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['Laparoscopic procedures have generally been considered to be contraindicated in patients with a history of laparotomy because of a high risk of enteric injury during the procedure. Laparoscopy-assisted gastrectomy (LAG) has been used increasingly in the treatment of early gastric cancer, but its indication for patients with a history of laparotomy remains unclear. The aim of the present study was to estimate whether LAG is contraindicated for the patient with a history of laparotomy (PSURG).', 'From January 2003 to March 2006, 139 patients with early gastric cancer underwent LAG with curative intent in our institute. Fifty were PSURG patients, and the remaining 89 patients underwent LAG without any history of laparotomy (NSURG). Operative and early postoperative outcomes were compared between the groups.', 'Appendectomy and gynecological surgery were the predominant procedures performed in the PSURG group prior to undergoing LAG, involving 28 patients (56.0%) and 16 patients (32.0%), respectively. Detachment of adhesion above the umbilicus was required in 25 PSURG patients (50.0%). There was no significant difference in operative and postoperative results between the two groups, although 1 PSURG patient developed symptoms of bowel injury on the first postoperative day, probably caused during the laparoscopic procedure for dissection of a jejuno-jejunal adhesion.'] Is previous laparotomy a contraindication to laparoscopy-assisted gastrectomy for early gastric cancer? | qiaojin/PubMedQA | 2 | [
-2.4498276710510254,
-1.0541521310806274,
2.6038084030151367
] |
['Acute Stanford type A aortic dissection (AAD) is associated with substantial perioperative mortality and morbidity.', 'N-terminal pro-brain natriuretic peptide (NT-proBNP) is a prognostic biomarker of outcome in cardiovascular disease. Its predictive power in patients undergoing emergency surgery for acute type A aortic dissection is yet unknown.', 'We prospectively measured pre-operative NT-proBNP in 104 patients (39 female, 35%; median age 61 years) undergoing emergency surgery for AAD during a 6-year study period. European System for Cardiac Operative Risk Evaluation risk scores were recorded and patients were followed for 30-day mortality and major adverse events (MAEs) as defined by the need for rethoracotomy, occurrence of postoperative heart failure, neurologic deficit, lung failure, renal failure, or sepsis.', 'Median logistic European System for Cardiac Operative Risk Evaluation in the cohort was 12 (interquartile range 7 to 19). During the first 30 days, 23 patients (22%) died, and 53 patients (51%) experienced MAEs. Median (interquartile range) NT-proBNP levels in survivors versus nonsurvivors were 328 pg/ml (157 to 569) versus 2,240 pg/ml (515 to 4,734; p < 0.001), and in patients without versus with MAEs, 227 pg/ml (107 to 328) and 719 pg/ml (442 to 2,287; p < 0.001), respectively. Adjusted odds ratios for increasing tertiles of NT-proBNP compared with the lowest tertile were 0.98 (95% confidence interval [CI] 0.18 to 5.33; p = 0.98) and 11.67 (95% CI 2.61 to 52.09; p = 0.001) for 30-day mortality and 9.07 (95% CI 2.58 to 31.83; p = 0.001) and 50.21 (95% CI 10.85 to 232.45; p < 0.001) for MAEs, respectively, indicating a significant association between pre-operative NT-proBNP levels and outcome.'] Does pre-operative N-terminal pro-brain natriuretic peptide predict outcome in type A aortic dissection? | qiaojin/PubMedQA | 2 | [
-1.4803112745285034,
-1.6808825731277466,
2.212627410888672
] |
['Cytomegalovirus (CMV) infection in transplant patients with special risk factors remains a major hazard. CMV-seronegative recipients with seropositive donors have the highest risk of developing acute CMV disease. We suggest that the HLA-type may influence the occurrence and the severity of primary CMV infection of these recipients and the measurement of the special HLA-types may be useful in the prediction of acute infection.', 'Since 1999 1213 cadaver kidney transplantations have been performed in our clinic. 163 of 1213 recipients were CMV-seronegative (13%) and 129 of them received the kidney from seropositive donors. All 129 patients received CMV infection prophylaxis. Of 129 CMV-seronegative patients 49 developed acute CMV infection (38%) during the first posttransplant year. CMV infection was diagnosed by CMV antigenemia test and serologic measurements (ELISA). The particular HLA-genotypes of the recipients were studied before the transplantation. The occurrence and the severity of CMV infection was investigated in association with HLA-types.', 'We found different acute CMV infection distribution in the careers and non-careers of investigated HLA-types: HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6 and HLA-DR11, but the differences were not significant in these HLA-types (P = 0.26, P = 0.37, P = 0.83, P = 0.07 and P = 0.37). While investigating HLA-DQ3, we found that of 68 DQ3-positive patients 32 (47%), of 61 DQ3-negative patients 17 (28%) had acute CMV infection and this difference was found to be significant. This result was confirmed by univariate and multivariate Cox Regression (P = 0.001) and the appropriate significance level was considered by Bonferroni correction.'] Is hLA-DQ3 a probable risk factor for CMV infection in high-risk kidney transplant patients? | qiaojin/PubMedQA | 2 | [
-1.439920425415039,
-1.518810510635376,
1.988642692565918
] |
['It was reported that the long-acting insulin analogue glargine induces cell proliferation in a human osteosarcoma cell line and therefore might induce or accelerate tumor growth. Induction of cell proliferation would be particularly relevant for insulin treatment of subjects with diabetes and the potential of bearing tumor cells (e.g., a history of a malignant disease).', 'Proliferation, apoptosis, and the expression levels of insulin receptor, IGF-I receptor, and insulin receptor substrate (IRS) 2 were analyzed in human pancreatic cancer cells (Colo-357) after incubation (72 h) with insulin glargine or regular human insulin at 0-100 nmol/l. A total of 125 subjects, after partial or total pancreatectomy due to pancreatic carcinoma, were analyzed over a median follow-up period of 22 months.', 'There was no significant difference between glargine and regular human insulin with respect to regulation of proliferation and apoptosis of Colo-357 cells. The expression levels of insulin receptor, IGF-I receptor, and IRS2 as a downstream molecule of both receptor signaling pathways were not altered at any concentration tested. The insulin receptor was downregulated to a similar degree by glargine and regular human insulin at high insulin concentrations (P < 0.0001 for glargine, P = 0.002 for regular human insulin). The median survival time after pancreatic surgery was 15 months. Survival analysis showed that the time-dependent proportion of patients who survived was identical in patients receiving insulin glargine versus insulin treatment without glargine and control subjects without diabetes after surgery (P = 0.4, three-sample comparison).'] Are proliferation of colo-357 pancreatic carcinoma cells and survival of patients with pancreatic carcinoma altered by insulin glargine? | qiaojin/PubMedQA | 2 | [
-2.018322467803955,
-1.4329935312271118,
2.4287877082824707
] |
['About 90% of patients with atopic dermatitis (AD) are colonized with Staphylococcus aureus. S. aureus worsens AD by secreting superantigens and structural molecules within the cell wall that induce skin inflammation. Therefore, S. aureus in the home may contribute to persistent skin inflammation and disease severity.', 'To quantify S. aureus burden in homes of participants with AD of varying severities.', "Participants with mild (n=18), moderate (n=14), severe (n=15), and no AD (n=15), collected dust from their bed and bedroom floor, and from their home vacuum cleaner bag. DNA was extracted from dust samples, and the S. aureus-specific femB gene was quantified using quantitative real-time PCR. Data was log-transformed, and then statistically analysed with anova, student's t-test, and Spearman's r.", "Participants with severe AD (geometric mean: 14.67 pg/mg dust) had significantly more S. aureus DNA in their bed dust than those with moderate (0.41 pg/mg dust, P<0.0001), mild (1.42 pg/mg dust, P=0.0051), and no AD [0.09 pg/mg dust, P<0.0001 (t-test)]. Similar patterns were observed for dust from the bedroom floors and vacuum bags. S. aureus DNA was highest in dust from beds as compared with bedroom floors or vacuum bags (medians: 1.51, 0.69, 0.21 pg/mg dust, respectively; P=0.007). Eczema Area and Severity Index scores correlated with S. aureus DNA from the bed (Spearman's r=0.7263; P=0.0004) and floor (0.6846; P=0.0002) dust, but not with the vacuum bag dust (0.3783; 0.0684)."] Is severe atopic dermatitis associated with a high burden of environmental Staphylococcus aureus? | qiaojin/PubMedQA | 2 | [
-1.5093411207199097,
-1.5659663677215576,
2.0683951377868652
] |
['To assess possible ergogenic properties of corticosteroid administration.', 'A balanced, double-blind, placebo-controlled design was used.', '28 well-trained cyclists and rowers.', "4 weeks' daily inhalation of 800 microg budesonide or placebo.", 'The subjects performed three incremental cycle ergometer tests until exhaustion, before and after 2 and 4 weeks of placebo or budesonide administration, to measure maximal power output (W(max)). Once a week they filled in a profile of mood state (POMS) questionnaire.', 'There was no significant difference in W(max) between the placebo (376 (SD 25) W) and the corticosteroid group (375 (36) W) during the preintervention test, and there were no significant changes in either group after 2 and 4 weeks of intervention. No effect of the intervention on mood state was found.'] Does four weeks ' corticosteroid inhalation augment maximal power output in endurance athletes? | qiaojin/PubMedQA | 2 | [
-1.5938156843185425,
-1.3837056159973145,
1.9401119947433472
] |
['To examine the physiological and social consequences that 9th and 10th grade adolescents experience as a result of experimenting with cigarette use, and whether consequences vary by level of experimentation and gender.', 'Data were collected between 2001 and 2004 from 395 adolescents attending two northern California public high schools. Analyses are limited to 155 adolescents who reported puffing on cigarettes or smoking whole cigarettes at any of four time points during the study.', 'The percentage of adolescents reporting consequences of smoking was as follows: any positive consequence (56%), felt relaxed (46%), looked cool (31%), looked grown-up (27%), became popular (17%), any negative consequence (56%), friends were upset (35%), trouble catching breath (29%), bad cough (26%), and got into trouble (23%). Ten percent of adolescents reported only experiencing negative consequences, 11% reported only positive consequences, 45% reported both negative and positive consequences, and 34% reported no consequences. Greater levels of experimentation were associated with greater likelihood of reporting positive or negative consequences. Few gender differences emerged.'] Do adolescents report both positive and negative consequences of experimentation with cigarette use? | qiaojin/PubMedQA | 1 | [
-0.43992114067077637,
2.069073438644409,
-2.1558704376220703
] |
['Nickel allergy has been studied by contact dermatitis groups around the world, and the frequency of nickel sensitivity has been reported to be decreasing in some populations.', 'To review the prevalence of nickel allergy as observed by the North American Contact Dermatitis Group from 1992 to 2004.', 'The computer database of the North American Contact Dermatitis Group was used to examine the prevalence of nickel allergy over the study period and to analyze it by time, sex, and age.', 'From 1992 to 2004, 25,626 patients were patch-tested. The percentage of women tested was fairly constant (61.4-66.3%). A steady increase in nickel sensitivity was seen from 1992 to 2004. Subgroup analysis did not identify a population with declining nickel allergy.'] Does detection of nickel sensitivity have increased in North American patch-test patients? | qiaojin/PubMedQA | 1 | [
-2.255056858062744,
1.0912182331085205,
0.36380434036254883
] |
['Peripheral artery disease (PAD) is common in patients on hemodialysis (HD). Recently, cilostazol has been reported to reduce target lesion revascularization (TLR) after percutaneous transluminal angioplasty (PTA) for PAD in the general population. This study aimed to clarify the effects of cilostazol administration on long-term patency after PTA in HD patients.', 'Three-hundred seventy-two consecutive lesions in 193 HD patients successfully undergoing PTA were enrolled in the study and divided into two groups: patients receiving 100 mg cilostazol twice daily in conjunction with standard therapy (130 lesions in 71 patients) and those not administered cilostazol (242 lesions in 122 patients). Effects of cilostazol on preventing restenosis after PTA in these patients were investigated.', 'Kaplan-Meier analysis demonstrated the 5-yr patency rate was significantly higher in the cilostazol group than in the control group [52.4 versus 32.9%, hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.39 to 0.77, P = 0.0005]. Cox multivariate analysis revealed that administration of cilostazol was an independent predictor of preventing restenosis (HR 0.56, 95% CI 0.36 to 0.87, P = 0.010). In 102 lesions matched after propensity score analysis, cilostazol had a beneficial effect on preventing restenosis (58.4 versus 34.7%, HR 0.47, 95% CI 0.30 to 0.75, P = 0.0017) and was an independent predictor of preventing restenosis (HR 0.50; 95% CI 0.26 to 0.87, P = 0.014) after multivariate Cox analysis.'] Does cilostazol improve long-term patency after percutaneous transluminal angioplasty in hemodialysis patients with peripheral artery disease? | qiaojin/PubMedQA | 2 | [
-1.6750165224075317,
-1.6054646968841553,
2.2748475074768066
] |
['Freud implied a link between inability to have a vaginal orgasm and psychosexual immaturity. Since Kinsey, many sexologists have asserted that no such link exists. However, empirical testing of the issue has been lacking.', 'The objective was to determine the relationship between different sexual behavior triggers of female orgasm and use of immature psychological defense mechanisms.', 'Women reported their past month frequency of different sexual behaviors and corresponding orgasm rates and completed the Defense Style Questionnaire (DSQ-40).', 'The association between ability to have vaginal intercourse orgasm (versus clitoral orgasm) and the use of DSQ-40 immature psychological defense mechanisms (associated with various psychopathologies) was examined.', 'In a sample of 94 healthy Portuguese women, vaginal orgasm (triggered solely by penile-vaginal intercourse) was associated with less use of DSQ-40 immature defenses. Vaginal orgasm was associated with less somatization, dissociation, displacement, autistic fantasy, devaluation, and isolation of affect. Orgasm from clitoral stimulation or combined clitoral-intercourse stimulation was not associated with less use of immature defenses, and was associated with more use of some immature defenses. In one regression analysis, more masturbation and less vaginal orgasm consistency made independent contributions to the statistical prediction of immature defenses. In another regression analysis, any use of extrinsic clitoral stimulation for intercourse orgasm, and lack of any vaginal orgasm, made independent contributions to the statistical prediction of immature defenses. Vaginally anorgasmic women had immature defenses scores comparable to those of established (depression, social anxiety disorder, panic disorder, and obsessive-compulsive disorder) outpatient psychiatric groups. Results were not confounded by social desirability responding or relationship quality.'] Is vaginal orgasm associated with less use of immature psychological defense mechanisms? | qiaojin/PubMedQA | 2 | [
-2.4736411571502686,
-0.6384721994400024,
2.170553207397461
] |
['Recent international prevalence studies of pelvic pain in men have estimates ranging between 2% and 10%. These studies conclude that it is an important international health problem.', "The aims of this study were to establish the first population-based study of pelvic pain in Australian men, and identify correlates with men's sexual and reproductive histories and other health conditions.", 'A representative household sample of 4,290 Australian men aged 16-64 years completed a computer-assisted telephone interview. They were asked about their experiences of pain in the pelvic region during the past 12 months.', 'Prevalence of correlates of pain associated with sexual intercourse, pain associated with urination, and pelvic pain not associated with intercourse or urination.', 'Five percent of men reported pain during urination, 5% reported pain related to sexual intercourse, and 12% of men reported other chronic pelvic pain. There was little overlap in reporting any of the three types of pelvic pain, with 18% of men reporting some form of pelvic pain. Men reporting any of the pain conditions were significantly more likely than other men to report a sexual experience when they had felt forced or frightened. Men reporting pain during intercourse and/or chronic pelvic pain were significantly more likely than other men to report same sex experience. All three groups of men with pelvic pain were more likely than other men to report some form of sexual difficulties. A report of ever receiving a diagnosis of depression or a report of anxiety was significantly associated with all forms of pelvic pain.'] Does prevalence and correlate of three types of pelvic pain in a nationally representative sample of Australian men? | qiaojin/PubMedQA | 1 | [
-0.7210850715637207,
0.11775089800357819,
-0.12923341989517212
] |
['Ozone (O(3)) exposure evokes asthma exacerbations by mechanisms that are poorly understood. We used a murine model to characterize the effects of O(3) on allergic airway inflammation and hyperresponsiveness and to identify factors that might contribute to the O(3)-induced exacerbation of asthma.', 'BALB/c mice were sensitized and challenged with Aspergillus fumigatus (Af). A group of sensitized and challenged mice was exposed to 3.0 ppm of O(3) for 2 h and studied 12 h later (96 h after Af challenge). Naive mice and mice exposed to O(3) alone were used as controls. Bronchoalveolar lavage (BAL) cellular and cytokine content, lung function [enhanced pause (P(enh))], isometric force generation by tracheal rings and gene and protein expression of Fas and FasL were assessed. Apoptosis of eosinophils was quantified by FACS.', 'In sensitized mice allergen challenge induced a significant increase of P(enh) and contractile force in tracheal rings that peaked 24 h after challenge and resolved by 96 h. O(3) inhalation induced an exacerbation of airway hyperresponsiveness accompanied by recurrence of neutrophils and enhancement of eosinophils 96 h after allergen challenge. The combination of allergen and O(3) exposure inhibited Fas and FasL gene and protein expression and eosinophil apoptosis and increased interleukin-5 (IL-5), granulocyte-macrophage-colony stimulating factor (GM-CSF) and G-CSF protein levels.'] Does ozone inhalation induce exacerbation of eosinophilic airway inflammation and hyperresponsiveness in allergen-sensitized mice? | qiaojin/PubMedQA | 2 | [
-2.4194352626800537,
-1.3059415817260742,
2.75213360786438
] |
['Airway epithelial cells have shown to be active participants in the defense against pathogens by producing signaling and other regulatory molecules in response to the encounter.', 'In previous manuscripts, we have studied the effect of house dust mite (HDM) extract on both an epithelial cell-line (H292) and primary nasal epithelial cell. When we compare these responses we conclude that the H292 cells more closely resemble nasal epithelium of healthy controls (share 107 probe-sets) than of allergic individuals (share 17 probe-sets).', 'Interestingly, probably because of an absent intraindividual variation between samples, more probe-sets (8280) change expression significantly in H292 than in either healthy (555) or allergic (401) epithelium.'] Does comparison of expression profiles induced by dust mite in airway epithelia reveal a common pathway? | qiaojin/PubMedQA | 2 | [
-2.4663209915161133,
-0.7692277431488037,
2.376352310180664
] |
['The current treatments for hepatocellular carcinoma (HCC) are poor, particularly for metastatic HCC. Intraportal transfusion of adeno-associated virus (AAV) leads to long-term and persistent transgenic expression in livers. Kallistatin, a novel angiogenesis inhibitor, exhibits anti-tumor activity. The aim of the study was to investigate whether intraportal injection of AAV-kallistatin could suppress local and metastatic HCC in mice.', 'An AAV vector encoding kallistatin was constructed, and its transduction efficiency by intraportal transfusion in livers was examined by RT-PCR, immunohistochemical and Western blotting analysis. The anti-tumor activity was tested in three HCC models including hepatic and subcutaneous human Hep3B HCC tumors in BALB/c athymic (nu/nu) mice, and subcutaneous mouse BNL HCC tumors in BALB/c mice. Tumor cell proliferation in situ was examined by anti-Ki-67 staining, and apoptosis by TUNEL.', 'Gene transfection by rAAV-kallistatin inhibited proliferation of human umbilical vein endothelial cells and HCC cells in vitro. Intraportal injection of rAAV-kallistatin resulted in persistent and specific expression of kallistatin in livers detected by RT-PCR and immunohistochemical analysis, and kallistatin protein in circulation detected by Western blotting analysis. Intraportal injection of rAAV-kallistatin significantly suppressed angiogenesis and growth of hepatic Hep3B tumors. The kallistatin released by hepatocytes into the circulation suppressed remote Hep3B and BNL tumors established subcutaneously. The rAAV-kallistatin gene therapy significantly inhibited tumor cell proliferation and induced apoptosis.'] Does adeno-associated virus-mediated expression of kallistatin suppress local and remote hepatocellular carcinomas? | qiaojin/PubMedQA | 2 | [
-2.4006330966949463,
-1.3748512268066406,
2.828409433364868
] |
['To determine the differential impact of maternal and paternal internalizing psychopathology on cognitive-behavioural treatment (CBT) outcome of anxiety-disordered children and adolescents.', 'Participants consisted of 127 children and 51 adolescents with a primary anxiety diagnosis. Children were randomly assigned to a standardized group CBT or individual CBT; adolescents received individual CBT. Parents received four training sessions. Participants were evaluated at pre- and post-treatment with a clinical interview and with self- and parent-reported questionnaires. Lifetime anxiety and mood disorders in parents were obtained with a clinical interview.', 'For children, no associations were found between maternal and paternal anxiety or mood disorders and treatment outcome. For adolescents, however, maternal lifetime anxiety disorders were positively associated with pre-post-treatment improvement in clinician severity ratings and with treatment success.'] Does maternal anxiety predict favourable treatment outcomes in anxiety-disordered adolescents? | qiaojin/PubMedQA | 1 | [
-2.25453782081604,
1.3040754795074463,
0.1642886847257614
] |
['A four-amino acid deletion was identified within the alpha 2C-adrenergic receptor (alpha 2C Del322-325) that, when homozygous, increases the risk of heart failure in African-Americans nearly six-fold. We hypothesised that homozygosity for the alpha 2C Del322-325 polymorphism may be a risk factor for heart failure due to idiopathic dilated cardiomyopathy (DCM) in black South Africans.', 'The alpha 2C Del322-325 polymorphism was genotyped in 37 patients with heart failure and 34 controls, all of black African ancestry. Genotyping was performed by a size-fractionation assay.', 'The patients studied ranged in age from 21 to 79 years with a mean age of 50 years, and 62% were male. No significant difference was observed in homozygosity for the alpha 2C Del322-325 polymorphism or in allele and genotype frequencies between patients and controls. The frequency of the allele containing the deletion was 0.54 in cases and 0.53 in controls. The genotype frequencies in the patients were consistent with those of the controls (p = 0.56).'] Is the alpha 2C Del322-325 adrenergic receptor polymorphism associated with heart failure due to idiopathic dilated cardiomyopathy in black Africans? | qiaojin/PubMedQA | 2 | [
-1.828221321105957,
-1.341094970703125,
2.175636053085327
] |
['Evidence of a role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of eating disorders (ED) has been provided by association studies and by murine models. BDNF plasma levels have been found altered in ED and in psychiatric disorders that show comorbidity with ED.', 'Since the role of BDNF levels in ED-related psychopathological symptoms has not been tested, we investigated the correlation of BDNF plasma levels with the Symptom Checklist 90 Revised (SCL-90R) questionnaire in a total of 78 ED patients.', 'BDNF levels, measured by the enzyme-linked immunoassay system, and SCL-90R questionnaire, were assessed in a total of 78 ED patients. The relationship between BDNF levels and SCL-90R scales was calculated using a general linear model.', 'BDNF plasma levels correlated with the Global Severity Index and the Positive Symptom Distress Index global scales and five of the nine subscales in the anorexia nervosa patients. BDNF plasma levels were able to explain, in the case of the Psychoticism subscale, up to 17% of the variability (p = 0.006).'] Do blood levels of brain-derived neurotrophic factor correlate with several psychopathological symptoms in anorexia nervosa patients? | qiaojin/PubMedQA | 2 | [
-2.035048246383667,
-1.2504456043243408,
2.274897336959839
] |
['The aim of this study was to investigate the effect of a topical FK506 nanospheric suspension in a rat model of penetrating keratoplasty.', 'FK506 nanospheres were prepared by using a biodegradable poly (lactic-co-glycolic acid) copolymer (PLGA). Its distribution in the eye and blood after a single instillation was examined in rabbits. Sprague-Dawley (SD) rats received corneal heterografts and were topically treated with phosphate-buffered saline (PBS), PLGA, FK-506 0.01% (nanospheres), or dexamethasone 0.05% solutions twice a day for 28 days. Rejection index and graft-survival time were recorded and compared between the four groups. Three grafts were collected at different time points for immunohistochemical studies.', 'In the cornea, the FK-506 concentration reached its peak within 1 h of a single eye-drop instillation and then decreased by half (1667.85 +/- 611.87 ng/g) at 8 h. FK-506 cannot be detected in rabbit blood. There were significant differences in the graft-survival time between the FK-506 nanosphere group (15.09 +/- 4.81 days) and the other three groups [PBS (7.90 +/- 1.20, t = -4.594, P < 0.001), PLGA (8.44 +/- 0.88, t = - 4.074, P = 0.001) and dexamethasone (10.44 +/- 1.42, t = -2.790, P = 0.012)]. The rejected corneas in the FK506 nanosphere group showed significantly fewer CD4, CD8, CD68, CD79, vascular endothelial growth factor, ICAM, and tumor growth factor-beta(1)-positive cells than those in the other groups.'] Does preliminary study of the effect of FK506 nanospheric-suspension eye drop on rejection of penetrating keratoplasty? | qiaojin/PubMedQA | 2 | [
-1.793815016746521,
-1.613610863685608,
2.4320950508117676
] |
['We previously showed epidermal growth factor receptor (EGFR) transactivation to be key mechanism in the regulation of resistance artery myogenic tone. Type 2 diabetes is associated with microvascular complications. We hypothesized that elevated EGFR phosphorylation contributes to resistance artery dysfunction in type 2 diabetes.', 'Diabetic db/db and nondiabetic (control) mice were treated with EGFR inhibitor (AG1478; 10 mg x kg(-1) x day(-1)) for 2 weeks. Isolated coronary artery and mesenteric resistance artery (MRA) were mounted in an arteriograph. Pressure-induced myogenic tone was increased in MRA and coronary artery from diabetic mice and normalized by AG1478. Phenylephrine-induced contraction and nitric oxide donor-induced relaxation were similar in all groups. Endothelium-dependent relaxation in response to shear stress and acetylcholine of MRA and coronary artery from diabetic mice was altered and associated with reduced endothelial nitric oxide synthase (eNOS) expression and phosphorylation. Treated diabetic mice with AG1478 improved coronary artery and MRA endothelial function and restored eNOS expression. Immunostaining and Western blot analysis showed increased endothelial and smooth muscle cell EGFR phosphorylation of MRA and coronary artery from diabetic mouse, which was reduced by AG1478. Primary cultured endothelial cells from resistance arteries treated with high glucose for 48 h showed an increase of EGFR phosphorylation associated with eNOS expression and phosphorylation decrease in response to calcium ionophore. Pretreatment of endothelial cells with AG1478 prevented the effect of high glucose.'] Does elevated epidermal growth factor receptor phosphorylation induce resistance artery dysfunction in diabetic db/db mice? | qiaojin/PubMedQA | 2 | [
-2.3904168605804443,
-1.3810468912124634,
2.816102981567383
] |
['The precise molecular targets of IFN-alpha therapy of melanoma are unknown but likely involve signal transducer and activator of transcription (STAT) 1 signal transduction within host immune effector cells. We hypothesized that intermediate and high doses of IFN-alpha would be equally effective in activating patient immune cells.', 'Eleven metastatic melanoma patients who were enrolled in a clinical trial of bevacizumab in combination with escalating doses of IFN-alpha-2b (5 megaunits/m(2) and then 10 megaunits/m(2)) were included in the study. Peripheral blood mononuclear cells (PBMC) were procured from patient blood just before therapy and again 1 h after each dose of IFN-alpha-2b and analyzed for the presence of phosphorylated STAT1, phosphorylated STAT2, and the induction of IFN-stimulated gene (ISG) transcripts.', 'Phosphorylated STAT1 was significantly greater at the 5 megaunits/m(2) dose compared with the 10 megaunits/m(2) dose of IFN-alpha-2b (P = 0.02). In contrast, no significant difference in phosphorylated STAT2 was observed at a dose of 5 megaunits/m(2) compared with 10 megaunits/m(2) (P = 0.20). There were also no significant differences in the induction of ISGs within PBMCs between the two doses (P > 0.4 for all ISGs). Suppressor of cytokine signaling 1 and 3 (two inhibitors of IFN-alpha signaling) transcripts were significantly higher among patient PBMCs following the 10 megaunits/m(2) dose of IFN-alpha (P < 0.001).'] Is iFN-alpha-2b-induced signal transduction and gene regulation in patient peripheral blood mononuclear cells enhanced by a dose increase from 5 to 10 megaunits/m2? | qiaojin/PubMedQA | 2 | [
-1.7361279726028442,
-1.602859377861023,
2.3329341411590576
] |
['While the phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway is typically known to regulate cell growth and survival, emerging evidence suggest a role for this pathway in regulating the behavioural responses to addictive drugs.', 'To investigate whether PI3K contributes to patterns of risky alcohol drinking in human, we investigated genetic variations in PIK3R1, encoding the 85 kD regulatory subunit of PIK, in 145 family trios consisting of 15-16 year old adolescents and their parents. Screening for mutations in exons, exon-intron boundaries and regulatory sequences, we identified 14 single nucleotide polymorphisms (SNPs) in the PIK3R1 gene region from exon 1 to the beginning of the 3\' untranslated region (UTR). These SNPs defined haplotypes for the respective PIK3R1 region. Four haplotype tagging (ht)SNPs (rs706713, rs2302975, rs171649 and rs1043526), discriminating all haplotypes with a frequency >or=4.5% were identified. These htSNPs were used to genotype adolescents from the "Mannheim Study of Risk Children" (MARC). Transmission disequilibrium tests in these adolescents and their parents demonstrated sex-specific association of two SNPs, rs2302975 and rs1043526, with patterns of risky alcohol consumption in male adolescents, including lifetime prevalence of drunkenness (p = 0.0019 and 0.0379, respectively) and elevated maximum amount of drinking (p = 0.0020 and 0.0494, respectively), as a measure for binge drinking pattern.'] Does nucleotide sequence variation within the PI3K p85 alpha gene associate with alcohol risk drinking behaviour in adolescents? | qiaojin/PubMedQA | 2 | [
-2.081685781478882,
-1.3141231536865234,
2.4087319374084473
] |
['Hyperhomocysteinaemia is independently associated with atherosclerotic disease. Methionine loading could improve the predictive value of hyperhomocysteinaemia by detecting mild disturbances in enzyme activity. The aims of this study were to determine the beneficial effect of methionine loading on the predictive value of homocysteine testing for long-term mortality and major adverse cardiac events (MACE).', 'In an observational study, 1122 patients with suspected or known vascular disease, underwent homocysteine testing, which was measured fasting and again 6 h after methionine loading. Hyperhomocysteinaemia was defined as a fasting level > or =15 micromol/L and post-methionine loading level > or =45 micromol/L or an increase of > or =30 micromol/L above fasting levels. Primary end-points were death and MACE. Multivariate Cox regression analysis was used, adjusting for all cardiac risk factors.', 'During follow up (mean 8.9 +/- 3.4 years), 98 patients died (8.7%), 86 had a MACE (7.7%), 579 patients had normal tests, 134 patients had only fasting hyperhomocysteinaemia, 226 only post-methionine hyperhomocysteinaemia and 183 patients had both. In multivariate analysis, overall survival and MACE-free survival were significantly worse for those with fasting hyperhomocysteinaemia, with hazard ratios of 1.86 (95% confidence interval (CI) 1.20-2.87) and 2.24 (95%CI 1.41-3.53), respectively. The addition of hyperhomocysteinaemia after methionine loading did not significantly increase the risk of death or MACE, with hazard ratios of 0.97 (95%CI 0.52-1.81) and 0.89 (95%CI 0.47-1.69), respectively.'] Does methionine loading enhance the predictive value of homocysteine serum testing for all-cause mortality or major adverse cardiac events? | qiaojin/PubMedQA | 2 | [
-1.303061842918396,
-1.5945932865142822,
1.8860574960708618
] |
['C-reactive protein (CRP) is an acute phase protein synthesized by the liver primarily in response to interleukin-6. Initial studies have suggested that inflammatory markers may have a role in predicting severity. We investigated whether admission and day 4 CRP could predict severity in community-acquired pneumonia.', 'A prospective study was carried out over a 2-year period in a large teaching hospital. CRP was measured on admission and on day 4. The outcomes of interest were: 30-day mortality; need for mechanical ventilation and/or inotropic support; development of complicated pneumonia (lung abscess, empyema, or complicated parapneumonic effusion); the value of predictive tests were assessed using multivariate logistic regression.', 'There were 570 patients included in the study; 30-day mortality was 9.6%. Low CRP levels showed a high negative predictive value for excluding 30-day mortality (CRP <10 mg/L=100%, CRP <50=99.1%, CRP <100=98.9%, CRP <200=94.9%). Low admission CRP levels <100 mg/L were independently associated with reduced 30-day mortality (odds ratio [OR] 0.18; 0.04-0.85), P=.03; need for mechanical ventilation and/or inotropic support (OR 0.21; 0.14-0.4), P=.002; and complicated pneumonia (OR 0.05; 0.01-0.35), P=.003. A CRP that fails to fall by 50% or more within 4 days of admission is independently associated with increased 30 day mortality (OR 24.5; 6.4-93.4), P <.0001; need for mechanical ventilation and/or inotropic support (OR 7.1; 2.8-17.8), P <.0001 and complicated pneumonia (OR 15.4; 6.32-37.6), P <.0001.'] Is c-reactive protein an independent predictor of severity in community-acquired pneumonia? | qiaojin/PubMedQA | 2 | [
-0.7589257955551147,
-1.818011999130249,
1.5505930185317993
] |
["A significant percentage of patients with Parkinson's disease (PD) continue to experience motor fluctuations and dyskinesias despite the association of dopamine agonists and levodopa with COMT or MAO-B inhibitors. The use of apomorphine infusion is limited by compliance while deep brain stimulation is feasible only for a small number of patients mostly because of age constraints.", 'To assess prospectively the effectiveness of duodenal levodopa infusion on quality of life as well as motor features in patients with advanced PD. In all but 1 case levodopa infusion was stopped at nighttime.', 'We report the outcome of 22 PD patients, followed for up to 2 years, who were on continuous duodenal levodopa/carbidopa infusion through percutaneous endoscopic gastrostomy.', "We found a significant reduction in 'off' period duration as well as dyskinesia severity (Unified Parkinson's Disease Rating Scale part IV, items 33 and 39). There was significant improvement in the 39-item Parkinson's Disease Quality of Life Questionnaire as well as in the Unified Parkinson's Disease Rating Scale part II up to the 2-year follow-up. Five patients withdrew: 2 for poor compliance and 3 for adverse events (1 was related to percutaneous endoscopic gastrostomy)."] Does duodenal levodopa infusion improve quality of life in advanced Parkinson 's disease? | qiaojin/PubMedQA | 2 | [
-2.378312349319458,
-1.0042979717254639,
2.4317562580108643
] |
['The interindividual variation in metabolism of inorganic arsenic (iAs), involving methylation via one-carbon metabolism, has been well documented, but the reasons remain unclear.', 'In this population-based study we aimed to elucidate the effect of nutrition on As methylation among women in Matlab, Bangladesh, where people are chronically exposed to iAs via drinking water.', 'We studied effects of macronutrient status using body mass index (BMI) among 442 women in early pregnancy (gestational week 8), and effects of micronutrient status (plasma folate, vitamin B12, zinc, ferritin, and selenium) among 753 women at gestational week 14. Arsenic metabolites in urine were measured by HPLC combined with hydride generation inductively coupled plasma mass spectrometry.', 'The median concentration of As in urine was 97 microg/L (range, 5-1,216 microg/L, adjusted by specific gravity). The average proportions of iAs, monomethylarsonic acid, and dimethylarsinic acid in urine in gestational week 8 were 15%, 11%, and 74%, respectively. Thus, the women had efficient As methylation in spite of being poorly nourished (one-third had BMIs < 18.5 kg/m2) and having elevated As exposure, both of which are known to decrease As methylation. The metabolism of iAs was only marginally influenced by micronutrient status, probably because women, especially in pregnancy and with low folate intake, have an efficient betaine-mediated remethylation of homocysteine, which is essential for an efficient As methylation.'] Does nutritional status have marginal influence on the metabolism of inorganic arsenic in pregnant Bangladeshi women? | qiaojin/PubMedQA | 2 | [
-2.1735196113586426,
-1.1649514436721802,
2.374420642852783
] |
['To show that heparin cryoprecipitation (HCP), an in vitro method of plasma purification, reduces the levels of in vivo modified proteins and non-traditional risk factors from plasma of atherosclerotic hemodialysis (HD) patients.', 'HCP was applied to plasma obtained from HD patients and controls, forming a precipitate--cryogel. Levels of fibrinogen, albumin, CRP, TNF-alpha, IL-6, advanced oxidation protein products, carbonylated fibrinogen and carbonylated albumin were determined in plasma before and after applying HCP and in the cryogel.', 'Treatment of HD plasma with HCP, beyond the significant reduction of the increased levels of all the above-mentioned molecules, reduced fibrinogen, TNF-alpha, carbonylated fibrinogen and carbonylated albumin to control levels which were simultaneously found in the cryogel.'] Does heparin cryoprecipitation reduce plasma levels of non-traditional risk factors for atherosclerosis in vitro? | qiaojin/PubMedQA | 2 | [
-2.656726598739624,
-1.1159014701843262,
2.8347716331481934
] |
['Interferons (IFNs) are known to have antiproliferative and immunoregulatory activities that are modulated through specific cell surface ligands, known as IFN-alpha, -beta, and -gamma receptors. The presence of these receptors and their impact on response to adjuvant therapy in patients with pancreatic cancer has not been determined.', 'Slides were prepared from 46 patients with pancreatic adenocarcinoma. Immunohistochemistry (IHC) was subsequently used to determine the expression of IFN- alpha/beta receptor-chain 2 (IFN-alpha/betaR) and IFN-gamma receptor-chain 1 (IFN-gammaR). The correlation between IFN receptor expression, tumor characteristics, and the overall patient response to adjuvant therapy were determined analytically.', 'The IHC performed for pancreatic adenocarcinoma demonstrated a high IFN-alpha/betaR expression in 4% (2/46) of patients, moderate expression in 20% (9/46) of patients, and faint or no expression in 76% (35/46) of patients. IHC confirmed a high expression of IFN-gammaR in 52% (24/46) of patients, moderate expression in 35% (16/46) of patients, and faint or no expression in the remaining 13% (6/46) of patients. Thirty-two (69.7%) patients received adjuvant therapy. Clinicopathological survey did not demonstrate any significant correlation between IFN-alpha/betaR and IFN-gammaR expression with regard to tumor size, vascular invasion, perineural invasion, lymph node metastases, or stage of disease. Use of adjuvant therapy was associated with increased survival in patients with IFN-alpha/betaR-positive tumors compared with patients with IFN-alpha/betaR-negative tumors (24 months versus 14.7 months in log rank test, p=0.012). The expression of IFN-gammaR, however, had no impact on patient survival (20 months vs 17 months; p=0.656, log rank test).'] Is interferon receptor alpha/beta associated with improved survival after adjuvant therapy in resected pancreatic cancer? | qiaojin/PubMedQA | 2 | [
-2.115257501602173,
-1.4531340599060059,
2.5653553009033203
] |
['To investigate the effects of endothelin (ET)-1 on fast axonal transport in the optic nerve.', 'Sterile sponge soaked in 1 nM ET-1 was applied to the optic nerve surface of adult Brown Norway rats for 1 hour, after which 20% horseradish peroxidase (HRP) was placed over the superior colliculi (SC). Rats were killed 2, 4, 6, 24, and 48 hours later; the retinas and optic nerves were removed and fixed; and cut sections were processed histochemically, to visualize the time course of HRP transport by light microscopy. Naive and saline controls were processed identically. Retinal ganglion cell (RGC) survival after acute ET-1 application was investigated in another group of animals. After retrograde labeling of RGCs with the fluorescent neurotracer Fluorochrome (FG; Fluorogold; Fluorochrome Inc., Denver, CO), 1 nM ET-1 was applied to the optic nerve. Rats were then killed 5, 10, and 21 days later. The retinas were whole mounted and FG-positive RGCs were imaged and quantified with fluorescence microscopy.', 'In naive controls, HRP labeling was observed over the entire nerve at 2 hours but had cleared by 48 hours. HRP labeling of RGCs started at 6 hours, and by 48 hours, uniform labeling was seen throughout the retina. In ET-1-treated optic nerves, transport of HRP was arrested at the distal portion of the nerve at 2 hours. Recovery of transport was evident from 4 hours. At 6 and 24 hours, all nerves showed full recovery with HRP-positive RGCs in the retina, but the ratio of the RGC counts in treated versus fellow untreated eyes (0.66 +/- 0.13 and 0.67 +/- 0.17, respectively) was less than that of the naive control (1.02 +/- 0.28 and 1.05 +/- 0.13, respectively) animals. At 48 hours, recovery was complete, and there was no significant difference in the ratio of RGC counts between ET-1 and naive control groups. No RGC loss was observed after ET-1 application.'] Does acute endothelin-1 application induce reversible fast axonal transport blockade in adult rat optic nerve? | qiaojin/PubMedQA | 2 | [
-1.8586782217025757,
-1.5852859020233154,
2.405921697616577
] |
['MK-0873 is a novel selective phosphodiesterase-4 inhibitor, which has been in development for the treatment of chronic obstructive pulmonary disease (COPD). In this indication, theophylline is still an important treatment, despite its relatively small therapeutic window. In view of this, it is important to investigate whether MK-0873 could affect the pharmacokinetics, safety and tolerability of theophylline, when both drugs are given concomitantly.', 'The objective of this study was to investigate the effect of multiple doses of oral MK-0873, a selective phosphodiesterase-4 inhibitor, on the pharmacokinetics, safety and tolerability profile of orally administered theophylline in healthy volunteers.', 'Eight healthy, non-smoking male subjects participated in this randomized, open-label, 2-period, cross-over study. In one period subjects received an oral dose of 2.5mg MK-0873 for 6 days co-administered with a single oral dose of 250 mg theophylline on day 5. The other period consisted of a single dose of 250 mg theophylline on day 1. In each period, blood samples were collected at predefined time points to evaluate theophylline pharmacokinetics.', 'All subjects completed the study. The study medications were generally well tolerated and no clinically relevant changes were observed in either treatment periods. No significant difference was found in the AUC 0-infinity (77.7 vs. 83.8h ng/ml; p=0.280) and Cmax (6.70 vs. 7.77 ng/ml; p=0.125) of theophylline between the MK-0873+theophylline and theophylline only treatment, and bioequivalence was demonstrated for AUC0-infinity (geometric mean ratio with 90% confidence interval: 0.930 (0.826, 1.047)).'] Does mK-0873 , a PDE4 inhibitor , influence the pharmacokinetics of theophylline in healthy male volunteers? | qiaojin/PubMedQA | 2 | [
-1.7665005922317505,
-1.5221710205078125,
2.322741985321045
] |
['During preconditioning by tumour necrosis factor-alpha (TNFalpha), activation of the signal transducer and activator of transcription-3 (STAT-3) but not Akt, is essential, whereas ischaemic cardiac preconditioning (IPC) requires both STAT-3 and Akt at the time of reperfusion. However, it is not known whether the same signalling pattern occurs during the preconditioning stimulus (trigger phase) and whether links exist between STAT-3 and Akt. Hence, our hypothesis is that concomitant activation or co-interaction between these two key signals is required during the trigger phase for IPC. Conversely, we proposed that there would be no such interaction when preconditioning was induced by TNFalpha (TNF-PC).', 'Cardiomyocytes, isolated from adult wild-type (WT) and cardiac-specific STAT-3 knockout (KO) mice, were exposed to simulated ischaemia (SI) reperfusion. Cells were preconditioned either by 30 min SI or by 30 min TNFalpha (0.5 ng/mL) in the presence or absence of AG490 (100 nM) or wortmannin (100 nM) to inhibit STAT-3 or Akt, respectively. Cell viability was evaluated by trypan blue, and phosphorylation levels of STAT-3 and Akt were measured by Western blot analysis. Similar experiments were conducted in isolated rat hearts subjected to an ischaemia-reperfusion insult. Both preconditioning stimuli failed to protect KO cardiomyocytes, and addition of AG490 abolished preconditioning in WT cardiomyocytes or isolated hearts. Wortmannin abolished the protection afforded by IPC, but did not affect TNF-PC in both models. Western blot analysis demonstrated that added wortmannin during IPC stimulus decreased STAT-3 phosphorylation while, conversely, AG490 reduced Akt phosphorylation.'] Is dual activation of STAT-3 and Akt required during the trigger phase of ischaemic preconditioning? | qiaojin/PubMedQA | 2 | [
-2.231945514678955,
-1.3907053470611572,
2.66074275970459
] |
['To examine the incidence of imageable metastases at the time of biochemical recurrence after radical prostatectomy and to determine whether prostate-specific antigen doubling time (PSADT) reliably predicts these imageable metastases.', 'Between October 2000 and October 2005, 1112 men underwent open radical retropubic prostatectomy by a single surgeon. All men were advised to undergo bone scintigraphy and an abdominal/pelvic imaging study at the time of biochemical recurrence. We ascertained the sensitivity, specificity, and positive and negative predictive values of a PSADT cut-point of 3 months to predict the presence of imageable metastases.', 'Seventy-four (6.7%) men developed a biochemical recurrence and imageable metastases were demonstrable in 7 cases. Imageable metastases were identified in 11.3% and 7.5% of men undergoing bone scans and abdominal/pelvic imaging, respectively. Extracapsular extension, and older age positive surgical margins, and PSADT were associated with a significantly greater risk of exhibiting imageable metastases. The sensitivity, specificity, and positive and negative predictive values of a PSADT cut-point of 3 months for predicting imageable metastasis were 100%, 98.0%, 87.5%, and 100%, respectively.'] Is prostate-specific antigen doubling time a reliable predictor of imageable metastases in men with biochemical recurrence after radical retropubic prostatectomy? | qiaojin/PubMedQA | 2 | [
-2.1579301357269287,
-1.346569538116455,
2.5599257946014404
] |
['Low-level laser therapy (LLLT) is a known modulator of inflammatory process. Herein we studied the effect of 660 nm diode laser on mRNA levels of neutrophils anti-apoptotic factors in lipopolysaccharide (LPS)-induced lung inflammation. STUDY DESIGN/METHODOLOGY: Mice were divided into 8 groups (n=7 for each group) and irradiated with energy dosage of 7.5 J/cm(2). The Bcl-xL and A1 mRNA levels in neutrophils were evaluated by Real Time-PCR (RT-PCR). The animals were irradiated after exposure time of LPS.', 'LLLT and an inhibitor of NF-kappaB nuclear translocation (BMS 205820) attenuated the mRNA levels of Bcl-xL and A1 mRNA in lung neutrophils obtained from mice subjected to LPS-induced inflammation.'] Does low-level laser therapy decrease levels of lung neutrophils anti-apoptotic factors by a NF-kappaB dependent mechanism? | qiaojin/PubMedQA | 2 | [
-2.1207115650177,
-1.372943639755249,
2.518195152282715
] |
['The da Vinci tele-robot necessitates the acquisition of new skills and surgical educators must develop standardized training programmes. It is possible that virtual reality (VR) computer simulation maybe used and it is necessary to define whether a simulator is an appropriate tool.', 'Ten surgical novices performed a series of five tasks, ten times on a commercially available VR robotic simulator. Two experts repeated the series of tasks twice in an attempt to validate the simulator.', 'Each of the five tasks displayed statistically significant learning curves. Error scores did not improve significantly over successive repetitions except in one task. The experts completed two of the tasks in a significantly faster time.'] Does short-phase training on a virtual reality simulator improve technical performance in tele-robotic surgery? | qiaojin/PubMedQA | 1 | [
-1.3083947896957397,
2.1226227283477783,
-1.433062195777893
] |
["In school-based samples of children, the Children's Eating Attitudes Test (ChEAT) has a four-factor structure; however, previous studies have not examined its factor structure in samples restricted to overweight youth.", 'The ChEAT was administered to 220 overweight (BMI>or=95th percentile) and 45 at-risk for overweight (BMI 85th-<95th percentile) children and adolescents. Factors were identified by a principal component analysis with varimax rotation. ChEAT factor scores of children with BMI>or=85th percentile were contrasted with those of 152 non-overweight (BMI 5th to <85th percentile) children and adolescents.', "Factor analysis generated four subscales described as 'body/weight concern,' 'food preoccupation,' 'dieting,' and 'eating concern.' ChEAT total score, body/weight concern, and dieting subscale scores were positively related to BMI-Z and body fat mass (p's<.05). Compared to non-overweight children, overweight and at-risk for overweight children had higher ChEAT total (9.9+/-7.4 vs. 6.6+/-7.8, p<.001), body/weight concern (3.2+/-3.1 vs. 1.3+/-3.0, p<.001), and dieting (1.8+/-2.2 vs. .8+/-2.3, p<.001) subscale scores."] Do structure analysis of the Children 's Eating Attitudes Test in overweight and at-risk for overweight children and adolescents? | qiaojin/PubMedQA | 2 | [
-0.9863724708557129,
-0.545875072479248,
0.7127031087875366
] |
['The Rho small guanosine triphosphatase Cdc42 is critical for diverse cellular functions, including regulation of actin organization, cell polarity, intracellular membrane trafficking, transcription, cell-cycle progression, and cell transformation. This implies that Cdc42 might be required for liver function.', 'Mice in which Cdc42 was ablated in hepatocytes and bile duct cells were generated by Cre-loxP technology. Livers were examined by histologic, immunohistochemical, ultrastructural, and serum analysis to define the effect of loss of Cdc42 on liver structure.', 'Mice lacking Cdc42 in their hepatocytes were born at Mendelian ratios. They did not show increased mortality but showed chronic jaundice. They developed hepatomegaly soon after birth, and signs of liver transformation, such as formation of nodules and tumors, became visible macroscopically at age 6 months. Hepatocellular carcinoma was observed 8 months after birth. Tumors grew slowly and lacked expression of nuclear beta-catenin. Lung metastases were observed at the late stage of carcinogenesis. Immunofluorescent examination and electron microscopy revealed severe defects in the liver. At the age of 2 months, the canaliculi between hepatocytes were greatly enlarged, although the tight junctions flanking the canaliculi appeared normal. Regular liver plates were absent. E-cadherin expression pattern and gap junction localization were distorted. Analysis of serum samples indicated cholestasis.'] Does continuous cell injury promote hepatic tumorigenesis in cdc42-deficient mouse liver? | qiaojin/PubMedQA | 2 | [
-2.5903656482696533,
-1.1573361158370972,
2.839130401611328
] |
["Intestinal fibrosis and stricture formation are serious complications of Crohn's disease, often requiring surgical intervention. Unfortunately, the mechanisms underlying intestinal fibrosis development are poorly understood, in part because of the lack of relevant animal models. Here, we present a novel murine model of severe and persistent intestinal fibrosis caused by chronic bacterial-induced colitis.", "Mice were treated with streptomycin 24 hours prior to oral infection with Salmonella enterica serovar Typhimurium. Tissues were analyzed for bacterial colonization and inflammation, and fibrosis was assessed by Masson's trichrome staining and collagen quantification. Expression of the profibrotic cytokines transforming growth factor-beta1, connective tissue growth factor and insulin-like growth factor-I was determined, and the cell types present in fibrotic tissues were assessed by immunohistochemistry.", 'Infection led to chronic Salmonella colonization of the cecum and colon followed by edema, mucosal ulcerations, and severe transmural inflammation. This pathology was accompanied by significantly elevated expression of transforming growth factor-beta1, connective tissue growth factor, and insulin-like growth factor-I along with extensive type I collagen deposition in the cecal mucosa, submucosa, and muscularis mucosa of infected mice. Fibrosis was evident by 7 days postinfection, peaking at day 21 and still present at day 70. The fibrotic regions were found to be rich in fibroblasts and myofibroblasts.'] Does chronic enteric salmonella infection in mice lead to severe and persistent intestinal fibrosis? | qiaojin/PubMedQA | 2 | [
-2.5445520877838135,
-1.2108607292175293,
2.8492841720581055
] |
['Several lines of evidence indicate a role for inflammatory processes in the development of cerebral aneurysms. Recently, polymorphisms in the promoter region of the interleukin 6 (IL6) gene were shown to be associated with intracranial aneurysmal disease. The purpose of this study was to verify the association of two functionally active polymorphisms (-174 G>C and -572 G>C) in the promoter region of the IL6 gene with the risk and clinical features of aneurysmal subarachnoid haemorrhage (SAH) in an Italian population.', 'A total of 179 consecutive aneurysmal SAH patients and 156 healthy controls were involved in the study. Cases and controls were genotyped for the -174 G<C and the -572 G<C biallelic polymorphisms of the IL6 gene. The frequencies of different promoter haplotypes were compared between cases and controls.', 'Allelic and genotypic frequencies of the examined polymorphism were not significantly different between cases and controls. Inferred haplotypes were not significantly different in both groups. Finally, the different IL6 genotypes did not seem to significantly modify the main clinical features of the disease.'] Are interleukin 6 gene polymorphisms associated with aneurysmal subarachnoid haemorrhage in an Italian population? | qiaojin/PubMedQA | 2 | [
-2.258096218109131,
-1.1774553060531616,
2.3911375999450684
] |
['It has been previously reported that the pollutant sodium sulfite (Na2SO3) can activate airway epithelial cells; however, there is as yet no evidence of any direct relationship between house dust mite allergen exposure and Na2SO3 with regards to the pathogenesis of airway allergy. This study investigated the effect of sulfite on mite-stimulated human airway epithelial cells.', 'The A549 human lung epithelial cell line was used as an in vitro model. Cells were treated with 10 microg/mL mite crude extract for 8 h and/or Na2SO3 (0, 10, 100, 500, 1000 and 5000 microM) for 16 h, and cell adhesion and dissociation on a cell culture plastic surface were quantitated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Changes in cell adhesion were also analyzed by monitoring the expression of the cell surface of adhesion molecules integrin alpha2 (CD49b) and integrin alpha6 (CD49f) using flow cytometry.', 'A549 cells treated with either mite crude extract only or Na2SO3 only did not show a significant increase in dissociation from the cell culture plastic surface. However, when cells were pretreated with mite extract for 8 h, followed by 16-h incubation with various concentrations of Na2SO3, cell dissociation was enhanced in a dose-dependent manner. A dose-dependent decrease of CD49b and CD49f expression was also seen in cells treated with Na2SO3 only and in mite-pretreated cells. Mite treatment decreased CD49b expression, and a cumulative effect was seen in cells further treated with Na2SO3.'] Does the air pollutant sodium sulfite enhance mite crude extract-stimulated detachment of A549 airway epithelium cells? | qiaojin/PubMedQA | 2 | [
-2.362558603286743,
-1.375168800354004,
2.781416416168213
] |
['Apolipoprotein E (APOE) genotypes have been associated with variations in plasma-lipid levels and with response to statins, although the influence of APOE on the response to statins remains controversial, especially in patients with diabetes. We sought to evaluate the association of the APOE genotype with the low-density lipoprotein cholesterol (LDLc)-lowering response to statins, in a large population-based cohort of patients with diabetes.', 'A total of 1383 patients, commencing statins between 1990 and 2006, were identified from the Genetics of Diabetes Audit and Research in Tayside Scotland database. Statin response was determined both by the minimum LDLc achieved, and by the failure of the patients to reach a clinical target LDLc (< or =2 mmol/l). APOE genotype and potential confounding covariates were entered into the linear and logistic regression models.', 'We found an association of APOE genotypes with both baseline and treatment responses. E2 homozygotes achieved lower LDLc levels (mean 0.6; confidence interval: 0.1-1.1 mmol/l) than E4 homozygotes (mean 1.7; confidence interval: 1.4-1.9 mmol/l; P=2.96 x 10). Minimum LDLc was associated by a linear trend with genotype. This relationship remained statistically significant after adjustment for baseline LDLc, adherence, duration, dose, smoking, and age. None of the E2 homozygotes failed to reach the target LDLc, compared with 32% of the E4 homozygotes (P=5.3 x 10).'] Are apolipoprotein E genotypes associated with lipid-lowering responses to statin treatment in diabetes : a Go-DARTS study? | qiaojin/PubMedQA | 2 | [
-1.7767246961593628,
-1.5148004293441772,
2.276549816131592
] |
['Digoxin is a known substrate of ATP-binding cassette B1 (ABCB1/MDR1). The results of studies on the association between ABCB1 polymorphisms and digoxin kinetics, however, remain contradictory. Almost all studies were small and involved only single dose kinetics. The goal of this study was to establish ABCB1 genotype effect on digoxin blood concentrations in a large cohort of chronic digoxin users in a general Dutch European population.', 'Digoxin users were identified in the Rotterdam Study, a prospective population-based cohort study of individuals aged 55 years and above. Digoxin blood levels were gathered from regional hospitals and laboratories. ABCB1 single nucleotide polymorphisms (SNPs) 1236C-->T, 2677G-->T/A, and 3435C-->T were assessed on peripheral blood DNA using Taqman assays. We studied the association between the ABCB1 genotypes and haplotypes, and digoxin blood levels using linear regression models adjusting for potential confounders.', 'Digoxin serum levels and DNA were available for 195 participants (56.4% women, mean age 79.4 years). All three ABCB1 variants were significantly associated with serum digoxin concentration (0.18-0.21 microg/l per additional T allele). The association was even stronger for the 1236-2677-3435 TTT haplotype allele [0.26 mug/l (95% CI 0.14-0.38)], but absent for other haplotypes (CGC allele considered referent), suggesting an interaction of SNPs in a causal haplotype instead of individual SNP effects.'] Are common ATP-binding cassette B1 variants associated with increased digoxin serum concentration? | qiaojin/PubMedQA | 2 | [
-1.756385326385498,
-1.5495387315750122,
2.3380484580993652
] |
['Patients expressing the tacrolimus-metabolizing enzyme, cytochrome P450 (CYP) 3A5, require more tacrolimus to reach target concentrations. We studied the influence of the CYP3A5(*)3 allele, which results in the absence of CYP3A5 protein, on tacrolimus dose and exposure, as well as the incidence of biopsy-proven acute rejection (BPAR) after renal transplantation.', 'A total of 136 patients participating in a prospective, randomized-controlled clinical trial with the primary aim of comparing the efficacy of a fixed-dose versus a concentration-controlled mycophenolate mofetil immunosuppressive regimen, were genotyped for CYP3A5(*)3. The patients described herein, participated in a pharmacogenetic substudy and were all treated with mycophenolate mofetil, corticosteroids and tacrolimus. Tacrolimus predose concentrations (C(0)) were measured on day 3 and 10, and month 1, 3, 6 and 12.', 'Compared with CYP3A5(*)3/(*)3 individuals (n=110), patients carrying at least one CYP3A5(*)1 (wild-type) allele (CYP3A5 expressers; n=26) had a lower tacrolimus C(0) on day 3 only (16.6 versus 12.3 ng/ml, respectively), whereas dose-corrected tacrolimus C(0) were significantly lower in the latter group at all time points. After day 3, the overall daily tacrolimus dose was 68% higher in CYP3A5 expressers (P<0.001). The incidence of BPAR was comparable between CYP3A5 expressers and nonexpressers (8 versus 16%, respectively; P=0.36).'] Is cYP3A5 genotype associated with a higher risk of acute rejection in tacrolimus-treated renal transplant recipients? | qiaojin/PubMedQA | 2 | [
-1.5486936569213867,
-1.7363698482513428,
2.2354445457458496
] |
['For the treatment of unresectable biliary tract carcinoma with hilar biliary stricture, antitumor therapy and biliary stenting should be addressed in terms of prolonged survival with a good quality of life. However, the endoscopic management of malignant hilar biliary strictures is difficult even for an expert endoscopist. We evaluated the efficacy and safety of the endoscopic deployment of multiple JOSTENT SelfX units in patients with hilar biliary strictures treated with or without chemotherapy.', 'Between November 2003 and December 2006, endoscopic deployment of multiple JOSTENT SelfX units in hilar biliary strictures by using a partial stent-in-stent procedure was performed on 41 consecutive patients with primary cholangiocarcinoma (n = 34) and gallbladder carcinoma (n = 7) at a gastroenterologic center of Okayama University Hospital. Thirty-three patients were treated with gemcitabine (n = 25) or S-1 (n = 8).', 'Metallic stent deployment was successfully accomplished in all cases via only endoscopic procedures. During the follow-up period (mean, 210 days), mean patency time was 150 days, and metallic stent obstruction occurred in 15 cases (37%). Although a repeat intervention was required in all metallic stent obstructed cases, the deployment of the second metallic or plastic stent was completed successfully. The remaining 26 cases (63%) required no interventions. The median overall survival period was only 235 days. However, that of the patients receiving chemotherapy was 392 days.'] Is endoscopic deployment of multiple JOSTENT SelfX effective and safe in treatment of malignant hilar biliary strictures? | qiaojin/PubMedQA | 2 | [
-1.5955359935760498,
-1.6717129945755005,
2.222315549850464
] |
['Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid-producing protein and cereal grains relative to their content of net alkali-producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults.', 'We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects.', 'Subjects were 384 men and women > or =65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight/weight x 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y.', 'At baseline, the mean urinary potassium excretion was 67.0 +/- 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (beta = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 +/- 3.6%.'] Do alkaline diets favor lean tissue mass in older adults? | qiaojin/PubMedQA | 2 | [
-0.8937563896179199,
-1.2309415340423584,
1.2143502235412598
] |
['Adenosine receptor activation at reperfusion has been shown to ameliorate ischemia-reperfusion injury of the spinal cord, but the effects of therapy given in response to ischemic injury are unknown. We hypothesized that adenosine receptor activation with ATL-146e would produce similar protection from ischemic spinal cord injury, whether given at reperfusion or in a delayed fashion.', 'Twenty-two New Zealand white rabbits were divided into three groups. All three groups, including the ischemia-reperfusion group (IR, n = 8), underwent 45 min of infrarenal aortic occlusion. The early treatment group (early, n = 8) received 0.06 mug/kg/min of ATL-146e for 3 h beginning 10 min prior to reperfusion. The delayed treatment group (delayed, n = 6) received ATL-146e starting 1 h after reperfusion. After 48 h, hind limb function was graded using the Tarlov score. Finally, lumbar spinal cord neuronal cytoarchitecture was evaluated.', 'Hemodynamic parameters were similar among the groups. Hind limb function at 48 h was significantly better in the early group (3.5 +/- 1.0) compared to the IR group (0.625 +/- 0.5, P < or = 0.01). There was a trend towards better hind limb function in the early group compared to the delayed group (2.4 +/- 1.1, P = 0.08). Hind limb function was similar between delayed and IR groups. Hematoxylin-eosin spinal cord sections demonstrated preservation of viable motor neurons in the early group compared to the delayed and IR groups.'] Does early adenosine receptor activation ameliorate spinal cord reperfusion injury? | qiaojin/PubMedQA | 2 | [
-1.7237850427627563,
-1.6187156438827515,
2.2640035152435303
] |
['Cystatin C-and creatinine-based methods were compared with (99m)-technetium-diethylene-triamine-penta-acetic acid ((99m)Tc-DTPA) plasma clearance (isotopic glomerular filtration rate [iGFR]) for detecting declining renal function.', 'Glomerular filtration rate (GFR) was monitored over a mean of 10.1 years in 85 subjects with type 1 diabetes (with an average of 5.6 measurements per individual). Baseline mean +/- SD iGFR of the cohort was 106.1 +/- 2.6 ml/min per 1.73 m(2). The rates of decline in GFR (DeltaGFR) were derived using linear regression.', 'In 19 of 85 subjects with declining renal function (i.e., DeltaiGFR >3.3 ml/min per 1.73 m(2) per year), DeltaGFR (ml/min per 1.73 m(2) per year) was 6.5 by iGFR, 4.2 by 10(4)/creatinine, 3.6 by Cockcroft-Gault formula, 3.4 by the Modification of Diet in Renal Disease (MDRD)-6 equation, and 3.5 by the MDRD-4 variable equation (P < 0.01 vs. iGFR). In comparison, DeltaGFR was 6.1 using the formula Cys-GFR = (86.7/cystatin C concentration) - 4.2 (not significant).'] Are serial measurements of cystatin C more accurate than creatinine-based methods in detecting declining renal function in type 1 diabetes? | qiaojin/PubMedQA | 2 | [
-0.9360145330429077,
-1.822989583015442,
1.7390751838684082
] |
['All-trans retinoic acid (tRA) induces differentiation in MCF-7 breast cancer cells, stimulates sodium/iodide symporter (NIS) gene expression, and inhibits cell proliferation. Radioiodine administration after systemic tRA treatment has been proposed as an approach to image and treat some differentiated breast cancer.', 'The objective of this work was to study the relative role of genomic and nongenomic pathways in tRA stimulation of NIS expression in MCF-7 cells.', 'We inspected the human NIS gene locus for retinoic acid-responsive elements and tested them for function. The effects of signal transduction pathway inhibitors were also tested in tRA-treated MCF-7 cells and TSH-stimulated FRTL-5 rat thyroid cells, followed by iodide uptake assay, quantitative RT-PCR of NIS, and cell cycle phase analysis.', 'Multiple retinoic acid response elements around the NIS locus were identified by sequence inspection, but none of them was a functional tRA-induced element in MCF-7 cells. Inhibitors of the IGF-I receptor, Janus kinase, and phosphatidylinositol 3-kinase (PI3K), significantly reduced NIS mRNA expression and iodide uptake in tRA-stimulated MCF-7 cells but not FRTL-5 cells. An inhibitor of p38 MAPK significantly reduced iodide uptake in both tRA-stimulated MCF-7 cells and TSH-stimulated FRTL-5 cells. IGF-I and PI3K inhibitors did not significantly reduce the basal NIS mRNA expression in MCF-7 cells. Despite the chronic inhibitory effects on cell proliferation, tRA did not reduce the S-phase distribution of MCF-7 cells during the period of NIS induction.'] Is retinoic acid stimulation of the sodium/iodide symporter in MCF-7 breast cancer cells mediated by the insulin growth factor-I/phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase signaling pathways? | qiaojin/PubMedQA | 2 | [
-2.469865083694458,
-1.2486463785171509,
2.727189064025879
] |
['To evaluate the impact of sperm defect severity and the type of azoospermia on the outcomes of intracytoplasmic sperm injection (ICSI).', 'This study included 313 ICSI cycles that were divided into two major groups according to the source of spermatozoa used for ICSI: 1) Ejaculated (group 1; n = 220) and 2) Testicular/Epididymal (group 2; n = 93). Group 1 was subdivided into four subgroups according to the results of the semen analysis: 1) single defect (oligo-[O] or astheno-[A] or teratozoospermia-[T], n = 41), 2) double defect (a combination of two single defects, n = 45), 3) triple defect (OAT, n = 48), and 4) control (no sperm defects; n = 86). Group 2 was subdivided according to the type of azoospermia: 1) obstructive (OA: n = 39) and 2) non-obstructive (NOA: n = 54). Fertilization (2PN), cleavage, embryo quality, clinical pregnancy and miscarriage rates were statistically compared using one-way ANOVA and Chi-square analyses.', 'Significantly lower fertilization rates were obtained when either ejaculated sperm with triple defect or testicular sperm from NOA patients (63.4 +/- 25.9% and 52.2 +/- 29.3%, respectively) were used for ICSI as compared to other groups ( approximately 73%; P < 0.05). Epididymal and testicular spermatozoa from OA patients fertilized as well as normal or mild/moderate deficient ejaculated sperm. Cleavage, embryo quality, pregnancy and miscarriage rates did not differ statistically between ejaculated and obstructive azoospermia groups. However, fertilization, cleavage and pregnancy rates were significantly lower for NOA patients.'] Is sperm defect severity rather than sperm Source associated with lower fertilization rates after intracytoplasmic sperm injection? | qiaojin/PubMedQA | 2 | [
-1.1248489618301392,
-1.654179334640503,
1.759582281112671
] |
['The human TTC4 protein is a TPR (tetratricopeptide repeat) motif-containing protein. The gene was originally identified as being localized in a genomic region linked to breast cancer and subsequent studies on melanoma cell lines revealed point mutations in the TTC4 protein that may be associated with the progression of malignant melanoma.', 'Here we show that TTC4 is a nucleoplasmic protein which interacts with HSP90 and HSP70, and also with the replication protein CDC6. It has significant structural and functional similarities with a previously characterised Drosophila protein Dpit47. We show that TTC4 protein levels are raised in malignant melanoma cell lines compared to melanocytes. We also see increased TTC4 expression in a variety of tumour lines derived from other tissues. In addition we show that TTC4 proteins bearing some of the mutations previously identified from patient samples lose their interaction with the CDC6 protein.'] Is the human TPR protein TTC4 a putative Hsp90 co-chaperone which interacts with CDC6 and shows alterations in transformed cells? | qiaojin/PubMedQA | 2 | [
-2.4292333126068115,
-0.9708777666091919,
2.4685940742492676
] |
['The blood brain barrier (BBB) and truncated trkB receptor on astrocytes prevent the penetration of brain derived neurotrophic factor (BDNF) applied into the peripheral (PNS) and central nervous system (CNS) thus restrict its application in the treatment of nervous diseases. As BDNF is anterogradely transported by axons, we propose that peripherally derived and/or applied BDNF may act on the regeneration of central axons of ascending sensory neurons.', 'The present study aimed to test the hypothesis by using conditioning lesion of the sciatic nerve as a model to increase the expression of endogenous BDNF in sensory neurons and by injecting exogenous BDNF into the peripheral nerve or tissues. Here we showed that most of regenerating sensory neurons expressed BDNF and p-CREB but not p75NTR. Conditioning-lesion induced regeneration of ascending sensory neuron and the increase in the number of p-Erk positive and GAP-43 positive neurons was blocked by the injection of the BDNF antiserum in the periphery. Enhanced neurite outgrowth of dorsal root ganglia (DRG) neurons in vitro by conditioning lesion was also inhibited by the neutralization with the BDNF antiserum. The delivery of exogenous BDNF into the sciatic nerve or the footpad significantly increased the number of regenerating DRG neurons and regenerating sensory axons in the injured spinal cord. In a contusion injury model, an injection of BDNF into the footpad promoted recovery of motor functions.'] Does peripherally-derived BDNF promote regeneration of ascending sensory neurons after spinal cord injury? | qiaojin/PubMedQA | 2 | [
-2.5546672344207764,
-1.1090867519378662,
2.746180534362793
] |
['To investigate the occurrence of adverse blood pressure (BP) events during transurethral microwave therapy (TUMT) for benign prostatic hyperplasia.', 'We conducted a retrospective study of the vital signs of 185 consecutive patients who received TUMT (via 6 devices) at 4 institutions from March 1, 2003, to September 18, 2005. Maximum change, percent change in systolic BP, diastolic BP, mean arterial pressures, heart rate, and oxygen saturation were evaluated.', 'Of the 185 patients, 77 patients (42%; 95% confidence interval [CI], 35%-49%) experienced an increase in systolic BP of more than 30 mm Hg during TUMT; 30 patients (16%; 95% CI, 12%-22%), an increase of more than 50 mm Hg; and 10 patients (5%; 95% CI, 3%-10%), an increase of more than 70 mm Hg. A greater than 20% change in systolic BP from baseline was observed in 95 patients (51%; 95% CI, 44%-58%). Many men experienced multiple events, with an average time of onset of 15.9 minutes into treatment. Significant differences were noted among the devices.'] Does blood pressure surge during office-based transurethral microwave therapy for the prostate? | qiaojin/PubMedQA | 2 | [
-1.9874705076217651,
-1.044566035270691,
2.1075263023376465
] |
['To evaluate data addressing use of anticoagulation in elderly patients with atrial fibrillation (AF), in particular those at risk of falls.', 'Primary literature was identified through PubMed MEDLINE (1966-December 2007) and EMBASE (1980-December 2007) using the search terms anticoagulation, warfarin, aspirin, elderly, falls, older persons, atrial fibrillation, bleeding, education, stroke, and use. Additional references were obtained through review of references from articles obtained.', 'Clinical studies evaluating warfarin and aspirin efficacy in AF, as well as studies evaluating anticoagulation and falls, elderly patients, and bleeding were considered for inclusion. Selection emphasis was placed on randomized studies of AF and those evaluating anticoagulation and falls.', 'Uncertainties over the optimal treatment for elderly patients with AF still exist. Variance in the guidelines is reflected in current practice, as some discrepancies are present. Warfarin is underprescribed in elderly patients, with only about 50% of eligible patients receiving therapy. Falls are most often cited as the reason for not using anticoagulants in an elderly patient. Three risk-benefit analyses have been performed, and all found that despite risks associated with warfarin, its benefits outweigh its risks even in patients who fall. Warfarin should be used rather than aspirin or no therapy in elderly patients at risk of falls. Anticoagulation education has been shown to reduce the risk of bleeding in the elderly and should be a vital part of warfarin management.'] Are use of anticoagulation in elderly patients with atrial fibrillation who at risk for falls? | qiaojin/PubMedQA | 2 | [
-2.8399643898010254,
-0.5350505709648132,
2.5153417587280273
] |
['Little is known about the capacity, mechanisms, or timing of growth in beta-cell mass in humans. We sought to establish if the predominant expansion of beta-cell mass in humans occurs in early childhood and if, as in rodents, this coincides with relatively abundant beta-cell replication. We also sought to establish if there is a secondary growth in beta-cell mass coincident with the accelerated somatic growth in adolescence.', 'To address these questions, pancreas volume was determined from abdominal computer tomographies in 135 children aged 4 weeks to 20 years, and morphometric analyses were performed in human pancreatic tissue obtained at autopsy from 46 children aged 2 weeks to 21 years.', 'We report that 1) beta-cell mass expands by severalfold from birth to adulthood, 2) islets grow in size rather than in number during this transition, 3) the relative rate of beta-cell growth is highest in infancy and gradually declines thereafter to adulthood with no secondary accelerated growth phase during adolescence, 4) beta-cell mass (and presumably growth) is highly variable between individuals, and 5) a high rate of beta-cell replication is coincident with the major postnatal expansion of beta-cell mass.'] Is beta-cell replication the primary mechanism subserving the postnatal expansion of beta-cell mass in humans? | qiaojin/PubMedQA | 2 | [
-2.832711935043335,
0.6100080013275146,
1.279461145401001
] |
['As many as 20-30% of women report an inability to orgasm during sexual intercourse. Some female sexual problems have been reported to cluster with psychological and social problems. Underlying personality type may play a role in the development or maintenance of such problems.', 'The aim of this study was to investigate whether certain domains of personality are associated with female coital orgasmic infrequency. To our knowledge this is the first such study in a large unselected population.', 'A total of 2632 women (mean age 51) from the TwinsUK registry completed questionnaires relating to personality and sexual behavior. Personality domains were assessed using the validated Ten-Item Personality Index (TIPI). Coital orgasmic frequency was measured using a seven-point Likert scale.', 'Using logistic regression, we investigated whether variations in five domains of personality are associated with female coital orgasmic infrequency. Discordant twin analysis was used to verify findings.', 'Introversion (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.7-3.7), emotional instability (OR 2.0, 95% CI 1.3-3.1), and not being open to new experience (OR 2.4, 95% CI 1.6-3.6) were significantly associated with orgasmic infrequency, whereas indices of agreeableness and conscientiousness were not significantly associated with orgasm frequency.'] Are normal variations in personality associated with coital orgasmic infrequency in heterosexual women : a population-based study? | qiaojin/PubMedQA | 2 | [
-2.3499248027801514,
-0.19866983592510223,
1.7632765769958496
] |
['The polycomb factor BMI-1 has recently been implicated in tumorigenesis of the central nervous system in several experimental animal models. However, the significance of BMI-1 in human glioma has not been investigated. Here we describe expression of the polycomb protein BMI-1 and its downstream targets p16(Ink4a) and MDM2 in both high- and low-grade human glioma.', 'Tumour samples were collected from 305 adult patients treated for primary grades 2-4 gliomas between 1980 and 2006 in Finland and Germany. BMI-1, p16 and MDM2 expression was evaluated using immunohistochemistry in representative paraffin-embedded tumour tissue. The significance of observed immunoreactivity, age at onset, gender, histopathological findings and proliferative index was analysed in univariate and multivariate survival models.', 'BMI-1 was expressed in all histologic types of diffuse gliomas. We found a significant correlation (P = 0.007) between the frequency of BMI-1 immunoreactive tumour cells and poor survival in World Health Organization grades II-III oligodendrogliomas and oligoastrocytomas (n = 62). The median survival of patients grouped by low, intermediate or high frequency of BMI-1 immunoreactive tumour cells was 191 months, 151 months and 68 months, respectively. This association was also significant in the Cox multivariate regression model. Nuclear p16 immunopositivity predicted better survival in astrocytomas and an inverse correlation between p16 expression and the Ki-67 mitotic index was also observed.'] Is stem cell protein BMI-1 an independent marker for poor prognosis in oligodendroglial tumours? | qiaojin/PubMedQA | 2 | [
-2.2410008907318115,
-1.3965438604354858,
2.678499698638916
] |
['Mutations in the essential myosin light chain (ELC) and regulatory myosin light chain (RLC) genes have been linked to sarcomeric hypertrophic cardiomyopathies in humans; however, the specific functions of the different myosin light chains during cardiogenesis in a vertebrate animal are not well understood.', 'Using zebrafish (Danio rerio) as a model organism, we have identified cmlc1 and cmlc2 as the main ELC and RLC orthologues, respectively, and have furthermore characterized their functions during cardiogenesis by morpholino technology. Depletion of either cmlc1 or cmlc2 using morpholino-modified antisense oligonucleotides leads to a disruption in sarcomere structure and compromises cardiac function as well, although through seemingly distinct mechanisms. While myosin still assembles into a novel rod-like structure in both morphants, the sarcomere length is longer in cmlc1 morphants than that in wild-type embryos, whereas it is shorter in cmlc2 morphants. In addition, cardiomyocyte size and number are increased upon depletion of cmlc1, resulting in a larger ventricular chamber volume; in contrast, depletion of cmlc2 leads to a reduction in cardiomyocyte size and number.'] Does depletion of zebrafish essential and regulatory myosin light chains reduce cardiac function through distinct mechanisms? | qiaojin/PubMedQA | 2 | [
-2.578493356704712,
-0.9307968020439148,
2.513592004776001
] |
['Oxidative stress has long been recognized as an important mediator of apoptosis in lens epithelial cells and also plays an important role in the pathogenesis of cataracts. (-)-Epigallocatechin gallate (EGCG), the most abundant component in green tea, has potent antioxidant activity. The goals of this study were to determine the protective effect of EGCG against H(2)O(2)-induced apoptotic death and the possible mechanisms involved in human lens epithelial (HLE) cells.', "HLEB-3, a human lens epithelial cell line, was exposed to various concentrations of H(2)O(2) and EGCG and subsequently monitored for cell death by the MTT assay and flow cytometric analysis using Annexin V and PI. The effect of EGCG in protecting HLE cells from cell death was determined by various assays after the cells were exposed to H(2)O(2). The ability of EGCG to block the accumulation of intracellular reactive oxygen species and the loss of mitochondrial membrane potential (Deltapsim) induced by H(2)O(2) was examined with dichlorofluorescein (DCF) fluorescence and 5,5',6,6'-tetrachloro-1,1',3,3'-tetrathylbenzimidazol carbocyanine iodide (JC-1). The expression of cytochrome c, caspase-9, caspase-3, and Bcl-2 family proteins was measured by western blotting. The changed expression of the mitogen activated protein kinase (MAPK) and Akt pathways was also detected by western blot.", 'In the present study, EGCG protected against cell death caused by H(2)O(2) in HLEB-3 cells. EGCG reduced the H(2)O(2)-induced generation of reactive oxygen species (ROS), the loss of mitochondrial membrane potential (Deltapsim), and the release of cytochrome c from the mitochondria into the cytosol. EGCG inhibited the H(2)O(2)-stimulated increase of caspase-9 and caspase-3 expression and the decrease of the Bcl-2/Bax ratio. Moreover, EGCG attenuated the reduced activation and expression of ERK, p38 MAPK, and Akt induced by H(2)O(2).'] Does epigallocatechin gallate protect against oxidative stress-induced mitochondria-dependent apoptosis in human lens epithelial cells? | qiaojin/PubMedQA | 2 | [
-2.411128044128418,
-1.3259308338165283,
2.7885069847106934
] |
['CC10, a 10-kDa anti-inflammatory protein secreted by bronchiolar Clara cells, is infrequently expressed in non-small cell lung cancer and its overexpression in non-small cell lung cancer cell lines results in a less malignant phenotype. Several lines of evidence have shown that bronchial dysplasia and sputum atypia are predictors of lung cancer. We investigated whether changes in CC10 expression correlate with regression of bronchial dysplasia and/or improvement in sputum abnormalities as measured by image cytometry.', 'High-risk smokers enrolled in a chemoprevention trial underwent serial bronchoscopies with biopsies and bronchoalveolar lavage (BAL) collection, sputum assessment by image cytometry, and blood collection. CC10 was measured by competitive ELISA in BAL and plasma. Logistic regression analyses were done to determine the associations between CC10 levels and the improvement in bronchial dysplasia and sputum cytometric assessment.', 'The net change in the BAL CC10 levels in subjects with improved bronchial lesions or improved sputum cytometry assessment was significantly higher than in those without improvement (P < 0.05). The odds ratio (95% confidence interval) associated with 1-unit increase in CC10 was 2.72 (1.31-5.64) for regression of dysplastic lesions and 2.94 (1.22-7.05) for improvement in sputum cytometry assessment after multivariate adjustment. Plasma CC10 was not significantly associated with either outcome.'] Are higher levels of the anti-inflammatory protein CC10 associated with improvement in bronchial dysplasia and sputum cytometric assessment in individuals at high risk for lung cancer? | qiaojin/PubMedQA | 2 | [
-2.0975539684295654,
-1.4631993770599365,
2.5661849975585938
] |
['We often see aggravation of eczematous skin lesions associated with bacterial infection, but the mechanism of this phenomenon is unclear. Staphylococcus aureus is known to colonize on the eczematous lesion and produce some exotoxins, which act as bacterial superantigens.', 'To investigate the potential role of superantigens in chronic dermatitis, we investigated the effect of staphylococcal enterotoxin B (SEB) on the skin reaction, the proliferative response and the cytokine production of local lymph node cells in the mouse model of contact hypersensitivity reaction.', 'Sensitized BALB/c mice were repeatedly challenged with dinitrofluorobenzene (DNFB), and intravenously injected with SEB and dinitrobenzne sulfonic acid sodium salt (DNBS). The ear swelling response was measured after DNBS injection. Cervical lymph node cells of those mice were cultured with DNBS in vitro. Their proliferative responses and the production of cytokines were assessed.', 'SEB markedly enhanced the flare-up reaction of ear swelling induced by DNBS, the proliferative response of lymph node cells and the production of IFN-gamma. In contrast, the production of IL-5 was decreased.'] Does staphylococcal enterotoxin B enhance a flare-up reaction of murine contact hypersensitivity through up-regulation of interferon-gamma? | qiaojin/PubMedQA | 2 | [
-2.546862840652466,
-1.2667667865753174,
2.8684892654418945
] |
['Loperamide, an opiate receptor agonist, does not cross the blood-brain barrier because it is a substrate for the permeability-glycoprotein (P-gp) efflux pump. We evaluated 11C-loperamide as a PET radiotracer to measure P-gp function in vivo.', 'Monkeys were injected with 11C-loperamide, and PET brain images were acquired for 120 min. The baseline scans were followed by scans acquired after administration of either of 2 P-gp inhibitors, (2R)-anti-5-{3-[4-(10,11-dichloromethanodibenzo-suber-5-yl)piperazin-1-yl]-2-hydroxypropoxy}quinoline trihydrochloride (DCPQ) or tariquidar. Both the PET scans and ex vivo measurements were obtained in P-gp knockout and wild-type mice.', 'Pharmacologic inhibition of P-gp in monkeys dose-dependently increased brain activity, with a 3.7-fold effect at the highest DCPQ dose (8 mg/kg intravenously). This increase of brain activity was not caused peripherally, because DCPQ insignificantly changed the plasma concentration and plasma protein binding of radiotracer. Furthermore, the structurally dissimilar inhibitor, tariquidar, also increased brain uptake with potency equal to that of DCPQ. P-gp knockout mice had 3-fold higher brain activity on PET than did wild-type animals. Four radiometabolites were detected in the plasma and brains of ex vivo mice. The most lipophilic radiometabolite was found to be comobile with reference dLop on high-performance liquid chromatography. The brain concentrations of 11C-loperamide and the putative 11C-dLop were about 16-fold greater in P-gp knockout mice than in wild-type mice.'] Are 11C-loperamide and its N-desmethyl radiometabolite avid substrates for brain permeability-glycoprotein efflux? | qiaojin/PubMedQA | 2 | [
-2.1838014125823975,
-1.4602218866348267,
2.670217514038086
] |
['Studies have shown that the addition of right precordial and left posterior leads to the standard 12-lead electrocardiogram (ECG) can significantly improve the sensitivity of exercise treadmill testing (ETT) for the diagnosis of myocardial ischemia.', 'The objective of this study was to determine the value of adding 2 rightsided (RV3, RV4) and 2 left posterior (V8, V9) auxiliary leads to enhance detection of myocardial ischemia in patients with chest pain identified as low risk.', 'The authors conducted a prospective study of all patients undergoing ETT as part of their management in a chest pain evaluation unit (CPEU) at a tertiary medical center from November 1999 to November 2001. Patients were considered low risk for acute coronary syndrome based on the clinical presentation to the CPEU, absence of ischemia on resting ECG, and negative initial cardiac markers. Diagnosis of coronary artery disease (CAD) was based on confirmatory testing, which included coronary angiography, myocardial stress scintigraphy, exercise echocardiography, or 30-day follow-up period.', 'The study cohort comprised 705 patients who underwent 16-lead ETT. Of these, 70 (10%) had positive ETT and CAD was confirmed by further evaluation in 26. ECG changes positive for ischemia were demonstrated on the standard 12-lead exercise ECG in 68 patients. An additional 2 patients had positive ECG alterations only in the 4 auxiliary leads on the 16-lead ECG. There was no significant difference in the sensitivity or positive predictive value between the 12- and 16-lead exercise ECG.'] Does use of additional electrocardiograph lead in low-risk patients undergoing exercise treadmill testing? | qiaojin/PubMedQA | 2 | [
-1.8902393579483032,
-1.4739784002304077,
2.368828058242798
] |
['Decision analytic techniques use formal specifications of utility for the four fundamental decision events: true positives, false positives, true negatives, and false negatives. An optimal policy is the one with the lowest expected net cost. In this paper, decision analytic techniques for treatment selection based on patient characteristics are applied to a resource-poor setting.', 'A cohort of 986 female sex workers in Antananarivo and Tamatave, Madagascar were tested for cervical infection at baseline and again 2 months later after presumptive treatment for gonorrhea and chlamydia.', 'Three equivalent approaches to identify the optimal policy based on patient characteristic subgroups are demonstrated. Two of them require exhaustive searches of all possible alternatives. The third identifies the optimal policy as an analytic expression that compares a decision function with a threshold and leads to a closed-form solution. With this approach, the optimal policy can be expressed in four equivalent forms using basic epidemiological measures: likelihood ratio, predicted probability of disease, logistic regression parameters, and total risk score.'] Does a formal decision analysis identify an optimal treatment strategy in a resource-poor setting? | qiaojin/PubMedQA | 2 | [
-2.5412709712982178,
0.4638933539390564,
1.228955626487732
] |
['The previous studies demonstrated that transforming growth factor-beta(1) (TGF-beta(1)) could upregulate the expression of aldose reductase (AR). The aim of this study is to clarify (investigate) the mechanism of TGF-beta(1)-induced AR expression.', "Real-time polymerase chain reaction and western blot were used to analyse the AR expression in mRNA and protein levels in human mesangial cells, and reporter assay was used to analyse the function of various sites within 5'-flanking region of AR gene in AR expression.", "TGF-beta(1) (4 ng/mL) stimulation could upregulate AR expression. The cells pretreated with pharmacological inhibitors, U0126 and PD98059 for blocking extracellular signal-related kinase (ERK) signalling pathway or SP6000125 for blocking c-Jun N-terminal kinase (JNK) signalling pathway, respectively, showed reduced expression of AR after TGF-beta(1) stimulation. Similarly, the cells transiently transfected with pCMVTAM67, which is an expression plasmid for DN-c-Jun showed decreasing AR expression. Reporter assay revealed that the 5'-promoter region of AR consisting of an AP-1 site and two putative antioxidant response elements (ARE) was responsible for TGF-beta(1) stimulation. Mutation of either ARE did not affect the promoter activity in the reporter assay while mutation of AP-1 site caused a significant decrease in the responsiveness to TGF-beta(1)."] Does transcription factor AP-1 regulate TGF-beta ( 1 ) -induced expression of aldose reductase in cultured human mesangial cells? | qiaojin/PubMedQA | 2 | [
-2.2956063747406006,
-1.2485358715057373,
2.5781707763671875
] |
['This study was to evaluate the correlation of urinary kallikrein to renal function, proteinuria and urinary cytokines in chronic kidney disease patients in a longitudinal follow up.', 'We measured urinary kallikrein and cytokines in 50 patients who were followed up for 12 months.', 'Using regression model we found that the kallikrein excretion (estimated by log kallikrein/creatinine) was positively correlated to log estimated glomerular filtration rate in the beginning and the end of follow up (P = 0.049 and 0.006, respectively). No correlation existed between kallikrein excretion and proteinuria. The kallikrein excretion decreased after 12 months of follow up, which was also associated with the decrease of log estimated glomerular filtration rate. There was a significant positive correlation between the log urinary kallikrein and monocyte chemoattractant protein-1 (MCP-1) concentration (correlation coefficient = 0.277; P = 0.049). Urinary kallikrein excretion was also positively correlated with serum MCP-1 level (correlation coefficient = 0.431; P = 0.002). No correlation existed between urinary kallikrein and transforming growth factor beta-1 or tumour necrosis factor-alpha concentration.'] Is urinary kallikrein excretion related to renal function change and inflammatory status in chronic kidney disease patients receiving angiotensin II receptor blocker treatment? | qiaojin/PubMedQA | 2 | [
-2.121060609817505,
-1.2763290405273438,
2.4679012298583984
] |
['MST1 and MST2 are the mammalian Ste20-related protein kinases most closely related to Drosophila Hippo, a major regulator of cell proliferation and survival during development. Overexpression of MST1 or MST2 in mammalian cells is proapototic; however, little is known concerning the physiologic regulation of the endogenous MST1/MST2 kinases, their role in mammalian cell proliferation, or the identity of the MST1/MST2 substrates critical to proliferative regulation.', 'We show that MST1 and MST2 activity increases during mitosis, especially in nocodazole-arrested mitotic cells, where these kinases exhibit both an increase in both abundance and activation. MST1 and MST2 also can be activated nonphysiologically by okadaic acid or H2O2. The MOBKL1A and MOBKL1B polypeptides, homologs of the Drosophila MATS polypeptide, are identified as preferred MST1/MST2 substrates in vitro and are phosphorylated in cells in an MST1/MST2-dependent manner in mitosis and in response to okadaic acid or H2O2. MST1/MST2-catalyzed MOBKL1A/MOBKL1B phosphorylation alters the ability of MOBKL1A/MOBKL1B to bind and regulate downstream targets such as the NDR-family protein kinases. Thus, MOBKL1A/MOBKL1B phosphorylation in cells promotes MOBKL1A/MOBKL1B binding to the LATS1 kinase and enables H2O2-stimulated LATS1 activation loop phosphorylation. Most importantly, replacement of endogenous MOBKL1A/MOBKL1B by a nonphosphorylatable mutant is sufficient to accelerate cell proliferation substantially by speeding progression through G1/S as well as mitotic exit.'] Does mOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibit cell proliferation? | qiaojin/PubMedQA | 2 | [
-2.318460702896118,
-1.1325910091400146,
2.457209348678589
] |
['This article examines the effects of early life socioeconomic conditions on the risk of cognitive impairment among oldest old persons in China. We also examine whether adult socioeconomic status mediates the association between early life socioeconomic status and cognitive impairment in old age.', 'Data derived from two waves (1998-2000) of the Chinese Longitudinal Healthy Longevity Survey. We estimated logistic and multinomial regression models of cognitive impairment for a nationwide sample of people aged 80 to 105 (N = 8,444).', 'Among both men and women, urban residence in early life as well as education was associated with lower odds of cognitive impairment at baseline. We found modest support for a protective effect of advantaged childhood background on the odds of cognitive impairment onset during the 2-year follow-up, especially among women.'] Does early life influence on cognitive impairment among oldest old Chinese? | qiaojin/PubMedQA | 1 | [
-2.1655399799346924,
1.8004136085510254,
-0.3611389994621277
] |
['Docetaxel induces an anti-tumor response in men with advanced prostate cancer (PCa); however, the side effects associated with docetaxel treatment can be severe, resulting in discontinuation of therapy. Thus, identification of an effective adjuvant therapy to allow lower doses of docetaxel is needed. Advanced PCa is typically accompanied by skeletal metastasis. Receptor activator of NFkB ligand (RANKL) is a key pro-osteoclastic factor. Targeting RANKL decreases establishment and progression of PCa growth in bone in murine models.', 'The efficacy of inhibiting RANKL, using a recombinant soluble RANK extracellular domain fused with the immunoglobulin Fc domain (RANK-Fc), was tested as an adjuvant therapy with docetaxel for PCa bone metastasis in a murine intra-tibial model.', 'The combination of RANK-Fc and docetaxel reduced tumor burden in bone greater than either treatment alone.'] Is rANKL inhibition an effective adjuvant for docetaxel in a prostate cancer bone metastases model? | qiaojin/PubMedQA | 2 | [
-2.399235486984253,
-1.291417121887207,
2.778438091278076
] |
['Abdominal obesity, particularly visceral adipose tissue (VAT), is associated with an increased risk of coronary heart disease (CHD). Despite an elevated risk of CHD mortality in persons with spinal cord injury (SCI), neither abdominal adipose tissue accumulation nor the validity of waist circumference (WC) has been determined in persons with SCI.', 'The objectives of this study were to compare total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and the ratio of VAT to SAT (VAT:SAT) between adults with SCI and age-, sex-, and WC-matched able-bodied (AB) controls and to determine the relation between WC and VAT in both groups.', 'Thirty-one men and women (n = 15 SCI and 16 AB) with a mean (+/-SD) age of 38.9 +/- 7.9 y participated in this cross-sectional study. Abdominal adipose tissue was quantified by computed tomography at L4-L5. WC was measured at 3 sites: lowest rib, iliac crest, and the midpoint between the lowest rib and iliac crest.', 'Persons with SCI had a 58% greater mean VAT (P = 0.003), 48% greater mean VAT:SAT (P = 0.034), and 26% greater mean TAT (P = 0.055) than did matched AB controls after differences in weight were accounted for. Mean SAT was not significantly different between groups. WC at all sites was correlated with VAT in both groups (SCI: 0.905 < or = r < or = 0.925; AB: 0.838 < or = r < or = 0.877; both P < 0.001).'] Are visceral adipose tissue and the ratio of visceral to subcutaneous adipose tissue greater in adults with than in those without spinal cord injury , despite matching waist circumferences? | qiaojin/PubMedQA | 2 | [
-1.1035062074661255,
-1.5802325010299683,
1.719691514968872
] |
['Delirium is a potentially life-threatening syndrome that is particularly common in elderly hospitalized patients, especially those with preexisting neurologic disorders. Nonpharmacological tactics can reduce the incidence and severity of delirium in acute care settings and antipsychotic drugs are widely used to treat established delirium. More effective preventive strategies could notably impact morbidity, mortality, and health care costs.', 'To determine whether antipsychotic drug prophylaxis reduces the incidence and severity of postoperative delirium in at-risk elderly patients.', 'We addressed the objective through development of a structured critically appraised topic that included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of cognitive disorders.', 'One randomized controlled trial addressed the question. In at-risk patients aged >70 years, oral haloperidol 0.5 mg TID, administered from up to 72 hours preoperatively until the third postoperative day, did not alter the incidence of postoperative delirium (15.1%) compared with placebo (16.5%; relative risk 0.91; 95% confidence interval 0.59-1.44). However, the study was underpowered for this primary outcome, possibly because both groups received nonpharmacological delirium prevention strategies. Haloperidol significantly reduced delirium severity ratings, delirium duration (from a mean of 11.8 to 5.4 days), and length of hospital stay in affected participants (from 22.6 to 17.1 day).'] Does adjunctive haloperidol prophylaxis reduce postoperative delirium severity and duration in at-risk elderly patients? | qiaojin/PubMedQA | 2 | [
-2.4751853942871094,
-0.9907441735267639,
2.6019840240478516
] |
['It has been reported that the prostate cancer detection rate in men with prostate specific antigen 2.5 ng/ml or greater undergoing saturation (20 cores or greater) prostate biopsy as an initial strategy is not higher than that in men who undergo 10 to 12 core prostate biopsy. At a median followup of 3.2 years we report the cancer detection rate on subsequent prostate biopsy in men who underwent initial saturation prostate biopsy.', 'Saturation prostate biopsy was used as an initial biopsy strategy in 257 men between January 2002 and April 2006. Cancer was initially detected in 43% of the patients who underwent saturation prostate biopsy. In the 147 men with negative initial saturation prostate biopsy followup including digital rectal examination and repeat prostate specific antigen measurement was recommended at least annually. Persistently increased prostate specific antigen or an increase in prostate specific antigen was seen as an indication for repeat saturation prostate biopsy.', 'During the median followup of 3.2 years after negative initial saturation prostate biopsy 121 men (82%) underwent subsequent evaluation with prostate specific antigen and digital rectal examination. Median prostate specific antigen remained 4.0 ng/ml or greater in 57% of the men and it increased by 1 ng/ml or greater in 23%. Cancer was detected in 14 of 59 men (24%) undergoing repeat prostate biopsy for persistent clinical suspicion of prostate cancer. No significant association was demonstrated between cancer detection and initial or followup prostate specific antigen, or findings of atypia and high grade prostatic intraepithelial neoplasia on initial saturation prostate biopsy. Cancers detected on repeat prostate biopsy were more likely to be Gleason 6 and organ confined at prostatectomy than were those diagnosed on initial saturation prostate biopsy.'] Does saturation technique decrease cancer detection during followup after initial prostate biopsy? | qiaojin/PubMedQA | 2 | [
-2.102320432662964,
-1.433483362197876,
2.5883970260620117
] |
['Statins are cholesterol-lowering drugs that have been proved to prevent cardiac events. Their direct effects on cardiac remodeling, when administered in programmed protein restricted animals, still are unknown.', 'Wistar male 6-month-old offspring from dams fed normal protein (NP, 19% of protein) or low-protein (LP, 5% of protein) during pregnancy and first 10 days after birth were studied. After weaning, male pups were allocated to untreated or treated groups with atorvastatin (low and high doses, 5 or 30 mg.kg.day) in two different periods (from 21 days old to 3 months old and from 3 to 6 months old). The blood pressure (BP) was 30% greater in untreated LP offspring than in treated offspring (from 165 +/- 6 mm Hg to 127 +/- 3 mm Hg, P < .01). After 1 month of treatment, only untreated LP offspring continued with high BP. Compared with untreated LP offspring, atorvastatin reduced blood glucose (less 30%, P < .05) and cardiomyocyte size (less 24%, P < .05), whereas untreated LP offspring had greater interstitial fibrosis (plus 74%, P < .01), reduction of myocardial vascularization (less 25%, P < .01) and major reduction of cardiomyocyte number (less 38%, P < .01) than treated LP offspring.'] Does atorvastatin attenuate cardiomyocyte loss in adult rats from protein-restricted dams? | qiaojin/PubMedQA | 2 | [
-1.8190653324127197,
-1.1690291166305542,
2.010928153991699
] |
['Signal transducer and activator of transcription 5a/b (Stat5a/b) is the key mediator of prolactin effects in prostate cancer cells via activation of Janus-activated kinase 2. Prolactin is a locally produced growth factor in human prostate cancer. Prolactin protein expression and constitutive activation of Stat5a/b are associated with high histologic grade of clinical prostate cancer. Moreover, activation of Stat5a/b in primary prostate cancer predicts early disease recurrence. Here, we inhibited Stat5a/b by several different methodologic approaches. Our goal was to establish a proof of principle that Stat5a/b is critical for prostate cancer cell viability in vitro and for prostate tumor growth in vivo.', 'We inhibited Stat5a/b protein expression by antisense oligonucleotides or RNA interference and transcriptional activity of Stat5a/b by adenoviral expression of a dominant-negative mutant of Stat5a/b in prostate cancer cells in culture. Moreover, Stat5a/b activity was suppressed in human prostate cancer xenograft tumors in nude mice. Stat5a/b regulation of Bcl-X(L) and cyclin D1 protein levels was shown by antisense suppression of Stat5a/b protein expression followed by Western blotting.'] Does transcription factor signal transducer and activator of transcription 5 promote growth of human prostate cancer cells in vivo? | qiaojin/PubMedQA | 2 | [
-2.4553637504577637,
-1.1041340827941895,
2.565486192703247
] |
['Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition [estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (HER)-2, all negative] is commonly used to identify such cases. EGFR and cytokeratin 5/6 are readily available positive markers of basal-like breast cancer applicable to standard pathology specimens. This study directly compares the prognostic significance between three- and five-biomarker surrogate panels to define intrinsic breast cancer subtypes, using a large clinically annotated series of breast tumors.', 'Four thousand forty-six invasive breast cancers were assembled into tissue microarrays. All had staging, pathology, treatment, and outcome information; median follow-up was 12.5 years. Cox regression analyses and likelihood ratio tests compared the prognostic significance for breast cancer death-specific survival (BCSS) of the two immunohistochemical panels.', 'Among 3,744 interpretable cases, 17% were basal using the triple-negative definition (10-year BCSS, 6 7%) and 9% were basal using the five-marker method (10-year BCSS, 62%). Likelihood ratio tests of multivariable Cox models including standard clinical variables show that the five-marker panel is significantly more prognostic than the three-marker panel. The poor prognosis of triple-negative phenotype is conferred almost entirely by those tumors positive for basal markers. Among triple-negative patients treated with adjuvant anthracycline-based chemotherapy, the additional positive basal markers identified a cohort of patients with significantly worse outcome.'] Does basal-like breast cancer defined by five biomarkers have superior prognostic value than triple-negative phenotype? | qiaojin/PubMedQA | 2 | [
-2.0939228534698486,
-1.501525640487671,
2.603445053100586
] |
['To measure plasma D-dimer levels in cirrhotic patients with and without ascites, assessing the effect of ascites resolution in D-dimer concentration.', 'Seventy consecutive cirrhotic patients (M = 44, F = 26, mean age 65 years, SD +/- 13), observed from October 2005 to March 2006 were enrolled. Circulating D-dimer levels were measured using a latex-enhanced, immunoturbidimetric test. In patients with ascites (n = 42) the test was repeated after ascites resolution.', 'Ascites was present in 42 patients (group A) and absent in 28 (group B). Group A patients had more advanced liver disease. Hepatocellular carcinoma (HCC) was diagnosed in 14 patients and was more frequent in group B. Above normal range D-dimers were found in 45/70 patients. High D-dimers were more frequent in group A than in group B (P = 0.001). High D-dimers were associated with presence of HCC (P = 0.048) only in group B. After ascites resolution, obtained in all patients, mean D-dimer values decreased in those 34 patients with high basal levels (P = 0.007), returning to normal in 17.'] Are high circulating D-dimers associated with ascites and hepatocellular carcinoma in liver cirrhosis? | qiaojin/PubMedQA | 2 | [
-1.7033642530441284,
-1.5094561576843262,
2.187605381011963
] |
["Evidence from randomized trials in the pre-sentinel lymph node biopsy era indicate that adjuvant treatment with high-dose interferon-alpha (IFN) increases recurrence-free survival (RFS) in patients with high-risk melanoma. However, to the authors' knowledge, the role of this treatment in selected patients with early stage III disease has not been well studied.", 'The clinical and pathologic characteristics of 486 patients undergoing surgical treatment for stage III melanoma were evaluated and the authors compared outcomes for those given adjuvant treatment with IFN with those patients who had surgery alone. A particular focus was on the effect of IFN therapy on RFS and overall survival (OS) among those patients with stage IIIA disease.', 'The median follow-up for the entire cohort was 5.2 years; the 5-year RFS and OS rates for the entire group were 41% and 53%, respectively. Adjuvant IFN was given to 141 patients (29%). On multivariate analysis, IFN was found to be the only independent predictor for RFS in patients with stage IIIA disease (hazards ratio of 0.4; 95% confidence interval, 0.2-0.9 [P = .02]). IFN was not found to be associated with increased RFS in patients with more advanced lymph node disease (stage IIIB and stage IIIC). IFN appeared to have no effect on OS in any patient with stage III disease.'] Is adjuvant high-dose interferon for cutaneous melanoma most beneficial for patients with early stage III disease? | qiaojin/PubMedQA | 2 | [
-1.8719111680984497,
-1.4779267311096191,
2.3966314792633057
] |
['TGF-beta is a multifunctional regulator of chondrocyte proliferation, differentiation, and extracellular matrix production. Dysregulation of TGF-beta action has been implicated in cartilage diseases such as osteoarthritis. TGF-beta signaling is transduced through a pair of transmembrane serine/threonine kinases, known as the type I (ALK5) and type II receptors. However, recent studies on endothelial cells have identified ALK1 as a second type I TGF-beta receptor and have shown that ALK1 and ALK5 have opposing functions in these cells. Here we examined ALK1 expression and its regulation of TGF-beta signaling and responses in human chondrocytes.', 'ALK1 expression in human chondrocytes was examined by RT-PCR and Western blot. The ability of ALK1 to form complexes with other TGF-beta receptors was determined by affinity labeling/immunoprecipitation and by immunoprecipitation followed by Western blot. The effect of ALK1 on TGF-beta1-induced signaling and responses was determined by varying ALK1 expression levels and measuring transcriptional activity using promoter/luciferase assays, Smad1/5 and Smad3 phosphorylation, and expression of type II collagen, PAI-1, and fibronectin.', 'Our results indicate that ALK1 is expressed in human chondrocytes and that it is a component of the TGF-beta receptor system, associating with ALK5, type II TGF-beta receptor, endoglin, and betaglycan. Furthermore, we show that both ALK1 and ALK5 are needed for TGF-beta-induced phosphorylation of intracellular mediators Smad1/5, whereas only ALK5 is essential for TGF-beta1-induced phosphorylation of Smad3. In addition, our results show that ALK1 inhibits, whereas ALK5 potentiates, TGF-beta-induced Smad3-driven transcriptional activity and the expression of PAI-1, fibronectin, and type II collagen in chondrocytes.'] Does aLK1 oppose ALK5/Smad3 signaling and expression of extracellular matrix components in human chondrocytes? | qiaojin/PubMedQA | 2 | [
-2.2958648204803467,
-1.2313352823257446,
2.557359218597412
] |
["In estrogen biosynthetic pathways, many enzymes are important for metabolism, detoxification, and bioavailability. Polymorphisms in these genes may have an effect on the enzymes' function. For example, higher expression and activation of biosynthetic enzymes and lower expression and activation of conjugation enzymes may lead to high toxicity or carcinogenesis. The authors hypothesized that single nucleotide polymorphisms (single nucleotide polymorphisms) of CYP1A1, CYP1A2, CYP1B1, CYP17, SULT1A1, SULT1E1, and SHBG genes may be risk factors for endometrial cancer.", "DNA samples from 150 cases of endometrial cancer and healthy controls (n = 165) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypic frequency of 13 different polymorphic loci on the CYP1A1 (m1, m2, m3, m4), CYP1A2 1F, CYP1B1 codon432, COMT codon158, CYP17, SULT1A1 (Arg213His, 14A/G, 85C/T in the 3' flanking region), SULT1E1-64G/A promoter region, and SHBG genes. Genotyping was validated by direct DNA sequencing. The authors also investigated the relation between expression of CYP1A1 in endometrial cancer tissues and genotypes of CYP1A1 m1.", "A decreased frequency of TC + CC genotype of the CYP1A1 m1 (T/C) polymorphism was observed in endometrial cancer patients compared with controls (OR = 0.42; 95% CI, 0.27-0.69). The T-A haplotype of CYP1A1 m1 and m2 was increased in endometrial cancer patients (P = .017). The frequency of CYP1A1 m1 T/C + C/C was higher in a high CYP1A1 expression group (P = .009). The authors also found that individuals carrying the variants of SULT1A1 codon213 and 2 single nucleotide polymorphisms in the 3' flanking region (14A/G and 85C/T) had an increased risk for endometrial cancer. The frequencies of G-A-C and A-G-T haplotypes of these 3 variants were higher in endometrial cancer patients (P < .0001; P = .0002). In addition, the frequency of combined genotypes (SULT1A1 213 GA + AA and CYP1A1 m1 TT) was higher in endometrial cancer patients. (OR, 4.58; 95% CI, 2.35-8.93)."] Are cYP1A1 , SULT1A1 , and SULT1E1 polymorphisms risk factors for endometrial cancer susceptibility? | qiaojin/PubMedQA | 2 | [
-2.1266329288482666,
-1.3630437850952148,
2.4772191047668457
] |
['User practices/rituals that involve concurrent use of tobacco and marijuana - smoking blunts and "chasing" marijuana with tobacco - are hypothesized to increase cannabis dependence symptoms.', 'Ethnographers administered group surveys to a diverse, purposive sample of marijuana users who appeared to be 17-35 years old.', 'New York City, including non-impoverished areas of Manhattan, the transitional area of East Village/Lower East Side, low-income areas of northern Manhattan and South Bronx, and diverse areas of Brooklyn and Queens.', '481 marijuana users ages 14-35, 57% male, 43% female; 27% White, 30% Black, 19% Latino, 5% Asian, 20% of other/multiple race.', 'Among many other topics, group surveys measured cannabis dependence symptoms; frequencies of chasing, blunt smoking, joint/pipe smoking, using marijuana while alone, and general tobacco use; and demographic factors.', 'Blunt smoking and chasing marijuana with tobacco were each uniquely associated with five of the seven cannabis dependence symptoms. Across symptoms, predicted odds were 2.4-4.1 times greater for participants who smoked blunts on all 30 of the past 30 days than for participants who did not smoke blunts in the past 30 days. Significant increases in odds over the whole range of the five-point chasing frequency measure (from never to always) ranged from 3.4 times to 5.1 times.'] Does smoking tobacco along with marijuana increase symptoms of cannabis dependence? | qiaojin/PubMedQA | 1 | [
-1.581339716911316,
1.0304391384124756,
-0.21053144335746765
] |
['Pharmacologic preconditioning with morphine has been shown to protect several kinds of tissues against ischemia-reperfusion injury. The aim of the present study was to investigate whether intravitreal administration of morphine induces structural protection against ischemic damage in a rabbit model of ischemic retinopathy.', 'Twenty-eight male white New Zealand rabbits were used. Animals in saline control group received 0.1 mL of phosphate-buffered saline (PBS) intravitreally with no postinjection ischemia. In the saline-control ischemia group, 15 minutes after injection of PBS, retinal ischemia was induced by raising intraocular pressure to 150 mmHg for 60 minutes. In three treatment-ischemia groups, morphine (1, 5, and 10 micromol/L) was administered intravitreally 15 minutes before induction of ischemia. In another experiment, naloxone (40 micromol/L) was administered 5 minutes before intravitreal administration of morphine (10 micromol/L) followed by 60 minutes of ischemia to investigate the role of opioid receptors in mediating the possible protective effect of morphine. Toxicity controls were performed with morphine (10 micromol/L) and naloxone (40 micromol/L) without ischemia. Histologic evaluation was performed for all groups on the seventh postoperative day.', 'Sixty minutes of ischemia led to severe cell loss in ganglion cell layer and thinning of the inner nuclear layer in saline-control ischemia compared to that of the nonischemia control group (P < 0.001). Thickness of the inner plexiform layer to the inner limiting membrane was significantly increased due to edema (P < 0.001). Administration of morphine in higher doses (5 and 10 micromol/L) significantly improved all of the above mentioned indices (P < 0.05). Administration of naloxone 15 minutes before morphine reversed most of the morphine protective effects.'] Does morphine pretreatment provide histologic protection against ischemia-reperfusion injury in rabbit retina? | qiaojin/PubMedQA | 2 | [
-2.014404535293579,
-1.5125958919525146,
2.5118865966796875
] |
["Alcohol abuse disorders emerge over time with repeated consumption of ethanol, but not all ethanol drinkers develop these disorders. There are pre-existing characteristics that indicate which drinkers are most likely to abuse alcohol. Adolescence, novelty seeking, and high stress reactivity are among the characteristics of the most vulnerable individuals. In addition, an individual's response to his or her first exposure to the drug influences future consumption. We assessed an array of behavioral and hormonal characteristics in adolescent (28-day-old) male rats before exposure to ethanol, and then determined which rats were most prone to high levels of alcohol drinking.", 'The assessments consisted of measures of anxiety (elevated plus maze), response to novelty (open field locomotion, novel object exploration), and circulating corticosterone levels after mild restraint and after the elevated plus maze task. After this test battery, the rats were placed in lickometer cages nightly (5 pm to 9 am) for evaluation of fluid consumption. Rats were first habituated to the cages with water in the lickometer bottles, and then given 10% (v/v) ethanol for 3 nights as the only available fluid. After this forced ethanol exposure, the rats were allowed to choose between 8% ethanol and water for 10 consecutive nights. After 2 nights of abstinence, the rats were again placed in the lickometer cages and given a choice between 8% ethanol and water to assess ethanol consumption in response to alcohol deprivation, a measure of relapse-like behavior.', 'Ethanol consumption on the third day of forced consumption was significantly correlated with ethanol consumption on days 8 to 10 of the choice phase, which in turn was significantly correlated to relapse-like consumption. Preference for ethanol was also significantly correlated with early consumption. Novel object exploration, open field activity, open arm time in the elevated plus maze, initial water consumption, and circulating corticosterone levels did not significantly predict deprivation-stimulated consumption.'] Does early ethanol consumption predict relapse-like behavior in adolescent male rats? | qiaojin/PubMedQA | 2 | [
-2.018601655960083,
-0.1605384200811386,
1.2688910961151123
] |
['The pathological effects of high alcohol (ethanol) consumption on gastrointestinal and hepatic systems are well recognized. However, the effects of ethanol intake on gastric and intestinal absorption and transport systems remain unclear. The present study investigates the effects of ethanol on the human peptide transporter 1 (hPepT1) which mediates the transport of di-and tripeptides as well as several orally administered peptidomimetic drugs such as beta-lactam antibiotics (e.g., penicillin), angiotensin-converting enzyme inhibitors, the anti-neoplastic agent bestatin, and prodrugs of acyclovir.', 'Xenopus oocytes were injected with hPepT1 cRNA and incubated for 3 to 10 days. Currents induced by glycyl-sarcosine (Gly-Sar), Ala-Ala (dipeptides), penicillin and enalapril measured in the presence or absence of ethanol were determined using an 8-channel 2-electrode voltage clamp system, with a membrane potential of -70 mV and 11 voltage steps of 100 milliseconds (from +50 mV to -150 mV in -20 mV increments).', 'Ethanol (200 mM) inhibited Gly-Sar and Ala-Ala currents by 42 and 30%, respectively, with IC(50)s of 184 and 371 mM, respectively. Ethanol reduced maximal transport capacity (I(max)) of hPepT1 for Gly-Sar without affecting Gly-Sar binding affinity (K(0.5) and Hill coefficient). Penicillin- and enalapril-induced currents were significantly less than those induced by dipeptides and were not inhibited by ethanol.'] Does ethanol inhibit functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes? | qiaojin/PubMedQA | 2 | [
-2.244109630584717,
-1.4225943088531494,
2.6707940101623535
] |
['Negative mood symptoms remain one of the major reasons for discontinuation of oral contraceptive pills. The aim of this study was to compare acoustic startle response and prepulse inhibition (PPI) in women with different experience of oral contraceptive pills.', 'Thirty women currently on combined oral contraceptives (COCs) with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects from treatment, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 32 women who had discontinued COC use due to adverse mood effects were included. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of musculus Orbicularis Oculi. Twenty pulse-alone trials (115dB 40ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115dB 40ms noise burst preceded at a 100ms interval by 20ms prepulses that were 72, 74, 78, or 86dB.', 'Patients with adverse mood effects of COCs exhibited lower levels of PPI with 86dB prepulse compared to COC users with no adverse effects of COCs (p<0.05). There was no difference in PPI between the two groups of prior COC users. No significant difference was found between the groups regarding acoustic startle response.'] Do patients with adverse mood effects from combined oral contraceptives have lower levels of prepulse inhibition than healthy controls? | qiaojin/PubMedQA | 2 | [
-1.8048568964004517,
-1.2381526231765747,
1.9582585096359253
] |
['To investigate the association between a vegetable-rich food pattern and obesity among Chinese adults.', 'A food pattern rich in vegetables is associated with lower risk of obesity and non-communicable chronic disease in Western countries. A similar food pattern is found in the Chinese population but the cooking method is different. A cross-sectional household survey of 2849 men and women aged 20 years and over was undertaken in 2002 in Jiangsu Province (response rate, 89.0%). Food intake was assessed by food frequency questionnaire. Factor analysis was used to identify food patterns. Nutrient intake was measured by food weighing plus consecutive individual 3-day food records. Height, weight and waist circumference were measured.', 'The prevalence of general obesity (BMI > or =28 kg m(-2)) was 8.0% in men and 12.7% in women, central obesity was 19.5% (> or =90 cm) and 38.2% (> or =80 cm), respectively. A four-factor solution explained 28.5% of the total variance in food frequency intake. The vegetable-rich food pattern (whole grains, fruits and vegetables) was positively associated with vegetable oil and energy intake. Prevalence of obesity/central obesity increased across the quartiles of vegetable-rich food pattern. After adjusting for sociodemographic factors and four distinct food patterns, the vegetable-rich pattern was independently associated with obesity. Compared with the lowest quartile of vegetable-rich pattern, the highest quartile had higher risk of general obesity (men, prevalence ratio (PR): 1.82, 95% confidence interval (CI): 1.05-3.14; women, PR: 2.25, 95% CI: 1.45-3.49).'] Is vegetable-rich food pattern related to obesity in China? | qiaojin/PubMedQA | 0 | [
0.23496024310588837,
-0.9929602146148682,
-0.18331807851791382
] |
['The NHLBI Family Heart Study (FHS) genome-wide linkage scan identified a region of chromosome 7q with a logarithm of odds score of 4.9 for body mass index (BMI).', 'We report the results of fine mapping the linkage peak using 1020 single nucleotide polymorphisms (SNPs) to test for association to obesity in families exhibiting linkage to chromosome 7. Association observed in linked families (284 obese cases/381 controls) was examined in an independent set of unrelated FHS participants (172 obese cases/308 controls) to validate the observed association. Two dichotomous obesity phenotypes were studied based on clinical BMI cutoffs and the sex-specific distribution of both BMI and leptin levels.', 'Using a P-value of 0.01 as criteria for association in the linked families, a P-value of 0.05 as criteria for association in the unrelated sample, and requiring consistency in the direction of the effect of the minor allele between the two samples, we identified two coding SNPs in the NYD-SP18 gene with minor alleles increasing the risk of obesity. Adjustment for exercise, smoking and FTO genotype did not influence the result in linked families, but improved the result in the unrelated sample. Carrying a minor allele of the nonsynonymous SNP rs6971091 conferred an odds ratio of at least 2 for obesity defined by both BMI and leptin levels.'] Is nYD-SP18 associated with obesity in the NHLBI Family Heart Study? | qiaojin/PubMedQA | 2 | [
-1.9073996543884277,
-1.3366276025772095,
2.321505069732666
] |
['A spliced variant of the human glucocorticoid receptor GRbeta has been implicated in glucocorticoid responsiveness in glaucoma. Over-expression of the FK506-binding immunophilin FKBP51 also causes a generalized state of glucocorticoid resistance. In the present study, the roles of FKBP51 in the nuclear transport of GRbeta and glucocorticoid responsiveness were investigated.', 'Human trabecular meshwork cells (GTM3 and TM5) and HeLa cells were treated with dexamethasone (DEX) and FK506 and transfected with GRbeta and FKBP51 expression vectors. Coimmunoprecipitation and Western blot analyses were performed to study interactions of FKBP51 and FKBP52 with GRalpha, GRbeta, Hsp90, or dynein. The cells were transfected with a GRE-luciferase reporter to evaluate the effects of DEX and FK506 and the overexpression of GRbeta and FKBP51 on glucocorticoid-mediated gene expression.', 'FKBP51 was involved in constitutive nuclear transport of both GRalpha and -beta in the absence of ligands. FKBP52 appeared to be solely responsible for the nuclear transport of ligand-activated GRalpha. DEX stimulated the translocation of GRalpha but not GRbeta. Overexpression of either GRbeta or FKBP51 stimulated GRbeta translocation and reduced DEX-induced luciferase in HeLa cells. FK506 did not alter DEX-induced translocation of GRalpha. However, FK506 increased the association of FKBP51 with GRbeta and stimulated DEX-induced translocation of GRbeta in normal TM cells, but not in glaucoma TM cells. Increased nuclear GRbeta significantly inhibited glucocorticoid responsiveness in TM cells.'] Does fK506-binding protein 51 regulate nuclear transport of the glucocorticoid receptor beta and glucocorticoid responsiveness? | qiaojin/PubMedQA | 2 | [
-2.363523006439209,
-1.3549954891204834,
2.71683406829834
] |
['The anti-tumoral activity of bisphosphonates (BPs) has been reported in leukemia. In this study, we attempted to evaluate the apoptotic effects of the BPs pamidronate (PAM) and zoledronic acid (ZOL) in chronic lymphocytic leukemia (CLL) samples, and to correlate it with clinical parameters and multidrug resistance (MDR) phenotype (P-glycoprotein and multidrug resistance-related protein expression and/or their functional activity).', 'Both BPs were able to induce apoptosis significantly. No correlation was observed between BP-induced apoptosis and clinical parameters or MDR phenotype.'] Do bisphosphonates induce apoptosis in CLL cells independently of MDR phenotype? | qiaojin/PubMedQA | 2 | [
-2.4852240085601807,
-1.1825661659240723,
2.7048122882843018
] |
['Inflammation and thrombosis are closely related processes, which may play a role in the pathogenesis, as well as complications, of inflammatory bowel disease (IBD). Platelet activation and platelet-leucocyte aggregation are increased and platelet aggregation is known to occur in the mesenteric vasculature in IBD. The aims of this study were to test the hypotheses that platelet-leucocyte aggregation, platelet activation and neutrophil activation occur in the mesenteric vessels of patients with ulcerative colitis (UC).', 'Platelet-leucocyte aggregates (PLAs), platelet activation (P-selectin expression) and neutrophil activation (L-selectin expression, which decreases on neutrophil activation) were assessed flow cytometrically in mesenteric arterial, and venous blood sampled in eight patients with UC and eight controls with colonic carcinoma undergoing intestinal resections.', 'In the patients with UC, the number of PLAs in the mesenteric vein exceeded that in the artery, the median rise being 38% (P=0.02). In UC, arterial PLA numbers were 0.17 (0.02-0.32) (median, range) x 10(9)/l versus venous 0.26 (0.09-1.6) x 10(9)/l (P=0.02). The median percentage increase was 45%. Mesenteric PLA formation did not occur in patients with colonic carcinoma [arterial 0.06 (0.03-0.49) x 10(9)/l vs. venous 0.05 (0.02-0.35) x 10(9)/l; P=0.55]. The median percentage change was +45% for UC patients and -5% for controls. No arteriovenous gradient was observed in P-selectin expression, but L-selectin expression (arbitrary units), increased in the mesenteric vasculature of the UC patients [arterial 839 (503-995), venous 879 (477-1035); P=0.03] and fell in those with colonic carcinoma [arterial 900 (660-959), venous 850 (546-957); P=0.04]. The median percentage change was +4% for UC and -7% for controls.'] Do platelet-leucocyte aggregates form in the mesenteric vasculature in patients with ulcerative colitis? | qiaojin/PubMedQA | 2 | [
-1.5436259508132935,
-1.6478760242462158,
2.141692638397217
] |
["To elucidate the molecular basis of the progressive enlargement of dorso-cervical adipose tissue, the so-called 'buffalo hump', that appears in a sub-set of patients with HIV-1/HAART-associated lipodystrophy.", "Analysis of the expression of marker genes of mitochondrial function, adipogenesis, inflammation and cell proliferation in ten 'buffalo hump' samples and ten subcutaneous fat samples from HIV-1-infected/HAART-treated patients, and in ten healthy controls.", 'Quantitative real-time polymerase chain reaction analysis of mitochondrial DNA and gene transcripts, and immunoblot for specific proteins.', "'Buffalo hump' patients had lower levels of mitochondrial DNA and mitochondrial DNA-encoded transcripts with respect to healthy controls. The uncoupling protein (UCP)-1 gene was expressed only in 'buffalo hump' fat. There were no significant changes in the expression of UCP2, UCP3 or of marker genes of adipogenesis in 'buffalo hump' patients relative to healthy controls. 'Buffalo hump' fat did not show the high expression of tumor necrosis factor-alpha and beta2-microglobulin identified in lipoatrophic subcutaneous fat from patients. The expression of the macrophage marker CD68 was also lower in 'buffalo hump' than in subcutaneous fat from patients. In contrast, 'buffalo hump' showed a higher expression of the cell proliferation marker PCNA."] Does differential gene expression indicate that 'buffalo hump ' is a distinct adipose tissue disturbance in HIV-1-associated lipodystrophy? | qiaojin/PubMedQA | 2 | [
-2.4908673763275146,
-1.0629994869232178,
2.631615161895752
] |
['To determine if intravenous infusion of a combination of oxytocin and ergometrine maleate is better than oxytocin alone to decrease blood loss at caesarean delivery for labour arrest.', 'Prospective, double-blinded, randomised controlled trial.', 'Mount Sinai Hospital, Toronto, Canada.', 'Women undergoing caesarean deliveries for labour arrest.', "Forty-eight women were randomised to receive infusion of either ergometrine maleate 0.25 mg + oxytocin 20 iu or oxytocin 20 iu alone, diluted in 1 l of lactated Ringer's Solution, immediately after delivery of the infant. Unsatisfactory uterine contractions after delivery were treated with additional boluses of the study solution or rescue carboprost. Blood loss was estimated based on the haematocrit values before and 48 hours after delivery.", 'The primary outcome was the estimated blood loss, while the secondary outcomes included the use of additional uterotonics, need for blood transfusion and the incidence of adverse effects.', 'The estimated blood loss was similar in the oxytocin-ergometrine and oxytocin-only groups; 1218 +/- 716 ml and 1299 +/- 774 ml, respectively (P = 0.72). Significantly fewer women required additional boluses of the study drug in the oxytocin-ergometrine group (21 and 57%; P = 0.01). Nausea (42 and 9%; P = 0.01) and vomiting (25 and 4%; P = 0.05) were significantly more prevalent in the oxytocin-ergometrine group.'] Does oxytocin-ergometrine co-administration reduce blood loss at caesarean delivery for labour arrest? | qiaojin/PubMedQA | 2 | [
-1.7943748235702515,
-1.503989338874817,
2.2763688564300537
] |
['Most experimental therapy studies are performed in mice that bear subcutaneous or orthotopic hepatoma but are otherwise healthy. We questioned whether a pre-existing fibrosis affects tumour development of implanted syngenic hepatoma cells. To further investigate a selected panel of factors involved in tumour growth, tumour organ samples were characterized for gene expression of vascular endothelial growth factor (VEGF)-A/-C, VEGF receptors Flt1, Flk-1, Flt-4 and for VEGF-A protein levels.', 'The presented data show that tumour sizes were 3.7-fold increased and fibrotic livers had numerous satellites. Increased tumour sizes were associated with elevated intratumoral VEGF-A protein amounts and intratumoral increased VEGF receptor gene expression levels in tumour tissue from fibrotic livers as compared with non-fibrotic livers. Additionally, intratumoral gene expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 were elevated in fibrotic mice.'] Is accelerated orthotopic hepatocellular carcinomas growth linked to increased expression of pro-angiogenic and prometastatic factors in murine liver fibrosis? | qiaojin/PubMedQA | 2 | [
-2.568591356277466,
-1.1429595947265625,
2.809788227081299
] |
['We evaluated implantation-associated quantitative changes in endometrial and peripheral natural killer (NK)-cell populations of pigs.', 'Natural killer cell populations were investigated in 10, 15, 20, 30 and 40 days pregnant and non-pregnant (NP) sows by flow cytometry, immunohistochemistry and morphometry.', 'The number of endometrial CD16(+) NK cells significantly declined at attachment phase of implantation and remained relatively low over the course of implantation. The CD16(+) NK cells in situ showed implantation-phase dependent density and localization. Prior to implantation, they substantially resided in the subepithelial stroma. As implantation advances, the density of NK cells into subepithelial stroma decreased while that of NK cells into glandular layer increased, suggesting implantation-induced re-location far from the attached conceptus. The number of CD56(+) lymphocytes was the greatest at pre-attachment phase of implantation, dropped at the time of attachment and increased up to end of early pregnancy period. The CD3(-) CD8(+) NK-cell number decreased significantly when the definitive placenta is established. No significant differences in the numbers of peripheral blood CD16(+), CD56(+) and CD3(-) CD8(+) NK cells between pregnant and NP animals as well as relative to the implantation phase were observed.'] Is superficial implantation in pigs associated with decreased numbers and redistribution of endometrial NK-cell populations? | qiaojin/PubMedQA | 2 | [
-2.459017038345337,
-1.091763973236084,
2.6857728958129883
] |
['To examine the association between skipping breakfast, daily energy, macronutrients and food intakes, and BMI in pre-school children.', "A cross-sectional study using information on children's food consumption and measured height and weight. Energy and macronutrient intakes of the children were derived from parent/day-care attendant's responses to 24 h recall interviews and eating behaviour questionnaires.", 'Data obtained from a representative sample (n 2,103) of children born in Quebec (Canada) in 1998.', 'One thousand five hundred and forty-nine children, with a mean age of 49 (sd 3.12) months.', "Ten per cent of children ate breakfast on fewer than 7 days per week. This behaviour was associated with a lower diet quality and concentrated energy intakes through higher protein intakes at lunch and the consumption of snacks higher in energy and carbohydrate in the afternoon and evening; yet total daily energy intakes were not significantly different from those of pre-school children who ate breakfast every day. Breakfast skippers' mean BMI increased as intake of energy, carbohydrates or servings of grain products increased; however, this was not the case for breakfast eaters. When Cole's cut-off for overweight/obesity was used, overweight/obesity in breakfast skippers was related to the dinner-time consumption of approximately 3,000 kJ (700 kcal) or more for energy intake, approximately 100 g or more of carbohydrates, or approximately 3 servings or more of grain products."] Is breakfast skipping associated with differences in meal patterns , macronutrient intakes and overweight among pre-school children? | qiaojin/PubMedQA | 2 | [
-1.390967845916748,
-0.15207979083061218,
0.6935120820999146
] |
['The purpose of this study was to quantitatively analyse laser scanning in vivo confocal microscopy images of the corneal epithelium and sub-basal nerve plexus in patients with keratoconus and to correlate these microstructural observations with corneal sensitivity.', 'A total of 31 eyes of 31 normal human subjects, and 27 eyes of 27 subjects with an established diagnosis of keratoconus were recruited. Twelve subjects with keratoconus had never worn contact lenses (K-NCL). Fifteen subjects with keratoconus wore contact lenses routinely (K-CL). All eyes were examined using slit-lamp biomicroscopy, Orbscan topography, non-contact corneal aesthesiometry, and laser scanning in vivo confocal microscopy.', 'Central corneal sensation was significantly lower in K-CL compared to normal (P=0.028). However, there was no significant difference in corneal sensation between the normal and K-NCL groups (P=0.059). Both sub-basal nerve density (P<0.001) and basal epithelial density (P<0.001) were significantly lower than normal in all keratoconic subjects. Central corneal sensation was only significantly correlated with sub-basal nerve density (P=0.001) and was not significantly correlated with any of the basal epithelial parameters. Sub-basal nerve density showed significant positive correlation with basal epithelial density (P<0.001).'] Do laser scanning in vivo confocal microscopy and quantitative aesthesiometry reveal decreased corneal innervation and sensation in keratoconus? | qiaojin/PubMedQA | 2 | [
-2.1490588188171387,
-1.2543261051177979,
2.512007474899292
] |
['Tai Chi Chuan, a traditional Chinese exercise, is thought to improve cardiopulmonary function in patients with chronic disease. This study investigated the effect of Tai Chi Chuan on the pulmonary function and daily symptoms of asthmatic children.', 'Thirty asthmatic children were enrolled into the study. Fifteen of the 30 children participated in a 12-week Tai Chi Chuan program and the remaining 15 constituted the control group. Prior to study participation, the pulmonary function of all enrolled children was assessed at rest, after exercise, and after exercise plus iced water. A 3-day symptoms questionnaire was also completed and a score obtained after each pulmonary function test.', 'There were no significant differences between the two groups in baseline pulmonary function and severity of asthmatic symptoms before study commencement, at rest, after exercise, or after exercise plus iced water. However, after the 12-week program, children in the Tai Chi Chuan group had a significant improvement in pulmonary function compared to the control group. Although there were no significant differences in post-training symptom scores at rest and after exercise between the two groups, under the stronger challenge of exercise plus iced water, children in the Tai Chi Chuan group had milder symptoms than those in the control group.'] Does tai Chi Chuan training improve the pulmonary function of asthmatic children? | qiaojin/PubMedQA | 1 | [
-1.6430851221084595,
1.7675504684448242,
-0.841307520866394
] |
['It is often a clinical dilemma to determine when to collect autologous peripheral blood progenitor cells (PBPCs) in patients who received prior chemotherapy. It is also challenging to predict if the collected cells will be enough for one or two transplants.', 'A total of 103 PBPC donors were followed to evaluate factors that predict poor autologous PBPC collection. The donors were categorized into three groups: plasma cell disorders (PCDs), lymphomas, and normal allogeneic donors.', 'Our evaluation showed that platelet (PLT) count before growth factor administration significantly correlated with total CD34+ cell yield (Spearman r = 0.38, p < 0.001). Further analysis showed this correlation was only significant in plasma cell disease patients who received prior chemotherapy (Spearman r = 0.5, p = 0.008). Baseline PLT counts did not correlate with PBPC collection yield in untreated PCD, lymphoma, and normal allogeneic donors. In addition, daily PLT count during PBPC harvest correlated with CD34+ cell yield for that day (Spearman r = 0.41, p < 0.001). With a multiple linear regression model (adjusted R(2) = 0.31, AIC = 63.1), it has been determined that the baseline PLT count significantly correlates with total CD34+ cell yield in treated PCD patients.'] Is platelet count a sensitive predictor of autologous peripheral blood progenitor cell collection yield in previously treated plasma cell disease patients? | qiaojin/PubMedQA | 2 | [
-1.7791385650634766,
-1.4999785423278809,
2.2789525985717773
] |
['Pentoxifylline (PTX) has been shown to reduce hepatic injury after normothermic ischemia and reperfusion (I-R) in rat liver.', 'The aim of this study was to evaluate the effects of PTX on liver expression of tumor necrosis factor alpha (TNFalpha) mRNA following normothermic liver I-R.', 'A segmental normothermic ischemia of the liver was induced in male Lewis rats by occluding the blood vessels including the bile duct to the median and left lateral lobes for 90 min. At the end of ischemia the nonischemic liver lobes were resected. Rats were divided into three groups: group 1, control Ringer lactate administration; group 2, PTX treatment; group 3, sham-operated control rats. PTX (50 mg/kg) was injected intravenously 30 min before and 60 min after induction of ischemia. Survival rates were compared and the serum activities of TNFalpha, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured. Histology of the liver was assessed 6 h after reperfusion. Liver TNFalpha mRNA was assessed by PCR amplification at 0, 60, 120, and 210 min after reperfusion.', 'PTX treatment significantly increased 7 day survival (93.3%) compared with nontreated control rats (46.6%, p<0.007). The extent of liver necrosis and the release of liver enzymes were significantly decreased after PTX treatment. Serum activities of TNFalpha were significantly decreased and liver expression of TNFalpha mRNA was inhibited after PTX treatment.'] Does pentoxifylline inhibit liver expression of tumor necrosis factor alpha mRNA following normothermic ischemia-reperfusion? | qiaojin/PubMedQA | 2 | [
-2.1184113025665283,
-1.5104621648788452,
2.6090917587280273
] |
['Overexpression of Bcl-2 is frequent in human cancers and has been associated with radioresistance. Here we investigated the potential impact of heavy ions on Bcl-2 overexpressing tumors.', 'Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) exposed to gamma-rays or heavy ions were assessed for the clonogenic survival, apoptosis and cell cycle distribution.', 'Whereas Bcl-2 cells were more resistant to gamma-rays (0.2keV/microm) and helium ions (16.2keV/microm) than Neo cells, heavy ions (76.3-1610keV/microm) yielded similar survival regardless of Bcl-2 overexpression. Carbon ions (108keV/microm) decreased the difference in the apoptotic incidence between Bcl-2 and Neo cells, and prolonged G(2)/M arrest that occurred more extensively in Bcl-2 cells than in Neo cells.'] Do energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2? | qiaojin/PubMedQA | 2 | [
-2.269134759902954,
-0.9521277546882629,
2.138701915740967
] |
['The objective of this study was to determine whether follicles grown within human ovarian cortical strip culture for 6 days in serum-free medium could be isolated at the secondary stage of pre-antral development and grown in vitro to the late pre-antral/early antral stage during a 4 day culture period.', 'Ovarian cortical biopsies were obtained from six women aged 26-40 years, with informed consent, during elective Caesarean section. Small tissue slices of ovarian cortex, with underlying stromal tissue removed, were cultured in serum-free medium for 6 days and at the end of this period pre-antral (secondary) follicles were dissected from the strips. Seventy-four intact pre-antral follicles ranging in size (66-132 microm) (mean size 100 microm +/- 3.4) were selected for further culture. Follicles were placed individually within V-shaped microwell culture plates in serum-free medium in the presence (n = 38) or absence (n = 36) of 100 ng/ml of human recombinant activin A.', 'Pre-antral follicles grown for 4 days in the presence of activin A grew to a larger size (mean diameter 143 microm +/- 7.4) than those grown in control medium (mean diameter 111 microm +/- 8) (P < 0.005). Ninety percent of follicles cultured in the presence of activin A increased in size during the first 2 days of culture compared with only 36% of follicles in control medium (P > 0.005). Of the follicles surviving the entire culture period, 30% of those cultured in the presence of activin A showed normal morphology with intact oocytes and antral formation. None of the follicles grown in control medium developed antral cavities and >90% of those follicles collected at the end of the culture period showed signs of oocyte degeneration.'] Does a two-step serum-free culture system support development of human oocytes from primordial follicles in the presence of activin? | qiaojin/PubMedQA | 2 | [
-1.185874104499817,
-1.6727757453918457,
1.8522703647613525
] |
['Sperm DNA fragmentation is a possible predictive parameter for male fertility status. The occurrence of M540 bodies in semen of subfertile subjects affects flow cytometric investigations in sperm. We set up a new method to evaluate DNA fragmentation excluding M540 bodies.', 'DNA fragmentation was evaluated by flow cytometry in semen of 75 subjects both by terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL, traditional method) and by double staining with TUNEL and propidium iodide (PI, new method).', 'The use of the new method revealed that TUNEL underestimates sperm DNA fragmentation in flow cytometry and showed two sperm populations stained with low (PI(dim)) and high (PI(br)) avidity for PI. The PI(dim) population is entirely composed of DNA fragmented sperm and its incidence shows highly significant negative correlations with morphology, motility, sperm count and concentration (respectively, r = -0.51, -0.52, -0.46 and -0.32, n = 75). DNA fragmentation in the PI(br) sperm population is independent from semen quality.'] Does nuclear staining identify two populations of human sperm with different DNA fragmentation extent and relationship with semen parameters? | qiaojin/PubMedQA | 2 | [
-2.0677621364593506,
-1.1535186767578125,
2.3953890800476074
] |
['Toxoplasma gondii is among the most successful parasites, with nearly half of the human population chronically infected. T. gondii has five sHsps [small Hsps (heat-shock proteins)] located in different subcellular compartments. Among them, Hsp20 showed to be localized at the periphery of the parasite body. sHsps are widespread, constituting the most poorly conserved family of molecular chaperones. The presence of sHsps in membrane structures is unusual.', 'The localization of Hsp20 was further analysed using high-resolution fluorescent light microscopy as well as electron microscopy, which revealed that Hsp20 is associated with the outer surface of the IMC (inner membrane complex), in a set of discontinuous stripes following the same spiralling trajectories as the subpellicular microtubules. The detergent extraction profile of Hsp20 was similar to that of GAP45 [45 kDa GAP (gliding-associated protein)], a glideosome protein associated with the IMC, but was different from that of IMC1 protein. Although we were unable to detect interacting protein partners of Hsp20 either in normal or stressed tachyzoites, an interaction of Hsp20 with phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate phospholipids could be observed.'] Is toxoplasma gondii Hsp20 a stripe-arranged chaperone-like protein associated with the outer leaflet of the inner membrane complex? | qiaojin/PubMedQA | 2 | [
-2.398348569869995,
-1.2466952800750732,
2.7976975440979004
] |
['Protein kinase A signaling has long been known to play an important role in cardiac function. Dysregulation of the protein kinase A system, caused by mutation of the protein kinase A regulatory subunit gene PRKAR1A, causes the inherited tumor syndrome Carney complex, which includes cardiac myxomas as one of its cardinal features. Mouse models of this genetic defect have been unsatisfactory because homozygote null animals die early in development and heterozygotes do not exhibit a cardiac phenotype.', 'To study the cardiac-specific effects resulting from complete loss of Prkar1a, we used cre-lox technology to generate mice lacking this protein specifically in cardiomyocytes. Conditional knockout mice died at day 11.5 to 12.5 of embryogenesis with thin-walled, dilated hearts. These hearts showed elevated protein kinase A activity and decreased cardiomyocyte proliferation before demise. Analysis of the expression of transcription factors required for cardiogenesis revealed downregulation of key cardiac transcription factors such as the serum response factor, Gata4, and Nkx2-5. Although heart wall thickness was reduced overall, specific areas exhibited morphological changes consistent with myxomatous degeneration in the walls of knockout hearts.'] Does heart-specific ablation of Prkar1a cause failure of heart development and myxomagenesis? | qiaojin/PubMedQA | 2 | [
-2.6357100009918213,
-0.8890601396560669,
2.5694010257720947
] |
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