAST PREVENTION DRUGS CALLED BIPHOSPHONATES (FOSAMAX, ACTONEL, BONIVA, RECLAST) LINKED TO UNPROVOKED FRACTURE OF THE FEMUR...ALSO LINKED TO OSTEONECROSIS OF THE JAW. Take calcium. Dr. Cox suggests Formula #2 which is calcium citrate (as opposed to calcium carbonates often sold in drugstores) in capsule form with hydrochloric acid for absorption, magnesium, manganese, vitamin D3 and an additional 5 000 units of vitamin D3 a day. Click here for more information. Increase Vitamin D3 intake to 5000 units a day. Exercise regularly with walking and free weight. Minimize caffeine and alcohol intake. from Bergman, GJD; Fan, T; McFetridge, JT; Sen, SS: Efficacy of vitamin D-3 supplementation in preventing fractures in elderly women: A meta-analysis. CURRENT MEDICAL RESEARCH AND OPINION 2010; 26 (5):1193-1201 The efficacy of vitamin D-3 in preventing fractures and falls has been explored in a number of clinical trials. However, recent evidence revealed new questions about the adequate doses of vitamin D-3 supplementation and its efficacy in fracture prevention independent of calcium supplements for various types of fractures. A meta-analysis to estimate the effectiveness of 800 IU daily vitamin D-3 supplementation for increasing bone mineral density (BMD) and preventing fractures in postmenopausal women was done on Medline and EMBASE for controlled trials comparing the effectiveness of cholecalciferol (vitamin D-3) against placebo with or without background calcium supplementation in the treatment of postmenopausal women. Results: Eight controlled trials evaluating the effect of vitamin D-3 supplementation with or without calcium were assessed. Of 12 658 women included in a Bayesian meta-analysis, 6089 received vitamin D-3 (with or without calcium) and 6569 received placebo (with or without calcium). Compared to placebo, vitamin D3 with calcium supplementation showed beneficial effects on the incidence of non-vertebral and hip fractures, while the effects on non-vertebral-non-hip fractures were associated with more uncertainty. Vitamin D-3 supplementation showed a 70% probability of being a better treatment than placebo for the prevention of non-vertebral fractures, hip fractures, and non-vertebral, non-hip fractures. Compared to calcium supplementation, vitamin D-3 plus calcium reduced non-vertebral fractures (OR 0.68, 95% CL 0.43-1.01) and non-vertebral, non-hip fractures, but did not reduce hip fractures. Key limitations to this analysis include a small number of studies and heterogeneity in the study populations. Conclusions: This meta-analysis supports the use of vitamin D3 of 800 IU daily to reduce the incidence of osteoporotic non-vertebral, hip, and non-vertebral-non-hip fractures in elderly women. Vitamin D-3 with calcium appears to achieve benefits above those attained with calcium supplementation alone for non-vertebral and non-vertebral-non-hip fractures. THORACIC KYPHOSIS SEVERITY INCREASES RISK OF VERTEBRAL FRACTURE. THORACIC KYPHOSIS INCREASES OVER A 3 YEAR PERIOD. comment from James M. Cox DC DACBR: If for no other condition than hyperkyphosis of the thoracic spine, f/d decompression is worth having in the doctor’s treatment bag. Posture control coupled with f/d is an excellent addition to thoracic kyphosis care when you consider the possible complications as described in the report by Roux et al. The relation of thoracic kyphosis, its influence on incident fractures and quality of life over three years in postmenopausal women with osteoporosis and the effect of strontium ranelate on thoracic kyphosis progression was studied on women with postmenopausal osteoporosis. Vertebral fractures were assessed on lateral thoracic radiographs performed at baseline and at three years according to standardized procedure. Kyphosis index (KI, %) was defined as the percentage ratio between the maximum depth of thoracic curvature and the height measured from the T4 to the T12 vertebrae. Baseline characteristics of the 3218 patients (1594 strontium ranelate, 1624 placebo) were mean age 73.3 years, spine bone mineral density (BMD) T-score (1-2-4)-3.1, femoral neck T-score -3.0, and KI 25.4%. In the placebo group, patients with the highest baseline KI experienced significantly more vertebral fractures than those with medium KIs or the lowest KIs. There was no difference in the risk of nonvertebral fractures according to baseline KI. Three-year changes in quality-of-life physical scores reflected significantly better status for patients in the lowest tertile of KI compared with those in the highest at baseline. Over three years, the kyphosis index increased for all patients, indicating worsening of thoracic kyphosis, whatever the presence of prevalent or incident vertebral fractures. This KI progression was lower in the strontium ranelate group than in the placebo group. Thoracic kyphosis is a risk factor for vertebral fractures over three years and influences physical capacity changes in postmenopausal women with osteoporosis. Thoracic kyphosis progression over three years is lower in a subgroup of strontium ranelate-treated patients compared with placebo-treated patients.

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This helps to explain the functional overlap among different cytokines.The common γ chain is an intracellular signaling molecule.These include IL-2, IL-4, IL-7, IL-9, and IL-15 (see Figure 12.6).Several cytokines use multichain receptors to mediate their effects on target cells and some of these receptors share at least one common receptor molecule called the **_common_ γ chain**.Finally, the **_chemokine receptors_** belong to a superfamily of serpentine **_G-protein-coupled receptors_** , so called because of their unique snakelike extracellular-cytoplasmic structural configuration and their association with G proteins, which mediate signal transduction (Figure 12.5). A growing list of CC and CXC chemokine receptors have been cloned, and some have been found to be promiscuous, since they can bind not only to chemokines but also to a diverse set of pathogens, including bacteria (e.g., _Streptococcus pneumo nia_, which binds to the platelet-activating factor [PAF] receptor), parasites (e.g., _Plasmodium vivax_ , which binds to the chemokine receptor known as Duffy blood-group antigen), and certain viruses (e.g., T-tropic HIV-1 strains that use the CXCR4 chemokine receptor, and M-tropic HIV-1 strains that use the CCR5 chemokine receptor for viral entry into T cells and macrophages, respectively). ### Common Cytokine Receptor Chains As noted earlier in this chapter, it is common for cytokines to have overlapping (redundant) functions: For example, both IL-1 and IL-6 induce fever and several other common biologic phenomena. Nonetheless, these cytokines also have properties that are unique. Several cytokines use multichain receptors to mediate their effects on target cells and some of these receptors share at least one common receptor molecule called the **_common_ γ chain**. These include IL-2, IL-4, IL-7, IL-9, and IL-15 (see Figure 12.6). The common γ chain is an intracellular signaling molecule. This helps to explain the functional overlap among different cytokines.Produced by so-called TH9 cells, IL-9 plays a major role in the immune response against helminthes, and it is assumed this is the cytokine's "physiologic" function.Similar to other molecules with the same function (e.g., IgE, see Chapter 15), IL-9, however, also participates in the pathogenic process of allergy, in particular asthma.

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Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the 'cheese effect'. After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.

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Isolation and characterization of a water-stress-inducible cDNA clone from Solanum chacoense. A rich source of valuable genes are wild species. Solanum chacoense Bitter with its extreme resistance to viruses, insects and drought, is a good example. In the present study, a stress gene, designated DS2, has been isolated from S. chacoense. We have shown that the expression of the gene is organ-specific being detected in leaf, stem and stolon, but not in root, tuber or flower. Treatment of detached leaves with abscisic acid (ABA), salicylic acid or methyl jasmonate resulted in only very moderate accumulation of DS2 mRNA. Thus, DS2 represents a very rare type of the water-stress-inducible genes whose signalling pathway is not primarily related to ABA. Based on DNA sequence analysis, DS2 encodes a putative protein starting with 20 amino acids homologous to the ABA- and water-stress-inducible, ripening-related (ASR) proteins of tomato continued by an insert of 155 amino acids structurally similar to certain LEAs (late embryogenesis-abundant proteins) and ending in 88 amino acids homologous again to the ASR sequences and to an unpublished partial cDNA fragment isolated from the root of rice. The N-terminal region of the DS2 protein is hydrophilic with ten 13-mer amino acid motifs and random coil structure. In contrast, the C-terminus predicts an alpha-helix and possesses a bipartite nuclear targeting sequence motif. These data suggest that the function of the DS2 may be the protection of the nuclear DNA from desiccation.

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Specific immune responses are either primary or secondary.Degradation of antigens by macrophages may lead to subsequent presentation of a portion of the antigen to immunocompetent lymphocytes to elicit a specifc immune response.They constitute about 5% to 10% of circulating lymphocytes. They do not mature in the thymus; however, during their development, they are genetically programmed to recognize transformed cells (i.e., cells infected with a virus or tumor cells). NK cells kill target cells in a similar fashion to that of cytotoxic CD8 T lymphocytes. After recognition of a transformed cell, they release perforins and granzymes (fragmentins), substances that create channels in the cell’s plasma membrane, which induces them to self-destruct (a process known as apoptosis). Their specific markers include CD16a, CD56, and CD94. and are transported throughout the body, where they are dispersed in the connective tissue. Lymphocytes undergo antigen-dependent activation in the secondary lymphatic organs. Immunocompetent lymphocytes (together with plasma cells derived from B lymphocytes and with macrophages) organize around reticular cells and their reticular fibers to form the adult effector lymphatic tissues and organs (i.e., lymphatic nodules, lymph nodes, tonsils, and spleen). Within these secondary (peripheral) lymphatic organs, T and B lymphocytes undergo antigen-dependent activation into effector lymphocytes and memory cells. Immune Responses to Antigens Inflammation is the initial response to an antigen. The initial reaction of the body to invasion by an antigen, either a foreign molecule or a pathogenic organism, is the nonspecific defense known as the inflammatory response. The infammatory response may either sequester the antigen, physically digest it with enzymes secreted by neutrophils, or phagocytose and degrade the antigen in the cytoplasm of macrophages. Degradation of antigens by macrophages may lead to subsequent presentation of a portion of the antigen to immunocompetent lymphocytes to elicit a specifc immune response. Specific immune responses are either primary or secondary.A primary immune response refers to the body’s first encounter with an antigen.This response is characterized by a lag period of several days before antibodies (mostly IgM) or specific lymphocytes directed against the invading antigen can be detected in the blood.

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Ibutilide is a Class III antiarrhythmic agent that is indicated for acute cardioconversion of atrial fibrillation and atrial flutter of a recent onset to sinus rhythm. It exerts its antiarrhythmic effect by induction of slow inward sodium current, which prolongs action potential and refractory period (physiology) of myocardial cells. Because of its Class III antiarrhythmic activity, there should not be concomitant administration of Class Ia and Class III agents. Ibutilide is marketed as Corvert by Pfizer. Administration resulted in successful heart rhythm control in 31-44% of patients within 90 minutes, with sustained polymorphic ventricular tachycardia in 0.9-2.5% of patients. It appears to show better results in atrial flutter as compared to atrial fibrillation. Mechanism of action Ibutilide, like other class III antiarrhythmic drugs, blocks delayed rectified potassium current. It does have action on the slow sodium channel and promotes the influx of sodium through these slow channels. Although potassium current seems to play a role, their interactions are complex and not well understood. Ibutilide's unique mechanism works by an activation of a specific inward sodium current, thus producing its therapeutic response in which a prolonged action potential increases myocytes’ cardiac refractoriness in case of atrial fibrillation and flutter. Pharmacokinetics Absorption Ibutilide is intravenously administered. It has a high first-pass metabolism, which results in a poor bioavailability when taken orally. Individual pharmacokinetic properties are highly viable during the clinical trial. Distribution Ibutilide has a relatively large volume of distribution among individual subjects, which is about 11L/kg. Approximately 40% of the drug is bound with plasma albumin of healthy volunteers in a trial. This is also approximately close to patients with atrial fibrillation and flutter. Metabolism Ibutilide has a high systemic plasma clearance that closes to the hepatic blood flow (29mL/min/kg). Its metabolic pathway is via liver's cytochrome P450 system by isoenzymes other than CYP3A4 and CYP2D6 by which the heptyl side chain of ibutilide is oxidized. With eight metabolites are detected in the urine, however, only one is an active metabolite that shares the similar electrophysiologic property of the Class III antiarrhythmic agents. The plasma concentration of this metabolite is only less than 10% of ibutilide. Excretion After administration of ibutilide, it is quickly excreted by renal pathway with a half-life of approximately 6 hours. Approximately 82% of a 0.01 mg/kg dose is excreted in the urine during the trial. Among those, around 7% is excreted as unchanged drug. The remainder of the drug is excreted in feces (about 19%). Adverse effects and contraindications Like other antiarrhythmics, ibutilide can lead to abnormal heart rhythms due to its ability to prolong the QT interval, which can lead to the potentially fatal abnormal heart rhythm known as torsades de pointes. Consequently, the drug is contraindicated in patients that are likely to develop abnormal heart rhythms; this includes persons that have had polymorphic ventricular tachycardia in the past, have a long QT interval, sick sinus syndrome, or a recent myocardial infarction, among others. Patient Information This medication will be given intravenously for your heart disease. You will have continuously ECG monitoring during the infusion and 4 hours after your infusion. Some of the minor side effects are headache and irregular heartbeat. If you experience chest pain and respiratory difficulties, you should report to your doctors immediately. See also Sematilide Risotilide References Antiarrhythmic agents Sulfonamides Secondary alcohols Pfizer brands Potassium channel blockers Anilines

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Endothelial keratoplasty (EK) is used increasingly for the management of cases with endothelial dysfunction. Long-term outcomes of the surgery are not widely reported in the literature. We report our experience of EK in Chinese eyes at a University teaching hospital. Retrospective analysis was performed for all cases of EK performed between 2005 and 2009. Data analyzed included indication for surgery, associated surgical procedures, complications, best-corrected visual acuity (BCVA) and overall graft survival. Overall, 22 eyes of 21 patients underwent EK (13 males, 8 females, mean age 71.8 ± 11.3 years). Pseudophakic bullous keratopathy was the leading indication for surgery (n = 12) followed by Fuchs’ endothelial dystrophy (n = 4), or both (n = 3). Other indications for surgery included failed penetrating keratoplasty (n = 2) and endothelial decompensation due to multiple surgeries (n = 1). Triple procedure was performed in 5 (22.7%) cases. Complications were noted in the form of postoperative interface hemorrhage (n = 2, 9%) and graft dislocation (n = 1, 4.5%). The mean postoperative endothelial cell density was 1069 ± 585.8 cells/mm2. The mean postoperative pachymetry was 675.8 ± 108.5 μm. The mean preoperative and postoperative intraocular pressure was 11.3 ± 3.2 and 13.9 ± 4.5 mmHg respectively. At the last follow-up (mean, 47.4 ± 13.7 months), BCVA was ≥20/70 in 9 (40.9%) cases. Causes of poor BCVA included primary graft failure (n = 4), graft decompensation (n = 4), advanced glaucoma (n = 2) and irreversible graft rejection (n = 2). Graft remained clear in 12 (54.5%) cases at the last follow-up. Average graft survival was 19.7 ± 17.7 months (median 17.5 months). Nearly half of the EK grafts in our study survived over a period of five years. Graft failure, glaucoma and graft rejection were the main causes of poor graft survival. Endothelial keratoplasty (EK) has become the treatment of choice in cases with corneal endothelial dysfunction in the presence of clear corneal stroma. Over the past few years, the spectrum of indications of EK is expanding ,. It has been performed with successful outcomes in cases with bullous keratopathy, Fuchs’ endothelial dystrophy, iridocorneal endothelial syndrome, posterior polymorphous dystrophy and congenital hereditary endothelial dystrophy ,. Furthermore, as the refinements in the surgical techniques progress, new reports of intraoperative problems, postoperative issues and complications continue to surface -. EK has managed to come at par with penetrating keratoplasty, a surgery that was established more than a century ago. Clearly, of all the variants of EK, descemet stripping endothelial keratoplasty (DSEK) is the most popular, and widely practiced by corneal surgeons around the world. Small incision, few sutures, mild astigmatism and fast visual recovery have enabled DSEK to become the first-choice surgery in suitable cases. Although current literature is continually replenished with information on modifications of EK, long-term outcomes are still under-reported -. We adopted deep lamellar endothelial keratoplasty (DLEK) in the year 2005. However, it was quickly replaced by the more popular DSEK in 2006. In this study, we report the outcomes of EK in Chinese eyes from our centre over a period of five years. To our knowledge, there were no previous reports on long-term outcomes of EK in Chinese eyes. This was a retrospective case series of all cases of endothelial keratoplasties that were performed in the Corneal Unit of a university hospital between 2005 and 2009. Our tertiary care hospital caters to the ophthalmic needs of a population of about 1.3 million. We performed the first endothelial keratoplasty (DLEK) at our hospital in January 2005 according to a previously described technique . DLEK was replaced by DSEK in the following year. Optical grade donor corneas with endothelial cell density >2000 cells/mm2 were used in all cases. All surgeries were performed using a standard surgical technique as described previously . For DSEK, the donor was prepared manually on an artificial anterior chamber using lamellar dissectors. Briefly, a 5.5 mm scleral tunnel wound was created 2.0 mm behind the temporal limbus. The Descemet’s membrane was scored and stripped under viscoelastic cover. Viscoelastic was gently irrigated before the insertion of graft. A 7.5 mm donor endothelial lenticule was folded in a 60/40 taco and inserted in the anterior chamber with a pair of forceps. The anterior chamber was filled with air at the end of the surgery. Postoperatively, the patient was instructed to lie supine for two hours. Topical methylprednisolone 1% eye drops 6 times a day and levofloxacin 0.5% eye drops four times a day were prescribed for first six weeks postoperatively. Weekly follow-up was scheduled for the first four weeks. Subsequently, patients were followed every 4–6 weeks. Corticosteroid eye drops were tapered off to four times daily over the next three months. By the end of one year postoperatively, all cases were using twice daily corticosteroids. In cases with graft rejection, hourly prednisolone acetate 1% eye drops were started for the first 3 days. Treatment was adjusted according to the response. Case records of patients who had undergone EK were retrieved from the medical records. Data analyzed included demographics, indication for surgery; type of EK performed, associated surgical procedures, complications, best-corrected visual acuity (BCVA) and overall graft survival. For the purpose of this study, graft survival was defined as the time period for which the graft remained clear after surgery. The study followed the tenets of the Declaration of Helsinki. Over the study period, 22 eyes of 21 patients underwent EK (13 males, 8 females). Mean age of the patients was 71.8 ± 11.3 years. The indications for surgery are described in Table 1. Four cases underwent DLEK and 17 underwent DSEK. Cataract extraction with intraocular lens implantation was performed in 5 (22.7%) cases. Mean follow-up of all cases was 47.4 ± 13.7 months. At the last follow-up, 15 (68.2%) cases had improved BCVA compared to the preoperative level. BCVA was ≥20/70 in 9 (40.9%) and ≥20/50 in 6 (27.3%) patients. Causes of poor final BCVA included primary graft failure (n = 4), graft decompensation (n = 4), advanced glaucoma (n = 2) and irreversible graft rejection (n = 2). Specular microscopy was not possible preoperatively because of media opacity due to bullous keratopathy. Preoperative pachymetry was not routinely performed in our cases. The mean postoperative endothelial cell density was 1069 ± 585.8 cells/mm2 (mean ± standard deviation). The average postoperative pachymetry was 675.8 ± 108.5 μm. The average preoperative and postoperative intraocular pressure was 11.3 ± 3.2 and 13.9 ± 4.5 mmHg respectively. Grafts remained clear in 12 (54.5%) cases at the last follow-up. Average graft survival was 19.7 ± 17.7 months (median 17.5 months). Postoperatively, interface hemorrhage was observed in 2 (9%) cases. Although interface irrigation was performed, the hemorrhage reappeared shortly thereafter in both cases. Spontaneous resolution of hemorrhage was noted in one of these cases over a period of 4 months. Graft failure ensued in the other case. One case (4.5%) of 85-year-old female underwent DSEK triple procedure for Fuchs’ endothelial dystrophy. Although the surgery was uneventful, she suffered from graft dislocation in the immediate postoperative period. Surgical repositioning of the donor lenticule was undertaken in the operating room along with intracameral injection of iso-expansile mixture of SF6 (20%) resulting in successful re-attachment of the graft. Primary graft failure was seen in 4 (18.2%) cases. One of these cases had a retrocorneal membrane. Late graft failure was seen in 4 (18.2%) cases due to poor endothelial survival. Re-graft was performed in one case with failed penetrating keratoplasty. Two cases (9.1%) suffered from graft rejection within the first 6 months of surgery. Reversal of rejection episode could not be achieved despite intensive corticosteroid therapy and consequently, these cases suffered from graft failure. Endothelial keratoplasty involves the selective replacement of diseased corneal endothelium with a healthy partial-thickness posterior corneal lenticule. The outcomes of EK have improved over the past 5 years with the introduction of different techniques that focused on reducing the incision size, performing atraumatic graft insertion into the eye and preventing graft dislocation . A few studies have analyzed the long-term outcomes of EK -. In a retrospective cohort study, Ang et al. showed that percent endothelial cell loss was lower in EK compared with penetrating keratoplasty at up to 3 years after the surgery. In another retrospective, interventional case series, Li et al. reported visual outcomes 3 years after EK. The authors reported a statistically significant trend toward improvement in the average best spectacle corrected visual acuity at postoperative month 6 and postoperative years 2 and 3 after EK. Price et al. showed that the 3-year survival rate did not differ significantly between EK and penetrating keratoplasty procedures. In the present study, we describe the long-term outcomes of endothelial keratoplasty in Chinese eyes operated at a single centre over a period of 5 years. The most common indication for surgery was bullous keratopathy in our study. Although EK is being performed for a variety of conditions associated with diseased corneal endothelium, pseudophakic bullous keratopathy and Fuchs’ endothelial dystrophy remain the leading indications for EK . This can be partly attributed to gradual increase in the number of cataract surgeries being performed all over the world. Although there were no intraoperative problems encountered in any of the cases in our study, the postoperative course was complicated by graft dislocation in one case that underwent DSEK along with cataract extraction and intraocular lens insertion for Fuchs’ endothelial dystrophy. Reattachment of the donor lenticule was achieved by intracameral tamponade using isoexpansile gas mixture. Graft dislocation is one of the most common complications of EK seen in the immediate postoperative period. In a recent report by the American Academy of Ophthalmology, nearly 85% of the studies reported graft dislocation after EK and dislocation rates varied from 0% to 82% . Main causes of graft dislocation include incomplete irrigation of viscoelastic, surgical trauma, and, rubbing or squeezing the eye in the early postoperative period . EK graft dislocation is typically evident within the initial week after surgery. Successful reattachment can be achieved in most cases by injection of air or gas between the graft and the iris similar to that in our case. Primary graft failure is the third most common complication of EK . The incidence of primary graft failure in our study matches well with the reported rates of 0% to 29% in the published literature . Primary graft failures represent a lack of endothelial function due to unhealthy tissue, unhealthy recipient circumstances or surgical technique. Primary graft failure in DSEK can also occur because of primary donor endothelial failure but is more often attributed to excessive endothelial cell trauma during the surgical procedure. A recent retrospective case–control study of Asian patients who underwent EK analyzed the risk factors in cases of primary graft failure. The rate of primary graft failure was 4.8% in this study. Significant risk factors associated with primary graft failure included graft insertion using a folding technique and a small donor diameter . In another retrospective analysis , the principal causes of graft failure or regraft within 3 years after EK were immunologic graft rejection (0.6%), endothelial decompensation (1.7%), and unsatisfactory visual or refractive outcome. We also encountered graft rejection in 9.1% of cases in our study. A typical episode of graft rejection after EK resembles the endothelial graft rejection after a conventional penetrating keratoplasty. Rejection rates vary from 0% to 45.5% among reported studies with follow-ups ranging from 3 to 24 months -. Although most graft rejection episodes after EK can be controlled with increased corticosteroid use, some cases can progress to graft failure as seen in our study. In our study, nearly half of the grafts were clear at the last follow-up. The main causes of poor graft survival were primary (n = 4) and late graft failure (n = 4), and advanced glaucoma (n = 2). The reported extrapolated graft survival from 13 reviewed studies at 1 year or beyond after EK ranges from 55% to 100% with an average of 94% graft survival at 1 year. In a recent study, a statistically significant trend toward improvement in visual acuity was reported up to 3 years after endothelial keratoplasty. Limitations of the present study include a retrospective design and small sample size. Also, we do not have data on endothelial cell counts and corneal thickness after EK. Nevertheless, our study presents the long-term follow-up outcomes after EK in Chinese eyes. Similar studies from other centers would be useful in order to compare EK and penetrating keratoplasty over an extended follow-up period. AY: conception and design. RK, VJ: acquisition of data. RK, VJ, LC: analysis and interpretation of data. AY, RK, VJ, LC, SR: drafting the manuscript or revising it critically. AY, RK, VJ, LC, SR: final approval of the manuscript.

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Effect of n-3 polyunsaturated fatty acids on membrane microdomain localization of tight junction proteins in experimental colitis. Ulcerative colitis (UC) is a gastrointestinal disorder characterized by an inflammatory process associated with mucosal damage. Many studies have shown that n-3 polyunsaturated fatty acids (PUFAs) possess anti-inflammatory effects in inflammatory bowel disease. The aim of this study was to investigate whether n-3 PUFAs could alleviate intestinal damage in experimental UC. In the present study, we found that in 2,4,6-trinitrobenzenesulfonic acid-induced colitic rats, the damage to the intestinal mucosa was accompanied by a disrupted tight junction (TJ) structure. In accordance with these changes, the distribution and expression of TJ proteins, including occludin, claudin-1, claudin-3, claudin-5, claudin-8 and ZO-1, in membrane microdomains was altered. The distribution of flotillin-1, a lipid raft marker protein, was also changed. Moreover, we found for the first time that n-3 PUFAs prevented redistribution of TJ proteins from Triton X-100-insoluble raft-like membrane microdomains to Triton X-100-soluble fractions. The expression of ZO-1, claudin-1, claudin-5 and claudin-8 was significantly elevated by n-3 PUFAs. n-3 PUFAs also attenuated the disruption of TJ structure and improved the histological score. Our results demonstrate that the expression and distribution of TJ proteins in TJ membrane microdomains might be affected in UC, and that such altered expression of TJ proteins in membrane microdomains in experimental UC is affected by n-3 PUFAs. These findings may have therapeutic potential in intestinal inflammation.

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Growth hormone treatment increases circulating lipoprotein(a) in children with chronic renal failure. Cardiovascular disease is the major cause of death in chronic renal failure (CRF) patients managed by dialysis or kidney transplantation. Whilst the use of human growth hormone (hGH) is of established benefit in CRF children particularly in those with short stature, in the present study we assessed in CRF children the effect of hGH treatment on circulating lipoprotein(a) [Lp(a)], a genetically determined cardiovascular risk factor. We studied 15 CRF children treated by dialysis or conventional therapy and after kidney transplantation. Overnight fasting blood samples were collected immediately before and after 6 months hGH treatment. In all but one of the children there was a significant increase in serum Lp(a) over the 6 month treatment period -(+)66.7% over the basal levels (range 14 to 180%). After the hGH treatment, in six children Lp(a) levels were elevated to above 300 mg/l, the cut-off level for increased coronary artery disease (CAD) risk. Concomitantly/children also had an increase in serum levels of IGF-I (+96.4%) and insulin (+85.8%). All children had an accelerated growth velocity during the treatment; there was no effect on serum creatinine. Our study shows that hGH treatment in CRF children, though beneficial in its growth promoting effects, increases the already characteristically high levels of serum Lp(a), a risk factor for CAD, and that serum Lp(a) monitoring during treatment with hGH may be useful in evaluating future cardiovascular risk.

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However, a positive pilot trial in children suggests further investigations are desirable.Essential oil terpenes used orally had shown some promise in dissolving small kidney stones in small, uncontrolled trials in adult patients, but these findings were not supported by controlled trials.For more examples of the clinical spasmolytic activity of peppermint oil and its value in irritable bowel syndrome, see the peppermint monograph. Carminatives relax sphincters and assist in the expulsion of intestinal gas. Their activity is somewhat related to spasmolytic activity. Certain essential oils or essential oil-containing herbs have been traditionally used as carminatives over many years. Oils of peppermint, sage and rosemary all relaxed Oddi's sphincter, but peppermint was the most active. The carminative activity of cardamom and dill was confirmed in human studies. However, they were also shown to cause oesophageal reflux and should be used cautiously in susceptible patients. Some essential oils are traditionally regarded as diuretics because they act as 'kidney irritants'. The infusion and essential oil of juniper berries as well as terpinen-4-ol were tested for diuresis response in rats. On initial dosing, all three test substances exhibited an antidiuretic effect, but a significant diuretic effect was established on repeated doses, with the infusion having the strongest effect. The 'irritant' effect of juniper oil on the kidneys was also investigated, since there are concerns in the literature about its long-term use. No nephrotoxic effects were observed in an animal model and the authors suggested that provided high-quality oil is used (distilled from the ripe berries), concerns about the kidney irritant effects of juniper are unfounded. Essential oil terpenes used orally had shown some promise in dissolving small kidney stones in small, uncontrolled trials in adult patients, but these findings were not supported by controlled trials. However, a positive pilot trial in children suggests further investigations are desirable.A proprietary product containing myrtle oil was popularly prescribed by doctors in Germany as an expectorant and mucolytic agent for acute and chronic bronchitis and sinusitis.The oil contains limonene, cineole and alpha-pinene.An expectorant activity for this oil was confirmed in a clinical trial in patients with chronic obstructive airways disease.

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A growing body of evidence indicates that a positive fetal fibronectin (fFN) test in cervical and/or vaginal fluids is associated with preterm delivery both in patients with threatened preterm labor and in symptomatic patients. A negative fFN test identifies patients at very low risk [bib_ref] Fetal fibronectin in cervical and vaginal secretions defines a patient population at..., Lockwood [/bib_ref] [bib_ref] Cervicovaginal fetal fibronectin for the prediction of spontaneous preterm birth in multiple..., Conde-Agudelo [/bib_ref]. A positive fFN test and/or increased cytokine concentrations in cervicovaginal fluid increase the predictive value of cervical ultrasonography to identify patients at risk for preterm delivery [bib_ref] Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness..., Honest [/bib_ref] [bib_ref] Prevention of preterm birth based on short cervix: symptomatic women with preterm..., Ness [/bib_ref] [bib_ref] A systematic review and quality assessment of systematic reviews of fetal fibronectin..., Smith [/bib_ref]. Actim Partus (phosphorylated insulin-like growth factor binding protein 1 -pIGFBP-1) test can be used for estimating the risk of preterm delivery. The test detects pIGFBP-1 in cervical secretions. Similarly to the fFN test, the Actim Partus test has been shown to efficiently rule out the risk of preterm or imminent delivery.

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Fluoroquinolones, and not chloroquine, appear to be the selective force for fluoroquinolone-resistant fecal E. coli in this setting. Rapid evolution to resistance following fluoroquinolone introduction points the need to implement resistant containment strategies when new antibacterials are introduced into resource-poor settings with high infectious disease burdens.

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With this book at hand, all those providing care during paediatric emergencies can be confident in having comprehensive and authoritative guidance on the recognition and management of life threatening conditions necessary to save a child’s life. Sonography of the gastrointestinal tract in fetuses, neonates and children entails no known biological risk, permits serial scanning and can provide information unobtainable with any other imaging modality. This book provides a comprehensive account of the current state of the art regarding sonography in this context. An introductory chapter compares the merits of sonography and magnetic resonance imaging of the fetal gastrointestinal tract. Subsequent chapters focus on the technique, pitfalls and findings in a wide variety of applications, including antropyloric diseases bowel obstruction, bowel wall thickening, colitis, appendicitis, intussusception, some abdominal wall and umbilical abnormalities, intraperitoneal tumors, and trauma. In each case the sonographic morphology is considered in depth with the aid of high-quality illustrations. A concluding chapter comprises a quiz based on 15 case reports. “Gastrointestinal Tract Sonography in Fetuses and Children” will be of value to all with an interest in this field. Winner of the The Writer’s League of Texas Discovery Prize, nonfiction. As a pediatric surgeon, Catherine Musemeche operates on the smallest of human beings, manipulates organs the size of walnuts, and uses sutures as thin as hairs to resolve matters of life or death. Working in the small space of a premature infant’s chest or abdomen allows no margin for error. It is a world rife with emotion and risk. Small takes readers inside this rarefied world of pediatric medicine, where children and newborns undergo surgery to resolve congenital defects or correct the damages caused by accidents and disease. It is an incredibly high-stakes endeavor, nerve-wracking and fascinating. Small: Life and Death on the Front Lines of Pediatric Surgery is a gripping story about a still little-known frontier. In writing about patients and their families, Musemeche recounts the history of the developing field of pediatric surgery—so like adult medicine in many ways, but at the same time utterly different. This is a field guide to the state of the art and science of operating on the smallest human beings, the hurts and maladies that afflict them, and the changing nature of medicine in America today, told by an exceptionally gifted surgeon and writer. Obtain evidence-based information to make timely and accurate diagnoses and treatment decisions. Continuing with this volume, Succinct Pediatrics is an ongoing series covering the entire scope of pediatric medicine. Each volume includes concise chapters with key features and invaluable tables and algorithms—resources health care professionals can use to deliver the highest quality of care. This third volume features 41 topics with key points and detailed therapies in neonatology, genetic and metabolic disorders, neurology, and developmental and behavioral disorders. Evidence-based levels of decision support are also provided throughout the book to provide insight into diagnostic tests and treatment modalities. This book provides readers with a comprehensive evaluation of paediatric radiographs in preparation for the demanding Rapid Reporting component of the Fellowship of the Royal College of Radiologists (FRCR) Part 2B examination, where the margin between pass and fail is very narrow. While other resources may include only a handful of paediatric images in a practice reporting packet, this book is dedicated solely to improving paediatric reporting skill and knowledge. It is designed to address an important deficiency identified in the FRCR Part 2B Examiners’ Report, in that “many candidates struggle with interpretation of paediatric imaging – even for common paediatric pathologies”. The ten practice tests presented, each with 30 images, will assist readers not only in passing the examination but also in the real world when they have to report paediatric radiographs independently. The range of cases covered, from neonate to adolescent, delivers a sound knowledge of both common paediatric fracture patterns and patterns which are subtler but require a definitive answer as to whether they are normal or abnormal. Guidance is also provided on how to describe each abnormality.

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Pendred syndrome is a genetic disorder leading to congenital bilateral (both sides) sensorineural hearing loss and goitre with euthyroid or mild hypothyroidism (decreased thyroid gland function). There is no specific treatment, other than supportive measures for the hearing loss and thyroid hormone supplementation in case of hypothyroidism. It is named after Dr Vaughan Pendred (1869–1946), the British doctor who first described the condition in an Irish family living in Durham in 1896. It accounts for 7.5% to 15% of all cases of congenital deafness. Signs and symptoms The hearing loss of Pendred syndrome is often, although not always, present from birth, and language acquisition may be a significant problem if deafness is severe in childhood. The hearing loss typically worsens over the years, and progression can be step-wise and related to minor head trauma. In some cases, language development worsens after head injury, demonstrating that the inner ear is sensitive to trauma in Pendred syndrome; this is as a consequence of the widened vestibular aqueducts usual in this syndrome. Vestibular function varies in Pendred syndrome and vertigo can be a feature of minor head trauma. A goitre is present in 75% of all cases. Genetics Pendred syndrome is inherited in an autosomal recessive manner, meaning that one would need to inherit an abnormal gene from each parent to develop the condition. This also means that a sibling of a patient with Pendred syndrome has a 25% chance of also having the condition if the parents are unaffected carriers. It has been linked to mutations in the PDS gene, which codes for the pendrin protein (solute carrier family 26, member 4, SLC26A4). The gene is located on the long arm of chromosome 7 (7q31). Mutations in the same gene also cause enlarged vestibular aqueduct syndrome (EVA or EVAS), another congenital cause of deafness; specific mutations are more likely to cause EVAS, while others are more linked with Pendred syndrome. Pathophysiology SLC26A4 can be found in the cochlea (part of the inner ear), thyroid and the kidney. In the kidney, it participates in the secretion of bicarbonate. However, Pendred syndrome is not known to lead to kidney problems. It functions as an iodide/chloride transporter. In the thyroid, this leads to reduced organification of iodine (i.e. its incorporation into thyroid hormone). Diagnosis People with Pendred syndrome present with a hearing loss either at birth or during childhood. The hearing loss is commonly progressive. In early stages it is usually a mixed hearing loss (both conductive and sensorineural hearing loss) because of a third window effect due to the inner ear malformation (widened vestibular aqueducts). A thyroid goitre may be present in the first decade and is usual towards the end of the second decade. MRI scanning of the inner ear usually shows widened or large vestibular aqueducts with enlarged endolymphatic sacs and may show abnormalities of the cochleae that are known as Mondini dysplasia. Genetic testing to identify the pendrin gene usually establishes the diagnosis. If the condition is suspected, a "perchlorate discharge test" is sometimes performed. This test is highly sensitive, but may also be abnormal in other thyroid conditions. If a goitre is present, thyroid function tests are performed to identify mild cases of thyroid dysfunction even if they are not yet causing symptoms. Treatment No specific treatment exists for Pendred syndrome. If thyroid hormone levels are decreased, thyroid hormone supplements may be required. Patients are advised to take precautions against head injury. References External links GeneReviews/NCBI/NIH/UW entry on Pendred Syndrome/DFNB4 NCBI Genes and Diseases Autosomal recessive disorders Membrane transport protein disorders Deafness Syndromes Congenital disorders of endocrine system

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Detection and diagnostic value of serum NSE and S100B protein levels in patients with seizures associated with mild gastroenteritis: A retrospective observational study. Benign convulsions with mild gastroenteritis (CwG) and febrile seizures (FS) associated with mild gastroenteritis are 2 different diseases in the spectrum of seizures associated with mild gastroenteritis. However, specific and useful indicators for the identification of the 2 diseases are lacking. A retrospective analysis was performed to compare the serum neuronal-specific enolase (NSE) and S100B protein levels between patients with these 2 diseases to evaluate the value of NSE and S100B for differential diagnosis between these 2 diseases.The clinical data and NSE and S100B protein levels of 81 children with seizure-associated mild gastroenteritis were collected. According to the axillary temperature at the time of convulsions, all patients were classified into an afebrile seizure (AFS) group, hereafter called the CwG group (n = 46), and a febrile seizure group (FS group, n = 35).The serum NSE level was higher in the CwG group than in the FS group (14.046 (11.095, 19.266) pg/ml and 9.034 (7.158, 12.165) pg/ml, respectively, P < .001); however, the serum S100B protein levels in the CwG and the FS group were not significantly different (P > .05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for NSE was 0.806, P = .000, which was statistically significant. The Youden index was largest (0.605) for a serum NSE cut-off value of 10.460 pg/ml, which yielded a sensitivity and specificity of 89% and 71%, respectively, for prediction of a CwG diagnosis.NSE may contribute to the differential diagnosis of CwG and FS associated with mild gastroenteritis.

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potassium and phosphate, are approaching the upper levels, then the diet can be reassessed and the patient can be informed of ways to moderate intake.Once clients are consuming adequate amounts, if their biochemical levels, e.g.Given the evidence from the international study, it would be worth considering prescribing water-soluble vitamins for those patients who agree to take them, but considerations include adherence and whether increasing the pill burden may have a detrimental effect. People who consume a limited range of foods or those whose weight is being maintained on modular feeds, e.g. fat, glucose and protein supplements, may still benefit from receiving a multivitamin and mineral supplement as opposed to just a water-soluble vitamin. If a multivitamin and mineral supplement is needed, it is wise to avoid ones that provide more than 100% of the recommended daily amount for the various vitamins and minerals, due to the potential risk of toxicity. 19.13 Conclusion It is recommended that all people living with HIV are screened at baseline to determine glomerular filtration rate (GFR) and also have urinalysis to ascertain if the patient is proteinuric. People with a higher risk of developing CKD (i.e. those with diabetes, hypertension or vascular disease, as well as those with a CD4 count <200 and a viral load >4000) should be screened annually. During the early stages of CKD (stages 1–3), potassium and phosphate restriction is not common but good control of diabetes, hypertension and lipid levels can be of benefit to help delay the progression of kidney disease. Clients at stage 4 and 5 renal disease may need dietary advice with regard to electrolyte restriction, i.e. potassium and phosphate, but this is dependent on biochemical levels and also nutritional status. Patients who are struggling to consume adequate amounts may not need dietary restrictions at that stage or may be able to have previous restrictions relaxed until their appetite is resolved. Once clients are consuming adequate amounts, if their biochemical levels, e.g. potassium and phosphate, are approaching the upper levels, then the diet can be reassessed and the patient can be informed of ways to moderate intake.Acknowledgements This chapter was reviewed by Iain Macdougall, Consultant Nephrologist BSc, MD, FRCP, Renal Department, King's College Hospital NHS Foundation Trust and Frank A Post MD PhD FCP(SA), Clinical Senior Lecturer, King's College London, Honorary Consultant Physician, King's College Hospital.References Armstrong KA, Campbell SB, Hawley CM, Johnson DW, Isbel NM.

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One of their chief objectives was to develop diagnostic consultations.Thus, in France in the 2000s, there were three successive national projects for battling Alzheimer's.The number of people afflicted with this illness has increased and public health actions have emphasized the need to improve diagnostics and create screening conditions to detect it earlier and earlier.5 # The MMSE in Practice: the Medical Relationship Reflected through the Administration of a Neuropsychological Test Aude Béliard ## Abstract In the last few decades, Alzheimer's disease has progressively appeared as a new plague and has been constructed as a public health problem in the United States and then in most Western countries including France. The number of people afflicted with this illness has increased and public health actions have emphasized the need to improve diagnostics and create screening conditions to detect it earlier and earlier. Thus, in France in the 2000s, there were three successive national projects for battling Alzheimer's. One of their chief objectives was to develop diagnostic consultations. This diffusion of the diagnosis of Alzheimer's disease and linked diseases was based on the establishment and spread of a number of neuropsychological tests of which the best known and most widely used is the Mini Mental State Examination (MMSE). ### Keywords a priori; Alzheimer's disease; Ambivalence; Cognitive function; Denial; Diagnosis; Interpretation; Reliability In the last few decades, Alzheimer's disease has progressively appeared as a new plague and has been constructed as a public health problem in the United States (Fox 1989; Lyman 1989) and then in most Western countries including France (Ngatcha-Ribert 2007). The number of people afflicted with this illness has increased and public health actions have emphasized the need to improve diagnostics and create screening conditions to detect it earlier and earlier. Thus, in France in the 2000s, there were three successive national projects for battling Alzheimer's. One of their chief objectives was to develop diagnostic consultations.This chapter studies neuropsychological tests with respect to their implementation and uses.

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Abarelix: abarelix-depot-F, abarelix-depot-M, abarelix-L, PPI 149, R 3827. Abarelix [Abarelix-Depot-F, Abarelix-Depot-M, Abarelix-L, PPI 149, R 3827, Plenaxis] is a peptide consisting of natural and artificial amino acids. In females, abarelix is an estrogen production antagonist with potential for the treatment of breast cancer, endometriosis and other reproductive hormone diseases. In males it is a testosterone production antagonist and has potential as hormonal therapy of prostate cancer. Depot formulations of abarelix (abarelix-depot-M and abarelix-depot-F) are being developed for hormonally responsive prostate cancer and endometriosis, respectively. Clinical development of the depot formulations is currently being conducted by Praecis Pharmaceuticals, the originators of the agent. A non-depot formulation, abarelix-L, was also being conducted for prostate gland volume reduction. Praecis Pharmaceuticals has entered into a number of licensing agreements covering abarelix. However, all agreements have since been terminated leaving Praecis to develop and commercialise the agent on its own. The terminated agreements include an agreement between Praecis and Roche for the commercialisation of abarelix in the US. This agreement was terminated in November 1998. Praecis Pharmaceuticals also entered into a collaborative agreement with Amgen in March 1999, whereby the companies would develop abarelix and Amgen would commercialise the drug in the US, Canada, Australia, Asia and several secondary markets. However, in September 2001, Praecis and Amgen announced that they were terminating the agreement for all indications. Praecis stated at the time that it remained committed to developing abarelix for both prostate cancer and endometriosis. Amgen had submitted 'Lotestrol' to the US Patent and Trademarks Office as a possible tradename for abarelix-depot-M. Lotestrol may also have been under consideration as a tradename for abarelix-depot-F. Praecis had also sold European, African, Latin American and Middle Eastern rights to abarelix to Sanofi-Synthélabo. However, in October 2001, Sanofi-Synthélabo announced that it had waived its rights to abarelix. Praecis confirmed in December 2000 that it had filed an NDA seeking FDA approval for abarelix in the US. In January 2001, the FDA granted the abarelix application priority review status. However, in June 2001, the FDA rejected the NDA for prostate cancer. The FDA requested that Praecis use existing data from the completed trials to analyse the allergic reactions that occurred in a small subset of patients. The FDA also expressed concerns over the lack of maintenance of testosterone suppression beyond the 3-month timeframe that occurred in a subset of patients. In February 2003, Praecis announced the re-submission of its NDA to the US FDA. The submission seeks approval for the use of abarelix in a defined subpopulation of advanced prostate cancer patients for whom the current hormonal therapies are not appropriate. Praecis plans to submit its regulatory application in Europe during the second quarter of 2003. Following the completion of a phase I/II trial of abarelix-L in prostate gland volume reduction, a phase IIIb study of the depot formulation was initiated in September 2001. The trial is comparing the effects of neoadjuvant hormonal therapy with depot formulations of leuprorelin or abarelix for prostate gland volume reduction. Abarelix-L is no longer mentioned on Praecis' website, suggesting that development of this formulation is no longer being pursued. The Financial Times (ft.com) reported in May 2001 that approximately 12 new anti-cancer agents are expected to be approved by the FDA through to the end of 2002, with the potential to generate total sales of US dollars 2.6 billion--abarelix is one of these products. The paper quoted analysts at Salomon Smith Barney predicting that abarelix could reach sales of US dollars 120 million for the indication of prostate cancer. However, in June 2001 the FDA rejected Praecis Pharmaceuticale FDA rejected Praecis Pharmaceuticals' NDA filing; this was later re-submitted in February 2003. A year earlier, in May 2000, the Financial Times (ft.com) stated that Credit Suisse First Boston had forecast abarelix to reach peak sales of 1 billion US dollars . Other analysts, at SG Cowen, predicted annual sales of US dollars 200 million for the first 3 years; however, this could increase to 1 billion US dollars if abarelix is also approved for the indication of endometriosis. Abarelix' main competitors at the time were said to be Lupron [TAP Pharmaceuticals], Viadur [Alza] and Zoladex [AstraZeneca].

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However, the inconsistent approach to measurement of anticipatory CIN and CIV and the use of unvalidated instruments preclude the comparison of results across studies. Further, these studies did not directly evaluate the relationship between acute CINV control itself and anticipatory CINV control. The applicability of the results of these studies to patients receiving modern, guideline-informed antiemetic prophylaxis is also unclear. In particular, dexamethasone was often not given to patients receiving highly emetogenic chemotherapy. The guideline development panel members were therefore unsure of the strength of the relationship between anticipatory CINV control and acute CINV control in the setting of modern, guideline-informed antiemetic prophylaxis. Given that anticipatory CINV appears to be a conditioned response, the guideline development panel recommends that the control of acute and delayed CINV be optimized for each child to avoid exposure to the negative stimulus required for conditioning to occur. Adherence to evidence-based guideline recommendations regarding CINV prevention has been shown to substantially improve complete acute CINV control. The guideline development panel therefore recommends that clinicians select antiemetic interventions using guidelines such as the POGO Guideline for the Prevention of Acute AINV in Children Receiving Antineoplastic Agents for chemotherapy agent-naïve patients.

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Do you have an interest in medicine or allied health professions such as physical therapy, occupational therapy, or athletic training? Are you interested in exercise assessment & prescription, nutrition, behavior change, or exercise physiology? If so, the Healthcare & Wellness Career Community will provide you with opportunities to learn about career paths you can take. A variety of career paths are possible for those interested in Healthcare and Wellness. Explore your options below. Click on the links found within each description to connect to the U.S. Bureau of Labor Statistics Occupational Outlook Handbook to dive deeper into each health-related career path and to compare and contrast options. Fitness instructors & personal trainers lead, teach, and motivate individuals or groups in exercise settings. Various settings include commercial fitness centers, corporate wellness programs, community-based centers, hospital-based fitness centers, strength & conditioning programs, and military wellness & recreation programs. They may work with people of all ages and skill levels. Several specialty certifications are available for fitness instructors. Educational level may vary but a minimum of a bachelor’s degree is recommended. Exercise physiologists develop fitness and exercise programs that help patients recover from chronic diseases and improve cardiovascular function. Some exercise physiologists are self-employed while others work for hospitals and healthcare providers to monitor exercise during rehabilitation programs. A minimum of a bachelor’s degree plus certification is recommended for entry-level employment. Some may go on to earn advanced degrees aimed at clinical or human performance research. Physical therapists help injured people improve their movement and manage their pain. Physical therapists often work as part of a team of clinicians in the rehabilitation and treatment of patients with chronic conditions, illnesses, or injuries. Physical therapy requires completion of a Doctor of Physical Therapy (DPT) degree after completing a series of prerequisite courses as part of a bachelor’s degree. Entry level jobs are available as PT aides or PT assistants with associate’s or bachelor’s degrees. Occupational therapists treat patients with illness, injury, or disability to help them regain activities of daily living. They help individuals to develop, recover, and improve these activities. Occupational therapists often work in clinics, hospitals, schools, senior care centers, and home health services. A graduate degree is required to become an occupational therapist after a bachelor’s degree has been completed. Athletic trainers specialize in preventing, diagnosing, and treating muscle and bone injuries and illnesses. Many athletic trainers work in educational settings, such as colleges, universities, and secondary schools. Others work in hospitals, clinics, and with professional sports teams. A graduate degree is now required to become certified as an athletic trainer. Certification is also required after extensive hands-on clinical training. Dietitians and nutritionists specialize in the use of food and nutrition to promote health and manage health conditions. They provide individuals with guidance on what to eat to meet their health-related goals. Dietitians must have a bachelor’s degree, along with the completion of an extensive internship in order to become a registered dietitian. Some in this field focus on nutrition or food science and work in industry using their knowledge of chemistry related to food products.

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Case report of early aseptic loosening of total hip arthroplasty in monostotic paget disease, a diagnostic challenge. Paget's disease of bone is a localised chronic osteopathy which produces bone deformities, bone hypervascularity, structural weakness and altered joint biomechanics. Although radiological diagnosis of Paget's disease of bone is usually straightforward, monostotic cases may potentially raise specific problems which require invasive and expensive procedures such as bone biopsies. The pelvis and upper femur are frequently affected, resulting in disabling hip disease that may require total hip arthroplasty. We report a case of Paget disease of bone in an 84-year-old woman, which was initially identified as avascular necrosis of the hip, reason for which she underwent total hip arthroplasty. During follow up, the patient complained about hip pain and in a few months she was not able to walk because of an early loosening with bone destruction. Radiological and laboratory exams were carried out with normal results except for alkaline phosphatase (AP). After treatment with biphosphonates hip pain relieved but hip reconstruction was not possible. In this paper we present an early aseptic loosening of hip arthroplasty due to monostotic Paget's disease of bone, a rare ethiology of loosening which poses particular diagnostic difficulties prompting an excessive use of excisional biopsies.

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[Acupuncture in the combined treatment of pyelonephritis]. In the treatment of pyelonephritis which continues to cause problems in practical uronephrology, the main efforts of the clinicians are now directed at enhancement of the patients resistance, improvement of renal blood flow and urodynamics. Acupuncture (AP) is thought capable to meet the above requirements. It was used in combined treatment of 102 pyelonephritis cases (51 with acute and 51 with chronic manifestations) showing intact renal function. According to radionuclide renography, a positive trend in the secretion and urodynamics of the upper urinary tract was demonstrable in 50% of the patients. Dynamic nephroscintigraphy reported a positive response in 60% of cases versus 25% in those treated without AP. AP promotion of earlier recovery or remission, reduction of the scope of chemotherapy, good short- and long-term response permit this modality to be recommended for application in urological and nephrological practice.

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The adrenal medulla (innervated by preganglionic sympathetic fibers) is also involved in the regulation of blood flow to skeletal muscles by causing vasoconstriction (via the neurotransmitter norepinephrine, which binds to vasoconstrictor alpha receptors) and some vasodilation (via the neurotransmitter epinephrine, which binds to vasodilator beta receptors) (Guyton, 1991).More specifically, superior and middle cervical ganglia send postganglionic fibers to the head and neck; the stellate (cervicothoracic) ganglion (in conjunction with a small contribution from the middle ganglion and possibly upper thoracic ganglia) supplies the upper extremities; thoracic ganglia supply the trunk; and lower lumbar and upper sacral ganglia furnish postganglionic fibers for the skin of the lower extremities (Jänig, 1990; Standring et al., 2008). Because sympathetic efferents innervate cutaneous effectors covering the entire body, nearly all spinal nerves are likely to contain postganglionic sympathetic fibers. The sympathetic innervation of these cutaneous effectors is controlled primarily by the hypothalamus, and stimulation of these effectors is important for thermoregulation. #### Blood Vessels Supplying Skeletal Muscles During muscle activity, vasodilation (and subsequent increased blood flow) is primarily a result of local muscle tissue effects; for example, decreased oxygen concentration in the contracting muscle causes the release of vasodilator substances. However, sympathetic fibers also innervate these blood vessels, providing continuous vasomotor tone, and when further activated they cause vasoconstriction (sympathetic vasodilator fibers also exist in some lower animals) (Guyton, 1991). The adrenal medulla (innervated by preganglionic sympathetic fibers) is also involved in the regulation of blood flow to skeletal muscles by causing vasoconstriction (via the neurotransmitter norepinephrine, which binds to vasoconstrictor alpha receptors) and some vasodilation (via the neurotransmitter epinephrine, which binds to vasodilator beta receptors) (Guyton, 1991).The axons enter the sympathetic chain ganglia through white rami communicantes and synapse in the stellate (cervicothoracic) ganglion and upper thoracic ganglia.In general, the postganglionic fibers leave the ganglion within gray rami to join spinal nerves and, subsequently, ventral rami destined to form the brachial plexus.

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Travis E. Grotz, M.D., is a surgical oncologist whose clinical and research interest and expertise focuses on minimally invasive approaches to gastrointestinal malignancies as well as the complex multidisciplinary and extended resection of advanced soft tissue sarcomas and gastrointestinal cancers with peritoneal metastasis. His clinical research focuses on optimizing outcomes for cancer patients through both retrospective studies as well as prospective clinical trials. Dr. Grotz's clinical research work focuses on evaluating novel and minimally invasive treatment strategies to improve perioperative outcomes for patients undergoing sarcoma, peritoneal and gastrointestinal surgeries. Specifically, he is looking at optimizing regional chemotherapy for gastrointestinal malignancies with peritoneal metastasis. Through better treatment sequencing, patient selection and novel agents he hopes to improve outcomes for patients treated with intraperitoneal chemotherapy. He also is evaluating the benefits of a minimally invasive surgical approach to both early and advanced gastric cancer patients. Dr. Grotz's translational interests involve incorporating immunotherapy into the complex multidisciplinary treatment of patients with advanced gastrointestinal malignancies. Utilizing patient's own immune system to reduce the cancer tumor burden prior to surgery, or to treat any residual microscopic cancer cells after surgery, or to prevent future recurrences after a complete surgical resection. Significance to patient care Dr. Grotz's research has the potential to assist in the development of novel or improved regional therapeutic treatments and ideal treatment sequencing for various types of cancers. In addition, his work may prevent and minimize postoperative complications in patients undergoing complex sarcoma, peritoneal or gastrointestinal cancer surgery. Regional therapies including HIPEC, isolated limb infusion and isolated limb perfusion.

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Hypothesis: environmental regulation of 5-hydroxymethylcytosine by oxidative stress. Many environmental toxins, such as heavy metals, air particles, and ozone, induce oxidative stress and decrease the levels of NADH and NADPH, cofactors that drive anabolic biochemical reactions and provide reducing capacity to combat oxidative stress. Recently, it was found that the Ten-eleven translocation (TET) protein family members, which oxidize 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in the DNA, is activated under high oxygen conditions by alpha ketoglutarate (α-KG), a cofactor produced by aerobic metabolism in the citric acid cycle. TET, Jumonji-family histone demethylases, and prolyl hydroxylase, a repressor of HIF1α under high oxygen conditions, all require alpha ketoglutarate (α-KG) as cofactors for their activation. The impact of the HIF1α and TET proteins, which appear to have opposing functions, reaches several aspects of human life-including cell growth regulation, embryonic stem cell maintenance, cell differentiation, and tumorigenesis. The role of metabolism on regulating global DNA methylation and chromatin organization is recently demanding greater attention from the biomedical research community. This article will discuss the possible role of TET activation and the regulation of 5-hmC and 5-mC levels in response to environmental stress. We will also discuss how 5-hmC and 5-mC levels at the promoters of specific genes might be a useful biomarker for exposure to environmental toxins.

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"Weekend effect" on stroke mortality revisited: Application of a claims-based stroke severity index in a population-based cohort study. Previous studies have yielded inconsistent results on whether weekend admission is associated with increased mortality after stroke, partly because of differences in case mix. Claims-based studies generally lack sufficient information on disease severity and, thus, suffer from inadequate case-mix adjustment. In this study, we examined the effect of weekend admission on 30-day mortality in patients with ischemic stroke by using a claims-based stroke severity index.This was an observational study using a representative sample of the National Health Insurance claims data linked to the National Death Registry. We identified patients hospitalized for ischemic stroke, and examined the effect of weekend admission on 30-day mortality with vs without adjustment for stroke severity by using multilevel logistic regression analysis adjusting for patient-, physician-, and hospital-related factors. We analyzed 46,007 ischemic stroke admissions, in which weekend admissions accounted for 23.0%. Patients admitted on weekends had significantly higher 30-day mortality (4.9% vs 4.0%, P < 0.001) and stroke severity index (7.8 vs 7.4, P < 0.001) than those admitted on weekdays. In multivariate analysis without adjustment for stroke severity, weekend admission was associated with increased 30-day mortality (odds ratio (OR), 1.20; 95% confidence interval [CI], 1.08-1.34). This association became null after adjustment for stroke severity (OR, 1.07; 95% CI, 0.95-1.20).The "weekend effect" on stroke mortality might be attributed to higher stroke severity in weekend patients. While claims data are useful for examining stroke outcomes, adequate adjustment for stroke severity is warranted.

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[Behavioral effects of febarbamate (MS-543): evaluation by ambulatory activity, active avoidance and passive avoidance in mice]. Febarbamate (MS-543: 100 and 10000 mg/kg, p.o.) neither produced significant change in the mouse's ambulatory activity after the single administration nor modified the ambulation-increasing effects of the following drugs: methamphetamine (2 mg/kg, s.c.), apomorphine (0.5 mg/kg, s.c.) and scopolamine (0.5 mg/kg, s.c.). MS-543 (100 and 1000 mg/kg, p.o.) scarcely affected the established active avoidance response in mice under a discrete shuttle avoidance situation. However, MS-543 (1000 mg/kg, p.o.) tended to enhance the decrease in response and/or avoidance rates induced by chlorpromazine (2 mg/kg, s.c.) and physostigmine (0.2 mg/kg, s.c.). Finally, the disruption of the step-through passive avoidance response induced by pre-training administration of scopolamine (0.5 mg/kg, s.c.) in a one trial task was reduced when MS-543 was administered before the scopolamine administration. However, the post-training administration of MS-543 was without effect on the scopolamine-induced disruption of the avoidance. Furthermore, no significant effect of MS-543 was observed in the multi-trial passive avoidance task. The present results suggest that MS-543 activates cholinergic function and possesses a slight sedative action.

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These cancers are more difficult to detect at an early stage because symptoms are vague and mimic other illnesses; the structures are hidden beneath the liver; and screening tests to detect cancer before symptoms appear are not yet developed. Bile duct tumors are difficult to detect. Dr. Kuvshinoff and the Roswell Park gastrointestinal team have access to a variety of innovative technologies to diagnose and treat these complicated cancers. Liver Function Tests: Higher than normal blood levels of substances made by the liver can indicate liver problems that may be caused by gallbladder or bile duct cancer. Tumor Marker Tests: The amounts of certain substances are measured in samples of blood, urine or tissue. Elevated levels of carcinoembryonic antigen and CA 19-9 are associated with gallbladder and bile duct cancers. Endoscopic Retrograde Cholangiopancreatography (ERCP): This x-ray of the bile ducts can reveal whether gallbladder or bile duct cancer has narrowed or blocked the ducts. A thin, lighted tube (endoscope) is passed through the mouth, esophagus, and stomach into the first part of the small intestine. A smaller tube (catheter) inserted through the endoscope into the bile ducts, delivers dye to the ducts and an x-ray is taken. If ducts are blocked, a fine tube may be inserted to unblock the duct, or placed (as a stent) to keep the duct open. Tissue biopsy may be done during this procedure. Endoscopic Ultrasound (EUS): A thin, lighted tube (endoscope) is passed through the patient's mouth and stomach into the first part of the small intestine. At the tip of the endoscope is an ultrasound device. The doctor slowly withdraws the endoscope from the intestine toward the stomach to make images of the pancreas and surrounding organs and tissues. A biopsy may be taken during this procedure to confirm diagnosis. Percutaneous Transhepatic Cholangiography (PTC): A thin needle inserted through the skin below the ribs injects dye into the liver, and an x-ray is taken. If a blockage is found, a stent in the liver can drain bile into the small intestine or a collection bag outside the body. Ultrasound Exam: High-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. Angiographic Computed Tomography (CT) Scan: A computer linked to an x-ray machine makes a series of very detailed high resolution pictures of areas inside the body, taken from different angles. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. Magnetic Resonance Imaging (MRI): A powerful magnet, radio waves, and a computer combine to make detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI). Magnetic Resonance Cholangiopancreatography (MRCP): MRI imaging where a dye is injected to in the gallbladder area to allow the gallbladder and bile ducts to be better detailed in the image. To create detailed pictures of blood vessels near the gallbladder, the dye may be injected into a vein, called magnetic resonance angiography (MRA). Fine Needle Aspiration (FNA) biopsy: A thin needle inserted into the gallbladder, duct or lymph node during an x-ray or ultrasound to remove a sample of cells or tissue for examination under a microscope to check for signs of cancer. Biopsy may be done during PTC or ERCP. Laparoscopy: Small incisions are made in the abdominal wall and a thin, lighted tube (laparoscope) is inserted to allow the physician to view the gallbladder and ducts, assess nearby tissues, take biopsies or remove tissue or organs.

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Proteomic analysis of excretory secretory products from Clonorchis sinensis adult worms: molecular characterization and serological reactivity of a excretory-secretory antigen-fructose-1,6-bisphosphatase. Clonorchis sinensis is a food-borne zoonotic parasite that resides in bile ducts and causes clonorchiasis, which may result in cholelithiasis, cholecystitis, hepatic fibrosis, and liver tumors. Although total excretory secretory products (ESP) of C. sinensis adults induce hepatic fibrosis in vivo in rats, the causative mechanism is not well understood. To study components of the ESP, C. sinensis culture medium was collected and analyzed using shotgun LC-MS/MS. We identified a total of 110 proteins, including glycometabolic enzymes (such as fructose-1,6-bisphosphatase (FBPase) and enolase), detoxification enzymes (such as glutamate dehydrogenase, dihydrolipoamide dehydrogenase and cathepsin B endopeptidase), and a number of RAB family proteins. To identify a potential causative agent for hepatic fibrosis, we expressed and purified a recombinant FBPase, a 1,041-bp gene product that encodes a 41.7-kDa protein with prototypical FBPase domains and that can form a tetramer with a molecular mass of 166.8 kDa. In addition, we found that FBPase is an antigen present in the ESP and in circulation. Immunofluorescence showed that FBPase localizes to the intestinal cecum and vitellarium in C. sinensis adults. Our results describe the components of the excretory secretory products from C. sinensis adult worms and suggest that FBPase may be an important antigen present in the ESP of C. sinensis and may lay the foundation for additional studies on the development of clonorchiasis-associated hepatic fibrosis.

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* Intermittent, fatigue-induced condition—do not treat surgically.* Surgical treatment—eyelid shortening or radical facelift; necessary for severely affected patients that have chronic ocular irritation.TREATMENT * Supportive care (topical lubricant or antibiotic-containing ointments) and good ocular and facial hygiene—sufficient for most mild disease.* History of bacterial conjunctivitis. CAUSES & RISK FACTORS * Usually secondary to breed-associated alterations in facial conformation and eyelid support. * Marked weight loss or muscle mass loss about the head and orbits—may result in acquired disease. * Tragic facial expression in hypothyroid dogs. * Scarring of the eyelids secondary to injury or after overcorrection of entropion—may result in cicatricial disease. DIAGNOSIS DIFFERENTIAL DIAGNOSIS * Usually clinically obvious. * Look for any underlying disorder in non-predisposed breeds and patients with late-age onset. * Loss of orbital or periorbital mass—may cause condition in patients with masticatory myositis. * Palpebral nerve paralysis—condition associated with lack of muscle tone of the orbicularis oculi muscles. CBC/BIOCHEMISTRY/URINALYSIS N/A OTHER LABORATORY TESTS * Possible masticatory myositis—test for auto-antibodies against type 2M muscle fibers. * Palpebral nerve paralysis or tragic facial expression—consider testing for hypothyroidism. IMAGING N/A DIAGNOSTIC PROCEDURES * Palpebral nerve paralysis—full neurologic evaluation; potential for hypothyroidism. * Secondary conjunctivitis—consider bacterial culture or cytologic examination to help select an appropriate topical antibiotic. * Fluorescein or rose bengal staining of the cornea and conjunctiva—may document corneal ulcerations; may reveal severity of the exposure problem. TREATMENT * Supportive care (topical lubricant or antibiotic-containing ointments) and good ocular and facial hygiene—sufficient for most mild disease. * Surgical treatment—eyelid shortening or radical facelift; necessary for severely affected patients that have chronic ocular irritation. * Intermittent, fatigue-induced condition—do not treat surgically.Neomycin/polymixin B/bacitracin (or others based on bacterial culture and sensitivity) q6–8h.* Lubricant eye drops and ointments—reduce conjunctival and corneal desiccation secondary to exposure.* Hypothyroid and masticatory myositis-induced conditions—may respond well to appropriate medical treatment of the underlying disease.

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Mixed incontinence is very common and occurs when symptoms of both stress and urgency types of incontinence are present. Often, symptoms of one type of incontinence may be more severe than the other. For example, you may have a weak pelvis floor due to childbirth, creating stress urinary incontinence. Sometimes that causes leakage when one laughs or sneezes. When this incontinence is combined with an Overactive Bladder, the best treatment usually addresses the more serious condition. In this case, the weak pelvic floor would be a great place to start treatment. As you might expect, mixed incontinence also shares the causes of both Stress Urinary Incontinence and Urgency Urinary Incontinence. Stress Urinary Incontinence often results when childbirth, pregnancy, sneezing, coughing, or other factors have compromised the muscles that support and control the bladder. This, in turn, causes leakage. Involuntary actions of the bladder muscles creates Urgency Urinary Incontinence. Damage to nerves of the bladder, the nervous system, or muscles themselves are usually the key causes. This damage may be caused by serious health issues including diabetes, MS, Parkinson’s disease, strokes, thyroid problems, and other surgery-related injuries. Your physician will be better able to work with you on the appropriate treatment path based on your diagnosis. To help get a better understanding of what is at the root of your specific incontinence, your doctor may have you keep a diary for a day or more as a record of when you urinate, intentionally or on accident. Your doctor may ask you to record the specific time as well as the amount of urine to provide additional data.

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See also **psychosexual development,** **psychosocial development**.Most children normally outgrow the tendency unless they have severe maladaptive or emotional problems.Toddlers and older children often use biting for expressing aggression toward their parents and other children, especially during play or as a means of gaining attention.Also called [**interproximal film image**. See also **bite wing radiograph**. bite wing radiograph, a dental radiograph that reveals the coronal portions of maxillary and mandibular teeth and portions of the interdental septa on the same film. See also **bite wing film image**. **Bite wing radiograph** _(Bird and Robinson, 2009)_ _Bithynia_ /b thin′ē· /, a genus of snails, species of which act as intermediate hosts to _Opisthorchis._ biting in childhood, a natural behavior trait and reflex action in infants, acquired at about 5 to 6 months of age in response to the introduction of solid foods in the diet and the beginning of the teething process. The activity represents a significant modality in the psychosocial development of the child, because it is the first aggressive action the infant learns, and through it the infant learns to control the environment. The behavior also confronts the infant with one of the first inner conflicts, because biting can produce both pleasing and displeasing results. Biting during breastfeeding causes withdrawal of the nipple and anxiety in the mother, yet it also serves as a means of soothing teething discomfort. Infants continue to use biting as a mechanism for exploring their surroundings. Toddlers and older children often use biting for expressing aggression toward their parents and other children, especially during play or as a means of gaining attention. Most children normally outgrow the tendency unless they have severe maladaptive or emotional problems. See also **psychosexual development,** **psychosocial development**.bitolterol mesylate /bitol′t rol mes′ilāt/, an orally inhaled bronchodilator.INDICATIONS: It is used in the treatment of bronchial asthma and reversible bronchospasm.CONTRAINDICATION: This product is contraindicated in patients who are known to be hypersensitive to it.

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It originates from the calcaneal tubercles, which may be palpable via the anterior aspect of the heel pad.When the toes are maximally dorsiflexed, the plantar aponeurosis is easily palpated along the medial border of the foot, from just distal to the heel pad as far as the first metatarsophalangeal joint.The tendon of extensor hallucis longus can be identified laterally; the tendons of extensor digitorum longus and fibularis tertius are further lateral as they pass deep to the inferior extensor retinaculum and immediately anterior to the lateral part of the distal tibia. More distally, the tendons of extensor digitorum longus and fibularis tertius diverge and may be traced to their insertions. The tendon of tibialis posterior winds posterior to the medial malleolus and then curves anteriorly in the interval between this bony landmark and the sustentaculum tali to reach the tuberosity of the navicular (see Fig. 78.20). The tendon is visible and palpable posterior to the malleolus when the foot is forcibly plantar flexed and inverted. The tendon of flexor digitorum longus lies immediately posterolateral to that of tibialis posterior. It curves forwards inferior to tibialis posterior and lies on the medial aspect of the sustentaculum tali. From there, it passes anteriorly and laterally to the centre of the plantar foot, where it divides into four tendons that pass to the lateral four toes. The tendon of flexor hallucis longus lies inferior to, and grooves, the sustentaculum tali. As it passes towards the great toe, it crosses the line of the flexor digitorum longus opposite the interval between the sustentaculum tali and the tuberosity of the navicular. Abductor hallucis may be seen in some subjects as a fleshy mass along the medial border of the foot, passing from the medial calcaneal tubercle to the first metatarso­phalangeal joint. When the toes are maximally dorsiflexed, the plantar aponeurosis is easily palpated along the medial border of the foot, from just distal to the heel pad as far as the first metatarsophalangeal joint. It originates from the calcaneal tubercles, which may be palpable via the anterior aspect of the heel pad.78.15).The midinguinal point is halfway between the anterior superior iliac spine and the pubic symphysis.The artery normally passes directly anterior to the hip joint; its course may be represented by the upper two-thirds of a line joining its entry point into the thigh with the adductor tubercle, when the thigh is flexed, slightly abducted and rotated laterally.

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In an animal model for Parkinson disease, researchers may resort to directly injuring brain tissue to produce a nigrostriatal dopamine deficiency to mimic the end result of progressive Parkinsonism [23].** Animal models sometimes bypass pathogenesis entirely.Cornelia de Lange syndrome is characterized by structural abnormalities of the face, limb reduction, growth delay, and mental retardation, a phenotype that cannot be replicated in _Drosophila melanogaster_. There are good examples of mouse model orthodiseases (see Glossary item, Orthodisease). Cisd2, a candidate aging-associated gene in humans, causes premature aging and a shortened lifespan in Cisd2-null mice [28]. Xeroderma pigmentosum, complementation group f, which causes photosensitivity and a heightened risk of early skin cancer in humans, can be simulated in mice with an XPF-dependent loss in telomeres. Ligneous conjunctivitis due to plasminogen deficiency in humans can be modeled by a similar conjunctivitis in mice lacking the plasminogen gene [29]. Rare rhabdoid tumors in humans are modeled by INI1-negative rhabdoid tumors in mice [30]. Having an orthodisease does not guarantee experimental success. Zebrafish, an organism popular among developmental biologists, can be infected with mycobacteria. A gene in the zebrafish was shown to modulate its susceptibility to mycobacterial infection 31]. Naturally, there was hope that the orthologous gene in humans would be associated with human susceptibility to tuberculosis. Despite a large study involving 9115 subjects, no such association was found [32]. As we learned in [Chapter 10, the genetic cause of a disease is different from its pathogenesis. **Though a gene mutation may be found in a human disease and its orthodisease, the pathogenesis of the disease (i.e., the cellular events that lead to the clinical expression of disease) may diverge considerably in animals and humans. ** Animal models sometimes bypass pathogenesis entirely. In an animal model for Parkinson disease, researchers may resort to directly injuring brain tissue to produce a nigrostriatal dopamine deficiency to mimic the end result of progressive Parkinsonism [23].When pathogenesis in different species is conserved, orthodiseases may teach us something about the pathogenesis of human disease [33].So far, experience would suggest that this is seldom the case.The same organisms used with great success by developmental biologists may fail miserably as disease response predictors in humans [34].

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A study by Kane and Hobbs [125] demonstrated that resting energy expenditure in CF patients increases as pulmonary disease progresses.Nutritional status is correlated with survival among patients with CF.Disease-specific pulmonary MNSs have also been beneficial for patients with cystic fibrosis (CF).Therefore feeding at 1.5–2.0 times the measured resting energy expenditure is sometimes necessary.A study by Frankfort and associates [122] also suggested that low-carbohydrate/high-fat MNSs may help manage postprandial dyspnea, which is sometimes associated with pulmonary diseases. In addition to the macronutrient distribution, it is also important not to overfeed patients with COPD because excessive energy intake can lead to lipogenesis, which results in large amounts of CO2 production. A study by Talpers _et al._ [124] compared three isocaloric TPN formulas of varying carbohydrate content (40%, 60%, and 75% of energy) in patients with ventilators. There were no differences in CO2 production among the three groups. In a second group of mechanically ventilated patients receiving a TPN formula providing 60% energy from carbohydrate, 20% energy from protein, and 20% energy from fat at varying caloric levels, those who received the highest caloric level (2.0 times the estimated resting energy expenditure) had the highest CO2 production. A similar study by Van den Berg and Stam [123] demonstrated that pulmonary function parameters were significantly better in patients receiving enteral formulas at 1.5 times versus 2.0 times the measured resting energy expenditure. Clinical opinions vary on the most appropriate feeding regimens for patients with COPD. However, studies have demonstrated that high-fat/low-carbohydrate MNSs improve biochemical parameters in COPD patients. While similar results may be achieved by varying the caloric content, it is important to recognize that many patients with COPD are malnourished and would benefit from nutritional repletion. Therefore feeding at 1.5–2.0 times the measured resting energy expenditure is sometimes necessary. Disease-specific pulmonary MNSs have also been beneficial for patients with cystic fibrosis (CF). Nutritional status is correlated with survival among patients with CF. A study by Kane and Hobbs [125] demonstrated that resting energy expenditure in CF patients increases as pulmonary disease progresses.Patients who received the low-carbohydrate/high-fat MNS experienced smaller increases in VCO2, RQ, and minute ventilation.Similar results were also demonstrated when the disease-specific MNS was compared to a medium-carbohydrate and a high-carbohydrate MNS during nighttime enteral feedings [126].

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In this report, the needs for hospitalization and limb amputation increased in proportion to the infection severity.The IDSA classification has the prospective validation result for severity [20].The infection category is very alike with the classification by Infective Disease Society of America (IDSA) (Table 18.2) [10]. The Grade 3 (moderate) DFI is defined as a local infection with erythema >2 cm or involving more deep structures than skin and subcutaneous tissue but not having the systemic inflammatory response sign. The Grade 4 (severe) is the same category of wound as Grade 3, but it has more than two systemic inflammatory responses. Systemic inflammatory responses are composed of (1) body temperature (>38 °C or <36 °C), (2) heart rate (>90 beats/min), (3) respiratory rate (>20 breaths/min or PaCO2 <32 mmHg), and (4) white blood cell count (>12,000 or <4000 cells/μL or 10 % immature (band) form). The IDSA classification has the prospective validation result for severity [20]. In this report, the needs for hospitalization and limb amputation increased in proportion to the infection severity.In the animal model, it has been proven that repetitive trauma without ischemia produces tissue inflammation and progresses to tissue necrosis [1].Abnormal high pressure is essential for the development of ulceration, but high pressure alone is not a direct cause of ulceration [8].Development of diabetic foot ulceration is critically related to peripheral neuropathy [13].

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ANTHONY KALES, M.D.; GILDON N. BEALL, M.D.; RALPH J. BERGER, PH.D.; GUNNAR HEUSER, M.D.; ALLAN JACOBSON, M.D.; JOYCE D. KALES, M.D.; ARTHUR H. PARMELEE JR., M.D.; RICHARD D. WALTER, M.D. Sleep begins with non-rapid eye movement (NREM) phases, and after 60 to 90 min, the first rapid eye movement (REM) period starts; thereafter, REM sleep occurs cyclically at about 90-min intervals. After infancy, the percentage of REM sleep remains relatively stable through life, while total sleep and stage 4 sleep decrease progressively with increasing age. Dream recall is most frequent if subjects are awakened from REM sleep but may also occur after awakening from NREM sleep. During REM sleep, neuronal and metabolic activity and antonomic functions such as heart rate, respirations, and blood pressure are at increased levels, often comparable to those of the waking state. Selective deprivation of REM or stage 4 sleep is followed by compensatory increases in the deprived stage on recovery nights. Total sleep deprivation in man produces on recovery nights an initial increase in stage 4 sleep over base-line levels, followed by increases in REM sleep. Behavioral changes are frequent after prolonged sleep deprivation, while behavioral changes associated with REM deprivation have been varied and subtle. Sleep alterations are induced by most psychotropic drugs; REM sleep is generally suppressed during drug administration and increased after drug withdrawal. Withdrawal of patients addicted to sedatives and antidepressants has produced marked rebound increases in the percentage of REM sleep. These REM sleep changes, together with the observations of nightmares and insomnia after withdrawal, may be significant in the development of dependence to these compounds. Published: Ann Intern Med. 1968;68(5):1078-1104.

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Lidocaine, Ropivacaine, and Dyclonine Compared for Ability to Attenuate Histamine-induced Bronchospasm. To assess the relation between attenuation of histamine-evoked bronchoconstriction and topical anesthesia, Groeben et al. compared the effects of aerosolized lidocaine, ropivacaine, and dyclonine in 15 volunteers with bronchial hyperreactivity. At initial screening visits, lung function measurements were performed, including baseline vital capacity, forced expiratory volume in 1 s, and maximal inspiratory flow at 50% of the vital capacity. Volunteers also underwent inhalational challenge with histamine to confirm bronchial hyperreactivity. On each of 4 study days, baseline lung function was assessed again. In random order, volunteers inhaled lidocaine (4%), ropivacaine (1%), dyclonine (1%), or saline (0.05 ml/kg). Lung function was assessed immediately after inhalation, and then histamine challenges were repeated. To effect the challenge, the team used starting concentrations of histamine diphosphate of 0.075 mg/ml and then trebled that on each subsequent challenge up to a dose of 18 mg/ml. Venous blood also was drawn at 5-min intervals for analysis of plasma concentrations of the anesthetics. At the screening evaluations, the inhaled histamine concentration necessary for a 20% decrease of forced expiratory volume in 1 s was 7.0 ± 5.0 mg/ml. Lidocaine and ropivacaine significantly increased it to 16.1 ± 12.9 and 16.5 ± 13.6 mg/ml, respectively. Despite producing profound topical anesthesia, dyclonine did not attenuate histamine-induced bronchospasm. In addition, dyclonine also might be considered contraindicated even as a topical anesthetic in patients with bronchial hyperreactivity because it also caused significant airway irritation. Although the mechanisms for attenuating histamine-induced bronchospasm are unclear, effects on airway smooth muscle or neural structures may explain partially the effects of lidocaine and ropivacaine seen in this study. Gretchen Henkel; Lidocaine, Ropivacaine, and Dyclonine Compared for Ability to Attenuate Histamine-induced Bronchospasm.. Anesthesiology 2001;94(3):5A-6A.

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The axillary inlet is continuous superiorly with the neck, and the lateral part of the floor opens into the arm.7.40A,B).Formed by the clavicle, the scapula, the upper thoracic wall, the humerus, and related muscles, the axilla is an irregularly shaped pyramidal space with: four sides, an inlet, and a floor (base) (Fig.7.40A).The suprascapular artery normally enters the posterior scapular region superior to the suprascapular foramen, whereas the nerve passes through the foramen. In the posterior scapular region, the vessel runs with the suprascapular nerve. In addition to supplying the supraspinatus and infraspinatus muscles, the suprascapular artery contributes branches to numerous structures along its course. The posterior circumflex humeral artery originates from the third part of the axillary artery in the axilla (Figs. 7.38 and 7.39). The posterior circumflex humeral artery and axillary nerve leave the axilla through the quadrangular space in the posterior wall and enter the posterior scapular region. The vessel supplies the related muscles and the glenohumeral joint. The circumflex scapular artery is a branch of the subscapular artery that also originates from the third part of the axillary artery in the axilla (Figs. 7.38 and 7.39). The circumflex scapular artery leaves the axilla through the triangular space and enters the posterior scapular region, passes through the origin of the teres minor muscle, and forms anastomotic connections with other arteries in the region. Veins in the posterior scapular region generally follow the arteries and connect with vessels in the neck, back, arm, and axilla. The axilla is the gateway to the upper limb, providing an area of transition between the neck and the arm (Fig. 7.40A). Formed by the clavicle, the scapula, the upper thoracic wall, the humerus, and related muscles, the axilla is an irregularly shaped pyramidal space with: four sides, an inlet, and a floor (base) (Fig. 7.40A,B). The axillary inlet is continuous superiorly with the neck, and the lateral part of the floor opens into the arm.7.40C).Apertures formed between muscles in the anterior and posterior walls enable structures to pass between the axilla and immediately adjacent regions (the posterior scapular, pectoral, and deltoid regions).The axillary inlet is oriented in the horizontal plane and is somewhat triangular in shape, with its apex directed laterally (Fig.7.40A,B).

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Henry's law does not carry the same weight in aviation medicine because the degree of change in atmospheric pressure per unit of distance is considerably less than the degree of change in water.Rapid ascent from depth causes the gas to come out of solution within the bloodstream, resulting in decompression sickness.The molecular dispersion seen with increases in gas volume at altitude (Boyle's law) means there is less chance of molecular collision with resulting generation of heat. Charles' law explains why the ambient temperature decreases with increased altitude. ### Dalton's Law Dalton's law states that the total barometric pressure at any given altitude equals the sum of the partial pressures of gases in the mixture ( _P t_ = _P_ 1 \\+ _P_ 2 \\+ _P_ 3... _P n_). Whereas oxygen still constitutes 21% of the atmospheric pressure at altitude, Boyle's law notes that each breath brings fewer oxygen molecules per breath to the lungs, and hypoxia results (Table 191-1). The clinical effect of Dalton's law is manifested as a decrease in arterial oxygen tension with increasing altitude. Table 191-1 Effects of Altitude on Oxygenation _P AO2,_ partial pressure of alveolar oxygen; _Pa CO2,_ partial pressure of arterial carbon dioxide. Initial physiologic responses to hypoxia include tachypnea and tachycardia. With prolonged exposure, oxygen supply to the brain becomes insufficient to support cerebral metabolism. Progressive cerebral hypoxia causes headache, nausea, drowsiness, fatigue, unconsciousness, and death. Although the onset and severity of symptoms may vary with individuals, no one is exempt from the effects of hypoxia. ### Henry's Law Henry's law states that the mass of gas absorbed by a liquid is directly proportional to the partial pressure of the gas above the liquid. Henry's law has its most familiar applications in diving medicine, in which the increased pressure exerted on gases in the body at depth forces the gases into solution in the bloodstream. Rapid ascent from depth causes the gas to come out of solution within the bloodstream, resulting in decompression sickness. Henry's law does not carry the same weight in aviation medicine because the degree of change in atmospheric pressure per unit of distance is considerably less than the degree of change in water.### Additional Stresses of Flight Other stresses of flight that can affect the patient or crew include temperature fluctuations, dehydration, noise, and vibration.Temperature changes may produce increases in metabolic rate and oxygen consumption.As noted, at altitude the moisture per volume of air falls.

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With ulcers, one should not risk drinking alcohol or taking medications for pain that contain aspirin since these medications can accelerate damage to a peptic ulcer.Here is where trouble can begin!Perhaps by evening, to be able to sleep, you take a medication to kill the pain.After 8 to 10 hours of walking or horseback riding, you will definitely be sore.Since red blood cells (needed to carry hemoglobin to transport oxygen), are destroyed at a rate that exceeds the production of new cells in the bone marrow, the overall result is anemia. In this situation, the treatment for spherocytosis is to remove the spleen. Be aware that if the spleen is ruptured, by a severe blow for example, a lot of blood will be lost. This internal bleeding can be critical! When this happens, you can now logically understand its connection with blood and why one bleeds a lot when the spleen is ruptured. Being in an automobile accident or kicked in that area by a horse is a sure way to get into trouble. Due to its position, in the case of an abdominal injury where ribs are broken on the left, the spleen is frequently ruptured as a result of crushing forces. Stomach – The stomach, also located in the LUQ, is situated under the diaphragm. It is a sacklike hollow organ that expands as one fills up on food and drink. It is in the stomach where foods are broken down by gastric juices. Within the stomach, glands that secrete mucus provide the lining with protection from these juices. We can get into trouble when the lining of the stomach is attacked by hydrochloric acid forming a crater called a Peptic Ulcer. This condition becomes particularly dangerous if you are not aware of its presence. Take the activity of a wilderness hike or hunt for example. After 8 to 10 hours of walking or horseback riding, you will definitely be sore. Perhaps by evening, to be able to sleep, you take a medication to kill the pain. Here is where trouble can begin! With ulcers, one should not risk drinking alcohol or taking medications for pain that contain aspirin since these medications can accelerate damage to a peptic ulcer.With time and knowledge, individuals so affected learn to take such medication only with food so to add some protection to the stomach.If you suffer from muscular aches and pains, be careful what you take to alleviate them.Small Intestine – The small intestine has an average length of 22 feet and is found in all four quadrants.

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"First of all your book is the best on the subject.CF.We have devoured your book (good fiber) and refer to it all the time."We have purchased your book and it has helped us more than any other means of information."My husband was diagnosed this year with eye malignant melanoma that has now metastasized on his liver.J.S."I have purchased and read your book with great interest and gratitude, as it is impeccably researched and written." B.P. "Just wanted to let you know that my wife is doing great. She was diagnosed in August with invasive ductal carcinoma, with node involvement. After 4 rounds of chemo her lymph nodes were clean -- 100%! We're pretty sure that the supplements you recommended had a lot to do with her positive outcome. Just wanted to say thank you for all of your books -- they've really been the foundation for her treatment program, and, we feel anyway, the reason for her positive response." G.W. "Thank you for all your help in your terrific book." M.O. "Your book is great. I have survived 6 1/2 years (ovarian cancer stage III) and, with the help of a naturopath, have been taking supplements and taking care with my diet. Your strategies have now been added to my arsenal of defense tools." C.L. "Your book became our nutritional bible in fighting multiple myeloma. The dragon-slayer drink into which we add nutritional supplements has made pill-taking much easier. I am a survivor." R.F. "Your recipes in the book are delicious!" H.M. "Your book was outstanding. I thought I knew a lot, but I learned a lot more from you. I don't expect to "hear" from my own cancer again." E.H. "In August 98 I was diagnosed with testicular cancer. After reading your book I started up a series of changes in my life style. After orchiectomy was done I decided not to go under chemo and followed instead a natural approach. I am doing pretty well. I already had a metastasis in the retroperitoneal area and this tumor has been decreased drastically." J.S. "My husband was diagnosed this year with eye malignant melanoma that has now metastasized on his liver. We have purchased your book and it has helped us more than any other means of information. We have devoured your book (good fiber) and refer to it all the time." CF. "First of all your book is the best on the subject.My wife was diagnosed with Stage 3 breast cancer in December 1999.She feels fantastic and super charged."K.S."I read your book and credit it with helping my 37 year old husband overcome non-hodgkins lymphoma which was misdiagnosed for over 6 months."M.K."...helping me to eat better to prevent a recurrence.Now in my 6' year."S.O.

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An overview of the pathogenic mechanisms involved in severe cases of COVID-19 infection, and the proposal of salicyl-carnosine as a potential drug for its treatment. Multiple organ failure in COVID-19 patients is a serious problem which can result in a fatal outcome. Damage to organs and tissues, including general lung dysfunction, develops as a consequence of ischemia, which, in turn, is caused by thrombosis in small blood vessels and hypoxia, leading to oxidative stress and inflammation. Currently, research is underway to screen existing drugs for antioxidant, antiplatelet and anti-inflammatory properties. Having studied the available publications concerning the mechanisms of damage to tissues and organs of patients with COVID-19, as well as the available treatment strategies, we propose to investigate salicyl-carnosine as a potential drug for treating COVID-19 patients. In a recent study, we described the drug's synthesis procedure, and showed that salicyl-carnosine possesses antioxidant, anti-inflammatory, and antiplatelet effects. Therefore, it can simultaneously act on the three pathogenetic factors involved in tissue and organ damage in COVID-19. Thus, we propose to consider salicyl-carnosine as a potential drug for the treatment of patients with severe cases of COVID-19 infection.

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Interaction with these receptors can be used to treat these tumors as well as to localize NETs by using radiolabeled somatostatin analogues (SRS).Between 80 and 100% of GI-NETs (carcinoids) and pNETs possess sst2, and many also have the other four sst subtypes.Bronchial carcinoids are usually detected by standard chest radiography and assessed by CT. Rectal, duodenal, colonic, and gastric carcinoids are usually detected by GI endoscopy. Because of their wide availability, CT and MRI are generally initially used to determine the location of the primary NETs and the extent of disease. NETs are hyper-vascular tumors, and with both MRI and CT, contrast enhancement is essential for maximal sensitivity, and it is recommended that generally triple-phase scanning be used. The ability of cross-sectional imaging and, to a lesser extent, SRS to detect NETs is a function of NET size. With CT and MRI, <10% of tumors <1 cm in diameter are detected, 30–40% of tumors 1–3 cm are detected, and >50% of tumors >3 cm are detected. Many primary GI-NETs (carcinoids) are small, as are insulinomas and duodenal gastrinomas, and are frequently not detected by cross-sectional imaging, whereas most other pNETs present late in the course of their disease and are large (>4 cm). Selective angiography is more sensitive, localizing 60–90% of all NETs; however, it is now used infrequently. For detecting liver metastases, CT and MRI are more sensitive than ultrasound, and with recent improvements, 5–25% of patients with liver metastases will be missed by CT and/or MRI. pNETs, as well as GI-NETs (carcinoids), frequently (>80%) overexpress high-affinity somatostatin receptors in both the primary tumors and the metastases. Of the five types of somatostatin receptors (sst1–5), radiolabeled octreotide binds with high affinity to sst2 and sst5, has a lower affinity for sst3, and has a very low affinity for sst1 and sst4. Between 80 and 100% of GI-NETs (carcinoids) and pNETs possess sst2, and many also have the other four sst subtypes. Interaction with these receptors can be used to treat these tumors as well as to localize NETs by using radiolabeled somatostatin analogues (SRS).Numerous studies, primarily in Europe, using gallium-68-labeled somatostatin analogues and positron emission tomography (PET) detection, demonstrate even greater sensitivity than with SRS with 111In-labeled somatostatin analogues.Although not yet approved in the United States, there are a number of centers starting to use this approach.

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The medical significance of miniaturised or microscopic biological microarray chips, commonly known as biochips, has caused a revolutionising effect on the global healthcare industry. The global ICT and electronics sector has reaped benefits by incorporating latest scientific research in biochip technology into various medical fields such as bioinformatics or molecular biology. The wide range of biochip applications and products have catapulted the growth of the global biochips market size at a remarkable level. The variable functionality of biochips is considered as a crucial advancement in medical technology. Performing abundant calculations in a few seconds and assessing the gene-decoding data by sending it to a computer quickly are the key features that have led to robust adoption of biochips. The global biochips market value is set to increase at a substantial CAGR through 2020. The principal trend driving the growth of the biochips market is their efficacy in identifying various cancerous diseases. Recent research in biotechnology has proved the gravity of medical benefits deduced by the use of biochips. The most crucial part of its medical approach is detection of cancerous cells and restricting their metastasizing in bloodstreams. The rising adoption of biochips as an integral component of cancer dialysis is inciting the growth of its global market. The influence of digital microfluidic biochips is growing in several biomedical fields, assisting the detection of bioterrorism agents and the analysis of gel-based and plate-based DNA arrays. Biochips are widely used to detect viral and bacterial agents that cause prevalent diseases such as anthrax, plague and smallpox. Detecting malignant cells in the body of a cancer patient helps the diagnosis in cancer treatments. Growth of personalised medicine has increased the demand for electronic biochips used for medical analysis by individual consumers. Less-invasive clinical procedures for installing biochips in the patient’s body are generating higher adoption in global medical organisations. Improving diagnostic methods and lowering expense through technical developments is also driving the demand for biochips. Even though the benefits drawn from biochip use are way more conducive for the market’s growth, there are a handful of compelling factors to limit the expanse of the global biochips market. Lack of proper knowledge about biochip technology is a prominent restraint lowering the demand for biochip products. The irregularities arriving in healthcare coverage around the world are also more likely to challenge the growth of biochips market. Variable cost and adoption of biochip technologies is likely to affect the personalisation of medicine, eventually lowering the revenues of the global biochips market. Companies such as Cepheid Inc., Sigma Aldrich Corp., EMD Milliproe, Calipher Life Sciences Inc. and Agilent Technologies are some of the top players in the global market for biochips. Affymetrix Inc., another leading biochip manufacturer, was the first company to introduce commercial biochips called GeneChips. Redefining strategies involved in location of manufacturing facilities, technology outsourcing, consumer base enhancement, and mergers and alliances have helped shape up the competition in the global biochips market.

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Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer - clinician's insight. Vascular targeted photochemotherapy (VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer (LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory conditions. In this review, methodologic aspects of padoporfin- and padeliporfin-mediated VTP and its clinical application in focal treatment of LPCa as well as future perspective of this method were presented. Physicochemical and pharmacokinetic parameters of padoporphin and padeliporfin using as VTP photosensitizers were described, as well as methodologic question of radiation delivery and dosimetry, and oxygen monitoring in cancer tissue in context of VTP safety and efficiency of LPCa focal therapy were discussed. The results of clinical trials concerning application of padoporfin- and padeliporfin-mediated VTP in LPCa were also presented. The future of VTP is development of protocols, founded on the real-time feedback and rules-based approach to make this strategy a standard procedure in LPCa treatment. To evaluate clinical potential of this procedure, a cost-effectiveness analysis is also necessary.

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Integrated analysis of miRNAs and transcriptomes in Aedes albopictus midgut reveals the differential expression profiles of immune-related genes during dengue virus serotype-2 infection. Mosquito microRNAs (miRNAs) are involved in host-virus interaction, and have been reported to be altered by dengue virus (DENV) infection in Aedes albopictus (Diptera: Culicidae). However, little is known about the molecular mechanisms of Aedes albopictus midgut-the first organ to interact with DENV-involved in its resistance to DENV. Here we used high-throughput sequencing to characterize miRNA and messenger RNA (mRNA) expression patterns in Aedes albopictus midgut in response to dengue virus serotype 2. A total of three miRNAs and 777 mRNAs were identified to be differentially expressed upon DENV infection. For the mRNAs, we identified 198 immune-related genes and 31 of them were differentially expressed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses also showed that the differentially expressed immune-related genes were involved in immune response. Then the differential expression patterns of six immune-related genes and three miRNAs were confirmed by real-time reverse transcription polymerase chain reaction. Furthermore, seven known miRNA-mRNA interaction pairs were identified by aligning our two datasets. These analyses of miRNA and mRNA transcriptomes provide valuable information for uncovering the DENV response genes and provide a basis for future study of the resistance mechanisms in Aedes albopictus midgut.

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Vasopressin Bolus Protocol Compared to Desmopressin (DDAVP) for Managing Acute, Postoperative Central Diabetes Insipidus and Hypovolemic Shock. <i>Introduction</i>. Management of postoperative central diabetes insipidus (DI) can be challenging from changes in volume status and serum sodium levels. We report a case successfully using a dilute vasopressin bolus protocol in managing hypovolemic shock in acute, postoperative, central DI. <i>Case Report</i>. Patient presented after bifrontal decompressive craniotomy for severe traumatic brain injury. He developed increased urine output resulting in hypovolemia and hypernatremia. He was resuscitated with intravenous fluids including a dilute vasopressin bolus protocol. This protocol consisted of 1 unit of vasopressin in 1 liter of 0.45% normal saline. This protocol was given in boluses based on the formula: urine output minus one hundred. Initial serum sodium was 148&#8201;mmol/L, and one-hour urine output was 1 liter. After 48 hours, he transitioned to 1-desamino-8-D-arginine vasopressin (DDAVP). Pre-DDAVP serum sodium was 149&#8201;mmol/L and one-hour urine output 320&#8201;cc. Comparing the bolus protocol to the DDAVP protocol, the average sodium was 143.8 &#177; 3.2 and 149.6 &#177; 3.2&#8201;mmol/L (<i>p</i> = 0.0001), average urine output was 433.2 &#177; 354.4 and 422.3 &#177; 276.0&#8201;cc/hr (<i>p</i> = 0.90), and average specific gravity was 1.019 &#177; 0.009 and 1.016 &#177; 0.01 (<i>p</i> = 0.42), respectively. <i>Conclusion</i>. A protocol using dilute vasopressin bolus can be an alternative for managing acute, central DI postoperatively, particularly in setting of hypovolemic shock resulting in a consistent control of serum sodium.

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Chlorine gas is a pulmonary irritant with intermediate water solubility that causes acute damage in the upper and lower respiratory tract. Occupational exposures constitute the highest risk for serious toxicity from high-concentration chlorine (see the image below). Mixing of chlorine bleach (sodium hypochlorite) with ammonia or acidic cleaning agents is a common source of household exposure. As with all poisons, the dose determines the toxicity. Exposure to low concentrations of chlorine for prolonged periods may have destructive effects, as might very short-term exposure to high concentrations. Chest radiograph of a 36-year-old chemical worker 2 hours postexposure to chlorine inhalant. She had severe resting dyspnea during the second hour, diffuse crackles/rhonchi on auscultation, and a partial pressure of oxygen of 32 mm Hg breathing room air. The radiograph shows diffuse pulmonary edema without significant cardiomegaly. Used with permission from Medical Aspects of Chemical and Biological Warfare, Textbook of Military Medicine. 1997: 256. Symptoms may vary depending on the degree of exposure. Exposure possibilities include acute low levels, acute high levels, and chronic low levels. Abnormalities include hypoxia (from bronchospasm or pulmonary edema) and metabolic acidosis. The metabolic acidosis may be hyperchloremic (nonanion gap). Chest radiograph findings are frequently normal initially but later may show nonspecific abnormalities, pulmonary edema, pneumonitis, mediastinal free air, myocardial depression, or signs of ARDS. Chlorine gas is a pulmonary irritant with intermediate water solubility that causes acute damage in the upper and lower respiratory tract. Chlorine gas was used as a chemical weapon in World War I. Currently, occupational exposures constitute the highest risk for serious toxicity from high-concentration chlorine. Mixing of chlorine bleach (sodium hypochlorite) with ammonia or acidic cleaning agents is a common source of household exposure. See Etiology. The respiratory and mucous membrane irritant effects of chlorine have been well known for many years. John Doughty, a New York City schoolteacher, first suggested use of chlorine gas as a chemical warfare agent during the American Civil War. This proposal was never acted upon during that war. Chlorine gas was officially introduced into the chemical warfare arsenal in 1915 at Ypres, Belgium. Accounts of chlorine attacks at Ypres describe an olive-green cloud rolling over the Allied positions, following the ground contours, and sinking into the trenches. Soldiers seeking safety in those trenches were overcome by the gas and experienced tearing eyes, vomiting, and difficulty breathing. They abandoned their trenches and suffered great losses from artillery and rifle fire. An estimated 93,800 tons of chlorine gas was produced during World War I, with more than half produced by Germany. Total gas casualties in World War I were estimated at almost 1.3 million troops. Of the 70,552 American soldiers poisoned with various gases in World War I, 1843 were exposed to chlorine gas. Chlorine was abandoned as a warfare agent when the use of gas masks was introduced and more effective compounds were created and deployed. Chlorine liquid is presently used in cleaning agents (eg, bleach, disinfectants), in water purification, and in the manufacture of items such as plastics. It is used in the following industries: pesticide, refrigerant, paper and pulp, textile, metallurgy, pharmaceutical, cosmetic, battery, water and sewage purification, and food processing. More than 200 significant industrial accidents involving chlorine have occurred since World War I. The most important aspect of treating patients exposed to chlorine gas is the provision of good supportive care. Provide supplemental oxygen as necessary. Positive pressure ventilation with positive end-expiratory pressure may improve oxygenation in patients with noncardiogenic pulmonary edema. Bronchospasm may require treatment with beta-agonists or other bronchodilators. Other medications that may be used include nebulized sodium bicarbonate and inhaled or systemic corticosteroids. See Treatment. Educate patients on the risks associated with the improper handling of chlorine pool chemicals and the improper mixing of household cleaning chemicals. For patient education resources, see Chemical Warfare, Personal Protective Equipment, and Bronchoscopy. Chlorine is a greenish-yellow, noncombustible gas at room temperature and atmospheric pressure. Prolonged exposure to chlorine gas may occur because its moderate water solubility delays onset of upper airway symptoms for several minutes. In addition, chlorine gas is heavier than air in its pure form, causing it to remain near ground level and increasing exposure time. The immediate effects of chlorine gas toxicity include acute inflammation of the conjunctivae, nose, pharynx, larynx, trachea, and bronchi. Irritation of the airway mucosa leads to local edema secondary to active arterial and capillary hyperemia. Plasma exudation into the alveoli results in pulmonary congestion and edema. The hallmark of pulmonary injury associated with chlorine toxicity is pulmonary edema, manifested clinically as dyspnea, adventitious lung sounds, and hypoxia. Noncardiogenic pulmonary edema is thought to occur when there is a loss of pulmonary capillary integrity, and subsequent transudation of fluid into the alveolus. The onset can occur within minutes or hours, depending upon severity of exposure. Persistent hypoxemia is associated with a higher mortality rate. In animal models of chlorine gas toxicity, immediate respiratory arrest occurs at 2000 ppm, with the lethal concentration for 50% of exposed animals in the range of 800-1000 ppm. Bronchial constriction occurs in the 200-ppm range, with evidence of effects on ciliary activity at exposure levels as low as 18 ppm. With acute exposures of 50 ppm and subacute inhalation as low as 9 ppm, chemical pneumonitis and bronchiolitis obliterans have been noted. Mild focal irritation of the nose and trachea without lower respiratory effects occur at 2 ppm. The eye is rarely damaged severely by chlorine gas toxicity; however, burns and corneal abrasions have occurred. Acids formed by the chlorine gas reaction with the conjunctival mucous membranes are partially buffered by the tear film and the proteins present in tears. Consequently, acid burns to the eye are typically limited to the epithelial and basement membrane, rarely extending to the deep endothelial cells. Acid burns to the periphery of the cornea and conjunctiva often heal uneventfully. Burns to the center of the cornea may lead to corneal ulcer formation and subsequent scarring. Occupational exposures constitute the highest risk for serious exposure to high-concentration chlorine. Other exposures occur during industrial or transportation accidents. Wartime exposure is rare but possible. Household exposure occurs with chlorination tablet accidents during swimming pool maintenance, [17, 18, 19] or with inappropriate mixing of sodium hypochlorite (bleach) cleaning agents with ammonia products, which produces chloramine gas. Typically, this occurs in an enclosed environment such as a restroom. Chlorine gas also may be released in the household by mixing sodium hypochlorite with acidic cleaning agents (toilet bowl cleaners). Internationally, chlorine gas accounts for the largest single cause of major toxic release incidents. Chlorine is used in chemical, paper, and textile industries, along with sewage treatment. In each of these industries, the potential exists for accidental release. Most individuals exposed to chlorine gas recover without significant sequelae. Even exposure to high-concentration chlorine gas is unlikely to result in significant, prolonged pulmonary disease. Morbidity from moderate and severe exposures is typically caused by noncardiogenic pulmonary edema. This may occur within 2-4 hours of exposure to moderate chlorine concentrations (25-50 ppm) and within 30-60 minutes of severe exposures (>50 ppm). In serious exposures, sloughing of the pulmonary mucosa occurs in 3-5 days, and oozing areas become covered with mucopurulent exudate. This chemical pneumonitis is often complicated by secondary bacterial invasion. Although no definite conclusion can be drawn concerning the long-term effects of an acute chlorine gas exposure, findings suggest increased risk of persistent nonspecific airway responsiveness. Furthermore, following an acute exposure, some patients with injured pulmonary epithelium have progressed to develop pulmonary fibrosis. Bronchiolitis obliterans and emphysema have also been described in patients following acute exposures. Hedges JR, Morrissey WL. Acute chlorine gas exposure. JACEP. 1979 Feb. 8(2):59-63. [Medline]. Zaky A, Bradley WE, Lazrak A, Zafar I, Doran S, Ahmad A, et al. Chlorine inhalation-induced myocardial depression and failure. Physiol Rep. 2015 Jun. 3 (6):[Medline]. Gilchrist HL, Matz PB. The residual effects of warfare gases: the use of chlorine gas, with report of cases. Med Bull Vet Adminis. 1933. 9:229-270. Agency for Toxic Substances and Disease Registry. Medical Management Guidelines for Chlorine. Available at http://www.atsdr.cdc.gov/MMG/MMG.asp?id=198&tid=36. Accessed: July 30, 2013. Nelson GD. Chloramines and Bronamines. Kirk RE, Othmer DF, eds. Concise Encyclopedia of Chemical Technology. New York: John Wiley and Sons; 1985. 256. Centers for Disease Control and Prevention. Ocular and respiratory illness associated with an indoor swimming pool--Nebraska, 2006. MMWR Morb Mortal Wkly Rep. 2007 Sep 14. 56(36):929-32. [Medline]. Schwartz DA. Acute inhalational injury. Occup Med. 1987 Apr-Jun. 2(2):297-318. [Medline]. Jones RN, Hughes JM, Glindmeyer H, Weill H. Lung function after acute chlorine exposure. Am Rev Respir Dis. 1986 Dec. 134(6):1190-5. [Medline]. Hayaishi O. Enzymatic hydroxylation. Am Rev Biochem. 1969. 38:21-44. Barrow CS, Alarie Y, Warrick JC, Stock MF. Comparison of the sensory irritation response in mice to chlorine and hydrogen chloride. Arch Environ Health. 1977 Mar-Apr. 32(2):68-76. [Medline]. Henderson Y, Haggard HW. Noxious Gases and the Principles of Respiration Influencing Their Action. 2nd ed. New York: Rienhold Publishing Corp; 1943. 171-3. Das R, Blanc PD. Chlorine gas exposure and the lung: a review. Toxicol Ind Health. 1993 May-Jun. 9(3):439-55. [Medline]. Adelson L, Kaufman J. Fatal chlorine poisoning: report of two cases with clinicopathologic correlation. Am J Clin Pathol. 1971 Oct. 56(4):430-42. [Medline]. Rotman HH, Fliegelman MJ, Moore T, Smith RG, Anglen DM, Kowalski CJ, et al. Effects of low concentrations of chlorine on pulmonary function in humans. J Appl Physiol. 1983 Apr. 54(4):1120-4. [Medline]. D'Alessandro A, Kuschner W, Wong H, Boushey HA, Blanc PD. Exaggerated responses to chlorine inhalation among persons with nonspecific airway hyperreactivity. Chest. 1996 Feb. 109(2):331-7. [Medline]. Shusterman D, Murphy MA, Balmes J. Influence of age, gender, and allergy status on nasal reactivity to inhaled chlorine. Inhal Toxicol. 2003 Oct. 15(12):1179-89. [Medline]. Babu RV, Cardenas V, Sharma G. Acute respiratory distress syndrome from chlorine inhalation during a swimming pool accident: a case report and review of the literature. J Intensive Care Med. 2008 Jul-Aug. 23(4):275-80. [Medline]. Martinez TT, Long C. Explosion risk from swimming pool chlorinators and review of chlorine toxicity. J Toxicol Clin Toxicol. 1995. 33(4):349-54. [Medline]. Wood BR, Colombo JL, Benson BE. Chlorine inhalation toxicity from vapors generated by swimming pool chlorinator tablets. Pediatrics. 1987 Mar. 79(3):427-30. [Medline]. Davis DS, Dewolf GB, Ferland KA, et al. Accidental Release of Air Toxins. Park Ridge, New Jersey: NDC; 1989. 6-9. Van Sickle D, Wenck MA, Belflower A, Drociuk D, Ferdinands J, Holguin F, et al. Acute health effects after exposure to chlorine gas released after a train derailment. Am J Emerg Med. 2009 Jan. 27(1):1-7. [Medline]. Jones R, Wills B, Kang C. Chlorine gas: an evolving hazardous material threat and unconventional weapon. West J Emerg Med. 2010 May. 11(2):151-6. [Medline]. [Full Text]. Department of Homeland Security/Federal Bureau of Investigation. April 23, 2008. Potential Terrorist Attack Methods. Available at http://www.gwu.edu/~nsarchiv/nukevault/ebb388/docs/EBB015.pdf. Accessed: July 30, 2013. Kowitz TA, Reba RC, Parker RT, Spicer WS Jr. Effects of chlorine gas upon respiratory function. Arch Environ Health. 1967 Apr. 14(4):545-58. [Medline]. Weill H, George R, Schwarz M, Ziskind M. Late evaluation of pulmonary function after acute exposure to chlorine gas. Am Rev Respir Dis. 1969 Mar. 99(3):374-9. [Medline]. Kaufman J, Burkons D. Clinical, roentgenologic, and physiologic effects of acute chlorine exposure. Arch Environ Health. 1971 Jul. 23(1):29-34. [Medline]. JONES AT. Noxious gases and fumes. Proc R Soc Med. 1952 Sep. 45(9):609-10. [Medline]. Lawson JJ. Chlorine exposure: a challenge to the physician. Am Fam Physician. 1981 Jan. 23(1):135-8. [Medline]. Shroff CP, Khade MV, Srinivasan M. Respiratory cytopathology in chlorine gas toxicity: a study in 28 subjects. Diagn Cytopathol. 1988 Mar. 4(1):28-32. [Medline]. Malo JL, Cartier A, Boulet LP, L'Archeveque J, Saint-Denis F, Bherer L, et al. Bronchial hyperresponsiveness can improve while spirometry plateaus two to three years after repeated exposure to chlorine causing respiratory symptoms. Am J Respir Crit Care Med. 1994 Oct. 150(4):1142-5. [Medline]. Francis HC, Prys-Picard CO, Fishwick D, Stenton C, Burge PS, Bradshaw LM, et al. Defining and investigating occupational asthma: a consensus approach. Occup Environ Med. 2007 Jun. 64(6):361-5. [Medline]. [Full Text]. Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures. Chest. 1985 Sep. 88(3):376-84. [Medline]. Ginsberg JP, Holbrook JR, Chanda D, Bao H, Svendsen ER. Posttraumatic stress and tendency to panic in the aftermath of the chlorine gas disaster in Graniteville, South Carolina. Soc Psychiatry Psychiatr Epidemiol. 2012 Sep. 47(9):1441-8. [Medline]. [Full Text]. Szerlip HM, Singer I. Hyperchloremic metabolic acidosis after chlorine inhalation. Am J Med. 1984 Sep. 77(3):581-2. [Medline]. Department of Labor: Occupational Safety and Health Administration (OSHA). General description and discussion of the levels of protection and protective gear (1910.120, App B). Available at http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=9767. Accessed: July 30, 2013. Baxter PJ, Davies PC, Murray V. Medical planning for toxic releases into the community: the example of chlorine gas. Br J Ind Med. 1989 Apr. 46(4):277-85. [Medline]. [Full Text]. O'Malley GF, Fasano C, Dominici P, Aguilera E. Eye irrigation is more comfortable with a lidocaine: containing irrigation solution compared with normal saline. J Trauma. 2008 May. 64(5):1360-2. [Medline]. Done AK. The toxic emergency, it's a gas. Emerg Med. 1976. 305-14. Vinsel PJ. Treatment of acute chlorine gas inhalation with nebulized sodium bicarbonate. J Emerg Med. 1990 May-Jun. 8(3):327-9. [Medline]. Cevik Y, Onay M, Akmaz I, Sezigen S. Mass casualties from acute inhalation of chlorine gas. South Med J. 2009 Dec. 102(12):1209-13. [Medline]. Nelson LS. Simple asphyxiants and pulmonary irritants. Goldfrank LR, ed. Goldfrank's Toxicologic Emergencies. 6th ed. Stanford, Conn: Appleton & Lange; 1998. 1523-38. Aslan S, Kandis H, Akgun M, Cakir Z, Inandi T, Görgüner M. The effect of nebulized NaHCO3 treatment on "RADS" due to chlorine gas inhalation. Inhal Toxicol. 2006 Oct. 18(11):895-900. [Medline]. Kramer CG. Chlorine. J Occup Med. 1967 Apr. 9(4):193-6. [Medline]. Chester EH, Kaimal J, Payne CB Jr, Kohn PM. Pulmonary injury following exposure to chlorine gas. Possible beneficial effects of steroid treatment. Chest. 1977 Aug. 72(2):247-50. [Medline]. Akdur O, Sozuer EM, Ikizceli I, Avsarogullari L, Ozturk F, Muhtaroglu S, et al. Experimental inhalation of chlorine gas produced with a different method; effects of N-acetyl cysteine on acute pulmonary damage. Toxicol Mech Methods. 2008 Jan. 18(9):739-43. [Medline]. Fanucchi MV, Bracher A, Doran SF, Squadrito GL, Fernandez S, Postlethwait EM, et al. Post-exposure antioxidant treatment in rats decreases airway hyperplasia and hyperreactivity due to chlorine inhalation. Am J Respir Cell Mol Biol. 2012 May. 46(5):599-606. [Medline]. [Full Text]. Department of Labor: Occupational Safety and Health Administration (OSHA). TABLE Z-1 Limits for Air Contaminants. Available at http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=9992. Accessed: July 30, 2013. Department of Labor: Occupational Safety and Health Administration (OSHA). Occupational Safety and Health Guideline for Chlorine Dioxide. Available at http://www.cdgenvironmental.com/sites/default/files/OHSA_ClO2.pdf. A section from a lung biopsy (hematoxylin and eosin stain; original magnification X 100) from a 36-year-old chemical worker taken 6 weeks postexposure to chlorine. At that time, the patient had no clinical abnormalities and a partial pressure of oxygen of 80 mm Hg breathing room air. The section shows normal lung tissues without evidence of interstitial fibrosis and/or inflammation. Used with permission from Medical Aspects of Chemical and Biological Warfare, Textbook of Military Medicine. 1997: 256.

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## Chapter 9 ## COMPLEMENTARY THERAPIES: ACUPUNCTURE, HYDROTHERAPY, AND THE MIND-BODY CONNECTION _What is acupuncture?_ _How does hydrotherapy fight viruses?_ _How does stress affect my immune system?_ _What is mental imagery?_ ### Acupuncture Time is acupuncture's ally.Melissa's mother called back in one week to joyously explain that Melissa's headaches were gone after five days of taking Scutellaria. The Scutellaria invoked an immune response against the viral infection. Melissa went on to recover nicely after the remedy. #### CASE STUDY 2 A retired judge sought my help with what was diagnosed by his medical doctor as a viral intestinal infection. After vacationing in Mexico, he suffered from severe fatigue, nausea, abdominal cramps, chills, and irritability. Antibiotics didn't work. I prescribed the homeopathic Nux Vomica. This medicine is indicated for intestinal cramps that accompany a flu or viral infection. Two days later, his fatigue, chills, and digestive symptoms were gone. #### CASE STUDY 3 When I first met Tyler, this three-year-old was crying from the pain of a severe ear infection. He had a high fever of 105 degrees Fahrenheit. His face was flushed; he tugged at his right ear; and his pupils were slightly dilated. Based on Tyler's symptoms, I immediately prescribed the homeopathic Belladonna. Within ten minutes, Tyler fell asleep. In twenty minutes, his temperature dropped to 100 degrees. By the next morning, Tyler was up and playing as if nothing had happened. Belladonna is one of the excellent homeopathic medicines for acute infections (viral or bacterial) where there is fever, flushed face, and an intensity of symptoms. ## Chapter 9 ## COMPLEMENTARY THERAPIES: ACUPUNCTURE, HYDROTHERAPY, AND THE MIND-BODY CONNECTION _What is acupuncture?_ _How does hydrotherapy fight viruses?_ _How does stress affect my immune system?_ _What is mental imagery?_ ### Acupuncture Time is acupuncture's ally.By the simplest of definitions, acupuncture is the insertion of very fine needles into specific spots on the skin, with the goal of affecting physiological functioning of the body.The first record of acupuncture dates back 4,700 years, when it was described in the _Huang Di Nei Jing (Yellow Emperor's Classic of Internal Medicine)_ , considered to be the world's oldest medical textbook.

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### Flower Essences Self-Heal and Yarrow Special Formula can serve as the foundational healing agents for a cold.Or sprinkle 5 drops of the formula on a cloth and inhale it directly, 2–3 times an hour when the condition is acute.Inhale with an electric diffusor for 5–10 minutes 6 times a day.### Other Remedies A gentle massage of the baby's abdomen may ease the spasms of colic. ## Common Cold Viral Infection Most people are well acquainted with the symptoms of the respiratory infection known as the common cold: stuffy and runny nose, sneezing, mucus buildup and discharge, watering eyes, headache, perhaps a sore throat and cough. The passages between the nose and the sinuses can become blocked, producing the stuffy, full feeling of sinus congestion. As with other viral infections, if your immune system is strong, you are less likely to catch a cold. A cold can be viewed as a way for the body to expel toxins, waste, and microorganisms that have built up to the point that the immune system cannot handle them normally. For this reason, you should not use a decongestant; it interferes with the body's cleansing process. If you are someone who tends to turn to antibiotics as a solution to infection, be forewarned that antibiotics have no effect on viral infections. Treatment for the common cold should include a protocol of immune support to aid the body in restoring its natural internal balance. ### Essential Oils Antiviral essential oils used in cases of a light cold or at the first sign of a cold coming on can stop a full-blown cold from developing, according to Kurt Schnaubelt, Ph.D., scientific director of the Pacific Institute of Aromatherapy in San Rafael, California. He recommends an inhalation formula of _Eucalyptus radiata_ (5 ml), _Eucalyptus globulus_ (2.5 ml), and Ravensare (2.5 ml) essential oils. Inhale with an electric diffusor for 5–10 minutes 6 times a day. Or sprinkle 5 drops of the formula on a cloth and inhale it directly, 2–3 times an hour when the condition is acute. ### Flower Essences Self-Heal and Yarrow Special Formula can serve as the foundational healing agents for a cold.Self-Heal supports the body's innate healing ability.Yarrow Special Formula strengthens and protects against environmental toxicity and stress.Take 4 drops of each 2–4 times daily, or as needed.### Food Therapy Eat: Garlic, cayenne, horseradish, curry, foods high in vitamin C (see part 3, "Food Therapy," p. 378).Drink plenty of fluids (diluted vegetable juices, soups, herbal tea, green tea).

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The changes in lipid profiles reported in this study would play a key role in the response of Lactobacilli to environmental stress.

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| deaths = | recovery_cases = | fatality_rate = | website = covidmaroc.ma }} The COVID-19 pandemic in Morocco is part of the worldwide pandemic of coronavirus disease 2019 () caused by severe acute respiratory syndrome coronavirus 2 (). The virus was confirmed to have spread to Morocco on 2 March 2020, when the first case COVID-19 case was confirmed in Casablanca. It involved a Moroccan expatriate residing in Bergamo, Italy, who arrived from Italy on 27 February. A second case was confirmed later that same day involving an 89-year-old woman Moroccan residing in Italy who had returned to Morocco on 25 February from Bologna, Italy. As the outbreak widened in Morocco, in mid-March the Government closed schools and suspended international passenger flights. , there have been 676,683 confirmed cases, of which 598,958 have recovered and 10,163 have died. The government officially counts that 14,981,732 citizens have received the first vaccine injection, of whom 10,870,130 have also received the second injection. Background On 12 January 2020, the World Health Organization (WHO) confirmed that a novel coronavirus was the cause of a respiratory illness in a cluster of people in Wuhan, Hubei, China, which was reported to the WHO on 31 December 2019. The case fatality ratio for COVID-19 has been much lower than SARS of 2003, but the transmission has been significantly greater, with a significant total death toll. Model-based simulations for Morocco suggest that the 95% confidence interval for the time-varying reproduction number R t has been stable below 1.0 since November 2020. Timeline First confirmed cases After the two cases confirmed on 2 March 2020, a third case was confirmed on 10 March 2020, a French tourist who arrived in Marrakesh. On the same day, one of the two first cases, a woman aged 89, died. On 11 March 2020, it was announced that the wife and daughter of the French tourist also tested positive, bringing the total cases to 5. That same day, a sixth case was declared in a woman in her sixties that came from France and that presented respiratory troubles on 7 March. On 13 March 2020, two cases were confirmed: a 39-year-old Moroccan man who had returned from Spain and a 64-year-old French woman. The recovery of patient 0 was reported by the Ministry of Health the same day. Subsequent cases March 2020 cases: On 14 March, ten cases were confirmed, including minister Abdelkader Aamara, bringing the total to 18. On 15 March 10 new cases were confirmed to have the virus, bringing the total number of cases to 28. On 16 March, nine cases were confirmed, bringing the total of cases to 37. On 17 March, the second death from the virus was confirmed while a Moroccan man who came from France tested positive. The same day, six new cases were confirmed, bringing the total to 44. On 18 March, ten cases were confirmed, bringing the total to 54. On 19 March, a second recovery was reported and nine new cases were confirmed, bringing the total to 63. On 20 March, a third death was reported and sixteen new cases were confirmed, bringing the total to 79. On 21 March at 00:30, seven new cases were confirmed, bringing the total to 86. The same day at 19:30, a third recovery was reported and ten more cases were confirmed, bringing the total to 96. The third recovery that was reported concerns the 64-year-old French-Senegalese national, who was the sixth recorded case in Morocco. On 22 March at 10:00, eight new cases were confirmed, with four additional cases were confirmed at 12:30 pm and another case at 14:30, bringing the total of positive cases to 109. The same day at 20:30, the fourth death from the virus was reported and six more cases were confirmed, bringing the total to 115. On 23 March at 11:00, seven new cases were confirmed, twelve more cases were confirmed at 12:30, nine additional cases were confirmed and two new recoveries were reported at 18:00, bringing the total of confirmed cases to 143. On 24 March at 18:00, the Ministry of health confirmed a new death bringing the total to 5, a 76-year-old man who returned from the Netherlands and had a chronic illness which weakened his immunity. The remission of an 80-year-old woman in Fquih Ben Salah was confirmed, bringing the total number of recoveries to 6. Twenty-seven new cases were confirmed, bringing the total of confirmed cases to 170. On 25 March, the Ministry of health confirmed a new death bringing the total to 6, a 65 years old person who suffered from chronic illnesses. The recovery of a 69 years old person was confirmed, bringing the total number of recoveries to 7. 55 new cases were confirmed, bringing the total of positive cases to 225. On 26 March, the Ministry of health confirmed four new deaths bringing the total to 10. A new recovery was confirmed, bringing the total number of recoveries to 8. 50 new cases were confirmed, bringing the total of positive cases to 275. On 27 March at 18:00, the Ministry of health confirmed eleven new deaths bringing the total to 21. Three new recoveries were confirmed, bringing the total number of recoveries to 11. 58 new cases were confirmed, bringing the total of positive cases to 333. The same day at 21:00, two additional deaths were reported and twelve new cases were confirmed, bringing the total number of confirmed cases to 345. On 28 March at 8:00, 13 new cases were confirmed, bringing the total of positive cases to 358. The same day at 18:00, the Ministry of health reported the number of confirmed cases as 359 and a new death was confirmed, bringing the total number of deaths to 24. Thirty-one more cases and one death were confirmed at 21:00, bringing the total up to 390 and 25, respectively. At 23:00, twelve new cases and a recovery were confirmed, bringing the total up to 402 and 12, respectively. On 29 March at 8:00, 35 new cases and one death were confirmed, bringing the total up to 437 and 26, respectively. The same day at 13:00, thirteen new cases were confirmed, bringing the total of positive cases to 450. At 18:00, thirteen additional cases were confirmed, bringing the total of confirmed cases to 463. At 21:00, the Ministry of health confirmed sixteen new positive cases, bringing the total to 479 On 30 March at 8:00, 37 new cases and one death were confirmed, bringing the total up to 516 and 27, respectively. The same day at 13:00, two deaths and one recovery were reported, bringing the total to 29 and 14, respectively. The same day at 18:00, the Ministry of health reported the number of confirmed cases as 534. The number of deaths and recoveries was confirmed as 33 and 14, respectively. On 31 March at 8:00, 40 new cases were recorded, bringing the total cases up to 574. The same day at 18:00, 28 new cases, three deaths and 10 recoveries were reported, the Ministry of health reported the number of confirmed cases as 602, the number of deaths as 36 and the number of recoveries 24. At 21:00, 15 new cases were reported making the total number of cases 617. April 2020 cases: On 1 April at 8:00, 21 new cases were confirmed. The same day at 13:00, one death and two recoveries were reported, the total number of deaths and recoveries was confirmed as 37 and 26, respectively. At 18:00, 4 additional new cases were reported. At 21:00, 12 more new cases, two deaths and three recoveries were confirmed bringing the total number of cases to 654. On 2 April at 8:00, 22 new cases were confirmed. The same day at 13:00, one death was reported, the minister of health confirmed the number of deaths and recoveries as 40 and 29, respectively. At 18:00, 4 additional deaths, 1 recovery, 15 new cases were reported. At 21:00, 17 more new cases and one recovery were confirmed bringing the total number of cases to 708, the total number of deaths to 44 and the total number of recoveries to 31. On 3 April at 8:00, 44 new cases, 4 recoveries and 3 deaths were reported. At 11:00, 15 additional recoveries were reported. At 18:00, 3 deaths, 7 recovery and 26 new cases were reported. At 22:00, 30 more new cases, one recovery and one death were confirmed bringing the total number of cases to 791, total number of deaths to 48, total number of recoveries to 57. There were 3,806 new cases in April, raising the total number of cases to 4,423. The death toll rose to 170. The number of recovered patients increased to 984, leaving 3,269 active cases at the end of the month. May 2020 cases: In May there were 3,384 new cases, bringing the total number of cases to 7,807. The death toll rose by 35 to 205. The number of recovered patients increased to 5,459. There were 2,143 active cases at the end of the month. June 2020 cases: On 24 June 2020 at 10:00, 349 new cases and 19 recoveries were reported, bringing the total number of cases and recoveries to 10,693 and 8426, respectively. The same day at 17:00, the Ministry of health reported the number of confirmed cases as 10,907 and the number of recoveries as 8468. There were 4,726 new cases in June, bringing the total number of confirmed cases to 12,533. The death toll rose by 23 to 228. The number of recovered patients increased to 8,920. There were 3,385 active cases at the end of the month. July 2020 cases: There were 11,789 new cases in July, raising the total number of confirmed cases to 24,322. The death toll rose by 125 to 353. The number of recovered patients nearly doubled to 17,658. At the end of the month there were 6,311 active cases. August 2020 cases: There were 38,268 new cases in August, raising the total number of confirmed cases to 62,590. The death toll rose by 788 to 1,141. There were 13,854 active cases at the end of the month. September 2020 cases: There were 58,593 new cases in September, raising the total number of confirmed cases to 121,183. The death toll rose to 2,152. October 2020 cases: There were 97,901 new cases in October, raising the total number of confirmed cases to 219,084. The death toll rose to 3,695. There were 34,114 active cases at the end of the month. November 2020 cases: There were 137,252 new cases in November, raising the total number of confirmed cases to 356,336. The death toll rose to 5,846. There were 45,199 active cases at the end of the month. December 2020 cases As the death toll passes 6,000, the government announces that it plans to vaccinate 80% of its citizens, starting with the Chinese-made Sinopharm BIBP vaccine. There were 82,857 new cases in December, taking the total number of confirmed cases to 439,193. The death toll rose to 7,388. The number of recovered patients increased to 407,504, leaving 24,301 active cases at the end of the month. January 2021 cases Morocco's first confirmed case of the B.1.1.7 variant was reported from Tanger-Med on 18 January. Mass vaccination began on 28 January, initially with 500,000 doses of the Sinopharm BIBP vaccine and two million doses of the Oxford–AstraZeneca vaccine (Covishield). There were 31,964 new cases in January, taking the total number of confirmed cases to 471,157. The death toll rose to 8,275. The number of recovered patients increased to 449,160, leaving 13,722 active cases at the end of the month. February 2021 cases There were 12,497 new cases in February, taking the total number of confirmed cases to 483,654. The death toll rose to 8,623. The number of recovered patients increased to 469,046, leaving 5,985 active cases at the end of the month. March 2021 cases By 14 March the total number of confirmed cases was 489,096, 8,733 deaths and 4,236,386 people have been vaccinated already. In March 2021, Morocco said that it will soon receive more batches of 4.2 million doses of the Sinopharm BIBP and Oxford–AstraZeneca vaccines and Sputnik V. There were 12,443 new cases in March, taking the total number of confirmed cases to 496,097. The death toll rose to 8,818. The number of recovered patients increased to 483,363, leaving 3,916 active cases at the end of the month. More than 4.3 million persons received at least one inoculation from 28 January to 31 March. April 2021 cases By 24 April 2021, the country had 508,530 confirmed cases with 8,983 deaths. On 30 April 2021, Morocco granted Carles Puigdemont asylum. According to a source from the Moroccan foreign ministry, the decision was made in due to "the principle of reciprocity to host the Catalan independence leader" after Sahrawi President Brahim Ghali was allowed to go to Spain to get treated for COVID-19. There were 15,152 new cases in April, taking the total number of confirmed cases to 511,249. The death toll rose to 9,023. The number of recovered patients increased to 497,651, leaving 4,575 active cases at the end of the month. May 2021 cases There were 7,967 new cases in May, taking the total number of confirmed cases to 519,216. The death toll rose to 9,147. The number of recovered patients increased to 507,125, leaving 2,944 active cases at the end of the month. June 2021 cases There were 12,145 new cases in June, taking the total number of confirmed cases to 531,361. The death toll rose to 9,296. The number of recovered patients increased to 517,576, leaving 4,489 active cases at the end of the month. July 2021 cases There were 92,167 new cases in July, raising the total number of confirmed cases to 623,528. The death toll rose to 9,785. The number of recovered patients increased to 561,930, leaving 51,813 active cases at the end of the month. More than 10 million persons received both vaccine doses from 28 January to 31 July. August 2021 cases There were 237,420 new cases in August, raising the total number of confirmed cases to 860,948. The death toll rose to 12,649. The number of recovered patients increased to 793,607, leaving 54,692 active cases at the end of the month. Nearly 15 million persons received both vaccine doses from 28 January to 31 August. September 2021 cases There were 72,123 new cases in September, raising the total number of confirmed cases to 933,071. The death toll rose to 14,267. The number of recovered patients increased to 906,160, leaving 12,644 active cases at the end of the month. More than 19 million persons received both vaccine doses from 28 January to 30 September. October 2021 cases There were 13,074 new cases in October, raising the total number of confirmed cases to 946,145. The death toll rose to 14,668. The number of recovered patients increased to 926,433, leaving 5,044 active cases at the end of the month. More than 22 million persons received both vaccine doses from 28 January to 31 October, with 1,394,802 receiving the third booster shot since the beginning of the month. Responses Transportation On 13 March 2020 the government of Morocco announced they were suspending all passenger flights and ferry crossings to and from Algeria, Spain and France until future notice. On 14 March 2020, the government announced it was suspending flights with an additional 25 countries. By that date, flights had been suspended to/from Algeria, Spain, France, Italy and China. On 15 March 2020, the Moroccan government decided to suspend all international flights, and did not announce an expected date for them to resume. It allowed a minority of flights for foreigners wishing to leave to board before completely shutting down its airports on the 22nd. On 21 June 2020, the government re-opened major airports to serve domestic flights only. On 9 July 2020, the government announced that international flights were to resume, with access only for Moroccans or for foreigners residing within the Kingdom. Incoming passengers were required to bring a COVID-19 test result from their country of departure, issued less than 48 hours of the time of arrival. Moroccans living outside of, or foreigners residing within the Kingdom were allowed to leave the country. On 4 September 2020, the government announced that foreigners who were allowed visa-free entry to Morocco can enter the Kingdom's territory conditionally, either through an invitation or a hotel reservation. Education On 13 March, the government decided to shut down all schools, effective 16 March until further notice. Classes were to be continued either online or through TV, with the use of the SNRT channels for levels of a certain importance, such as the Baccalaureate level. On 11 April, the Ministry of Education announced that tests and exams will take place normally, but later in the year, and admittance to next levels will be based on the same criteria as before, to ensure equity in grades and notes, instead of admitting students based on their grades of the previous semester. On 12 May, the Ministry of Education announced that tests and exams are cancelled for primary and secondary education, while Bac exam will be held in July and first year of Bac will be held in September. Students aren't going back to school until September 2020. State of health emergency A state of health emergency has been in place in Morocco since 20 March 2020. Morocco's Interior Ministry first initially declared it and a subsequent national lockdown on 19 March 2020, to take effect on 20 March 2020 at 6:00 pm local time and to remain in effect until 20 April 2020 with possibility to extend for a longer period. The directive allows for the government to impose restrictions on freedom of movement, which includes curfews and travel restrictions, and other preventative measures. The lockdown required the authorisation of local state officials for citizens to leave their homes, while making exceptions for workers at supermarkets, pharmacies, banks, gas stations, medical clinics, telecommunications companies, and essential freelance jobs. A direct 24-hour hotline was set up to "reinforce direct communication and urge vigilance to fight the impact of the coronavirus pandemic and safeguard the health of citizens." In April 2020, the government pardoned 5,654 prisoners, and it put forward procedures to protect inmates from the COVID-19 outbreak. The state of emergency raised concern from activists and non-governmental organizations, as 91,623 people were prosecuted by 22 May 2020 for crimes which included violating the health emergency law. On 22 March 2020, the Ministry of Culture ordered all print newspapers in the country to suspend production and distribution, and suggested they use alternative methods to do so. On 18 April 2020, the Moroccan government declared the extension of the state of emergency until 20 May. According to an article published in Le Desk on 21 April, the Moroccan government outsourced its quarantine strategy to the Boston Consulting Group. On 18 May 2020, the Moroccan government declared the extension of the state of emergency for another three weeks, until 10 June. On 9 June 2020, the government announced a plan to establish two main zones: The First Zone, composed of 59 prefectures and provinces where the health situation was under control: Oriental region, Béni Mellal-Khénifra region, Drâa-Tafilalet region, Souss-Massa region, Guelmim-Oued Noun region, Laâyoune-Sakia El Hamra region, Dakhla-Oued Ed-Dahab region, M'diq-Fnideq, Tétouan, Fahs-Anjra, Al Hoceima, Chefchaouen, Ouezzane, Meknès, Ifrane, Moulay Yacoub, Sefrou, Boulemane, Taounate, Taza, Khemisset, Sidi Kacem, Sidi Slimane, Settat, Sidi Bennour, Chichaoua, Al Haouz, El Kelâa des Sraghna, Essaouira, Rehamna, Safi and Youssoufia. The Second Zone, composed of 16 prefectures and provinces where the situation was moderately controlled: Tanger-Assilah, Larache, Fez, El Hajeb, Rabat, Salé, Skhirat-Témara, Kénitra, Casablanca, Mohammadia, El Jadida, Nouaceur, Médiouna, Ben Slimane, Berrechid and Marrakech. Note that commercial activities such as cafés, or any sort of event were still prohibited in both zones. The national lockdown was gradually periodically lifted throughout the month of June. In the second half of July 2020, as cases spiked up again (over 10,000 active cases, up from around 200 at the start of the month), the government shifted many regions back to Zone 2, locked down more cities and re-established high-alert quarantine in heavily affected cities. On 21 December 2020, the Moroccan government announced it would impose a nightly curfew, alongside other restrictive measures, to take effect on 23 December as part of its response to the spread of the virus. Initially announced for a three-week period, the measures were gradually extended alongside the state of health emergency. The nightly curfew was extended throughout Ramadan, and was then shortened by four and a half hours on 22 May. A new surge in cases was reported in July 2021, partly due to loose control of health measures in the country, coupled with new variants of the virus, in particular Delta, going from 4,751 cases per day on July 1st to 53,876 on August 1st. This prompted the government to retighten health measures, including increasing the duration of the nightly curfew, banning travel to and from Casablanca, Agadir and Marrakech (with the exception of vaccinated individuals and those with a permit), and enforcing the wearing of masks. On 23 August, the government extended the state of health emergency until 31 October at the earliest, the first time it did so by more than a month. The nightly curfew was reduced by 2 hours starting from 11 pm on 1 October, in response to a decreasing trend of daily cases and amid the ongoing vaccination campaign. It was eventually lifted on 10 November, although the government continues to advise taking precautionary measures. Emergency Fund On 15 March, King Mohammed VI announced the creation of an emergency fund (labelled as Fonds spécial pour la gestion de la pandémie du Coronavirus (Covid-19)) to upgrade health infrastructure and support the worst affected economic sectors. The fund has a volume of 10 billion dirham ($1 billion). Fighting disinformation Some critics of the government have been arrested for allegedly spreading fake news on coronavirus. Ramadan The government announced that being outside shelter between the hours of 8 pm and 6 am during the Muslim holy month of Ramadan (1441 AH / 2020 BCE) (which started on 25 April) is strictly forbidden for any reason except for special cases, such as logistics. Others On 26 March 2020, Saadeddine Othmani, the head of government, announced a country wide hiring stop until the end of the coronavirus crisis. Promotions are also to be postponed until the situation has come under control. The health and security sectors are exempted from this order. On 6 April 2020 (effective the 7th), the government obliged its citizens to wear face masks. The government announced that for the public sector, salaries will be cut by one day for every month for 3 months (March, April and May). On 22 June 2020, the Foreign Minister Nasser Bourita announced the cancellation of the 2020 , the annual travel of about three million Moroccan people from Europe to Morocco during the summer months. Statistics Cumulative number of cases, deaths and recoveries New cases per day Deaths per day Recoveries per day By region See also COVID-19 pandemic in Africa COVID-19 pandemic by country and territory COVID-19 vaccination in Morocco Notes References External links Official website about Covid-19 in Morocco (by Health Ministry) Track of Covid-19 data in Morocco (by Health Ministry – Sehhty agency) Official website for statements about Covid-19 in Morocco (by Interior Ministry) Covid-19 news in Morocco (by Maghreb Agence of Press) Covid-19 data & statistics in Morocco (by 2M) Covid-19 data & statistics in Morocco (by Hespress) Covid-19 data & statistics in Morocco (by Le360) Statistics about Coronavirus pandemic in Morocco Pasteur Institute in Morocco H. Zine, E. M. Lotfi, M. Mahrouf, A. Boukhouima, Y. Aqachmar, K. Hattaf, D. F. M. Torres and N. Yousfi, Modeling the spread of COVID-19 pandemic in Morocco. arXiv:2010.04146, 8 October 2020. H. Zine, A. Boukhouima, E. M. Lotfi, M. Mahrouf, D. F. M. Torres and N. Yousfi, A stochastic time-delayed model for the effectiveness of Moroccan COVID-19 deconfinement strategy, Math. Model. Nat. Phenom. 15 (2020), Art. 50, 14 pp. Morocco Coronavirus pandemic Coronavirus pandemic Morocco Health in Morocco Disease outbreaks in Morocco

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The relationship between intestinal hypoperfusion and serum d-lactate levels during experimental intra-abdominal hypertension. Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) may result from several clinic situations and carries high morbidity and mortality risk, particularly in intensive care unit patients. The clinical spectrum changes from splanchnic hypoperfusion and intestinal ischemia to multiple organ failure. Previous studies demonstrated that serum D-lactate levels may be an early indicator in intestinal ischemia. This study aimed to investigate the relationship between intestinal ischemia and serum D-lactate levels during experimental IAH. Thirty-two male Wistar Albino rats weighing 250+/-50 g were divided into four groups. Three different intra-abdominal pressure (IAP) levels supplied by placement of an intraperitoneal Peritofix catheter and iso-osmotic polyethylene glycol infusion. Each of the IAP levels (15, 20, and 25 mm Hg groups) was checked with the monitor system and fixed for an hour. Control-group animals were not subjected to increased IAP. One hour later, 5-ml blood samples were taken for measurement of serum D-lactate levels and 2-cm intestinal tissue samples were taken 5 cm proximal to the ileocecal valve for histopathologic examination. Elevated serum D-lactate levels were recorded in animals with higher IAP levels. There was a positive correlation between serum D-lactate levels and IAP levels. Histological examinations of the intestinal tissue samples showed no significant pathologic changes in concordance with intestinal ischemia. Serum D-lactate levels may be an early indicator for increased IAP pressure before intestinal ischemic changes occur.

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Our research focuses one side on the molecular and cellular mechanisms underlying physiological adult neurogenesis while addressing on the other the possibility of inducing via cellular reprogramming de novo genesis of neurons in brain areas that are naturally devoid of neurogenesis. Figure 1. Neuronal (ßIII tubulin staining, green) and oligodendroglial (NG2 staining, red) progeny of neural stem cells isolated from the adult subventricular zone (Ortega et al., 2013). Two regions in the mammalian brain are capable of life-long production of new neurons and glia: the subgranular zone (located right under the granule cell layer of the dentate gyrus of the hippocampus) and the subventricular zone bordering the lateral ventricle. Both regions harbor neural stem cells capable of self-renewal as well of producing progeny that differentiates into distinct types of neurons and glia. The latter comprise oligodendroglia which is responsible for the formation of the myelin sheaths enwrapping nerve fibers that degenerate in diseases like multiple sclerosis. We investigate the mode of cell division of neural stem cells and the mechanisms that regulate the decision whether a undifferentiated cell gives rise to neuron or glia (Costa et al., 2011; Ortega et al., 2011). A key question which we study intensely concerns the issue whether one and the same neural stem cell generates both neuron and oligodendroglia. By means of time-lapse videomicroscopy we were able to show that adult subventricular zone neural stem cells in vitro produce either neuronal or oligodendroglial progeny, but never both (Ortega et al., 2013). Moreover, we found that the generation of new oligodendroglia can be selectively enhanced upon stimulation of the Wnt signaling pathway. These findings were fully corroborated in the adult subventricular zone in vivo. This data provide important evidence for the possibility of selectively enhancing oligodendrogliogenesis, thereby opening eventually new avenues for the treatment of diseases like multiple sclerosis. The video shows the lineage progression of a single neural stem cell isolated from the adult subventricular Zone. Another theme of our research concerns the question how newly generated neurons integrate into a pre-existing neural network. Surprisingly, many adult-generated neurons die soon after their birth (for review see (Bergami and Berninger, 2012)). To better understand the process of incorporation of adult-generated neurons into the neuronal circuitry we developed a method which allows for following the establishment of synaptic contacts onto newly generated neurons in vivo over time (Deshpande et al., 2013). Neurons generated in the subgranular zone migrate over short distance into the granular layer where they differentiate in granule neurons. With the help of a modified rabies virus we can examine how the innervation of newly generated granule neurons by their presynaptic partners evolves over time. Using this approach we found that 1-2 weeks after their birth new neurons receive synaptic contacts from neurons of their immediate vicinity, i.e., local interneurons. Only 1-2 weeks later synaptic inputs from more distant brain areas arrive, such as cholinergic input from the medial septum. Finally, only at the end of their maturation process (3-5 weeks) new granule neurons become innervated by pyramidal neurons in the entorhinal cortex and thus form part of the classical trisynaptic hippocampal circuit. The changes in the innervation pattern suggest that during the course of their maturation newly generated neurons exert distinct influences on hippocampal information processing. Figure 2. Tracing of presynaptic innervation of newborn granule neurons in the adult hippocampus. Newly generated granule neurons were labeled by a retrovirus (red). Some of these were subsequently infected by a rabies virus (yellow). Starting from these granule neurons the rabies virus spread over one synapse to presynaptic partners of the new neurons (green) (Deshpande et al., 2013). Within the adult nervous system neurogenesis is a highly restricted phenomenon. Other brain areas such as the cerebral cortex are devoid of ongoing neurogenesis. However, the cerebral cortex is afflicted in many neurodegenerative diseases such as Alzheimer’s Disease and stroke, causing massive neurological deficits. We follow an approach to induce de novo neurogenesis via cellular reprogramming. To this end we introduce transcription factors which are known to play pivotal roles in the generation of neurons during embryonic development into non-neuronal cells using virus-based vectors. Then we examine whether such genetically modified cells adopt neuronal properties. Indeed we could previously show that astroglia isolated from the brain of young mice can be reprogrammed in vitro into excitatory and inhibitory neurons by forced expression of neurogenin-2 (Neurog2) and achaete-scute complex homologue-1 (Ascl1), respectively (Heinrich et al., 2010; Heinrich et al., 2011). In a recent study we succeeded to translate these findings to cells of human origin. Using the two transcription factors Ascl1 and Sox2 we were able to convert brain pericytes, i.e., a cell type tightly associated with the brain microvasculature, into functional induced neurons (Karow et al., 2012). This finding supports our hypothesis that brain resident cells can be recruited towards the de novo genesis of neurons (for review see (Karow and Berninger, 2013)). Based on these studies our current research aims now at converting non-neuronal cells into functional nerve cells directly in the cerebral cortex in situ.

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Neo-nervegenesis in 3D dynamic responsive implant for inguinal hernia repair. Qualitative study. Prosthetic repair of inguinal hernias is one of the most performed surgical procedures. Nevertheless, high rates of complications affect the surgical treatment. Implant fixation, poor-quality tissue ingrowth and mesh shrinkage seem to be involved in postoperative complications, discomfort and chronic pain following inguinal hernia repair. To address these issues a multilamellar shaped 3D dynamic responsive prosthesis has been developed. This new implant, positioned fixation-free to obliterate the hernia opening, thanks its inherent dynamic compliance during inguinal movements, has demonstrated to induce an enhanced biological response. The ingrowth of newly formed muscle fibers, arteries and veins in a surrounding of viable connective tissue could be evidenced into the implant fabric. This appears to be quite different from the fibrotic plaque, typical biologic response of conventional meshes. In addition to myocytes and vessels, newly ingrown nerves have also been detected in the prosthetic structure.

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Later, you move on to alternate walking and jogging, then slow jogging, then up to running, and only then return—cautiously—to speed workouts.First you just walk.Actually, you don't—at least not right away.So how do you start back to running?That's a trick question—the correct answer is that you don't even think about doing track workouts at this point.Occasionally, Mike forgets to wear his orthotics or tries not to use them for a particular race or training run. When he does, the pain comes right back to remind him that running can sometimes literally be a pain in the butt. **SYMPTOMS AND TREATMENT OPTIONS** SCIATICA **YOU MAY HAVE THIS PROBLEM IF YOU EXPERIENCE:** Pain in the lower back Pain in the buttocks Pain that radiates down the thigh to the knee or even the foot _Warning: If you feel pain that radiates below the buttock level, seek immediate medical attention._ **YOUR DOCTOR MAY PRESCRIBE:** Ice Cross-training Orthotics Physical therapy Strengthening exercises Injected or oral anti-inflammatories **HOW YOU CAN HELP PREVENT THIS PROBLEM:** Do hamstring stretch exercises (see description) Do press-ups for flexibility (see description) Do modified situps to strengthen your abdomen (see description) Do reverse situps to strengthen your back (see description) Take care not to strain your back during daily activities ## 22 ## **Training While You Heal** After any injury, you must slowly return to running. How slowly? Much slower than you might think. For instance, say you'd been doing track workouts before your injury at 80 seconds per quarter-mile interval. What pace and distance do you run your first few weeks' back? That's a trick question—the correct answer is that you don't even think about doing track workouts at this point. So how do you start back to running? Actually, you don't—at least not right away. First you just walk. Later, you move on to alternate walking and jogging, then slow jogging, then up to running, and only then return—cautiously—to speed workouts.They have become somewhat lazy and vulnerable.Muscles and bones weaken during disuse.It took time to build them up before your injury, and after you've recovered, it will take time to build them back up so they can take the tremendous forces of running without getting strained or injured.In addition, chances are pretty good that your initial injury has not completely healed.

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Respiratory epithelial ion transport in patients with disseminated bronchiectasis. The nosological limits between disseminated bronchiectasis and cystic fibrosis (CF) remain unclear. In patients with isolated congenital bilateral absence of the vas deferens, a forme fruste of the CF disease, a normal baseline nasal transepithelial potential difference (PD) but an impaired response to pharmacological interventions have been reported. The purpose of the present study was to explore ion transport in respiratory epithelium from patients with disseminated bronchiectasis. The PD under both baseline and pharmacological interventions was investigated in 13 healthy subjects, six patients with genetically proven CF and 15 patients with disseminated bronchiectasis as confirmed by computed tomography scan. Baseline PD was similar in the control and bronchiectasis groups but, as expected, was significantly more negative in the CF group. Patients with bronchiectasis responded to pharmacological tests (sequential perfusion with amiloride, chloride-free solution, isoprenaline and uridine triphosphate (UTP) similarly to healthy subjects. In contrast, CF patients exhibited an increased response to amiloride and an impaired response to chloride-free solution and isoprenaline. The data show that patients with disseminated bronchiectasis exhibit normal electrophysiological properties in their nasal epithelium. Nasal transepithelial potential difference including pharmacological tests may appear a valuable diagnostic procedure for cystic fibrosis with disseminated bronchiectasis.

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Helicobacter pylori strains expressing the vacuolating cytotoxin interrupt phagosome maturation in macrophages by recruiting and retaining TACO (coronin 1) protein. Recent evidence suggests that persistence of Helicobacter pylori can be explained, at least in part, by the failure of macrophages to kill bacteria. The fate of type 1 H. pylori strain LC11, which expresses the cag pathogenicity island (PAI) and the vacuolating cytotoxin, and type 2 strain LC20, which lacks both these virulence factors, was determined following infection of the murine macrophage cell line RAW 264.7 or the human macrophage-like cell line THP-1. Helicobacter pylori strain LC11 displayed enhanced survival in macrophages in comparison with strain LC20 (4.0 +/- 0.2 versus 2.1 +/- 0.6 log CFU ml-1, P < 0.01) at 24 h. Phagosomes containing strain LC11 showed reduced co-localization with LysoTracker Red, higher levels of expression of the early endosome marker EEA1 expression and lower expression of the late endosome/lysosome marker LAMP1 relative to internalized strain LC20, both at 2 h and 24 h. These findings indicate that, in contrast to strain LC20, strain LC11 resides in a compartment with early endosome properties and does not fuse with lysosomes. In addition, phagosomes containing LC11 recruited and retained a higher percentage of TACO (coronin 1) protein in comparison with phagosomes containing strain LC20. Furthermore, IFN-gamma stimulation facilitated maturation of phagosomes containing strain LC11 in association with the release of TACO and a reduction in bacterial survival. We have demonstrated through the use of isogenic cagA-, cagE-/picB- and vacA- mutant strains, that VacA plays a significant role in the interruption of the phagosome maturation. Taken together, these results indicate that, following phagocytosis, H. pylori strains expressing the vacuolating cytotoxin arrest phagosome maturation in association with the retention of TACO.

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Influence of statins on postoperative wound complications after inguinal or ventral herniorrhaphy. The lipid-lowering agents, statins, are the most commonly prescribed class of drugs in the western world. Because of their widespread use, many patients undergo surgical procedures while on statins. Statins, in addition to cholesterol-lowering effects, also have anticoagulant, immunosuppressive, and antiproliferative properties that may affect the risk of local wound complications. This study investigated the relationship between statins and postoperative wound complications in a large cohort of patients undergoing inguinal or ventral hernia repair. Data mining was performed in the Veterans Integrated Service Network (VISN)16 Data Warehouse. This database contains clinical and demographic information about all veterans cared for at the ten VA Medical Centers that comprise the South Central VA Healthcare Network in the mid-south region of the US. Aggregate data (age, body mass index, smoking history, gender, race, history of diabetes, statin use, and postoperative wound complications) were obtained for all patients who underwent inguinal or ventral hernia repair during the period October 1, 1996-November 30, 2004. During the period of the query, 10,782 patients (10,676 male, 106 female), 1,242 (11.5%) of whom received statins, underwent herniorrhaphy. Statin use did not affect the risk of wound infection or delayed wound healing. Statin use was, however, associated with an increased rate of local postoperative bleeding complications (P=0.01). When the type of hernia, age, smoking, diabetes, and body mass index were included in a multivariate analysis, statins remained borderline significant as an independent predictor of wound hematoma/postoperative bleeding (P=0.04), odds ratio 1.6 (95% CI 1.03-2.44). Patients who undergo inguinal herniorrhaphy while on statins have an increased risk of postoperative wound hematoma/hemorrhage. Focus on additional factors that may affect the propensity to postoperative bleeding and on meticulous intraoperative hemostasis are particularly important in such patients.

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* Patients with underlying coagulopathies may need whole blood, frozen plasma, or fresh frozen plasma to replace clotting factors.* May need transfusions (whole blood or packed red blood cells) in patients with severe gastroduodenal hemorrhage.* Severe hypoproteinemic patients may require colloids and/or plasma to increase vascular oncotic pressure.* Abdominal ultrasound can also screen for abnormalities in the pancreas, liver, kidneys, and other abdominal organs as source of hematemesis. * Gastrointestinal scintigraphy, if available, may be used to localize gastrointestinal blood loss. DIAGNOSTIC PROCEDURES * Endoscopy to evaluate the mucosal appearance of the esophagus, stomach, and upper small intestinal tract once extra-gastrointestinal causes are ruled-out. * Biopsy mucosal lesions and submit for histopathology to determine the nature of the underlying gastrointestinal disease. * Abdominocentesis may identify septic peritonitis. * Obtain fine needle aspirates or biopsy specimens of cutaneous or intra-abdominal masses to identify neoplasia/disease. PATHOLOGIC FINDINGS * Gastroduodenal inflammation and hemorrhage. * Ulcers may have more necrosis, microthrombi, and hemorrhage, and deeper penetration than erosions. TREATMENT APPROPRIATE HEALTH CARE * Treat any underlying causes. * Treat on an outpatient basis if the cause is identified and removed, vomiting is not excessive, and gastroduodenal bleeding is minimal. * Inpatients—those with severe gastroduodenal bleeding, ulcer perforation, excessive vomiting, and/or septic peritonitis. NURSING CARE * Intravenous fluids to maintain hydration. * May need aggressive intravenous fluid treatment for shock—crystalloids and/or colloids. * Severe hypoproteinemic patients may require colloids and/or plasma to increase vascular oncotic pressure. * May need transfusions (whole blood or packed red blood cells) in patients with severe gastroduodenal hemorrhage. * Patients with underlying coagulopathies may need whole blood, frozen plasma, or fresh frozen plasma to replace clotting factors.ACTIVITY Restricted DIET * Discontinue oral intake if vomiting.* When feeding is resumed, feed small amounts in multiple feedings.CLIENT EDUCATION * NSAIDs should be administered to pets only under the guidance of a veterinarian.* Administration of NSAIDs can result in gastroduodenal ulcerations and perforations.

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Almost all patients are 50 years of age or older.,,,, Mantle cell lymphoma usually manifests with widespread disease with involvement of lymph nodes and a variety of extranodal sites, and GI involvement is common.The bowel normally harbors hyperplastic lymphoid tissue in the terminal ileum (Peyer patches), but hyperplastic lymphoid tissue in other portions of the intestine, if prominent, may suggest lymphoma. This problem may arise with lymphoid polyps, polypoid lesions composed of reactive lymphoid tissue that may be found in the colon. Large collections of hyperplastic lymphoid tissue may develop in the rectum; these have been referred to as rectal tonsils. These are large, discrete nodules of organized lymphoid tissue with reactive follicles, often showing florid hyperplasia, located in the lamina propria or submucosa. Rectal tonsils may be accompanied by overlying cryptitis, mild architectural distortion, intraepithelial lymphocytes (IELs), and lymphoepithelial lesions, typically without crypt obliteration. In lymphoid follicular proctitis, a condition characterized by congested, nodular mucosa and often associated with rectal bleeding, reactive lymphoid tissue, including lymphoid follicles, is found in the distal portion of the GI tract. Familiarity with these entities and appreciation of the follicular architecture, with large B cells mostly confined to follicles, can help the clinician to avoid overdiagnosis as lymphoma. ## Mantle Cell Lymphoma #### Clinical Features Among lymphomas with involvement of the GI tract at presentation, mantle cell lymphoma is uncommon., Mantle cell lymphoma affects middle-aged or older adults, with a male preponderance. Almost all patients are 50 years of age or older.,,,, Mantle cell lymphoma usually manifests with widespread disease with involvement of lymph nodes and a variety of extranodal sites, and GI involvement is common.This type of lymphoma often takes the form of innumerable polyps, which is termed multiple lymphomatous polyposis; this pattern is particularly prevalent in the intestines.The ileocecal region tends to contain the largest polyps., In some cases, particularly when mantle cell lymphoma involves the stomach, it takes the form of a smaller number of protruded, ulcerated, or fold-thickening lesions.

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The predictive value of early treatment response in antipsychotic-naive patients with first-episode psychosis: Haloperidol versus olanzapine. Early antipsychotic response predicts outcomes for psychotic patients, but recent evidence suggests that this may not be true for patients treated with olanzapine. In this study, we assessed the predictive value of early response to olanzapine or haloperidol in 75 antipsychotic-naive, first-episode psychosis inpatients. Patients were assessed weekly using the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Young Mania Rating Scale (YMRS). Regression analyses were used to determine whether improvement at week 2 or week 3 predicted improvement at hospital discharge. The majority of patients in both groups experienced a decrease in symptom severity of ≥50% at week 2. In the haloperidol group, week 2 improvement predicted improvement at discharge for all measures except the HAM-A. In the olanzapine group, week 2 improvement only predicted improvement at discharge for HAM-D scores. However, week 3 improvement in the olanzapine group predicted improvement at discharge for all measures except the HAM-A. Olanzapine non-responders at week 3 (but not week 2) benefited from having olanzapine switched to another antipsychotic. These results suggest that a 2 week trial of haloperidol is sufficient to predict treatment outcomes, while a 3 week trial is required for olanzapine.

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„Infections are cleared by cellular and humoral immunity“ 1908 Paul Ehrlich: Ehrlich (1908). Über Antigene und Antikörper. Einleitung in „Handbuch der Immunitätsforschung“. P.1 -10 Very nice overview about the knowledge of antibody and antigen in 1908. Any Substance that combines directly after the key-lock principle (→ Emil Fischer, 1894) with B cell receptor or antibodies (→ Paul Ehrlich) or T cell receptors or MHC Immunogen Substance that induces a humoral or T cell-mediated immune response Hapten Antigen that binds to immune receptors but does not induce an immune response Allergen A substance that provokes an allergic reaction Tolerogen A substance that invokes a specific immune non-responsiveness Superantigen A class of antigens that cause non-specific activation of T-cells, resulting in polyclonal T cell activation and massive cytokine release. IMMUNOGEN. A molecule which can elicit the production of specific antibody upon injection into a suitable host. ANTIGEN. A molecule which can be specifically recognized and bound by an antibody. 2-1. DEFINITIONS a. An antigen is traditionally defined as any substance that will cause production of antibodies and which reacts specifically with those antibodies. This term, however, is incomplete because it emphasizes the production of immunoglobulins. Therefore, the term immunogen was introduced to include biological processes involving proliferation of lymphocytes and synthesis of specific substances or recognition molecules which can specifically combine with the inducing antigen. In physiochemical terms, antigens are macromolecules that possess a high degree of internal chemical complexity. They are soluble or easily solubilized by phagocytic cells of the animal and are foreign to the animal. b. A hapten is defined as a small molecule which by itself cannot stimulate antibody synthesis but will combine with the antibody once formed. When the hapten is conjugated to a protein molecule called a carrier, it can elicit an immune response. 2-2. IMMUNOGENICITY Immunogenicity may be defined as that property of a substance (immunogen) that endows it with the capacity to provoke a specific immune response. Antigenicity, on the other hand, is the property of a substance (antigen) that allows it to react with the products of the specific immune response. Substances that are immunogenic are always antigenic, but antigens are not necessarily immunogenic. a. Antigen Factors. (1) Molecular weight. As a general rule, for a molecule to be immunogenic it should have a molecular weight of 10,000 or more. The greater the molecular weight of a substance, the more likely it is to function as an antigen. (2) Molecular complexity. Large molecular size alone is not enough to confer antigenicity on a substance. A molecule must possess a certain degree of chemical complexity; generally, immunogenicity increases with structural complexity. (3) Solubility. Molecules that are insoluble in body fluids and cannot be converted to a soluble form by tissue enzymes are poor antigens. (4) Foreignness. A substance that the body does not recognize as belonging to or being a part of itself. b. Host-Related Factors. (1) Nonspecific factors. The response to a given immunogen is not only a function of the physiochemical properties of the substance, but also is influenced by several host-related factors, including genetic makeup, age, and host environmental and nutritional status. Existing disease in the host may alter immune response capability. (2) Antigen dose and administration route. As a rule, low antigen doses induce the formation of small amounts of antibody with high affinity and specificity. Low doses injected frequently over long periods of time will induce greater response than large doses over a short period of time. The route of antigen administration greatly affects the nature of the immune response. Ehrlich The antotoxic substance inhibits the morbigenic action of the toxin by neutralizing the toxin, combining with the latter to form a compound of a chemical nature which is devoid of toxicity and without action on the organism. According to this theory, the influence of the antitoxin on the toxin is direct, and does not require the intervention of the living cellular protoplasm. Such was also the belief of Prof. Ehrlich. 39 Savante Arrhenius Svante Arrhenius Sweden Nobel Prize Chemistry 1903 Developed theoretical basis for electro- lytic dissociation and chemical reaction → Nobel Prize Chemisty in 1903 The Arrhenius equation: Formuates emperature dependence of the reaction rate constant, and therefore, rate of a chemical reaction. Ehrlich, P (1897). Wertbemessung des Diphterieheilserums - Grundlagen. Klin Jahrb. 6:299 Winau F, Westphal O, Winau R (2004). "Paul Ehrlich--in search of the magic bullet". Microbes Infect. 6 (8): 786–9. Ehrlich and Angelo Knorr demonstrated that neutralization is less rapid in dilute solutions than in concentrated ones. Svante Arrhenius demonstrated the occurrence of limited reactions between antitoxin and toxin analogous to the esterification of an alcohol by an acid, and in such a manner that there always exists, in a mixture of these two substances, a certain quantity of free toxin and antitoxin. the antitoxin inhibits the noxious action of the toxin, even outside the living organism, by uniting with it to form a compound in identically the same manner as when a strong base and a strong acid are brought together. Toxins and Venoms and Their Antibodies. By EM. Pozzi-Eso-T. Authorized Translation by Alfred I. Cohn, Phar.D. i2mo, vii pages. 47 Savante Arrhenius Svante Arrhenius Sweden Nobel Prize Chemistry 1903 Developed theoretical basis for electro- lytic dissociation and chemical reaction → Nobel Prize Chemisty in 1903 The Arrhenius equation: Formuates emperature dependence of the reaction rate constant, and therefore, rate of a chemical reaction. 53 Immunochemistry regarding the chemical description of the immune response, and Many researchers perceived the interaction between toxin (antigen) and antitoxin (antibody) is a chemical reaction Ehrlich: the toxin-antitoxin reaction is not bound to living matter, but can also take place in vitro. 9 Controversy between Arrhenius and Ehrlich, as well as the larger part of the debate within the Karolinska Institute over a Nobel prize to Ehrlich, Ehrlich: Regarded the relationship between toxins and antitoxins as a chemical neutralisation, that is to say, as a definite one-way reaction, Arrhenius looked at it as a reversible process of equilibration, which followed general physical laws. years, eccentric . As head of the Frankfurt Institute for Experimental Therapy he developed a highly demanding and autocratic style of leadership. The crux of the dispute, then, was the nature of the immune response. Focusing on the molecular structure of the immune reactants, Ehrlich claimed that the interaction of toxin and antitoxin implied a high degree of specificity and, thus, resulted in definite chemical bonds. In principle, he presumed the process to be irreversible, although he admitted that, under certain in vitro conditions, it could be reversible. Apart from some remarkable exceptions which will be discussed later, Arrhenius agreed with Ehflich about the pertinent facts; his criticism lay in their appropriate interpretation. Concentrating on the reactants' physical properties, Arrhenius studied the kinetics and stoichiometry of the process and concluded that the reactions in question were similar to those taking place in highly dissociated electrolytes, so that the result of the process were loose, reversible chemical bindings. According to him, the physical laws which underlay chemical reactions in general should also be applied in immunochemistry. As later developments in biochemistry have shown, neither of these standpoints was totally incorrect, and during the following decades the differences between the two positions gradually disappeared. At that time, however, they seemed unsurmountable. Als seine bedeutendste Leistung ist die Ausarbeitung der Grundlagen der elektrolytischen Dissoziation anzusehen. Svante Arrhenius Sweden Nobel Prize Chemistry 1903 in Stockholm) war ein schwedischer Physiker und Chemiker und Nobelpreisträger für Chemie. The Arrhenius equation is a simple, but remarkably accurate, formula for the temperature dependence of the reaction rate constant, and therefore, rate of a chemical reaction. 60 By the mid-1930s, Pauling was beginning to understand that simply knowing the structures of individual proteins was not enough. The essence of life resulted not from individual molecules, but from the interactions between them. How did organisms make offspring that carried their specific characteristics? How did enzymes recognize and bind precisely to specific substrate molecules? How did the body produce antibodies that recognized and bound to specific foreign, invading antigens? How did proteins, these flexible, delicate, complex molecules, have the uncanny ability to recognize and interact with specific molecules? These questions all fell under the heading of biological specificity. To this topic Pauling directed much of his attention during the late 1930s and 1940s. To understand biological specificity, Pauling decided to work first with antibodies and antigens, the understanding of which immunologists such as Karl Landsteiner were beginning to perfect. Pauling met and spoke with Landsteiner on several occasions, and he began his own research program in the late 1930s combining Landsteiner's methods with his own most recent chemical techniques. During a decade of antibody experiments, carried out through the late 1940s, Pauling built a detailed picture of the binding of antibody and antigen at the molecular level. His findings were surprising. Pauling demonstrated that the precise binding of antigen to antibody was accomplished not by typical chemical means, but rather through the shapes of molecules. He discovered that an antibody fits an antigen as a glove fits a hand. Their shapes were complementary. When the fit was tight, the surfaces of antibody and antigen came into very close contact, making possible the formation of many weak bonds that operated at close quarters and were relatively unimportant in traditional chemistry--van der Waals' forces, hydrogen bonds, and so forth. To work, the fit had to be incredibly precise. Even a single atom out of place could significantly affect the binding. Having demonstrated the importance of complementary structure with antibodies, Pauling extended his idea to other biological systems, including the interaction of enzymes with substrates, odors with olfactory receptors, and even the possibility of genes composed of two complementary molecules. Pauling's idea that biological specificity was due in great part to complementary "fitting" of large molecules to one another was essential in the development of molecular biology. The path of his research now formed a broad arc, from early work on the chemical bond as a determinant of molecular structure; through finding out the structures of large molecules, first inorganic substances, then biomolecules; and, finally, to elucidating the interactions between large biomolecules. By the early 1950s, Pauling felt that he had discovered the essentials of life at the molecular level. He was ready for something new. Landsteiner realized that while proteins were immunogenic (capable of inducing an immune response) the lack of structural knowledge of proteins made using them to study the chemical specificity of "serological reactions" impossible. He turned to the use of small molecules which had a defined chemical composition to study antibody specificity. Landsteiner was the first to systematically develop and chart the use of small molecules as probes of antibody recognition. One important observation to come out of Landsteiner's investigations was that small molecules, in of themselves, are not capable of inducing an immune response. To circumvent this, he found that small molecules could be covalently attached to a carrier protein to engender an immune response. These small molecules, called haptens, contained a diazonium group, a functionality that readily forms a covalent bond with surface-bound lysines on a carrier protein. While this diazonium group strategy has been replaced with other methods of covalent linkage, immunization with hapten-carrier protein conjugates is still practiced today to obtain hapten-specific antibodies. One important observation to come out of Landsteiner's investigations was that small molecules, in of themselves, are not capable of inducing an immune response. To circumvent this, he found that small molecules could be covalently attached to a carrier protein to engender an immune response. These small molecules, called haptens, contained a diazonium group, a functionality that readily forms a covalent bond with surface-bound lysines on a carrier protein. While this diazonium group strategy has been replaced with other methods of covalent linkage, immunization with hapten-carrier protein conjugates is still practiced today to obtain hapten-specific antibodies. One important observation to come out of Landsteiner's investigations was that small molecules, in of themselves, are not capable of inducing an immune response. To circumvent this, he found that small molecules could be covalently attached to a carrier protein to engender an immune response. These small molecules, called haptens, contained a diazonium group, a functionality that readily forms a covalent bond with surface-bound lysines on a carrier protein. While this diazonium group strategy has been replaced with other methods of covalent linkage, immunization with hapten-carrier protein conjugates is still practiced today to obtain hapten-specific antibodies. Antisera againts small organic molecules, in of themselves, are not capable of inducing an immune response. To circumvent this, he found that small molecules could be covalently attached to a carrier protein to engender an immune response. These small molecules, called haptens, contained a diazonium group, a functionality that readily forms a covalent bond with surface-bound lysines on a carrier protein. While this diazonium group strategy has been replaced with other methods of covalent linkage, [(a) Erlanger, B. F. In Methods in Enzymology; Academic Press: San Diego, 1980; Vol. 70, pp (b) Brinkley, M. Bioconj. Chem. 1992, 3, 2-13. 22] immunization with hapten-carrier protein conjugates is still practiced today to obtain hapten-specific antibodies. Landsteiner demonstrated that antibodies exhibited regioselective binding behavior R designates the acid groups (COOH or SO3H or AsO3H2) Figure 3. Reproduction of Table 21 taken from reference 21 showing the cross-reactivity between serum derived via immunization with a 3-aminobenzenesulfonic acid hapten and various small molecule (antigen)-protein conjugates. One important observation to come out of Landsteiner's investigations was that small molecules, in of themselves, are not capable of inducing an immune response. To circumvent this, he found that small molecules could be covalently attached to a carrier protein to engender an immune response. These small molecules, called haptens, contained a diazonium group, a functionality that readily forms a covalent bond with surface-bound lysines on a carrier protein. While this diazonium group strategy has been replaced with other methods of covalent linkage, immunization with hapten-carrier protein conjugates is still practiced today to obtain hapten-specific antibodies. Landsteiner realized that while proteins were immunogenic (capable of inducing an immune response) the lack of structural knowledge of proteins made using them to study the chemical specificity of "serological reactions" impossible. He turned to the use of small molecules which had a defined chemical composition to study antibody specificity. Landsteiner was the first to systematically develop and chart the use of small molecules as probes of antibody recognition. 64 serum derived from immunization with 3-aminobenzenesulfonic acid exhibits very limited cross-reactivity with the corresponding ortho and para regioisomers. However, as would be expected, considerable precipitation is observed when the hapten itself is used. These results indicated that shape-selectivity plays a major role in antibody recognition. Figure 3. Reproduction of Table 21 taken from reference 21 (Landsteiner, K. The Specificity of Serological Reactions; Harvard University Press: Cambridge, Massachusetts, 1945, p 156. ) showing the cross-reactivity between serum derived via immunization with a 3-aminobenzenesulfonic acid hapten and various small molecule (antigen)-protein conjugates. R designates the acid groups (COOH or SO3H or AsO3H2) Figure 3. Reproduction of Table 21 taken from reference 21 showing the cross-reactivity between serum derived via immunization with a 3-aminobenzenesulfonic acid hapten and various small molecule (antigen)-protein conjugates. commenced a careful biochemical study of the nature of antitoxins, and after numerous experiments on the fractionation of antitoxic sera reached the conclusion that antitoxins in horse serum are associated with globulins precipitated by half saturation with ammonium sulphate. Michael Heidelberger was the first to apply mathematics to the reaction of antibodies and their antigens (the "precipitin reaction"). Heidelberger's calculations launched decades of research that helped reveal the specificity, function, and origin of antibodies. As early as 1898 with his assistant Tito Carbone he commenced a careful biochemical study of the nature of antitoxins, and after numerous experiments on the fractionation of antitoxic sera reached the conclusion that antitoxins in horse serum are associated with globulins precipitated by half saturation with ammonium sulphate. [Antibody] [Antigen = SSSIII] Heidelberger, M., and KendaIl, F. E. (1929). A QUANTITATIVE STUDY OF THE PRECIPITIN REACTION BETWEEN TYPE III PNEUMOCOCCUS POLYSACCHARIDE AND PURIFIED HOMOLOGOUS ANTIBODY J. Exp. Med., 1929,60, 809. 77 The study of antibodies began in 1890 when Emil von Behring and Kitasato Shibasaburō described antibody activity against diphtheria and tetanus toxins. Behring and Kitasato put forward the theory of humoral immunity, proposing that a mediator in serum could react with a foreign antigen. Their idea prompted Paul Ehrlich to propose the side chain theory for antibody and antigen interaction in 1897, when he hypothesized that receptors (described as “side chains”) on the surface of cells could bind specifically to toxins – in a "lock-and-key" interaction – and that this binding reaction was the trigger for the production of antibodies. Other researchers believed that antibodies existed freely in the blood and, in 1904, Almroth Wright suggested that soluble antibodies coated bacteria to label them for phagocytosis and killing; a process that he named opsoninization. 78 The first use of the term "antibody" occurred in a text by Paul Ehrlich. The term Antikörper (the German word for antibody) appears in the conclusion of his article "Experimental Studies on Immunity", published in October 1891, which states that "if two substances give rise to two different antikörper, then they themselves must be different". However, the term was not accepted immediately and several other terms for antibody were proposed; these included Immunkörper, Amboceptor, Zwischenkörper, substance sensibilisatrice, copula, Desmon, philocytase, fixateur, and Immunisin. The word antibody has formal analogy to the word antitoxin and a similar concept to Immunkörper. 79 In the 1920s, Michael Heidelberger and Oswald Avery observed that antigens could be precipitated by antibodies and went on to show that antibodies were made of protein. The biochemical properties of antigen-antibody binding interactions were examined in more detail in the late 1930s by John Marrack. The next major advance was in the 1940s, when Linus Pauling confirmed the lock-and-key theory proposed by Ehrlich by showing that the interactions between antibodies and antigens depended more on their shape than their chemical composition. In 1948, Astrid Fagreaus discovered that B cells, in the form of plasma cells, were responsible for generating antibodies. 80 Further work concentrated on characterizing the structures of the antibody proteins. A major advance in these structural studies was the discovery in the early 1960s by Gerald Edelman and Joseph Gally of the antibody light chain, and their realization that this protein was the same as the Bence-Jones protein described in 1845 by Henry Bence Jones. Edelman went on to discover that antibodies are composed of disulfide bond-linked heavy and light chains. Around the same time, antibody-binding (Fab) and antibody tail (Fc) regions of IgG were characterized by Rodney Porter. Together, these scientists deduced the structure and complete amino acid sequence of IgG, a feat for which they were jointly awarded the 1972 Nobel Prize in Physiology or Medicine. The Fv fragment was prepared and characterized by David Givol. While most of these early studies focused on IgM and IgG, other immunoglobulin isotypes were identified in the 1960s: Thomas Tomasi discovered secretory antibody (IgA) and David S. Rowe and John L. Fahey identified IgD, and IgE was identified by Kikishige Ishizaka and Teruki Ishizaka as a class of antibodies involved in allergic reactions. 81 Genetic studies identifying the basis of the vast diversity of these antibody proteins when somatic recombination of immunoglobulin genes was by Susumu Tonegawa in 1976. 82 The concept of the idiotype of immunoglobulins emerged in the early 1960s from two different approaches, one by Oudin with rabbit antibodies, the other by Kunkel and analysis of the immunochemical characteristics of human myeloma proteins. At the time, Oudin had described the allotypic specificities as defining antigenic characteristics of a group of individuals within a given animal species. This was observed for rabbit immunoglobulins and was the consequence of allelic variants of both the heavy and light chains. It was then found that when rabbit antibodies prepared against Salmonella typhi were injected into another rabbit expressing the same (known) allotypes, they induced the synthesis of antibodies that specifically recognized the anti-Salmonella antibodies raised in the first rabbit. It was also shown that they did not react with normal rabbit serum taken before the Salmonella injection, thereby excluding that they identified a new allotypic specificity. Idiotypic specificities were thus defined as antigenic specificities characteristic of one antibody (the idiotype) produced by one animal and specific for one given antigen. Antibodies produced by the second animal were termed anti-idiotypic antibodies. Idiotypes are also referred to as Ab1 while anti-idiotypes are referred to as Ab2, in a simplified nomenclature. At the same time, Kunkel was comparing the immunochemical characteristics of human myeloma proteins with those of normal immunoglobulins. He found that antibodies raised against one given myeloma protein, which cross-reacted against normal immunoglobulins, became specific for the immunizing protein once extensively adsorbed on normal immunoglobulins. This was taken as indicative of determinants specific for any given monoclonal product, although it was not entirely clear whether it was also linked to the pathological "abnormal" nature of the myeloma protein. Structural analysis confirmed, as anticipated, that idiotypic determinants, or idiotopes, were present on the Fab fragments and, more precisely, on the variable regions of H and/or L chains (see Immunoglobulin Structure), depending on the idiotype. Extensive analysis of idiotype structure performed by a combination of immunochemical and structural analysis of anti-hapten antibodies revealed several types of idiotopes. Some Ab1-Ab2 interactions could be inhibited by a hapten of Ab1, indicating that the corresponding idiotopes were part of the antibody combining site, whereas other were not. Genetic analysis also revealed that some idiotypic specificities were common to several idiotypes, whereas others were strictly specific for one given Ab1, leading to the distinction of public and private idiotypes, a notion that was directly related to the dual origin of antibody diversity, germline encoded and somatically generated. Idiotypy was studied extensively when it was discovered that the cascade Ag(X) ^ Ab1 ^ Ab2 could be continued and amplified in a large idiotypic network of interactions, providing a basis for autoregulation of the immune system. An especially interesting observation was that Ab2 could induce certain Ab3 molecules that resembled Ab1 in that they could bind the original Ag(X) antigen. This led to the definition of the "internal image" of the antigen, proposed by Jerne, containing the idea that the collection of normal immunoglobulins of an individual could represent a huge population of internal images of the outside antigen world. It also stimulated approaches of idiotypic vaccines that could have been used in place of classical antigens, an interesting idea whenever antigens were either difficult to identify or poorly immunogenic. Polyclonal antibodies (or antisera) are antibodies that are obtained from different B cell resources. They are a combination of immunoglobulin molecules secreted against a specific antigen, each identifying a different epitope. These antibodies are typically produced by immunization of a suitable mammal, such as a mouse, rabbit or goat. Larger mammals are often preferred as the amount of serum that can be collected is greater. An antigen is injected into the mammal. This induces the B-lymphocytes to produce IgG immunoglobulins specific for the antigen. This polyclonal IgG is purified from the mammal’s serum. Generation of HGPRT- or TK- myeloma lines Both these genes reside on the X chromosome and thus a single mutation is sufficient for generating HGPRT- or TK- phenotypes. These are produced by culturing the cells in the presence of 6-thioguanine or 8-azaguanine for selection of HGPRT- mutants or in the presence of bromodeoxyuridine for selection of TK- mutants. 6-thioguanine or 8-azaguanine are hypoxanthine analogues and bromodeoxyuridine is a thymidine analogue. Thus in the presence of HGPRT and TK these analogues are incorporated into DNA. Thus HGPRT+ or TK+ cells will die but HGPRT- or TK- cells will survive and be selected (see Base analogues for selection of HGPRT- and TK- myeloma cell lines). Fusion of myeloma pairs. Before conducting the fusion experiment involving B lymphocytes and myeloma cells, Cesar Milstein and his colleague utilised a similar approach. This experiment established that the antibody H and L chains of each partner were expressed in a co-dominant manner in the hybrid (see Fig Fusion of two Ig producing hybridoma line). This result was very important because it suggested that, in a B lymphocyte-myeloma hybrid, the H and L chains of the B lymphocytes could be expressed. The actual fusion experiment that established monoclonal antibodies is reported in the Fig: Continuous cultures of fused cells secreting antibody of predefined specificity. This experiment confirmed the co-dominant expression of the antibody chains and led to the isolation of the first monoclonal antibody with predefined antigen specificity after somatic cell fusion (see additioal Fig). Fusion of myeloma pairs. Why hybridoma technology is so effective. The procedure of somatic cell hybridisation developed by Kohler and Milstein has revolutionised immunochemistry. Why is it so effective ? It is so effective for two reasons: The first is that the antibodies produced in this way employ B cells from hyper-immune animals. These cells therefore have undergone stringent antigen selection and affinity maturation and, when immortalised, will yield high-affinity, monoclonal antibodies. The second reason is that the fusion procedure itself selects for blast cells. Therefore, if a final boost is carried out 2-3 days before fusion, the frequency of antigen-specific clones among the population of hybrid myelomas is very high. Humanisation of rodent antibodies in order to facilite their therapeutic applications was carried in two steps (see Fig Protein engineering of mouse monoclonal antibodies for therapeutic applications). In the first the VH and VL domains are cloned and sequence and inserted in plasmids carrying sequences corresponding to CH1, CH2 and CH3 domains for the Heavy chain and to the CL domain for the Light chain and the plasmids used in order to enable expression of a recombinant form of the antibody in suitable mammalian cell hosts. These chimeric antibodies proved to be much less imunognic than their mouse counterparts. In a second step the CDRs of the mouse antibody were grafted onto human V scaffold yielding, essentially a human antibody. These 'humanised' antibodies are the proteins of choice for applications in patients in vivo. Hapten (Stabiles Analog zum Übergangszustand) Instabiler Übergangszustand Amino- phosphonsäure L.C.Hsieh-Wilson, P.G.Schultz, and R.C.Stevens. Proc. Natl. Acad. Sci. USA, 93: (1996). Download ppt "History of Immunology Part 3: IMMUNOCHEMISTRY – The Antibody Problem" Specific Defenses of the Host: The Immune Response Immunogen: A substance that induces a specific immune response Antigen (Ag): A substance that reacts. Resistência dos Materiais, 5ª ed. 1. Complement System 2. Antigen Specific Receptors K.J. Goodrum Department of Biomedical Sciences 2005. Complement Terry Kotrla, MS, MT(ASCP)BB Fall 2007. The Immune Response 1Dr. Nikhat Siddiqi. All vertebrates have an immune system capable of distinguishing molecular “self” from “nonself” and then destroying. Adaptive Immunity Central objective: Protect against foreign invaders Create memory of invasion to prevent recurrent infection. Antibodies & Antigens1 Antibodies Also chap 5 pp Self-Test Questions: Chap 4: all Chap 5: D all MolnQuiry. Gamma Globulins Dr Gihan Gawish. Drmsaiem IMMUNOGLOBULINS DR. Mohammed Saiemaldahr FACULTY OF APPLIED MEDICAL SCIENCES KAAU. Chapter 4: Serology Concepts. What is an antigen?  An antigen is any substance that elicits an immune response and is then capable of binding to the. Antigens, Immunogens, Epitopes, and Haptens: Antigen: a molecule or part of a molecule that is recognized by the immune system. The term is associated.

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Inhibition of survivin and Aurora B induces mitotic cell arrest in mesothelioma cells after irradiation. These two proteins may be potential therapeutic targets for the enhancement of radiotherapy in malignant pleural mesothelioma.

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Because of the potential for chronic pain and disabilities if treatment is delayed or improperly performed in carpal tunnel syndrome (CTS) cases, timely diagnosis and treatment is essential to avoid medical malpractice and personal injury lawsuits. A thorough preoperative assessment, meticulous surgical technique, and careful monitoring of patients postoperatively maximizes patient outcomes and satisfaction in LASIK surgery. The hand functions–with its tendons, nerves, vascular circulation, multiple carpal bones, metacarpals, and phalanges–is a very complex part of our body and requires expert specialist medical care. Acetaminophen is one of the most common pharmaceuticals associated with poisoning. Failure to promptly administer N-acetylcysteine (NAC) or to consider co-ingestants in these cases increases the risk of a medical malpractice or personal injury lawsuit. The epidemic of obesity is responsible for the increase of diabetes in pregnancy; The increase in shoulder dystocia and neurologic injury at the time of birth is one result. All exposures to crude oil, no matter how seemingly insignificant, may prove consequential in medical-legal cases. Children and pregnant mothers are at significant risk. Falls among patients in skilled nursing facilities (SNF) are an important factor in generating plaintiff actions in personal injury lawsuits. Physicians have been held liable for failure to diagnose stroke, hemorrhage and infection and obtain appropriate consultation. A high index of suspicion, however, is necessary in medical malpractice or personal injury lawsuits. Many of the medical-legal risks in general surgery are applicable to transplantation surgery. Obtaining informed consent for the surgical procedure is paramount. For clinical studies Institutional Review Board (IRB) approval may be required. Heart disease is the leading cause of death for women in the U.S.. Delays in seeking treatment for cardiovascular disease (CVD) is partly explained by the different symptoms women present that physicians often miss. Failure to diagnose and reduce hip dislocations in the first 6 hours or to overlook a fracture diminishes the prognosis and can lead to a medical malpractice or personal injury lawsuit.

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### **Can vitamin D reduce the risk of breast cancer?She did not receive chemotherapy or radiation and the cancer drug Tamoxifen (the estimated benefit from these treatments was minimal given certain characteristics of her cancer), but she did add 30 minutes of walking to her routine; cut back on processed and fatty foods; and started taking supplements prescribed by Alschuler.**WHERE TO GO:** For information on genetic testing or for help finding a health care professional trained in genetics, contact the National Cancer Institute's Cancer Information Service at 800-4-CANCER. To find a naturopathic doctor who specializes in oncology, check with the Oncology Association of Naturopathic Physicians at oncanp.org. ### **Should I ask for an MRI exam, a BRCA1 or other tests? ** An MRI can reveal a tumor that's too small to be detected by a physical exam or is missed by a mammogram. "An MRI is valuable as a secondary diagnostic tool," says Alschuler. "I know several patients who had a suspicious finding on a mammogram and followed up with ultrasound or an MRI and discovered cancer." That's what happened to Cathy Gergen, 48, a human resources manager for a construction company in Arizona. After she discovered a lump in her right breast, she immediately scheduled a mammogram and ultrasound. When the tests produced conflicting results (the mammogram showed no thickening or lump; the ultrasound did), Gergen's surgeon ordered an MRI, which revealed a tumor. "If I hadn't felt the lump myself, I would have gone for a regular mammogram and thought everything was OK," she says. After reviewing her options with both a traditional surgeon and Alschuler, Gergen had a double mastectomy. She did not receive chemotherapy or radiation and the cancer drug Tamoxifen (the estimated benefit from these treatments was minimal given certain characteristics of her cancer), but she did add 30 minutes of walking to her routine; cut back on processed and fatty foods; and started taking supplements prescribed by Alschuler. ### **Can vitamin D reduce the risk of breast cancer?Vitamin D is converted into a hormone that helps to prevent normal cells from becoming cancerous and, in some cases, induces established cancer cells to stop growing and die.Researchers are working to determine whether boosting vitamin D status after a breast cancer diagnosis can lower the odds of cancer spreading.

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• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.• Tell patient to immediately report signs or symptoms of allergic reaction, such as hives.Emphasize that it's not just a vitamin.Stress importance of taking leucovorin as prescribed with high-dose methotrexate therapy.** _5-FU:_ enhanced fluorouracil toxicity _Methotrexate, other folic acid antagonists:_ negated therapeutic and toxic effects of these drugs _Phenobarbital, phenytoin, primidone:_ negated anticonvulsant effect, increased frequency of seizures in susceptible children #### **Patient monitoring** Monitor serum creatinine and methotrexate levels every 24 hours. Monitor closely for adverse reactions. Continue leucovorin therapy, hydration, and urinary alkalization until serum methotrexate level drops below 10-8 M. Monitor CBC with white cell differential and platelet count before leucovorin/5-FU therapy starts. Repeat weekly during first two courses and then once each cycle at anticipated white blood cell nadir. • Check electrolyte levels and liver function tests before each treatment for first three cycles. Thereafter, check before every other cycle. • Assess for adequate hydration when giving with 5-FU or high-dose methotrexate. • Watch for hypersensitivity reactions, especially anaphylactoid reactions. #### **Patient teaching** • Teach patient about drug and protocol. Stress importance of taking leucovorin as prescribed with high-dose methotrexate therapy. Emphasize that it's not just a vitamin. • Tell patient to immediately report signs or symptoms of allergic reaction, such as hives. • As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.This inhibition causes initial increase and then profound decrease in luteinizing hormone and follicle-stimulating hormone levels and, ultimately, reduces testosterone and estrogen sex hormones.

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Hypersensitivity to valproic acid Hepatic disease Hepatic impairment, significant Urea cycle disorders Mitochondrial disorder, POLG-related Pregnancy (migraine headache prophylaxis use)

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A short hairpin RNA or small hairpin RNA (shRNA/Hairpin Vector) is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression via RNA interference (RNAi). Expression of shRNA in cells is typically accomplished by delivery of plasmids or through viral or bacterial vectors. shRNA is an advantageous mediator of RNAi in that it has a relatively low rate of degradation and turnover. However, it requires use of an expression vector, which has the potential to cause side effects in medicinal applications. The promoter choice is essential to achieve robust shRNA expression. At first, polymerase III promoters such as U6 and H1 were used; however, these promoters lack spatial and temporal control. As such, there has been a shift to using polymerase II promoters, which are inducible, to regulate shRNA expression. Delivery Expression of shRNA in cells can be obtained by delivery of plasmids or through viral or bacterial vectors. Delivery of plasmids to cells through transfection to obtain shRNA expression can be accomplished using commercially available reagents in vitro. However, this method is not applicable in vivo and thus has limited utility. Use of a bacterial vector to obtain shRNA expression in cells is a relatively recent approach. It builds off research showing that recombinant Escherichia coli, containing a plasmid with shRNA, fed to mice can knock-down target gene expression in the intestinal epithelium. This approach was used in 2012 in clinical trials to try to treat patients with Familial Adenomatous Polyposis. A variety of viral vectors can be used to obtain shRNA expression in cells including adeno-associated viruses (AAVs), adenoviruses, and lentiviruses. With adeno-associated viruses and adenoviruses, the genomes remain episomal. This is advantageous as insertional mutagenesis is avoided. It is disadvantageous in that the progeny of the cell will lose the virus quickly through cell division unless the cell divides very slowly. AAVs differ from adenoviruses in that the viral genes have been removed and they have diminished packing capacity. Lentiviruses integrate into sections of transcriptionally active chromatin and are thus passed on to progeny cells. With this approach there is increased risk of insertional mutagenesis; however, the risk can be reduced by using an integrase-deficient lentivirus. Mechanism of action Once the vector has integrated into the host genome, the shRNA is then transcribed in the nucleus by polymerase II or polymerase III depending on the promoter choice. The product mimics pri-microRNA (pri-miRNA) and is processed by Drosha. The resulting pre-shRNA is exported from the nucleus by Exportin 5. This product is then processed by Dicer and loaded into the RNA-induced silencing complex (RISC). The sense (passenger) strand is degraded. The antisense (guide) strand directs RISC to mRNA that has a complementary sequence. In the case of perfect complementarity, RISC cleaves the mRNA. In the case of imperfect complementarity, RISC represses translation of the mRNA. In both of these cases, the shRNA leads to target gene silencing. Applications in gene therapy Due to the ability of shRNA to provide specific, long-lasting, gene silencing there has been great interest in using shRNA for gene therapy applications. Three examples of shRNA-based therapies are discussed below. Gradalis, Inc. developed the FANG vaccine, which is used in treatment of advanced cancers. FANG relies on a bifunctional shRNA (bi-shRNA) against the immunosuppressive transforming growth factors (TGF) β1 and β2. Autologous tumor cells were harvested from patients and a plasmid encoding the bifunctional shRNA and granulocyte-macrophage colony-stimulating factor (GMCSF) was introduced ex vivo through electroporation. These cells were later irradiated and injected back into the patient. Marina Biotech developed CEQ508 which is used to treat Familial Adenomatous Polyposis. CEQ508 uses a bacterial vector to deliver shRNA against β-catenin. Gradalis, Inc. developed bifunctional shRNA-STMN1 (pbi-shRNA STMN1), which is used to treat advanced and/or metastatic cancers. This pbi-shRNA STMN1 is against stathmin 1 and is delivered intratumorally through bilamellar invaginated vesicle (BIV) lipoplex (LP) technology. Several challenges typically confront shRNA-based therapeutics. The most significant challenge is delivery. shRNA is typically delivered through use of a vector, and although they are generally efficient, they pose significant safety concerns. In particular, viral based gene therapy approaches have proved dangerous in past clinical trials. In the first generation of retro viral gene therapy, some patients treated with viral vectors for Wiskott–Aldrich syndrome developed acute T-cell leukaemia. This was determined to have been caused by viral vector insertion location. Potential oversaturation of RISC is also a problem. If the shRNA is expressed at levels that are too high, the cell might not be able to correctly process the endogenous RNA which could cause significant problems. Another challenge is the possibility that the patient might mount an immune response against the therapy. Finally, there might be off-target effects and the shRNA could silence other unintended genes. In developing successful new shRNA-based therapeutics, all of these challenges must be taken into account. See also Small interfering RNA References RNA RNA interference

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3.If none of these suggestions help with their control, it might be that the level of this pattern is too high for the individual to perform properly; in this case, choose the Pull-over pattern described below.Maintaining the visualization, have the individual repeat their leg lift to see if it improves the quality of the movement.d. Releasing chronic gripping around the spine, pelvis, and/or hips with a foam roll or through tactile cuing can also be helpful. For example, you can cue them to: "Let your ischial tuberosities (or sits bones) go wide" or "Imagine your hip joint is like a tire on an axle—the leg (tire) spins around the pelvis (axle) as you lift your leg." 2. _Abdominal distension._ The most common and indicative sign of a non-optimal core stabilization strategy is abdominal distension. The individual will bear down—essentially they are performing a Valsalva's maneuver—for TPC stabilization, rather than being able to use an optimal internal pressure strategy for stabilization, contributes to abdominal distension. Generally increased erythema (flushing) of their face and an inability to communicate because they are overly braced and bearing down will be noted. To combat this, use any of the previous suggestions above to help in controlling the issue, especially cuing them into their breathing. a. Cue the individual's awareness of their transversus abdominis or pelvic floor by demonstrating where it is. Show them on a model or in a picture how the transversus abdominis wraps around the core, the pelvic floor covers the bottom of their pelvis, and how it is an analogous structure to the respiratory diaphragm. b. Try any of the previous cues for activating the DMS and see which one resonates best with your client. Maintaining the visualization, have the individual repeat their leg lift to see if it improves the quality of the movement. If none of these suggestions help with their control, it might be that the level of this pattern is too high for the individual to perform properly; in this case, choose the Pull-over pattern described below. 3.This may result in increased tension, tightness, and even cramping in their superficial hip flexors during hip flexion; this is a common contributor to femoroacetabular impingement syndrome (see Appendix V).

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Latanoprost and pigmentation. Latanoprost is a prostaglandin analogue with well-established efficacy in the treatment of open-angle glaucoma and ocular hypertension. Once-daily administration of this drug for up to 5 years is generally well tolerated both locally and systemically. While most reported side effects have been classified as mild in intensity, an increase in iris, eyelash, and periocular pigmentation has been associated with prostaglandin analogue use in some patients. Follow-up studies of patients withdrawn from latanoprost treatment suggest that the increased iridial pigmentation is irreversible while changes in eyelash and periocular skin pigmentation are reversible after cessation of therapy. Concern as to whether latanoprost affects proliferation of iridial melanocytes or other cellular components prompted investigation into its mechanism of action. All available evidence from in vitro, in vivo, and clinical studies suggests that latanoprost does not induce melanocyte proliferation. Morphologic study of human peripheral iridectomy specimens did not reveal any significant latanoprost-induced pathologic change in the iris. There was no evidence of melanin granules blocking the outflow pathways in treated patients. Stimulation of melanogenesis in iridial melanocytes, perhaps through an effect on tyrosinase, appears to account for induction of melanin production. Additional studies are in progress to further elucidate the mechanism of latanoprost-induced increased iridial pigmentation.

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The three tube current values yielded similar results for SUV calculation.

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EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways. Homocysteine (Hcy) induced vascular endothelial injury leads to the progression of endothelial dysfunction in atherosclerosis. Epigallocatechin gallate (EGCG), a natural dietary antioxidant, has been applied to protect against atherosclerosis. However, the underlying protective mechanism of EGCG has not been clarified. The present study investigated the mechanism of EGCG protected against Hcy-induced human umbilical vein endothelial cells (HUVECs) apoptosis. Methyl thiazolyl tetrazolium assay (MTT), transmission electron microscope, fluorescent staining, flow cytometry, western blot were used in this study. The study has demonstrated that EGCG suppressed Hcy-induced endothelial cell morphological changes and reactive oxygen species (ROS) generation. Moreover, EGCG dose-dependently prevented Hcy-induced HUVECs cytotoxicity and apoptotic biochemical changes such as reducing mitochondrial membrane potential (MMP), decreasing Bcl-2/Bax protein ratio and activating caspase-9 and 3. In addition, EGCG enhanced the protein ratio of p-Akt/Akt, endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) formation in injured cells. In conclusion, the present study shows that EGCG prevents Hcy-induced HUVECs apoptosis via modulating mitochondrial apoptotic and PI3K/Akt/eNOS signaling pathways. Furthermore, the results indicate that EGCG is likely to represent a potential therapeutic strategy for atherosclerosis associated with Hyperhomocysteinemia (HHcy).

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Antiproliferative and antiapoptotic effects of crel may occur within the same cells via the up-regulation of manganese superoxide dismutase. Rel/nuclear factor kappaB transcription factors were shown to have either pro- or antiapoptotic as well as pro- or antiproliferative functions, and it is often assumed that the outcome of their activation depends on the cell type or cellular context. Inconsistent with this assumption, we show here that cRel is able in one cell type to inhibit proliferation, protect against apoptosis induced by tumor necrosis factor alpha (TNF-alpha) + cycloheximide (CHX), and increase the basal rate of apoptosis. Both the effects of proliferation inhibition and protection against TNF-alpha + CHX-induced apoptosis are massive and occur in the same cells. Using reverse transcription-PCR, Western blot and immunofluorescence, and transactivation assays, we found that the manganese superoxide dismutase (MnSOD), an enzyme that converts O2*- in H2O2, is up-regulated by cRel through a kappaB site in intron 2. Inhibition of MnSOD induction by antisense oligonucleotides and overexpression of MnSOD respectively reverts and mimics both the antiproliferative and antiapoptotic effects of cRel, suggesting that they both occur via the induction of this gene. On one hand, MnSOD could improve the efficiency of cRel-overexpressing cells in eliminating toxic O2*- produced on TNF-alpha treatment, explaining why they escape TNF-alpha-induced apoptosis. On the other hand, cRel-overexpressing cells should accumulate H2O2. We present evidence linking this H2O2 accumulation to the proliferation arrest induced by cRel. Therefore, different effects on proliferation and apoptosis could arise from the induction of MnSOD and thus coexist in cRel-overexpressing cells.

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116, p. 973; Freedman JE, Loscalzo J: Arterial and Venous Thrombosis, Chap.115, p. 965; Arruda VR, High KA: Coagulation Disorders, Chap.58, p. 457; Konkle BA: Disorders of Platelets and Vessel Wall, Chap.For a more detailed discussion, see Konkle BA: Bleeding and Thrombosis, Chap.For PE or arterial or deep-vein thrombosis, 250,000 IU over 30 min, then 100,000 IU/h for 24 h (PE) or 72 h (arterial or deep-vein thrombosis). (3) Urokinase—for PE, 4400 IU/kg IV over 10 min, then 4400 (IU/kg)/h IV for 12 h. Fibrinolytic therapy is usually followed by a period of anticoagulant therapy with heparin. Fibrinolytic agents are contraindicated in pts with (1) active internal bleeding; (2) recent (<2–3 months) cerebrovascular accident; (3) intracranial neoplasm, aneurysm, or recent head trauma. **ANTIPLATELET AGENTS** Aspirin inhibits platelet function by blocking the ability of cyclooxygenase (COX-1) to synthesize thromboxane A2. The thienopyridines (ticlopidine and clopidogrel) inhibit ADP-induced platelet aggregation by blocking its receptor (P2Y12). Dipyridamole acts by inhibiting phosphodiesterase, which permits cAMP levels to increase and block activation. Glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists block the integrin receptors on the platelet and prevent platelet aggregation. Three such agents are now in use: abciximab, an Fab antibody fragment that binds to the activated form of GPIIb/IIIa; eptifibatide, a cyclic heptapeptide that includes the KGD tripeptide motif that the GPIIb/IIIa receptor recognizes; and tirofiban, a tyrosine derivative that mimics the KGD motif. Aspirin (160–325 mg/d) plus clopidogrel (400-mg loading dose then 75 mg/d) may be beneficial in lowering incidence of arterial thrombotic events (stroke, MI) in high-risk pts. Antiplatelet agents are useful in preventing strokes, complications from percutaneous coronary interventions, and progression of unstable angina. For a more detailed discussion, see Konkle BA: Bleeding and Thrombosis, Chap. 58, p. 457; Konkle BA: Disorders of Platelets and Vessel Wall, Chap. 115, p. 965; Arruda VR, High KA: Coagulation Disorders, Chap. 116, p. 973; Freedman JE, Loscalzo J: Arterial and Venous Thrombosis, Chap.118, p. 988, in HPIM-18.### **CHAPTER 71 Cancer Chemotherapy** #### **BIOLOGY OF TUMOR GROWTH** Two essential features of cancer cells are uncontrolled growth and the ability to metastasize.

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The root can also be used in prepared ointments to help soothe the inflammation of arthritis.A self-prescribed dose should be no more than half a teaspoon in a daily cup of tea, and should not be continued for more than a month.The strength of wild indigo root lies somewhere between that of echinacea and goldenseal.Wild indigo root is also a liver tonic, helping to detoxify the body.Healthy mast cells have a tight weave that can keep deviant material out of the bloodstream—bacteria, pollen, and protein that has not been properly broken down. Turmeric contains corsitin, a bioflavonoid that can strengthen the mast cells over time. Many doctors use turmeric for allergies. You might think of the lining of your trachea or sinuses as fabric. Tears or holes in this fabric, or a loose weave, allow things like pollen to enter the bloodstream where they trigger an exaggerated response in the immune system, leading to inflammation and all the symptoms of allergy. Turmeric heals the cracks and tightens the weave, providing greater resistance to allergens. In the same way, food allergies can be lessened by strengthening the mast cell tissue in the intestinal tract. Although it should not be taken as a panacea, turmeric is very safe and is already used in many foods. It can also be taken in capsule form or made as a tea. **WILD INDIGO ROOT** Wild indigo root is not a very popular herb, but it is valuable for its direct antimicrobial activity, helping to fight infections throughout the body and particularly the upper respiratory tract. More important, wild indigo root stimulates the gastrointestinal tract to maintain its levels of hydrochloric acid. This is the first line of defense in the immune system. Without an adequate level of hydrochloric acid in the stomach, microorganisms that enter with the ingestion of food may pass through the stomach and enter the lymphatic or blood systems. Wild indigo root is also a liver tonic, helping to detoxify the body. The strength of wild indigo root lies somewhere between that of echinacea and goldenseal. A self-prescribed dose should be no more than half a teaspoon in a daily cup of tea, and should not be continued for more than a month. The root can also be used in prepared ointments to help soothe the inflammation of arthritis.Shake frequently.Then strain and apply as needed.**PART THREE** **Mental Health and Psychological Well-Being** Psychological disorders are common in America.In a given year, approximately 27 percent of Americans over the age of 18—about a quarter of the adult population—have a mental disorder that can be diagnosed.

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The case with Anna and Jill is definitely a case for contacting the local Child Protection Services if the parents continue to act in a way that hinders treatment.Waiting to do so may only lead to a doctor's delay and possibly more problems for the child.The risk of odontological infections in relation to general health has been debated, but only a few years ago there was a case in a Scandinavian country where untreated oral infections originating from dental decay had lethal consequences. Despite great efforts the child did not receive adequate dental or medical care. In the background were complicating factors connected to social circumstances. Getting back to Jill and Anna, it is obvious that the dentist has to act. But looking back, the dentist has to ask her/himself if the case could be handled differently. Being anxious about general anesthesia is not uncommon. Thus, the dentist has to focus carefully on information when presenting the treatment plan and the need for general anesthesia to the parents. There may be understandable reasons for the parent's' anxiety. Maybe the twins have been through medical events that have been problematic, or someone in the close family has had problems in a medical setting. Plausibly also cultural aspects can play a role as the medical care system varies a lot between different countries and cultural settings and in particular, families with an immigrant background may have had other experiences of general anesthesia than that of the dental team. The Jill and Anna case points to how important, but also challenging, communication with the family can be. It is recommended to seek advice from specialists in pediatric dentistry or from other colleagues already at an early stage if the dentist feels that it is difficult to engage parents in a treatment plan that is in the best interest of the child. Waiting to do so may only lead to a doctor's delay and possibly more problems for the child. The case with Anna and Jill is definitely a case for contacting the local Child Protection Services if the parents continue to act in a way that hinders treatment.Research involving humans has a dark history and acts of cruelty have been carried out in the name of science, e.g., on prisoners of war and refugees in concentration camps during World War II.This led to an intensified discussion in the world community about ethics and to a number of incentives and declarations.

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Aushealth Physiotherapy "Your Northern Beaches Physio" are experts in treating Shoulder Pain on the Northern Beaches in Sydney. Shoulder pain is an incredibly common condition we see regularly in our clinic. It can be so debilitating and have a huge impact on your daily life – stopping you from doing things you like. Often it will keep you awake at night with a burning pain down your arm or stop you from reaching into the cupboards above your head. It can be a result of a specific incident or accident, or it can just start for no apparent reason. Pain can be a result of direct trauma, repetition or overuse, degeneration or referred pain from another joint such as the neck or upper back. Your shoulder is an extremely mobile joint (think of a golf ball sitting on a tee) that allows you to perform amazing tasks with your upper limb. But this mobility comes at a cost. It means that your shoulder relies heavily on muscle control to be able to achieve movement safely (think keeping the golf ball sitting safely on the centre of the tee). When you have a muscle imbalance (quite often weak muscles at the back and tight muscles in the front) or a traumatic event like a fall, the head of the humerus (golf ball) will no longer sit in the centre of its joint (the tee) and you will experience pain. This is the basis of many shoulder injuries. The most common shoulder injuries include: Shoulder dislocation/subluxation, Rotator cuff injury and/or tendinopathy, Frozen Shoulder (Adhesive capsulitis), subacromial impingement or bursitis due to dysfunction of bony and muscular structures and labral injuries. It is also very common that shoulder pain can be referred from injury or dysfunction to the neck and/or mid back. When dealing with shoulder pain, like other musculoskeletal injuries, it is imperative that you have a thorough assessment to ascertain your diagnosis and the correct line of treatment for your shoulder. This is what we do at Aushealth Physiotherapy. Our experienced Physiotherapists not only focus on your shoulder joint, but also look at surrounding joints to see if they are impacting on your injury. They will then take you through an individualised shoulder rehabilitation program which includes manual therapy (hands on treatment) strengthening, stretching, postural re-education and specific function tasks based on what you want to get out of the treatment. We also run a specific shoulder program called “Keep your Cuff” for patients suffering a rotator cuff injury. This 6-12 week program produces excellent improvements in shoulder pain and function and can help you regain confidence in your shoulder (and quite often avoid shoulder surgery). Watch our fantastic video on rotator cuff injuries below. Speaking of shoulder surgery, we work closely with the shoulder surgeons on the Northern Beaches to get people back to being strong following surgery, whether it be in our hydrotherapy pool, in the clinic or in our specialised gym. Our shoulder patients get great results. So, if you have shoulder pain, don’t put up with it. Let us help you get back to doing what you love, getting a good night sleep and living a painfree life. Give Aushealth Physiotherapy "Your Northern Beaches Physio" a call on 9905 0048 to make and appointment (or simply Book Online) and take the first step away from shoulder pain.

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We believe that health starts in the digestive system. After all, you are what you eat, and cannot repair your body from everyday wear and tear if you aren’t digesting well. As hormones and stress levels fluctuate, our bowels do not move as much as they should, and colonics are an important addition to any health or detoxification program. If you are not having a bowel movement after every meal, you are constipated, which can lead to IBS, diverticulitis and even colon cancer. Colon hydrotherapy can help balance the immune system, detoxify the body, rehydrate and even help patients to lose weight. While the process may see strange, most people feel remarkably better after the therapy, and get them frequently. At your first appointment you will have a brief meeting with one of our doctors, and they will determine if you are a candidate for the therapy. If you are pregnant or lactating, you should wait until you no longer are due to possible toxins being mobilized in your system which could be theoretically passed on to your baby. Other contraindications include inflammatory bowel diseases like Crohn’s and Ulcerative Colitis or having had recent abdominal surgery. After the doctor interviews you, they will perform an abdominal exam, and may do a digital rectal exam. If those are normal, they will insert the speculum and leave you in the hands of our capable and highly trained therapists. During the process the therapist will introduce water slowly into your intestines. This can be very hydrating, and it will also loosen any impacted matter in your colon. When you feel the urge to go, you communicate that to your therapist, and they reverse the flow on the machine and the waste exits through a waste tube. We use a closed system, which we feel is more hygienic and comfortable than the open system. Your therapist may repeat the process from 5-15 times during a session, and you are in complete control of the situation the entire time. Human Reconstruction offers one of the lowest prices for colonics in the Sacramento area. We have two wonderful colon hydrotherapists, Meredith and Stephanie, and charge only $65 a session so it is economical for you to keep your bowels happy and healthy. We are located in Fair Oaks, California, close to Roseville, Sacramento and Folsom. Call 916.241.9325 and feel better today.

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