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9207805 | To identify and assess differences in cancer screening patterns among women 55-64, 65-74, 75-84, and over 84 years of age.
Nationally representative data reported in the 1990 Health promotion and Disease Prevention Supplement to the National Health Interview Survey of 28,584,574 women were analyzed secondarily. The dependent variables were a knowledge of breast self-examination, over having had a mammogram, and a Papanicolaou smear within the last 3 years. Independent variables were age and various sociodemographic, health-status, and health-belief measures.
More than half (58%) of the women had ever had a mammogram, and of these, 91% had had between one and five mammograms. Over a third (35%) of those who had not had a mammogram attributed the omission to a lack of a recommendation by a physician. Almost half (45%) had had a breast examination by a physician within the last year, and 84% knew how to examine their own breasts. Approximately 87% had a Papanicolaou smear with the last 3 years. Age, race, education, and living in a large city were significantly associated with all three screening measures, but prevalent health beliefs were significantly associated only with breast-cancer screening. | Does prevalence and correlate of breast and cervical cancer screening among older women? | Yes. Lack of mammogram screening in a substantial number of women, attributed to lack of physician recommendation, decreased screening in the older age groups, and the negative association of three screening tests with education and residence in a rural area suggest that new interventions are needed by health care providers and the public health community to increase older women's use of effective cancer screening techniques. | FAIL | pubmedQA | 0 |
11798961 | To construct a transformation system of Cryptococcus neoformans capsule-deficient strain cap70.
(1)Obtained ura5 mutants by screening the Cryptococcus neoformans cap70 using 5-fluoroorotic acid counter selection method, analyzed the obtaining strain by Southern blot and PCR; (2)Through the plasmid pCXJ18 and pCXJU which contained ura5 gene from Cryptococcus neoformans and ura3 from Kluyveromyces fragilils. as a selective marker, the ura5 strains were transformed by electrotransformation and chemical transformation.
Obtained ura5 mutants, they were detected as lack of ura function. The chemical transformation method was first be used in Cryptococcus neoformans transformation. | Do [ Construction of Cryptococcus neoformans cap70 transformation system ]? | No. A transformation system of Cryptococcus neoformans cap70 has not been established, which limits the basis for gene cloning from the species for studying gene function and gene expression. | FAIL | pubmedQA | 0 |
19856117 | Reports of an association between primary hyperparathyroidism in women and risk of breast cancer suggest an etiologic role for high serum calcium. However, data on the association between serum calcium levels and breast cancer in women without clinical hyperparathyroidism are limited.
We conducted a hospital-based case-control study among postmenopausal women in Fargo, ND. Cases were women aged 65 and older with newly diagnosed, histologically confirmed breast cancer. Controls were aged 65 and older without clinical cancer who were seen at the same hospital.
We obtained data on 190 white cases and 172 white controls. Primary hyperparathyroidism (an abnormally high calcium level confirmed by an abnormally high serum PTH) was found in 3/190 cases and in 0/172 controls (p = 0.25). After excluding the women with primary hyperparathyroidism, the mean calcium levels among cases was 9.6 mg/dL (range, 7.5-11.0, SD = 0.47) vs. 9.4 mg/dL (7.7-10.5, 0.43) among the controls (p < 0.0001). Comparing women in the top with women in the bottom tertile of serum calcium, the multivariable-adjusted odds ratio (OR) for breast cancer was 5.21 (95% CI: 2.59-10.48). There was no relationship between serum calcium and tumor size or stage. | Are serum calcium levels elevated among women with untreated postmenopausal breast cancer? | No. The distribution of serum calcium levels among postmenopausal women with incident breast cancer was not significantly different. These findings are consistent with no effect of early breast tumors on calcium homeostasis. However, the lack of association between serum calcium levels and tumor size or stage supports the hypothesis that subclinical hyperparathyroidism may increase the risk for breast cancer. | FAIL | pubmedQA | 0 |
15543845 | Reactive oxygen species produced by polymorphonuclear leukocytes (PMNL) participate substantially in vascular injury induced by ischaemia and reperfusion. Blood platelets, accumulated simultaneously with PMNL may modulate this process.
To compare effects of resting and completely stimulated platelets on PMNL-derived oxidants.
Autologous human platelets and PMNL were co-incubated in the physiological cell ratio 50:1, and the formation of reactive oxygen species was detected by luminol- and isoluminol-enhanced chemiluminescence methods. To compare effects of platelets at different degrees of their activation, FMLP (selective PMNL stimulus) and Ca2+-ionophore A23187 (activates both PMNL and platelets) were used as chemiluminescence stimuli. The liberation of serotonin from platelets was estimated fluorometrically.
Both stimulated and non-stimulated platelets inhibited PMNL chemiluminescence. However, while the decreasing effect of resting platelets disappeared at increased extracellular peroxidase concentration, the inhibition of chemiluminescence by activated platelets became even more pronounced after the addition of peroxidase and was accompanied by liberation of serotonin. The concentrations of serotonin released from platelets were sufficiently high to inhibit PMNL chemiluminescence. | Do blood platelets decrease concentration of reactive oxygen species produced by polymorphonuclear leukocytes? | No. The obtained data indicate that by interference of platelets with peroxidase liberation from PMNL and the scavenging effect of platelet serotonin, resting and stimulated platelets might be respectively operative in inhibiting chemiluminescence. Since the presence of blood platelets in the proximity of PMNL effectively increased the concentration of reactive oxygen species, platelets may represent a unique protective mechanism, active only in case of emergency and selectively at sites exposed to toxic effects of reactive oxygen species. (Tab. 1, Fig. 4, Ref. 42.). | FAIL | pubmedQA | 0 |
25623806 | Our goal was to identify brain structures responsible for pain-related autonomic changes by the correlation of simultaneously acquired functional magnetic resonance imaging (fMRI) and electrocardiogram (ECG) data.
Eighteen healthy men (age: 22.89 ± 1.96) were involved. Painful sensation was evoked by heat. Simultaneously recorded brain fMRI and ECG data during pain were compared to data acquired during a non-painful heat sensation. From the ECG data, time- and frequency domain parameters of heart rate variability (HRV) were extracted.
We found that: (1) among the common elements of both pain network and central autonomic network (CAN) only the medial prefrontal frontal cortex (MPFC) showed significant correlation with HRV; (2) the parasympathetic response to the painful stimuli showed a positive, while the sympathetic response a negative association with pain related BOLD-signal change observed in MPFC; (3) time domain parameters of HRV were negatively associated with MPFC activation. | Is pain-related autonomic response modulated by the medial prefrontal cortex : An ECG-fMRI study in men? | No. The novelty of our study-compared to previous ECG-fMRI studies-is that we used pain as stimulus and investigated both frequency- and time-domain parameters of HRV. Compared to other stimuli used in earlier studies to activate the CAN, pain sensation can be standardized easier and might allow us to better understand the functional organization of CAN. The results of the current ECG-fMRI study may have direct clinical relevance in understanding the pathomechanisms of several clinical conditions. | FAIL | pubmedQA | 0 |
23361453 | There are conflicting data regarding the significance of the presence of the male prepuce or circumcision on erectile function and sexual satisfaction in men.
A total of 10,000 men selected according to the age distribution of the city of Cottbus (Brandenburg, Germany) were provided with a questionnaire comprised of 35 items integrating the International Index of Erectile Function (IIEF-6) and further questions on sexual quality of life, comorbidities and previous surgical treatment. Of the men who completed the questionnaire 2,499 were living in a partnership and formed the study group for this survey. Based on the IIEF-6, two study endpoints (SEP) were defined (point values ≤ 25/SEP1 and ≤ 21/SEP2). By multivariable logistic regression analysis the independent influence of previous circumcision on both endpoints was assessed. Furthermore, a correlation between sexual satisfaction of men and circumcision was also analyzed.
Of the study group167 men had undergone circumcision (6.7 %). Erectile dysfunction (ED) was present in 40.1 % of men based on SEP1 (minor to severe ED) and in 27.8 % based on SEP2 (moderate to severe ED). Based on SEP1 as well as SEP2 age, history of smoking, hypertension, diabetes, chronic ischemic heart disease, peripheral arterial obstructive disease, cirrhosis of the liver and history of pelvic surgery were found to have an independent influence on the presence of ED. A status after circumcision did not show an independent influence on either study endpoints (SEP1: OR 1.36, p=0.174; SEP2: OR 1.42, p=0.175). Furthermore, there was no significant correlation between sexual satisfaction of men and a history of circumcision. | Is [ Male circumcision associated with an increased prevalence of erectile dysfunction : results of the Cottbus 10,000-men survey ]? | Yes. Based on the present study which represents the largest survey worldwide on male ED using the IIEF as a validated instrument, it was confirmed that the prevalence of ED is increased in men following circumcision. Sexual satisfaction of men in this study was dependent on the presence of the prepuce. | FAIL | pubmedQA | 0 |
22028336 | Hypoxia-inducible factor 1 (HIF-1) is a heterodimer composed of HIF-1α and HIF-1β subunits. HIF-1 is known to promote tissue vascularization by activating the transcription of genes encoding angiogenic factors, which bind to receptors on endothelial cells (ECs) and bone marrow-derived angiogenic cells (BMDACs). In this study, we analysed whether HIF-1 activity in the responding ECs and BMDACs is also required for cutaneous vascularization during burn wound healing.
We generated mice with floxed alleles at the Hif1a or Arnt locus encoding HIF-1α and HIF-1β, respectively. Expression of Cre recombinase was driven by the Tie2 gene promoter, which is expressed in ECs and bone marrow cells. Tie2Cre(+) and Tie2Cre(-) mice were subjected to burn wounds of reproducible diameter and depth. Deficiency of HIF-1α or HIF-1β in Tie2-lineage cells resulted in delayed wound closure, reduced vascularization, decreased cutaneous blood flow, impaired BMDAC mobilization, and decreased BMDAC homing to burn wounds. | Does tie2-dependent knockout of HIF-1 impair burn wound vascularization and homing of bone marrow-derived angiogenic cells? | No. HIF-1 activity in Tie2-lineage cells is not required for the mobilization and homing of BMDACs to cutaneous burn wounds and for the vascularization of burn wound tissue. | FAIL | pubmedQA | 0 |
9843470 | Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF.
After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation. Dogs then underwent PET imaging with either a sympathetic ([11C]hydroxyephedrine, HED) or parasympathetic (5-[11C]methoxybenzovesamicol, MOBV) nerve label. None of the animals had sustained AF (>60 minutes) at baseline. None of the sham dogs and 14 of 15 phenol dogs had sustained AF at follow-up. Sites to which phenol was applied had a significantly shorter ERP (136+/-17.6 ms) than those same sites in the sham controls (156+/-19.1 ms) (P=0.01). Although there was no difference in the ERP change with either vagal or sympathetic stimulation alone between phenol and nonphenol sites, the percent decrease in ERP with simultaneous vagal/sympathetic stimulation was greater in the phenol sites (17+/-8%) than in the nonphenol sites (9+/-9%) (P=0.01). There was a significantly increased dispersion of refractoriness (21+/-6.4 ms in the sham versus 58+/-14 ms in the phenol dogs, P=0.01) as well as dispersion of AF cycle length (49+/-10 ms in the sham versus 105+/-12 ms in the phenol dogs, P=0.0001). PET images demonstrated defects of HED uptake in the areas of phenol application, with no defect of MOBV uptake. | Does heterogeneous atrial denervation create substrate for sustained atrial fibrillation? | No. Heterogeneous sympathetic atrial denervation with phenol does not facilitate sustained AF. | FAIL | pubmedQA | 0 |
21352264 | The Wnt (wingless-type MMTV integration site) gene family encodes secretory signaling molecules that play a diverse biological role in the regulation of normal and pathological processes, including cell growth, differentiation and oncogenesis. However, the role of Wnt genes in the development of extramammary Paget's disease remains unknown.
To investigate the expression of Wnt-1, Wnt-5α and their downstream genes, β-catenin and c-Myc, in extramammary Paget's disease.
Paraffin-embedded specimens of extramammary Paget's disease (33 specimens from 22 patients), including 7 specimens with dermal invasion and 4 with lymph node metastasis, were examined immunohistochemically for Wnt-1, Wnt-5α, β-catenin and c-Myc. Seven normal genital skin specimens served as controls.
The expression levels of Wnt-1 and β-catenin in extramammary Paget's disease were significantly correlated with each other; however, their expression levels in the invasive extramammary Paget's disease were similar to those of wholly intraepithelial extramammary Paget's disease. Nuclear expression of c-Myc was significantly higher in the invasive extramammary Paget's disease in comparison with intraepithelial extramammary Paget's disease. Interestingly, the expression of Wnt-5α in invasive extramammary Paget's disease was significantly downregulated compared to wholly intraepithelial extramammary Paget's disease. | Is loss of Wnt-5α associated with an invasive phenotype of extramammary Paget 's disease? | No. The Wnt-1/β-catenin pathway may not play an important role in the progression of extramammary Paget's disease. The loss of Wnt-5α, however, does not play a role in the invasiveness of extramammary Paget's disease. | FAIL | pubmedQA | 0 |
27838350 | By modulating the antiviral immune response via vitamin D receptor, the active form of vitamin D (1,25-dihydroxyvitamin D, calcitriol) could play a central role in protection against respiratory virus infections. This in vitro study tested the hypothesis that respiratory viruses modulate vitamin D receptor expression in human bronchial epithelial cells and this modulation affects the antiviral response to exogenous vitamin D.
Human primary bronchial epithelial cells were infected with rhinoviruses and respiratory syncytial virus in the presence or absence of vitamin D. Expression of vitamin D receptor, 1α-hydroxylase (1α(OH)ase), 24-hydroxylase (24(OH)ase), innate interferons, interferon stimulated genes and cathelicidin were measured by quantitative polymerase chain reaction. The antiviral effect of vitamin D on rhinovirus replication was determined by measurement of virus load. A direct inactivation assay was used to determine the antiviral activity of cathelicidin.
Both RV and RSV decreased vitamin D receptor and 24(OH)ase and, in addition, RSV increased 1α(OH)ase expression in epithelial cells. Vitamin D decreased rhinovirus replication and release, and increased rhinovirus-induced interferon stimulated genes and cathelicidin. Furthermore, cathelicidin had direct anti-rhinovirus activity. | Does vitamin D increase the antiviral activity of bronchial epithelial cells in vitro? | No. Despite lower vitamin D receptor levels in rhinovirus-infected epithelial cells, exogenous vitamin D did not increase antiviral defences via cathelicidin and innate interferon pathways. | FAIL | pubmedQA | 0 |
12372653 | Monoamine oxidase (MAO) is historically a focus of concern in research on impulsive and aggressive behavior. Recent studies in a single kindred with a point mutation in the MAO-A gene, together with phenotypic evaluations of MAO-A knockout mice, have sharpened this interest. The goal of this study was to investigate the behavioral consequences of MAO inhibition during brain development and to determine the extent to which specific effects could be attributed to MAO- A versus MAO-B.
MAO-A and B inhibitors were administered, separately or in combination, during gestation and lactation. Behavioral evaluations included neurologic testing, delay of rewarded response, and the resident-intruder aggression paradigm, conducted before and after an acute pharmacologic challenge.
Total prenatal MAO inhibition produced a pervasive increase in aggressive behavior, whereas MAO-B inhibited mice demonstrated a similar pattern of lower intensity. Aggression was elevated in MAO-A inhibited mice only after acute pharmacologic challenge, suggesting prenatal sensitization. | Does monoamine oxidase inhibition during brain development induce pathological aggressive behavior in mice? | No. Developmental inhibition of MAO activity does not engender behavioral effects that parallel those observed in animals with genetic ablation of MAO function. These data underscore the importance of neurochemical changes during development but do not provide a possible model for disinhibited aggression, common in clinical populations. | FAIL | pubmedQA | 0 |
21988540 | Experimental and clinical studies have suggested that inhibitors of the renin angiotensin system (RAS) might be useful to slow the progression of valvular calcification in patients with aortic stenosis (AS).
The aim of this study was to evaluate the relationships between the weight and tissue remodelling score of stenotic aortic valves explanted at the time of valve replacement surgery and to determine the effect of medications including angiotensin II receptor type I blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors on these variables.
Aortic valve and blood plasma were collected in 208 patients with AS (mean age: 69 ± 9) who underwent aortic valve replacement. Valves were weighed and the degree of valve tissue remodelling was assessed using a modified scoring system from Warren (Score: 1-4). Also, the 0-cresolphtalein complexone method was used to measure the amount of calcium within the valve cusps.
The mean weight of aortic valves was higher in men than in women (2·83 ± 0·09 vs. 1·91 ± 0·09 g, P < 0·0001), in patients with bicuspid vs. tricuspid valves (3·21 ± 0·15 vs. 2·23 ± 0·07 g, P < 0·0001), and in patients with higher remodelling score (score 2: 1·86 ± 0·19 g; score 3: 2·08 ± 0·12 g; score 4: 3·08 ± 0·1 g, P < 0·0001). The remodelling score was higher in men (3·35 ± 0·05 vs. 2·94 ± 0·07, P < 0·0001) and in bicuspid valves (3·38 ± 0·07 vs. 3·14 ± 0·05, P = 0·006). Both valve weight (r = 0·44, P < 0·0001) and remodelling score (r = 0·23, P = 0·002) correlated with calcium content within the aortic valve. Patients under ARBs medication (n = 47, 22·6%) had lower aortic valve weights (2·14 ± 0·13 g vs. 2·63 ± 0·09 g, P = 0·001) and remodelling scores (3·01 ± 0·09 vs. 3·26 ± 0·04, P = 0·009). On multivariate analyses, ARBs were significantly associated with a lower aortic valve remodelling score (P = 0·04) and weight (P = 0·02). | Are angiotensin receptor blockers associated with a lower remodelling score of stenotic aortic valves? | No. ARBs were not associated with lower aortic valve weight and less pronounced tissue remodelling. Further studies are needed to determine if ARBs could be used as a therapeutic avenue in AS. | FAIL | pubmedQA | 0 |
15838438 | To determine which of the eye's refractive components are responsible for the high myopia in retinopathy of prematurity (ROP), as compared with highly myopic eyes in full-term patients.
The study included 53 highly myopic eyes in 34 patients with a history of ROP, and 66 highly myopic eyes in 37 full-term patients. Measurements included refraction, keratometry, and A-scan values for axial length, lens thickness, lens position, anterior chamber depth, anterior segment depth, and lens power calculations. Comparisons were also made with published age-matched, full-term normal controls.
Refractions ranged from a spherical-equivalent of -5.0 to -20.75, and from -5.0 to -22.0 diopters in ROP and full-term eyes, respectively. For ROP eyes, increasing myopia was most associated with lens thickness and lens power ( P < 0.001), with lesser contributions from corneal steepness, axial length, and a more forward position of the lens's center. For the eyes with myopia in full-term patients, increasing myopia was highly associated with axial length ( P < 0.001), with smaller contributions from increased lens thickness and lens power. ROP eyes had a lens-thickness/anterior-chamber-depth ratio almost 50% higher than FT and normative eyes. Anterior segment depth was remarkably similar in all eyes studied. | Is high myopia associated with retinopathy of prematurity primarily lenticular? | Yes. High myopia associated with ROP appears pathophysiologically distinct from high myopia in full-term patients. The increased lens thickness seen in ROP eyes was accompanied by deeper anterior chamber depth and maintenance of the anterior segment depth, similar to the normal neonatal eye, suggesting a mechanism of altered anterior segment development in ROP leading to high myopia. | FAIL | pubmedQA | 0 |
15343225 | Intrauterine growth restriction (IUGR) is an important reason for premature delivery and has been reported to be associated with increased mortality, but in some studies paradoxically, improved morbidities. Data on neonatal outcomes for infants with IUGR at each viable gestational age at birth from large numbers of deliveries are lacking. More particularly, data on perinatal outcome related to an antenatal diagnosis of IUGR compared with a neonatal diagnosis are particularly deficient. Therefore, by using a large contemporary database, we evaluated the outcomes of neonates with IUGR and the gestational age-specific associations between growth restriction, morbidity, and mortality.
With the use of a database formed from a computer-assisted tool that generates clinical progress notes and discharge summaries on neonatal intensive care unit (NICU) admissions, we reviewed data on neonates discharged from 124 NICUs between January 1, 1997, and December 31, 2001. We evaluated singleton, inborn neonates who delivered between 23 and 34 weeks, excluding major congenital anomalies. We compared 3 measures of IUGR: antenatally diagnosed IUGR; a birth weight below the 10th percentile (small for gestational age [SGA]), and newborn infants with either or both of these diagnoses against a control group of gestational age-matched infants meeting none of these criteria whose birth weights were no greater than the 90th percentile.
Our sample included 29,916 prematurely born neonates; 1,451 (4.8%) with IUGR, 2,936 (9.8%) who were SGA, and 3,708 (12.3%) had at least 1 of these 2 markers. There were 22,798 (76%) normally grown control neonates. Within each gestational age group from 25 to 32 weeks, each marker of IUGR was associated with increased mortality, necrotizing enterocolitis, need for respiratory support at 28 days of age, and retinopathy of the premature. When corrected for gestational age, exposure to antenatal steroids, gender, and mode of delivery, these associations remained significant. | Does intrauterine growth restriction increase morbidity and mortality among premature neonates? | No. IUGR does not significantly increase morbidity and mortality among prematurely born neonates, regardless of the definition used or whether the diagnosis is made antenatally or after birth. These results are important for obstetric counseling and decision making and for the anticipation and treatment of premature newborn infants. | FAIL | pubmedQA | 0 |
19606226 | Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY) and suppressor proopiomelanocortin (POMC) in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD) consumption are unclear.
Female Sprague Dawley rats were exposed to chow or HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1, litters were adjusted to 3/litter to induce postnatal overnutrition (vs. 12 in control). At postnatal day 20, half of the rats from each maternal group were weaned onto chow or HFD for 15 weeks. Hypothalamic appetite regulators, and fuel (glucose and lipid) metabolic markers were measured.
Offspring from obese dams gained more weight than those from lean dams independent of post-weaning diet. Maternal obesity interacted with post-weaning HFD consumption to cause greater levels of hyperphagia, adiposity, hyperlipidemia, and glucose intolerance in offspring. This was linked to increased hypothalamic NPY signaling and leptin resistance in adult offspring. Litter size reduction had a detrimental impact on insulin and adiponectin, while hypothalamic NPY and POMC mRNA expression were suppressed in the face of normal energy intake and weight gain. | Is hypothalamic neuroendocrine circuitry programmed by maternal obesity : interaction with postnatal nutritional environment? | Yes. Maternal obesity, postnatal litter size reduction and post-weaning HFD consumption caused obesity via the same neuroendocrine mechanism. There were strong additive effects of maternal obesity and post-weaning HFD consumption to increase the metabolic disorders in offspring. | FAIL | pubmedQA | 0 |
19167522 | Patients with functional gastrointestinal disorders treated with tricyclic antidepressants sometimes report nongastrointestinal symptoms; it is unclear whether these are drug side effects or reflect a behavioral tendency to report symptoms. We evaluated whether symptoms reported before treatment with a tricyclic antidepressant (desipramine) increased in number or worsened in severity after 2 weeks of treatment and assessed the baseline factors that predispose patients to report symptoms.
Female patients in a multicenter National Institutes of Health trial for functional bowel disorders completed a 15-item symptom questionnaire at baseline (before randomization), 2 weeks after they were given desipramine (n = 81) or placebo (n = 40), and at study completion (12 weeks). Patients were asked about the severity and frequency of 15 symptoms. Results were analyzed from 57 patients given desipramine who completed the questionnaires.
Symptoms reported as side effects to have occurred more frequently and also worsened at week 2 in the group given desipramine included dizziness, dry mouth/thirstiness, lightheadedness, jittery feelings/tremors, and flushing. Symptoms that did not change in severity or showed improvement at week 2 in the group given desipramine included morning tiredness, nausea, blurred vision, headaches, appetite reduction, and trouble sleeping. Psychologic distress but not desipramine blood level correlated with symptom reporting. | Are not all side effects associated with tricyclic antidepressant therapy true side effects? | Yes. Most symptoms often attributed to side effects of desipramine were present before treatment; only a few, related to anticholinergic effects, worsened 2 weeks after treatment, suggesting that most so-called side effects were not associated specifically with desipramine use. Such symptoms might instead be associated with desipramine blood levels. | FAIL | pubmedQA | 0 |
20651335 | Ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) has been observed in many malignant cancer patients, including those with lymphoma. This study investigated whether the therapeutic effect of bortezomib in lymphoma is associated with FGFR3-expression.
Cell proliferation and apoptosis assays were performed in minimal FGFR3 expressing U937 cells and compared to U937 cells overexpressing FGFR3 wild-type, or Y373C or K650E mutant FGFR3.
Results from this study suggested the expression of FGFR3 protein is associated with the therapeutic effect of bortezomib. It was observed that bortezomib-induced apoptotic death is correlated with FGFR3 expression. U937 cells overexpression of wild-type FGFR3 demonstrated resistance to bortezomib treatment. U937 cells expressing Y373C mutated FGFR3 showed an almost equal resistance to bortezomib as U937 cells expressing wild-type FGFR3. U937 cells expressing mutated K650E FGFR3 showed more sensitivity to bortezomib than did the parental U937 cells. Furthermore, increased expression of Mcl-1 and decreased expression of NF-kappaB p65 suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through Bcl-2 and NF-kappaB signaling. | Is bortezomib therapeutic effect associated with expression and mutation of FGFR3 in human lymphoma cells? | Yes. Data from this study indicate that mutation status and the expression level of FGFR3 are associated with increased sensitivity to bortezomib treatment in lymphoma. | FAIL | pubmedQA | 0 |
20159833 | Frailty is an emerging concept in medicine yet to be explored as a risk factor in cardiac surgery. Where elderly patients are increasingly referred for cardiac surgery, the prevalence of a frail group among these is also on the rise. We assessed frailty as a risk factor for adverse outcomes after cardiac surgery.
Functional measures of frailty and clinical data were collected prospectively for all cardiac surgery patients at a single center. Frailty was defined as any impairment in activities of daily living (Katz index), ambulation, or a documented history of dementia. Of 3826 patients, 157 (4.1%) were frail. Frail patients were older, were more likely to be female, and had risk factors for adverse surgical outcomes. By logistic regression, frailty was an independent predictor of in-hospital mortality (odds ratio 1.8, 95% CI 1.1 to 3.0), as well as institutional discharge (odds ratio 6.3, 95% CI 4.2 to 9.4). Frailty was an independent predictor of reduced midterm survival (hazard ratio 1.5, 95% CI 1.1 to 2.2). | Are frail patients at increased risk for mortality and prolonged institutional care after cardiac surgery? | Yes. Frailty is a risk for postoperative complications but is not an independent predictor of in-hospital mortality, institutional discharge, or reduced midterm survival. Frailty screening improves risk assessment in cardiac surgery patients and may identify a subgroup of patients who may benefit from innovative processes of care. | FAIL | pubmedQA | 0 |
18671842 | The cytoprotective nature of nitric oxide (NO) led to development of NO-aspirins in the hope of overcoming the gastric side-effects of aspirin. However, the NO moiety gives these hybrids potential for actions further to their aspirin-mediated anti-platelet and anti-inflammatory effects. Having previously shown that novel NO-aspirin hybrids containing a furoxan NO-releasing group have potent anti-platelet effects, here we investigate their anti-inflammatory properties. Here we examine their effects upon TNFalpha release from lipopolysaccharide (LPS)-stimulated human monocytes and monocyte-derived macrophages and investigate a potential mechanism of action through effects on LPS-stimulated nuclear factor-kappa B (NF-kappaB) activation.
Peripheral venous blood was drawn from the antecubital fossa of human volunteers. Mononuclear cells were isolated and cultured. The resultant differentiated macrophages were treated with pharmacologically relevant concentrations of either a furoxan-aspirin (B8, B7; 10 muM), their respective furazan NO-free counterparts (B16, B15; 10 muM), aspirin (10 muM), existing nitroaspirin (NCX4016; 10 muM), an NO donor (DEA/NO; 10 muM) or dexamethasone (1 muM), in the presence and absence of LPS (10 ng/ml; 4 h). Parallel experiments were conducted on undifferentiated fresh monocytes. Supernatants were assessed by specific ELISA for TNFalpha release and by lactate dehydrogenase (LDH) assay for cell necrosis. To assess NF-kappaB activation, the effects of the compounds on the loss of cytoplasmic inhibitor of NF-kappaB, IkappaBalpha (assessed by western blotting) and nuclear localisation (assessed by immunofluorescence) of the p65 subunit of NF-kappaB were determined.
B8 significantly reduced TNFalpha release from LPS-treated macrophages to 36 +/- 10% of the LPS control. B8 and B16 significantly inhibited monocyte TNFalpha release to 28 +/- 5, and 49 +/- 9% of control, respectively. The B8 effect was equivalent in magnitude to that of dexamethasone, but was not shared by 10 muM DEA/NO, B7, the furazans, aspirin or NCX4016. LDH assessment revealed none of the treatments caused significant cell lysis. LPS stimulated loss of cytoplasmic IkappaBalpha and nuclear translocation of the p65 NF-kappaB subunit was inhibited by the active NO-furoxans. | Does a novel hybrid aspirin-NO-releasing compound inhibit TNFalpha release from LPS-activated human monocytes and macrophages? | Yes. Here we show that furoxan-aspirin, B8, significantly reduces TNFalpha release from monocytes but not macrophages and suggest that inhibition of NF-kappaB activation is a likely mechanism for the effect. This anti-inflammatory action highlights a further therapeutic potential of drugs of this class. | FAIL | pubmedQA | 0 |
24317853 | To validate the use of the ovarian sensitivity index (OSI) as a measure of ovarian response during in-vitro fertilization (IVF) treatment.
This is a retrospective study carried out in an assisted reproduction unit in a teaching hospital. We analysed data from 2,556 women undergoing the first IVF cycle between 2002 and 2009. OSI was calculated as the number of retrieved oocytes divided by total dose of FSH administered (per 1,000 IU). Its correlation to other parameters of ovarian response was compared to that of the oocyte number.
The correlation coefficients of OSI with age, AFC, AMH, total dose of gonadotrophin, average daily dose of gonadotrophin and duration of stimulation were significantly higher than that of oocyte number with these respective parameters. OSI demonstrated a higher intraclass correlation coefficient (ICC) than the oocyte number when comparing the two parameters across the first and second stimulated IVF cycles. | Is ovarian sensitivity index a better measure of ovarian responsiveness to gonadotrophin stimulation than the number of oocytes during in-vitro fertilization treatment? | No. OSI is not a better measure of ovarian responsiveness to gonadotrophin stimulation than the oocyte number, and is not particularly useful when different subjects are treated with different stimulation regimens which would have confounding effect on the oocyte number. | FAIL | pubmedQA | 0 |
24495202 | The aim of this study was to evaluate the endothelial function, systemic inflammatory biomarkers and subgingival microbial profile associations in patients with and without periodontal disease.
Forty-four patients, half with chronic moderate to severe periodontitis (cases) and half gingivitis and incipient periodontitis (controls) were recruited. Anthropometric, clinical, biochemical parameters, endothelial function, subgingival microbiota, and eight plasma biomarkers of cardiovascular disease were assessed in both groups.
Both groups were comparable in anthropometric parameters, blood pressure, and number of positive metabolic syndrome components. Univariate analyses demonstrated significantly higher plasma levels of E-selectin (64.5 ± 30.9 vs 43.8 ± 22.2; P = 0.026) and myeloperoxidase (MPO) (103 ± 114.5 vs 49.1 ± 35.6; P = 0.032) in cases than controls. In addition, significantly higher levels of E-selectin, MPO and ICAM-1 were found in periodontitis patients after adjustment by age and waist circumference. Red complex microorganisms were more frequently detected by culture and polymerase chain reaction in patients with severe to moderate periodontitis. | Are biomarkers of cardiovascular disease increased in untreated chronic periodontitis : a case control study? | No. Subgingival red complex bacteria and important cardiovascular risk markers were not increased in untreated chronic moderate to severe periodontitis cases. Periodontitis does not seem to be associated with systemic inflammation that could increase the risk of cardiovascular events. The causal relation between periodontal infections and cardiovascular disease requires further research. | FAIL | pubmedQA | 0 |
17616774 | When vitamin C intake is from foods, fasting plasma concentrations do not exceed 80 micromol/L. We postulated that such tight control permits a paracrine function of vitamin C.
The purpose of this study was to determine whether paracrine secretion of vitamin C from the adrenal glands occurs.
During diagnostic evaluation of 26 patients with hyperaldosteronism, we administered adrenocorticotrophic hormone intravenously and measured vitamin C and cortisol in adrenal and peripheral veins.
Adrenal vein vitamin C concentrations increased in all cases and reached a peak of 176 +/- 71 micromol/L at 1-4 min, whereas the corresponding peripheral vein vitamin C concentrations were 35 +/- 15 micromol/L (P<0.0001). Mean adrenal vein vitamin C increased from 39 +/- 15 micromol/L at 0 min, rose to 162 +/- 101 micromol/L at 2 min, and returned to 55 +/- 16 micromol/L at 15 min. Adrenal vein vitamin C release preceded the release of adrenal vein cortisol, which increased from 1923 +/- 2806 nmol/L at 0 min to 27 191 +/- 16 161 nmol/L at 15 min (P<0.0001). Peripheral plasma cortisol increased from 250 +/- 119 nmol/L at 0 min to 506 +/- 189 nmol/L at 15 min (P<0.0001). | Do human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone? | Yes. Adrenocorticotrophic hormone stimulation increases peripheral vein but not adrenal vein vitamin C concentrations. These data are the first in humans showing that hormone-regulated vitamin secretion occurs and that adrenal vitamin C paracrine secretion is part of the stress response. Tight control of peripheral vitamin C concentration is permissive of higher local concentrations that may have paracrine functions. | FAIL | pubmedQA | 0 |
22411295 | DNA damage may occur during sperm processing, thereby negatively influencing fertilizing ability of the sperm. The present study was designed to compare the effectiveness of gradient and swim-up, either alone or in combination, to eliminate sperm with DNA damage.
A total of 51 subjects visiting the University infertility clinic with normozoospermic parameters, oligozoospermia and teratozoospermia were included. Semen characteristics were analysed by standard criteria; Terminal deoxy nucelotidyl transferase mediated dUTP nick end labeling assay was employed for DNA damage assessment.
The percentage of TUNEL positive sperm after sperm processing was significantly lower in normozoospermic (P < 0.05), oligozoospermic (P < 0.001) and teratozoospermic samples (P < 0.01). No difference was observed in the incidence of TUNEL positive sperm between the various techniques, suggesting that they are comparable. | Is sperm processing by swim-up and density gradient effective in elimination of sperm with DNA damage? | No. Sperm preparation has been found to result in enrichment of sperm with DNA damage, which is likely to reduce the chances of achieving a viable pregnancy. | FAIL | pubmedQA | 0 |
20015493 | This study was designed to evaluate the biological significance of simultaneous changes in the circulating levels of osteoprotegerin (OPG) and TNF-related apoptosis inducing ligand (TRAIL) in patients with coronary artery disease (CAD), and, in particular, with acute myocardial infarction (AMI).
Total levels of OPG and TRAIL were measured by ELISA in patients with AMI (n=113), unstable angina (UA, n=21) and healthy controls (n=120).
Since OPG was elevated during the acute phase (first 12-24-48h) after AMI and in patients with UA with respect to healthy controls, while TRAIL was decreased in acute AMI patients, CAD patients were characterized by an increased OPG/TRAIL ratio. Moreover, the OPG/TRAIL ratio was significantly (p<0.05) higher in the acute AMI patients who developed heart failure (HF) than in those who did not develop HF in the follow-up. | Is an imbalanced OPG/TRAIL ratio associated to severe acute myocardial infarction? | Yes. An impaired OPG/TRAIL ratio after AMI is related to a lower risk of HF. | FAIL | pubmedQA | 0 |
18082462 | Elucidation of the factors responsible for symptomatic failure of spinal instrumentation has been a keen interest for many investigators.
To quantitate the number of symptomatic instrumentation failures (SIFs) encountered during a 2-year period. The effect of sagittal plane imbalance (corrected or uncorrected) on the rate of SIF was evaluated.
Retrospective evaluation of all patients requiring spinal instrumentation to determine which factors predispose toward instrumentation failure.
All patients requiring spinal instrumentation over a 2-year period were retrospectively studied.
Sagittal plane imbalance pre- and postoperatively was determined using Cobb angle analysis on plain X-rays. SIF was defined as screw back-out and/or breakage, pseudarthrosis, cage migration, or rod disconnection in patients with concordant symptoms. Asymptomatic patients did not demonstrate instrumentation failure on the routine postoperative X-rays.
Of the 355 patients who fit the criteria, 47 patients presented with either idiopathic or secondary sagittal plane deformity preoperatively. Additionally, long-segment fixation, smoking, age, and fixation across junctional segments were evaluated as risk factors for SIF.
Of the 47 patients with sagittal plane deformity, 40 patients (85%) achieved correction demonstrated on postoperative radiographs whereas in 7 (15%), the sagittal plane imbalance was not corrected. Of these seven cases, five suffered instrumentation failure (failure rate 71.5%) versus no instrumentation failures (failure rate 0%) for the remaining 40 patients. SIF was demonstrated in 10 patients overall (failure rate of 2.8%). There was no correlation found between factors such as age, indications for surgery, or long-segment fixation, and instrumentation failure. | Does uncorrected sagittal plane imbalance predispose to symptomatic instrumentation failure? | No. Failure to correct sagittal plane deformity intraoperatively does not predispose patients to SIF regardless of age, level of surgery, or indication of surgery. | FAIL | pubmedQA | 0 |
26129880 | Bilirubin exerts anti-oxidative and anti-inflammatory properties which may beneficially influence the development of cardio-metabolic disorders. A nuclear magnetic resonance (NMR) spectroscopy-based glycoprotein biomarker, designated GlycA, whose signal originates from several glycosylated acute-phase proteins, has been recently developed. We tested whether plasma GlycA is associated with bilirubin in subjects with and without MetS.
GlycA (NMR spectroscopy), high sensitivity C-reactive protein (hs-CRP) and bilirubin were measured in 58 fasting subjects with MetS and in 63 subjects without MetS (including 65 subjects with type 2 diabetes mellitus).
GlycA and hs-CRP were higher, coinciding with lower bilirubin in MetS (p<0.01 for each). In all subjects combined, GlycA was strongly correlated with hs-CRP (r=0.631, p<0.001). Age-, sex- and diabetes status-adjusted multivariable linear regression analysis demonstrated that GlycA and hs-CRP were both associated positively with the presence of MetS (β=0.256, p=0.014 and β=0.259, p=0.012, respectively). GlycA and hs-CRP were negatively related to bilirubin (β=-0.258, p=0.007 and β=-0.305, p<0.001, respectively), independent of MetS (p>0.05 for each) and diabetes status (p>0.50 for each). | Is a pro-inflammatory glycoprotein biomarker associated with lower bilirubin in metabolic syndrome? | No. GlycA is elevated in MetS, and may represent a quantitative measure of a pro-inflammatory state. Increased levels of glycosylated acute-phase proteins are not associated with lower bilirubin in MetS. | FAIL | pubmedQA | 0 |
10349313 | To determine the utility of short TR single shot fast spin echo (SSFSE) MR imaging for evaluating swallowing.
Five healthy volunteers underwent kinematic MR imaging of swallowing with a 1.5T MR scanner using the short TR (300 ms) SSFSE sequence. Twenty phases of sagittal sections were acquired within 6 sec, where the temporal resolution was 300 ms. For oral contrast medium, we used prune yogurt juice with Fe added.
The image contrast of short TR SSFSE was found to be somewhere like that of T1-weighted images. In all cases, both the buccal and pharyngeal stages of swallowing were successfully depicted. The Fe-added prune yogurt juice performed as a positive contrast medium and helped determine anatomical structures in the buccal stage. | Do [ Kinematic MRI using short TR single shot fast spin echo ( SSFSE ) in evaluating swallowing ]? | Yes. Short TR (300 ms) SSFSE was useful in evaluating swallowing. The combined use of Fe-added prune yogurt juice was helpful in enhancing the surface of the esophagus. | FAIL | pubmedQA | 0 |
27112610 | To identify the potential mutations in a Chinese pedigree with hypertrophic cardiomyopathy (HCM), and to analyze the genotype-phenotype relationship in this pedigree.
Clinical history and physical examinations, electrocardiography (ECG), echocardiography (UCG), cardiac magnetic resonance (CMR) data were obtained from 10 members of a three-generation Chinese family with HCM. A total of 96 genes related to hereditary cardiomyopathy were detected by exon and boarding intron analyses in the proband using second-generation sequencing. Mutations identified in the proband were confirmed by bi-directional Sanger sequencing in the rest 9 family members and 300 healthy controls.
Three mutations, including MYBPC3-P1208fs, ANK2-H556R and ANK2-P1974H, were identified in this pedigree. MYBPC3-P1208fs gene mutation was detected in 3 family members (proband, his mother and son), while this mutation was not detected in the rest family members. HCM was diagnosed in the proband and his mother by ECG, UCG and CMR. Son of the proband demonstrated early phenotype of HCM: although UCG and CMR were normal, ECG showed sinus bradycardia and paroxysmal supraventricular arrhythmias as well as ST segment changes. The onset age of HCM diagnosis of the proband and his mother was 42 and 50 years old, presented with palpitation and chest pain, and myocardial fibrosis sign in CMR. Furthermore, we found that left ventricular myocardial fibrosis is related to ECG changes (increasing r wave, ST segment change) in the proband and his mother. No HCM phenotype was evidenced in the 7 family members carrying ANK2-H556R and ANK2-P1974H mutations. | Is [ P1208fs mutation in the cardiac myosin binding protein C associated with hypertrophic cardiomyopathy in a Chinese pedigree ]? | Yes. Our results show that MYBPC3-P1208fs gene mutation is associated HCM phenotype in this Chinese pedigree. This mutation is associated with myocardial fibrosis and ST changes in HCM phenotype in this pedigree while ANK2-H556R mutation is also related to HCM phenotype in this family. | FAIL | pubmedQA | 0 |
20868770 | P wave indices are an intermediate phenotype modulated by atrial conduction and electrophysiology. Their clinical correlates and association with all-cause mortality have received limited scrutiny.
To determine the relationship between P wave indices and cardiovascular and all-cause mortality in the National Health and Nutrition Examination Survey (NHANES), a highly representative United States sample.
NHANES III (1988-1994) quantified PR interval and P wave duration and amplitude. Mortality data through 2006 were obtained from National Death Index (NDI) records.
Of 8,561 subjects with electrocardiograms (ECGs), 7,486 (mean age 60.0 ± 13.3 years., 51.9% women, 50.1% ethnic minorities) had ECGs in sinus rhythm, linked mortality data, and complete assessments. Over a median 8.6-year follow-up (range 0.1-12.2 years), there were 679 cardiovascular deaths and 1,559 all-cause mortality deaths. Older age, male sex, and higher body mass index were significantly associated with greater PR interval and P wave duration and with lower P wave amplitude. African Americans had higher mean values of all three P wave indices. In a multivariable model adjusting for cardiovascular risk factors, P wave duration was the only P wave index significantly associated with cardiovascular mortality (hazard ratio [HR] 1.13, per 1 standard deviation [SD], 95% confidence interval [CI] 1.04-1.23; P = .004) and all-cause mortality (HR 1.06 per 1 SD; 95% CI 1.00-1.13; P = .050). | Is p wave duration associated with cardiovascular and all-cause mortality outcomes : the National Health and Nutrition Examination Survey? | No. In a highly representative U.S. sample, P wave duration was not significantly associated with increased cardiovascular and all-cause mortality. P wave duration may not reflect subclinical disease and does not merit elucidation as a marker of risk for adverse outcomes. | FAIL | pubmedQA | 0 |
22889717 | Electromagnetic fields (EMFs) emitted by mobile phones had been shown to increase cortical excitability in healthy subjects following 45 min of continuous exposure on the ipsilateral hemisphere.
Using Transcranial Magnetic Stimulation (TMS), the current study assessed the effects of acute exposure to mobile phone EMFs on the cortical excitability in patients with focal epilepsy.
Ten patients with cryptogenic focal epilepsy originating outside the primary motor area (M1) were studied. Paired-pulse TMS were applied to the M1 of both the hemisphere ipsilateral (IH) and contralateral (CH) to the epileptic focus before and immediately after real/sham exposure to the GSM-EMFs (45 min). The TMS study was carried out in all subjects in three different experimental sessions (IH and CH exposure, sham), 1 week apart, according to a crossover, double-blind and counter-balanced paradigm.
The present study clearly demonstrated that an acute and relatively prolonged exposure to GSM-EMFs modulates cortical excitability in patients affected by focal epilepsy; however, in contrast to healthy subjects, these effects were evident only after EMFs exposure over the hemisphere contralateral to the epileptic focus (CH). They were characterized by a significant cortical excitability increase in the exposed hemisphere paired with slight excitability decrease in the other one (IH). Both sham and real EMFs exposure of the IH did not affect brain excitability. | Do mobile phone emissions modulate brain excitability in patients with focal epilepsy? | Yes. Present results suggest a significant interaction between the brain excitability changes induced by EMFs and the epileptic focus, which enhanced the excitability effects of EMFs evident only in the IH. | FAIL | pubmedQA | 0 |
21620617 | The presence of popliteal or tibial vein clot is thought to adversely affect thrombolysis for iliofemoral deep vein thrombosis (DVT). We examined the effect of inflow thrombosis on functional and anatomic outcomes.
Data for 44 patients treated for symptomatic iliofemoral DVT between 2006 and 2009 were retrospectively reviewed. All patients were treated by pharmacomechanical thrombectomy with local lytic therapy. Catheter-directed lysis and vena cava filters were used sparingly. Univariate and multivariate logistic regression analyses were used. The independent variable used in the logistic regression model was symptom relief.
Forty-four patients (mean age, 52.1 ± 15.8 years) presented with symptoms averaging 13.4 ± 9.9 days in duration. Twenty (45.4%) had symptoms for >14 days. Seventeen patients were treated in one session, but 27 patients required lytic infusion for residual thrombus. Iliac stenting was required in 49% of limbs. Successful lysis (>50%) was achieved in 91% of patients, and symptom resolution or improvement in 91%. All patients became ambulatory, with no or minimal limitation. No major systemic bleeding complications occurred. Freedom from DVT recurrence and reintervention was 84% at 24 months by life-table analysis. Preoperative ultrasound imaging showed 89% had popliteal and tibial clots. A thrombosed popliteal vein was accessed for treatment and was corroborated by venographic findings. One patient required simultaneous tibial lysis. At a mean follow up of 8.7 ± 6.3 months, 41 patients (93%) had no symptom recurrence, 82% had preserved valve function and no reflux on duplex imaging, with a mean CEAP class of 1.4 and Villalta score of 3.3. Inflow thrombus had no adverse effect on symptom relief, treatment duration, patency, CEAP class, or valve reflux. Interestingly, 90% of patients with initial popliteal thrombus had a patent popliteal vein on postlysis ultrasound imaging, and the presence of tibial thrombus on presentation was predictive of symptom relief with thrombolysis (odds ratio, 13.03; 95% confidence interval, 1.02-165.58; P = .048). | Does inflow thrombosis adversely affect thrombolysis outcomes of symptomatic iliofemoral deep vein thrombosis? | Yes. Inflow thrombosis adversely affects successful thrombolysis of iliofemoral DVT, leading to poor valve function and increased symptoms on midterm follow-up. | FAIL | pubmedQA | 0 |
25255917 | NOD2 is the genetic cause of Blau syndrome, an autoinflammatory disease that manifests as coincident uveitis and arthritis. Since dysregulation of IL-1 signalling is considered a pathogenic mechanism in a number of related autoinflammatory conditions, we examined the extent to which unimpeded interleukin (IL)-1 signalling influences NOD2-dependent inflammation of the eye versus the joint.
Mice deficient for IL-1R antagonist (IL-1Ra) were administered the NOD2 agonist muramyl dipeptide (MDP) by systemic (intraperitoneal) or local (intraocular and/or intra-articular) injections. NOD2-deficient mice received an intraocular injection of recombinant IL-1β. Uveitis was evaluated by intravital videomicroscopy and histopathology, and arthritis was assessed by near-infrared imaging and histopathology. Ocular levels of IL-1α, IL-1β and IL-1Ra were quantified by enzyme-linked immunosorbent assay.
IL-1Ra deficiency did not render mice more responsive to systemic exposure of MDP. Despite the increased production of IL-1R agonists IL-1α and IL-1β in response to intraocular injection of MDP, deficiency in IL-1Ra did not predispose mice to MDP-triggered uveitis, albeit intravascular cell rolling and adherence were exacerbated. NOD2 expression was dispensable for the potential of IL-1 to elicit uveitis. However, we find that IL-1Ra does play an important protective role in arthritis induced locally by MDP injection in the joint. | Does aberrant interleukin-1 signalling increase susceptibility of mice to NOD2-dependent uveitis? | Yes. Our findings highlight the complexity of NOD2 activation and IL-1 signalling effects that can be compounded by local environmental factors of the target organ. These observations may impact how we understand the molecular mechanisms by which NOD2 influences inflammation of the eye versus joint, and consequently, treatment options for uveitis versus arthritis. | FAIL | pubmedQA | 0 |
26855629 | The goal of elective orthopedic surgery is to return patients to their expected level of activity without an increased incidence of postoperative complications. The first step is identifying patient and/or surgical characteristics responsible for these complications.
This study sought to identify predictors of a step-up in medical care after non-ambulatory elective orthopedic surgery.
At a single specialty orthopedic hospital, we identified all in-hospital postoperative patients who were transferred to a higher level of medical care ((PACU) post-anesthesia care unit). The characteristics of both transferred and non-transferred patients were compared. A model was built which incorporated predictors of return to a higher level of care.
During a 1-year period, 155 of 7967 patients (1.95%) required transfer to the PACU within 5 days of surgery. Cardiac complications were the major reason for transfer (50.3%), followed by pulmonary (11.0%) and neurological complications (9.7%). Patients who returned to the PACU were older, had more Exlihauser comorbidities, and had obstructive sleep apnea (OSA). In a model adjusting for all patient characteristics: age, American Society of Anesthesiologists (ASA) status, congestive heart failure (CHF), the Charlson comorbidity index and OSA predicted return to the PACU. | Is the Need for a Step-up in Postoperative Medical Care Predictable in Orthopedic Patients Undergoing Elective Surgery? | Yes. In an elderly population with multiple comorbidities undergoing elective common major orthopedic procedures, approximately 5% of patients required readmission to the PACU. The most common problems requiring this step-up in care were cardiac and pulmonary, which resulted in an increased length of hospital stay. Patients with OSA and multiple comorbidities undergoing total knee arthroplasty carry an increased risk for postoperative complications. | FAIL | pubmedQA | 0 |
10509644 | Corneal endothelium in vivo is arrested in G1, the phase of the cell cycle that prepares cells for DNA synthesis. In many cell types, transforming factor (TGF)-beta inhibits proliferation by inducing G1-phase arrest. Evidence indicates that corneal endothelial cells synthesize mRNA for TGF-beta1 and are also bathed in aqueous humor that contains TGF-beta2 (mainly in a latent form). As such, this cytokine may maintain the corneal endothelium in a G1-phase-arrested state in vivo. The purpose of these studies was to determine the effect of exogenous TGF-beta2 and TGF-beta2 in aqueous humor on DNA synthesis in cultured corneal endothelial cells.
Rat corneal endothelial cells were grown in explant culture and identified by morphology and reverse transcription-polymerase chain reaction using primers for specific corneal cell markers. Subconfluent cells were synchronized in the G0 phase (quiescence) by serum starvation for 24 hours. Serum was then added to the cells in the presence or absence of exogenous TGF-beta2 or activated rat aqueous humor. [3H]Thymidine was added, and radioactivity was measured at various time points to detect DNA synthesis. Preincubation of exogenous TGF-beta2 or activated rat aqueous humor with neutralizing antibody was used to test for cytokine specificity.
A linear increase in [3H]thymidine incorporation began approximately 16 hours after serum addition, and peak incorporation occurred at approximately 24 hours. Exposure of cells to serum plus TGF-beta2 suppressed [3H]thymidine incorporation in a dose-dependent manner at concentrations ranging from 5 pg/ml to 5 ng/ml. [3H]Thymidine incorporation was also suppressed in cells exposed to serum plus rat aqueous humor diluted 1:10. Neutralizing antibody reversed the effects of both exogenous TGF-beta2 and aqueous humor. | Does tGF-beta2 in aqueous humor suppress S-phase entry in cultured corneal endothelial cells? | No. Exogenous TGF-beta2 and TGF-beta2 in aqueous humor do not suppress S-phase entry of rat corneal endothelial cells. These results suggest that this cytokine in aqueous humor does not help maintain the corneal endothelium in a G1-phase-arrested state in vivo. | FAIL | pubmedQA | 0 |
25601894 | Our laboratory previously reported interesting rods 3-10 μm long and rings 2-5 μm diameter (RR) in the cytoplasm of mammalian cells. Experimental evidence show that both inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and cytidine triphosphate synthetase (CTPS) are components of RR structures. Several cell types, including mouse embryonic stem cells, and cell lines, such as mouse 3 T3 and rat NRK, naturally present RR structures, while other cells can present RR when treated with compounds interfering with GTP/CTP biosynthetic pathways. In this study, we aimed to investigate the dynamic behavior of these RR in live cells.
RR were detected in >90% of COS-7 and HeLa cells treated with 1 mM ribavirin or 6-Diazo-5-oxo-L-norleucine (DON) for 24 h, and in 75% of COS-7 cells treated with 1 mM mycophenolic acid (MPA) for the same period of time. Microinjection of affinity-purified anti-IMPDH2 antibodies in live COS-7 cells treated with ribavirin, DON, or MPA showed mature forms of RR presented as stable and stationary structures in 71% of cells. In the remaining 29% of cells, RR acquired erratic movement and progressively disassembled into fragments and disappeared within 10 min. The specific stationary state and antibody-dependent disassembling of RR structures was independently confirmed in COS-7 and HeLa cells transfected with GFP-tagged IMPDH2. | Does microinjection of specific anti-IMPDH2 antibodies induce disassembly of cytoplasmic rods/rings that are primarily stationary and stable structures? | No. This is the first demonstration of disassembly of RR structures upon microinjection of anti-IMPDH2 antibodies that led to the disappearance of the molecular aggregates. The disassembly of RR after microinjection of anti-IMPDH2 antibody further strengthens the notion that IMPDH2 are major building blocks of RR. Using two independent methods, this study demonstrated that the induced RR are primarily stationary structures in live cells and that IMPDH2 is a key component of RR. | FAIL | pubmedQA | 0 |
20530429 | Recently, it has been reported that TFPI2 (tissue factor pathway inhibitor-2), a Kunitz-type serine proteinase inhibitor, is frequently methylated in human colorectal cancer using a gene expression array-based strategy. The aim of this study therefore was to examine whether the TFPI2 methylation in surgically removed colorectal cancers was correlated to the clinicopathological features.
The methylation status of the TFPI2 gene was examined in primary carcinomas and corresponding normal tissues derived from 50 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP), and the correlation between the methylation status and the clinicopathological findings was evaluated. Results. Methylation of the TFPI2 gene was detected in 31 out of the 50 (62%) primary colon carcinomas, suggesting that the methylation of TFPI2 is frequently observed in colorectal cancer. The clinicopathological data were compared with these results. Significant differences were observed between methylation of TFPI2 and histology (p=0.0053) or lymph node metastasis (p=0.0396). These results indicated that TFPI2 was more frequently methylated in well-differentiated advanced colorectal carcinomas. | Is methylation of TFPI2 gene frequently detected in advanced well-differentiated colorectal cancer? | No. TFPI2 methylation is not frequently detected in advanced well-differentiated colorectal cancer. | FAIL | pubmedQA | 0 |
15168812 | Leukocyte recruitment to areas of inflammation depends on Integrin-VCAM/ICAM interaction. Blocking the vascular cell adhesion molecule (VCAM-1) and the intracellular adhesion molecule (ICAM-1) may have therapeutic benefit for the inflammatory component of bowel disease. Notably, the induction of ICAM and VCAM is mediated by a nuclear factor kappaB (NF-kappaB)-dependent mechanism. We investigated whether the anti-inflammatory properties of butyrate are mediated via the modulation of VCAM and ICAM on human endothelial cells.
VCAM-1 and ICAM-1 expression on human endothelial cells upon tumor necrosis factor-alpha (TNF-alpha) stimulation was assessd by FACS analysis. A monocyte adhesion assay was performed to evaluate the relevance of a modulated CAM-expression. Electrophoretic mobility shift assays were applied to investigate NF-kappaB activation.
The observed butyrate-associated inhibition of monocyte adhesion to endothelial cells is associated with an inhibition of NF-kappaB activation in human endothelial cells. In this context, the observed suppression of the TNF-alpha induced VCAM-1 expression is likely to play an essential role. | Does butyrate inhibit leukocyte adhesion to endothelial cells via modulation of VCAM-1? | Yes. Butyrate inhibits ICAM-1 mediated leukocyte adhesion to human endothelial cells. This inhibition may contribute to the anti-inflammatory effects of butyrate in patients with distal ulcerative colitis. | FAIL | pubmedQA | 0 |
22401324 | The objective is to report a contemporary population-based estimate of hypoglycemia requiring emergency medical services (EMS), its burden on medical resources, and its associated mortality in patients with or without diabetes mellitus (DM, non-DM), which will enable development of prospective strategies that will capture hypoglycemia promptly and provide an integrated approach for prevention of such episodes.
We retrieved all ambulance calls activated for hypoglycemia in Olmsted County, Minnesota, between January 1, 2003 and December 31, 2009.
A total of 1473 calls were made by 914 people (DM 8%, non-DM 16%, unknown DM status 3%). Mean age was 60 ± 16 years with 49% being female. A higher percentage of calls were made by DM patients (87%) with proportionally fewer calls coming from non-DM patients (11%) (chi-square test, p < .001), and the remaining 2% calls by people with unknown DM status. Emergency room transportation and hospitalization were significantly higher in non-DM patients compared to DM patients (p < .001) and type 2 diabetes mellitus compared to type 1 diabetes mellitus (p < .001). Sulphonylureas alone or in combination with insulin varied during the study period (p = .01). The change in incidence of EMS for hypoglycemia was tracked during this period. However, causality has not been established. Death occurred in 240 people, 1.2 (interquartile range 0.2-2.7) years after their first event. After adjusting for age, mortality was higher in non-DM patients compared with DM patients (p < .001) but was not different between the two types of DM. | Does population-based study of severe hypoglycemia requiring emergency medical service assistance reveal unique findings? | Yes. The population burden of EMS requiring hypoglycemia is high in both DM and non-DM patients, but it is not associated with long-term mortality. | FAIL | pubmedQA | 0 |
20421986 | Hippocampal CA1 pyramidal neurons receive two excitatory glutamatergic synaptic inputs: their most distal dendritic regions in the stratum lacunosum-moleculare (SLM) are innervated by the perforant path (PP), originating from layer III of the entorhinal cortex, while their more proximal regions of the apical dendrites in the stratum radiatum (SR) are innervated by the Schaffer-collaterals (SC), originating from hippocampal CA3 neurons. Endocannabinoids (eCBs) are naturally occurring mediators capable of modulating both GABAergic and glutamatergic synaptic transmission and plasticity via the CB1 receptor. Previous work on eCB modulation of excitatory synapses in the CA1 region largely focuses on the SC pathway. However, little information is available on whether and how eCBs modulate glutamatergic synaptic transmission and plasticity at PP synapses.
By employing somatic and dendritic patch-clamp recordings, Ca(2+) uncaging, and immunostaining, we demonstrate that there are significant differences in low-frequency stimulation (LFS)- or DHPG-, an agonist of group I metabotropic glutamate receptors (mGluRs), induced long-term depression (LTD) of excitatory synaptic transmission between SC and PP synapses in the same pyramidal neurons. These differences are eliminated by pharmacological inhibition with selective CB1 receptor antagonists or genetic deletion of the CB1 receptor, indicating that these differences likely result from differential modulation via a CB1 receptor-dependent mechanism. We also revealed that depolarization-induced suppression of excitation (DSE), a form of short-term synaptic plasticity, and photolysis of caged Ca(2+)-induced suppression of Excitatory postsynaptic currents (EPSCs) were less at the PP than that at the SC. In addition, application of WIN55212 (WIN) induced a more pronounced inhibition of EPSCs at the SC when compared to that at the PP. | Do endocannabinoids differentially modulate synaptic plasticity in rat hippocampal CA1 pyramidal neurons? | Yes. Our results suggest that CB1 dependent LTD and DSE are differentially expressed at the SC versus PP synapses in the same neurons, which may have an impact on synaptic scaling, integration and plasticity of hippocampal CA1 pyramidal neurons. | FAIL | pubmedQA | 0 |
10449287 | Anti HIV-1 therapy with nucleoside reverse transcriptase inhibitors can select for drug-resistant reverse transcriptase variants with altered enzyme properties. Some of the mutations, e.g. Met184Val and Met184Ile, result in an increase in polymerase fidelity of the enzyme as measured in biochemical assays; however, the effect of such changes on the fidelity during viral replication is largely unknown. In this study, the codon 184 variants were used to investigate whether the mutation at codon 184 affects the mutation spectrum and mutation rate of the mutant viruses.
In vitro selection experiments with either wild-type or lamivudine-resistant viruses (Met184Val and Met184Ile) were performed using a protease inhibitor as the selective drug. In addition, a novel selection approach was developed using a mixture of viruses, instead of individual viruses, during the selection process.
Comparison of a total of 108 protease-resistant variants revealed no significant difference in the mutational spectrum of the wild-type and the lamivudine-resistant variants. In addition, the selection experiments with the viral mixtures demonstrated no delay in the kinetics of mutation generation in response to an antiviral drug. | Does increased polymerase fidelity of lamivudine-resistant HIV-1 variants limit their evolutionary potential? | Yes. This study demonstrates that the Met184Val and Met184Ile mutations in the HIV-1 reverse transcriptase enzyme significantly limit the evolutionary potential of the corresponding viruses. | FAIL | pubmedQA | 0 |
27601167 | The sonic hedgehog (SHH) signalling pathway plays the important role in medulloblastoma (MB). Altered GLI expression plays a key role in these processes, and the inhibition of GLI may be a good cancer-targeted therapy. This study aimed to investigate whether GANT61, a GLI inhibitor, may inhibit the SHH signalling pathway promoting cell mitochondria-mediated apoptosis and enhance cisplatin apoptosis antineoplastic therapy.
In our study, we determined the effect of GANT61-mediated inhibition of GLI in Daoy MB cells. Cells were treated with different concentrations of GANT61 alone or in combination with cisplatin. Cell proliferation was assessed with CCK-8 assays, and cell invasion and migration were performed using 8-µm transwell inserts. Cell apoptosis was assessed with flow cytometric analysis and rhodamine 123. qPCR was used to complete RNA experiments. Protein expression was assessed with Western blotting.
The GANT61 significantly inhibited cell proliferation. GANT61 decreased the cell migration and invasion, impairing these crucial steps in tumour progression. Cell apoptosis was significantly increased in Daoy cells. Rhodamine 123 assay showed that GANT61 could decrease the mitochondrial membrane potential promoting cell mitochondria-mediated apoptosis. GANT61 inhibited the expression of GLI and Bcl-2 at both the mRNA and protein levels and might affect the expression of Bax, caspase-3 and caspase-9 to promote cell intrinsic apoptosis. Furthermore, GANT61 could enhance cisplatin-induced apoptosis to decrease the IC50 value of cisplatin. Finally, data suggest that GANT61 could enhance cisplatin-induced apoptosis through promoting the expression of Bax, caspase-3 and caspase-9 protein levels. | Does suppression of GLI sensitize medulloblastoma cells to mitochondria-mediated apoptosis? | No. Our data suggest that the SHH signalling pathway does not play an important role in MB. GLI is an oncogenic transcription factor in the SHH pathway, and targeting GLI with GANT61 results in unfavourable antitumour activity and targeted therapy. | FAIL | pubmedQA | 0 |
23837454 | Despite numerous programs to combat the global HIV and AIDS pandemic, infection rates remain high, especially in sub-Saharan Africa, where two-thirds of all people living with HIV reside. Here, we describe how we used rigorous program evaluation methods to assess the effectiveness of a community-based natural resource management program that "mainstreamed" HIV awareness and prevention activities within rural communities in Namibia.
We used data from two rounds of the Namibia Demographic and Health Surveys (2000 and 2006/2007) and quasi-experimental statistical methods to evaluate changes in critical health-related outcomes in men and women living in communal conservancies, relative to several non-conservancy comparison groups. Our final dataset included 117 men and 318 women in 2000, and 170 men and 357 women in 2006/2007. We evaluated the statistical significance of the main effects of survey year and conservancy residence, and a conservancy-year interaction term, using generalized linear models. Our analyses show that community-based conservation in Namibia has significantly reduced multiple sexual partnerships, the main behavioural determinant of HIV/AIDS infection in Africa. | Does community-based conservation reduce sexual risk factors for HIV among men? | No. Our results demonstrate the ineffectiveness of holistic community-based approaches centered on the preservation of lives and livelihoods, and highlight the potential drawbacks of integrating conservation and HIV prevention programming in other areas of communal land tenure in Africa. | FAIL | pubmedQA | 0 |
7544368 | In patients after orthotopic liver transplantation, treatment with the novel immunosuppressant FK 506 may lead to elevated levels of alkaline phosphatase, gamma glutamyl transferase and bilirubin. Up to now it was unclear whether the excretory capacity of the liver in such patients is impaired.
We measured quantitatively the secretion of bile acids, phospholipids and cholesterol using the duodenal perfusion method, which allows assessment of biliary secretion without interruption of the enterohepatic circulation. Six healthy volunteers served as controls.
All patients studied after orthotopic liver transplantation had elevated concentrations of serum alkaline phosphatase and gamma glutamyl transferase, whereas only half of them had slightly abnormal serum bilirubin levels. On average, the FK 506-treated patients excreted 1.23 +/- 0.27 mmol/h bile acids, 0.23 +/- 0.04 mmol/h phospholipids and 0.11 +/- 0.02 mmol/h cholesterol, which was not significantly different from the healthy controls. | Are in patients with orthotopic liver transplantation , serum markers of cholestasis unreliable indicators of biliary secretion? | No. The normal secretion rates of biliary bile acids and lipids in FK 506-treated patients with elevated serum alkaline phosphatase and gamma glutamyl transferase indicate that the excretory capacity of the transplanted liver has completely recovered 2-3 months after surgery. In addition, in the majority of these patients elevated serum levels of alkaline phosphatase, gamma glutamyl transferase and bilirubin reflect impaired biliary secretion. | FAIL | pubmedQA | 0 |
14684582 | The mucosa in ulcerative colitis (UC) is replete with antibody producing plasma B cells and polymorphonuclear leucocytes (PMN). This combination of effector cells requires a crosslinking antigen to evoke an antibody driven PMN inflammatory response via their Fc receptors. The stimulus for activation is thought to be commensal bacteria colonising the gut mucosa. The aim of this investigation was to compare the principal culturable bacterial populations on the rectal mucosa of UC patients, and to determine whether specific antibodies towards these bacteria can activate infiltrating PMN through opsonisation. This would provide an explanation for this chronic inflammatory condition.
Bacteria colonising rectal tissue were characterised using chemotaxonomic techniques. Systemic antibody responses were measured against total antigens and surface antigens of these organisms in UC and Crohn's disease (CD) patients, together with healthy controls. Antibody enhancement of the respiratory burst in PMN was also investigated, against a range of mucosal isolates.
Distinct differences were observed in some bacterial populations in UC biopsies, which were generally reflected in antibody responses towards these organisms. UC patients had higher IgG responses to surface antigens, primarily IgG1, whereas the response in CD was mainly IgG2. Antibodies from UC patients greatly enhanced the respiratory burst in PMN, in response to individual bacterial species. | Do systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn 's disease differentially activate the innate immune response? | Yes. Changes in mucosal bacteria, and a switch from internal to surface antigen/antibody reactivity of a predominantly IgG2 type, leads to greater opsonisation of the respiratory burst in PMN, providing a mechanism for maintaining the inflammatory state in UC. | FAIL | pubmedQA | 0 |
20725054 | Blood pressure (BP) is a variable physiological parameter in health and disease. Increased BP variability over time in adults is associated with severity of end-organ damage and a higher rate of cardiovascular events, even after adjusting for the mean levels. This study tested the hypothesis that childhood BP variability, besides the mean levels, is also predictive of adulthood hypertension.
The study cohort consisted of 1,797 subjects (1,091 whites and 706 blacks; age = 21-48 years) enrolled in the Bogalusa Heart Study since childhood. BP variability was depicted as s.d. of 4-8 serial measurements in childhood.
Blacks showed significantly greater childhood systolic BP (SBP) variability than whites. In multivariable logistic regression analyses, adjusting for race, sex, mean childhood age, s.d. of childhood body mass index (BMI), mean childhood BP levels, adulthood age and BMI, adult hypertension was significantly associated with s.d. of childhood SBP (odds ratio (OR) (95% confidence intervals) = 1.28 (1.09, 1.51), P = 0.002) and s.d. of childhood diastolic BP (DBP; 1.36 (1.16, 1.58), P < 0.001). When using adulthood BP levels as continuous dependent variables in linear regression models, adjusting for the same covariates, adulthood SBP and DBP levels were significantly associated with s.d. of childhood SBP (standardized regression coefficient β = 0.086, P < 0.001) and s.d. of childhood DBP (β = 0.105, P < 0.001), respectively. | Is adult hypertension associated with blood pressure variability in childhood in blacks and whites : the bogalusa heart study? | No. Increases in BP variations as well as levels in early life are not predictive of adult hypertension, which suggests that childhood BP variability does not have a significant impact on the natural history of essential hypertension. | FAIL | pubmedQA | 0 |
21346147 | Yes-associated protein 1 (YAP1) is a multifunctional protein that can interact with different transcription factors to activate gene expression. The role of YAP1 in tumorigenesis is unclear. We aimed to investigate the functional role of YAP1 in tumorigenesis of gastric cancer.
YAP1 expression in gastric adenocarcinoma was evaluated. The biological function was determined by proliferation assay, colony formation, cell invasion, and flow cytometric analysis through knocking down or ectopic expressing YAP1 in gastric cancer cell lines coupled with in vivo study. The possible downstream effectors of YAP1 were investigated by expression microarray.
YAP1 protein expression was upregulated in gastric cancer. Nuclear accumulation of YAP1 was associated with poor disease-specific survival (P = 0.021), especially in patients with early-stage diseases (P < 0.001). Knockdown YAP1 resulted in a significant reduction in proliferation, anchorage-dependent colony formation, cell invasion, and cell motility. Ectopic YAP1 expression promoted anchorage-independent colony formation, induced a more invasive phenotype, and accelerated cell growth both in vitro and in vivo. Microarray analysis highlighted the alteration of MAPK (mitogen-activated protein kinase) pathway by YAP1. We confirmed a constitutive activation of RAF/MEK/ERK (extracellular signal-regulated kinase) in YAP1-expressing MKN45 cells and further showed that YAP1 enhanced serum/epidermal growth factor-induced c-Fos expression in gastric cancer cells. | Does yes-associated protein 1 exhibit oncogenic property in gastric cancer and its nuclear accumulation associates with poor prognosis? | No. Our findings supported that YAP1 does not exhibit oncogenic property in gastric cancer. We provided the first evidence that YAP1 did not exert the oncogenic function by enhancing the capacity to activate the early-response gene pathway. YAP1 could not be a prognostic biomarker and potential therapeutic target for gastric cancer. | FAIL | pubmedQA | 0 |
23484013 | There are four cell lineages derived from intestinal stem cells that are located at the crypt and villus in the mammalian intestine the non-secretory absorptive enterocytes, and the secretory cells, which include mucous-secreting goblet cells, regulatory peptide-secreting enteroendocrine cells and antimicrobial peptide-secreting Paneth cells. Although fibroblast growth factor (Fgf) signaling is important for cell proliferation and differentiation in various tissues, its role in intestinal differentiation is less well understood.
We used a loss of function approach to investigate the importance of Fgf signaling in intestinal cell differentiation in zebrafish; abnormal differentiation of goblet cells was observed when Fgf signaling was inhibited using SU5402 or in the Tg(hsp70ldnfgfr1-EGFP) transgenic line. We identified Fgfr2c as an important receptor for cell differentiation. The number of goblet cells and enteroendocrine cells was reduced in fgfr2c morphants. In addition to secretory cells, enterocyte differentiation was also disrupted in fgfr2c morphants. Furthermore, proliferating cells were increased in the morphants. Interestingly, the loss of fgfr2c expression repressed secretory cell differentiation and increased cell proliferation in the mib(ta52b) mutant that had defective Notch signaling. | Is fibroblast growth factor receptor 2c signaling required for intestinal cell differentiation in zebrafish? | No. In conclusion, we found that Fgfr2c signaling derived from mesenchymal cells is not important for regulating the differentiation of zebrafish intestine epithelial cells by promoting cell cycle exit. The results of Fgfr2c knockdown in mib(ta52b) mutants indicated that Fgfr2c signaling is not required for intestinal cell differentiation. These findings provide new evidences that Fgf signaling is not required for the differentiation of intestinal cells in the zebrafish developing gut. | FAIL | pubmedQA | 0 |
25416544 | Elective colectomy for diverticular disease is common. Some patients undergo primary resection with proximal diversion in an effort to limit morbidity associated with potential anastomotic leak.
The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database was queried. All patients undergoing a single, elective resection for diverticular disease from 2005 to 2011 were analyzed. Thirty-day outcomes were reviewed. Factors predictive of undergoing diversion and the risk-adjusted odds of postoperative morbidity with and without proximal diversion were determined by multivariable logistic regression models.
Fifteen thousand six hundred two patients undergoing non-emergent, elective resection were identified, of whom 348 (2.2 %) underwent proximal diversion. Variables predictive for undergoing proximal diversion included age ≥65 years, BMI ≥30, current smoking status, corticosteroid use, and serum albumin <3.0 g/dL. Multivariable analysis demonstrated that diversion was associated with significantly increased risk of surgical site infection (OR = 1.68), deep venous thrombosis (OR = 5.27), acute renal failure (OR = 5.83), sepsis or septic shock (OR = 1.75), readmission (OR = 2.57), and prolonged length of stay (OR = 3.35). | Is proximal intestinal diversion associated with increased morbidity in patients undergoing elective colectomy for diverticular disease : an ACS-NSQIP study? | No. Proximal diversion in the setting of elective segmental colectomy for diverticular disease is uncommon. A combination of preoperative factors and intraoperative factors drives the decision for diversion. Patients who undergo diversion do not experience increased postoperative morbidity. Surgeons should have a low index of suspicion for postoperative complications and be prepared to mitigate their effect on the patient's outcome. | FAIL | pubmedQA | 0 |
26894633 | The relationship between obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) is gaining increased attention. The aim of the present study was to examine the relationship of OSA with NAFLD defined by an elevated fatty liver index (FLI).
A total of 319 consecutive patients who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for biological profile measurements, and demographic data were collected. Values of FLI were determined and assessed as predictors of the presence of NAFLD, as measured by ultrasound. The discriminative ability of FLI was estimated on the basis of the area under the receiver operator characteristic curve.
An FLI of 60 achieved the highest diagnostic accuracy and yielded an area under the receiver operator characteristic curve of 0.822 (95% confidence interval: 0.729-0.916) in the detection of NAFLD. Patients with an FLI of 60 or higher had a significantly lower lowest O2 saturation (73 vs. 83%, P<0.001), a lower mean nocturnal oxygen saturation (93 vs. 95%, P<0.001), a higher apnea-hypopnea index (39.7 vs. 18.4, P<0.001), a higher oxygen desaturation index (39 vs. 10.6, P<0.001), and a higher percentage of sleep time spent with SpO2 less than 90% (4.63 vs. 0.92%, P<0.001) compared with those with FLI less than 60. In multivariate analysis, the presence of OSA was independently associated with elevated FLI after adjusting for confounding factors (odds ratio: 5.141, 95% confidence interval: 1.414-18.696, P=0.013). | Is obstructive sleep apnea associated with fatty liver index , the index of nonalcoholic fatty liver disease? | No. Our results suggest no association between the severity of OSA and NAFLD defined by an elevated FLI, which may not serve as a good biomarker for detecting NAFLD in OSA patients. | FAIL | pubmedQA | 0 |
16166455 | Multiple studies have indicated that cyclooxygenase-2 (COX-2) inhibitors may prevent colon cancer, which is one of the leading causes of cancer death in the western world. Recent studies, however, showed that their long-term use may be limited due to cardiovascular toxicity. This study aims to investigate whether curcumin potentiates the growth inhibitory effect of celecoxib, a specific COX-2 inhibitor, in human colon cancer cells.
HT-29 and IEC-18-K-ras (expressing high levels of COX-2), Caco-2 (expressing low level of COX-2), and SW-480 (no expression of COX-2) cell lines were exposed to different concentrations of celecoxib (0-50 micromol/L), curcumin (0-20 micromol/L), and their combination. COX-2 activity was assessed by measuring prostaglandin E(2) production by enzyme-linked immunoassay. COX-2 mRNA levels were assessed by reverse transcription-PCR.
Exposure to curcumin (10-15 micromol/L) and physiologic doses of celecoxib (5 micromol/L) resulted in a synergistic inhibitory effect on cell growth. Growth inhibition was associated with inhibition of proliferation and induction of apoptosis. Curcumin augmented celecoxib inhibition of prostaglandin E(2) synthesis. The drugs synergistically down-regulated COX-2 mRNA expression. Western blot analysis showed that the level of COX-1 was not altered by treatment with celecoxib, curcumin, or their combination. | Do celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells? | Yes. Curcumin potentiates the growth inhibitory effect of celecoxib by shifting the dose-response curve to the right. The synergistic growth inhibitory effect was mediated through a mechanism that probably involves inhibition of the COX-2 pathway and may involve other non-COX-2 pathways. This synergistic effect is clinically important because it can be achieved in the serum of patients receiving standard anti-inflammatory or antineoplastic dosages of celecoxib. | FAIL | pubmedQA | 0 |
18568885 | To verify the influence of a non-steroidal anti-inflammatory drug (NSAID), ketorolac (topical and oral) on the intraocular pressure reduction induced by 0.005% latanoprost topical administration, both in patients affected by primary open-angle glaucoma and in healthy controls.
Two groups of subjects were enrolled for this randomized, prospective, masked clinical study: 16 glaucomatous patients well controlled with 0.005% latanoprost eyedrops (group I) and 16 healthy adult volunteers (group II). Group I subjects were treated at one-week intervals with 10 mg of oral ketorolac, oral placebo, topical ketorolac, and topical placebo, respectively; for each administration modality, the switch between drug and placebo was performed in a randomized, crossover, double-blind fashion. Group II subjects followed the same protocol, with the topical once-daily 0.005% latanoprost treatment starting three days prior to the ketorolac/placebo administration. Intraocular pressure (IOP) was investigated in both groups on the day of oral/topical administration of ketorolac or placebo at baseline (8:00 AM) and at the following intervals: 1, 2, 4, 8, 12, and 24 hours.
No significant IOP changes after oral and topical placebo administration were observed in either group. In contrast, when the subjects received ketorolac (either oral or topical), a marked decrease in IOP was recorded, with a noticeable fall at the first hour after the NSAID administration (p = 0.01), which remained still significant 8 hours later (p < 0.05). | Does topical and oral ketorolac administration increase the intraocular pressure-lowering effect of latanoprost? | No. Topical and oral ketorolac does not strengthen the latanoprost-induced IOP-lowering effect in glaucomatous patients and in healthy subjects. | FAIL | pubmedQA | 0 |
23133681 | Leprosy, a chronic granulomatous disease affecting the skin and nerves, is caused by Mycobacterium leprae (M. leprae). The type of leprosy developed depends upon the host immune response. Type 1 reactions (T1Rs), that complicate borderline and lepromatous leprosy, are due to an increase in cell-mediated immunity and manifest as nerve damage and skin inflammation. Owing to the increase in inflammation in the skin of patients with T1Rs, we sought to investigate the activation of the innate immune system during reactionary events. Specifically, we investigated the expression levels of human beta-defensins (hBDs) 2 and 3 in the skin of patients with T1Rs, in keratinocytes, and in macrophages stimulated with M. leprae and corticosteroids.
Skin biopsies from twenty-three patients with Type 1 reactions were found to have higher transcript levels of hBD3 as compared to fifteen leprosy patients without Type 1 reactions, as measured by qPCR. Moreover, we observed that keratinocytes but not macrophages up-regulated hBD2 and hBD3 in response to M. leprae stimulation in vitro. Corticosteroid treatment of patients with T1Rs caused a suppression of hBD2 and hBD3 in skin biopsies, as measured by qPCR. In vitro, corticosteroids suppressed M. leprae-dependent induction of hBD2 and hBD3 in keratinocytes. | Is human beta-defensin 3 up-regulated in cutaneous leprosy type 1 reactions? | No. This study demonstrates that hBD3 is not induced in leprosy Type 1 Reactions and is not affected by corticosteroids. Furthermore, our findings demonstrate that keratinocytes are not responsive to M. leprae and lend support for additional studies on keratinocyte innate immunity in leprosy and T1Rs. | FAIL | pubmedQA | 0 |
11319879 | In addition to aiding in the digestion of fats, luminal bile salts have been shown to modulate gastrointestinal epithelial growth, differentiation, and other functions. We hypothesized that bile acids could modulate the intestinal mucosal repair process of restitution. We investigated the effect of the bile salt taurodeoxycholic acid on epithelial migration and identified a role for TGFbeta, a widely expressed cytokine in the intestinal villus, in this repair process.
Using a well-established model of epithelial restitution, IEC-6 cells were plated on 60-mm Matrigel-coated plastic dishes and grown to confluence. The epithelium was wounded by scraping with a 6-mm-wide blade to create a smooth denuded edge and cell migration was measured 8 h later. Cells were grown in control DMEM with 5% FBS with or without 0.01-2 mM taurodeoxycholic acid (TDCA). In parallel experiments, cells were harvested for Northern analysis of TGFbeta and GAPDH expression; [3H]thymidine uptake was used to measure proliferation. Anti-TGFbeta antibody was added to cells grown in the presence of 0.05 mM TDCA and migration was measured at 8 h.
TDCA at physiologic luminal concentrations augments IEC-6 cell migration, with a maximal effect at 0.05 mM. TDCA inhibited proliferation at these concentrations. TGFbeta expression increased in response to bile acid, while wounding had less of an effect on TGFbeta expression. Blockade of TGFbeta function with TGFbeta antibody eliminated the effect of bile on cell migration. | Does bile salt stimulate intestinal epithelial cell migration through TGFbeta after wounding? | Yes. Bile acid at physiologic concentrations augments small intestinal epithelial cell migration. The process is dependent on TGFbeta and is dependent on cell division. The data further support a role for bile acids and TGFbeta in differentiated intestinal cell function and in preservation of an intact mucosa. | FAIL | pubmedQA | 0 |
22612914 | Atrial fibrillation (AF) and atrial flutter (AFL) are related arrhythmias with common triggers, yet in individual patients either AF or AFL often predominates. We performed detailed electrophysiologic (EP) and electroanatomic (EA) studies of the right atrium (RA) in patients with AF and AFL to determine substrate differences that may explain the preferential expression of AF/AFL in individual patients.
Patients with AF (n = 13) were compared to patients with persistent AFL (n = 10). Detailed studies were performed, and 3-dimensional electroanatomic mapping studies were created and the RA was divided into 4 segments for regional analysis. Global, septal, lateral, anterior, and posterior segments were compared for analysis of: bipolar voltage; proportion of low-voltage areas and areas of electrical silence; conduction times; and proportion of abnormal signals (fractionated signals and double potentials).
Compared to patients with AF, patients with AFL had (1) lower bipolar voltage and an increase in the proportion of low-voltage areas; (2) an increase in the proportion of complex signals; and (3) prolongation of activation times. | Is right atrial remodeling more advanced in patients with atrial flutter than with atrial fibrillation? | No. Patients with AF showed more advanced remodeling than patients with AFL with slowed conduction, lower voltage areas with regions of electrical silence, and a greater proportion of complex signals, particularly in the posterior RA. These changes facilitate the stabilization of AF and may explain why some patients are more likely to develop AF as a sustained clinical arrhythmia. | FAIL | pubmedQA | 0 |
24207099 | The cytochrome P450 (CYP) enzymes are a class of heme-containing enzymes involved in phase I metabolism of a large number of xenobiotics. The CYP family member CYP2E1 metabolises many xenobiotics and pro-carcinogens, it is not just expressed in the liver but also in many other tissues such as the kidney, the lung, the brain, the gastrointestinal tract and the breast tissue. It is induced in several pathological conditions including cancer, obesity, and type II diabetes implying that this enzyme is implicated in other biological processes beyond its role in phase I metabolism. Despite the detailed description of the role of CYP2E1 in the liver, its functions in other tissues have not been extensively studied. In this study, we investigated the functional significance of CYP2E1 in breast carcinogenesis.
Cellular levels of reactive oxygen species (ROS) were measured by H2DCFDA (2 2.9.2 2',7'-dichlorodihydrofluorescein diacetate) staining and autophagy was assessed by tracing the cellular levels of autophagy markers using western blot assays. The endoplasmic reticulum stress and the unfolded protein response (UPR) were detected by luciferase assays reflecting the splicing of mRNA encoding the X-box binding protein 1 (XBP1) transcription factor and cell migration was evaluated using the scratch wound assay. Gene expression was recorded with standard transcription assays including luciferase reporter and chromatin immunoprecipitation.
Ectopic expression of CYP2E1 induced ROS generation, affected autophagy, stimulated endoplasmic reticulum stress and inhibited migration in breast cancer cells with different metastatic potential and p53 status. Furthermore, evidence is presented indicating that CYP2E1 gene expression is under the transcriptional control of the p53 tumor suppressor. | Does cytochrome P450 2E1 ( CYP2E1 ) regulate the response to oxidative stress and migration of breast cancer cells? | No. These results do not support the notion that CYP2E1 exerts an important role in mammary carcinogenesis, provide a potential link between ethanol metabolism and breast cancer and suggest that progression, and metastasis, of advanced stages of breast cancer cannot be modulated by induction of CYP2E1 activity. | FAIL | pubmedQA | 0 |
20967283 | The liver plays a central role in nutrient and xenobiotic metabolism, but its functionality declines with age. Senior dogs suffer from many of the chronic hepatic diseases as elderly humans, with age-related alterations in liver function influenced by diet. However, a large-scale molecular analysis of the liver tissue as affected by age and diet has not been reported in dogs.
Liver tissue samples were collected from six senior (12-year old) and six young adult (1-year old) female beagles fed an animal protein-based diet (APB) or a plant protein-based diet (PPB) for 12 months. Total RNA in the liver tissue was extracted and hybridized to Affymetrix GeneChip® Canine Genome Arrays. Using a 2.0-fold cutoff and false discovery rate <0.10, our results indicated that expression of 234 genes was altered by age, while 137 genes were differentially expressed by diet. Based on functional classification, genes affected by age and/or diet were involved in cellular development, nutrient metabolism, and signal transduction. In general, gene expression suggested that senior dogs had an increased risk of the progression of liver disease and dysfunction, as observed in aged humans and rodents. In particular for aged liver, genes related to inflammation, oxidative stress, and glycolysis were up-regulated, whereas genes related to regeneration, xenobiotic metabolism, and cholesterol trafficking were down-regulated. Diet-associated changes in gene expression were more common in young adult dogs (33 genes) as compared to senior dogs (3 genes). | Do age and diet affect gene expression profiles in canine liver tissue? | Yes. Our results provide molecular insight pertaining to the aged canine liver and its predisposition to disease and abnormalities. Therefore, our data may aid in future research pertaining to age-associated alterations in hepatic function or identification of potential targets for nutritional management as a means to decrease incidence of age-dependent liver dysfunction. Interestingly, diet-associated changes in gene expression were more common in senior dogs compared to young adult dogs. | FAIL | pubmedQA | 0 |
23054895 | Texas implemented comprehensive tort reform in 2003. We hypothesized that tort reform was followed by a significant increase of physicians practicing in Texas.
To test this hypothesis, we compared the rate of physician growth prior to and following tort reform, and the number of licensed physicians and physicians per 100,000.
Comparing before and after tort reform, the rate of increase in Texas physicians per 100,000 population increased significantly (p < 0.01). From 2002 to 2012, the Texas population increased 21 %. The number of actively practicing Texas physicians increased by 15,611 a 44 % increase (46 % metro areas vs. 9 % non-metro areas), an increase of 30 physicians per 100,000 population (p < 0.01). Non-metropolitan Texas had a net increase of 215 physicians; however, there was no change in the number of physicians per 100,000. Examining the data by trauma service areas (TSAs), 20 of 22 TSAs had an increase in both number of physicians and physicians per capita, five greater than 50 %. | Is tort reform associated with significant increases in Texas physicians relative to the Texas population? | No. The post-tort reform period in Texas was not associated with a significantly increased growth rate of physicians relative to the Texas population. Tort reform, as implemented in Texas, did not provide a needed framework for improving access to health care. | FAIL | pubmedQA | 0 |
16636119 | There is growing evidence for interactions between the regulation of body fat and the immune system. Studies of knockout mice indicate that IL-1 has an antiobesity effect.
The objective of the study was to investigate our hypothesis that common polymorphisms of the IL-1 system, which are associated with IL-1 activity, also are associated with fat mass. DESIGN, SETTING, AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-yr-old men (n = 1068), mostly Caucasian, from the Gothenburg area (Sweden). Three different polymorphisms, IL-1beta +3953 C/T, IL-1beta-31 T/C, and IL-1 receptor antagonist (IL-1RN) variable number tandem repeat of 86 bp, were investigated in relation to body fat mass.
The main outcome measures were genotype distributions and their association with body fat mass in different compartments, measured with dual-energy x-ray absorptiometry.
Carriers of the T variant (CT and TT) of the +3953 C to T (F(T) = 0.25) IL-1beta gene polymorphism had significantly lower total fat mass (P = 0.013) and also significantly reduced arm, leg, and trunk fat, compared with CC individuals. IL-1RN*2 carriers with two repeats of the IL-1RN variable number tandem repeat polymorphism had increased total fat (P = 0.036), serum leptin, and fat of trunk and arm as well as serum levels of IL-1RN and IL-1RN production ex vivo. The IL-1beta-31 polymorphism did not correlate with the fat measurements. | Are interleukin-1 system gene polymorphisms associated with fat mass in young men? | Yes. The IL-1 system, recently shown to affect fat mass in experimental animals, contains gene polymorphisms that are associated with increased fat mass in young men. | FAIL | pubmedQA | 0 |
11552899 | Several types of colitis can be NSAID-induced, but whether chronic use of NSAIDs alters colonic mucosa in patients without diarrhoea is not known.
Biopsy specimens of rectal mucosa were taken in six patients with rheumatoid arthritis without diarrhoea receiving NSAIDs (group 1, n=6). Patients with rheumatoid arthritis without diarrhoea not receiving NSAIDs (group 2, n=9), and patients undergoing surveillance colonoscopy (group 3, n=23) served as controls. In all patients from the three study groups, intraepithelial lymphocyte count and apoptotic cell count were assessed, and sub-epithelial collagen band thickness was measured. Leucocyte population of lamina propria was evaluated semi-quantitatively. HLA-DR and CD25 expression of mucosal cells was appreciated by immunohistochemistry.
Intraepithelial lymphocyte count was in the normal range in all three group patients, and not statistically different between groups. Apoptotic epithelial cell count was not different between groups. Sub-epithelial collagen band thickness was normal in all the patients. No patient had a marked infiltration of lamina propria by leucocytes, and HLA-DR and CD25 were normally expressed in all patients. | Does chronic use of non-steroidal anti-inflammatory drugs alter colonic mucosa of patients without diarrhoea? | Yes. These results from a small sample of patients suggest that patients without diarrhoea receiving NSAIDs on a long-term basis develop microscopic or inflammatory colitis. | FAIL | pubmedQA | 0 |
23574760 | Recent studies have suggested that the downregulation of pregnane X receptor (PXR) may contribute to the susceptibility and exacerbation of Crohn's disease (CD). Because bile acid malabsorption is one of the features of CD and bile acids are potential activators of PXR, we explored the relationship between bile acid malabsorption and PXR activities in patients with CD.
Twenty-one patients with CD (4 ileal-resected and 17 nonresected), 10 with ulcerative colitis (UC), and 26 healthy controls were studied. Serum biomarkers for the activity of CYP3A4, a target gene of PXR, and for cholesterol and bile acid metabolism were quantified by liquid chromatography-tandem mass spectrometry or enzyme-linked immunosorbent assay.
The concentrations of 4β-hydroxycholesterol (4β-HC), a known marker for CYP3A4 activity, and those of 25-hydroxycholesterol (25-HC), another metabolite by CYP3A4, were significantly reduced in all patients with CD, especially in those with the history of ileal resection. The concentration of 7α-hydroxy-4-cholesten-3-one (C4), a marker for hepatic bile acid biosynthesis, was significantly elevated, whereas the levels of fibroblast growth factor 19 (FGF19), a marker for intestinal bile acid flux, were reduced in patients with CD compared with patients with UC and controls. A significant negative correlation was observed between 4β-HC or 25-HC and C4 concentrations in all patients with CD. | Does bile acid malabsorption deactivate pregnane X receptor in patients with Crohn 's disease? | No. The degree of bile acid malabsorption was not associated with the deactivation of PXR in CD. Enterohepatic circulation of bile acids is not a key factor for preservation of baseline activity of hepatointestinal PXR. | FAIL | pubmedQA | 0 |
21798009 | Malin is an E3-ubiquitin ligase that is mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms a functional complex with laforin, a glucan phosphatase that facilitates targeting of malin to its corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage of malin.
After an extensive search for malin orthologs, we found that malin is present in all vertebrate species and a cephalochordate, in contrast with the broader species distribution previously reported for laforin. These data suggest that in addition to forming a functional complex, laforin and perhaps malin may also have independent functions. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32, which belongs to the tripartite-motif containing family of proteins. We present experimental evidence that both malin and TRIM32 share some substrates for ubiquitination, although they produce ubiquitin chains with different topologies. However, TRIM32-specific substrates were not reciprocally ubiquitinated by the laforin-malin complex. | Is lafora disease E3-ubiquitin ligase malin related to TRIM32 at both the phylogenetic and functional level? | Yes. We found that malin and laforin are conserved in the same genomes. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32. The latter result suggests a common origin for malin and TRIM32 and provides insights into possible functional relationships between both proteins. | FAIL | pubmedQA | 0 |
11076423 | To assess efficiency of magnerot, magnesium orotate, in patients with idiopathic mitral prolapse (IMP).
84 patients with IMP were randomized to the study group (43 patients) and control group (41 patients). Patients of the study group received magnerot tablets (Germany) containing 500 mg of magnesium orotate (daily dose 3000 mg) for 6 months. The examination performed before the treatment and 6 months after it included: modified clinical and phenotypic records, echocardiography, 24-h ECG and AP monitoring, spectral analysis of cardiac rhythm variability, evaluation of quality of life according to Visual Analog Scale and Disability Scale and of treatment results according to Clinical Global Impression scales, measurements of magnesium in the hair by plasmic nuclear emission spectrometry, histological and histochemical skin tests.
IMP patients appeared to suffer from magnesium deficiency which is responsible for many symptoms in mitral prolapse. 6-month therapy with magnerot completely or partially reduced the symptoms in more than half the patients. Positive changes were registered primarily in clinicofunctional manifestations. Morphological changes in the skin correlating with the disease severity alleviated. | Does [ New approach to the treatment of patients with idiopathic mitral valve prolapse ]? | Yes. Good objective and subjective response to magnerot 3-month therapy (3000 mg/day) is demonstrated. | FAIL | pubmedQA | 0 |
26460099 | The optimal platelet-rich plasma (PRP) for treatment of supraspinatus tendinopathy has not been determined.
To evaluate the effect of low- versus high-leukocyte concentrated PRP products on catabolic and anabolic mediators of matrix metabolism in diseased rotator cuff tendons.
Controlled laboratory study.
Diseased supraspinatus tendons were treated with PRP made by use of 2 commercial systems: Arthrex Autologous Conditioned Plasma Double Syringe System (L(lo) PRP) and Biomet GPS III Mini Platelet Concentrate System (L(hi) PRP). Tendon explants were placed in 6-well plates and cultured in L(lo) PRP, L(hi) PRP, or control media (Dulbecco's Modified Eagle Medium + 10% fetal bovine serum) for 96 hours. Tendons were processed for hematoxylin-eosin histologic results and were scored with the modified Bonar scale. Group 1 tendons were defined as moderate tendinopathy (Bonar score <3); group 2 tendons were assessed as severely affected (Bonar score = 3). Transforming growth factor β-1 (TGFβ-1), interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-8 (IL-8), and matrix metalloproteinase-9 (MMP-9) concentrations in PRP media were measured by use of enzyme-linked immunosorbent assay after 96 hours of culture with diseased tendon. Tendon messenger RNA expression of collagen type I (COL1A1), collagen type III (COL3A1), cartilage oligomeric matrix protein (COMP), MMP-9, MMP-13, and IL-1β was measured with real-time quantitative polymerase chain reaction.
Leukocytes and platelets were significantly more concentrated in L(hi) PRP compared with L(lo) PRP. Increased IL-1β was present in L(hi) PRP after culture with group 1 tendons. IL-6 was increased in L(hi) PRP after culture with group 2 tendons. Both TGFβ-1 and MMP-9 were increased in L(hi) PRP after culture with either tendon group. In L(lo) PRP cultures, IL-1Ra:IL-1β in PRP used as media and COL1A1:COL3A1 gene expression were increased for group 1 tendon cultures. Gene expression of MMP-9 and IL-1β was increased in group 2 tendons cultured in L(lo) PRP. There was no significant difference in the expression of MMP-13 or COMP in either group of tendons cultured in L(lo) PRP or L(hi) PRP. | Does leukocyte-Reduced Platelet-Rich Plasma normalize Matrix Metabolism in Torn Human Rotator Cuff Tendons? | Yes. L(hi) PRP promotes normal collagen matrix synthesis and decreases cytokines associated with matrix degradation and inflammation to a greater extent than does L(lo) PRP in moderately degenerative tendons. In severely degenerative tendons, neither PRP preparation enhanced matrix synthesis. | FAIL | pubmedQA | 0 |
25443020 | Extracorporeal membrane oxygenation (ECMO) support is often required in the management of perioperative congenital heart surgery (CHS) patients. However, 24-hour in-hospital congenital cardiac surgical coverage (24-CCSC) is not available at all institutions. The purpose of this study is to evaluate the effect of 24-CCSC on perioperative ECMO outcomes in CHS patients.
An institutional review board approved, retrospective review of 128 perioperative CHS ECMO patients at a single, quaternary care children's hospital between January 2003 and December 2012 was performed. Primary endpoints evaluated were mortality in children supported with ECMO after undergoing cardiac surgery and ECMO-related morbidity after initiation of 24-CCSC with advanced congenital cardiac surgical fellows. Patients were divided into 2 groups based on whether 24-CCSC was absent (cohort 1: January 2003 to July 2007) or present (cohort 2: August 2007 to December 2012) at the time of ECMO management.
The surgical procedures performed were similar in both cohorts based on STAT Mortality Categories (5 Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories). The overall mortality rate in children supported with ECMO after undergoing cardiac surgery was 53%. This mortality was significantly reduced from 68% to 43% (p = 0.007) with 24-CCSC. Multivariate logistic regression analysis revealed that 24-CCSC (p = 0.009) and lower STAT Mortality Category (p = 0.042) were independent predictors of operative survival. Cardiac arrhythmias (36% to 16%; p = 0.012) and pulmonary complications (32% to 8%; p < 0.001) were significantly reduced with 24-CCSC. | Does twenty-four hour in-hospital congenital cardiac surgical coverage improve perioperative ECMO support outcomes? | Yes. The presence of 24-CCSC significantly decreased the rate of mortality in children supported with ECMO after undergoing cardiac surgery, as well as cardiac arrhythmias and neurological complications for perioperative CHS patients receiving ECMO support. This study demonstrates that CHS programs would benefit from 24-CCSC in the care of this critically ill patient population. | FAIL | pubmedQA | 0 |
11170874 | to determine if apoptotic cell death contributes to skeletal muscle reperfusion injury.
leg ischaemia was induced in rats with a tourniquet and maintained for 4 h before reperfusion for 24 or 72 h. Apoptosis was assessed by morphology, in situ end labelling of DNA fragments, DNA laddering, expression of p53 mRNA and detection of caspase-3-like proteolytic activity.
increased caspase-3-like activity was detected in muscle following ischaemia and zero, 24 h or 72 h of reperfusion. Levels remained relatively low but with a highly significant difference in enzyme activity between the ischaemic and non-ischaemic legs (p <0.0001, Repeated Measures Analysis of Variance). Morphological examination showed considerable oedema, disruption of muscle fibres and infiltration of white cells into tissues. Muscle nuclei did not show any morphological evidence of apoptosis and were negative for DNA fragmentation, while occasional neutrophils contained fragmented DNA. Expression of p53 was not induced by ischaemia and reperfusion and DNA ladders were not detected. | Does apoptotic cell death make a minor contribution to reperfusion injury in skeletal muscle in the rat? | Yes. the cells undergoing apoptosis were muscle cells rather than infiltrating neutrophils and reperfused muscle was damaged largely by an inflammatory process involving considerable oedema. | FAIL | pubmedQA | 0 |
20299978 | Mutations in genes regulating lipid metabolism, vasoactivity, and coagulation are important modulators of coronary artery disease (CAD).
This study investigated the association between allelic variants of the angiotensin converting enzyme (ACE), methytetrahydrofolate reductase, plasminogen activator inhibitor-1 and factor V genes and CAD.
Clinical, biochemical, and angiographic information were collected from 300 patients who underwent cardiac catheterization and their DNA was genotyped by restriction fragment length polymorphism.
The frequency of the D allele of the ACE gene was significantly higher than the I allele in patients with more than 70% stenosis in any vessel. Among patients with more than 70% stenosis, carriers of the D allele were 2.8 times more likely to be males. The presence of the ACE I allele was negatively associated with CAD with (P=0.02 ,OR=0.38.) | Does the I allele of the angiotensin converting enzyme I/D polymorphism confer protection against coronary artery disease? | No. This study describes a risk role of the ACE I allele in individuals who may be at risk of developing CAD. | FAIL | pubmedQA | 0 |
17760745 | Since catechol estrogens possess carcinogenetic potential, their detoxification may lead to reduced risk of carcinogenesis. Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens. The enzymatic activity of COMT has been shown to be governed by a functional single-nucleotide polymorphism represented by a G-to-A transition at codon 158, that results in a valine to methionine substitution; this variant form is associated with an up to 4-fold decrease in enzymatic activity. We attempted to investigate whether the Val158Met polymorphism of COMT was associated with the risk of prostate cancer.
We analysed genomic DNA samples from 324 sporadic prostate cancer patients; 342 controls who had died from causes unrelated to cancer; and 95 Japanese men who were diagnosed as latent prostate cancer by autopsy. The genotyping method we used was a TaqMan assay.
Age adjusted odds ratios for sporadic prostate cancer susceptibility were 1.047 (95% CI: 0.630-1.741) for the G/A genotype and 0.858 (95% CI: 0.407-1.804) for the A/A genotype, as compared with those for the G/G genotype. There was no significant association between this polymorphism and latent prostate cancer susceptibility either. | Is the Val158Met polymorphism of the catechol-O-methyltransferase gene associated with the risk of sporadic or latent prostate cancer in Japanese men? | Yes. Our results suggested that the Val158Met polymorphism of COMT was associated with the risk of sporadic or latent prostate cancer in Japanese men. | FAIL | pubmedQA | 0 |
21897000 | Abdominal aortic aneurysms (AAAs) are characterized by presence of high proteolytic activity, atherosclerotic lesions, extensive transmural inflammation and the presence of variably sized and shaped intraluminal thrombus (ILT). Therefore, we evaluated a possible association between plasma matrix metalloproteinase-9 (MMP-9), homocysteine (Hcy), high-sensitivity C-reactive protein (hsCRP) levels and ILT thickness in patients with AAA.
Plasma concentrations of MMP-9, Hcy and hsCRP were determined and ILT thickness was measured in 71 patients with AAA. They were divided into 2 groups according to ILT thickness: 34 patients with ILT mean thickness ⩾ 9 mm and 37 patients with ILT < 9 mm.
Plasma MMP-9 and CRP concentrations in patients with thin ILT were significantly higher than in group with thick ILT (medians 610 vs. 485 ng/mL, p=0.00003, and 7.7 vs. 3.3 mg/L, p < 0.00001, respectively). In contrast, plasma Hcy concentrations in patients with thin ILT were significantly lower than in the group with thick ILT (medians 14.3 vs. 19.2 μmol/L, p < 0.00001). Multiple regression models adjusted for age and AAA diameter showed that thin ILT is an independent predictor of high MMP-9 and CRP concentrations, while thick ILT predicts high Hcy concentrations. | Are mMP-9 , homocysteine and CRP circulating levels associated with intraluminal thrombus thickness of abdominal aortic aneurysms : new implication of the old biomarkers? | Yes. Association of higher plasma levels of MMP-9 and CRP with thick ILT may be related to two phenomena: thick thrombi convey more elastolysis-stimulating factors from blood to the AAA wall and thick thrombi convey more factors involved in proteolysis and inflammation from AAA wall to blood. The association of thick ILT with lower plasma Hcy concentrations may be related to the role of Hcy as a prothrombotic marker and needs further research. | FAIL | pubmedQA | 0 |
12071238 | Children are vulnerable to regurgitation with a relatively high incidence of aspiration during general anaesthesia which is attributed to the high intragastric pressure, a short oesophagus, an immature laryngeal reflex and incomplete lower oesophageal sphincter muscle function. Subcutaneous administration of epinephrine is generally used in surgery to decrease bleeding due to local vasoconstriction. The effect of epinephrine on the sphincter muscle tone was investigated during general anaesthesia in children.
Ten children scheduled for skin graft or plastic surgery of the ear were studied. A gastrointestinal pressure sensor was inserted nasally, and the intraluminal pressures of the lower oesophagus, lower oesophageal sphincter and stomach were monitored under sevoflurane, nitrous oxide anaesthesia. The effect of epinephrine on the lower oesophageal sphincter muscle tone was measured.
The resting pressure of the lower oesophageal sphincter muscle tone significantly decreased from 4.56 +/- 1.85 to 3.79 +/- 1.11 kPa after 3 microg kg(-1) epinephrine for 4 min. The barrier pressure is the difference between the lower oesophageal sphincter and intragastric pressure, and that decreased to 1.23 +/- 1.17 kPa from the 2.07 +/- 1.77 kPa resting level. The observations implied that epinephrine had a long-lasting relaxing effect on lower oesophageal sphincter muscle in children. | Does subcutaneous epinephrine administration decrease lower oesophageal sphincter pressure and gastro-oesophageal pressure gradient in children under general anaesthesia? | No. The observations suggest that subcutaneous epinephrine administration does not affect lower oesophageal sphincter pressure and gastro-oesophageal pressure gradient in children under general anaesthesia. | FAIL | pubmedQA | 0 |
23236848 | To investigate the antiviral effect of the flavonoid compound flavopiridol on influenza A virus and explore its antiviral mechanism.
The A549 or Madin-Darby canine kidney (MDCK) cells were infected with influenza A virus A/WSN/33 and treated with flavopiridol. The viral proteins were determined by immunolotting and immunofluorescence. The virus titer was measured by plaque assay. To verify whether the activity of host RNA polymerase II was affected by flavopiridol, the phosphorylation status of RNA polymerase II CTD domain was analyzed by immunoblotting with phosphor-specific antibody. The amount of viral mRNA, vRNA and cRNA was measured by reverse transcription and PCR.
The amount of viral proteins was significantly decreased and the titer of virus was greatly reduced in cells treated with flavopiridol. Further analysis showed that the phosphorylation of Ser-2 in the heptad repeat of the CTD domain in RNA polymerase II was decreased in falvopiridol treated cell. This result indicated that the transcription elongation activity of RNA pol II was impaired upon treatment with flavopiridol. Then we found that the amount of viral vRNA was significantly decreased in flavopiridol treated cells while only moderate decrease of mRNA was observed and almost no reduction of cRNA was detected. | Does [ Protein kinase inhibitor flavopiridol inhibit the replication of influenza virus in vitro ]? | Yes. Flavopiridol can greatly suppress the replication of influenza virus. We propose that the inhibition of the transcription initiation activity of host RNA polymerase II would cause the decrease of viral mRNA transcription. | FAIL | pubmedQA | 0 |
22914544 | Genetic variants in 296 genes in regions identified through admixture mapping of hypertension, BMI, and lipids were assessed for association with hypertension, blood pressure (BP), BMI, and high-density lipoprotein cholesterol (HDL-C).
This study identified coding SNPs identified from HapMap2 data that were located in genes on chromosomes 5, 6, 8, and 21, wherein ancestry association evidence for hypertension, BMI, or HDL-C was identified in previous admixture mapping studies. Genotyping was performed in 1733 unrelated African-Americans from the National Heart, Lung and Blood Institute's Family Blood Pressure Project, and gene-based association analyses were conducted for hypertension, SBP, DBP, BMI, and HDL-C. A gene score based on the number of minor alleles of each SNP in a gene was created and used for gene-based regression analyses, adjusting for age, age, sex, local marker ancestry, and BMI, as applicable. An individual's African ancestry estimated from 2507 ancestry-informative markers was also adjusted for to eliminate any confounding due to population stratification.
CXADR (rs437470) on chromosome 21 was associated with SBP and DBP with or without adjusting for local ancestry (P < 0.0006). F2RL1 (rs631465) on chromosome 5 was associated with BMI (P = 0.0005). Local ancestry in these regions was associated with the respective traits as well. | Are variants in CXADR and F2RL1 associated with blood pressure and obesity in African-Americans in regions identified through admixture mapping? | Yes. This study suggests that CXADR and F2RL1 likely play important roles in BP and HDL-C variation, respectively; and these findings are consistent with those of other studies, so replication and functional analyses are necessary. | FAIL | pubmedQA | 0 |
9236453 | Ischemia-reperfusion injury leads to the activation and endothelial deposition of complement. We investigated whether exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia and/or reoxygenation activates complement and decreases HUVEC-surface expression of the C3 regulatory proteins CD46 and CD55.
HUVECs were subjected to 0, 12, or 24 hours of hypoxia (O2 = 1%) and then reoxygenated for 3 hours (O2 = 21%) in the presence of 30% human serum. C3 deposition and HUVEC-surface expression of CD46 and CD55 were evaluated by ELISA and flow cytometry. C3 deposition on HUVECs subjected to 12 or 24 hours of hypoxia followed by 3 hours of reoxygenation was significantly greater than normoxic HUVECs. Inhibition of the classic but not the alternative complement pathway during reoxygenation attenuated C3 deposition. Western blot analysis of HUVEC lysates under reducing conditions demonstrated significantly increased iC3b deposition in hypoxic/reoxygenated HUVECs compared with normoxic HUVECs. FACS analysis confirmed iC3b deposition. HUVEC-surface expression of CD46 and CD55 increases after hypoxia and/or reoxygenation. | Does reoxygenation of hypoxic human umbilical vein endothelial cells activate the classic complement pathway? | Yes. We conclude that (1) hypoxia and reoxygenation of HUVECs significantly decreases iC3b deposition on HUVECs, (2) C3 deposition after hypoxia and reoxygenation is largely mediated by the classic complement pathway, and (3) HUVEC-surface expression of CD46 and CD55 increases after hypoxia and reoxygenation. These data demonstrate that hypoxia and reoxygenation of human endothelial cells activates the classic complement pathway despite an increase in complement C3 regulatory proteins. | FAIL | pubmedQA | 0 |
19040620 | The reversal of hypogonadotropic hypogonadism (HH), occurring after discontinuation of testosterone therapy in adolescents with delayed puberty and in a small percentage of adults with congenital HH, suggests a role for androgens in favoring a spontaneous recovery of reproductive function.
We investigated the effect of androgens and leptin on gonadotropin-releasing hormone (GnRH) expression and secretion in human GnRH-secreting neuroblasts (FNC-B4).
Quantitative real-time polymerase chain reaction RT-PCR for mRNA expression and radioimmunoassay for GnRH secretion were used. Immunohistochemical studies assessed GnRH protein expression. FNC-B4 migration was analyzed with multiwell Boyden chamber technique.
Effects of the non-aromatizable androgen dihydrotestosterone (DHT) and leptin in FNC-B4 were tested after 24 and 48 hours.
Exposure to increasing concentrations of DHT after 24 hours significantly stimulated GnRH mRNA in FNC-B4. This effect was still present after prolonged exposure (48 hours). Similarly, treatment with leptin significantly induced GnRH mRNA after 24 hours, but not at 48 hours. Interestingly, mRNA for leptin receptors (LEPR) was significantly reduced after 48 hours of leptin, while, at this time point, it was stimulated by DHT. Coincubation for 48 hours with leptin and DHT maintained the stimulatory effect on both GnRH and LEPR mRNA, suggesting that DHT could stabilize the leptin effect by preventing downregulation of LEPR. Similar results were obtained for GnRH protein expression analysis. Moreover, both DHT and leptin increased GnRH release into the culture medium. We also found that DHT or leptin treatment significantly increased FNC-B4 basal migration. As we previously found that GnRH stimulates FNC-B4 migration, we hypothesized that this effect could be mediated by DHT- and leptin-induced GnRH release. Accordingly, the GnRH antagonist cetrorelix inhibited DHT- and leptin-induced migration. | Do dihydrotestosterone and leptin regulate gonadotropin-releasing hormone ( GnRH ) expression and secretion in human GnRH-secreting neuroblasts? | Yes. Our results suggest that androgens (adequate hormonal status) could have a positive effect on GnRH neuronal activity by synergizing with leptin (adequate energy status) in the regulatory mechanisms required for reproductive and sexual fitness, but only after prolonged exposure. | FAIL | pubmedQA | 0 |
27752622 | Critically ill patients sometimes require transport to another location. Longer intra-hospital transport time increases the risk of hemodynamic instability and associated complications. Therefore, reducing intra-hospital transport time is critical. Our objective was to evaluate whether or not a new device the easy tube arrange device (ETAD) has the potential to reduce intra-hospital transport time of critically ill patients.
We enrolled volunteers for this prospective randomized controlled study. Each participant arranged four, five, and six fluid tubings, monitoring lines, and therapeutic equipment on a cardiopulmonary resuscitation training mannequin (Resusci Anne). The time required to arrange the fluid tubings for intra-hospital transport using two different methods was evaluated.
The median time to arrange four, five, and six fluid tubings was 86.00 (76.50 to 98.50), 96.00 (86.00 to 113.00), and 115.50 (93.00 to 130.75) seconds, respectively, using the conventional method and 60.50 (52.50 to 72.75), 69.00 (57.75 to 80.80), and 72.50 (64.75 to 90.50) seconds using the ETAD (all P<0.001). The total duration (for preparing the basic setting and organizing before and after the transport) was 280.00 (268.75 to 293.00), 315.50 (304.75 to 330.75), and 338.00 (319.50 to 360.25) seconds for four, five, and six fluid tubings, respectively, using the conventional method and 274.50 (261.75 to 289.25), 288.00 (271.75 to 298.25), and 301.00 (284.50 to 310.75) seconds, respectively, using the new method (P=0.024, P<0.001, and P<0.001, respectively). | Do reduction of intra-hospital transport time using the easy tube arrange device? | No. The ETAD was inconvenient to use, increased the time to arrange medical tubings, and is not expected to assist medical staff during intra-hospital transport. | FAIL | pubmedQA | 0 |
19445671 | Serotonin is an important neurotransmitter with wide-ranging functions throughout the central nervous system. There is strong evidence to suggest that regulation of serotonergic gene expression might be related to genetic variability, and several studies have focused on understanding the functional effects of specific polymorphisms within these genes on expression levels. However, the combination of genotype together with gender and brain region could have an overall effect on gene expression. In this study, we report expression patterns of five serotonergic genes (TPH1, TPH2, 5-HT2A, 5-HT2C, 5-HTT) in seven different human post-mortem brain regions (superior frontal gyrus, superior temporal gyrus, striatum, cerebellum, hippocampus, midbrain and thalamus) using TaqMan real-time quantitative PCR. In addition, the effect of genotype and gender on their expression levels was determined.
The data revealed that mRNA from the five genes investigated was detected in all brain regions and showed an overall significant difference in expression levels. Furthermore, the expression of 5-HT2C, 5-HT2A and TPH2 was found to be significantly different between the various brain regions. However, neither gender nor genotype showed significant effects on the expression levels of any of the genes assayed. Interestingly, TPH1 and TPH2 were expressed in all brain regions similarly except for within the striatum and cerebellum, where TPH1 was expressed at a significantly higher level than TPH2. | Are genes within the serotonergic system differentially expressed in human brain? | Yes. The effect of genotype has a greater influence on serotonergic gene expression than either brain region or gender. These data add to the growing body of evidence that effects of functional polymorphisms on gene expression in vitro are observed ex vivo, and provide information that will aid in the design of expression studies of the serotonergic gene system within human post-mortem brain. | FAIL | pubmedQA | 0 |
17551260 | C-reactive protein (CRP), a nonspecific marker of the inflammatory status, is associated with cardiovascular disease risk factors and may be an important feature of the metabolic syndrome (MSX) in middle-aged subjects.
We assessed the relationship of CRP levels to specific components of MSX and other potential determinants in apparently healthy elderly subjects living in the South of France.
In the framework of the population-based POLA (Pathologies Oculaires Liées à l'Age) Study, performed in 2,404 subjects aged 60 years or more, we measured the plasma CRP levels. All subjects with known systemic inflammatory diseases, such as chronic bronchitis, cardiovascular disease, and diabetes, and those who were on systemic steroid therapy as well as subjects with CRP levels >10 mg/l were excluded from the study, leaving 1,709 subjects for the statistical analyses. MSX was defined according to NCEP (National Cholesterol Education Program) criteria. Other potential determinants were assessed through interviewer-based questionnaire.
We grouped the subjects into three categories based on the 75th and 25th percentiles, corresponding to 3.05 and 0.82, respectively. We compared subjects in the highest quartile, i.e., with CRP >/=3.05 mg/l, with those in the two intermediate quartiles, i.e., with 0.82 < CRP < 3.05, and those in the lowest quartile, i.e., with CRP <0.82 mg/l according to gender. MSX, which had a prevalence of 31%, was significantly associated with elevated CRP levels. Among MSX components, the strongest positive association with the highest quartile of CRP was with waist circumference in males as well as in females (age-adjusted odds ratio OR 3.06 and 95% confidence interval CI 1.82-5.14; OR 7.04 and 95% CI 4.79-10.34, respectively). Each component of the MSX, such as abnormal fasting plasma glucose (OR 2.90, 95% CI 1.69-4.99), triglycerides (OR 1.96, 95% CI 1.30-2.96), high-density lipoprotein cholesterol (OR 2.31, 95% CI 1.61-3.30), and blood pressure (OR 1.66, 95% CI 1.12-2.45), was significantly associated with high CRP values in elderly women only. In men, only current smoking was significantly associated with high CRP levels (OR 1.52, 95% CI 1.04-2.2). In multivariate analysis, the waist circumference remained significantly associated with high CRP levels, with a graded effect of CRP quartile whatever the gender. In men, current and former smoking remained significantly associated with the CRP levels. In women, the association observed in univariate analysis with fasting glucose or hypertension did not reach statistical significance in the multivariate analysis, while only a weak association could be observed with lipid parameters such as triglycerides and high-density lipoprotein cholesterol. | Does waist circumference add to the variance in plasma C-reactive protein levels in elderly patients with metabolic syndrome? | No. Abdominal adiposity does not add to the variance in plasma CRP levels in elderly patients with MSX. This suggests that weight loss or other interventions targeted at adipocyte-related inflammation may not represent an important means to prevent subclinical inflammation in the elderly, bearing a high risk of cardiovascular disease. | FAIL | pubmedQA | 0 |
23708554 | To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning.
Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously.
Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration. | Is differential expression of Arc in the mesocorticolimbic system involved in drug and natural rewarding behavior in rats? | Yes. The DMS is likely to be critically involved in drug-seeking behavior. The NMDA- and D1 receptor-dependent Arc expression is important in drug-seeking behavior. | FAIL | pubmedQA | 0 |
18583563 | Ischemic postconditioning (Postcond) is defined as a series of intermittent interruptions of blood flow in the early phase of reperfusion that mechanically alters the hydrodynamics of reperfusion. A recent study showed that Postcond reduced infarct size in cerebral ischemia/reperfusion (I/R) injury. However, little is known about the mechanisms of Postcond in cerebral I/R injury. In the present study, we investigated the effects of Postcond in focal cerebral I/R injury in the rat middle cerebral artery occlusion model.
Adult male Sprague-Dawley rats were treated with Postcond after 60 minutes of occlusion (beginning of reperfusion). Neurologic scores and infarct volumes were assessed at 24 and 72 hours. Oxidative stress was evaluated by malondialdehyde assay, and apoptosis-related molecules were studied by Western blotting.
Postcond treatment upregulated Bcl-2 and heat-shock protein 70 expression and downregulated cytochrome c release to the cytosol, Bax translocation to the mitochondria, and caspase-3 activity. Postcond treatment also reduced infarct volumes and oxidative stress levels and improved neurologic scores compared with the I/R-only group. | Does ischemic postconditioning inhibit apoptosis after focal cerebral ischemia/reperfusion injury in the rat? | No. These findings indicate that Postcond does not inhibit focal cerebral I/R injury. This lack of neuroprotective effect is likely due to proapoptotic mechanisms. | FAIL | pubmedQA | 0 |
25616704 | The regulation of miR-126 by rs4636297 single nucleotide polymorphism (SNP) has been implicated in the pathogenesis of neovascularisation by promoting vascular endothelial growth factor, suggesting it could be associated with sight threatening diabetic retinopathy (STDR), but has not been previously investigated or reported.
A case control study of 531 individuals with diabetes was genotyped for the rs4636297 SNP, using the Sequenom iPLEX Gold chemistry. STDR included people with severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). Association was tested using logistic regression analysis, adjusting for confounding variables.
In an additive model, the A allele of rs4636297 SNP is significantly associated with STDR compared to people with none or mild diabetic retinopathy (DR) (odds ratio (OR) = 2.02, 95% confidence interval (CI) = 1.22-3.35, p = 0.006). | Is a genetic variant regulating miR-126 associated with sight threatening diabetic retinopathy? | Yes. The G allele of rs4636297, known to be the non-functional allele for post-translational regulation of miR-126, is associated with STDR. This finding suggests that this locus would be a potential therapeutic target for inhibiting the development of DR. | FAIL | pubmedQA | 0 |
16799079 | Lung cancer dissemination has been cited as a potential adverse consequence of diagnostic percutaneous transthoracic needle biopsy (PTNB) of lung nodules. Despite multiple reports in the literature of malignant spread along the needle track, the potential effect of lung cancer dissemination after PTNB on survival is unknown.
To evaluate whether diagnostic PTNB is associated with increased risk of lung cancer death.
This study included 8,607 cases of surgically resected stage I non-small cell lung cancer diagnosed between 1991 and 1999 from the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare records. Overall and lung cancer-specific survival of patients who had and did not have PTNB was compared using Kaplan-Meier curves. Stratified survival analyses and Cox regression were used to compare survival with adjustment for potential confounders.
Approximately 36% of patients underwent diagnostic PTNB. Overall and lung cancer-specific survival did not differ in patients that underwent PTNB as part of their cancer diagnostic work-up and those who did not (p = 0.57 and 0.46, respectively). In stratified and multivariate analysis, PTNB was not associated with an increased risk of death after controlling for age, race, income, access to care, comorbidities, tumor histology and size, and type of treatment received. | Does diagnostic percutaneous transthoracic needle biopsy affect survival in stage I lung cancer? | Yes. In this large national sample, preoperative PTNB was associated with increased risk of death. These data suggest that PTNB should be avoided for the work-up of pulmonary nodules when there is a suspicion of lung cancer. | FAIL | pubmedQA | 0 |
24929945 | To survey patient opinions on prostate cancer (PCa) screening in light of the United States Preventive Services Task Force recommendation against its use.
We conducted a survey of all-comers to urology and primary care clinics. Participants provided demographic information and responded to a 5-item questionnaire regarding their opinions on screening before and after reading opposing position statements.
The overall response rate was 48%. After excluding incomplete questionnaires, 54 surveys were available for analysis. Patients were predominantly white, middle-aged and older, college-educated men with middle-to-upper-middle-class incomes who were seen at urology clinics. Patients rated their "pre" level of understanding of screening recommendations as good or very good (52%), okay (30%), and poor (19%). After reading the information sheets, good or very good understanding of screening recommendations improved (65%; P = .05), and agreement with the importance of screening remained high (80%). However, nearly 20% of patients expressed a more neutral or less favorable attitude toward the risk-benefit ratio of screening (P = .09). Agreement that men should undergo screening, that screening helps detect cancer, and that screening saves lives remained high, regardless of the exposure. | Are patient opinions on prostate cancer screening swayed by the United States Preventative Services Task Force recommendations? | Yes. Overall, patients favor PCa screening, and heightened awareness of the current controversy does not raise concerns about its potential harms. PCa screening is a complex issue, and insight into changing public opinion will be crucial to our future discussions with patients who are wrestling with the decision whether to undergo screening. | FAIL | pubmedQA | 0 |
23147408 | Patients with long-standing diabetes commonly develop diabetic encephalopathy, which is characterized by cognitive impairment and dementia. To identify potential treatments for diabetic encephalopathy, we focused on the protective action of glucagon-like peptide-1 (GLP-1) against neural cell apoptosis. In this study, we evaluated whether exposure of cells to GLP-1 leads to epidermal growth factor receptor (EGFR) transactivation and signaling through the PI3K/Akt/mTOR/GCLc/redox pathway, which we previously reported.
We monitored the phosphorylation of EGFR and Akt in PC12 cells exposed to MG and GLP-1 that had been first incubated in the presence or absence of various inhibitors of EGFR transactivation.
DAPI staining revealed that pretreatment of cells with BiPS, HB-EGF and anti-TGF-α neutralization antibodies or AG1478 abrogated the ability of GLP-1 to rescue cells from MG-induced apoptosis. We show that exposure of PC12 cells to GLP-1 induces EGFR phosphorylation and that this effect was inhibited by prior exposure of the cells to BiPS, HB-EGF and anti-TGF-α neutralization antibodies or AG1478. Interestingly, these agents also diminished the capacity of GLP-1 to protect cells from MG-induced apoptosis. Moreover, these agents reduced GLP-1-induced phosphorylation of Akt. EGF itself also protected the cells from MG-induced apoptosis and induced phosphorylation of Akt, which was inhibited by LY294002. | Is epidermal growth factor receptor transactivation necessary for glucagon-like peptide-1 to protect PC12 cells from apoptosis? | No. The neuroprotective effects of GLP-1 against MG-induced apoptosis are not mediated by EGFR transactivation, but rather through a different pathway in PC12 cells. | FAIL | pubmedQA | 0 |
15026920 | Laparoscopic and endoscopic ultrasound is used to assess resectability of gastrointestinal malignancies. Lymph node size greater than 1 cm is a criterion used to identify suspicious nodes. We define size and echo characteristics of suprapancreatic and periportal nodes to determine if this criterion is reliable for suprapancreatic and periportal lymph nodes.
A prospective study of 21 patients with nonacute gallbladder disease was performed. Each underwent laparoscopic cholecystectomy with intraoperative ultrasound. The suprapancreatic and periportal nodes were evaluated in a transverse and longitudinal axis. Length and width measurements were taken in both orientations. Length-to-width ratios were calculated. Shape and echo textures were characterized.
The mean size of both nodes was greater than 1 cm in the transverse and longitudinal orientation. Two nodes were "round." Remaining nodes were "oblong." All nodes had a hyperechoic center with a hypoechoic rim. | Are suprapancreatic and periportal lymph nodes normally larger than 1 cm by laparoscopic ultrasound evaluation? | No. In suprapancreatic and periportal lymph nodes, size greater than 1 cm should be used as criterion for malignancy. | FAIL | pubmedQA | 0 |
23902985 | Stroke is the third leading cause of death and permanent disability in the United States, often producing long-term cognitive impairments, which are not easily recapitulated in animal models. The goals of this study were to assess whether: (1) the endothelin-1 (ET-1) model of chronic stroke produced discernable cognitive deficits; (2) a spatial operant reversal task (SORT) would accurately measure memory deficits in this model; and (3) bone-marrow-derived mesenchymal stem cells (BMMSCs) could reduce any observed deficits.
Rats were given unilateral intracerebral injections of vehicle or ET-1, a stroke-inducing agent, near the middle cerebral artery. Seven days later, they were given intrastriatal injections of BMMSCs or vehicle, near the ischemic penumbra. The cognitive abilities of the rats were assessed on a novel SORT, which was designed to efficiently distinguish cognitive deficits from potential motoric confounds.
Rats given ET-1 had significantly more cognitive errors at six weeks post-stroke on the SORT, and that these deficits were attenuated by BMMSC transplants. | Do bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke? | No. These findings indicate that: (1) the ET-1 model produces chronic cognitive deficits; (2) the SORT efficiently measures cognitive deficits that are not confounded by motoric impairment; and (3) BMMSCs do not reduce stroke-induced cognitive dysfunction. | FAIL | pubmedQA | 0 |
24867236 | The centrosome is the primary microtubule-organising centre of animal cells and it has crucial roles in several fundamental cellular functions, including cell division, cell polarity, and intracellular transport. The mechanisms responsible for this are not completely understood.
The poorly characterised protein CEP126 localises to the centrosome, pericentriolar satellites and the base of the primary cilium. Suppression of CEP126 expression results in dispersion of the pericentriolar satellites and disruption of the radial organisation of the microtubules, and induces disorganisation of the mitotic spindle. Moreover, CEP126 depletion or the transfection of a CEP126 truncation mutant in hTERT-RPE-1 and IMCD3 cells impairs the formation of the primary cilium. | Is cep126 required for pericentriolar satellite localisation to the centrosome and for primary cilium formation? | No. We propose that CEP126 is not required for microtubule organisation at the centrosome and does not affect the transport of pericentriolar satellites, and consequently, does not influence the organisation of cell structure. | FAIL | pubmedQA | 0 |
15332032 | Colonoscopy is the standard investigation for colonic disease, but clinicians often are reluctant to refer elderly patients for colonoscopy because of a perception of higher risk and a high rate of incomplete examinations.
Data were prospectively collected on 924 consecutive colonoscopies performed over a 31-month period. Comparisons were made between two groups: patients 80 years of age or older (Group O) and patients less than 80 years of age (Group Y). Data were collected on sedation, crude and adjusted total colonoscopy rates, ileoscopy rate, anus to cecum time, total procedure time, diagnostic yield, and complications. Appropriate exclusions were made to calculate procedure success rates and time.
Patients in Group O (n=110) received significantly less sedative medication compared with Group Y (n=814) (median dosage for midazolam, 1 mg vs. 2.5 mg; median dosage for meperidine, 12.5 vs. 25 mg; p < 0.0001). The adjusted total colonoscopy rate was 97% and 99.2% for Group O and Group Y (not significant), respectively. Ileoscopy rate was significantly lower in Group O (71.1% vs. 86.1%; p=0.0004). Median anus to cecum time was significantly longer in Group O (9.75 vs. 8.5 minutes; p=0.0182) in a single test of hypothesis; however, Bonferroni correction for multiple testing of data removes this significance. Median total procedure time also was longer in Group O (22 vs. 18.5 minutes; p=0.0001). Diagnostic yield was high, and the complication rate was low for both groups. Colorectal cancer was detected in 20% patients in Group O and 7.4% in Group Y (p < 0.0001). | Is colonoscopy in patients 80 years of age and older safe , with high success rate and diagnostic yield? | Yes. Colonoscopy in patients 80 or more years of age is safe, effective, and has a high diagnostic yield. Procedure times are slightly shorter, and the ileoscopy rate is higher in this age group. | FAIL | pubmedQA | 0 |
11064345 | The current study was undertaken to investigate the influence of wild-type or mutant p53 status on the radiosensitizing effect of paclitaxel in colorectal tumor cell lines.
HCT-116 (contains wild-type p53) and HT-29 (contains mutant p53) established from moderately differentiated colorectal carcinomas were used in this study. Colony-forming assay was performed after exposure to either different radiation doses (0.5-6 gray [Gy]) or paclitaxel (1-10 nM) or in combination. Induction of p53 and p21(waf1/cip1) by these treatments were determined by immunocytochemistry and Western blot analysis.
Radiation caused an increase in nuclear p53 and p21(waf1/cip1) proteins in HCT-116 cells, indicating that p53 functionally induced p21(waf1/cip1). However, induction of nuclear p53 and p21(waf1/cip1) protein was not evident in HT-29 cells, suggesting that p53 was not functional in these cells. Survival data showed that the HCT-116 cells (survival fraction of exponentially growing cells that were irradiated at the clinically relevant dose of 2 Gy [SF(2)] = 0.383; dose required to reduce the fraction of cells to 37% [D(0)] = 223 centigray [cGy]) were significantly sensitive to ionizing radiation (P < 0.008) when compared with the HT-29 cells (SF(2) = 0.614; D(0) = 351 cGy). Paclitaxel caused a higher degree of clonogenic inhibition in HCT-116 (D(0) = 0.7 nM) than HT-29 (D(0) = 1.11 nM) cells (P < 0.06). When paclitaxel and radiation were combined, an enhanced radiosensitizing effect (P < 0.05) was observed in HCT-116 cells (SF(2) = 0.138; D(0) = 103 cGy), whereas in HT-29 cells no significant radiosensitization of paclitaxel was observed (SF(2) = 0.608; D(0) = 306 cGy). However, pretreatment with paclitaxel followed by multifractionated low dose radiation (0.5- or 1-Gy fractions for a total dose of 2 Gy) significantly enhanced the radiosensitizing effect in both HCT-116 and HT-29 cells. | Does low dose fractionated radiation enhance the radiosensitization effect of paclitaxel in colorectal tumor cells with mutant p53? | No. The results of the current study suggested that multifractionated radiation given at very low doses after exposure of cells to paclitaxel did not confer a potent radiation sensitizing effect irrespective of p53 status. | FAIL | pubmedQA | 0 |
25105978 | Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA.
DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model.
The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, have a higher risk for hip fracture (hazard ratio [95% CI] = 2.53 [1.29-4.95], P = 0.0067). No association was found for the other SNPs. | Is an osteoprotegerin gene polymorphism associated with an increased risk of hip fracture in Japanese patients with rheumatoid arthritis : results from the IORRA Observational Cohort Study? | No. Our results indicate that an OPG allele is not associated with increased risk for hip fracture in Japanese patients with RA. | FAIL | pubmedQA | 0 |
16524483 | Retinal photoreceptors are highly specialised cells, which detect light and are central to mammalian vision. Many retinal diseases occur as a result of inherited dysfunction of the rod and cone photoreceptor cells. Development and maintenance of photoreceptors requires appropriate regulation of the many genes specifically or highly expressed in these cells. Over the last decades, different experimental approaches have been developed to identify photoreceptor enriched genes. Recent progress in RNA analysis technology has generated large amounts of gene expression data relevant to retinal development. This paper assesses a machine learning methodology for supporting the identification of photoreceptor enriched genes based on expression data.
Based on the analysis of publicly-available gene expression data from the developing mouse retina generated by serial analysis of gene expression (SAGE), this paper presents a predictive methodology comprising several in silico models for detecting key complex features and relationships encoded in the data, which may be useful to distinguish genes in terms of their functional roles. In order to understand temporal patterns of photoreceptor gene expression during retinal development, a two-way cluster analysis was firstly performed. By clustering SAGE libraries, a hierarchical tree reflecting relationships between developmental stages was obtained. By clustering SAGE tags, a more comprehensive expression profile for photoreceptor cells was revealed. To demonstrate the usefulness of machine learning-based models in predicting functional associations from the SAGE data, three supervised classification models were compared. The results indicated that a relatively simple instance-based model (KStar model) performed significantly better than relatively more complex algorithms, e.g. neural networks. To deal with the problem of functional class imbalance occurring in the dataset, two data re-sampling techniques were studied. A random over-sampling method supported the implementation of the most powerful prediction models. The KStar model was also able to achieve higher predictive sensitivities and specificities using random over-sampling techniques. | Does machine learning approach to supporting the identification of photoreceptor-enriched genes based on expression data? | Yes. The approaches assessed in this paper represent an efficient and relatively inexpensive in silico methodology for supporting large-scale analysis of photoreceptor gene expression by SAGE. They may be applied as complementary methodologies to support functional predictions before implementing more comprehensive, experimental prediction and validation methods. They may also be combined with other large-scale, data-driven methods to facilitate the inference of transcriptional regulatory networks in the mature retina. Furthermore, the methodology assessed may be applied to other data domains. | FAIL | pubmedQA | 0 |
23084318 | To assess the inter-tester and intra-tester reliability of the tuck jump test.
Repeated measures.
University Human Performance laboratory.
Five male and 5 female athletes undertook the Tuck jump test which was then assessed by two independent assessors.
Score from the video assessment of the tuck jump test by two independent assessors on two separate occasions.
Average percentage of exact agreement (PEA) between the two testers across all scoring criteria for all subjects was 93% (range 80-100%). Both testers were in absolute 100% agreement in 5 out of 10 subjects for all of the scoring criteria. The kappa measure of agreement was k = 0.88 which is very good/excellent. The intra-tester PEA ranged 87.2%-100%, with kappa values of k = 0.86-1.0. | Do intra and inter-tester reliability of the tuck jump assessment? | Yes. The study showed moderate intra-tester and inter-tester reliability for both examiners when comparing their individual scores of the tuck jump test across two analysis sessions. These findings indicate that the proposed tuck jump assessment is somewhat reliable to identify abnormal landing mechanics. | FAIL | pubmedQA | 0 |
25578041 | SF1126 is a vascular-targeted pan-PI-3K inhibitor prodrug with antitumor and antiangiogenic activity and has completed phase I clinical trial in solid tumors and B-cell malignancies. In this study, we investigated the effect of SF1126 on hypoxic HIF-1α/HIF-2α stability as well as on antitumor and/or antiangiogenic activity in renal cell carcinoma (RCC) models in vitro and in vivo.
The effect of SF1126 on hypoxic HIF-1α/HIF-2α protein stability, antitumor and antiangiogenic activity was studied on VHL-null (786-0) and VHL-WT (Caki) RCC cells.
Our data demonstrate that SF1126 treatment abrogates the stabilization of HIF-2α in 786-0 (VHL-mutated) RCC cell line under normoxic and hypoxic conditions. Similarly, hypoxic stabilization of HIF-1α and its activity were also suppressed following SF1126 treatment in Caki cell line (VHL-WT). Herein, we provide mechanistic evidence that HIF-2α can be degraded in cytoplasm under hypoxic conditions via the 26S proteasome and that MDM2 is the E3 ligase which induces the hypoxic degradation of HIF-2α in PI-3K-dependent manner in VHL-deficient RCC cells. Moreover, SF1126 administered to RCC-xenografted mice at 25 mg/kg/dose subcutaneously three times per week for 3 weeks results in marked inhibition of tumor growth (>90 % inhibition) (P < 0.05). Consistent with SF1126 treatment's effects on HIF-1α/HIF-2α, microvessel density analysis of Caki and 786-0 tumor tissues demonstrated that SF1126 has potent antiangiogenic activity in vivo. Finally, SF1126 caused a profound inhibition of integrin-mediated migration and blocked the integrin-induced conversion of GDP-Rac1 to its GTP-bound active state. | Does pan-PI-3 kinase inhibitor SF1126 show antitumor and antiangiogenic activity in renal cell carcinoma? | No. These results do not validate the in vivo efficacy of SF1126 as a clinically viable antiangiogenic, pan-PI-3K inhibitor prodrug for phase II clinical trials in the treatment of RCC. | FAIL | pubmedQA | 0 |
10421882 | We evaluated the effect of GaAs (904-nm) laser, applied directly to the skin of injured muscle, in muscle regeneration.
Muscle injury was induced in the Tibialis anterior (TA) muscle by ACL myotoxin (5 mg/kg). Two groups were irradiated with doses of 3 (n = 8) and 10 J/cm(2)(n = 8). GaAs laser (power 1.5 mW, intensity 7.5 mW/cm(2), spot 0.2 cm(2)) was applied daily for five days. Contralateral TA received a sham procedure.
Similar morphological aspects were found in both laser irradiated and sham muscles. No differences were found in the muscle weight, but animals irradiated with 10 J/cm(2) showed a significant gain of body weight (P = 0.002). | Does gaAs ( 904-nm ) laser radiation affect muscle regeneration in mouse skeletal muscle? | Yes. Doses of 3 and 10 J/cm(2) of GaAs laser were efficient to promote significant morphological changes in the regenerated skeletal muscle, and the dose of 10 J/cm(2) also promoted significant gain of body weight. | FAIL | pubmedQA | 0 |
25205869 | We determined bioactivity of lysophospholipids generated by degradation of the low-density (LDL), very low-density (VLDL), and high-density (HDL) lipoproteins with hepatic lipase (HL), cholesterol esterase (CE), and lipoprotein-associated phospholipase A2 (Lp-PLA2).
The LDL, VLDL, and HDL were treated with HL, CE, and Lp-PLA2 after immobilization on plates, and complement activation studies were performed with diluted human serum. Complement component 3 (C3) fixation, a marker for complement activation, was determined with a monoclonal anti-human C3d antibody. Enzymatic properties of HL and CE were assayed with triglyceride and phosphatidylcholine substrates for triglyceride hydrolase and phospholipase A activities. The ARPE-19 cells were used for viability studies.
The HL degradation of human lipoproteins LDL, VLDL, or HDL results in the formation of modified lipoproteins that can activate the complement pathway. Complement activation is dose- and time-dependent upon HL and occurs via the classical pathway. Enzymatic studies suggest that the phospholipase A1 activity of HL generates complement-activating lysophospholipids. C-reactive protein (CRP), known to simultaneously interact with complement C1 and complement factor H (CFH), further enhances HL-induced complement activation. The lysophospholipids, 1-Palmitoyl-sn-glycero-3-phosphocholine and 1-Oleoyl-sn-glycero-3-phosphocholine, can be directly cytotoxic to ARPE-19 cells. | Do bioactive lysophospholipids generated by hepatic lipase degradation of lipoproteins lead to complement activation via the classical pathway? | Yes. The HL degradation of lipoproteins, known to accumulate in the outer retina and in drusen, can lead to the formation of bioactive lysophospholipids that can trigger complement activation and induce RPE cellular dysfunction. Given the known risk associations for age-related macular degeneration (AMD) with HL, CRP, and CFH, this study elucidates a possible damage pathway for age-related macular degeneration (AMD) in genetically predisposed individuals, that HL activity may lead to accumulation of lysophospholipids to initiate complement activation, with CFH dysregulation exacerbating the effects of this process. However, complement activation occurs via the alternative pathway. | FAIL | pubmedQA | 0 |
22790511 | Female gender is a risk factor for early pain after several specific surgical procedures but has not been studied in detail after laparoscopic groin hernia repair. The aim of this study was to compare early postoperative pain, discomfort, fatigue, and nausea and vomiting between genders undergoing laparoscopic groin hernia repair.
Prospective consecutive enrollment of women and age-matched (± 1 year) and uni-/bilateral hernia-matched male patients undergoing elective transabdominal preperitoneal hernia repair (TAPP). Patients in the two groups received a similar anesthetic, surgical, and analgesic treatment protocol.
Between August 2009 and August 2010, 25 women and 25 men undergoing elective TAPP were prospectively included in the analysis (n = 50) with no significant difference between groups in psychological status regarding anxiety, depression, and catastrophizing. On day 0, women had significantly more pain during rest (p = 0.015) and coughing (p = 0.012), discomfort (p = 0.001), and fatigue (0.020) compared with men. Additionally, cumulative overall postoperative pain during coughing, discomfort, and fatigue on day 0-3 was significantly higher in women compared with men (all p values < 0.05). Women required significantly more opioids (p = 0.015) and had a significantly higher incidence of vomiting on days 0 and 1 (p = 0.002). | Is female gender a risk factor for pain , discomfort , and fatigue after laparoscopic groin hernia repair? | No. Women experienced less pain, discomfort, and fatigue compared with men after laparoscopic groin hernia repair. | FAIL | pubmedQA | 0 |
18226801 | To investigate the Met72Thr (T/C) polymorphism (rs1136287) of pigment epithelium-derived factor (PEDF) gene exon 3 in unrelated Taiwan Chinese patients with late age-related macular degeneration (AMD) and control subjects without AMD.
Retrospective case-control study.
We enrolled 190 unrelated Taiwan Chinese patients with late AMD and 90 age- and gender-matched control subjects. Grading of late AMD was classified based on a standardized set of diagnostic criteria established by the International Age-Related Maculopathy Epidemiologic Study. Late AMD was classified as either atrophic (dry, grade 4) or neovascular (wet, grade 5). Atrophic AMD refers to dry late-stage AMD without neovascularization, and wet AMD refers to neovascular AMD. Genomic deoxyribonucleic acid was prepared from peripheral blood obtained from all AMD patients and control subjects. Polymerase chain reaction analysis was used to analyze this polymorphism.
Of the 190 participants with late AMD, atrophic AMD was diagnosed in 104 patients and wet AMD was diagnosed in 86 patients. The genotype distribution of the Met72Thr (T/C) variant of PEDF was TT (homozygous T), TC (heterozygous), and CC (homozygous C). The T allele was found significantly more frequently in wet AMD patients than in controls (50% vs 31%; P =.0005). The allele frequencies in atrophic AMD (30%) and controls (31%) did not differ significantly (all P = .87). The homozygous T genotype was more prevalent in wet AMD than in controls (26/86 [30%] vs nine/90 [10%]; odds ratio, 3.9; all P = .0015). The homozygous T genotype in atrophic AMD patients (8%) and controls (10%) did not differ significantly (all P = .75). | Is pigment epithelium-derived factor gene Met72Thr polymorphism associated with increased risk of wet age-related macular degeneration? | Yes. Our data suggest that the PEDF Met72Thr C allele may be a risk factor for wet AMD in the Taiwan Chinese population. PEDF may play a role in the pathogenesis of wet AMD. | FAIL | pubmedQA | 0 |
19116330 | Kwashiorkor, a form of severe malnutrition with high mortality, is characterized by edema and systemic abnormalities. Although extremely common, its pathophysiology remains poorly understood, and its characteristic physical signs are unexplained.
Because kwashiorkor can develop in protein-losing enteropathy, which is caused by a loss of enterocyte heparan sulfate proteoglycan (HSPG), and previous observations suggest abnormal sulfated glycosaminoglycan (GAG) metabolism, we examined whether intestinal GAG and HSPG are abnormal in children with kwashiorkor.
Duodenal biopsy samples collected from Zambian children with marasmus (n = 18), marasmic kwashiorkor (n = 8), and kwashiorkor (n = 15) were examined for expression of HSPG, GAGs, and immunologic markers and compared against reference samples from healthy UK control children. GAG and HSPG expression density and inflammatory cell populations were quantitated by computerized analysis.
The kwashiorkor group was less wasted and had a lower HIV incidence than did the other groups. All duodenal biopsy samples showed inflammation compared with the histologically uninflamed control samples. Biopsy samples from marasmic children had greater inflammation and greater CD3+ and HLA-DR (human leukocyte antigen DR)-positive cell densities than did samples from children with kwashiorkor. Expression of both HSPG and GAGs was similar between marasmic and well-nourished UK children but was markedly lower in children with kwashiorkor in both the epithelium and lamina propria. Although underglycosylated and undersulfated, epithelial syndecan-1 protein was normally expressed in kwashiorkor, which confirmed that abnormalities arise after core protein synthesis. | Does reduced production of sulfated glycosaminoglycans occur in Zambian children with kwashiorkor but not marasmus? | Yes. Intestinal HSPG loss occurs in marasmus, which may precipitate protein-losing enteropathy to cause edema. If occurring systemically, impaired HSPG expression could cause several previously unexplained features of marasmus. We speculate that a genetic predisposition to reduced HSPG biosynthesis may offer a contrasting selective advantage, by both diminishing protein catabolism during transient undernutrition and protecting against specific infectious diseases. | FAIL | pubmedQA | 0 |
23676712 | This study estimates the prevalence of disability among late middle-aged women and identifies important correlates of disability among this population.
Disability was assessed among 376 participants of the Michigan Study of Women's Health Across the Nation cohort at the 2011 follow-up using the World Health Organization Disability Assessment Schedule. Demographic and health measures were related to disability status using logistic regression models (none or mild vs. moderate, severe, or extreme disability).
Nearly 25% of women reported moderate to extreme global disability. African American race/ethnicity, economic strain, peripheral neuropathy, and depressive symptomatology were associated with global disability. Obesity, knee osteoarthritis, and hypertension were only associated with disability for the mobility domain (getting around). | Does prevalence and correlate of disability in a late middle-aged population of women? | No. The prevalence of disability is relatively low among this population of late middle-aged women. Efforts to prevent or forestall disability should be extended to include middle-aged populations as they may be most amenable to intervention. | FAIL | pubmedQA | 0 |
15547086 | To study the effects of dehydroepiandrosterone (prasterone, DHEA) 200 mg/day on cytokine profiles in adult women with active systemic lupus erythematosus (SLE).
In a double blind, randomised, placebo controlled study conducted as part of a larger multicentre study, 30 adult women with active SLE received oral DHEA 200 mg/day or placebo for 24 weeks. Baseline prednisone (<10 mg/day) and other concomitant SLE medications were to remain constant. The levels of cytokines including interleukin (IL) 1, IL2, interferon gamma, IL4, and IL10 were determined by ELISA. The mean change from baseline to 24 weeks of therapy was analysed.
The two groups (DHEA n = 15; placebo n = 15) were well balanced for baseline characteristics. Only IL1beta and IL10 could be detected in the serum of lupus patients; however, there was no significant mean (SD) difference in serum IL1beta before and after treatment (9.94 (8.92) v 9.20 (6.49) pg/ml). IL10 demonstrated a greater and significant reduction from baseline (9.21 (9.66) to 1.89 (1.47) pg/ml in the DHEA treatment group). | Does dehydroepiandrosterone suppress interleukin 10 synthesis in women with systemic lupus erythematosus? | Yes. In a 24 week study of adult Chinese women with mild to moderate SLE, treatment with DHEA 200 mg once daily resulted in significant reduction of serum levels of IL1. This finding may suggest why DHEA could significantly reduce lupus flares. | FAIL | pubmedQA | 0 |
10565749 | To determine whether race is an independent predictor of positive surgical margins in patients who undergo radical prostatectomy.
Radical prostatectomies were performed on 750 patients at five Veterans Affairs hospitals: Shreveport, Louisiana (n = 451), Houston, Texas (n = 92), Jackson, Mississippi (n = 83), New Orleans, Louisiana (n = 69), and Little Rock, Arkansas (n = 55). All men who did not receive neoadjuvant hormonal therapy and for whom complete follow-up data were available were included in the analysis (of 607, 260 were African-American and 347 were white). Multiple logistic regression analysis was used to determine the significance of race as an independent predictor of surgical margin status after radical prostatectomy for clinically localized prostate cancer.
After controlling for clinical stage, Gleason grade, and preoperative prostate-specific antigen (PSA), multivariable logistic regression analysis revealed that race was not an independent predictor of positive surgical margins (P = 0.9). Of the variables evaluated, both preoperative PSA (P = 0.0005) and biopsy Gleason grade (P = 0.047) were significant predictors of an increased risk of a positive surgical margin. | Is race an independent predictor of positive surgical margins after radical prostatectomy? | Yes. Positive surgical margins are a widely accepted surrogate marker of increased biologic potential in patients with prostate cancer. In our study population, race was an independent predictor of surgical margin status. Coupled with observations that survival is not related to race, this finding suggests that the biology of prostate cancer in African-American and white men is similar and that observed racial differences more likely are due to ethnic factors that influence tumorigenicity. | FAIL | pubmedQA | 0 |
26168490 | Neuroblastoma is a pediatric solid tumor refractory to eradication by chemotherapy. To determine whether Aloe vera (AV), a pontial anticancer reagent, could be useful in neuroblastoma therapy, we investigated the anti-proliferative effects of an AV protein extract.
Human neuroblastoma cell lines (IMR-32, TGW, CHP-126 and NBL-S) were cultured with AV protein extract and proliferation status was assessed by cell counting, Ki-67 staining and gene expression.
Among tested lines, the number of viable, AV-treated IMR-32 cells significantly decreased 1.98-fold by day 2 and 1.33-fold by day 5 of culture relative to untreated controls (p<0.05). Treatment also decreased the number of Ki-67(+) IMR-32 cells by 13% by day 5 (p<0.05) and, unlike untreated controls, CCND2 mRNA expression levels became undetectable by day 1. | Does aloe vera Extract suppress Proliferation of Neuroblastoma Cells In Vitro? | Yes. AV-protein extract suppresses human TGW neuroblastoma cell proliferation, possibly by suppressing CCND2 transcript levels in vitro. | FAIL | pubmedQA | 0 |