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['To investigate the pathways by which cyclic AMP (cAMP) stimulates glucagon-like peptide-1 (GLP-1) secretion, using the GLUTag enteroendocrine cell line.', 'GLP-1 release from GLUTag cells was measured in response to agents that increase cAMP, and single cells were studied by fluorescence calcium imaging and electrophysiology to evaluate the underlying pathways.', 'Pituitary adenylate cyclase-activating polypeptide increased cAMP levels and stimulated GLP-1 release from GLUTag cells. Agents that increase cAMP levels, including forskolin plus 3-isobutyl-1-methylxanthine (fsk/IBMX), triggered a rise in the intracellular calcium concentration and enhanced the response to glucose by increasing both the number of cells responding to glucose and the magnitude of calcium responses in individual cells. Importantly, fsk/IBMX also stimulated GLP-1 release and intracellular calcium elevation even in the absence of nutrients. fsk/IBMX triggered membrane depolarisation and the firing of action potentials, associated with a +14 mV shift in the voltage-dependence of activation of hyperpolarisation-activated currents and the closure of a background potassium conductance.'] Does cyclic AMP trigger glucagon-like peptide-1 secretion from the GLUTag enteroendocrine cell line? | qiaojin/PubMedQA | 2 | [
-2.641340970993042,
-1.0694823265075684,
2.773434638977051
] |
['Aortic regurgitation (AR) causes left ventricular (LV) volume overload, leading to progressive LV dilatation and dysfunction. In the present study it was examined whether blockade of angiotensin II type 1 receptor (AT1) could improve survival in cases of chronic severe AR.', 'AR was induced by puncturing the aortic valves of wild-type (WT) and AT1a knockout (KO) mice. Mice that survived for 4 weeks after the operation were deemed to be a model of chronic severe AR and were followed up for 50 weeks (WT, n=29; KO, n=31). Baseline measurements made 4 weeks after surgery showed similar LV cavity and function in both genotypes. These conditions progressively worsened in both genotypes, but 16 weeks after baseline, KO mice showed significantly less LV dilatation, hypertrophy and interstitial fibrosis than WT mice. Cardiac mRNA expression of B-type natriuretic peptide and type I collagen was lower in KO than WT mice. The 50-week mortality rate was significantly lower among KO (45.2%) than WT (86.2%) mice, and postmortem findings indicated that the lower mortality was attributable to a lower incidence of congestive heart failure.'] Does genetic disruption of angiotensin II type 1a receptor improve long-term survival of mice with chronic severe aortic regurgitation? | qiaojin/PubMedQA | 2 | [
-2.1472222805023193,
-1.385486364364624,
2.52200984954834
] |
['Evidence has implicated the retina as a principal controller of refractive development. In the present study, the retinal transcriptome was analyzed to identify alterations in gene expression and potential signaling pathways involved in form-deprivation myopia of the chick.', 'One-week-old white Leghorn chicks wore a unilateral image-degrading goggle for 6 hours or 3 days (n = 6 at each time). Total RNA from the retina/(retinal pigment epithelium) was used for expression profiling with chicken gene microarrays (Chicken GeneChips; Affymetrix, Santa Clara, CA). To identify gene expression level differences between goggled and contralateral nongoggled eyes, normalized microarray signal intensities were analyzed by the significance analysis of microarrays (SAM) approach. Differentially expressed genes were validated by real-time quantitative reverse transcription-polymerase chain reaction (qPCR) in independent biological replicates.', 'Small changes were detected in differentially expressed genes in form-deprived eyes. In chickens that had 6 hours of goggle wear, downregulation of bone morphogenetic protein 2 and connective tissue growth factor was validated. In those with 3 days of goggle wear, downregulation of bone morphogenetic protein 2, vasoactive intestinal peptide, preopro-urotensin II-related peptide and mitogen-activated protein kinase phosphatase 2 was validated, and upregulation of endothelin receptor type B and interleukin-18 was validated.'] Does form-deprivation myopia in chick induce limited changes in retinal gene expression? | qiaojin/PubMedQA | 2 | [
-2.464686870574951,
-1.3164595365524292,
2.806159257888794
] |
['Chronic kidney disease (CKD) patients show evidence of chronic inflammation with mononuclear cell activation which is mainly caused by uraemia itself and is exacerbated by haemodialysis. Small fragments of bacterial DNA (DNAb) are ubiquitous contaminants, which are capable of passing through dialyser membranes causing the stimulation of cells of the immune system. The aim of this study was to evaluate whether DNAb contamination may have an effect on apoptosis of activated monocytes from CKD-5 patients.', 'To test the ability of DNAb to stimulate the inflammatory response, mononuclear cells from 10 chronic kidney disease patients who had not begun haemodialysis (ND-CKD-5) and 10 patients undergoing regular dialysis (HD) were cultured in the presence and absence of DNAb. Ten healthy subjects were used as controls.', 'The percentage of IL-1beta cells was higher in HD patients than in ND-CKD-5 (33.9 +/- 3.0% vs 20.0 +/- 2.3%, P < 0.001) and controls (9.4 +/- 2.1%, P < 0.001). The presence of DNAb induced an increase in the percent of cells expressing IL-1beta in controls, ND-CKD5 and HD patients. In addition, the DNAb also increased the release of cytokines in all groups, the effect was more marked in ND-CKD5 and HD than in controls. DNAb only inhibited apoptosis of activated mononuclear cells from, ND-CKD (17.5 +/- 2.8% vs 12.3 +/- 2.6%, P < 0.01) and HD patients (27 +/- 2.5% vs 14.6 +/- 2.9%, P < 0.01).'] Does bacterial DNA prolong the survival of inflamed mononuclear cells in haemodialysis patients? | qiaojin/PubMedQA | 2 | [
-2.1139614582061768,
-1.345306396484375,
2.4537580013275146
] |
['Behavioral sensitization to the locomotor stimulant effects of ethanol may be related to neuroadaptations within glutamatergic systems. Previous research has suggested that the N-methyl-D: -aspartate (NMDA) subclass of glutamate receptors is critical for the development of ethanol sensitization. We hypothesized that sensitization to ethanol would be associated with changes in sensitivity to NMDA receptor ligands.', 'DBA/2J and heterogeneous stock (HS) mice were injected with ethanol or saline for 12 days and tested for their acute and sensitized responses to the locomotor effects of ethanol in automated activity monitors. After this treatment phase, mice were challenged with MK-801, ethanol, or ketamine, and locomotor activity was measured for 20 to 60 min. Other ethanol-sensitized and nonsensitized mice were assessed for sensitivity to the effects of NMDA after tail-vein infusions.', 'There was no evidence for cross-sensitization to MK-801 or ketamine, or altered sensitivity to NMDA in ethanol-sensitized animals, in any experiment. In one experiment, previously ethanol-treated HS mice developed tolerance to the locomotor stimulant effects of ketamine.'] Does behavioral sensitization to ethanol result in cross-sensitization to NMDA receptor antagonists? | qiaojin/PubMedQA | 2 | [
-2.409137487411499,
-1.2276062965393066,
2.6792349815368652
] |
['We aimed to compare the level of thrombocytopenia in cirrhotic patients with HBV and those with HCV, and to investigate whether the reduced serum level of IL-6 in patients with HCV is responsible for the lower platelet count compared to those with HBV through the effect on serum thrombopoietin level.', 'Fifty-three patients with liver cirrhosis, 28 of who were HBV- seropositive (Group A), 25 of who were HCV- seropositive (Group B) and 15 healthy controls were enrolled in this study.', 'Platelet count in group B [75 (1.5-99) K/microL] were lower than those of group A [140 (62-374) K/microL] (p < 0.001). The median levels of serum thrombopoietin in patients [group A: 31.9 (31-113) pg/mL and group B: 38.0 (31.2-102) pg/mL] and controls [31.3 (31-153) pg/mL] did not show statistically significant difference. The patients compared to controls, had higher serum IL-6 levels [3.6 (2-1150) vs. 2.0 (2-9.9) pg/mL], (p < 0.01), which showed similarity in group A and B patients [3.65 (2-1150) vs. 3.3 (2-45) pg/mL], (p=NS). Serum thrombopoietin level was not correlated with serum IL-6 levels in any group. Serum thrombopoietin and IL-6 levels had no relationship with platelet count and with Child-Pugh score.'] Does thrombopoietin or interleukin-6 have no effect on thrombocytopenia of cirrhosis? | qiaojin/PubMedQA | 2 | [
-0.9982282519340515,
-1.6312661170959473,
1.6185098886489868
] |
['The aim of the study was to define the clinical characteristics and outcome of patients found to have undetected hepatocellular carcinomas (HCC) at liver transplantation. Patients who underwent liver transplantation and were unexpectedly found to have a HCC despite prior workup showing normal alpha-fetoprotein levels and/or no visible radiological lesion were defined as having an undetected HCC.', 'Thirty-two of these patients had a histological diagnosis of HCC in the explanted liver. Undetected HCC was defined as a carcinoma found only on pathological evaluation of the explanted liver, with a pre-OLT workup showing a normal serum alpha-fetoprotein (AFP) level (<20 ng/mL) and/or no suspicious lesion on preoperative radiological evaluation.', 'Nine patients had a tumor that met the criteria for an undetected HCC. The most common cause for transplantation was cryptogenic cirrhosis (44.4%). Tumor size was 2 cm or less in all patients, vascular invasion was detected in 11.1% of the patients, and tumor, node, metastasis (TNM) classification was stage I in 77.8%. Eight patients (88.9%) remained alive at the cessation of the analysis with a mean follow-up of 60 +/- 30.4 months. There was no tumor recurrence in any patient. Statistical analysis showed significant differences between undetected and detected HCCs when causes of pretransplantation liver disease, peak AFP level, tumor size, number of tumors, presence of vascular invasion or pathological differentiation were compared. Undetected HCCs were associated with a better survival rate after liver transplantation (p = 0.008).'] Is undetected hepatocellular carcinoma in patients undergoing liver transplantation : associated with favorable outcome? | qiaojin/PubMedQA | 2 | [
-2.023435592651367,
-1.4381319284439087,
2.4750165939331055
] |
['To investigate the complication profile and the long-term functional outcome of combined pars plana vitrectomy and scleral-fixated sutured posterior chamber lens (PC IOL) implantation.', 'Retrospective, consecutive, interventional case series.', 'The records of 63 patients (mean age, 67.5 years) were reviewed retrospectively (follow-up, 12 to 132 months; mean, 43.5 months). The underlying ocular pathologic features; the intraoperative, early (within two weeks after surgery), and late complications (more than two weeks after surgery); final best-corrected visual acuity (BCVA); and the refractive outcome were recorded.', 'Fifty-nine of 63 procedures (93.7%) were performed without complications. Intraoperative complications included vitreous hemorrhage (n = 2), a retinal tear (n = 1), and a rupture of the iris base (n = 1). Early complications included transient raise of intraocular pressure (IOP; n = 19), transient vitreous hemorrhage (n = 2), scleral tunnel insufficiency (n = 5), pupillary capture of intraocular lens [IOL] (n = 6), persistent vitreous (n = 3), and choroidal hemorrhage (n = 1). Late complications occurred in 12 patients: rhegmatogenous retinal detachment (n = 4), proliferative vitreoretinopathy retinal detachment secondary to the underlying ocular pathologic features (n = 2), choroidal hemorrhage (n = 1), macular pucker (n = 1), and IOL dislocation (n = 4), including two cases of suture break. Mean BCVA in logarithm of the minimum angle of resolution units improved significantly from 1.025 (standard deviation [SD], 0.654) to 0.766 (SD, 0.750; P = .03). Mean cylindric equivalent significantly changed from 0.92 diopters (D; SD, 1.075) to 1.76 D (SD, 1.344; P = .005).'] Do long-term safety and functional outcome of combined pars plana vitrectomy and scleral-fixated sutured posterior chamber lens implantation? | qiaojin/PubMedQA | 2 | [
-2.1224639415740967,
-1.5178929567337036,
2.684089422225952
] |
['Open appendicectomy is the traditional standard treatment for appendicitis. Laparoscopic appendicectomy is perceived as a procedure with greater potential for complications and longer operative times. This paper examines the hypothesis that unsupervised laparoscopic appendicectomy by surgical trainees is a safe and time-effective valid alternative.', 'Medical records, operating theatre records and histopathology reports of all patients undergoing laparoscopic and open appendicectomy over a 15-month period in two hospitals within an area health service were retrospectively reviewed. Data were analysed to compare patient features, pathology findings, operative times, complications, readmissions and mortality between laparoscopic and open groups and between unsupervised surgical trainee operators versus consultant surgeon operators.', 'A total of 143 laparoscopic and 222 open appendicectomies were reviewed. Unsupervised trainees performed 64% of the laparoscopic appendicectomies and 55% of the open appendicectomies. There were no significant differences in complication rates, readmissions, mortality and length of stay between laparoscopic and open appendicectomy groups or between trainee and consultant surgeon operators. Conversion rates (laparoscopic to open approach) were similar for trainees and consultants. Unsupervised senior surgical trainees did not take significantly longer to perform laparoscopic appendicectomy when compared to unsupervised trainee-performed open appendicectomy.'] Is unsupervised laparoscopic appendicectomy by surgical trainees safe and time-effective? | qiaojin/PubMedQA | 2 | [
-1.8651829957962036,
-1.068986415863037,
2.034485340118408
] |
['The AlloMap gene expression test is used for the non-invasive detection of rejection. However, the impact of early post-transplant ischemic injury on subsequent AlloMap gene expression analysis has not been evaluated before.', 'Sixty seven heart transplant recipients, mean age 53 years, were evaluated at a mean 34 months post-transplant. AlloMap score was determined on the same day of heart biopsies. Nineteen patients had evidence of early post-transplant ischemic injury (Injury group). These were compared with the remaining 48 patients, Control group.', 'Using multiple regression model with a backward selection method, post-transplant ischemic injury was found to be associated with significant increased AlloMap score compared with controls (31.5 +/- 4.6 vs. 26 +/- 6.2, p < 0.001). The Injury group had increased transplant vasculopathy (KM 5-year freedom from vasculopathy: 34% vs. 52%, p = 0.015), than Controls.'] Is post-transplant ischemic injury associated with up-regulated AlloMap gene expression? | qiaojin/PubMedQA | 2 | [
-1.4430404901504517,
-1.33805251121521,
1.8341600894927979
] |
['The innate immunopathogenesis responsible for the susceptibility to hepatocyte injury in chronic hepatitis B surface antigen carriers is not well defined. In this study, hepatitis B virus (HBV) transgenic mice (named HBs-Tg) were oversensitive to liver injury after immunologic [polyinosinic:polycytidylic acid or concanavalin A (ConA)] or chemical (CCl4) triggering. It was then found that the nonhepatotoxic low dose of ConA for wild-type mice induced severe liver injury in HBs-Tg mice, which was dependent on the accumulated intraheptic natural killer (NK) cells. Expressions of NKG2D ligands (Rae-1 and Mult-1) in hepatocytes were markedly enhanced upon ConA stimulation in HBs-Tg mice, which greatly activated hepatic NK cells via NKG2D/Rae-1 or Mult-1 recognition. Interestingly, the presence of NK T cells was necessary for NK cell activation and worked as positive helper cell possibly by producing interferon-gamma and interleukin-4 in this process.'] Does increased susceptibility to liver injury in hepatitis B virus transgenic mice involve NKG2D-ligand interaction and natural killer cells? | qiaojin/PubMedQA | 2 | [
-2.4445927143096924,
-1.299378752708435,
2.833329677581787
] |
['Regular physical activity has been shown to improve outcome of acute myocardial infarction (AMI) in the elderly population. The aim of this study was to evaluate whether the positive role of an active lifestyle on cardiac prognosis extends to elderly patients with AMI who undergo primary percutaneous transluminal coronary angioplasty (PTCA).', 'We prospectively studied 180 patients with AMI aged > or = 70 years and treated with primary PTCA. In all patients, physical activity levels before AMI were quantified by a score derived from the Physical Activity Scale for the Elderly (PASE). Cardiac deaths and nonfatal cardiac events were evaluated within 30 days and 1-year from primary PTCA.', 'A high PASE score was significantly associated with a strong reduction of 30-day cardiac deaths (from 23.1% to 4%; P for trend = .021) and overall nonfatal events (from 21.1% to 10%; P for trend = .01). Accordingly, at 1 year of follow-up, the incidence of cardiac mortality and nonfatal events significantly decreased with increasing PASE score (from 28.8% to 8% and from 55.7% to 14.5%, respectively). Logistic regression analysis indicated that physical activity before AMI was an independent predictor of increased survival in those patients that showed the highest PASE scores. In addition, at 6 months of follow-up, although low ejection fraction and recurrent angina strongly predicted 1-year mortality, high PASE scores still predicted a better outcome.'] Does an active lifestyle improve outcome of primary angioplasty in elderly patients with acute myocardial infarction? | qiaojin/PubMedQA | 2 | [
-1.7649657726287842,
-1.2078235149383545,
1.9821703433990479
] |
['Histone deacetylases (HDACs) have been linked to cell cycle control in various models, involving regulation of the cyclin-dependent kinase inhibitor p27(Kip1).', 'Here, we demonstrate that HDAC inhibition by trichostatin A reduces S-phase kinase-associated protein 2 mRNA and protein abundance. Furthermore, in contrast to HDAC1, recruited to the skp2 promoter in the G(0) phase, HDAC3 is bound in early S phase. Activating function of HDAC3 towards the skp2 gene has been validated using RNA interference techniques. siRNAs, targeting HDAC3 specifically, reduced skp2 transcription.'] Is hDAC3 linked to cell cycle machinery in MiaPaCa2 cells by regulating transcription of skp2? | qiaojin/PubMedQA | 2 | [
-2.347917079925537,
-1.0917634963989258,
2.4420762062072754
] |
['To examine longitudinal data about depression in relationship to glycemic control and as a risk factor for diabetic retinopathy (DR). Depression is a common psychiatric disorder among diabetic persons and has been shown in cross-sectional studies to be associated with the vascular complications of diabetes.', 'A total of 483 African-American patients with Type 1 diabetes had a baseline examination and 6-year follow-up examination. Evaluations at both visits included administering the Beck Depression Inventory (BDI), a detailed ophthalmologic examination, retinal photographs, and measurement of glycosylated hemoglobin as an index of glycemic control. Six-year progression of DR between baseline and follow-up visits was evaluated from the change in retinopathy severity using the Early Treatment of Diabetic Retinopathy Study grading scale.', 'Patients with high BDI scores at both baseline and 6-year follow-up visits had significantly higher baseline glycosylated hemoglobin values (p = .01), and were more likely to show progression of DR (odds ratio (OR) = 2.44; 95% confidence interval (CI): 1.01-5.88; p = .049) and progression to proliferative diabetic retinopathy (PDR) (OR = 3.19; 95% CI: 1.30-7.87; p = .01) than patients with low BDI scores at both visits. This was independent of baseline medical risk factors for DR.'] Is depression a risk factor for poor glycemic control and retinopathy in African-Americans with type 1 diabetes? | qiaojin/PubMedQA | 2 | [
-1.851338505744934,
-1.1862305402755737,
2.00778865814209
] |
['To test whether abnormal sensorimotor plasticity in focal hand dystonia is a primary abnormality or is merely a consequence of the dystonic posture.', 'This study used the paired associative stimulation (PAS) paradigm, an experimental intervention, capable of producing long term potentiation (LTP) like changes in the sensorimotor system in humans. PAS involves transcranial magnetic stimulation combined with median nerve stimulation. 10 patients with cranial and cervical dystonia, who showed no dystonic symptoms in the hand, and nine patients with hemifacial spasm (HFS), a non-dystonic condition, were compared with 10 healthy age matched controls. Motor evoked potential amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in the abductor pollicis brevis and the first dorsal interosseus muscles.', 'Patients with dystonia showed a stronger increase in corticospinal excitability than healthy controls and patients with HFS. In addition, patients with dystonia showed a loss of topographical specificity of PAS induced effects, with a facilitation in both the median and ulnar innervated muscles. While PAS conditioning led to a prolonged CSP in healthy controls and patients with HFS, it had no effect on the duration of the CSP in patients with cranial and cervical dystonia.'] Does abnormal plasticity of sensorimotor circuits extend beyond the affected body part in focal dystonia? | qiaojin/PubMedQA | 2 | [
-2.574050188064575,
-1.0549066066741943,
2.6522669792175293
] |
['To examine the contribution of tumor necrosis factor alpha (TNF) microsatellite (a to e) polymorphism to the genetic risk of developing rheumatoid arthritis (RA) in a northwestern Colombian population.', 'This was an association study in which 108 RA patients and 222 matched individuals were enrolled. HLA-DRB1 and DQB1 polymorphisms were evaluated to examine for linkage disequilibrium between these loci and TNF micro- satellites. Genotyping was performed using denaturing polyacrylamide gels and polymerase chain reaction-sequence techniques.', 'By unconditional logistic regression analysis, the TNFa6 allele (OR=2.37, 95%CI 1.07-5.24) and the TNFb4 allele (OR=3.01, 95%CI 1.07-9.00) were observed to be associated with disease. These associations were independent of HLA-DR and HLA-DQ since linkage disequilibrium between HLA class II and TNF microsatellites was not observed. In addition, patients with the TNFa8 allele had a five times greater risk of developing extra-articular manifestations as compared to patients without this allele (OR=5.07, 95%CI 1.14-22.52), regardless of age and the duration of disease. Haplotype analysis disclosed a protective effect for TNFa7/b7/c1/d4/e3/-308G/-238G.'] Is tNF microsatellites polymorphism associated with rheumatoid arthritis . Confirming evidence in northwestern Colombians? | qiaojin/PubMedQA | 2 | [
-1.990207314491272,
-1.489403247833252,
2.54430890083313
] |
['Chromosome 8q24 is a region of compelling interest for prostate cancer (PRCA). Linkage, association, and admixture analysis initially indicated the region. Subsequently, several variants at 8q24 have been found to independently associate with PRCA. One compelling hypothesis is allelic heterogeneity, whereby multiple variants affect the regulation of the same gene. In addition to potential allelic heterogeneity, 8q24 exhibits strong linkage disequilibrium over vast distances and is prone to chromosomal aberrations.', 'Allelic heterogeneity and complex chromosomal structure are factors that hinder progress towards gene identification using association. Linkage techniques, however, are robust to allelic heterogeneity and therefore can contribute important localization information. We have used a linkage-based localization technique to perform recombinant mapping in eight high-risk Utah pedigrees.', 'Using pedigree-based recombinant mapping we identify a 5.7 Mb region at 8q24.21-22, between markers D8S1774 and D8S557. Considering our region with the localization previously presented, we can delimit the 8q24 PRCA locus to a 2.0 Mb consensus interval from 127.5 to 129.5 Mb.'] Does statistical recombinant mapping in extended high-risk Utah pedigrees narrow the 8q24 prostate cancer locus to 2.0 Mb? | qiaojin/PubMedQA | 2 | [
-1.6431500911712646,
-1.3547289371490479,
2.087430000305176
] |
['To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients.', 'Primary cultures of VKC-derived fibroblasts (VKC-FBs) were exposed to increasing NGF concentrations (1-500 ng/ml) to evaluate and compare the expression of alpha-smooth muscle actin (alphaSMA, a defining myofibroblast marker), collagens (types I and IV), and metalloproteinases and tissue inhibitors (MMP9/TIMP1, MMP2/TIMP2) at the biochemical as well as molecular levels.', 'Endogenous NGF was increased in the VKC-FB supernatant, as compared to healthy-FB supernatant. VKC-FBs expressed alphaSMA and increased types I and IV collagens. VKC-FBs, and in particular all alphaSMA positive cells, expressed both trkA(NGFR) and p75(NTR), while healthy-FBs only expressed trkA(NGFR). Exogenous NGF did not change alphaSMA expression, while alphaSMA expression was enhanced by specific neutralization of p75(NTR). NGF (10 ng/ml) exposure significantly decreased type I collagen expression, without affecting type IV collagen, and increased MMP9mRNA and protein.'] Does nerve growth factor have a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva? | qiaojin/PubMedQA | 2 | [
-2.3294308185577393,
-1.3697795867919922,
2.759794235229492
] |
['Ocular melanoma is the leading intraocular malignancy. There is no effective treatment for metastatic ocular melanoma. We sought a treatment targeting the tumor microenvironment as well as the tumor cells.', 'Migration of HUVEC cells, the ability of HUVEC cells to form tubes, and proliferative capacity of a human ocular melanoma cell line were tested in the presence of lenalidomide and sorafenib alone and in combination. The compounds were also tested in a rat aortic ring assay and were tested in a highly aggressive human ocular melanoma xenograft model.', 'Lenalidomide and Sorafenib inhibit HUVEC ability to migrate and form tubes and when used in combination the inhibition is increased. The agents alone and in combination inhibit outgrowth in the rat aortic ring model. The combination of the agents improved the inhibition over either single agent. In a xenograft model, combination therapy inhibited tumor growth over inhibition by single agent alone in a significant fashion (p < 0.004: lenalidomide and p < 0.0035: sorafenib). Furthermore, spontaneous lung metastasis development was completely inhibited in the combination treated animals. Sixty percent of vehicle treated animals developed lung metastases compared to 50% of lenalidomide treated animals, and 33% of sorafenib treated animals.'] Is combination therapy targeting the tumor microenvironment effective in a model of human ocular melanoma? | qiaojin/PubMedQA | 2 | [
-2.2725188732147217,
-1.3214633464813232,
2.667595624923706
] |
['Thymic stromal derived lymphopoietin (TSLP) is preferentially and highly expressed in the thymus, but its function in T cell development is not clear.', 'We report here that TSLP, independently or in combination with IL-7, enhances thymopoiesis in the murine fetal thymic organ culture (FTOC) model. Furthermore, TSLP preferentially increases the number and proliferation of the (DN1 and DN2) pro-T progenitor cells, and FTOC lobes from TSLP receptor-null mice show a decreased number of these cells. Finally, DN1-DN2 cells expanded with TSLP in vitro are functional T progenitors that are able to differentiate into mature T cells in fetal or adult thymus organs.'] Is tSLP involved in expansion of early thymocyte progenitors? | qiaojin/PubMedQA | 2 | [
-2.5639843940734863,
-1.0702617168426514,
2.7191128730773926
] |
['The changes in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However, it has remained difficult to differentiate between NASH and nonprogressive NAFLD by clinical examination. We investigated the interrelationships between serum high-sensitivity C-reactive protein (hs-CRP) and the pathogenesis and progression of NASH.', 'Hs-CRP was measured in 100 patients with histologically verified NAFLD (29 with steatosis and 71 with NASH), and a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to measure the intrahepatic mRNA expressions of CRP and interleukin (IL)-6.', 'The results of a multiple regression analysis revealed that in comparison with cases of steatosis, hs-CRP was significantly elevated (P = 0.0048) in cases of NASH. Furthermore, among patients with NASH, hs-CRP was significantly elevated in those with advanced fibrosis compared with that in those with mild fibrosis (P = 0.0384), even after adjustment for age, sex, presence of diabetes, body mass index, visceral fat area, subcutaneous fat area, homeostasis model assessment for insulin resistance, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol. The results of the RT-PCR analysis showed that intrahepatic mRNA expression of CRP, but not IL-6, was increased in patients with NASH compared with those with steatosis (P = 0.0228).'] Is high-sensitivity C-reactive protein an independent clinical feature of nonalcoholic steatohepatitis ( NASH ) and also of the severity of fibrosis in NASH? | qiaojin/PubMedQA | 2 | [
-2.231025218963623,
-1.4510867595672607,
2.6884827613830566
] |
['Cancer-testis antigens (CTAGs) are expressed solely in germ cells and in malignant tissues. They are targets of immune responses mediated by cytotoxic T cells in some cancers, and there is much interest in developing vaccines that induce these responses. The purpose of the present study was to ascertain the frequency of expression of CTAGs in breast cancer.', 'Breast tumours were collected sequentially in the Southampton Tumour Bank from donors who had given written informed consent. Stored samples where there was sufficient material were sampled in sequence. An initial series of 42 tumours was screened for expression of 17 different CTAGs. A second panel of 40 tumours was screened for the expression of those antigens present in the first panel.', 'Ninety-three per cent of tumours in the first series expressed at least one CTAG, and 62% expressed the single antigen CTAG1. Eighty per cent of tumours in the second series expressed at least one CTAG, 50% expressing CTAG1. Tumours exhibiting higher risk features tended to express more CTAGs.'] Is breast cancer a promising target for vaccination using cancer-testis antigens known to elicit immune responses? | qiaojin/PubMedQA | 2 | [
-2.0521669387817383,
-1.0418630838394165,
2.1978955268859863
] |
['Profilins are critical to cytoskeletal dynamics in eukaryotes; however, little is known about their viral counterparts. In this study, a poxviral profilin homolog, ectromelia virus strain Moscow gene 141 (ECTV-PH), was investigated by a variety of experimental and bioinformatics techniques to characterize its interactions with cellular and viral proteins.', 'Profilin-like proteins are encoded by all orthopoxviruses sequenced to date, and share over 90% amino acid (aa) identity. Sequence comparisons show highest similarity to mammalian type 1 profilins; however, a conserved 3 aa deletion in mammalian type 3 and poxviral profilins suggests that these homologs may be more closely related. Structural analysis shows that ECTV-PH can be successfully modelled onto both the profilin 1 crystal structure and profilin 3 homology model, though few of the surface residues thought to be required for binding actin, poly(L-proline), and PIP2 are conserved. Immunoprecipitation and mass spectrometry identified two proteins that interact with ECTV-PH within infected cells: alpha-tropomyosin, a 38 kDa cellular actin-binding protein, and the 84 kDa product of vaccinia virus strain Western Reserve (VACV-WR) 148, which is the truncated VACV counterpart of the orthopoxvirus A-type inclusion (ATI) protein. Western and far-western blots demonstrated that the interaction with alpha-tropomyosin is direct, and immunofluorescence experiments suggest that ECTV-PH and alpha-tropomyosin may colocalize to structures that resemble actin tails and cellular protrusions. Sequence comparisons of the poxviral ATI proteins show that although full-length orthologs are only present in cowpox and ectromelia viruses, an ~ 700 aa truncated ATI protein is conserved in over 90% of sequenced orthopoxviruses. Immunofluorescence studies indicate that ECTV-PH localizes to cytoplasmic inclusion bodies formed by both truncated and full-length versions of the viral ATI protein. Furthermore, colocalization of ECTV-PH and truncated ATI protein to protrusions from the cell surface was observed.'] Does an ectromelia virus profilin homolog interact with cellular tropomyosin and viral A-type inclusion protein? | qiaojin/PubMedQA | 2 | [
-2.3260982036590576,
-1.3014644384384155,
2.7369160652160645
] |
['During planning and execution of reaching movements, the activity of cortical motor neurons is modulated by a diversity of motor, sensory, and cognitive signals. Brain-machine interfaces (BMIs) extract part of these modulations to directly control artificial actuators. However, cortical modulations that emerge in the novel context of operating the BMI are poorly understood.', 'Here we analyzed the changes in neuronal modulations that occurred in different cortical motor areas as monkeys learned to use a BMI to control reaching movements. Using spike-train analysis methods we demonstrate that the modulations of the firing-rates of cortical neurons increased abruptly after the monkeys started operating the BMI. Regression analysis revealed that these enhanced modulations were not correlated with the kinematics of the movement. The initial enhancement in firing rate modulations declined gradually with subsequent training in parallel with the improvement in behavioral performance.'] Do cortical modulations increase in early sessions with brain-machine interface? | qiaojin/PubMedQA | 1 | [
-2.7571327686309814,
0.9592381119728088,
0.8760263919830322
] |
['Ischemia-reperfusion (IR) injury causes tissue injury and endothelial dysfunction. There is evidence that oxidative stress plays an important role.', 'We tested if IR-induced endothelial dysfunction could be prevented by administration of the antioxidant vitamin C. Twenty-six healthy male subjects and eight male patients with peripheral arterial disease (PAD) were enrolled in this randomised placebo-controlled study. Forearm blood flow (FBF) measurements in response to the vasodilators acetylcholine (ACh; endothelium-dependent agonist) or nitroglycerin (NTG; endothelium-independent) were performed before and after forearm ischemia for 20 min. FBF responses were reassessed during reperfusion with intra-arterial co-administration of 24 mg/min vitamin C or placebo. In six volunteers responses to the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) were also assessed before and after ischemia with and without vitamin C.', 'ACh-induced vasodilation was blunted in subjects receiving placebo after reperfusion (p<0.05 versus baseline). Administration of vitamin C completely prevented impaired responsiveness. NTG-induced vasodilation was not affected by reperfusion or vitamin C. This finding was consistent in patients with PAD and impaired endothelial function, where local vitamin C infusion restored FBF reactivity to ACh before and after IR injury (p<0.05 versus baseline). Again, NTG-induced vasodilation was not affected. Blunted L-NMMA responses seen during reperfusion could be completely reversed by vitamin C.'] Does intra-arterial vitamin C prevent endothelial dysfunction caused by ischemia-reperfusion? | qiaojin/PubMedQA | 2 | [
-2.3363454341888428,
-1.4404702186584473,
2.812072515487671
] |
['Doxazosin is an antihypertensive agent with largely unknown effects on arterial stiffness and vasodilation. The aim of this study was to determine the effect of the addition of doxazosin extended-release (ER) to the standard management of hypertension in patients with inadequately controlled blood pressure (BP) on arterial stiffness and arterial vasodilation.', 'Twenty patients with inadequately controlled hypertension were treated with 4 mg doxazosin ER daily for 16 weeks as an adjunct to their existing antihypertensive regimen.', 'Doxazosin ER add-on therapy was associated with significantly reduced systolic (P < 0.0001) and diastolic (P = 0.0003) BP, improved arterial stiffness (determined by digital volume pulse analysis (P = 0.048) and albuterol-mediated arterial vasodilation (P = 0.030).'] Does add-on therapy with doxazosin in patients with hypertension influence arterial stiffness and albuterol-mediated arterial vasodilation? | qiaojin/PubMedQA | 2 | [
-2.3522818088531494,
-1.329017162322998,
2.7325305938720703
] |
['The contribution of genetic factors to aspirin treatment failure (ATF) for secondary prevention is not settled in patients with ischemic stroke.', 'We assessed the polymorphisms VNTR (A, B, C, D) of glycoprotein (GP) Ibalpha, 807C/T of GP Ia/IIa, and Pl(A1/A2) of GP IIb/IIIa, and the 5-year incidence of major recurrent events in 82 stroke patients with no major sources of cardioembolism (mean age 70, SD 9.0 years; female gender 23%). Using a structured interview, all participants confirmed good compliance with aspirin (100-300 mg/day) for secondary prevention. Demographics and atherothrombotic risk factors assessed included diabetes, hypertension, dyslipemia, smoking, and coronary heart disease.', 'Thirty-one stroke patients had one recurrent stroke or myocardial infarction within 33 (7-48) months of aspirin onset, while 51 patients demonstrated an uneventful clinical course. Female gender (p < 0.05), diabetes (p < 0.05), dyslipemia (p < 0.05), and the BC genotype of VNTR (25.8 vs. 7.8%, p < 0.05) were more prevalent in patients in whom aspirin failed to prevent clinical events than in those in whom it did not. The BC genotype of VNTR was the only factor that remained associated with ATF in an age-, sex-, and risk factor-adjusted logistic regression analysis (OR 9.6, 95% CI 1.5-61.0).'] Is the BC genotype of the VNTR polymorphism of platelet glycoprotein Ibalpha overrepresented in patients with recurrent stroke regardless of aspirin therapy? | qiaojin/PubMedQA | 2 | [
-1.8309866189956665,
-1.5335478782653809,
2.4083220958709717
] |
['Hemophagocytic lymphohistiocytosis (HLH) is a syndrome composed of macrophage activation syndrome (MAS), infection-associated hemophagocytosis syndrome (IAHS), malignancy-associated HLH and genetic HLH. Differentiation of MAS from IAHS and other HLH is important for early appropriate treatment.', 'A retrospective analysis was used to differentiate childhood MAS from IAHS and other HLH in Chang Gung Memorial Hospital (CGMH), Kaohsiung. All relevant clinical features, laboratory data, treatments and outcomes were analysed.', 'Seventeen patients with childhood HLH were found at CGMH, Kaohsiung in the past decade, and could be classified into 3 categories: IAHS (9 patients), MAS (5 patients), and HLH of unknown etiology (3 patients). The diagnosis of MAS first appeared in this hospital in 2001. Patients with IAHS tended to be younger than those with MAS. Boys were more frequently found in the IAHS group whereas girls (with systemic lupus erythematosus or juvenile idiopathic arthritis) were more frequently found in the MAS group. The majority of mortality cases were noted in the IAHS group (44%, 4/9). All patients with MAS survived with early cyclosporine A treatment.'] Does childhood macrophage activation syndrome differ from infection-associated hemophagocytosis syndrome in etiology and outcome in Taiwan? | qiaojin/PubMedQA | 2 | [
-2.2083780765533447,
-0.8968716859817505,
2.1564650535583496
] |
['It is well established that tobacco use is associated with mental disorders. However, the association between tobacco use and mental disorders has not yet been examined sufficiently in prospective, population-based studies. The current study is aimed at examining whether smoking is associated with first-ever incidence of mental disorders.', 'We conducted a prospective, population-based epidemiological study (the Netherlands Mental Health Survey and Incidence Study: NEMESIS) in which a representative sample of adults aged 18-64 years (n = 7076) were interviewed to establish the presence of a broad range of mental disorders. We re-interviewed them at 1 year (n = 5618; response 79.4%) and 3 years (n = 4796; 67.8%) after baseline.', 'The presence of mental disorders was assessed according to DSM-III-R criteria with the Composite International Diagnostic Interview (CIDI), which was administered by trained lay interviewers. Tobacco use was assessed by asking respondents whether they had smoked in the past year, and how many cigarettes they smoked.', 'Subjects who smoked but never had a mental disorder in their life, had an increased risk of developing a mental disorder (P < 0.01), and this remained significant after correcting for major risk indicators of mental disorders.'] Is smoking associated with first-ever incidence of mental disorders : a prospective population-based study? | qiaojin/PubMedQA | 2 | [
-2.587247133255005,
0.5823982357978821,
1.1978061199188232
] |
['Oxidative phosphorylation dysfunction of hepatocyte mitochondria is involved in the pathophysiology of organ dysfunction following obstructive jaundice (OJ). However the time period from biliary occlusion to the occurrence of the dysfunction has not been determined decisively.', 'To evaluate the early effects (1 d and 7 d) of OJ on liver mitochondria respiratory function in rats.', 'Male Wistar rats (200-250 g) were randomly divided into the following 3 groups: laparotomy plus OJ for 24 h (1d group) (n = 10); laparotomy plus OJ for 7 d (7d group) (n = 10); sham control procedure (CTR group) (n = 12). At the end of OJ periods, total serum bilirubin level, hepatic enzyme activity levels (GOT, GTP, Gama-GT, ALP), mitochondrial respiration phases S3 and S4, as well as the respiratory control ratio (RC = S3/S4), and ADP consumption/oxygen consumption (ADP/O) ratio, were determined.', 'Total serum bilirubin, activity of most hepatic enzymes, and O2 consumption during basal (S4) respiration were increased in the 1d and 7d groups (ANOVA, p = 0.05 vs. CTR). After ADP addition, the O2 consumption rate (S3) in the 1d group remained similar to the CTR rate (ANOVA p > .05), while the RC rate was reduced (ANOVA, p = 0.001) vs. CTR. The effects observed on mitochondrial respiration in the 1d group were exacerbated in the 7d group.'] Does obstructive jaundice induce early depression of mitochondrial respiration in rat hepatocytes? | qiaojin/PubMedQA | 2 | [
-2.0032362937927246,
-1.5595645904541016,
2.5021605491638184
] |
['To investigate the effect of interferon (IFN)-alpha and IFN-gamma pretreatment on mitomycin C (MMC)-induced cell death in human Tenon fibroblasts (HTFs) and the mechanisms by which IFN-alpha and IFN-gamma modulate the susceptibility of HTFs to MMC.', 'HTFs were pretreated with IFN-alpha and IFN-gamma for 48 hours before 5-minute application of 0.4 mg/mL MMC. Cell death after 48 hours was determined by Annexin V/propidium iodide (PI) staining and lactate dehydrogenase (LDH) release assay. Fas, Fas-ligand, and Bcl-2 expression were determined by flow cytometry. Fas associated death domain (FADD), Bax, cytochrome c, and caspase expression were determined by Western blot analysis and immunofluorescence staining.', 'MMC treatment increased cell death and upregulated Fas and FADD expression, but had no effect on Fas-Ligand, Bax, Bcl-2, or cytochrome c. Neither IFN-alpha nor IFN-gamma alone induced HTF death, but each increased cell death 2 days after MMC treatment in a dose-dependent fashion. Combination IFN-alpha and IFN-gamma had a synergistic effect. IFN-alpha and IFN-gamma pretreatment increased Fas expression. Fas upregulation was associated with increased sensitivity to MMC. IFN pretreatment increased procaspase-8, procaspase-9, and procaspase-3 expression, and caspase-3 activation. Caspase-8, caspase-3, and broad caspase inhibitors, but not caspase-9 inhibitor, inhibited MMC-induced cell death in nonpretreated and IFN-pretreated cells.'] Do interferon-alpha and interferon-gamma sensitize human tenon fibroblasts to mitomycin-C? | qiaojin/PubMedQA | 2 | [
-2.341423511505127,
-1.3988715410232544,
2.776209831237793
] |
['Information on the excretion of dietary phytate in humans under different conditions is limited. The purpose of this study was to investigate fecal excretion of dietary phytate and phosphorus in a group of young and elderly women consuming high and low phytate diets.', 'Fifteen young and fourteen elderly women were fed two experimental diets, high phytate and low phytate, for 10 days each with a washout period of 10 days between the two diet periods. Duplicate diet samples from two different menus and complete fecal samples were collected for 5 days during each diet period and analyzed for phytate and phosphorus contents. Mean daily excretions and percentages of dietary intakes of phytate and phosphorus were calculated.', 'Dietary phytate level does impact phytate excretion, but the effect was observed only in young subjects. Fecal phytate excretion of young subjects during the high phytate diet (313 mg/d) was significantly higher than during the low phytate diet (176 mg/d), however, that of elderly subjects did not vary with dietary phytate levels. Phosphorus excretion, net absorption, and apparent absorption rate were affected by dietary phytate level but not by the age of the subjects.'] Does fecal phytate excretion vary with dietary phytate and age in women? | qiaojin/PubMedQA | 2 | [
-1.3078361749649048,
-0.09291238337755203,
0.6135790348052979
] |
['Differential rearing environments affect a number of behaviors displayed by rats in adulthood. For example, rats reared in an impoverished condition (IC; reared alone in hanging metal cages), social condition (SC; reared in standard shoebox cages, 2 per cage), or enriched condition (EC; reared in a large metal cage with bedding, 14 novel objects, and 10 cohorts) display clear differences in the amount of drug they consume and/or self-administer through operant responding. Animals reared in an EC consume greater amounts of ethanol compared with rats reared in an IC when provided free access, but it is not known how differential rearing conditions affect operant responding for ethanol.', 'Twenty-eight male Long-Evans rats were reared in 1 of 3 environments (IC, SC, or EC) during postnatal days 21 to 111. At the conclusion of the rearing period, all rats underwent sucrose/ethanol fading and then were tested for lever press responding for 10% ethanol as well as ethanol preference.', 'Rats reared in an IC responded for 10% ethanol at significantly higher rates than SC and EC rats. A greater percentage of IC rats were able to switch lever responding when the ethanol availability was changed to a second lever. Lastly, the IC group was the only one to display a clear preference for 10% ethanol when both this fluid and water were available.'] Do differential rearing conditions alter operant responding for ethanol in outbred rats? | qiaojin/PubMedQA | 1 | [
-1.4200810194015503,
0.8059809803962708,
-0.26544925570487976
] |
['The decision among young people to drink is complex and reflects multiple domains of influence. This paper applies the results from a previous test of an externalizing-based model predicting heavy drinking and alcohol problems in the probands from the San Diego Prospective Study to evaluate how similar characteristics relate to the decision to drink in their offspring.', "Data were generated from multiple sources for 152 offspring with a mean age of 17.2 years. Information on the family histories, personal alcohol and other substance use, socioeconomic stratum, the child's gestational problems, and additional characteristics were gathered from face-to-face interviews with a parent approximately every 5 years between their mid-20s and mid-40s. Data regarding the drinking status and additional variables applicable to the offspring were extracted from the 25-year (T25) epoch of the family evaluations using data supplied directly by the offspring. The relationships of variables to the drinking status in that generation were determined through correlations, regression analyses, and an AMOS-based structural equation model (SEM).", 'Significant correlations to the drinking status in offspring were observed for age, but not for sex. Using age-adjusted backgrounds and data supplied by the offspring at T25, the most robust correlations to the drinking status were seen for a disinhibition measure, peer drinking, expectations of the effects of alcohol, and the history of having worked outside the home. When placed into an SEM, the former 3 variables performed in a manner similar to that observed in the original probands in the prediction of the drinking status, in a model with good fit characteristics.'] Does patterns and correlate of drinking in offspring from the San Diego Prospective Study? | qiaojin/PubMedQA | 2 | [
-2.2764384746551514,
-0.07950994372367859,
1.4958114624023438
] |
['The C57BL/6 mouse model has been used extensively in alcohol drinking studies, yet significant differences in ethanol preference between substrains exist. Differences in ethanol-induced dopamine release in the ventral striatum could contribute to this variability in drinking behavior as dopamine has been implicated in the reinforcing properties of ethanol.', 'A 2-bottle choice experiment investigated the difference in ethanol preference between C57BL/6J and C57BL/6NCrl animals. Microdialysis was used to determine dopamine release and ethanol clearance in these 2 substrains after intraperitoneal injections of 1.0, 2.0 and 3.0 g/kg ethanol or saline.', 'C57BL/6J mice exhibited significantly greater ethanol preference and less ethanol-stimulated dopamine release compared with C57BL/6NCrl mice. The intraperitoneal injections of ethanol caused a significant increase in dopamine in both substrains at all 3 doses with significant differences between substrains at the 2 highest alcohol doses. Saline injections had a significant effect on dopamine release when given in a volume equivalent to the 3 g/kg ethanol dose. Ethanol pharmacokinetics were similar in the 2 substrains at all 3 doses.'] Is ethanol preference inversely correlated with ethanol-induced dopamine release in 2 substrains of C57BL/6 mice? | qiaojin/PubMedQA | 2 | [
-1.615273118019104,
-1.3880269527435303,
1.9553040266036987
] |
['Transforming growth factor-beta1 (TGF-beta1), a key biological mediator following ionizing radiation, plays a role in a complex tissue reaction involved in local radiation-induced pathological damage. Knocking out Smad3 (S3KO), a downstream signaling intermediate in the TGF-beta pathway, in mice protects their skin from radiation damage as demonstrated by decreased epithelial acanthosis and dermal fibrosis as compared to Smad3 wild-type (S3WT) mice.', 'The present study was designed to investigate the molecular mechanisms contributing to increased radioprotection in the absence of Smad3.', 'Primary dermal fibroblasts derived from S3WT and KO mice were exposed to 5Gy ionizing radiation in vitro. Western blot analyses, immunocytochemistry, and reporter transfections were used to dissect the radiation-induced events.', 'There was increased phosphorylation of ERK-MAPK, p53 and H2A.X in S3KO compared to the S3WT fibroblasts, implicating them in a key signaling cascade in response of these cells to radiation. Pro-fibrotic gene expression was decreased in S3KO fibroblasts post-irradiation.'] Does absence of Smad3 confer radioprotection through modulation of ERK-MAPK in primary dermal fibroblasts? | qiaojin/PubMedQA | 2 | [
-2.459082841873169,
-1.2736971378326416,
2.7946174144744873
] |
['It was the aim of this study to evaluate the serum levels of cathepsin D (Cath D) as a diagnostic tool in patients with renal cell carcinoma (RCC) in comparison with healthy volunteers.', 'Cath D serum levels were measured in serum samples obtained preoperatively from 32 patients with histologically confirmed RCC versus 30 healthy individuals using an enzyme immunoassay. Additionally, for the tumor group, Cath D serum levels were correlated with tumor stage and grade as determined according to the 2002 TNM classification.', 'The serum Cath D concentration was not significantly different in patients with RCC compared with healthy individuals (mean 16.58 vs. 16.64 ng/ml; p = 0.43). Furthermore, there was no significant association between Cath D serum levels and several patient or tumor characteristics such as tumor stage, tumor grade, lymph node status, presence of metastasis, gender or age.'] Are cathepsin D serum levels a valid serum marker in renal cell carcinoma? | qiaojin/PubMedQA | 2 | [
-2.1430840492248535,
-1.315251111984253,
2.548727512359619
] |
['Follow-up study.', 'To estimate the influence of fear avoidance beliefs (FAB) on 1-year low back pain (LBP)-related sick leave.', 'As opposed to Anglo-Saxon and Northern European subjects, in Spanish LBP patients the influence of FAB on disability and quality of life is virtually irrelevant.', 'Twelve primary care and 9 hospital services from 7 different regions of Spain recruited 165 workers who visited the National Health Service for LBP. None was excluded. On their first visit and 14 days later, patients were given 2 independent Visual Analogue Scales (VAS) for LBP and leg pain, as well as the validated Spanish versions of the Fear Avoidance Beliefs (FABQ), Roland-Morris (RMQ), and SF-12 questionnaires. During the following 12-month period, the number of days on sick leave because of LBP was registered.', 'Differences in sick leave throughout the study period were associated with baseline differences in chronicity, severity of low back (not referred) pain, disability, FAB, physical and mental quality of life, being on sick leave when entering the study, and duration of previous sick leave. Ordinal logistic regression models showed that each additional point in the total FAB baseline score increases by 2.4% the odds of being on sick leave for up to 60 days during the following year and by 7.7% the odds of being sick listed for 61 days or more. Corresponding figures for FAB-Work scores are 4.2% and 11%. No variable modifies the effect of FAB on sick leave.'] Do fear avoidance beliefs influence duration of sick leave in Spanish low back pain patients? | qiaojin/PubMedQA | 2 | [
-1.562593936920166,
-0.33245494961738586,
0.9472545981407166
] |
['A genetic association study to comprehensively investigate variations of melatonin receptor 1B gene polymorphism by a set of tagging single nucleotide polymorphisms (tagSNPs) derived from the International Hapmap project.', 'To determine whether melatonin receptor 1B (MTNR1B) gene polymorphisms are associated with the predisposition and/or disease severity of adolescent idiopathic scoliosis (AIS).', 'Linkage studies suggested a genetic predisposition for AIS. In addition, evidence showed that AIS might be related to melatonin deficiency and dysfunction of melatonin signaling pathway. Locating in one of the chromosomal regions linked to AIS, MTNR1B gene is a potential candidate gene for AIS.', 'This study was carried out in 2-stage case-control analysis: 1) initial screening (472 cases and 304 controls) and 2) separate replication test (342 cases and 347 controls) to confirm results in the screening. In the first screening stage, 5 tagSNPs were selected to cover most of the genetic variation in the MTNR1B gene. In the second stage, SNPs showing association in the screening stage were studied in a separate replication sample set to confirm the association. Genotyping was performed by PCR-RFLP.', 'The first stage showed a putative association between rs4753426 and AIS, which was confirmed in the replication sample set. By meta-analysis, the frequency of C allele of this SNP locating in the promoter was significantly higher in the cases than controls (P = 0.006 aftermeta-analysis). Subjects with the CC genotype had an odds ratio of 1.29 for AIS. Another SNP rs741837 in promoter region, being moderate linkage disequilibrium with rs4753426, was also marginally associated with AIS.'] Is melatonin receptor 1B ( MTNR1B ) gene polymorphism associated with the occurrence of adolescent idiopathic scoliosis? | qiaojin/PubMedQA | 2 | [
-1.9739092588424683,
-1.5226867198944092,
2.4705426692962646
] |
['Selective serotonin reuptake inhibitor (SSRI) antidepressant drugs have a delayed onset and commonly produce an incomplete therapeutic response. The therapeutic actions of SSRIs are thought to depend on increased forebrain extracellular serotonin (5-HT), after desensitization of somatodendritic 5-HT(1A) autoreceptors. Here we determined whether concurrent glucocorticoid receptor (GR) blockade enhances these neurochemical responses to the SSRI fluoxetine.', 'Male rats were treated (3, 7, or 14 days) with either fluoxetine (10 mg/kg IP) or vehicle once daily, in combination with either a GR antagonist (Org 34850 15 mg/kg SC or Org 34517 25 mg/kg SC) or vehicle twice daily. After treatment, 5-HT in the medial prefrontal cortex was measured by microdialysis.', 'Chronic fluoxetine treatment (14 days) raised basal 5-HT and also attenuated the fall in 5-HT after acute systemic administration of fluoxetine (10 mg/kg IP), indicating desensitization of 5-HT(1A) autoreceptors. Concurrent chronic administration (14 days) of Org 34850 or Org 34517 enhanced the fluoxetine-induced increase in basal 5-HT. Org 34850 also hastened the 5-HT(1A) autoreceptor desensitization induced by chronic fluoxetine treatment. Org 34850 alone (14 days) failed to alter basal 5-HT or 5-HT(1A) autoreceptor desensitization.'] Do glucocorticoid receptor antagonists hasten and augment neurochemical responses to a selective serotonin reuptake inhibitor antidepressant? | qiaojin/PubMedQA | 2 | [
-2.1453073024749756,
-1.4505643844604492,
2.622882843017578
] |
['APOBEC3G (A3G) and APOBEC3C (A3C), 2 members of the APOBEC family, are cellular cytidine deaminases displaying broad antiretroviral activity. A3G inhibits hepatitis B virus (HBV) production by interfering with HBV replication without hypermutating the majority of HBV genomes. In contrast, A3C has little effect on HBV DNA synthesis. The aim of this study was to further dissect the mechanisms by which A3G and A3C interfere with the HBV life cycle. Immunoprecipitation experiments demonstrated that both A3G and A3C bind to the HBV core protein. A ribonuclease (RNase) treatment resulted in the nearly complete dissociation of the HBV core protein from A3G, whereas the HBV core-A3C complex was more stable. Interestingly, the majority of the newly synthesized HBV DNA genomes displayed extensive G-to-A mutations in the presence of A3C, whereas no A3C-induced HBV RNA mutations were detected. These findings support a model in which the RNA-dependent entrapment of A3G into the preassembly complex hampers subsequent steps in capsid formation. On the other hand, A3C is readily packaged into replication-competent capsids and efficiently deaminates newly synthesized HBV DNA.'] Is hepatitis B virus DNA subject to extensive editing by the human deaminase APOBEC3C? | qiaojin/PubMedQA | 2 | [
-2.4308717250823975,
-1.082835078239441,
2.55423641204834
] |
['Myofibroblasts derived from portal fibroblasts are important fibrogenic cells in the early stages of biliary fibrosis. In contrast to hepatic stellate cells, portal fibroblasts have not been well studied in vitro, and little is known about their myofibroblastic differentiation. In this article we report the isolation and characterization of rat portal fibroblasts in culture. We demonstrate that primary portal fibroblasts undergo differentiation to alpha-smooth muscle actin-expressing myofibroblasts over 10-14 days. Marker analysis comparing portal fibroblasts to hepatic stellate cells demonstrated that these are distinct populations and that staining with elastin and desmin can differentiate between them. Portal fibroblasts expressed elastin at all stages in culture but never expressed desmin, whereas hepatic stellate cells consistently expressed desmin but never elastin. Immunostaining of rat liver tissue confirmed these results in vivo. Characterization of portal fibroblast differentiation in culture demonstrated that these cells required transforming growth factor-beta (TGF-beta): cells remained quiescent in the presence of a TGF-beta receptor kinase inhibitor, whereas exogenous TGF-beta1 enhanced portal fibroblast alpha-smooth muscle actin expression and stress fiber formation. In contrast, platelet-derived growth factor inhibited myofibroblastic differentiation. Portal fibroblasts were also dependent on mechanical tension for myofibroblastic differentiation, and cells cultured on polyacrylamide supports of variable stiffness demonstrated an increasingly myofibroblastic phenotype as stiffness increased.'] Do transforming growth factor-beta and substrate stiffness regulate portal fibroblast activation in culture? | qiaojin/PubMedQA | 2 | [
-2.486072301864624,
-1.2956416606903076,
2.8177409172058105
] |
['Chronic obstructive pulmonary disease (COPD) is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 (CaCC(1)) was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of CaCC(1) and mucus overproduction in the airway of Chinese patients with COPD, the expressions of CaCC(1), MUC5AC and mucus in bronchial tissues were examined.', 'Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July in 2004. Twenty-five patients were diagnosed as the patients with COPD overproduction, and other 20 were the control subjects. The expressions of CaCC(1), MUC5AC and mucin in bronchial tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization with digoxigenin (DIG)-labeled RNA probe, immunohistochemical and alcian blue-periodic acid Schiff (AB-PAS) staining, respectively.', "Compared with the control group, the stronger expressions of CaCC(1) were further detected throughout the bronchial tissues from patients with COPD (P < 0.01). Furthermore, the stronger expressions of the CaCC(1) mRNA were related to the severity of airflow obstruction. Samples from COPD showed a stronger staining for MUC5AC than those in control subjects (P < 0.01) and AB-PAS staining revealed more mucins in COPD patients' submucosal gland comparing with that in control subjects (P < 0.01). Expression levels of the CaCC(1) mRNA were respectively negatively correlated with the patients' forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) data, FEV(1)% predicted data, V(50)% predicted data, V(25)% predicted data (r = -0.43, r = -0.43, r = -0.35, r = -0.36, P < 0.01, P < 0.01, P < 0.05, P < 0.05). While the expression levels of the CaCC(1) mRNA were well correlated with the expression levels of the MUC5AC mRNA of airway epithelium and the PAS-AB stained area of submucosal glands (r = 0.39, r = 0.46, P < 0.05, P < 0.01). Expression levels of the MUC5AC mRNA were negatively correlated with the patients' FEV(1)/FVC data (P = 0.01), FEV(1)% pred data (P = 0.01), V(50)% predicted data, V(25)% predicted data (r = -0.53, r = -0.53, r = -0.48, r = -0.43, P < 0.01, P < 0.01, P < 0.01, P < 0.01). While the expression levels of the MUC5AC mRNA were well correlated with the positively PAS-AB stained area of submucosal gland (P < 0.05), and the correlation coefficients were 0.43."] Is increased expression of human calcium-activated chloride channel 1 correlated with mucus overproduction in the airways of Chinese patients with chronic obstructive pulmonary disease? | qiaojin/PubMedQA | 2 | [
-1.996772050857544,
-1.4723225831985474,
2.4862899780273438
] |
['Perioperative administration of immunoenriched diets attenuates the perioperative inflammatory response and reduces postoperative infection complications. However, many questions still remain unresolved in this area, such as the length of diet administration, diet composition, and the mechanisms involved. We performed an open, randomized, triple-arm study comparing the effect of two perioperative feeding regimens with a postoperative one.', '46 candidates for major elective surgery for malignancy in the upper gastrointestinal tract were randomized to drink preoperatively either 1 L of an immunoenriched formula (Impact) for 5 days (IEF group) or 1 L of Impact plus (Impact enriched with glycine) for 2 days (IEF plus group). The same product as the patient received preoperatively was given to both groups for 7 days postoperatively. In the control group (CON group), patients only received Impact for 7 days postoperatively; there was no preoperative treatment. The main outcome measures were postoperative C-reactive protein (CRP) serum levels.', 'In the two preoperatively supplemented groups (treatment groups), perioperative endotoxin levels, CRP (postoperative day 7), and TNF-alpha (postoperative days 1 and 3) levels were significantly lower compared to the CON group (p < .01). Furthermore, the length of postoperative IMU/ICU stay (Impact 1.9 +/- 1.3 days; Impact plus 2.2 +/- 1.1 days; control group 5.9 +/- 0.8 days) and length of hospital stay (Impact 19.7 +/- 2.3 days; Impact plus 20.1 +/- 1.3 days; control group 29.1 +/- 3.6 days) were both reduced in the treatment groups compared to the control group. Infectious complications (Impact 2/14 (14%); Impact plus 5/17 (29%); control group 10/15 (67%)) also showed a trend toward reduction in the treatment groups.'] Does preoperative immunonutrition suppress perioperative inflammatory response in patients with major abdominal surgery-a randomized controlled pilot study? | qiaojin/PubMedQA | 2 | [
-1.9185541868209839,
-1.4980323314666748,
2.4345388412475586
] |
['Inhibins are dimeric glycoproteins belonging to the TGF-beta1 family and are composed of an a-subunit (INH-alpha) and one of two possible beta-subunits (betaA or betaB; INH-betaA and INH-betaB). They have a substantial function in human reproduction and also seem to play an important role in endocrine-responsive tumors. Interestingly, there is an association between interferon and TGF-beta expression. However, this relationship has not been assessed in endometrial tissue regarding inhibin/activin expression. Therefore, the aim of this study was to determine expression changes of inhibin/activin subunits in the endometrial Ishikawa carcinoma cell line after stimulation with interferon-beta1a.', 'The Ishikawa cell line was cultured until confluence was observed (after 2 days). After adding interferon-beta1a (1000 IE/ml) Ishikawa cells were immunohistochemical analyzed for INH-alpha, INH-betaA and INH-betaB subunits. Experiments were performed in triplicates. The immunohistochemical expression was analyzed with a semiquantitative score (IRS) and statistical analysis was performed.', 'Immunohistochemical reaction with INH-alpha could not be demonstrated in unstimulated cells, while it was significantly up-regulated in interferon-stimulated cells (p < 0.02). INH-betaA and INH-betaB were primarily observed during the mitotic phases of unstimulated cells. After stimulation their expression was significantly higher (p < 0.05 each) compared to controls and could be observed not only during mitotic phases but also in nonmitotic cells.'] Is the immunohistochemical expression of the inhibin/activin subunits up-regulated by interferon-beta1a in Ishikawa cell line? | qiaojin/PubMedQA | 2 | [
-2.2420380115509033,
-1.3740448951721191,
2.647968292236328
] |
['Inhibins are dimeric glycoproteins, belonging to the transforming growth factor beta (TGF-beta) family, composed of an alpha-subunit (INH-alpha) and one of two possible beta-subunits (betaA or betaB). Additionally two further beta-subunits (betaC and betaE) have been cloned, although their function remains still quite unclear. The detection by immunohistochemistry of inhibin/activin subunits has been proposed as a useful marker of trophoblastic diseases. Interestingly, a complete mole cannot be easily differentiated from a partial mole. Therefore, the aim of this study was to determine expression changes of the five inhibin/activin subunits in partial and complete moles.', 'Histologically diagnosed complete (n = 6) and partial (n = 3) hydatidiform moles were immunohistochemical analyzed for INH-alpha, INH-betaA, INH-betaB, INH-betaC and INH-betaE subunits. The immunohistochemical reaction in intermediate trophoblast was analyzed with a semiquantitative score (IRS) and statistical analysis was performed.', 'Immuno-histochemical reaction with INH-alpha, INH-betaA, INH-betaB, INH-betaC and INH-betaE subunits was demonstrated in hydatidiform moles. The INH-betaA and INH-betaB expression was significantly higher in complete compared to partial moles (p < 0.05 each), while INH-alpha, INH-betaC and INH-betaE did not demonstrate any statistically significant differences.'] Are inhibin/activin subunits immunohistochemically expressed in complete and partial hydatidiform moles? | qiaojin/PubMedQA | 2 | [
-2.04837965965271,
-1.5016639232635498,
2.553403377532959
] |
['Thirty-two African American and 23 non-Hispanic white women were compared for experimental pain threshold and tolerance to thermal, ischemic, and cold pressor pain. Approximately half of each group had prior mood disorders (17 African Americans, 13 non-Hispanic whites), though all were free of current mood disturbance. Women with prior mood disorders were less sensitive to ischemic pain than women with no prior mood disorders (P < .05), whereas African Americans were more sensitive to ischemic pain than non-Hispanic whites, though only at pain tolerance (P < .001). For cold pressor pain, the effects of race were only seen in women with prior mood disorders, since African Americans with prior mood disorders were more sensitive than non-Hispanic whites with prior mood disorders (P < .05). These results indicate that experimental pain sensitivity in women is influenced by both race and histories of mood disorders.'] Do race and histories of mood disorders modulate experimental pain tolerance in women? | qiaojin/PubMedQA | 1 | [
-1.0602473020553589,
1.8329558372497559,
-1.457777976989746
] |
['There is increasing evidence that matrix metalloproteinases (MMPs) may contribute to the pathogenesis of COPD, but their role in humans is not completely understood. We performed this study to quantify the expression of MMP-2 in a population of COPD patients at different stages of severity.', 'We collected surgical specimens from 46 subjects, as follows: 10 smokers with severe COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage III-IV); 13 smokers with mild/moderate COPD (GOLD stage I-II); 12 control smokers; and 11 nonsmoking control subjects. We quantified MMP-2 expression in alveolar macrophages, alveolar walls, peripheral airways, and pulmonary arterioles by immunohistochemistry.', 'In all compartments, MMP-2 expression was increased both in smokers with severe COPD and in smokers with mild/moderate COPD compared to control smokers and nonsmokers (p < 0.05 for all comparisons). Only in alveolar macrophages was MMP-2 expression increased in smokers with severe COPD compared to smokers with mild/moderate COPD (p = c0.002). Moreover, MMP-2 expression was inversely related to values of FEV1/FVC ratio (p < 0.0001; r = -0.71) and Pao2 (in millimeters of Hg) [p = 0.005; r = -0.49], and was positively related to emphysema score (p = 0.01; r = 0.65) and residual volume percent predicted (p = 0.04; r = 0.49). A stepwise increase in the total number of alveolar macrophages was observed in the four groups of subjects examined, with the highest value in those with severe COPD.'] Is matrix metalloproteinase-2 protein in lung periphery related to COPD progression? | qiaojin/PubMedQA | 2 | [
-1.4898087978363037,
-1.649731993675232,
2.0881154537200928
] |
['CGS-26303 inhibits endothelin converting enzyme (ECE)-1 more specifically than phosphoramidon. We have studied the effect of CGS-26303 on ECE-1 expression in bovine aortic endothelial cells.', 'ECE-1 activity and big endothelin (ET)-1 levels were measured by ELISA, ECE-1 expression using western and northern blot and promoter activity using transfection assays.', 'ECE-1 activity was completely inhibited by CGS-26303 25 microM and phosphoramidon 100 microM. CGS-26303 and phosphoramidon, though not thiorphan, a neutral endopeptidase (NEP) inhibitor, stimulated ECE-1 expression in cells (maximal effect at 16 h, 25 microM). Cycloheximide abolished that effect. CGS-26303 induced ECE-1 mRNA expression and ECE-1 promoter activity. CGS-35066, a selective ECE-1 inhibitor, mimicked the effects of CGS-26303, suggesting that the effect was specific to ECE-1 inhibition. Big ET-1 accumulated in the cells and in the supernatants after CGS-26303 treatment. Neither exogenously added ET-1 nor the blockade of their receptors with bosentan modified ECE-1 protein. When big ET-1 was added to cells, significant increases in ECE-1 protein content and ECE-1 promoter activity were found. Bosentan did not block those effects. CGS-26303 did not modify prepro-ET-1 expression. CGS-26303 and big ET-1 induced the same effects in human endothelial cells, at lower doses.'] Does the peptidase inhibitor CGS-26303 increase endothelin converting enzyme-1 expression in endothelial cells through accumulation of big endothelin-1? | qiaojin/PubMedQA | 2 | [
-2.1219232082366943,
-1.411462664604187,
2.5185728073120117
] |
['Pneumocystis jirovecii, formerly carinii, pneumonia (PCP) poses a life-threatening risk to oncology patients. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis virtually eliminates the risk of infection; however, many patients cannot tolerate TMP-SMZ. We performed a retrospective analysis to determine the PCP breakthrough rate in pediatric oncology patients receiving intravenous pentamidine as second line PCP prophylaxis.', 'We conducted a retrospective chart review of pediatric oncology patients who received intravenous pentamidine from 2001 to 2006 at our institution. The diagnosis, age and bone marrow transplant (BMT) status were determined. A subset of patients had review of their records to determine the justification for discontinuing TMP-SMZ. Children who developed symptoms of pneumonia with a clinical suspicion of PCP underwent bronchoscopy, allowing for identification of Pneumocystis.', 'A total of 232 patients received 1,706 doses of intravenous pentamidine and no toxicities were identified. The main reasons for discontinuing TMP-SMZ were bone marrow suppression and drug allergy. Three children developed PCP, equating to a breakthrough rate of 1.3%. Two of these children had undergone BMT (1.9% breakthrough rate) and both were under the age of two (6.5% breakthrough rate).'] Is intravenous pentamidine effective as second line Pneumocystis pneumonia prophylaxis in pediatric oncology patients? | qiaojin/PubMedQA | 2 | [
-2.296656847000122,
-1.3357172012329102,
2.74104905128479
] |
['Nutritional status is an important factor that determines hospital stay, and the Subjective Global Assessment (SGA) is a candidate tool for nutritional screening on admission. However, the significance of the SGA has not been evaluated well in the ward for digestive diseases. We conducted the present study to test whether the SGA predicts hospital stay of these patients.', 'Two hundred sixty-two patients with digestive diseases were consecutively enrolled between July 2004 and April 2005. They consisted of 145 males and 117 females and included 110 patients with cancer. Disease category was gastrointestinal in 94, hepatic in 111, and biliary/pancreatic in 57. The SGA was performed by a certified dietician. Effects of SGA and other nutritional parameters on hospital stay were examined by simple and multiple regression analysis.', 'Among tested variables, simple regression analysis identified the SGA, disease category, presence of malignancy, serum albumin level, percent triceps skinfold thickness, and percent arm muscle circumference as significant predictive parameters for hospital stay. Multiple regression analysis revealed that the SGA had the best predictive power, followed by the presence of malignancy and disease category.'] Does nutritional screening with Subjective Global Assessment predict hospital stay in patients with digestive diseases? | qiaojin/PubMedQA | 2 | [
-2.1507046222686768,
-0.6893922686576843,
1.977221965789795
] |
['Although the inflammatory response is a prerequisite for wound healing, excessive activation of the innate immune system can induce epithelial cell damage and apoptosis, which may further compromise dermal integrity. In a noninfectious burn wound model, we previously demonstrated that topical inhibition of p38 MAPK, an important inflammatory signaling pathway, attenuated epithelial cell damage and apoptosis. We now question whether attenuating local inflammation would weaken bacterial wound resistance and compromise host defense.', 'Rats received 30% total body surface area burn, and the wound was treated with topical application of a p38 MAPK inhibitor or vehicle. At 24 hours after injury, burn wounds were inoculated with Pseudomonas aeruginosa. At 48 hours postinjury, animals were sacrificed, and the burn wound was analyzed.', 'Inoculating burn wounds induced significant bacterial growth. Dermal inflammatory changes were markedly accentuated in the inoculated animals. Topical p38 MAPK inhibition reduced the proinflammatory cytokine expression in the burn wounds and neutrophil sequestration with or without bacterial inoculation. Interestingly, the bacterial wound growth was significantly attenuated in animals treated with topical p38 MAPK inhibitor.'] Does topical p38 MAPK inhibition reduce bacterial growth in an in vivo burn wound model? | qiaojin/PubMedQA | 2 | [
-2.54231333732605,
-1.1115810871124268,
2.679861068725586
] |
['Changes in training are likely to affect the professionalization process, but such complex social phenomena are poorly studied by quantitative research methodologies. In contrast, qualitative research designs are more effective in exploring complex social processes. The objective of this study was to use a qualitative methodology to explore how professional responsibilities are perceived by surgical trainees and faculty in the current academic environment.', 'Semi-structured individual interviews of 43 surgical residents and faculty (ranging from second year residents to senior faculty) were conducted at 2 academic institutions. The interviews consisted of open-ended questions, followed by discussion of 4 written, case-based scenarios on specific issues related to professional responsibilities. All interviews were audio-recorded and transcribed, and then analyzed for emergent themes by 3 researchers using a grounded theory approach.', "In discussing professional responsibilities, the motivations that shaped participants' responses reflected a balance between 4 major factors: (1) patient care, (2) education, (3) self, and (4) collegial relationships. Patient care was described as being at the center of professional responsibility, but it did not necessarily supersede other factors. Rather, patient care was described as a collective responsibility, operationalized through teamwork, communication, and trust."] Is patient care a collective responsibility : perceptions of professional responsibility in surgery? | qiaojin/PubMedQA | 1 | [
-2.4978842735290527,
2.0282857418060303,
-0.1654643714427948
] |
['The hyperpolarization-activated nucleotide-gated channel--HCN4 plays a major role in the diastolic depolarization of sinus atrial node cells. Mutant HCN4 channels have been found to be associated with inherited sinus bradycardia.', 'Sixteen members of a family with sinus bradycardia were evaluated. Evaluation included a clinical questionnaire, 12-lead ECGs, Holter monitoring, echocardiography, and treadmill exercise testing. Eight family members (5 males) were classified as affected. All affected family members were asymptomatic with normal exercise capacity during long-term follow-up. Electrophysiological testing performed on 2 affected family members confirmed significant isolated sinus node dysfunction. Segregation analysis suggested autosomal-dominant inheritance. Direct sequencing of the exons encoding HCN4 revealed a missense mutation, G480R, in the ion channel pore domain in all affected family members. Function analysis, including expression of HCN4 wild-type and G480R in Xenopus oocytes and human embryonic kidney 293 cells, revealed that mutant channels were activated at more negative voltages compared with wild-type channels. Synthesis and expression of the wild-type and mutant HCN4 channel on the plasma membrane tested in human embryonic kidney 293 cells using biotinylation and Western blot analysis demonstrated a reduction in synthesis and a trafficking defect in mutant compared with wild-type channels.'] Is point mutation in the HCN4 cardiac ion channel pore affecting synthesis , trafficking , and functional expression associated with familial asymptomatic sinus bradycardia? | qiaojin/PubMedQA | 2 | [
-2.421729803085327,
-1.2818089723587036,
2.782316207885742
] |
['Biological pacemaking has been performed with viral vectors, human embryonic stem cells, and adult human mesenchymal stem cells (hMSCs) as delivery systems. Only with human embryonic stem cells are data available regarding stability for >2 to 3 weeks, and here, immunosuppression has been used to facilitate survival of xenografts. The purpose of the present study was to determine whether hMSCs provide stable impulse initiation over 6 weeks without the use of immunosuppression, the "dose" of hMSCs that ensures function over this period, and the catecholamine responsiveness of hMSC-packaged pacemakers.', 'A full-length mHCN2 cDNA subcloned in a pIRES2-EGFP vector was electroporated into hMSCs. Transfection efficiency was estimated by GFP expression. I(HCN2) was measured with patch clamp, and cells were administered into the left ventricular anterior wall of adult dogs in complete heart block and with backup electronic pacemakers. Studies encompassed 6 weeks. I(HCN2) for all cells was 32.1+/-1.3 pA/pF (mean+/-SE) at -150 mV. Pacemaker function in intact dogs required 10 to 12 days to fully stabilize and persisted consistently through day 42 in dogs receiving > or =700,000 hMSCs (approximately 40% of which carried current). Rhythms were catecholamine responsive. Tissues from animals killed at 42 days manifested neither apoptosis nor humoral or cellular rejection.'] Do xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart? | qiaojin/PubMedQA | 2 | [
-2.228832960128784,
-1.3312785625457764,
2.577697277069092
] |
['To compare the respective pregnancy outcomes of cycles undergoing fresh elective single-blastocyst transfer (eSBT) and double-blastocyst transfer (DBT) after IVF.', 'Retrospective medical record review.', 'Academic medical center.', 'Couples undergoing fresh blastocyst transfer after IVF.', 'One thousand, four hundred, ninety-nine consecutive IVF cycles from January 1, 2002 through March 31, 2006 at the Massachusetts General Hospital Fertility Center were reviewed. Patients undergoing fresh blastocyst transfer (eSBT, n = 52; DBT, n = 187) were identified.', 'Respective pregnancy outcomes and the trend in twin gestations in all cycles undergoing blastocyst transfer, before and after the introduction of the eSBT program.', 'Statistically similar rates of biochemical pregnancy (76.9% vs. 77.6%), clinical pregnancy (61% vs. 63.4%), live birth (53.8% vs. 54.4%), and pregnancy loss (20% vs. 18.6%) per embryo transfer were observed for fresh eSBT and DBT cycles, respectively. Twin rates for eSBT were statistically significantly lower than for DBT cycles (3.1% vs. 51%). Fresh eSBT and DBT cryopreserved 2.8 vs. 1.7 blastocysts per cycle, respectively. Twenty-four months after the start of eSBT, the twin rate per transfer for all cycles undergoing blastocyst transfer (1, 2, or 3 blastocysts) was statistically significantly reduced from 47.2% to 22.9%, whereas the twin rate per transfer for all embryo transfers in women younger than 35 years of age was statistically significantly reduced from 28.8% to 15.6%.'] Does single-blastocyst transfer decrease twin gestation without affecting pregnancy outcome? | qiaojin/PubMedQA | 2 | [
-0.9614081978797913,
-1.0443775653839111,
1.0407328605651855
] |
['There is evidence that IFN gamma plays an important role in ovarian cancer development. IFN gamma produces numerous antitumor effects and it may be evasion of these effects which allows tumor progression. We postulate that genetic instability in tumor cells may lead to modulation of expression of the IFN gamma receptor, thus leading to altered tumor biology and patient prognosis. This hypothesis would support the theory of immunoediting in ovarian cancer.', 'Using tissue microarray technology of 339 primary ovarian cancers, the expression of IFN gamma receptor was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors was studied.', 'Tumors expressing high levels of IFN gamma receptor had significantly improved survival (P=0.017) compared with tumors expressing low levels of the receptor; this was also seen with complete receptor loss (P=0.014). Factors shown to predict prognosis independently of each other were the following: age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. The level of IFN gamma receptor expression and complete receptor loss were independently predictive of prognosis on multivariate analysis. There was no correlation between receptor status and any of the standard clinicopathologic variables.'] Is loss of IFN gamma receptor an independent prognostic factor in ovarian cancer? | qiaojin/PubMedQA | 2 | [
-2.4369208812713623,
-1.1713578701019287,
2.7006754875183105
] |
['Cholangiopathies are characterized by progressive dysregulation of the balance between proliferation and death of cholangiocytes. In the course of cholestasis, cholangiocytes undergo a neuroendocrine transdifferentiation and their biology is regulated by neuroendocrine hormones. Glucagon-like peptide-1 (GLP-1), secreted by neuroendocrine cells, sustains beta-cell survival in experimental diabetes and induces the neuroendocrine transdifferentiation of pancreatic ductal cells. GLP-1 receptor (GLP-1R) selective agonist exendin-4 is used in humans as a novel therapeutic tool for diabetes. The aim of this study was to define if GLP-1 modulates cholangiocyte biologic response to cholestasis.', 'Expression of GLP-1R in cholangiocytes was determined. Effects on cholangiocyte proliferation of the in vitro and in vivo exposure to GLP-1 or exendin-4, together with the intracellular signals, were then studied. Synthesis of GLP-1 by cholangiocytes and the effects of GLP-1R blockage on their growth were also determined.', 'Cholangiocytes express the GLP-1 receptor, which is up-regulated in the course of cholestasis. GLP-1 and exendin-4 increase cholangiocyte growth both in vitro and in vivo. The GLP-1R signal is mediated by the phosphatidyl-inositol-3-kinase, cAMP/Protein Kinase A, and Ca(2+)-CamKIIalpha but not by the ERK1/2 and PKCalpha pathways. Proliferating cholangiocytes synthesize GLP-1: neutralization of its action by GLP-1R antagonist blunts cholangiocyte response to cholestasis.'] Do glucagon-like peptide-1 and its receptor agonist exendin-4 modulate cholangiocyte adaptive response to cholestasis? | qiaojin/PubMedQA | 2 | [
-2.445700168609619,
-1.2707908153533936,
2.719195604324341
] |
['The mechanisms underlying neurologic impairment in celiac disease remain unknown. We tested whether antineuronal antibody-positive sera of patients with celiac disease evoke neurodegeneration via apoptosis in vitro.', 'SH-Sy5Y cells were exposed to crude sera, isolated immunoglobulin (Ig) G and IgG-depleted sera of patients with and without celiac disease with and without neurologic disorders, and antineuronal antibodies. Adsorption studies with gliadin and tissue transglutaminase (tTG) were performed in celiac disease sera. Apoptosis activated caspase-3, apaf-1, Bax, cytochrome c, cleaved caspase-8 and caspase-9 and mitochondrial respiratory chain complexes were evaluated with different methods.', 'SH-Sy5Y cells exposed to antineuronal antibody-positive sera and isolated IgG from the same sera exhibited a greater percentage of TUNEL-positive nuclei than that of antineuronal antibody-negative sera. Neuroblasts exposed to antineuronal antibody-negative celiac disease sera also showed greater TUNEL positivity and apaf-1 immunolabeled cells than controls. Antigliadin- and anti-tTG-depleted celiac disease sera had an apoptotic effect similar to controls. Anti-caspase-3 immunostained cells were greater than controls when exposed to positive sera. The mitochondrial respiratory chain complex was reduced by positive sera. Western blot demonstrated only caspase-9 cleavage in positive sera. Cytochrome c and Bax showed reciprocal translocation (from mitochondria to cytoplasm and vice versa) after treatment with positive sera.'] Do sera of patients with celiac disease and neurologic disorders evoke a mitochondrial-dependent apoptosis in vitro? | qiaojin/PubMedQA | 2 | [
-2.293283700942993,
-1.374023199081421,
2.697768211364746
] |
['Human uterine leiomyomas are very common smooth muscle cell tumors that occur in reproductive-age women and are the leading reason for performing hysterectomies. The present study was conducted to explore the potential mechanism behind the effects exerted by dominant-negative estrogen receptors (DNERs) delivered by adenovirus to leiomyoma cells to ascertain the utility of DNERs as a novel strategy for treatment of uterine fibroids.', 'We investigated the ability of DNER to affect estrogen response element (ERE) activity induced by wild-type estrogen receptor (ER) by using the adenovirus ERE luciferase (Ad-ERE-luc) system in ELT3 cells and the effect of graded doses of DNER (10, 50, and 100 plaque-forming units/cell) on the expression of some selected genes controlling cultured human leiomyoma cell proliferation (cyclin D1, Cox2, PCNA, VEGF, and EGF), apoptosis (Bcl2 and Bax), estrogen metabolism (COMT), and extracellular matrix formation (MMP(1)) as well as progesterone receptors (A and B) were assessed using Western blot analysis. These genes are all regulated by estrogen and/or progesterone.', 'DNER has the ability to suppress the ERE luc activity induced by wild-type ER (P < 0.01) and significantly (P < 0.05) reverse the expression of all estrogen- and progesterone-regulated genes in this study.'] Does adenovirus-mediated delivery of a dominant-negative estrogen receptor gene in uterine leiomyoma cells abrogate estrogen- and progesterone-regulated gene expression? | qiaojin/PubMedQA | 2 | [
-2.516096353530884,
-1.2220103740692139,
2.8162920475006104
] |
['Kisspeptin, the endogenous ligand of the G protein-coupled receptor 54, is a key regulator of the hypothalamo-pituitary-gonadal (HPG) axis. GPR54-null mice exhibit reproductive dysfunction, and exogenous kisspeptin potently stimulates the HPG axis in rodents, primates, and human males. The effects of kisspeptin administration to human females are unknown.', 'Our objective was to investigate the effects of kisspeptin on LH release during the menstrual cycle in female volunteers.', 'Bolus sc kisspeptin-54 was administered to female volunteers, and plasma gonadotropins were measured.', 'The study took place at a hospital clinical research facility.', 'Subjects were healthy female volunteers with regular menstrual cycles.', '1) Volunteers received a sc bolus injection of kisspeptin-54 (0, 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 nmol/kg; n = 3-4 per dose) in the follicular phase; and 2) volunteers (n = 8) received a sc bolus injection of either kisspeptin-54 (0.4 nmol/kg) or saline in random order during each phase of the menstrual cycle.', 'Plasma gonadotropins were measured.', '1) Kisspeptin-54 caused a dose-dependent increase in mean LH over time at doses from 0.2-6.4 nmol/kg. 2) Kisspeptin-54 increased plasma LH compared with saline injection in all phases of the cycle. The effect of kisspeptin was greatest in the preovulatory phase and least in the follicular phase of the cycle [mean increase in LH over baseline (IU/liter) +/- sem for follicular phase was 0.12 +/- 0.17; preovulatory phase, 20.64 +/- 2.91 (P < 0.001 vs. follicular phase); luteal phase, 2.17 +/- 0.79 (P < 0.01 vs. follicular phase)].'] Does kisspeptin-54 stimulate gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women? | qiaojin/PubMedQA | 2 | [
-2.006621837615967,
-1.4553136825561523,
2.413827896118164
] |
['To determine if gene transfer of the ATP-sensitive potassium (K(ATP)) channel can reverse age-related erectile dysfunction in the rat, as the K(ATP) channel is an important subtype of potassium channels regulating smooth muscle tone.', 'In an in vitro study, gene were transferred using cDNA of the K(ATP) channel in cultured human corporal smooth muscle (CSM) cells and human embryonic kidney (HEK) cells. After gene transfer, the activities of transferred channels were assessed by the patch-clamp technique. In an in vivo study, 15 old rats were used for groups of gene therapy and nine young adult rats were used as normal controls. The old rats were divided into three groups, i.e. controls and two gene-transfer groups (Kir6.1 + SUR2B and Kir6.2 + SUR2B). The intracavernosal pressure (ICP) response to cavernosal nerve stimulation was assessed after intracorporal injection with naked cDNA of the K(ATP) channel. The transgene expression of the K(ATP) channel was examined by reverse transcription-polymerase chain reaction (RT-PCR) in rats transfected with cDNA of Kir 6.1 and 6.2.', 'The transferred gene of the K(ATP) channel was functionally active and appropriate for gene transfer. The mean (sem) ratio of ICP to systemic blood pressure in the gene-transfer groups, at 79.4 (1)% and 76.5 (2.6)% (both eight rats) was significantly higher than that in age-matched control rats, at 59.4 (3.3)% (eight), and similar to that in the young control rats, at 77.1 (2.7)% (nine). The RT-PCR showed expression of Kir6.1 and 6.2 genes in the transfected groups.'] Does gene transfer of the K ( ATP ) channel restore age-related erectile dysfunction in rats? | qiaojin/PubMedQA | 2 | [
-1.5872468948364258,
-1.5420491695404053,
2.088848114013672
] |
['Ankle/brachial pressure is used as a predictor for the outcome of femoro-popliteal bypass. It has been suggested that a mean inferior mesenteric artery stump pressure (IMASP) below 40 mmHg after aortic reconstruction may be similarly predictive of postoperative ischemic colitis. No previous report has considered IMASP as a predictor of the integrity of colorectal anastomosis. The aim of the study is to examine the correlation between IMASP and anastomotic leakage rate after left colectomy.', 'From April 2004 to March 2006, 99 patients undergoing left colon resection by a single surgeon were measured for their IMASP and arm systemic pressure (SP). All but two patients were operated for carcinoma of the colon or rectum. Sixty-nine patients had primary anastomosis without diverting stomies.', 'The stump mean pressure varied from 24 to 75 mmHg. Seventy-nine patients (79.8%) had pressures equal or above 40 mmHg. IMASP/SP ratios ranged from 0.21 to 0.7. Sixty-seven patients (67.7%) had IMASP/SP ratios equal or above 0.4. Two patients were found to have postoperative leakage of anastomosis. Their IMASP were 35 and 70 mmHg, and their IMASP/SP ratios were 0.28 and 0.62, respectively. We could not identify a significant difference between the two groups, and the pressure of the inferior mesenteric artery could not be proven to be a relevant predictor of anastomotic leakage.'] Is inferior mesenteric artery stump pressure an unreliable predictor of the outcome of colorectal anastomosis? | qiaojin/PubMedQA | 2 | [
-1.834384799003601,
-1.4983419179916382,
2.333871364593506
] |
['To investigate the prevalence and clinical correlates of anti-heparin platelet factor 4 antibodies (anti-HPF4) in systemic lupus erythematosus (SLE) patients with and without antiphospholipid antibodies (aPL).', 'Sera and clinical data were obtained from the Hospital for Special Surgery Autoimmune Disease Registry for 78 aPL-positive and 91 aPL-negative SLE patients without heparin-induced thrombocytopenia (HIT). Controls were 90 blood donors of comparable age and sex. Sera were assayed for anti-HPF4, IgG/IgM antiphospholipid antibodies (APhL), and IgG/IgM anti-beta2-glycoprotein 1 antibodies (anti-beta 2GP1). Serotonin release assays (SRAs) were performed for subjects with positive anti-HPF4.', 'Positive anti-HPF4 was seen in 9% of aPL-positive SLE patients, 4% of aPL-negative SLE patients and 1% of controls (p = 0.026, aPL-positive SLE vs controls). Two of 12 subjects with positive anti-HPF4 had reactive SRAs. In SLE patients, anti-HPF4 significantly correlated with IgM APhL, IgM anti-beta2GP1, and inversely with complement C4. In immunoabsorption experiments, there was partial cross-reactivity of IgM anti-HPF4 with IgM APhL, but not with IgM anti-beta 2GP1. SLE patients with positive anti-HPF4 had increased odds of the antiphospholipid syndrome (APS; odds ratio (OR) 4.5, p = 0.019), and APS with arterial thrombosis (OR 6.1, p = 0.007). In multivariate linear regression analyses, APS and IgM APhL were independently associated with anti-HPF4.'] Are anti-heparin platelet factor 4 antibodies in systemic lupus erythematosus associated with IgM antiphospholipid antibodies and the antiphospholipid syndrome? | qiaojin/PubMedQA | 2 | [
-2.1563546657562256,
-1.4976080656051636,
2.677621841430664
] |
['Metabolic syndrome (MetS) develop by accumulation of excess central obesity occurring insulin resistance. In 2005, the Japanese Society of Internal Medicine, in collaboration with seven other Japanese societies defined the diagnostic criterion for Japan-specific MetS. Smoking also causes insulin resistance to develop. To clarify whether smoking is correlated with MetS and how long MetS remains after smoking cessation we undertook a retrospective study.', 'The subjects comprised of 22,892 Japanese who visited the Health-Care Center at Jikei University Hospital in Tokyo for medical check-ups. The participants completed a simple, self-administered questionnaire on their lifestyle including smoking information. MetS was diagnosed with the above criterion. The odds ratio (OR) with a 95% confidential interval (95%CI) of MetS was calculated using multiple logistic regression analysis adjusted by age and gender.', 'Compared with never smokers (n=9,434: 41%), the odds ratio (95% CI) of MetS onset for current smokers (n=7,634: 33%) and past smokers (n=5,824: 25%) were 1.20 (1.07-1.35) and 1.21 (1.08-1.37). In the current smokers, the odds ratio of MetS increased with the smoking number, and it significantly occurred by smoking > or = 20 cigarettes per day. After quitting, the longer cessation period is related to the lesser chance of developing of MetS. But, MetS remained for at least 10 years and over in the subjects who smoked 20 or more cigarettes per day, and for over 20 years in the subjects who smoked 40 cigarettes and more.'] Does risk of metabolic syndrome persist twenty years after the cessation of smoking? | qiaojin/PubMedQA | 0 | [
0.40752729773521423,
-1.3347009420394897,
0.053115442395210266
] |
["Growth hormone controls many facets of a cell's biology through the transcription factors Stat5a and Stat5b (Stat5). However, whole body deletion of these genes from the mouse does not provide portentous information on cell-specific cytokine signaling. To explore liver-specific functions of Stat5, the entire Stat5 locus was deleted in hepatocytes using Cre-mediated recombination. Notably, Stat5-mutant mice developed fatty livers and displayed impaired proliferation of hepatocytes upon partial hepatectomy (PHx). Loss of Stat5 led to molecular consequences beyond the reduced expression of Stat5 target genes, such as those encoding suppressor of cytokine signaling 2 (SOCS2), Cish, and insulin-like growth factor 1 (IGF-1). In particular, circulating growth hormone levels were increased and correlated with insulin resistance and increased insulin levels. Aberrant growth hormone (GH)-induced activation of the transcription factors Stat1 and Stat3 was observed in mutant livers. To test whether some of the defects observed in liver-specific Stat5 deficient mice were due to aberrant Stat1 expression and activation, we generated Stat1(-/-) mice with a hepatocyte-specific deletion of Stat5. Concomitant loss of both Stat5 and Stat1 restored cell proliferation upon PHx but did not reverse fatty liver development. Thus the molecular underpinnings of some defects observed in the absence of Stat5 are the consequence of a deregulated activation of other signal transducers and activators of transcription (STAT) family members."] Does loss of signal transducer and activator of transcription 5 lead to hepatosteatosis and impaired liver regeneration? | qiaojin/PubMedQA | 2 | [
-2.441321849822998,
-1.1969201564788818,
2.702540874481201
] |
['Aceruloplasminemia is an inherited iron overload disorder caused by a mutation in the ceruloplasmin gene and characterized by iron accumulation in both the liver and brain. The aim of this study was to elucidate the molecular pathogenesis of aceruloplasminemia by a functional analysis of mutant ceruloplasmin.', 'The effects of nonsense mutations including Y694ter, W858ter and R882ter were studied by the expression in cultured cells.', 'A biogenesis study demonstrated that the Y694ter and W858ter mutants showed protein synthesis identical to that of wild type protein, however, the mutants were retained in the endoplasmic reticulum (ER), while R882ter mutant was secreted out. Site-directed mutagenesis analyses suggested that Cys-881 was necessary for the secretion of the truncated ceruloplasmin. The W858ter mutant decreased viability in the transfected cells. The expression and the promoter activity of glucose-regulated protein 78 that is an ER stress sensor protein, were up-regulated in the transfected cells.'] Is cys-881 essential for the trafficking and secretion of truncated mutant ceruloplasmin in aceruloplasminemia? | qiaojin/PubMedQA | 2 | [
-2.484081983566284,
-1.050445795059204,
2.556182861328125
] |
['Animal models have demonstrated that maternal undernutrition or early gestation glucocorticoid exposure induces endothelial dysfunction in the offspring.', 'We sought to determine whether early gestation dexamethasone (DEX) exposure is further associated with increased vascular superoxide anion production.', "DEX (0.28 mg/kg/day i.v. for 48 h) was administered to pregnant ewes at 27-28 days' gestation (term 145 days). Tissues were harvested from DEX-exposed and control lambs at 125 days' gestation (n = 6 for each group) and 4 months following delivery (n = 9 and 12, respectively).", 'By lucigenin-enhanced chemiluminescence, coronary and mesenteric arteries from DEX-exposed fetuses exhibited diminished basal superoxide production (both p < 0.01). Similarly, DEX-exposed carotid arteries from 4-month-old lambs had decreased superoxide production (p < 0.01) that localized to the endothelium by endothelial cell culture and dihydroethidium fluorescence. In contrast, DEX-exposed coronary arteries from the 4-month-old sheep had increased superoxide production (p < 0.05). Although early gestation DEX exposure did not alter lipid peroxidation, DEX exposure was associated with significantly increased renal and cerebral cortex aconitase activity (consistent with decreased protein oxidation). These changes occurred in the absence of alterations in renal cortex superoxide dismutase activity.'] Is endothelial superoxide production altered in sheep programmed by early gestation dexamethasone exposure? | qiaojin/PubMedQA | 2 | [
-2.4125540256500244,
-1.3030489683151245,
2.8163769245147705
] |
['Immunophilin ligands and phosphodiesterase type 5 (PDE5) inhibitors are touted to promote erectile function recovery after cavernous nerve (CN) injury. However, the mechanisms for their effects remain unclear.', 'To compare the erection recovery effects of the immunophilin ligand FK506 and the PDE5 inhibitor sildenafil after CN injury and determine whether they involve antioxidative and/or antiapoptotic mechanisms.', 'Initial experiments established conditions of our CN injury model in adult male Sprague-Dawley rats. Subsequently, we evaluated treatment effects 14 days after: (i) unilateral CN injury (UNI) + saline (vehicle control); (ii) UNI + FK506 (5 mg/kg once daily, subcutaneous x 5 days); (iii) UNI + sildenafil (20 mg/kg every 8 hours, subcutaneous x 7 days); (iv) UNI + FK506/sildenafil; and (v) sham surgery.', 'Intracavernous pressure (ICP) measurement after CN electrical stimulation to assess erectile function and Western blot analysis of expressions of glutathione peroxidase (GPX; antioxidant enzyme), nitrotyrosine (NT; oxidative stress marker), and phosphorylated and total Akt (antiapoptotic factor) in penes.', 'In the UNI model, GPX expression was increased at Days 1 and 7, while p-Akt expression decreased at Day 1 and returned to baseline at Day 7. GPX expression was significantly higher in the UNI + FK506 group compared with the saline-treated group (P < 0.05). ICP increased in all treatment groups compared with that of the saline-treated group (P < 0.05). NT levels were increased after saline treatment (P < 0.05) but not after FK506 and sildenafil treatment, alone or in combination. GPX was localized to nerves coursing through the penis and to smooth muscle and endothelium of the dorsal vein and arteries.'] Do fK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms? | qiaojin/PubMedQA | 2 | [
-2.326704263687134,
-1.408612608909607,
2.784165859222412
] |
['Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues to impaired glucose homeostasis during chronic ethanol feeding is not known. As other models of insulin resistance, such as obesity, are characterized by an infiltration of macrophages into adipose tissue, as well as changes in the expression of adipocytokines that play a central role in the regulation of insulin sensitivity, we hypothesized that chronic ethanol-induced insulin resistance would be associated with increased macrophage infiltration into adipose tissue and changes in the expression of adipocytokines by adipose tissue.', 'Male Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair-fed a control diet for 4 weeks. The effects of chronic ethanol feeding on insulin-stimulated glucose utilization were studied using the hyperinsulinemic-euglycemic clamp technique, coupled with the use of isotopic tracers. Further, macrophage infiltration into adipose tissue and expression of adipocytokines were also assessed after chronic ethanol feeding.', 'Hyperinsulinemic-euglycemic clamp studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and decreased insulin-mediated suppression of hepatic glucose production. Chronic ethanol feeding decreased glucose uptake in epididymal, subcutaneous, and omental adipose tissue during the hyperinsulinemic-euglycemic clamp, but had no effect on glucose disposal in skeletal muscle. Chronic ethanol feeding increased the infiltration of macrophages into epididymal adipose tissue and changed the expression of mRNA for adipocytokines: expression of mRNA for monocyte chemoattractant protein 1, tumor necrosis factor alpha, and interleukin-6 were increased, while expression of mRNA for retinol binding protein 4 and adiponectin were decreased in epididymal adipose tissue.'] Is chronic ethanol-induced insulin resistance associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines? | qiaojin/PubMedQA | 2 | [
-2.5889692306518555,
-1.0626100301742554,
2.751358985900879
] |
['To determine the optimal timing for orchiopexy, we evaluated the histological parameters of the cryptorchid testis.', 'We prospectively performed testicular biopsy in a total of 65 consecutive children with palpable unilateral inguinal cryptorchid testes. For controls, we used testicular histological slides from 15 age-matched children with testicular tumor. To investigate the fertility potential, we analyzed the parameters including mean tubular diameter (MTD), mean tubular fertility index (MTFI), germ cell count/tubule (GCC), Sertoli cell index (SCI) and interstitial fibrosis index (IFI).', 'The MTFI and GCC in children < or =1 years of age were significantly higher than those of other older age groups. The MTFI, GCC and IFI were significantly better in patients < or =2 years of age when compared to those of > 2 years. Compared to the controls, the MTFI and GCC in the patients were significantly worse in those aged > 2 years at surgical repair. In the < or =2-year age group, the MTFI and GCC of the cryptorchid testis showed a decreasing tendency with age, which were contrasting with the ascending curves in the control and the curves crossed at 1-2 years of age in each parameter.'] Do histological evidences suggest recommending orchiopexy within the first year of life for children with unilateral inguinal cryptorchid testis? | qiaojin/PubMedQA | 2 | [
-2.0924265384674072,
-1.3684598207473755,
2.490121841430664
] |
['To demonstrate the effects of hypoxia on proliferation and differentiation of human limbal epithelial cells in vitro.', 'Primary human limbal epithelial cells were harvested from the rim of donor corneas. Colony-forming efficiency (CFE) and cell proliferation were observed in standard (20% O(2)) or hypoxic (2% O(2)) culture conditions. Cell cycle, forward scatter (FSC) and side scatter (SCC) of cells were analyzed by flow cytometry. Proliferating cells were also observed by pulse labeling (2 hours) with BrdU and Ki67 staining. Apoptosis was detected by TUNEL assay. Isolated colonies were examined by immunohistochemistry against K15, p63, involucrin, and K3. Involucrin expression was also analyzed by Western blot analysis.', 'Both CFE and proliferation of limbal epithelial cells was significantly enhanced in hypoxia. Flow cytometry revealed a higher fraction of hypoxic cells in the G(0)/G(1)-phase and fewer cells in the S-phase, compared with normoxia. However, there was no difference in the uptake of BrdU during a 2-hour pulse, suggesting that hypoxic colonies contained rapidly cycling cells. Apoptotic cells were sparse in both groups, and hypoxic cells showed lower FSC compared with normoxic cells. Although there was no difference in the staining pattern of K15, p63, and Ki67, cells cultivated in normoxia expressed higher levels of the differentiation markers involucrin and K3. Significantly higher involucrin expression was also observed by Western blot.'] Does hypoxia enhance the expansion of human limbal epithelial progenitor cells in vitro? | qiaojin/PubMedQA | 2 | [
-2.2622547149658203,
-1.3625156879425049,
2.6726861000061035
] |
['To determine effects of daily intake of 1/2 cup pinto beans, black-eyed peas or carrots (placebo) on risk factors for coronary heart disease (CHD) and diabetes mellitus (DM) in free-living, mildly insulin resistant adults over an 8 week period.', 'Randomized, crossover 3x3 block design. Sixteen participants (7 men, 9 women) received each treatment for eight-weeks with two-week washouts. Fasting blood samples collected at beginning and end of periods were analyzed for total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, triacylglycerols, high-sensitivity C-reactive protein, insulin, glucose, and hemoglobin A1c.', 'A significant treatment-by-time effect impacted serum TC (p = 0.026) and LDL (p = 0.033) after eight weeks. Paired t-tests indicated that pinto beans were responsible for this effect (p = 0.003; p = 0.008). Mean change of serum TC for pinto bean, black-eyed pea and placebo were -19 +/- 5, 2.5 +/- 6, and 1 +/- 5 mg/dL, respectively (p = 0.011). Mean change of serum LDL-C for pinto bean, black-eyed pea and placebo were -14 +/- 4, 4 +/- 5, and 1 +/- 4 mg/dL, in that order (p = 0.013). Pinto beans differed significantly from placebo (p = 0.021). No significant differences were seen with other blood concentrations across the 3 treatment periods.'] Does pinto bean consumption reduce biomarkers for heart disease risk? | qiaojin/PubMedQA | 2 | [
-1.4734013080596924,
-1.6057648658752441,
2.0486936569213867
] |
['We reviewed our experience with the Dornier Doli S lithotriptor to address 2 questions. 1) What is the stone-free rate? 2) Can a stone-free outcome be predicted by preoperative computerized tomography?', 'The records of 76 consecutive patients undergoing shock wave lithotripsy for solitary urinary calculi 5 to 20 mm in diameter were studied retrospectively. Pretreatment noncontrast computerized tomography was reviewed to determine Hounsfield density. The shock wave lithotripsy outcome was determined at 12 weeks on imaging and categorized as 1) stone free, 2) any residual fragments or 3) stone unchanged.', 'Of the patients 28 (37%) were stone free, 11 (14%) had residual fragments and 37 (49%) had stones that remained unchanged on computerized tomography after a single treatment with shock wave lithotripsy using a Dornier Doli S. Stones of patients rendered stone free had a lower median density compared to stones in patients with residual fragments and unchanged stones (684 vs 1,034 and 920 HU, respectively, p = 0.04). The stone-free rate for stones less than 1,000 HU was 46% vs 17% for stones 1,000 HU or greater (p = 0.01).'] Does shock wave lithotripsy correlate with stone density on preoperative computerized tomography? | qiaojin/PubMedQA | 2 | [
-0.725623369216919,
-1.6088485717773438,
1.3494150638580322
] |
['Follicular thyroid tumours present several genetic alterations such as aneuploidy, RAS mutations and PAX8/PPARgammarearrangements. The molecular basis of aneuploidy remains undefined in the majority of human cancers. It has been proposed that mutations in RAS oncogenes could be related to chromosomal instability, although this issue remains controversial. The aim of our study was to investigate the correlation between aneuploidy, RAS mutations and PAX8/PPARgamma gene rearrangement in thyroid follicular tumours.', 'Ploidy status was determined by flow cytometry in 111 thyroid lesions (42 follicular thyroid adenomas, 27 follicular thyroid carcinomas, 19 follicular variants of papillary thyroid carcinoma, 20 poorly differentiated thyroid carcinomas and 3 anaplastic thyroid carcinomas). RAS mutations and PAX8/PPARgamma fusion gene were investigated in 101 and 87 of these samples, respectively.', 'Altogether, 12 of 50 (24%) diploid tumours presented RAS mutation which contrasts with 3 of 51 (5.9%; P = 0.0124) RAS mutations in the group of aneuploid tumours. The aneuploid tumours harbouring RAS mutations were two poorly differentiated carcinomas and one follicular variant of papillary thyroid carcinoma with poorly differentiated areas. None of the tumours with RAS mutations expressed the PAX8/PPARgamma fusion gene. Three of five (60%) follicular thyroid adenomas and 1 of 7 (14%) follicular thyroid carcinomas, with the PAX8/PPARgamma fusion gene, were aneuploid.'] Are aneuploidy and RAS mutations mutually exclusive events in the development of well-differentiated thyroid follicular tumours? | qiaojin/PubMedQA | 2 | [
-1.6781359910964966,
-1.4852197170257568,
2.1393465995788574
] |
['The purpose of this study was to develop a clinically applicable high-efficiency percutaneous means of therapeutic gene delivery to the failing heart.', 'Substantial advances in the understanding of the cellular and molecular basis of heart failure (HF) have recently fostered interest in the potential utility of gene and cell therapy as novel therapeutic approaches. However, successful clinical translation is currently limited by the lack of safe, efficient, and selective delivery systems.', "We developed a novel percutaneous closed-loop recirculatory system that provides homogeneous myocardial delivery for gene transfer in the failing large animal heart. After 4 weeks' rapid pacing in adult sheep to induce HF, the animals were randomly allocated to receive either adenovirus expressing a pseudophosphorylated mutant (AdS16E) of phospholamban (PLN) or Ad-beta-galactosidase (AdLacZ).", 'Two weeks after gene delivery, in the presence of continued pacing, left ventricular (LV) ejection fraction had significantly improved in the AdS16E-treated animals (27 +/- 3% to 50 +/- 4%; p < 0.001), whereas a further decline occurred in the AdLacZ group (34 +/- 4% to 27 +/- 3%; p < 0.05). In conjunction, AdS16E delivery resulted in significant reductions in LV filling pressures and end-diastolic diameter (both p < 0.05). In conjunction, AdS16E-treated animals showed significant improvement in the expression of PLN and Ca2+-adenosine triphosphatase activity. In separate animals, recirculating AdLacZ delivery was shown to achieve superior myocardial gene expression in contrast to intracoronary delivery and was associated with lower systemic expression.'] Does percutaneous cardiac recirculation-mediated gene transfer of an inhibitory phospholamban peptide reverse advanced heart failure in large animals? | qiaojin/PubMedQA | 2 | [
-2.2891416549682617,
-1.4351332187652588,
2.714555501937866
] |
['This study sought to evaluate the impact of obesity on patient radiation dose during atrial fibrillation (AF) ablation procedures under fluoroscopic guidance.', 'Obesity is a risk factor for AF and its recurrence after ablation. It increases patient radiation dose during fluoroscopic imaging, but this effect has not been quantified for AF ablation procedures.', 'Effective radiation dose and lifetime attributable cancer risk were calculated from dose-area product (DAP) measurements in 85 patients undergoing AF ablation guided by biplane low-frequency pulsed fluoroscopy (3 frames/s). Three dose calculation methods were used (Monte Carlo simulation, dose conversion coefficients, and depth-profile dose curves).', 'Median DAP for all patients was 119.6 Gy x cm2 (range 13.9 to 446.3 Gy x cm2) for procedures with a median duration of 4 h and 83 +/- 26 min of fluoroscopy. Body mass index was a more important determinant of DAP than total fluoroscopy time (r = 0.74 vs. 0.37, p < 0.001), with mean DAP values per hour of fluoroscopy of 58 +/- 40 Gy x cm2, 110 +/- 43 Gy x cm2, and 184 +/- 79 Gy x cm2 in normal, overweight, and obese patients, respectively. The corresponding effective radiation doses for AF ablation procedures were 15.2 +/- 7.8 mSv, 26.7 +/- 11.6 mSv, and 39.0 +/- 15.2 mSv, respectively (Monte Carlo). Use of conversion coefficients resulted in higher effective dose estimates than other methods, particularly in obese patients. Mean attributable lifetime risk of all-cancer mortality was 0.060%, 0.100%, and 0.149%, depending on weight class.'] Is obesity a major determinant of radiation dose in patients undergoing pulmonary vein isolation for atrial fibrillation? | qiaojin/PubMedQA | 2 | [
-0.8062335252761841,
-1.7953441143035889,
1.6002416610717773
] |
['The purpose of this work was to evaluate whether ventricular repolarization dynamicity predicts major arrhythmic events in patients with idiopathic dilated cardiomyopathy (DCM).', 'Arrhythmic risk stratification in patients with DCM is still an open issue. Ventricular repolarization analysis should provide relevant information, but QT interval and QT dispersion failed in predicting arrhythmic risk.', 'The following parameters were evaluated in 179 consecutive DCM patients without history of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) at enrollment: QRS duration, QT interval corrected for heart rate, and QT dispersion at electrocardiogram (ECG); left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter at echocardiogram; and nonsustained ventricular tachycardia (NSVT), heart rate variability (standard deviation of RR intervals), and ventricular repolarization dynamicity as measured by means of 24-h ECG monitoring, by calculating the slope of linear regression analysis of QT end and RR intervals (QTe-slope) and the value of mean QT end corrected for heart rate.', 'During a mean follow-up of 39 months, 9 patients died suddenly and 15 experienced VT and/or VF. At multivariate analysis, LVEF (p = 0.047), NSVT (p = 0.022), and QTe-slope (p = 0.034) were significantly associated with arrhythmic events. Among the patients with a low LVEF, NSVT and/or steeper QTe-slope identified a subgroup at highest arrhythmic risk.'] Does ventricular repolarization dynamicity provide independent prognostic information toward major arrhythmic events in patients with idiopathic dilated cardiomyopathy? | qiaojin/PubMedQA | 2 | [
-1.922247290611267,
-1.5108959674835205,
2.4384396076202393
] |
['Articular cartilage is separated from subchondral bone by the tidemark and a calcified cartilage zone. Advancement of the calcified region and tidemark duplication are both hallmarks of osteoarthritis (OA). Currently the mechanisms controlling post-natal articular cartilage mineralization are poorly understood. The objective of this study is to test the hypothesis that cellular communication between different cartilage layers regulates articular chondrocyte mineralization.', 'Co-culture models were established to evaluate the interaction of chondrocytes derived from the surface, middle and deep zones of articular cartilage. The cultures were stimulated with triiodothyronine (T3) to promote chondrocyte hypertrophy. The effects of zonal chondrocyte interactions on chondrocyte mineralization were examined over time.', 'Co-culture of deep zone chondrocytes (DZCs) with surface zone chondrocytes (SZCs) suppressed the T3-induced increase in alkaline phosphatase (ALP) activity and related mineralization. Moreover, SZC-DZC co-culture was associated with a significantly higher parathyroid hormone-related peptide (PTHrP) expression when compared to controls. When PTHrP(1-40) was added to the DZC-only culture, it suppressed DZC ALP activity similar to the inhibition observed in co-culture with SZC. In addition, treatment with PTHrP reversed the effect of T3 stimulation on the expression of hypertrophic markers (Indian hedgehog, ALP, matrix metalloproteinases-13, Type X collagen) in the DZC cultures. Moreover, blocking the action of PTHrP significantly increased ALP activity in SZC+DZC co-culture.'] Does interaction between zonal populations of articular chondrocytes suppress chondrocyte mineralization and this process is mediated by PTHrP? | qiaojin/PubMedQA | 2 | [
-2.467254877090454,
-1.311603307723999,
2.8028101921081543
] |
['Several studies have examined the factors involved with expansion of the coagulation volume following radiofrequency ablation (RFA). Ferucarbotran contains superparamagnetic iron oxide that generates heat in a radiofrequency electric field and may have an effect on the area affected by RFA. We attempted to determine whether ferucarbotran administration expands radiofrequency-ablated volume using a rabbit model.', "A total of 15 male Japanese white rabbits (16 weeks old) were used and divided into three groups of five each. A 1-mL saline solution was given intravenously into a dorsal ear vein in the control group, whereas 1 mL ferucarbotran solution (0.016 mL/kg bodyweight) was given to the common-dose group and 1 mL of a twofold concentrated ferucarbotran solution (0.032 mL/kg bodyweight) was given to the high-dose group. RFA was performed with a cool-tip electrode 4 h after the administration and immediately thereafter the rabbits were killed, and the volume of the ablated area measured using magnetic resonance imaging (MRI). Following the MRI analysis, the rabbit's livers were resected, and the maximum short axis diameter of the ablated area in each was measured.", 'None of the rabbits died during the RFA procedure. The volume of the ablated area estimated on MR images in the ferucarbotran-administered groups was larger than that in the control group. Further, our macroscopic assessment showed that the maximum short axis diameter had a tendency to increase with ferucarbotran administration.'] Does ferucarbotran expand area treated by radiofrequency ablation in rabbit livers? | qiaojin/PubMedQA | 2 | [
-1.894338607788086,
-1.5599677562713623,
2.4839110374450684
] |
['To evaluate diagnostic instruments for assessment of nutritional status in patients with rheumatoid arthritis (RA) in relation to objective body composition data.', 'Study subjects include 60 in-ward patients (83% women, median age 65 years). Anthropometric measures and the nutritional tools Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA), Malnutrition Universal Screening Tool (MUST) and Nutritional Risk Screening tool 2002 (NRS-2002). Body composition was determined by dual-energy X-ray absorptiometry and fat-free mass index (FFMI; kg/m(2)) and fat mass index (FMI; kg/m(2)) were calculated.', 'Mean body mass index (BMI) for RA women and men were 24.4 and 26.9 kg/m(2), respectively. Twelve per cent of the women and none of the few men had BMI<18.5 kg/m(2), that is, the cutoff value for malnutrition. FFMI indicated 52% of the women and 30% of the men to be malnourished. The sensitivity and specificity for BMI to detect malnutrition according to FFMI were 27 and 100%, whereas for arm muscle circumference the sensitivity was 36% and the specificity 89% and for triceps skin fold 43 and 93%, respectively. For MNA, sensitivity was 85% and specificity 39% and for SGA 46 and 82%. Both MUST and NRS-2002 had sensitivity of 45% and specificity of 19%.'] Is malnutrition in women with rheumatoid arthritis revealed by clinical anthropometrical measurements or nutritional evaluation tools? | qiaojin/PubMedQA | 2 | [
-1.0108115673065186,
-1.7047488689422607,
1.7975187301635742
] |
['A longitudinal assessment of the association between pain-related fear and joint motions in 36 participants with subacute low back pain.', 'To determine how the psychologic construct of pain-related fear maps to motor behavior in standardized reaching tasks.', 'Pain-related fear is a significant predictor of avoidance behavior and occupational disability in individuals with low back pain. However, it is not currently known how pain-related fear maps to motor behavior.', 'Participants with an episode of subacute LBP were tested at 3, 6, and 12 weeks following pain onset. Participants performed reaching tasks at comfortable and fast-paced movement speeds to 3 targets (high, middle, low) located in a midsagittal plane. Three-dimensional joint motions of the thoracic spine, lumbar spine, and hip were recorded using an electromagnetic tracking device. Group differences in joint excursions were assessed using 2 groups (high pain-related fear, low pain-related fear) x 3 times (3, 6, 12 weeks) x 2 movement speeds (comfortable, fast paced) x 3 target heights (high, middle, low) MANOVAs.', 'Individuals with high pain-related fear had smaller excursions of the lumbar spine for reaches to all targets at 3 and 6 weeks, but not at 12 weeks following pain onset.'] Is pain-related fear associated with avoidance of spinal motion during recovery from low back pain? | qiaojin/PubMedQA | 2 | [
-2.204681873321533,
-0.44286873936653137,
1.6418348550796509
] |
['During the malignant transformation of breast tissues, the pre-mRNA precursor splicing of specific genes can be flexibly regulated, leading to the formation of different forms or amounts of mRNA in response to the cellular microenvironment, and is frequently associated with cell tumorigenesis and may even cause tumor metastasis. Regulation of pre-mRNA splicing by serine-arginine (SR)-rich phosphoprotein is hypothesized to be associated with tumor cell metastasis.', 'We enrolled 55 breast cancer patients (32 with lymph node metastasis; LNM) with paired tissue samples consisting of cancerous and tumor-adjacent normal portions and assayed these tissues for gene expression of the SR family using quantitative real-time RT-PCR (qRT-PCR), then evaluated an association with LNM of breast cancer. Furthermore, we examined whether increased expression of a specific SR gene was associated with the presence of specific CD44 spliced variants using qualitative reverse-transcription PCR (RT-PCR).', 'Support for our hypothesis came from the observations that breast tumor tissues displayed higher level of SRp40 expression as compared with the paired non-cancerous tissues, which manifested the significant association between increased SRp40 expression and LNM (OR=4.48, 95% CI, 1.08-19.50, P=0.018). In addition, the primary tumors of breast with increased expression of SRp40 gene were associated with the presence of the large CD44 inclusion variants, CD44v2, CD44v3, CD44v5, and CD44v6 (P<0.05).'] Is increased expression of SRp40 affecting CD44 splicing associated with the clinical outcome of lymph node metastasis in human breast cancer? | qiaojin/PubMedQA | 2 | [
-2.2512094974517822,
-1.2479121685028076,
2.5595955848693848
] |
['Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of endothelial cell apoptosis. The pathway mediating endothelial cell apoptosis has not been fully established. Here we investigated the participation of peroxisome proliferator-activated receptor gamma (PPARgamma) and p53 in the apoptosis of human umbilical vein endothelial cells (HUVECs).', 'HUVECs pretreated with either PPARgamma antagonist or PPARgamma small interfering RNA (siRNA) suppressed PEDF-induced apoptosis as determined by TUNEL assay, annexin V-FITC/PI staining, and cleavage of procaspase-8, -9, -3. PEDF sequentially induced PPARgamma and p53 expression as observed in immunoblotting and immunofluoresence assays. PEDF also increased the transcriptional activity of PPARgamma as evident from electromobility shift assays, and p53 as determined by the phosphorylation and acetylation of p53 and the induction of Bax. The induction of p53 by PEDF was abolished by either PPARgamma antagonist or PPARgamma siRNA. PEDF-mediated HUVEC apoptosis and cleavage of procaspases were significantly attenuated by p53 siRNA.'] Does pEDF induce p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells? | qiaojin/PubMedQA | 2 | [
-2.447880268096924,
-1.3216891288757324,
2.804257869720459
] |
['Lipoprotein lipase (LPL) is a key enzyme in the metabolism of triglyceride (TG)-rich lipoproteins. LPL in the preheparin serum (Pr-LPL) mass reflects the insulin sensitivity of diabetic patients (DM) receiving neither insulin nor hypoglycemic agents.', 'To determine whether Pr-LPL mass is a marker of insulin resistance in ambulatory type 2 DM receiving oral hypoglycemic agents, we measured Pr-LPL mass using an enzyme immunoassay in 107 ambulatory DM aged 64.9+/-11.5 y.', 'Pr-LPL mass was inversely correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) (-0.363, p<0.001), insulin (-0.351, p<0.001), and lnTG (-0.402, p<0.001), and was positively correlated with HDL-C (0.471, p<0.001). The correlation between Pr-LPL mass and HOMA-IR was equally strong in men and women. Despite medications, hypertension, dyslipidemia, and metabolic syndrome were associated with low Pr-LPL mass. Multiple regression analysis revealed that HOMA-IR was the strongest predictor of Pr-LPL mass. Pr-LPL mass remained constant from 07:30 to 17:30 h.'] Is preheparin lipoprotein lipase mass a practical marker of insulin resistance in ambulatory type 2 diabetic patients treated with oral hypoglycemic agents? | qiaojin/PubMedQA | 2 | [
-1.995324730873108,
-1.5360136032104492,
2.523653984069824
] |
['Steatosis and metabolic abnormalities seem to be frequent and deleterious in chronic hepatitis C. Changes in glucose homeostasis and in adiponectin levels, an adipokine with anti-inflammatory and insulin-sensitive properties, were evaluated in patients with chronic hepatitis C according to steatosis, liver fibrosis and body mass index.', 'Seventy-three patients with chronic hepatitis C (40 men, 33 women) infected with genotypes non-3 and 22 healthy controls (11 men and 11 women) were included in the study and all had a biochemical evaluation, including metabolic parameters, adiponectin measurement, and a liver biopsy. Insulin sensitivity was assessed with the HOMA 1-IR insulin resistance model.', 'Steatosis was found in 65.7% of the patients and significant fibrosis (METAVIR F2-F4) was present in 28.7%. The presence of steatosis could only be predicted by fibrosis, whereas significant fibrosis could be predicted by steatosis and age. Adiponectin levels were significantly decreased (-32%) with the severity of the steatosis. Although overweight chronic hepatitis C patients (body mass index>or=25 kg/m2) had insulin resistance and hypoadiponectinemia, lean chronic hepatitis C patients (body mass index<25 kg/m2) had already significantly higher glycemia and lower adiponectin levels than in controls.'] Are glucose intolerance and hypoadiponectinemia already present in lean patients with chronic hepatitis C infected with genotype non-3 viruses? | qiaojin/PubMedQA | 2 | [
-1.9325923919677734,
-1.3027842044830322,
2.2424488067626953
] |
['Cardiac surgery using cardiopulmonary bypass (CPB) is performed widely, given the progress in cardioprotective methods. However, endotoxemia caused by CPB leads to systemic inflammatory response syndrome and deterioration of organ function. We evaluated the effectiveness of endotoxin removal with a polymyxin B-immobilized hemoperfusion cartridge (PMX) in CPB.', 'Pigs weighing about 25 kg were divided into control (n = 5) and PMX (n = 5) groups. Normothermic CPB was performed in the control group, while endotoxin was removed with PMX under normothermic CPB in the PMX group. Endotoxin removal was performed from the start to end of CPB. The end-systolic pressure-volume ratio (E(max)), left ventricular pressure (LVP), maximum and minimum rates of increase in LVP (+/-LVdp/dt), and cardiac output (CO) were measured 2 h after CPB, and the recovery rates of the parameters were compared between the two groups. A histopathological study was also conducted.', 'The recovery rates of E(max), CO, and LVP were significantly better (P < 0.05) in the PMX group than in the control group. The PaO(2) 2 h after CPB was significantly higher (P < 0.05) in the PMX group than in the control group. The interleukin (IL)-8 level 2 h after CPB was significantly lower (P < 0.05) in the PMX group. Histopathologically, the heart and pulmonary tissues were better preserved in the PMX group.'] Does endotoxin removal with a polymyxin B-immobilized hemoperfusion cartridge improve cardiopulmonary function after cardiopulmonary bypass? | qiaojin/PubMedQA | 2 | [
-1.9628323316574097,
-1.5887174606323242,
2.547607898712158
] |
['AGHD is associated with osteoporosis. We examined PTH circadian rhythmicity and PTH target-organ sensitivity in 23 patients with AGHD with low BMD and 20 patients with AGHD with normal BMD. Patients with low BMD had a blunted nocturnal rise in PTH concentration and reduced PTH target-organ sensitivity compared with patients with normal BMD; these factors may be important in the pathogenesis of AGHD-related osteoporosis.', 'Adult growth hormone deficiency (AGHD) is associated with decreased BMD. Reduced parathyroid gland sensitivity to changes in calcium and reduced PTH target-organ sensitivity may underlie the pathogenesis of AGHD-related osteoporosis. A blunted nocturnal PTH rise has been reported in AGHD and may contribute to the reduction in BMD. We examined the difference in PTH concentration and markers of bone metabolism in patients with AGHD with normal and low BMD.', 'Forty-three patients with AGHD consented to the study. Twenty-five patients were growth hormone (GH) naïve (GH-N, 13 had BMD femoral neck or lumbar spine T-score < -1.0), and 18 patients had received GH for >2 yr (GH-R, 10 had BMD T-score < -1.0). Patients were hospitalized for 24 h, where blood samples were collected every 0.5 h and urine samples were collected every 3 h for PTH, calcium, phosphate, NcAMP, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], type-I collagen beta C-telopeptide (betaCTX), and procollagen type-I amino-terminal propeptide (PINP). Serum calcium was adjusted for albumin (ACa).', 'Low BMD GH-N and GH-R patients exhibited a reduced nocturnal rise in PTH concentration compared with patients with normal BMD (p < 0.001). GH-N low BMD patients had significantly higher 24-h mean PTH (p < 0.001) than GH-N normal BMD patients, with significantly lower 24-h mean NcAMP, ACa, and 1,25(OH)(2)D (p < 0.01), suggesting a reduction in renal PTH sensitivity. GH-R low BMD patients had significantly lower 24-h mean PTH, NcAMP, ACa, and 1,25(OH)(2)D (p < 0.01) than GH-R normal BMD patients, suggesting reduced renal PTH action. Lower PTH concentration in the presence of lower ACa may reflect reduced sensitivity of the parathyroid calcium-sensing receptor to changes in ACa concentration in the GH-R low BMD patients.'] Is pTH circadian rhythm and PTH target-organ sensitivity altered in patients with adult growth hormone deficiency with low BMD? | qiaojin/PubMedQA | 2 | [
-1.9886388778686523,
-1.5597530603408813,
2.5049936771392822
] |
['The presence of biliary obstruction in patients with gallbladder cancer (GBC) is generally viewed as an indicator of advanced disease, inoperability and poor prognosis.', 'Data was collected from patients with GBC with obstructive jaundice who underwent resection during the period January 2001 to October 2003. Systematic analysis of prospective data was undertaken; patients were analyzed for resectability, post-operative morbidity, mortality and disease-free survival.', 'During this period 14 patients with GBC with biliary obstruction underwent resection with curative intent. In these jaundiced patients, the resectability rate was 27.45% (14 of 51). In the jaundiced group the mortality was 7.14% the morbidity rate 50%, the mean disease free survival was 23.46 months (median 26 months and range of 2 to 62 months). Seven patients (50%) survived more than two years.'] Is biliary obstruction in gall bladder cancer sine qua non of inoperability? | qiaojin/PubMedQA | 2 | [
-2.523066759109497,
-0.34680482745170593,
1.8965250253677368
] |
['Chronic treatment with neuroleptics causes, as a side effect, tardive dyskinesia in humans; however, the mechanisms involved in its pathophysiology remain unclear.', 'The purpose of this study was to examine the effects of diphenyl diselenide, an organoselenium compound with antioxidant properties, in an animal model of vacuous chewing movements (VCMs) induced by long-term treatment with fluphenazine.', 'Adult male rats were treated during 24 weeks with fluphenazine (25 mg/kg, intramuscularly [i.m.], once every 21 days) and diphenyl diselenide (1 mg/kg, subcutaneously, three times a week). VCMs and body weight gain were quantified every 3 weeks. The fluphenazine treatment produced VCMs in the majority of the treated rats (87% after 24 weeks). Concomitant treatment with diphenyl diselenide decreased the prevalence of VCMs to 50%. Additionally, we separated the rats that developed or did not develop VCMs. We did not find any statistical differences among the groups when oxidative stress parameters were evaluated. Chronic fluphenazine treatment significantly decreased [(3)H]-dopamine uptake. Concomitant treatment with diphenyl diselenide was not able to prevent this decrease in those rats that developed VCMs.'] Does diphenyl diselenide decrease the prevalence of vacuous chewing movements induced by fluphenazine in rats? | qiaojin/PubMedQA | 2 | [
-2.3679544925689697,
-1.2130638360977173,
2.6329007148742676
] |
['There is conflicting evidence about the propensity of trans fatty acids (TFAs) to cause obesity and insulin resistance. The effect of moderately high intake of dietary monounsaturated TFAs on body composition and indices of glucose metabolism was evaluated to determine any pro-diabetic effect in the absence of weight gain.', 'Male African green monkeys (Chlorocebus aethiops; n=42) were assigned to diets containing either cis-monounsaturated fatty acids or an equivalent diet containing the trans-isomers (approximately 8% of energy) for 6 years. Total calories were supplied to provide maintenance energy requirements and were intended to not promote weight gain. Longitudinal body weight and abdominal fat distribution by computed tomography scan analysis at 6 years of study are reported. Fasting plasma insulin, glucose, and fructosamine concentrations were measured. Postprandial insulin and glucose concentrations, and insulin-stimulated serine/threonine protein kinase (Akt), insulin receptor activation, and tumor necrosis factor-alpha concentrations in subcutaneous fat and muscle were measured in subsets of animals.', 'TFA-fed monkeys gained significant weight with increased intra-abdominal fat deposition. Impaired glucose disposal was implied by significant postprandial hyperinsulinemia, elevated fructosamine, and trends toward higher glucose concentrations. Significant reduction in muscle Akt phosphorylation from the TFA-fed monkeys suggested a mechanism for these changes in carbohydrate metabolism.'] Does trans fat diet induce abdominal obesity and changes in insulin sensitivity in monkeys? | qiaojin/PubMedQA | 2 | [
-2.7722413539886475,
-0.46730998158454895,
2.2776870727539062
] |
['The drug K201 (JTV-519) increases inotropy and suppresses arrhythmias in failing hearts, but the effects of K201 on normal hearts is unknown.', 'The effect of K201 on excitation-contraction (E-C) coupling in normal myocardium was studied by using voltage-clamp and intracellular Ca(2+) measurements in intact cells. Sarcoplasmic reticulum (SR) function was assessed using permeabilised cardiomyocytes.', 'Acute application of <1 micromol/L K201 had no significant effect on E-C coupling. K201 at 1 micromol/L decreased Ca(2+) transient amplitude (to 83+/-7%) without affecting I(Ca,L) or the SR Ca(2+) content. At 3 micromol/L K201 caused a larger reduction of Ca(2+) transient amplitude (to 60+/-7%) with accompanying reductions in I(Ca,L) amplitude (to 66+/-8%) and SR Ca(2+) content (74+/-9%). Spontaneous SR Ca(2+) release during diastole was induced by increasing intracellular [Ca(2+)]. At 1 micromol/L K201 reduced the frequency of spontaneous Ca(2+) release. The effect of K201 on SR-mediated Ca(2+) waves and Ca(2+) sparks was examined in beta-escin-permeabilised cardiomyocytes by confocal microscopy. K201 (1 micromol/L) reduced the frequency and velocity of SR Ca(2+) waves despite no change in SR Ca(2+) content. At 3 micromol/L K201 completely abolished Ca(2+) waves and reduced the SR Ca(2+) content (to approximately 73%). K201 at 1 micromol/L reduced Ca(2+) spark amplitude and frequency. Assays specific to SR Ca(2+)-ATPase and RyR2 activity indicated that K201 inhibited both SR Ca(2+) uptake and release.'] Does k201 modulate excitation-contraction coupling and spontaneous Ca2+ release in normal adult rabbit ventricular cardiomyocytes? | qiaojin/PubMedQA | 2 | [
-2.0837008953094482,
-1.5350556373596191,
2.6305270195007324
] |
['This study investigates the effect of leukoaraiosis on patients presenting with cognitive impairment after lacunar stroke.', 'Fourty-six patients with cognitive impairment and newly discovered lacunar stroke detected by brain magnetic resonance imaging underwent neuropsychological testing.', 'Patients with both lacunar infarct and leukoaraiosis performed less well on cognitive measures, compared to those with lacunar infarcts alone. Additionally, leukoaraiosis severity inversely correlated with cognitive performance.'] Does cognitive performance after lacunar stroke correlate with leukoaraiosis severity? | qiaojin/PubMedQA | 2 | [
-2.2995104789733887,
-1.034165859222412,
2.372307062149048
] |
['Anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment in the mouse ovary. We hypothesize that in women AMH signaling also regulates the usage of the primordial follicle pool and hence influences the onset of menopause. Since age at menopause has a strong genetic component, we investigated the role of AMH signaling using a candidate gene approach.', 'In two large population-based cohorts of Dutch post-menopausal women (n = 2381 and n = 248), we examined the association between two polymorphisms, one in the AMH gene and one in the AMH type II receptor (AMHR2) gene, and natural age at menopause.', 'The AMH Ile(49)Ser polymorphism (rs10407022) was not associated with age at menopause in either cohort. In the Rotterdam cohort, the AMHR2 -482 A > G polymorphism (rs2002555) was associated with age at menopause in interaction with the number of offspring (P = 0.001). Nulliparous women homozygous for the G-allele entered menopause 2.6 years earlier compared with nulliparous women homozygous for the A-allele (P = 0.005). In the LASA cohort, women with the G/G genotype tended to enter menopause 2.8 years earlier compared with the A/A genotype (P = 0.063).'] Is a polymorphism in the AMH type II receptor gene associated with age at menopause in interaction with parity? | qiaojin/PubMedQA | 2 | [
-1.9610658884048462,
-1.3420220613479614,
2.314772605895996
] |
['Identification of patients at high risk of death is critical for appropriate management of patients and health care resources. The impact of repeated heart failure (HF) hospitalization on mortality has not been studied for a large community population with HF. We aimed to characterize survival of patients in relation to the number of HF hospitalizations.', "Using the health care utilization databases, we identified a cohort of patients with a first hospitalization for HF among all residents of British Columbia between 2000 and 2004. Survival time was measured after patients' first and each subsequent HF hospitalization. Kaplan-Meier cumulative mortality curves were constructed after each subsequent HF hospitalization. Hazard ratios for the number of HF hospitalizations were estimated using a multivariate Cox regression adjusting for major comorbidities.", 'Of 14,374 patients hospitalized for HF, 7401 died during the 24,766 person-years of follow-up. Mortality significantly increased after each HF hospitalization. After adjusting for age, sex, and major comorbidities, the number of HF hospitalizations was a strong predictor of all-cause death. Median survival after the first, second, third, and fourth hospitalization was 2.4, 1.4, 1.0, and 0.6 years. Advanced age, renal disease, and history of cardiac arrest attenuated the impact of the number of HF hospitalizations.'] Do repeated hospitalizations predict mortality in the community population with heart failure? | qiaojin/PubMedQA | 1 | [
-1.3741018772125244,
0.3959009349346161,
0.13408908247947693
] |
['It is uncertain whether atherosclerosis is accelerated in premenopausal and postmenopausal patients with long-term well-controlled systemic lupus erythematosus (SLE).', 'We measured the intima-media thickness (IMT) of the carotid arteries and the cardio-ankle vascular index (CAVI) in 39 women with SLE and in age- and sex-matched controls.', 'In the premenopausal state, carotid plaque was detected only in SLE patients (36%). In the postmenopausal state, the maximum IMT was about 2-fold greater in SLE patients than in control subjects (1.3+/-0.7 vs. 0.7+/-0.2 mm, p<0.001). CAVI was higher in both the premenopausal and postmenopausal SLE patients. The serum amyloid A protein (SAA) was higher in SLE patients in the premenopausal state (p=0.025), while remnant like particle-cholesterol (RLP-C), the homeostasis model assessment of insulin resistance (HOMA-IR), and SAA were significantly increased in postmenopausal SLE patients (p=0.001, p<0.001 and p<0.05, respectively). Multiple regression analysis revealed that the maximum IMT was associated with cumulative PSL dosage (p=0.027) and SAA (p=0.074) in the premenopausal SLE patients, and with HOMA-IR (p<0.001) in the postmenopausal SLE patients.'] Is atherosclerosis accelerated in patients with long-term well-controlled systemic lupus erythematosus ( SLE )? | qiaojin/PubMedQA | 2 | [
-1.982450008392334,
-1.5355156660079956,
2.4967234134674072
] |
['Hereditary Hemochromatosis (HH) is a genetic disease associated with iron overload, in which individuals homozygous for the mutant C282Y HFE associated allele are at risk for the development of a range of disorders particularly liver disease. Conformational diseases are a class of disorders associated with the expression of misfolded protein. HFE C282Y is a mutant protein that does not fold correctly and consequently is retained in the Endoplasmic Reticulum (ER). In this context, we sought to identify ER stress signals associated with mutant C282Y HFE protein expression, which may have a role in the molecular pathogenesis of HH.', 'Vector constructs of Wild type HFE and Mutant C282Y HFE were made and transfected into HEK293 cell lines. We have shown that expression of C282Y HFE protein triggers both an unfolded protein response (UPR), as revealed by the increased GRP78, ATF6 and CHOP expression, and an ER overload response (EOR), as indicated by NF-kappaB activation. Furthermore, C282Y HFE protein induced apoptotic responses associated with activation of ER stress. Inhibition studies demonstrated that tauroursodeoxycholic acid, an endogenous bile acid, downregulates these events. Finally, we found that the co-existence of both C282Y HFE and Z alpha 1-antitrypsin protein (the protein associated with the liver disease of Z alpha 1-antitrypsin deficiency) expression on ER stress responses acted as potential disease modifiers with respect to each other.'] Does expression of hereditary hemochromatosis C282Y HFE protein in HEK293 cells activate specific endoplasmic reticulum stress responses? | qiaojin/PubMedQA | 2 | [
-2.5023248195648193,
-1.1926164627075195,
2.7507102489471436
] |
['In a mammalian host, the cell surface of African trypanosomes is protected by a monolayer of a single variant surface glycoprotein (VSG). The VSG is central to antigenic variation; one VSG gene is expressed at any one time and there is a low frequency stochastic switch to expression of a different VSG gene. The genome of Trypanosoma brucei contains a repertoire of > 1000 VSG sequences. The degree of conservation of the genomic VSG repertoire in different strains has not been investigated in detail.', "Eighteen expressed VSGs from Ugandan isolates were compared with homologues (> 40 % sequence identity) in the two available T. brucei genome sequences. Fourteen homologues were present in the genome of Trypanosoma brucei brucei TREU927 from Kenya and fourteen in the genome of T. b. gambiense Dal972 from Cote d'Ivoire. The Ugandan VSGs averaged 71% and 73 % identity to homologues in T. b. brucei and T. b. gambiense respectively. The sequence divergence between homologous VSGs from the three different strains was not random but was more prevalent in the parts of the VSG believed to interact with the host immune system on the living trypanosome."] Do variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific? | qiaojin/PubMedQA | 2 | [
-2.026512861251831,
-0.7780210375785828,
1.906559944152832
] |
['Mutations in the human polycystic kidney disease-1 (hPKD1) gene result in ~85% of cases of autosomal dominant polycystic kidney disease, the most frequent human monogenic disease. PKD1 proteins are large multidomain proteins involved in a variety of signal transduction mechanisms. Obtaining more information about members of the PKD1 family will help to clarify their functions. Humans have five hPKD1 proteins, whereas sea urchins have 10. The PKD1 proteins of the sea urchin, Strongylocentrotus purpuratus, are referred to as the Receptor for Egg Jelly, or SpREJ proteins. The SpREJ proteins form a subfamily within the PKD1 family. They frequently contain C-type lectin domains, PKD repeats, a REJ domain, a GPS domain, a PLAT/LH2 domain, 1-11 transmembrane segments and a C-terminal coiled-coil domain.', 'The 10 full-length SpREJ cDNA sequences were determined. The secondary structures of their deduced proteins were predicted and compared to the five human hPKD1 proteins. The genomic structures of the 10 SpREJs show low similarity to each other. All 10 SpREJs are transcribed in either embryos or adult tissues. SpREJs show distinct patterns of expression during embryogenesis. Adult tissues show tissue-specific patterns of SpREJ expression.'] Are the 10 sea urchin receptor for egg jelly proteins ( SpREJ ) members of the polycystic kidney disease-1 ( PKD1 ) family? | qiaojin/PubMedQA | 2 | [
-2.3596763610839844,
-0.896112322807312,
2.2772881984710693
] |
['Enterobacteria and cytokines both play roles in the pathophysiology of NSAID-induced enteropathy. Toll-like receptor (TLR) 4 recognises lipopolysaccharide (LPS), resulting in activation of an inflammatory cascade via the accessory protein MyD88.', 'To investigate role of TLR4 in inflammatory responses in indomethacin-induced enteropathy.', 'Indomethacin was administered p.o. to non-fasting rats and mice to induce small intestinal damage. The extent of such damage was evaluated by measuring the injured area stained dark blue with Evans blue. Rats were given antibiotics (ampicillin, aztreonam or vancomycin) p.o., or intraperitoneal LPS (a TLR4 ligand) or neutralising antibodies against neutrophils, tumour necrosis factor (TNF)-alpha, or monocyte chemotactic protein (MCP)-1. Furthermore, the intestinal ulcerogenicity of indomethacin was examined in TLR4-mutant, TLR4(-/-), and MyD88(-/-) mice.', 'Indomethacin induced small intestinal damage with an increase in expression of TNF-alpha and MCP-1 in both rats and mice. Antibodies against neutrophils, TNF-alpha and MCP-1 inhibited the damage by 83%, 67% and 63%, respectively, in rats. Ampicillin and aztreonam also inhibited this damage, and decreased the number of Gram-negative bacteria in the small intestinal contents of the rat. However, vancomycin, which exhibited no activity against Gram-negative bacteria, had no preventive effect against this damage. Administration of LPS 1 h after indomethacin aggravated the damage, whereas LPS pretreatment inhibited it with reduction of expression of TLR4 and cytokines. In TLR4-mutant mice, the damage and cytokine expression were markedly inhibited. TLR4(-/-) and MyD88(-/-) mice were also resistant to the damage.'] Is non-steroidal anti-inflammatory drug-induced small intestinal damage Toll-like receptor 4 dependent? | qiaojin/PubMedQA | 2 | [
-2.4072914123535156,
-1.356134295463562,
2.7866759300231934
] |
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