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Influence of trehalose 6,6'-dimycolate (TDM) during mycobacterial infection of bone marrow macrophages. The relative role of surface lipids in the innate macrophage response to infection with mycobacteria remains unknown. Trehalose 6,6'-dimycolate (TDM), a major component of the mycobacterial cell wall, can elicit hypersensitive as well as T-cell-independent foreign body responses. The T-cell-independent contribution of TDM to the primary macrophage response to mycobacterial infection was investigated. Bone-marrow-derived macrophages isolated from C57BL/6 mice were infected with native Mycobacterium tuberculosis (MTB) or with MTB delipidated using petroleum ether extraction methods. The removal of surface lipids caused decreased bacterial survival in macrophages, but there was no loss of bacterial growth in broth culture. Bacterial survival within macrophages was restored upon reconstitution of the bacteria with purified TDM. The cytokine and chemokine parameters of the macrophage responses were also investigated. The amounts of IL-1beta, TNF-alpha, IL-6 and MIP-1alpha produced were significantly reduced following delipidation, but were restored upon reconstitution with TDM. The amount of IL-12 produced, but not the amount of IL-10 produced, was also significantly reduced upon macrophage infection with delipidated MTB. Furthermore, nitric oxide responses were not impaired upon infection with delipidated MTB, suggesting that intracellular survival and macrophage secretion of cytokines and chemokines are differentially controlled. These studies indicate that TDM is a major component contributing to the innate macrophage responses to MTB infection.

Electromigration methods for amino acids, biogenic amines and aromatic amines. Methods of electromigration in laboratory apparatus of small-bore size have recently undergone development at a remarkably rapid pace, leading to a variety of new analytical techniques. One such technique is called "capillary electrophoresis" (CE), which is further classified on the basis of electromigration mode, viz., "capillary zone electrophoresis" (CZE), which, in turn, has several variations. This review aims to give a short overview of the various electromigration methods for amino compounds by using CE. Firstly, this review briefly summarizes the detection methods employed for detection of monoamines and polyamines by CE for both native and derivative forms. Next, current CE methods are described, and their applications to detection of amino acids, biogenic amines, aromatic amines, including heteroaromatic amines and their enantiomers, are introduced from representative papers. Finally, new methods for single-cell analysis and microchip CE techniques are focused on.

[Radioresistance mechanisms of side population cells in mouse melanoma cell line B16]. As it was shown by us earlier, side population (SP) cells are more resistant to the low-LET radiation than the other part of mouse melanoma B16 cells (Matchuk et al., 2012). The aim of our research was finding some mechanisms of radioresistance, therefore we analyzed SP and nonSP cell cycle distribution, spontaneous and radiation induced DNA double-strand breaks (number of γH2AX foci) and intracellular NO concentration. The results indicate that SP cells have significantly less DNA double-strand breaks after irradiation at dose of 3 Gy than nonSP cells (24.4 vs 40.3, accordingly, P < 0.05 Mann-Whitney Ucriterion). SP cells are more quiescent compared to nonSP G1/G0 fraction is 85 vs 39%, accordingly, P < 0.01 Mann-Whitney U criterion). Most nonSP cells reside in S, G2/M phases (61%), believed to be rather radiosensitive. Thus, the difference of SP and nonSP cells radiosensitivity can be partly explained by peculiarities of cell cycle distribution. NO concentration is 1.5 times higher in SP than nonSP cells (P < 0.05 Mann-Whitney U criterion); since it is known that NO inhibits apoptosis, being one of the mechanisms of genetic stability maintenance, greater number of spontaneous DNA double-strand breaks in SP cells is unsurprising (P < 0.05 Mann-Whitney U criterion). The above-listed results explain considerably the higher resistance of SP cells to the action of low-LET radiation in comparison with other melanoma B16 cells. Further study of this question can become the basis for development of tools to target SP cells and, ultimately, more effective cancer treatment.

Klebsiella pneumoniae in endodontic therapy. Report of a case. A 48-year-old man underwent endodontic treatment of the lower left central incisor. In the course of treatment two acute exacerbations occurred. Penicillin therapy was initiated at the time of the first exacerbation. It was ineffective, and a culture of the purulent exudate was taken at the time of the second acute response. The causative organism was Klebsiella pneumoniae, which was found to be sensitive to tetracyclines. After tetracycline therapy, endodontic therapy was completed. Healing has been uneventful.

A possible fragile-site at Yq12: case report and possible relevance to de novo structural rearrangements of the Y-chromosome. In a routine chromosome study it was noted that cells from a patient had different lengths of Y-chromosome: 20% of the cells had a Y-chromosome with about 40% of the normal length of heterochromatin, whereas the majority of cells had an average size Yq12 region. A break within Yq12 was found in 3-4% of the cells with the long Yq12 chromosome, indicating the presence of a possible new fragile site. The frequency of cells with the 2 different sizes of Y-chromosomes was unaffected by culture conditions, as was the frequency of cells with a break or gap. Possible consequences of a fragile-site within Yq12 are discussed.

Urine metabolomics insight into acute kidney injury point to oxidative stress disruptions in energy generation and H2S availability. Acute kidney injury (AKI) is one of the main complications in acute care medicine and a risk factor for chronic kidney disease (CKD). AKI incidence has increased; however, its diagnosis has limitations and physiopathological mechanisms are underexplored. We investigated urine samples, aiming to identify major metabolite changes during human AKI evolution. Metabolic signatures found were further explored for a potential link to severity of injury. Twenty-four control subjects and 38 hospitalized patients with AKI were recruited and urine samples were collected at the time of diagnosis, during follow-up and at discharge. Nuclear magnetic resonance (NMR) was used in a first discovery phase for identifying potential metabolic differences. Target metabolites of interest were confirmed by liquid chromatography-mass spectrometry (LC-MS/MS) in an independent group. Underlying metabolic defects were further explored by kidney transcriptomics of murine toxic AKI. Urinary 2-hydroxybutyric acid, pantothenic acid, and hippuric acid were significantly downregulated and urinary N-acetylneuraminic acid, phosphoethanolamine, and serine were upregulated during AKI. Hippuric acid, phosphoethanolamine, and serine showed further downregulation/upregulation depending on the metabolite in acute tubular necrosis (ATN) AKI compared to prerenal AKI. Kidney transcriptomics disclosed decreased expression of cystathionase, cystathionine-β-synthase, and ethanolamine-phosphate cytidylyltransferase, and increased N-acetylneuraminate synthase as the potentially underlying cause of changes in urinary metabolites. A urinary metabolite panel identified AKI patients and provided insight into intrarenal events. A urine fingerprint made up of six metabolites may be related to pathophysiological changes in oxidative stress, energy generation, and H2S availability associated with AKI. The urinary metabolome reflects AKI evolution and severity of injury. Kidney transcriptomics revealed enzymatic expression changes. Enzymatic expression changes may be the potentially underlying cause of changes in urine metabolites. Identified metabolite changes link oxidative stress, energy generation, and H2S availability to AKI.

Cellular immunity for prevention and clearance of HIV infection. Despite the major strides that have been made in HIV therapy with the advent of potent anti-retroviral drugs, these medications are quite expensive and are still not readily available for the vast majority of infected individuals worldwide. Even when available, the long-term toxicities associated with anti-retroviral medications and the frequent emergence of drug-resistance mutations can complicate therapy, making the formulation of effective vaccines imperative. This chapter will review the current state of understanding regarding cell-mediated immune responses that are associated with control of HIV replication. This knowledge has generated sound hypotheses regarding the prospects for augmenting cell-mediated immunity through immune-based therapies. With regard to prophylactic vaccines, it is presently unclear which vaccine-induced immune responses will protect against infection. While much progress has been made in formulating vaccine constructs designed to elicit cell-mediated immune responses, sterilizing immunity is unlikely to be achieved with the current vaccines. However, the ability to control viremia and prevent disease progression in animal infection models looks promising. The ability to measure immune responses has also advanced markedly over the past few years and will allow investigators to more accurately measure the immunogenicity of vaccine constructs, and correlate the magnitude and breadth of these responses with protection.

Effect of eicosapentaenoic acid on the proliferation and incidence of apoptosis in the colorectal cell line HT29. Fish oil has been shown to reduce the induction of colorectal cancer in animal models by a mechanism which may involve suppression of mitosis, increased apoptosis, or both. We used the human colonic adenocarcinoma cell line HT29 to explore the effects of the long-chain n-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on cell proliferation and death in vitro. Cells were cultured in media containing EPA at 5, 10, and 15 microg/mL. Cell number and thymidine incorporation were used to quantify proliferation, and cell cycle effects were studied using flow cytometry. Gel electrophoresis, annexin-V binding, and morphological criteria were used to characterize apoptosis. Adherent cells and freely floating detached cells were treated as two distinct populations. In the presence of EPA at 10 and 15 microg/mL there was a marked reduction in the growth rate of adherent HT29 colonies, owing to an increased detachment of adherent cells. After treatment with 10 or 15 microg/mL EPA the proportion of adherent cells in S-phase increased, indicating either a block in late S-phase or early G2. Floating cells showed evidence of extensive DNA cleavage, but the proportion of floating cells with sub GO DNA content declined on treatment with 10 or 15 microg/mL EPA even though the number of floating cells increased. We conclude that EPA does not inhibit mitosis of adherent cells, but increases the rate at which they become detached from the substrate, probably at an early stage in the initiation of apoptosis. This mechanism may be analogous to "anoikis," or induction of apoptosis in response to loss of cell contact, and may contribute to the anticarcinogenic effects of fish oil in vivo.

Eccrine squamous syringometaplasia in an allogenic stem cell transplant patient undergoing chemotherapy. Eccrine squamous syringometaplasia (ESS) is a rare finding defined as metaplastic change of the cuboidal epithelial cells of eccrine glands into two or more layers of squamous epithelial cells. We present a patient who developed ESS after induction of CLAG chemotherapy [2-Chlorodeoxyadenosine (2-CdA) with cytarabine (Ara-C) and (granulocyte-colony stimulating factor) G-CSF] for management of the blast crisis of his chronic myelogenous leukemia (CML). Our patient's ESS eruption presented with a variety of morphologies, thus multiple skin biopsies were taken to determine the possible diagnosis(es). All skin biopsies showed ESS and the eruption resolved with topical corticosteroids after CLAG therapy was finished.

Influence of endotoxin on graft-versus-host disease after bone marrow transplantation across major histocompatibility barriers in mice. Much clinical and experimental data suggest that infection and graft-versus-host disease (GVHD) are intimately associated, and that bacterial endotoxin (ET), a potent immunostimulant, influences the severity of GVHD. We have used a cell-wall-deficient mutant of Escherichia coli (E coli J5) to study the effect of active and passive immunization against ET in a murine model of GVHD induced by major histocompatibility antigens. CBA/Ca (H-2k) mice were irradiated and grafted with 1 X 10(7) bone marrow cells from C57BL/B6 (H-2b) donors. Groups of mice were immunized against J5: either actively immunized with killed J5 cells or pure J5 lipopolysaccharide, or passively immunized with rabbit anti-J5 antiserum (R alpha J5). Controls included irradiation controls, negative controls (syngeneic graft), positive controls (conventional mice receiving allogeneic graft), mice immunized with normal rabbit serum, Freund's adjuvant (FA), or human serum albumin (HSA) in FA. Active immunization with J5 exacerbated the effects of GVHD as indicated by increased weight loss (P = 0.002) and earlier death (P = 0.043). In contrast, immunization with HSA protected against weight loss (P = 0.028), and improved survival (P = 0.008). Passive immunization with J5 had no effect. These observations support the hypothesis that ET influences the pathogenesis of GVHD, and provide a useful model for studying the effects of ET in a well-defined immunological system.

Gradual implementation of first trimester screening in a population with a prior screening strategy: population based cohort study. To evaluate the implementation of first trimester screening in the Czech Republic during 1996-2007 on the number of infants born with numerical chromosomal anomalies, the gestational age at diagnosis and the number of invasive procedures. A population based cohort study. National Registry of Congenital Anomalies, 53 Czech Republic Genetic Departments. About 100,000 pregnancies per year. Primary outcomes were the rates of fetuses and newborns with diagnosed numerical chromosomal anomalies and the gestational age at diagnosis. Secondary outcomes were the rates of chorion villus sampling (CVS) and amniocenteses and the contribution of age groups on the detection rate of trisomy 21. The number of newborns with Down's syndrome decreased from 5.42/10,000 in 1996 to 3.66/10,000 newborns in the 2007. The total incidence of Down's syndrome increased from 13.42 to 20.66/10,000. The detection rate in women <35 years increased from 35.59 in 1996 to 45.08 in 2007; in women >35 years from 23.73 to 38.52. The number of amniocenteses/detected case of Down's syndrome was 124 in 1996 and 123 in 2007. The corresponding number of CVS decreased dramatically from 83 in 1996 to 10 in 2007. Despite the increase of maternal age and the corresponding increase of Down's syndrome, the number of newborns with Down's syndrome decreased. Implementation of the first trimester combined screening leads to a shift towards earlier diagnosis of all major chromosomal abnormalities.

Phase I study of intravenous ASA404 (vadimezan) administered in combination with paclitaxel and carboplatin in Japanese patients with non-small cell lung cancer. ASA404 (5,6-dimethylxanthenone-4-acetic acid, vadimezan), a flavone-8-acetic acid analogue, is a novel tumor-vascular disrupting agent. In this study, the safety and tolerability, pharmacokinetics and pharmacodynamics of ASA404 in combination with standard therapy of paclitaxel and carboplatin (P/C) were assessed. A total of 15 Japanese patients with stage IV advanced non-small cell lung cancer were enrolled and P/C plus ASA404 at three dose levels (600-1800 mg/m(2)) was administered every 3 weeks. Dose limiting toxicities were observed in two patients during Cycle 1 of ASA404 treatment (Grade 3 febrile neutropenia at ASA404 1200 mg/m(2) and Grade 3 QT prolongation at ASA404 1800 mg/m(2)) and the incidence of dose limiting toxicity was ≤1/3. The most frequently reported adverse events were injection site pain, peripheral sensory neuropathy, alopecia, neutropenia, nausea, anorexia and arthralgia, which were similar to those seen in previous Phase I/II studies. Pharmacokinetic analysis revealed the plasma area under the curve (AUC) of total ASA404 increased in a mostly dose-proportional manner within the dose range investigated. Administration of ASA404 raised plasma 5-hydroxyindole-3-acetic acid level dose-dependently by 116 and 204% after 1200 and 1800 mg/m(2) doses, respectively. Partial response was observed in four patients (27%), and seven patients (47%) exhibited stable disease. Overall, the safety and preliminary efficacy profiles were comparable to those seen in non-Japanese patients in previous Phase I and Phase II studies, and support the further evaluation of ASA404 (1800 mg/m(2)) in Phase III studies in combination with P/C in Japanese patients with advanced non-small cell lung cancer.

Nuclear magnetic resonance studies on the mechanism of regulation of glycogenolysis in contracting skeletal muscle. In vitro biochemical experiments showed that glycogenolysis can be regulated by two different mechanisms; i.e., Ca regulation at the phosphorylase step and phosphate-product regulation at the phosphofructokinase step. Recent studies on glycogenolysis in living vertebrate skeletal muscles by use of 31P nuclear magnetic resonance (NMR) presented evidence that glycogenolysis in vivo is regulated by Ca released from the sarcoplasmic reticulum. The present 31P NMR studies on living frog skeletal muscle indicated that glycogenolysis is further regulated by the phosphate products accumulated as the result of contractile activities. Therefore it was concluded that the glycogenolysis in vivo is actually regulated by the two mechanisms as predicted by in vitro biochemical studies.

Identification and amino acid sequence of the deoxynucleoside triphosphate binding site in Escherichia coli DNA polymerase I. We have labeled the large fragment of Escherichia coli DNA polymerase I (Pol I) with pyridoxal 5'-phosphate, a substrate binding site directed reagent for DNA polymerases [Modak, M. J. (1976) Biochemistry 15, 3620-3626]. A covalent attachment of pyridoxal phosphate to Pol I results in the loss of substrate binding as well as the polymerase activity. The inactivation was found to be strictly dependent on the presence of a divalent metal ion. Four moles of pyridoxal phosphate was found to react per mole of the enzyme, while in the presence of substrate deoxynucleoside triphosphate only 3 mol of pyridoxal phosphate was bound. To identify the substrate-protected site on the enzyme, tryptic peptides from enzyme labeled with pyridoxal phosphate and tritiated borohydride, in the presence and absence of substrate, were resolved on a C-18 reverse-phase column. A single peptide containing the substrate-protected site was identified and further purified. The amino acid composition and sequence analysis of this peptide revealed it to span residues 756-775 in the primary acid sequence of Pol I. Lys-758 of this sequence was found to be the site of the pyridoxal phosphate reaction. It is therefore concluded that Lys-758 is the site of binding for the metal chelate form of nucleotide substrates in E. coli DNA polymerase I.

The interaction between cytokines and neurotransmitters in depression and stress: possible mechanism of antidepressant treatments. No Abstract

Toward family-centered inpatient medical care: the role of parents as participants in medical decisions. To determine parental participation in medical decision-making (MDM) during hospitalization and its association with parental self-efficacy and to explore other factors associated with participation. We surveyed parents of children admitted to a pediatric medical unit to measure parental report of participation in MDM during hospitalization and self-efficacy with physician interactions (categorized into tertiles). We performed multivariate logistic regression to evaluate the association between self-efficacy and parental participation, controlling for potential confounders. One hundred thirty of 278 eligible parents completed surveys and 86% reported participating in MDM about their child's care. After adjusting for covariates, parents with scores in the middle and highest self-efficacy tertiles had higher odds of participating in MDM compared with parents in the lowest tertile. Younger parents and parents of previously hospitalized children were also more likely to participate although parents with a high school education or less were less likely. Self-efficacy was significantly associated with parental participation in MDM during hospitalization after adjusting for confounding factors. Interventions to increase self-efficacy may also improve parental participation in MDM.

qBrain-2, a POU domain gene expressed in quail embryos. We isolated a quail class III POU domain gene, qBrain-2, which was cloned from a cDNA library of E5 embryos. Northern blot and in situ hybridization analyses showed that qBrain-2 was expressed in developing central nervous system and adult brain. Moreover, qBrain-2 transcripts showed a dynamic distribution in embryonic central nervous system. Its transcripts were dominantly detected in the ventricular zone of the developing brain and spinal cord, but rarely in the differentiated region of mantle zone as well as the non-neuronal roof plate and floor plate. This suggests that qBrain-2 is involved in proliferation and differentiation of the neuroepithelial cells of quail central nervous system.

[Application of array-based comparative genomic hybridization in precise diagnosis of unbalanced chromosome aberration]. To evaluate the method of array-based comparative genomic hybridization (array-CGH) in identifying unbalanced chromosome aberrations. Four cases that could not be diagnosed by conventional cytogenetic technique were selected to undergo array-CGH analysis. DNA samples were extracted and hybridized with the Affymetrix SNP 6.0 arrays using Human Mapping SNP6.0 assay kit following the manufacturer's standard protocol. The data were analyzed by two professional software packages, GCOS and Genotyping Console. By using array-CGH technique, all the four cases were diagnosed precisely through identifying two duplications and two complex derivative chromosomes. Array-CGH is an effective method for whole-genome identification of unbalanced chromosomal aberrations with high sensitivity and specificity. It has a great value to investigate the correlations between genotype and phenotype in clinical service, especially in prenatal diagnosis.

Changes in mACh, NMDA and GABA(A) receptor binding after lateral fluid-percussion injury: in vitro autoradiography of rat brain frozen sections. Adult rats were subjected to a moderate lateral fluid percussion injury (FPI), followed by survival periods of 2 and 12 h. Regional NMDA subtype glutamate, muscarinic acetylcholine and GABA(A) receptor binding in various brain regions was analysed by quantitative in vitro autoradiography and short-lived positron emission tomography tracers [11C]cyano-dizocilpine, 4-N-[11C]methylpiperidylbenzilate (4-N-[11C]MPB), and [11C]flumazenil, respectively. The binding potential (BP, Bmax/KD) was calculated. The data with [11C]cyano-dizocilpine showed a significant decrease in BP bilaterally for the frontoparietal cortex and hippocampus at both time points, in comparison with that of the sham-operated controls. At 12 h the decrease was significantly more prominent for the ipsilateral cortex and hippocampus than for the contralateral side. The BP of 4-N-[11C]MPB was significantly decreased after 2 h for the trauma-side hippocampus, and after 12 h it had decreased for the trauma-site cortex and the bilateral hippocampus. The [11C]flumazenil exhibited a significant decrease in BP for the trauma-site cortex and the underlying hippocampus by 2 h after the traumatic brain injury. After 12 h a significantly decreased BP was observed only for the trauma-site cortex. The finding of a decreased BP demonstrates the involvement of these receptor systems in the development of cellular dysfunction, which is widespread and not limited to the site of lateral FPI.

Effect of oral chronic intoxication with sodium arsenite on murine giardiasis. Chronic exposure to toxicants alters immune function that can affect the ability of the host to mount a response to infection. Giardiasis is a gastrointestinal disease in which subtle alteration in immunity of the host can transform the normal acute infection into a chronic one. In this work we used a murine giardiasis model to evaluate the effect of chronic oral intoxication with sodium arsenite on the characteristics of giardiasis. BALB/c mice were intoxicated during 45 days with water containing 50, 125 or 250 microg/mL sodium arsenite. Each group was then inoculated with G. muris cysts. Cysts excreted in the feces were isolated and quantified. The toxic effect of arsenic on intestinal trophozoites was evaluated using G. lamblia trophozoites cultured in vitro with different arsenic concentrations, corresponding to equivalent concentrations of arsenic found in the gut lumen of intoxicated mice. Mice intoxicated with 125 and 250 microg/mL of sodium arsenite and infected with G. muris cysts displayed a shorter period of cysts excretion and were resistant to secondary infection with the parasite. In vitro studies showed that G. lamblia trophozoites were able to grow in presence of high sodium arsenite concentrations, suggesting the absence of a direct toxic effect on the parasite in the gut. Since a longer period of Giardia cysts excretion is associated with suppression of the immune system, the earlier clearance of primary G. muris infection in intoxicated mice suggests the induction of an immune modification that leads to an improved ability of mice to overcome the infection.

Automatic mode switching of implantable pacemakers: I. Principles of instrumentation, clinical, and hemodynamic considerations. Automatic mode switching (AMS) is now a programmable function in most contemporary dual chamber pacemakers. Atrial tachyarrhythmias are detected when the sensed atrial rate exceeds a "rate-cutoff," "running average," "sensor-based physiological" rate, or using "complex" detection algorithms. AMS algorithms differ in their atrial tachyarrhythmia detection method, sensitivity, and specificity and, thus, respond differently to atrial tachyarrhythmia in terms of speed to the AMS onset, rate stability of the response, and speed to resynchronize to sinus rhythm. AMS is hemodynamically beneficial, and most patients with atrial tachyarrhythmias are symptomatically better with an AMS algorithm in their pacemakers. New diagnostic capabilities of pacemaker especially stored electrograms not only allow programming of the AMS function, but enable quantification of atrial fibrillation burden that facilitate clinical management of patients with implantable devices who have concomitant atrial tachyarrhythmia.

Gas Chromatography-Mass Spectrometry and Analysis of the Serum Metabolomic Profile Through Extraction and Derivatization of Polar Metabolites. Metabolite profiling in complex biological matrices such as serum requires high-throughput technologies capable of accurate and reproducible quantitative analysis and detection of slight differences in metabolite concentrations. Gas chromatography-mass spectrometry (GC-MS) is widely used for characterizing the metabolome. This chapter summarizes the necessary preparatory steps required to profile the metabolome using GC-MS. While this chapter focuses on evaluating polar metabolites in serum samples, the methods can be adapted to quantify nonpolar metabolites in other biological matrices.

Coronary vascular response to adrenergic stimulation in exercise-conditioned dogs. The present study was designed to determine whether daily exercise alters adrenergic and muscarinic neural control of coronary blood flow during resting and exercising conditions in the conscious dog. Mean left circumflex artery blood flow (CBF), mean coronary blood pressure, and heart rate were measured during resting conditions (55 +/- 9 ml/min, 108 +/- 6 mmHg, and 93 +/- 2 beats/min, respectively) and during submaximal exercise (85 +/- 9 ml/min, 108 +/- 7 mmHg, and 210 +/- 15 beats/min). Injection of phentolamine into the left circumflex coronary artery during treadmill exercise resulted in a 10 +/- 1% increase in CBF before training (untrained, UT) and a 21 +/- 6% increase after 4-5 wk of daily exercise (partially trained, PT) (P less than 0.02 UT vs. PT). Intracoronary atenolol or propranolol caused a 15 +/- 6% reduction in CBF during exercise in dogs before and after PT. While the dogs were lying quietly at rest intracoronary injections of norepinephrine initially increased CBF 85%, followed by a prolonged 19 +/- 9% decrease in CBF. CBF decreased 16 +/- 3% after intracoronary injection of phenylephrine. After PT the coronary vasoconstriction following norepinephrine and phenylephrine injections was significantly potentiated (31 +/- 6 and 35 +/- 4%, respectively). These data suggest that exercise training caused significant changes in the coronary vascular response to alpha-receptor stimulation so that an alteration in the neural control of the coronary circulation occurred.

Molecular diffusion and slip boundary conditions at smooth surfaces with periodic and random nanoscale textures. The influence of periodic and random surface textures on the flow structure and effective slip length in Newtonian fluids is investigated by molecular dynamics (MD) simulations. We consider a situation where the typical pattern size is smaller than the channel height and the local boundary conditions at wetting and nonwetting regions are characterized by finite slip lengths. In the case of anisotropic patterns, transverse flow profiles are reported for flows over alternating stripes of different wettability when the shear flow direction is misaligned with respect to the stripe orientation. The angular dependence of the effective slip length obtained from MD simulations is in good agreement with hydrodynamic predictions provided that the stripe width is larger than several molecular diameters. We found that the longitudinal component of the slip velocity along the shear flow direction is proportional to the interfacial diffusion coefficient of fluid monomers in that direction at equilibrium. In case of random textures, the effective slip length and the diffusion coefficient of fluid monomers in the first layer near the heterogeneous surface depend sensitively on the total area of wetting regions.

Regulation of complement-3 protein expression in human and mouse oviducts. The human oviduct derived embryotrophic factor-3 (ETF-3) contains complement protein-3 (C3) and its derivates. Although C3 is not embryotrophic, it is converted into the embryotrophic derivative, iC3b in the presence of embryos and oviductal cells. The regulation of C3 production in the oviduct is not known. The objectives of this study were to investigate the effects of presence of preimplantation embryos and hormones on C3 expression in the oviducts in vitro and in vivo. The expression of C3 in the oviduct of pregnant mice was compared to that of pseudo-pregnant mice. The hormonal action on C3 expression was studied in the ovariectomized mouse oviducts and human oviductal epithelial (OE) cells. The results showed that the level of C3 mRNA in the mouse oviduct was high on Day 1 and Day 2, but decreased to a minimum on Day 4 of pregnancy, whereas that of pseudo-pregnancy remained relatively stable within the same period. The protein levels of C3 and iC3b specific fragments, alpha-115 and alpha-40, respectively in the mouse oviductal luminal fluid were highest on Day 3 of pregnancy, when the embryos were expected to be most sensitive to the embryotrophic activity of ETF-3. Estrogen elevated C3 expression in the ovariectomized mouse oviduct and the OE cells. Progesterone suppressed estrogen-induced C3 expression in the mouse oviduct, but had no effect on OE cells. In conclusion, the presence of embryo and steroid hormones regulate the synthesis and secretion of oviductal C3.

θ power responses in mild Alzheimer's disease during an auditory oddball paradigm: lack of theta enhancement during stimulus processing. There is evidence that theta responses reflect cognitive performance: good performances are associated with a decrease in tonic theta power as well as an increase in phasic theta power. In the present study, both tonic and phasic theta activity were analysed in 22 patients with mild Alzheimer's disease (AD), and 16 healthy elderly controls. Single-trial theta power responses were evaluated by an active auditory oddball paradigm along an early poststimulus window (0-250 ms) and a late time window (250-500 ms), and then compared to prestimulus theta power during both target tone and standard tone processing. The main findings were: (1) in AD patients, there was an increased prestimulus theta power, as well as no significant poststimulus theta power increase upon both target and non-target stimulus processing; (2) in healthy aged controls, only during target tone processing, an enhancement of both early and late theta responses relative to the prestimulus baseline was found. Moreover, healthy controls had a frontal dominance of theta power. The results might indicate that, during target processing, theta response is not functionally sensitive in AD and cannot be involved in processing demands as efficiently as in healthy controls. From a psychophysiological point of view, this might suggest an impairment of attentional allocation resources. The psychological implications might be related to selective attention/working-memory impairment from the early stage of the disease. Our data confirm that both tonic and phasic theta are relevant indicators of cognitive performance: the lack of a phasic theta and an increase in tonic theta are congruous findings in cognitive decline. Another factor worth noting is that in AD patients theta response is not dominant at the frontal site (as observed in healthy controls), indicating a weaker frontal lobe network reactivity during stimulus processing.

Potentiation of lipopolysaccharide-inducible cyclooxygenase 2 expression by C2-ceramide via c-Jun N-terminal kinase-mediated activation of CCAAT/enhancer binding protein beta in macrophages. Ceramide, formed by sphingomyelinase, is involved in the expression of cyclooxygenase-2 (COX-2). This study examines the effect of C2-ceramide (C2), a cell-permeable ceramide analog, on the lipopolysaccharide (LPS)-inducible COX-2 expression and signaling pathways. C2 did not induce COX-2 but potentiated LPS-inducible COX-2 expression in Raw264.7 cells, whereas dihydro-C2 was inactive. Treatment of cells with C2 notably increased LPS-inducible CCAAT/enhancer binding protein (C/EBP) DNA binding. Antibody supershift experiments revealed that LPS-induced C/EBP DNA binding activity depended on C/EBP beta and C/EBP delta but not C/EBP alpha, C/EBP epsilon or CBP/p300. C/EBP beta contributed to C2-enhanced DNA binding activity. 4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl) 1H-imidazole (SB203580), a p38 kinase inhibitor, completely inhibited LPS-inducible and C2-potentiated LPS-inducible COX-2 expression. Enhancement of LPS-inducible COX-2 expression and C/EBP DNA binding by C2 was abrogated in dominant-negative mutant of JNK1 [JNK1(-)] cells. 2'-Amino-3'-methoxyflavone (PD98059) or stable transfection with dominant-negative mutant of MKK1 decreased COX-2 induction by LPS but failed to inhibit C2-enhanced LPS induction of COX-2. Transfection with dominant-negative mutant of C/EBP inhibited the ability of C2 to potentiate the induction of COX-2 by LPS. In LPS-treated cells, C2 enhanced both the nuclear translocation and the expression of LPS-inducible C/EBP beta with an increase in AP-1 DNA binding activity. These enhancements were abolished by JNK1(-) transfection. AP-1 decoy oligonucleotide suppressed C2-potentiated C/EBP beta expression, indicating that AP-1 was responsible for C2-mediated C/EBP beta expression. These results demonstrate that C2 increases C/EBP beta-mediated COX-2 induction by LPS and that the pathway of JNK1 but not ERK1/2 is responsible for C/EBP beta activation involving activator protein-1-mediated enhanced C/EBP beta expression.

The value of sputum 8-isoprostane in detecting oxidative stress in mild asthma. Exhaled nitric oxide and induced sputum eosinophils are well established as direct markers of inflammation/oxidative stress in asthma. Recently, it has been proposed that sputum 8-isoprostane concentrations may present a reliable index for measuring oxidative stress in asthmatic patients. We assessed the value of sputum 8-isoprostane in mild asthma in children and adolescents. Patients with newly diagnosed asthma (children, n = 23; adults, n = 14) and age-matched healthy controls (children, n = 13; adults, n = 15) were studied. Lung function was measured by spirometry, sputum was induced by hypertonic saline, and fractional exhaled nitric oxide (FeNO) was measured with standard methods. Cell differential counts were obtained from sputum slides and the concentration of 8-isoprostane was measured with an enzyme immunoassay from sputum supernatants. High-quality sputum specimens could be obtained from 10 children and 10 adults, and the sputum analyses were conducted only for the representative specimens. Asthmatics had increased FeNO (children 35.5 vs. 11.9 ppb; adults 81.1 vs. 16.6 ppb; p < 0.001) and sputum eosinophils (children 2.4% vs. 1.4%; adults 10.4% vs. 0.2%; p = 0.005) compared to healthy controls. There was a significant correlation between FeNO and eosinophils (R = 0.65; p < 0.0001). Sputum 8-isoprostane was not elevated in asthmatics compared to healthy subjects (children 81.1 vs. 89.9 and adults 76.9 vs. 73.4 pg/mL) and did not correlate with lung function or other measurements of airway inflammation. However, increased 8-isoprostane levels were detected in patients with chronic obstructive pulmonary disease (n = 11, 184.7 pg/mL, used as controls for assays). In agreement with earlier studies, FeNo is sensitive in detecting oxidative/nitrosative stress in asthmatic airways. However, our results suggest that 8-isoprostane may not be sensitive in reflecting oxidant burden in mild asthma.

Analysis of DNA probes for the prenatal diagnosis of cystic fibrosis. Cystic fibrosis is a common autosomal recessive disease in white persons. Prenatal diagnosis by DNA analysis became possible in families with a child who is affected by cystic fibrosis when the probes pJ3.11, metH and metD, which are linked closely to the cystic fibrosis gene (CF) were described. The recent description of the XV-2c and KM.19 probes has improved the prenatal diagnosis of cystic fibrosis greatly. The KM.19 probe alone was informative in eight of 12 families that were studied while XV-2c was informative in eight of 12 families that were studied while XV-2c was informative in only two of the 12 families. In contrast, the use of the pJ3.11, metH and metD probes in combination allowed full diagnosis in six of the 12 families. The combined use of the CF-linked probes produced informative data for all 12 families. Therefore, in most families with at least one affected living child, the first-trimester diagnosis of cystic fibrosis is possible with fetal DNA that has been prepared from chorionic villous samples. Strong linkage disequilibrium was found with both the KM.19-PstI polymorphism and the XV-2c-TaqI polymorphism and the CF gene.

[Fundus autofluorescence patterns of drusen in age-related macular degeneration]. To investigate the characteristics of fundus autofluorescence (FAF) patterns of drusen in patients with nonexudative age-related macular degeneration (AMD). It was a retrospective case series study. Spatial distribution and intensity of FAF of 63 cases (78 eyes) with nonexudative AMD were recorded using a confocal scanning laser ophthalmoscopy (cSLO, Heidelberg Retina Angiograph 2, HRA2, Heidelberg, Germany), the excitation light used was at 488 nm (argon laser), emission light at 514 nm (barrier filter), and fundus field-of-view at 30-degrees. Color fundus photographs were obtained with Kowa Nonmyd 7. Three-dimensional fundus images were captured by spectral domain optical coherence tomography (Topcon, 3D OCT-1000, Japan). The FAF changes did not correlate topographically with visible fundus changes and 3D-OCT images in 78 eyes with drusen in nonexudative AMD. The majority of these eyes (68 out of 78) showed abnormal FAF signal of drusen at the posterior pole, which could be classified into seven different patterns according to their different features: minimal, focal confluent, linear, patchy, lace-like, speckled and scattered changes. In the remaining 10 eyes, the small lesions presented in color fundus photos were not detected in FAF examination. Therefore, a homogeneous background signal similar to the normal fundus was obtained by FAF examination. In addition, 15 patients exhibited abnormal autofluorescence in both eyes, 13 of them showed asymmetrical FAF changes, indicating that asymmetrical lesions might be presented. Various patterns of abnormal FAF can be clearly imaged with HRA2-cSLO in nonexudative AMD, reflecting different stages of this disease. Periodic observation of drusen with FAF examination is of great clinical value in the estimation of occurrence and development of AMD.

Developmental Studies of Maize-Infesting Picture-Winged Flies (Diptera: Ulidiidae). Eleven species of picture-winged flies (Diptera: Ulidiidae) attack maize (Zea mays L.) in the Americas. Field and laboratory studies were used to determine developmental times on sweet corn ears for the three most common species attacking the crop in the United States, Chaetopsis massyla (Walker), Euxesta eluta Loew, and Euxesta stigmatias Loew. Egg plus larval stage developmental times were evaluated in early Spring and late Fall 2009, and late Spring 2010, by placing newly deposited eggs in protected ears in the field. Newly formed puparia were removed daily from cages and held in the laboratory to determine pupal developmental times. Developmental times were compared with flies reared on artificial diet in the laboratory. Ear- and diet-reared adults were held until their death to determine adult longevity. Developmental times, including for pupae from ear-reared larvae, were significantly affected by species and season. All three species required nearly twice as long to complete development in the late Fall compared to late Spring studies. Flies required 3-13 d longer to complete development on artificial diet than on ears. Euxesta eluta adults lived two to three times longer than the other species, and females of all species lived 10-15% longer than males. Species and seasonal developmental times are discussed in relation to ear developmental times and control strategies. It is estimated that 16-19 generations per year of all three fly species can develop in the field in the sweet corn production area of southern Florida.

Surgery of the naso-frontal angle. The naso-frontal angle is one of the features that most markedly determines the morphology of the human face. Two main morphological elements must be taken into consideration: the slope of the forehead and the line of nasal dorsum. For a balanced physiognomy, nevertheless, it is necessary to achieve a correct interaction of the length and width of nasal pyramid, the naso-labial angle, and the chin. Closer examination of the naso-frontal angle shows that a cranial or caudal shift in its position affects the length of the dorsum; however, the fundamental aspect characterizing the naso-frontal angle is its width: it may be normal, too wide, or too narrow. Turning to surgical correction, the authors state that it is easier to modify an over-narrow angle, than one that is too wide. The authors show the single surgical techniques adopted for the correction of the angle, emphasizing the personal method applied to the overwide angle.

Antibodies to tumor necrosis factor alfa attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat. Tumor necrosis factor (TNF)alpha, a pivotal cytokine involved in inflammation, is produced primarily by Kupffer cells in the liver. It has been shown that inactivation of Kupffer cells prevents alcohol-induced liver injury; therefore, the purpose of this study was to determine if neutralizing anti-TNF-alpha antibody is also effective. Male Wistar rats were exposed to ethanol (11 to 12 g x kg(-1) x d[-1]) continuously for up to 4 weeks via intragastric feeding using an enteral feeding model. Before ethanol exposure, polyclonal anti-mouse TNF-alpha rabbit serum was injected (2.0 mg/kg intravenously). There were no significant differences in body weight, mean ethanol concentration, or cyclic patterns of ethanol in urine when ethanol- and ethanol plus antibody-treated groups were compared. Expression of TNF-alpha and macrophage inflammatory protein 2 (MIP-2) messenger RNA (mRNA), determined using reverse transcription-polymerase chain reaction, was three- to four-fold higher in livers of ethanol-treated rats than in those of rats fed an ethanol-free, high-fat control diet. In addition, MIP-2 levels were also elevated when detected by Northern blot analysis. Anti-TNF-alpha antibody did not affect expression of mRNA for interleukin (IL) 1alpha, IL-6, transforming growth factor beta1, or TNF-alpha. However, MIP-2 mRNA expression, which is regulated by TNF-alpha, was decreased significantly by anti-TNF-alpha antibody treatment. Serum aspartate transaminase levels were elevated in ethanol-treated rats to 136 +/- 12 IU/L after 4 weeks but only reached 90 +/- 5 IU/L (P < .05) in rats treated with anti-TNF-alpha antibody. The hepatic inflammation and necrosis observed in ethanol-fed rats were attenuated significantly by antibody treatment, and steatosis was not. These results support the hypothesis that TNF-alpha plays an important role in inflammation and necrosis in alcohol-induced liver injury and that treatment with anti-TNF-alpha antibody may be therapeutically useful in this disease.

Using a silicone-based dressing as a primary wound contact layer. The use of silicone-based dressings as a primary contact layer for wound care can prevent epithelial stripping, pain and sensitivity and have been widely available for nearly 20 years. Cuticell Contact from BSN medical is the latest silicone-based dressing to add to the armoury of the wound care clinician. Using documented case studies the author explores the reasoning behind why clinicians should consider re-examining the use of silicone dressings.

A Novel Class of N-Sulfonyl and N-Sulfamoyl Noscapine Derivatives that Promote Mitotic Arrest in Cancer Cells. Noscapine displays weak anticancer efficacy and numerous research efforts have attempted to generate more potent noscapine analogues. These modifications included the replacement of the N-methyl group in the 6'-position with a range of substituents, where N-ethylcarbamoyl substitution was observed to possess enhanced anticancer activity. Herein, we describe advances in this area, namely the synthesis and pharmacological evaluation of a series of N-sulfonyl and N-sulfamoyl noscapine derivatives. A number of these sulfonyl-containing noscapinoids demonstrated improved activities compared to noscapine. ((R)-5-((S)-4,5-Dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-((1-methyl-1H-imidazol-4-yl)sulfonyl)-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinoline) (14 q) displayed sub-micromolar activities of 560, 980, 271 and 443 nM against MCF-7, PANC-1, MDA-MB-435 and SK-MEL-5 cells, respectively. This antiproliferative effect was also maintained against drug-resistant NCI/AdrRES cells despite high expression of the multidrug efflux pump, P-glycoprotein.

Implementation of a Reductive Route of One-Carbon Assimilation in Escherichia coli through Directed Evolution. Endowing biotechnological platform organisms with new carbon assimilation pathways is a key challenge for industrial biotechnology. Here we report progress toward the construction of formatotrophic Escherichia coli strains. Glycine and serine, universal precursors of one-carbon compounds oxidized during heterotrophic growth, are produced from formate and CO2 through a reductive route. An adaptive evolution strategy was applied to optimize the enzymatic steps of this route in appropriate selection strains. Metabolic labeling experiments with 13C-formate confirm the redirected carbon-flow. These results demonstrate the high plasticity of the central carbon metabolism of E. coli and the applicative potential of directed evolution for implementing synthetic pathways in microorganisms.

Increase in G protein-coupled receptor autoantibodies with decline of cardiac function in hypercholesterolemic rats. This study aimed to explore the effects of diet-induced hypercholesterolemia (HC) on the production of G protein-coupled receptor autoantibodies and to elucidate the potential mechanisms involved. Male Wistar rats were fed a normal or high-cholesterol diet for 8 weeks. Cardiac function, autoantibodies against G protein-coupled receptors, the beat frequency of neonatal cardiomyocytes, the CD4+/CD8+ T-lymphocyte ratio and lymph leukocyte counts in the spleen were determined. Diet-induced hypercholesterolemia significantly increased the levels of autoantibodies against α1- and β1-adrenergic receptors and the angiotensin II type 1 receptor in sera, as well as the CD4+/CD8+ T-lymphocyte ratio and lymph leukocyte count in the spleen, and decreased cardiac function. There were strong negative correlations between the levels of autoantibodies and cardiac injury. The present study demonstrates, for the first time, that G protein-coupled receptor autoantibodies exist in the sera of hypercholesterolemic rats and that the levels of these autoantibodies are related to cardiac function, which implies that these cardiac receptor autoantibodies may play a role in cardiac dysfunction in hypercholesterolemic rats.

[Synthesis of a lens-specific antigen (delta-crystallin) in rudimentary chicken adenohypophysis]. The synthesis of two lens-specific proteins, delta- and beta-crystallins, by adenohypophyseal anlage of 4-day chick embryos was studied by the immunofluorescence technique in conjunction with autoradiography. Isolated anlages were incubated for 16 hours in a culture medium containing 14c-leucine. The synthesis was determined with the use of an unlabelled carrier, extract of chick lens, as well as of antisera against delta- and beta-crystallins. 14C-Leucine incorporation was found to occur only in delta-crystalline precipitation line rather than in beta-crystallin line. This evidence attests to the synthesis of delta-crystalline by the chick embryo adenohypophyseal anlage. The results are in agreement with the previously obtained immunohistochemical data on delta-crystalline localization in cells of the developing adenohypophysis.

Coupling of cytoskeleton functions for fibroblast locomotion. Using a chick cell phenotype specialised for locomotion with morphometric measurements made possible by modern instrumentation technology, we have reinvestigated motile functions in fibroblast locomotion. Quantitative analysis of rapid fluctuations in cell form and organelle distribution during locomotion showed many significant correlations between different parts of the cell despite much irregularity in individual displacements over the time scale of the order of one second. These broke down when external perturbations caused changes in shape or direction. Partial energy deprivation caused the cells to lose control of shape and organelle distribution even though forward protrusion continued unaffected. Cytoplasmic displacements shown by marker mitochondria correlated with adjacent fluctuations at the leading edge, and drug treatments which increased the amplitude of mitochondrial movements caused visible protrusions in projected positions at the leading edge. We conclude that fibroblast locomotion may be driven coordinately by a common set of motility mechanisms and that this coordination may be lost as a result of physical or pharmacological disturbance. Taking our evidence with results from other Laboratories, we propose the following cytoskeleton functions. (i) Protrusive activity, probably based on solation--gelation cycles of the actin based cytoskeleton and membrane recycling which provides cellular and membrane components for streaming through the cell body to the leading edge; this is Ca++ sensitive but relatively energy insensitive. (ii) Constraining activity on the cell membrane and on certain organelles to maintain shape and so facilitate directionality and the drawing along of the trailing body; this is Ca++ insensitive but relatively energy sensitive. (iii) Channeling function of microtubules to direct the flow towards multiple foci on the leading edge, and so determine cell polarity. Such a mechanism of locomotion for fibroblasts has many features consistent with evidence for other cell types, especially amoebae and leukocytes.

Oxalate digestibility in Neotoma albigula and Neotoma mexicana. The cactus specialist, Neotoma albigula, tolerates high concentrations of potentially harmful oxalate compounds in its diet. Previous research has shown that oxalate compounds are broken down by intestinal micro-organisms. Thus the ability of N. albigula to utilize a diet high in oxalates may be a consequence of the adaptation of the microflora rather than its own evolution. To test this hypothesis, the oxalate degradation ability of N. albigula was compared with that of N. mexicana, a generalist herbivore. Apparent oxalate digestibility was not significantly different in the two species, when tested using field-acclimated individuals. Analysis of scats recovered from traps indicated that both species were consuming oxalates in the wild. I conclude that the ability of these herbivores to tolerate oxalates is a natural consequence of the utilization of microbial fermentation to degrade the structural carbohydrates of plants coupled with the high adaptive and evolutionary potential of the microflora.

Modification of proteins in endothelial cell death during oxidative stress. Exposure of bovine aortic endothelial cells in vitro to oxidative stress causes a cascade of changes in cell function, culminating in cell death if the stress is sufficiently severe. Oxidative modification of proteins, as measured by the reaction of 2,4-dinitrophenylhydrazine with carbonyl groups of oxidized proteins, increased three- to fourfold in endothelial cells exposed to hydrogen peroxide or to a xanthine/xanthine oxidase system. The increase in oxidative modification of protein occurred rapidly, preceding loss of cellular ATP and eventual cell death. Oxidative modification of protein was paralleled by loss of activity of the key metabolic enzymes, glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The finding that oxidative modification of protein is an early event following oxidative stress suggests that oxidative modification of protein is not only a marker for oxidative damage but also a causal factor in oxidative injury.

Isolation and partial characterization of three rumen Lactobacillus plantarum bacteriophages. The first isolation of Lactobacillus plantarum bacteriophages from ruminal fluid is reported. Three bacteriophages were characterized on the basis of plaque morphology, host ranges, stability, electron microscopic morphology and DNA restriction endonuclease digestion patterns. They formed clear plaques and are placed in group A of Bradley's scheme and have identical host ranges. Bacteriophages were stable to urea and chloroform. They were relatively thermostable but partially inactivated by rumen fluid and by acetate. DNA restriction analysis showed that phage L20 had different numbers of cleavage sites in comparison with the next two phages.

Risks and protective factors associated with symptoms of depression in low-income African American and Caucasian women during pregnancy. This article describes the risks and protective factors for symptoms of depression in pregnancy among low-income African American and Caucasian women. Data were collected from 130 women who were between 16 and 28 weeks' gestation and enrolled in an urban prenatal clinic. The questionnaires used in the face-to-face interviews consisted of sociodemographic items, the Beck Depression Inventory (BDI-II), the Prenatal Psychosocial Profile (PPP), 3 items from the Jarel Spiritual Well-Being Scale, the Spiritual Perspective Scale, and 4 items on health risk behaviors. Twenty-seven percent of the women reported depressive symptoms at levels indicating risk for clinical depression. However, there were no significant differences between African American and Caucasian women. Sociodemographic factors accounted for 13% of the variance (P < .01) in BDI-II scores. Psychosocial and behavioral risk factors accounted for an additional 19% of the BDI-II variance (P < .001), and psychosocial and spiritual resources accounted for 7% of the variance (P < .001), resulting in these variables accounting for 54% of the total variance in BDI-II scores. Higher levels of stress, lower levels of self-esteem and social support, and higher religiosity had a significant relationship with more symptoms of depression. This supports the need to routinely screen for and to assess factors associated with depressive symptoms in pregnant low-income women.

Automated mass detection in contrast-enhanced CT colonography: an approach based on contrast and volume. The purpose of this feasibility study was to design and test an algorithm for automating mass detection in contrast-enhanced CT colonography (CTC). Five patients with known colorectal masses underwent a pre-surgical contrast-enhanced (120 ml volume 1.6 g iodine/s injection rate, 60 s scan delay) CTC in high spatial resolution (16-slice CT: collimation: 16x0.75 mm, tablefeed: 24 mm/0.5 s, reconstruction increment: 0.5 mm). A CT-density- and volume-based algorithm searched for masses in the colonic wall, which was extracted before by segmenting and dilating the colonic air lumen and subtracting the inner air. A radiologist analyzed the detections and causes of false positives. All masses were detected, and false positives were easy to identify. Combining CT density with volume as a cut-off is a promising approach for automating mass detection that should be further refined and also tested in contrast-enhanced MR colonography. More information under http://www.screening.info.

Identifying new risk factors for Pseudomonas aeruginosa pneumonia in intensive care units: experience of the French national surveillance, REA-RAISIN. Pseudomonas aeruginosa is an important pathogen of complicated pneumonia in intensive care units (ICUs). Our objective was to determine 'patient' and 'ward' risk factors for P. aeruginosa pneumonia among patients with nosocomial pneumonia in ICU. Data from the 2004-2006 prospective French national nosocomial infection surveillance in ICUs (REA-RAISIN) were used, including patients admitted for >48 h in ICU and who developed nosocomial pneumonia. Only first pneumonia was considered and categorised as either P. aeruginosa pneumonia or other micro-organism pneumonia. Multilevel logistic regression model (patient as first level and ward as second) with P. aeruginosa pneumonia as binary outcome was performed. Of 3,837 included patients from 201 different wards, 25% had P. aeruginosa pneumonia. P. aeruginosa was significantly more frequent in late onset pneumonia. Higher probability of P. aeruginosa pneumonia was associated with higher age and length of mechanical ventilation, antibiotics at admission, transfer from a medical unit or ICU, and admission in a ward with higher incidence of patients with P. aeruginosa infections. Lower probability of P. aeruginosa was associated with traumatism and admission in a ward with high patient turnover. Our analyses identified a patient's profile and some ward elements that could make suspect P. aeruginosa in case of nosocomial pneumonia.

Electrocerebral inactivity as a temperature effect: unlikely as an isolated etiology. Although hypothermia is a cause of occasional cerebral inactivity, it appears that this change occurs only at temperatures well below those seen in most clinical conditions, even in intensive care units. Loss of EEG activity occurs at temperatures below the room temperature in the typical hospital. With elevated temperature, decline in voltage can occur, but it would appear that total cerebral inactivity does not occur solely from hyperthermia, and that the development of such records should strongly suggest to the clinician that there is some additional problem most likely involving anoxia or inadequate vascular supply, if it is clear that drugs are not the responsible factor. Extreme temperature change is usually medically provoked if well monitored. In the very special circumstances where temperature is deliberately varied, it appears that EEG activity can be expected to persist from 66 degrees to 106 degrees F. "Electrocerebral inactivity" should raise the possibility that etiologies other than temperature effect alone are involved.

Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging. Verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. We have demonstrated that such deficits do not extend to working memory for tones in a substantial number of patients even when verbal working memory is impaired. In this study we used functional magnetic resonance imaging to study the neural basis of this dissociation of auditory verbal and nonverbal working memory in individuals with schizophrenia. While undergoing functional magnetic resonance imaging, 12 schizophrenic patients and 12 matched control subjects performed auditory Word Serial Position Task and Tone Serial Position Task. Both tasks produced activation in frontal cortex and temporal and parietal lobes of the cerebrum in both groups. While robust activation was observed in the left inferior frontal gyrus (areas 6, 44, and 45) in the control group during the Word Serial Position Task, activation in the patient group was much reduced in these areas and failed to show the same task-specific activation as in controls. Reduced activation in patients was not confined to the inferior frontal gyrus, but also extended to a medial area during the Tone Serial Position Task and to premotor and anterior temporal lobe areas during both tasks. These findings support the hypothesis that abnormalities in cortical hemodynamic response in the inferior frontal gyrus underlie the verbal working memory deficit in schizophrenia. The relationship of verbal working memory deficits to other cognitive functions suggests that abnormal functioning in the speech-related areas may reflect a critical substrate of a broad range of cognitive dysfunctions associated with schizophrenia.

Viral mutations, TCR antagonism and escape from the immune response. Persistent viruses use several mechanisms to evade the immune response, including the generation of mutations that affect TCR recognition. It has recently been reported that spontaneous mutations at TCR contact sites within individual viral epitopes in certain persistent human viruses can abrogate or antagonize the recognition of the corresponding wild-type epitope, and it has been suggested that such mutations may contribute to viral persistence.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry of DNA-Pt(II) complexes. Matrix-assisted laser desorption ionization (MALDI) time-of-flight mass spectrometry has been used to characterize the reaction products of the 18-mer deoxyribonucleotide d(AACGGTTAACCGTTAATT) with [Pt(NH3)3(H2O)]2+ and cis-[Pt(NH3)2(H2O)2]2+. Characteristic peaks corresponding to different monofunctional adducts (18-mer+n[Pt(NH3)3]) (n = 1, 2, 3 and 4) have been observed with the triamino-monoaqua complex. With the diamino-diaqua cis-Pt complex, formation of a chelate (18-mer+[Pt(NH3)2]) involving two adjacent guanines has been demonstrated. A good correlation between MALDI and polyacrylamide gel electrophoresis results is observed.

Exenatide (a GLP-1 agonist) expresses anti-inflammatory properties in cultured human monocytes/macrophages in a protein kinase A and B/Akt manner. Incretin-based therapies in the treatment of type 2 diabetes mellitus are associated with significant improvements in glycemic control, which are accompanied by a beneficial impact on atherosclerosis. Macrophages are essential in the development of atherosclerotic plaques and may develop features that accelerate atherosclerosis (classically activated macrophages) or protect arterial walls against it (alternatively activated macrophages). Therefore, we explored whether beneficial actions of exenatide are connected with the influence on the macrophages' phenotype and synthesis of inflammatory and anti-inflammatory cytokines. Monocytes/macrophages were harvested from 10 healthy subjects. Cells were cultured in the presence of exenatide, exendin 9-39 (GLP-1 antagonist), LPS, IL-4, PKI (PKA inhibitor) and triciribine (PKB/Akt inhibitor). We measured the effects of the above-mentioned compounds on markers of macrophages' phenotype (inducible nitrous oxide (iNOS), arginase 1 (arg1) and mannose receptors) and concentration of nitrite, IL-1β, TNF-α and IL-10. Exenatide significantly increased the level of IL-10 and decreased both TNF-α and IL-1β in LPS-treated monocytes/macrophages. Furthermore exenatide increased the expression of arg1-a marker of classical activation and reduced the LPS-induced expression of iNOS-a marker of classical activation. According to experiments with protein kinases inhibitors we found that proinflammatory markers were protein kinase A dependent, whereas the activation of alternative activation was similarly reliant on protein kinase A and B/Akt. We showed that exenatide skewed the macrophages phenotype toward anti-inflammatory phenotype and this effect is predominantly attributable to protein kinase A and to a less extent to B/Akt activation.

Lipid-AuNPs@PDA nanohybrid for MRI/CT imaging and photothermal therapy of hepatocellular carcinoma. Multifunctional theranostic nanoparticles represent an emerging agent with the potential to offer extremely sensitive diagnosis and targeted cancer therapy. Herein, we report the synthesis and characterization of a multifunctional theranostic agent (referred to as LA-LAPNHs) for targeted magnetic resonance imaging/computed X-ray tomography (MRI/CT) dual-mode imaging and photothermal therapy of hepatocellular carcinoma. The LA-LAPNHs were characterized as having a core-shell structure with the gold nanoparticles (AuNPs)@polydopamine (PDA) as the inner core, the indocyanine green (ICG), which is electrostatically absorbed onto the surface of PDA, as the photothermal therapeutic agent, and the lipids modified with gadolinium-1,4,7,10-tetraacetic acid and lactobionic acid (LA), which is self-assembled on the outer surface as the shell. The LA-LAPNHs could be selectively internalized into the hepatocellular cell line (HepG2 cells) but not into HeLa cells due to the specific recognition ability of LA to asialoglycoprotein receptor. Additionally, the dual-mode imaging ability of the LA-LAPNH aqueous solution was confirmed by enhanced MR and CT imaging showing a shorter T1 relaxation time and a higher Hounsfield unit value, respectively. In addition, the LA-LAPNHs showed significant photothermal cytotoxicity against liver cancer cells with near-infrared irradiation due to their strong absorbance in the region between 700 and 850 nm. In summary, this study demonstrates that LA-LAPNHs may be a promising candidate for targeted MR/CT dual-mode imaging and photothermal therapy of hepatocellular carcinoma.

Paradoxical embolism: an underestimated entity. A plea for comprehensive work-up. Forty-one cases of arterial embolism were reviewed. The work-up included M + 2D echocardiography in 29 patients (71%), arteriography in 22 (54%), both echocardiography and arteriography in 19 (46%), and abdominal aortic ultrasound in 18 (43%). The sources of emboli were probable cardiac (8 = 20%)--mural cardiac thrombus detected by echocardiogram; possible cardiac (12 = 29%)--arrhythmias or other cardiac pathology detected without mural thrombus; probable arterio-arterial (7 = 17%)--proximal arterial thrombus detected; probable paradoxical embolism (2 = 5%)--fulfills the Johnson criteria with cardiac defect and right-to-left shunt detected by contrast echo in one patient and cardiac catheterization in the other; possible paradoxical embolism (3 = 7%)--meets two of three Johnson criteria without evidence of other source; and unknown source (9 = 22%)--conventional work-up negative or incomplete. Five of nine patients (56%) less than 50 years old had probable or possible paradoxical embolism, while in two patients (22%), the origin was unknown. (1) A significant proportion of patients with an arterial embolus are discharged with the source of emboli unknown, (2) paradoxical embolism must be considered and contrast saline or transesophageal echocardiogram should be done in patients under 50 years old.

A proton-dependent zinc uptake in PC12 cells. Intracellular pH in pheochromocytoma (PC12) cells was manipulated by 'acid loading' the cells and the effect of such a change on radioactive zinc uptake was studied. It was found that zinc uptake was stimulated in cells loaded with protons without causing any measurable change in the intracellular pH. To confirm our assumption that the proton flux due to zinc entry is too small to be measured, we calculated the pH change that one would expect because of zinc influx. The intrinsic buffer capacity of PC12 cells was determined to be 8.03 mM/pH unit and was used in these calculations. It was found that at the five-minute incubation, zinc uptake occurring under our experimental conditions could cause a pH change of 0.000277 pH units per minute (assuming a 1:2 zinc:proton stoichiometry). This study adds a new dimension towards understanding the role played by intracellular pH in causing zinc entry into cells.

TDCPP protects cardiomyocytes from hypoxia-reoxygenation injury induced apoptosis through mitigating calcium overload and promotion GSK-3β phosphorylation. TDCPP, Tris (1, 3-dichloro-2-propyl) phosphate belongs to a group of chemicals known as triester organophosphate flame retardants, It can alter calcium homeostasis at much lower concentrations in normal conditions, but the mechanism is unclear till now. Calcium overload is a leading cause of apoptosis in myocardial ischemia/reperfusion (I/R) injury, thus how to mitigate Ca2+-overload is deserved to be investigated. We therefore hypothesized that TDCPP could attenuate cardiomyocytes apoptosis in I/R injury. H/R (hypoxia/reoxygenation) experiments in vitro were used to simulate in vivo I/R injury. The present study aimed to explore the potential effect of TDCPP in cardiomyocytes after H/R injury, Ca2+ imaging technique was used to explore SOCE(store-operated calcium entry) and Ca2+-overload levels, western blot technique was used to explore the potential target, the cell morphology, cell viability and mitochondrial membrane potential were also detected. The results have shown that: TDCPP could decrease SOCE, restore H9c2 cell viability, mitigate Ca2+-overload in H/R injury and reduce the mitochondrial membrane potential. Furthermore, TDCPP decreased STIM1 expression and promoted GSK3β phosphorylation. Collectively, for the first time, this study suggest the antiapoptosis roles of TDCPP in H/R injury are via mitigation Ca2+-overload and promoting GSK-3β phosphorylation.

Isolation and characterization of a bacteriophage and its potential to disrupt multi-drug resistant Pseudomonas aeruginosa biofilms. A lytic Pseudomonas aeruginosa bacteriophage, vB_PaeM_LS1, was isolated and characterized herein. To examine the eligibility of bacteriophage vB_PaeM_LS1 as a therapeutic bacteriophage, we analysed its genome and compared it to similar bacteriophages. Genome of bacteriophage vB_PaeM_LS1 consisted of a linear, double-stranded DNA molecule 66,095 bp in length and with 55.7% G + C content. Neighbor-joining analysis of the large subunit terminase showed that bacteriophage vB_PaeM_LS1 had similarity to the Pbunavirus genus. The potential of the lytic bacteriophage to disrupt Pseudomonas aeruginosa biofilms was assessed by scanning electron microscopy and bacterial counts. This study revealed that the bacteriophage vB_PaeM_LS1 with its lytic effect showed a high potential impact on the inhibition of the growth of Pseudomonas aeruginosa biofilm formation.

An evaluation of mesotherapy solutions for inducing lipolysis and treating cellulite. The aim of this study was to evaluate the lipolytic potential of solutions used in the practice of cosmetic mesotherapy to stimulate lipolysis, cause local fat reduction and reduce the appearance of cellulite. The mesotherapy solutions were tested in a human fat cell assay using the fold induction of glycerol generation as a measure of lipolysis. The following mesotherapy solutions were tested: aminophylline; yohimbine; isoproterenol; melilotus; aminophylline with melilotus; aminophylline with isoproterenol; aminophylline with isoproterenol and yohimbine; aminophylline with isoproterenol and lidocaine; and aminophylline with isoproterenol, yohimbine and lidocaine. Isoproterenol (P<0.002), aminophylline (P<0.00004) and yohimbine (P<0.001) stimulated lipolysis compared to the buffer control. The lipolysis stimulated by melilotus (P<0.01) and isoproterenol (P<0.002) was enhanced by aminophylline (P<0.001 and P<0.001, respectively). The lipolytic stimulation by aminophylline and isoproterenol (P<0.0009), and by aminophylline and isoproterenol with yohimbine (P<0.0007) was inhibited by lidocaine, not significant compared to buffer control for aminophylline and isoproterenol, but aminophylline, isoproterenol and yohimbine still stimulated lipolysis more than control, P<0.05). Isoproterenol, aminophylline, yohimbine and melilotus stimulate lipolysis alone, and lipolysis is further enhanced by combining lipolytic stimulators in mesotherapy solutions. Lidocaine is antilipolytic and should be removed from mesotherapy solutions designed for local fat reduction.

[Treatment of rhegmatogenous retinal detachment complicated by vitreous hemorrhage]. 8 cases of rhegmatogenous retinal detachment associated with vitreous hemorrhage were treated by first removing the blood through vitrectomy followed by routine retina reattachment procedures, such as searching for retinal breaks with indirect ophthalmoscopy and scleral buckling or encircling. Among 6 cases followed up, only 1 cases relapsed due to PVR traction. The points of note during operation were mentioned and the relationship between retinal breaks with vitreous hemorrhage and posterior vitreous detachment discussed.

[Effects of chemotherapy and radiotherapy of malignant testicular tumors on residual testicular tissue]. By morphologic and morphometric investigations of the residual testis after treatment of testicular cancer the deleterious effect of chemo- and radiotherapy are estimated. Approximately 4-5 years after treatment the reversibility of spermatogenesis is better in patients chemotherapy than in patients after radiotherapy.

Unoccupied alpha(v)beta3 integrin regulates osteoclast apoptosis by transmitting a positive death signal. Cell/matrix detachment is a general inducer of programmed cell death, an event mediated by loss of integrin/ligand association. Because alpha(v)beta3 is the major integrin expressed by the osteoclast, we asked whether its occupancy promotes survival of the resorptive cell. Thus, we generated wild-type preosteoclasts and placed them on selective matrix proteins. Consistent with the posture that alpha(v)beta3 occupancy promotes survival, preosteoclasts plated on native collagen, a matrix not recognized by the integrin, undergo apoptosis 4-fold faster than those on the alpha(v)beta3 ligand, vitronectin. To further explore the role of alpha(v)beta3 in osteoclast apoptosis, wild-type and beta3-/- preosteoclasts were suspended and apoptosis determined, with time. Beta3-/- preosteoclasts, in suspension, undergo a rate of apoptosis only 40-60% of that of their wild-type counterparts, indicating that unoccupied alpha(v)beta3 transmits a positive death signal that we find regulated by caspase-8. Attesting to specificity of the unoccupied integrin-transmitted death signal, apoptosis in the absence of alpha(v)beta3 is mediated by capsase-9. We have shown that the resorptive defect of beta3-/- osteoclasts is rescued by wild-type beta3 cDNA but not by one bearing a S752P mutation. To determine whether the same holds true regarding osteoclast apoptosis, we constructed lentivirus vectors encoding green fluorescent protein, wild-type beta3, or beta3S752P. Once again, native beta3-/- preosteoclasts were protected against apoptosis. Similar to its effect on bone resorption, transduced wild-type beta3 normalizes the apoptotic rate of beta3-/- preosteoclasts. Unexpectedly, however, beta3S752P transductants also die at a rate indistinguishable from wild type. Thus, unoccupied alpha(v)beta3 integrin regulates osteoclast apoptosis via a component of the integrin that is different than that regulating resorption.

Cardiac rehabilitation programs markedly improve high-risk profiles in coronary patients with high psychological distress. Adverse behavioral profiles, particularly depression and hostility, increase the risk of coronary artery disease (CAD) and affect recovery after CAD events. We sought to determine the effects of outpatient phase II cardiac rehabilitation and exercise training (CRET) programs in CAD patients with high levels of psychological distress. We studied 500 consecutive patients both before and after phase II CRET programs and compared 109 patients with the highest quintile of psychological distress (HD) with 115 patients with the lowest quintile of psychological distress (LD). At baseline, patients with HD were younger (P < 0.001), had higher weight (+11%; P < 0.001), body mass indices (BMI) (+9%; P < 0.01), triglycerides (+66%; P < 0.0001), and glycosylated hemoglobin (+9%; P = 0.03), and had higher scores for depression, hostility, anxiety, and somatization (all P < 0.0001), but had lower values for exercise capacity (-15%; P = 0.02), high-density lipoprotein (HDL) cholesterol (-10%; P < 0.01), and total quality of life (QoL) (-26%; P < 0.0001), and all 6 major components of QoL compared with LD. After CRET, patients with HD had significant reductions in weight (-2%; P < 0.01), % fat (-6%; P < 0.001), BMI (-2%, P < 0.01), and scores for anxiety (-49%), depression (-47%), somatization (-34%) and hostility (-38%) (all P < 0.0001), and increases in exercise capacity (+54%; P < 0.0001), HDL cholesterol (+10%; P < 0.0001), and total QoL (+23%; P < 0.0001), and the 6 components of QoL studied. Compared with patients with LD, those with HD had statistically greater improvements in HDL (P = 0.03), triglycerides (P = 0.03), BMI (P = 0.02), as well as all behavioral characteristics and QoL (P < 0.0001), and had similar improvements in all other factors assessed. These data support the routine assessment of high-risk behavioral characteristics in patients with CAD and demonstrate the marked improvements that occur after phase II CRET programs in CAD patients with high psychological distress.

[Post-circumcision tetanus in Dakar, Senegal]. This study aimed at describing the epidemiology, clinical features and prognosis of post-circumcision tetanus at the infectious diseases clinic in Fann Hospital in Dakar. Data were collected retrospectively for analysis from patients' files recorded from January 1, 1999 to December 31, 2006. 54 cases were included, accounting for 4% of all tetanus cases admitted to the clinic during the study period (54 cases/1291). The patients' average age was 9 +/- 3.7 years old (range = 1-17 years) and 52% of them were schoolboys. In most cases (76%), tetanus symptoms occurred beyond 7 days after circumcision. The average delay from onset of the disease to admission was 2.3 days (range = 0-6 days). The circumcision took place at home in 39% of cases, in health center in 35% of cases and in unspecified area in 26% of cases. The majority of patients (85%) had never received tetanus vaccine and, in 72% of the cases, the circumciser was designated as a male nurse. Generalized tetanus was observed in all cases, most of which was a mild form of the disease (63%). During hospitalisation, thirteen patients (24%) had complications among which diaphragmatic and intercostal muscle spasms (3 cases), bacteraemia (5 cases), respiratory infection (4 cases), urinary tract infection (4 cases), and fracture of the vertebrae (1 case). The case fatality rate was 7.4% (4 deaths). Vaccination together with health education of the population as well as a better sensitization of the practitioners are necessary to eradicate tetanus after circumcision.

Future preventive and therapeutic targets for transfusion-related acute lung injury. Transfusion-related acute lung injury (TRALI) has been the leading cause of transfusion-associated death for nearly a decade. Recent TRALI mitigation strategies focused on reduction of leukocyte antibodies in high volume plasma products appear to be successful in reducing TRALI events and deaths, but additional preventive measures are needed. Future possibilities include, screening of donors for neutrophil antibodies, processing of blood products to reduce or remove biologic response modifiers, and the more judicious use of blood. There are currently no specific TRALI therapies. The pathogenesis of TRALI and acute lung injury-acute respiratory distress syndrome (ALI-ARDS) is quite similar; both involving interactions of activated platelets, neutrophils, and pulmonary endothelium resulting in lung damage, capillary leak, and pulmonary edema. Greater understanding of these interactions and the key molecules involved will lead to development of potential new targets for therapy. In this review, future possible preventive measures to further reduce the occurrence of TRALI will be discussed, including TRALI caused by biologic response modifiers (BRMs), like bioactive lipids and sCD40L, which are not addressed by current preventive actions that only target leukocyte antibodies in high-volume plasma products. Insights already gained from studies of ALI-ARDS treatments will be summarized and discussed as possible therapeutic targets for treatment of patients experiencing TRALI.

Redirecting Killer T Cells through Incorporation of Azido Sugars for Tethering Ligands. The genetic expression of chimeric antigen receptors (CARs) on the surfaces of T cells enables the redirection of T cell specificity. To enhance the versatility of T cells as tumor-specific killers, we developed a nongenetic approach by which azide-containing sialic acids were metabolically incorporated into T cells to modify cellular sialyl glycans. After successful display of these moieties on the T cells, small-molecule ligands such as RGD and folate (as proof-of-concept, rather than supersized antibodies) were clicked orthogonally, leading to highly selective time- and dose-dependent cytotoxicity to integrin αv β3 - and folate-receptor-positive cells, respectively. This chemical approach provides a facile platform for rational design of tumor-specific cytotoxic T cells for targeted immunotherapy.

Variations in indwelling urinary catheter use in four Australian acute care hospitals. To identify the point prevalence of indwelling urinary catheters (IDCs) in adult inpatients in acute care hospitals, and to describe the indications for IDC insertion based on patient age, gender, specialty and hospital. Catheter-associated urinary tract infections (CAUTIs) are preventable healthcare-associated infections. IDC duration is the strongest predictor of CAUTI, and little is known about characteristics of patients who receive an IDC. Two single-day point prevalence surveys collected baseline patient data as part of a larger pre-post control-intervention study. Surveys were conducted at four acute care hospitals in NSW, Australia, for all adult patients. Data collection included IDC presence, insertion details and urine culture collection. Point prevalence data were linked with electronically extracted patient demographic data. This study is presented in line with STROBE checklist (See Supplementary File 1). Data from 1,630 patients were analysed, with 196 patients (12%) identified as having an IDC on the survey dates. IDC prevalence rates were higher in males (13%) than in females (11%). Critical care had the highest rate of patients with IDCs (42%). Urine cultures were collected in 70 patients with an IDC (43%). Findings indicated similar rates of IDC use in males and females, and there was no significant difference in age between patients with or without an IDC. However, indication for IDC varied by patient age and gender. High rates of urine culture collection may represent routine collection. IDC use is found across genders, all age groups and specialties. Nurses should be aware that any of their patients may have an IDC and be particularly aware of certain indications based on patient age and gender. Routine urine culture collection is not advised, and instead, nurses should be guided by clinical decision-making tools.

Perinatal outcome in pregnancies complicated by pulmonary tuberculosis. To assess the perinatal outcome of pregnancies complicated by active pulmonary tuberculosis. The perinatal outcome of 79 gravidas with pulmonary tuberculosis was compared with that of 316 normal gravidas of similar age, parity and socioeconomic status. The mean birthweight of infants (2649 g) born to tuberculous mothers was 215 g less than that of control group (P < 0.001). Pulmonary tuberculosis was associated with an approximate 2-fold increase in prematurity (22.8% vs. 11.1%, P < 0.01), small for gestational age (20.2% vs. 7.9%, P < 0.005) and low birthweight neonates (34.2% vs. 16.5%, P < 0.001), and 6-fold increase in perinatal deaths (10.1% vs. 1.6%, P < 0.001). The adverse perinatal outcome was pronounced in cases with late diagnosis, incomplete and irregular treatment, and advanced pulmonary lesions. Maternal tuberculosis is a high-risk perinatal condition. The study emphasizes the need for early diagnosis and treatment of tuberculosis, preferably before pregnancy, regular medical supervision and good perinatal care for tuberculous mothers.

Palmitate-induced changes in energy demand cause reallocation of ATP supply in rat and human skeletal muscle cells. Mitochondrial dysfunction has been associated with obesity-related muscle insulin resistance, but the causality of this association is controversial. The notion that mitochondrial oxidative capacity may be insufficient to deal appropriately with excessive nutrient loads is for example disputed. Effective mitochondrial capacity is indirectly, but largely determined by ATP-consuming processes because skeletal muscle energy metabolism is mostly controlled by ATP demand. Probing the bioenergetics of rat and human myoblasts in real time we show here that the saturated fatty acid palmitate lowers the rate and coupling efficiency of oxidative phosphorylation under conditions it causes insulin resistance. Stearate affects the bioenergetic parameters similarly, whereas oleate and linoleate tend to decrease the rate but not the efficiency of ATP synthesis. Importantly, we reveal that palmitate influences how oxidative ATP supply is used to fuel ATP-consuming processes. Direct measurement of newly made protein demonstrates that palmitate lowers the rate of de novo protein synthesis by more than 30%. The anticipated decrease of energy demand linked to protein synthesis is confirmed by attenuated cycloheximide-sensitivity of mitochondrial respiratory activity used to make ATP. This indirect measure of ATP turnover indicates that palmitate lowers ATP supply reserved for protein synthesis by at least 40%. This decrease is also provoked by stearate, oleate and linoleate, albeit to a lesser extent. Moreover, palmitate lowers ATP supply for sodium pump activity by 60-70% and, in human cells, decreases ATP supply for DNA/RNA synthesis by almost three-quarters. These novel fatty acid effects on energy expenditure inform the 'mitochondrial insufficiency' debate.

The Nab2 and Stat6 genes share a common transcription termination region. The two Nab genes, coding for transcriptional corepressors of NGFI-A (Egr-1, Krox24, zif268) and Krox20, have been localized to two regions of the genome, each of which contains at least two members of the Stat gene family. The association of the two Nab genes with the Stat clusters on mouse chromosomes 1 and 10 (human chromosomes 2 and 12) suggest that a Nab gene was involved in at least one of the duplication events that resulted in dispersion of the primordial Stat gene pair to three different mouse chromosomes. Sequencing of the Nab2 genomic locus revealed that it is situated very close to the Stat6 gene. The transcripts of the two genes converge, such that the 3' ends of the Stat6 and Nab2 mRNAs overlap by 58 bp. Both transcripts terminate within a 78-bp region that is absolutely conserved between mouse and human. Analysis of Nab2 cDNA revealed that there is an alternatively spliced form of the Nab2 transcript (lacking exon 3) that produces a protein that lacks the ability to repress transcription by NGFI-A and Krox20.

The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause extensive translational inaccuracy in vivo. The oxazolidinone family is a new class of synthetic antibiotics that bind to the bacterial 50S ribosomal subunit. Two members of the family, linezolid and XA043, were examined for their effects on translational fidelity using a lacZ reporter gene in vivo. Both promoted highly significant frameshifting and nonsense suppression. Chloramphenicol, a peptidyl transferase inhibitor, affected translational fidelity in a similar fashion. Neither the oxazolidinones nor chloramphenicol stimulated misincorporation of amino acid residues at position 461 in the lacZ gene. In contrast, the aminoglycosides gentamicin and paromomycin, which interact with the decoding region of the 30S subunit, caused significant misincorporation but only modest increases in frameshifting or stop codon readthrough of the lacZ gene. We conclude that effects on translational fidelity may play a significant role in the mechanism of action of the oxazolidinones.

Childhood and adolescent injuries in elementary schools in north-western Uganda: extent, risk and associated factors. Childhood injuries remain understudied in Uganda. The objective of this study was to determine the extent, nature and determinants of school-related childhood injury risk in north-western Uganda. A cohort of 1000 grade fives from 13 elementary schools was followed-up for one term. Survival and multi-level modelling techniques compared the risk rates across gender, schools and locations. Childhood injuries are common in north-western Uganda. Most of them occur during travel, breaks, practical classes and gardening, while walking, playing, learning and digging. Most injuries result from collisions with objects, sports and falls. Two-thirds of children receive first aid and hospital care. Times to injury were 72.1 and 192.9 person days (p = 0.0000). Gender differences in time to event were significant (p = 0.0091). Girls had better survival rates: cumulative prevalence of childhood injury was 36.1%; with significant gender differences (p = 0.007). Injury rate was 12.3/1000 person days, with a hazard ratio of 1.4. Compared to girls, boys had a 37% higher injury rate (p = 0.004). Rates varied among schools. Associated factors include sex and school. Rural-urban location and school differences do influence childhood injury risk. Childhood injuries are common: the risk is high, gender- and school-specific. Determinants include gender and school. Location and school contexts influence injury risk.

A retrospective study of patient falls in a psychiatric hospital. 1. While falls on medical-surgical units are the focus of extensive research, falls on inpatient psychiatric units are an understudied critical event. 2. The purposes of this study were to identify the variables associated with psychiatric patient falls and to use that information to assess risk and, therefore, prevent falls in this population. 3. The psychiatric patient at risk for falling is described as a woman with a prior history of falls; less than 65 years of age; experiencing anxiety and agitation; and receiving a sedative, a tranquilizer, and a laxative. Additionally, this patient is more likely to fall in a community area.

Nucleotide sequence analysis of the 23S ribosomal RNA-encoding gene of Bartonella bacilliformis. We report the cloning and characterization of the 23S ribosomal RNA (rRNA)-encoding gene (rDNA) of Bartonella bacilliformis (Bb). The 2821-bp gene is preceded by an 11-nucleotide (nt) inverted repeat (IR) located 81 nt upstream in the tRNA(Ala)-23S rDNA intergenic spacer. The gene is followed by an 8-nt IR, five nt downstream in the 23S-5S rDNA intergenic spacer. The nt sequence of the Bb 23S rDNA is most similar to the 23S rDNA of Rhodopseudomonas palustris (Rp), with 85.4% sequence identity. The Bb 23S rDNA has 77.8% identity to the same gene from Escherichia coli (Ec). Secondary structure predictions indicate that the large subunit (LSU) Bb rRNA contains two smaller stem-loops at nt 1459-1544 and 1658-1685, as compared to the corresponding loops from Ec (nt 1405-1597 and 1707-1751, respectively). In addition, the Bb 23S rRNA has a large 72-nt stem-loop at nt 130-201, as compared to the Ec 18-nt stem-loop (nt 131-148). There is no Bb homologue of the 15-nt stem-loop at the 3' end of the Ec molecule (nt 2791-2805). The Bb 23S rRNA lacks the large stem-loop present in the LSU rRNA of closely related Rhodobacter sphaeroides (Rs) (nt position 1225-1331) which is thought to be involved in cleavage of 23S RNA precursor molecules into 16S and 14S rRNA species. This is the first LSU rDNA nt sequence for any member of the Bartonellaceae family.

Management of otoscierosis--an Irish perspective. The last 30 years have seen a gradual change in the management of otosclerosis. The aim of this study is to evaluate the current practice amongst Irish otolaryngology consultants by a questionnaire and to compare it with the practice currently followed in Great Britain. Thirty-eight responses (67.9%) were available for analysis. The overall trend is towards centralisation with a reduction in the number of surgeons undertaking stapes surgery (39%). The majority of consultants (67%) who undertake stapes surgery would operate for a unilateral conductive loss and 67% would undertake bilateral stapes surgery. Stapedotomy is the only operation performed (100%) with none of the consultants performing partial or total stapedectomies.

Polymorphisms in the RAS and cardiac function. Since the discovery of the polymorphism in the angiotensin converting enzyme (ACE) and the consequences of this polymorphism on the activity levels of the enzyme, numerous association studies have been performed. However, these investigations do not often adhere to the most stringent criteria for such studies. The initial study reporting a positive association of the ACE polymorphism and myocardial infarction showed an increased risk of the DD genotype. This initial association was eventually refuted by a large, well conducted association study, which found a risk ratio of 1.02 after combining their own data with all published data. Although such large, well conducted association studies have not been performed in left ventricular (LV) hypertrophy, the association between DD genotype and hypertrophy is more convincing with a 192% excess risk of LV hypertrophy in untreated hypertensives. The role of ACE genotype in LV growth is well established, especially in athletes. In heart failure, large studies or meta-analyses have not been performed, because most studies have selected different end-points. This hampers a proper meta-analysis of the results obtained in associations with heart failure. As most association studies do not fulfill the criteria for good association studies and use too small sample sizes, it remains important to perform a meta-analysis to add meaning to the results of such studies. Above all, it is important to obey the rules set for association studies, large sample size, small P values, report associations that make biological sense and alleles that affect the gene product in a physiologically meaningful way.

A multicenter, phase I dose-escalating study of docetaxel, cisplatin and S-1 for advanced gastric cancer (KDOG0601). This dose-escalation study of a combination of docetaxel, cisplatin and S-1 investigated the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), recommended dose (RD) and antitumor activity in advanced gastric cancer. Patients received docetaxel (40 mg/m(2)), cisplatin (DIV on day 1) and S-1 (40 mg/m(2) p.o., twice daily, on days 1-14 every 28 days). The starting dose of cisplatin was 60 mg/m(2) (level 1); the dose was escalated to 70 (level 2) and 80 mg/m(2) (level 3) in a stepwise fashion. Fourteen patients were enrolled. The MTD of cisplatin was 80 mg/m(2) (level 3). DLT was grade 3 diarrhea, febrile neutropenia and delayed resumption of treatment. The RD of cisplatin was considered to be 70 mg/m(2) (level 2). DLT was liver dysfunction, occurring in only 1 patient at level 2. The response rate was 69.2% (9/13). For combined treatment with docetaxel, cisplatin and S-1 in patients with advanced gastric cancer, RD were docetaxel 40 mg/m(2), cisplatin 70 mg/m(2) and S-1 80 mg/m(2)/day. This regimen yields a high rate of tumor response and can be administered safely. Phase II studies of this regimen are under way.

Novel GRN Mutations in Alzheimer's Disease and Frontotemporal Lobar Degeneration. During the twentieth century, frontotemporal dementia (FTD) was often misdiagnosed, confused with Alzheimer's disease or psychiatric disorders, jeopardizing care and research. To analyze the FTD genes in the DNA samples of patients belonging to families clinically classified as probable Alzheimer's disease (FAD) in the early 1990s and not carrying mutation in the three main genes linked to FAD (Presenilin 1, Presenilin 2, and Amyloid precursor protein). The genetic screening was performed on 63 probands diagnosed as FAD before the early 2000s. Four patients out of the 63 studied (4/63, 6.3%) resulted as carrying four different GRN genetic variations: p.T272SfsX10, p.R110X, p.C149LfsX10, and p.W304C. The first two mutations (p.T272SfsX10, p.R110X) are the most frequent ones in Italy in FTD patients; the latter two (p.C149LfsX10 and p.W304C) are not described in the scientific literature. Our data suggest that it can be important to re-examine FAD patients diagnosed when the FTD spectrum was not well recognized and the causative FTD genes had not yet been identified. Moreover, we propose initially analyzing genes associated with the first form of suspected dementia and, if the results are negative, studying genes implicated in the other form of dementia.

Tissue shrinkage and unbiased stereological estimation of particle number and size. This paper is a review of the stereological problems related to the unbiased estimation of particle number and size when tissue deformation is present. The deformation may occur during the histological processing of the tissue. It is especially noted that the widely used optical disector may be biased by dimensional changes in the z-axis, i.e. the direction perpendicular to the section plane. This is often the case when frozen sections or vibratome sections are used for the stereological measurements. The present paper introduces new estimators to be used in optical fractionator and optical disector designs; the first is, as usual, the simplest and most robust. Finally, it is stated that when tissue deformation only occurs in the z-direction, unbiased estimation of particle size with several estimators is possible.

Ripper procedure for determining sulfur dioxide in wine: collaborative study. Twenty-three laboratories analyzed 5 replicate wine samples according to a specified version of the Ripper direct iodometric titration for sulfur dioxide. Each sample was analyzed for (A) free SO2, (B) total SO2, and (C) iodine-reactive substances other than SO2. Although variation of A with temperature and of A and B with time of analysis were anticipated, analysis of covariance showed no significant reduction in error when these variables were taken into account. Error did vary with SO2 level and wine type, red vs white. Pooled estimates of precision (within-laboratory error) in mg SO2/L wine were, for white wine: (A) 3.3, (B) 10.4, (C) 1.9; for red wine: (A) 3.8, (B) 7.3, (C) 1.9. Pooled estimates of systematic (between-laboratory) error in mgSO2/L wine were, for white wine: (A) 2.7, (B) 16.6, (C) 2.1; for red wine: (A) 4.3, (B) 15.1, (C) 3.0. Although rapid and convenient, the Ripper method is severely limited by poor precision and large systematic error. The Ripper method is not recommended for adoption by the AOAC.

Bone lesions in histiocytosis X. Sixty-two patients with histiocytosis X were followed for an average of 5 years. The patients were classified into three groups: general visceral types (14 cases), multiple eosinophilic granulomas (nine cases), and solitary eosinophilic granulomas (39 cases). One hundred bony lesions were noted in 60 of the 62 patients. The bone lesions showed progressive improvement in single and multiple eosinophilic granulomas independent of treatment type. After biopsy, patients received no treatment unless there was a dangerous extension into the soft tissues because of its site, i.e., in the skull. In the general visceral types, chemotherapy was effective in visceral sites and in extensions of the tumor outside the bone but did not alter the natural history of the bony lesion.

Differences between females and males in axial spondyloarthritis: data from a real-life cross-sectional cohort. Objective: Axial spondyloarthritis (axSpA) is a chronic inflammatory joint disease that usually presents with axial symptoms, but can also present with peripheral and extra-articular manifestations. It occurs equally in females and males. The diagnostic delay for axSpA is 5-7 years, and is significantly longer in females than in males. The aim of this study is to investigate the difference in disease characteristics between females and males with axSpA and to stratify this difference according to human leucocyte antigen (HLA)-B27 status. Method: Clinical characteristics, spondyloarthritis (SpA) features, disease activity parameters, X-rays of sacroiliac joints, and laboratory results were assessed in a real-life cross-sectional cohort of 389 patients with a clinical diagnosis of axial or peripheral SpA, and compared between genders. Results: Of 389 patients included, 313 had a clinical diagnosis of axSpA [females vs males, 131 (42%) vs 182 (58%), respectively]. Females had less radiographic axSpA according to the modified New York criteria (38.9% vs 63.7%, respectively), had a higher erythrocyte sedimentation rate [(median (interquartile range) 11 (5-23) vs 8 (3-16) mm/h), and reported higher disease activity by the Bath Ankylosing Spondylitis Disease Activity Index (mean ± sd 5.2 ± 2.1 vs 4.6 ± 2.2). No differences were found in clinical characteristics or SpA features, or when stratifying for HLA-B27 status. Conclusions: In this real-life cohort of patients with axSpA, although males more often had structural damage on X-rays, females had similar disease with regard to SpA features and at least equal disease activity parameters compared to males.

[Diagnostic value of out-patient lymph node biopsy]. Authors review their outpatient lymph node biopsies in order to verify safety and diagnostic accuracy. They didn't observe any complication and in every case, the procedure provided the correct diagnosis. Lymph node biopsy is the procedure of choice to study the pharmacologic therapy non responsive lymph node pathology that is not surely defined by fine needle aspiration, as almost always in lymphomas.

The Fas signalling pathway and its role in the pathogenesis of cancer. Tumor cells frequently exhibit de novo expression of Fas ligand (FasL/CD95L). Coupled with resistance to Fas-mediated apoptosis, FasL expression enables many cancers to deliver a pre-emptive strike or 'counterattack' against the immune system. New studies also indicate that FasL expression on tumor cells could confer a double advantage to these cells by stimulating their own proliferation. However, pro-inflammatory effects of FasL have also been observed. New findings are beginning to reconcile the paradoxical effects of FasL, with the clinical significance of the Fas counterattack only beginning to emerge.

Gonadotropin-releasing hormone (GnRH) and its receptor in human meningiomas. Meningiomas are the most common neoplasms of the central nervous system and are more frequent in women than in men. Many studies have been conducted to determine whether the progesterone receptor (PR) and estrogen receptor (ER) are present or absent in meningiomas. No previous studies, however, have investigated the status (presence or absence) of gonadotropin-releasing hormone (GnRH) and its receptor (GnRH-R), two major factors related to PR and ER, in meningiomas. This study aims to determine the status of GnRH and GnRH-R and to elucidate the correlations of GnRH and GnRH-R with PR, ER, and clinical features in meningiomas. Eighty-two specimens of human meningiomas were obtained for immunohistochemical analysis with anti-GnRH, anti-GnRH-R, anti-PR, anti-ER, and anti-Ki-67 (MIB-1) antibodies, and for RT-PCR analysis of the mRNA expressions of GnRH and GnRH-R. Correlations of GnRH and GnRH-R with PR, ER, Ki-67, and clinical features such as age, sex, tumor grade, and tumor histology were assessed. Seventy-eight (95.1%) of the 82 meningiomas reacted positively in the cytoplasm for the GnRH-R. Forty-nine (59.8%) of the 82 cases reacted positively in the cytoplasm for the GnRH. The positive immunoreactivity for GnRH-R and GnRH was confirmed by the RT-PCR analyses of mRNA. Forty-seven (96%) of the 49 cases with positive immunoreactivity for GnRH-R also had positive immunoreactivity for GnRH. PR expression was higher in the tumors positive for GnRH-R (p=0.002), and a significantly higher proportion of tumors from male patients exhibited positive immunoreactivity for GnRH (p=0.02). No significant correlations were found between the status of GnRH-R or GnRH with other clinicopathological features. Over half of meningiomas may be regulated by GnRH-GnRH-R expression in an autocrine fashion. This unique expression profile of GnRH and GnRH-R may open the way to the development of GnRH analogs as a treatment tool in the future.

The role of isolated limb perfusion for melanoma confined to the extremities. Isolated limb perfusion with Melphalan is the best treatment option to control symptomatic multiple small in-transit metastases. When lesions are bulky, Isolated Limb Perfusion (ILP) with Tumor Necrosis Factor (TNF) + Melphalan is superior as in soft tissue sarcoma. TNF changes the pathophysiology, greatly enhances the uptake of Melphalan and destructs selectively the vasculature of large tumors. To date, ILP is not indicated in an adjuvant setting.

Cloning and characterization of a novel L-arabinose isomerase from Bacillus licheniformis. Based on analysis of the genome sequence of Bacillus licheniformis ATCC 14580, an isomerase-encoding gene (araA) was proposed as an L-arabinose isomerase (L-AI). The identified araA gene was cloned from B. licheniformis and overexpressed in Escherichia coli. DNA sequence analysis revealed an open reading frame of 1,422 bp, capable of encoding a polypeptide of 474 amino acid residues with a calculated isoelectric point of pH 4.8 and a molecular mass of 53,500 Da. The gene was overexpressed in E. coli, and the protein was purified as an active soluble form using Ni-NTA chromatography. The molecular mass of the purified enzyme was estimated to be approximately 53 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 113 kDa by gel filtration chromatography, suggesting that the enzyme is a homodimer. The enzyme required a divalent metal ion, either Mn(2+)or Co(2+), for enzymatic activity. The enzyme had an optimal pH and temperature of 7.5 and 50 degrees C, respectively, with a k (cat) of 12,455 min(-1) and a k (cat)/K (m) of 34 min(-1) mM(-1) for L-arabinose, respectively. Although L-AIs have been characterized from several other sources, B. licheniformis L-AI is distinguished from other L-AIs by its wide pH range, high substrate specificity, and catalytic efficiency for L-arabinose, making B. licheniformis L-AI the ideal choice for industrial applications, including enzymatic synthesis of L-ribulose. This work describes one of the most catalytically efficient L-AIs characterized thus far.

The far lateral transpontomedullary sulcus approach to pontine cavernous malformations: technical report and surgical results. Pontine cavernous malformations (CMs) located on a peripheral pontine surface or the fourth ventricular floor are resectable lesions, but those deep within the pons away from a pial surface are typically observed. However, the anterior bulge of the pons formed by the brachium pontis creates a unique entry point for access to deep pontine lesions from below, working upward through the pontomedullary sulcus. We developed a transpontomedullary sulcus (TPMS) approach to these lesions. The TPMS approach used the far lateral craniotomy and upper vagoaccessory triangle to define the surgical corridor. The entry point was above the olive, lateral to the pyramidal tracts and cranial nerve (CN) VI, above the preolivary sulcus and CN XII, and medial to CNs VII and VIII and CNs IX through XI. Four patients underwent this approach. All presented with hemorrhage and CN VI palsies. All pontine CMs were resected completely. Three patients were improved or unchanged, with good outcomes (modified Rankin Scale score ≤2) in all patients. The central pons remains difficult territory to access, and new surgical corridors are needed. The bulging underbelly of the pons allows access to pontine lesions deep to the pial surface from below. The far lateral TPMS approach is a novel and more direct alternative to the retrosigmoid transmiddle cerebellar peduncle approach. Unlike the retrosigmoid approach, the TPMS approach requires minimal parenchymal transgression and uses a brainstem entry point medial to most lower CNs. Favorable results demonstrate the feasibility of resecting pontine CMs that might have been previously deemed unresectable.

The Value of the Combined Assessment of COPD in Accurate Characterization of Stable COPD. There is evidence showing a tendency to upgrade COPD severity previously staged with spirometric-based GOLD (GOLD 1234) when using the new GOLD combined disease assessment (GOLD ABCD). The aim of our study was to compare the GOLD 1234 classification in a population of stable COPD patients with the GOLD ABCD classification to determine whether stable COPD was upgraded when using this new classification. After an observational study of a stable COPD cohort (n = 112), 61 patients (54.5%) had an increase in their COPD severity when moving from the old GOLD 1234 classification to the current GOLD ABCD assessment (p < 0.01). 42 patients (37.5%) had no change in severity of COPD. 9 patients COPD were assessed to be better on using GOLD ABCD. This study highlights previously missed high-risk patients when reviewing stable COPD. Continued incorporation of GOLD ABCD will translate into better evidence-based management.

A series of thyroplasty cases under general anaesthesia. Thyroplasty is an operation on the upper airway to improve voice quality in patients with unilateral vocal cord paralysis. It requires access to an uninstrumented larynx and a functional assessment of vocal cord medialization. It is a difficult anaesthetic procedure that requires sharing the airway with the surgeon. We describe an anaesthetic technique to give good operating conditions and a safe airway, using total intravenous anaesthesia, a laryngeal mask airway and intraoperative fibreoptic endoscopic assessment of the larynx, and present a series of 13 patients. Other anaesthetic techniques for thyroplasty are described and discussed.

Potential of amorphous microporous silica for ibuprofen controlled release. Amorphous microporous silica (AMS) xerogel materials were synthesized in an acid-catalyzed sol-gel process. The porosity of AMS was adapted by varying sol-gel synthesis parameters including the molar hydrolysis ratio (r-value), HCl:Si molar ratio, the type of silicon alkoxide source and the solvent. AMS particles of millimeter size were loaded with ibuprofen, by heat treatment and melt impregnation. In vitro release experiments were performed in simulated gastric and intestinal fluid. The release kinetics were critically depending on the AMS particle size distribution and the micropore diameter. The release was interpreted as configurational diffusion in the AMS micropores. The stability of unloaded and ibuprofen loaded AMS material upon storage was investigated using nitrogen physisorption, DSC analysis and in vitro release experiments. Ibuprofen loaded AMS formulations show remarkable stability, which can be attributed to the presence of ibuprofen molecules in the channels, functioning as scaffolds to support the pore structure.

[Tadalafil improves total testosterone, IIEF score and SEP in old and middle-aged males with late-onset hypogonadism]. To observe the clinical effect of tadalafil combined with testosterone undecanoate on late-onset hypogonadism (LOH) in old and middle-aged males. A total of 125 old and middle-aged (40 to 60 years) males with LOH were randomly assigned to a treatment group (n = 65) and a control group (n = 60) to be treated with tadalafil + testosterone undecanoate and testosterone undecanoate alone, respectively. We compared the levels of total testosterone (T), IIEF scores and the patients' sexual encounter profile (SEP) diaries before and 4 weeks after medication. The T level, IIEF score and SEP score were significantly improved in both groups after medication as compared with the baseline (P < 0.05), and even more so in the treatment than in the control group (P < 0.05). Tadalafil combined with testosterone undecanoate, superior to testosterone undecanoate alone, can improve the T level, IIEF score and SEP score in old and middle-aged males with LOH and increase their sexual satisfaction and self-confidence.

ADAMTS13 turns 3. It has now been 3 years since the von Willebrand factor (VWF)-cleaving protease implicated in thrombocytopenic purpura (TTP) pathogenesis was identified as ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13). More than 50 ADAMTS13 mutations resulting in familial TTP have been reported. Considerable progress has also been realized toward understanding the role of ADAMTS13 in normal hemostasis, as well as the mechanisms by which ADAMTS13 deficiency contributes to TTP pathogenesis. Measurement of ADAMTS13 activity in TTP and other pathologic conditions also remains a focus of a substantial clinical research effort. Building on these studies, continued investigation of ADAMTS13 and VWF holds considerable promise for advancing the understanding of TTP pathogenesis and should lead to improved diagnosis and treatment for this important hematologic disease.

Mismatch of aortotomy and saphenous vein graft size: a simple solution. Bleeding may occur at the proximal anastomosis of an aortocoronary bypass graft due to the aortotomy being larger than the vein graft diameter. This results in the wall of the vein being under tension, so that the anastomotic suture or further stitches may cut through. A partial thickness suture placed as a pursestring around the aortotomy may alleviate this situation, resulting in a smaller aortotomy with reduced vein wall tension, improved hemostasis, and a more satisfactory anastomotic vein contour.

[The informed society--illusion or reality?]. Information about reality conveyed by electronic images leads to naiveté--"I saw it with my own eyes"--and thus to the special credibility of television. There is a lack of awareness of "a reduced perspective" (H. Imdahl), of the fact that the television camera selects images for inclusion. Selection is very much influenced by the journalists' attitudes. Since the views of the experts often diverge greatly from those of journalists on important contemporary questions and the media predominantly reflect the views of the journalists, this gives rise to the problem of a "well-informed society," which in many respects is an illusion.

Susceptibility of various microorganisms to chlorhexidine. The susceptibility to chlorhexidine of bacteria in aerobic, facultatively anaerobic and anaerobic isolates from clinical specimens of wounds, urine, saliva, and dental plaque was studied. Agar diffusion tests using 50 microng chlorhexidine discs and agar dilution tests were performed and the MIC values correlated with inhibition zone diameters. Anaerobic plaque strains were isolated and tested by the agar dilution method in an anaerobic glove box. Regression lines obtained for five agar media demonstrated a good correlation between zone diameters and MIC values. There was a broad range of susceptibility to chlorhexidine among both Gram-positive and Gram-negative strains. Low MIC values were noted for staphylococci, S. mutans, S. salivarius and E. coli, while strains of Proteus, Pseudomonas and Klebsiella were less susceptible. S. sanguis showed intermediate susceptibility with both low and high MIC values. Among the anaerobic isolates tested, the strains most susceptible to chlorhexidine were Propionibacterium and Selenomonas, While the least susceptible strains were Gram-negative cocci resembling Veillonella.

Should the presence of an antiphospholipid antibody affect the duration of anticoagulant treatment in patients with venous thromboembolism? A 44-year-old otherwise healthy woman has completed 3 months of anticoagulation therapy for a first episode of unprovoked pulmonary embolism. At the time of diagnosis and before the initiation of anticoagulation, she was found to have an elevated IgG anticardiolipin antibody (ACLA), which was measured at 42 IgG phospholipid (GPL) units (reference range, <15 GPL units) with negative lupus anticoagulant (LAC) testing. Should this laboratory finding affect the recommended duration of anticoagulant therapy?

[The optimization of the use of economic resources for vaccination against hepatitis B in professionals in the health area]. In order to optimize the employment of financial resources to be allocated for hepatitis B vaccination programs involving health care workers, two different aspects were studied: the need of a pre-vaccination screening and the efficacy of low-doses schedules of HBV vaccine by the intradermal (ID) route. The economical analysis (a cost-minimization study) showed that when the prevalence of immune individuals is higher than 11% it is more cost-effective to perform pre-vaccination screening. This situation was observed in the employees group. For students and doctors vaccination without screening was the best approach. Regarding the schedules, 3 doses of HBV vaccine by the intramuscular (IM) route (group A) were compared to first dose by the ID route and second and third doses by the IM route (group B) and to first and second doses by the ID route and the last dose by the IM route (group C). After the third dose, soroconversion rates in groups A and B (92% and 93%, respectively) and geometric mean titers of antiHBs (1278 UI/L and 789.6 UI/L) were similar, and both were different from group A (p < 0.05), showing that alternative vaccination schedules may be cost-effective.

Changes in SNAI1 and VIM gene expression in Caco2 cells after cocultivation with bacteria from colorectal cancer biopsies. The development of distant metastases is the final stage in the progression of solid cancer and is responsible for the majority of cancer-related deaths. Epithelial-mesenchymal transition (EMT) is involved in cancer progression and metastasis. In the present study we used different types of intracellular bacteria isolated from colorectal cancer biopsies to examine their effect on the expression of SNAI1 and VIM genes in Caco2 cell line. SNAI1 gene expression was significantly decreased after cocultivation of Caco2 cells with Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabilis, Enterococcus faecalis, Klebsiella pneumoniae and Bacillus cereus, respectively (P<0.05). We observed more than 2-fold increase in VIM gene expression within Caco2 cells after cocultivation with Proteus vulgaris. On the other hand, VIM gene expression decreased by half after cocultivation with Pseudomonas aeruginosa and Proteus mirabilis (P<0.05). Our data suggest bacteria presented in colorectal carcinoma tissues may cause changes in gene expression of EMT-associated genes. Further research is needed to find out whether bacteria are capable to support EMT and cancer progression.

Bone Regeneration with a Combination of Adipose-Derived Stem Cells and Platelet-Rich Plasma. Mesenchymal stem cells (MSCs) have the potential to directly differentiate into osteogenic cells and efficiently regenerate bone tissue. Adipose-derived stem cells (ASCs) have the potential to differentiate into an osteogenic lineage, too. In addition, ASCs can be readily harvested in large numbers with low donor-site morbidity. Meanwhile, recent reports have demonstrated that platelet-rich plasma (PRP) contains a variety of growth factors and may be a powerful biological autologous cocktail of growth factors for tissue engineering.We have shown that ASC/PRP admixture had dramatic effects on bone regeneration in a rat calvarial defect model, not only through the osteogenic potential of ASCs, but also through the release of cytokines by platelets in PRP, which, in turn, support ASCs.In this chapter, we introduce the bone regeneration using a combination of ASCs and PRP in a rat calvarial defect model.

The role of smooth muscle cells in atherosclerosis. The smooth muscle cells within the human atherosclerotic plaque differ from the cells of the media. These phenotype changes, the mechanisms responsible, and their possible relevance to the formation of the plaque are discussed.

Cardiac arrest after acute hyperphosphatemia. Symptoms of hyperphosphatemia usually relate to the associated hypocalcemia. In a 33-year-old patient accidental infusion of a bolus of potassium phosphate (5 ml intravenously) was immediately followed by cardiac arrest. During CPR, clinically important hypocalcemia or hyperkalemia was not detected, but serum phosphorus was significantly increased. Because acute phosphate load can precipitate life-threatening cardiac arrhythmias, familiarity with doses and rate of infusion of phosphate is extremely important.

Alternative caregiving figures and their role on adult attachment representations. The present work represents the first Italian study investigating whether and how mothers who describe unloving experiences with both parents during childhood could become more secure as adults (termed earned-secures). The sample consisted of 94 women from northern Italy. All the subjects were administered the Adult Attachment Interview (AAI) and fill in a screening test evaluating depressive symptoms. No significative differences were found regarding depressive symptomatology across the different attachment classifications. The majority of the samples (84%) remember an important alternative support figure during childhood (before 12 years old). Earned-secures significantly differ from continuous-secure and insecure groups (F = 27.202; p ≤ 0.01) on the amount of the emotional support from the main alternative support figure and on the average amount of emotional support across alternative support figures (F = 10.44; p ≤ 0.01). The majority of alternative support figures (80%) were grandparents. A corrective emotional experience allows the subject to work through his negative childhood experiences and acquire modalities of interaction that enable him/her to function more effectively in the world. The clinical implications of this study will be discussed. Attachment theory. Clinical implications of attachment experiences. Corrective emotional experience.