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['To investigate the effect of the Cdk5 inhibitor olomoucine on corneal debridement wound healing in vivo.', "Corneal debridement wounds of 1.5 mm were made on the ocular surface of CD-1 mice. A 20 microl drop of 15 microM olomoucine in 1% DMSO was applied to the wound area immediately after wounding and again after 6 h. Control mice received identical applications of 1% DMSO. Mice were euthanized after 18 h, two weeks, and three weeks for evaluation of wound healing and restratification. Corneas were stained with Richardson's dye, photographed, and processed for histology and immunofluorescence as whole mounts or paraffin sections. The remaining wound area at 18 h was measured by image analysis. Scratch wounded cultures of human corneal-limbal epithelial cells (HCLE) were used to examine the effect of olomoucine on matrix metalloproteinase (MMP) expression in vitro. MMP-2 and MMP-9 were detected by immunofluorescence and immunoblotting.", 'Olomoucine treatment significantly enhanced corneal wound closure without increasing inflammation or infiltration of polymorphonuclear leukocytes 18 h after wounding (p<0.05). The increased localization of MMP-9 within epithelial cells at the wound edge was further enhanced by olomoucine while the expression of MMP-2 was reduced. Olomoucine treatment of scratch wounded HCLE cells produced similar changes in MMP-9 and MMP-2 expression. The examination of treated corneas two and three weeks after wounding showed normal epithelial restratification with no evidence of inflammation or stromal disorganization.'] Does the Cdk5 inhibitor olomoucine promote corneal debridement wound closure in vivo? | qiaojin/PubMedQA | 2 | [
-2.3460781574249268,
-1.4374033212661743,
2.8317322731018066
] |
['The probability that a patient has common bile duct stones (CBDS) is a key factor in determining diagnostic and treatment strategies. This prospective cohort study evaluated the accuracy of clinical models in predicting CBDS for patients who will undergo cholecystectomy for lithiasis.', 'From October 2005 until September 2006, 335 consecutive patients with symptoms of gallstone disease underwent cholecystectomy. Statistical analysis was performed on prospective patient data obtained at the time of first presentation to the hospital. Demonstrable CBDS at the time of endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative cholangiography (IOC) was considered the gold standard for the presence of CBDS.', 'Common bile duct stones were demonstrated in 53 patients. For 35 patients, ERCP was performed, with successful stone clearance in 24 of 30 patients who had proven CBDS. In 29 patients, IOC showed CBDS, which were managed successfully via laparoscopic common bile duct exploration, with stone extraction at the time of cholecystectomy. Prospective validation of the existing model for CBDS resulted in a predictive accuracy rate of 73%. The new model showed a predictive accuracy rate of 79%.'] Are clinical models inaccurate in predicting bile duct stones in situ for patients with gallbladder? | qiaojin/PubMedQA | 2 | [
-2.214296340942383,
-1.1634232997894287,
2.4216976165771484
] |
['To determine if the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification of lupus nephritis (LN) is helpful in predicting renal outcome.', 'A total of 92 patients with LN who underwent renal biopsy in our hospital were re-classified according to the ISN/RPS 2003 criteria.', 'The mean patient age was 36.8 yrs and the median observation period was 65 months. The relative frequency for each class was as follows: Class I (minimal mesangial LN) 0%, Class II (mesangial proliferative LN) 13%, Class III (focal LN) 17%, Class IV (diffuse LN) 60% and Class V (membranous LN) 10%. Within Class IV, diffuse segmental (Class IV-S) was 25% and diffuse global (Class IV-G) 75%. During the observation period, renal function was more likely to deteriorate in Class IV-G cases than in Class IV-S cases. Importantly, when Class IV-G was subdivided into cases involving active lesion alone [IV-G (A)] or chronic lesion [IV-G (A/C)], the majority of cases in IV-G (A) was nephrotic, but responded well to therapy. In contrast, renal function declined only in IV-G (A/C) cases. Patients with Class IV-G (A/C) had persistent proteinuria in spite of intensified therapies. Moreover, the higher proportion of chronic lesions was related with the deterioration of renal function.'] Is revised classification of lupus nephritis valuable in predicting renal outcome with an indication of the proportion of glomeruli affected by chronic lesions? | qiaojin/PubMedQA | 2 | [
-2.067110538482666,
-1.2121906280517578,
2.388947010040283
] |
['Elderly patients with heart failure undergoing urgent major surgery suffer substantial cardiac morbidity and mortality. Levosimendan, a novel calcium sensitizer, enhances myocardial contractility while simultaneously having vasodilatory and cardioprotective properties. This could be advantageous in perioperative management of heart failure patients.', 'Ten consecutive patients with symptomatic heart failure and left ventricular ejection fraction <35% undergoing urgent hip fracture repair were studied. Levosimendan was administered with an infusion rate of 0.1 microg kg(-1) min(-1) in a total dose of 12.5 mg starting a minimum of 2 h prior to surgery. Haemodynamic parameters were obtained at baseline and at 4, 8, 12, 16, 20, 24, 28, 36 and 48 h after start of levosimendan. B-type natriuretic peptide was measured on admission and after 48 h.', 'Patients were 86 +/- 7 yr (mean +/- SD) of age. Levosimendan significantly increased cardiac index from 2.4 +/- 0.3 L min(-1) m(-2) at baseline to 3.2 +/- 0.6 L min(-1) m(-2) after 24 h by increases in stroke volume index (baseline 27 +/- 5 mL m(-2), after 24 h 37 +/- 10 mL m(-2), P < 0.05). Systemic vascular resistance index significantly decreased from 2718 +/- 841 to 1964 +/- 385 dyn s cm-5 m(-2) within 24 h. Haemodynamic changes exerted by levosimendan persisted up to 48 h. B-type natriuretic peptide plasma concentrations decreased from 1143 +/- 792 to 935 +/- 724 ng L(-1) after 48 h (P = 0.006).'] Does levosimendan infusion improve haemodynamics in elderly heart failure patients undergoing urgent hip fracture repair? | qiaojin/PubMedQA | 2 | [
-1.3720773458480835,
-1.7367552518844604,
2.108755111694336
] |
['We hypothesized that advanced information and communication technology (ICT) would be acceptable to parents in a pediatric surgical, and diagnostic imaging day care setting.', "After Ethics Committee approval, we distributed surveys, over a one-month period, to parents of children arriving for day care surgery or diagnostic imaging. Parents indicated their acceptance of various proposed modes of postoperative discussion of healthcare i.e.; face-to-face, videophone, or telephone. Parents were also asked to describe their receptiveness to scheduling non-emergency hospital appointments online and to receiving electronic media describing their child's surgery and postoperative management. Parental education, income, and familiarity with the Internet were also assessed.", 'A total of 451 surveys (84% response rate) were returned. Most parents (95%) had access to the Internet and 70% did their banking online. Forty-two percent of the parents had at least a university education and 63% had an annual family income > $50,000 Canadian. The majority of parents (98%) accepted face-to-face interaction, while only 35% and 37% of parents were receptive to videophone and telephone interviews, respectively. Computer availability (P = 0.001) and online banking (P = 0.011) were the only variables that predicted those parents who were in favour of using videophone technology. Parents were receptive to instruction electronic media (80%) and booking appointments online (61%).'] Are parents reluctant to use technological means of communication in pediatric day care? | qiaojin/PubMedQA | 1 | [
-1.4693565368652344,
1.2061245441436768,
-0.5062189698219299
] |
['Hepatocyte transplantation following liver irradiation (IR) and partial hepatectomy (PH) leads to extensive liver repopulation. We investigated the changes in the liver induced by IR explaining the loss of reproductive integrity in endogenous hepatocytes.', 'Right lobules of rat liver underwent external beam IR (25 Gy). A second group was subjected to additional 33% PH of the untreated left liver lobule. Liver specimens and controls were analyzed for DNA damage, apoptosis, proliferation and cell cycle related genes (1 hour to up to 12 weeks).', 'Double strand breaks (phosphorylated histone H2AX) induced by IR rapidly declined within hours and were no longer detectable after 4 days. No significant apoptosis was noted and steady mRNA levels (B-cell lymphoma 2-associated X protein (BAX), caspase 3 and 9) were in line with the lack of DNA fragmentation. However, gene expression of p53 and p21 in irradiated liver tissue increased. Transcripts of cyclin D1, proliferating cell nuclear antigen (PCNA), and cyclin B augmented progressively, whereas cyclin E was only affected moderately. Following PH, irradiated livers displayed persistently high protein levels of p21 and cyclin D1. However, cell divisions were infrequent, as reflected by low PCNA levels up to four weeks.'] Does irradiation as preparative regimen for hepatocyte transplantation cause prolonged cell cycle block? | qiaojin/PubMedQA | 2 | [
-2.471719741821289,
-1.3374615907669067,
2.8760299682617188
] |
['Up to now, two loci have been involved in XX sex-reversal in mammals following loss-of-function mutations, PIS (Polled Intersex Syndrome) in goats and R-spondin1 (RSPO1) in humans. Here, we analyze the possible interaction between these two factors during goat gonad development. Furthermore, since functional redundancy between different R-spondins may influence gonad development, we also studied the expression patterns of RSPO2, 3 and 4.', 'Similarly to the mouse, RSPO1 shows a sex-dimorphic expression pattern during goat gonad development with higher levels in the ovaries. Interestingly, the PIS mutation does not seem to influence its level of expression. Moreover, using an RSPO1 specific antibody, the RSPO1 protein was localized in the cortical area of early differentiating ovaries (36 and 40 dpc). This cortical area contains the majority of germ cell that are surrounded by FOXL2 negative somatic cells. At latter stages (50 and 60 dpc) RSPO1 protein remains specifically localized on the germ cell membranes. Interestingly, a time-specific relocation of RSPO1 on the germ cell membrane was noticed, moving from a uniform distribution at 40 dpc to a punctuated staining before and during meiosis (50 and 60 dpc respectively). Interestingly, also RSPO2 and RSPO4 show a sex-dimorphic expression pattern with higher levels in the ovaries. Although RSPO4 was found to be faintly and belatedly expressed, the expression of RSPO2 increases at the crucial 36 dpc stage, as does that of FOXL2. Importantly, RSPO2 expression appears dramatically decreased in XX PIS-/- gonads at all three tested stages (36, 40 and 50 dpc).'] Do r-spondin1 and FOXL2 act into two distinct cellular types during goat ovarian differentiation? | qiaojin/PubMedQA | 2 | [
-1.9639331102371216,
-1.168017864227295,
2.142190456390381
] |
['Neuropeptide Y (NPY), agouti related peptide (AgRP), cocaine and amphetamine-regulated transcript (CART) and melanocortins, the products of the proopiomelanocortin (POMC), are hypothalamic peptides involved in feeding regulation and energy homeostasis. Recent evidence has demonstrated their expression in rat and human placenta.', 'In the current study, we have investigated the expression of those neuropeptides in the rat placenta by real-time PCR using a model of maternal food restriction.', 'Our results showed that placental-derived neuropeptides were regulated through pregnancy and following food restriction.'] Are food-intake-regulating-neuropeptides expressed and regulated through pregnancy and following food restriction in rat placenta? | qiaojin/PubMedQA | 2 | [
-2.6981725692749023,
-0.8518889546394348,
2.6473941802978516
] |
['Keratinocyte growth factor (KGF) has been shown to induce breast cancer metastasis in animal models. cDNA microarrays have revealed that KGF increased Wilms tumor 1 (WT1) and focal adhesion kinase (FAK) expression in breast cancer cells. The role of WT1 and FAK in KGF signaling was investigated.', 'A cell culture wounding model was used to study the effects of WT1 and FAK down-regulation on KGF-induced proliferation and motility in breast cancer cells.', 'WT1 down-regulation inhibited KGF-mediated proliferation and motility of breast cancer cells, while FAK down-regulation inhibited proliferation, but had no significant effect on cell motility. WT1 down-regulation, but not FAK down-regulation, led to Erk1,2 inactivation.'] Do wilms ' tumor 1 protein and focal adhesion kinase mediate keratinocyte growth factor signaling in breast cancer cells? | qiaojin/PubMedQA | 2 | [
-2.544236898422241,
-0.83511883020401,
2.434959888458252
] |
['EpCAM serves as an attractive target for immunotherapy due to its expression on the surface of most epithelial cancer cells. Urothelial carcinoma of the renal pelvis (RP-UC) comprises 2.4-4.6% of tumors of the lower urinary tract. To assess the expression of EpCAM in RP-UC a retrospective study was performed.', 'Tumor tissue from 42 patients with RP-UC was selected from the archives of the Institute of Pathology, Medical University of Innsbruck, Austria. EpCAM expression was demonstrated by immunohistochemistry using the mouse monoclonal antibody ESA.', 'EpCAM overexpression was significantly associated with high grade and invasive behaviour (p = 0.014 and p = 0.029) and the presence of lymph node metastases (p = 0.031), but not with the extent of nodal involvement (p = 0.12).'] Is epCAM overexpression associated with high-grade urothelial carcinoma in the renal pelvis? | qiaojin/PubMedQA | 2 | [
-2.3468551635742188,
-1.310892939567566,
2.7793965339660645
] |
['This prospective study examined association between circulating plasma DNA, microsatellite alterations (MA), p53 mutations with time to relapse and survival in surgically treated non-small cell lung cancer (NSCLC) patients (pts).', 'Plasma samples, adjacent lung tissue, and lung tumor tissue specimens were collected from consecutive patients with stage I-III NSCLC. Blood samples of 66 matched healthy donors with positive smoking history were collected as controls. The plasma DNA amount was determined by real-time PCR. The analysis of MA at loci D3S1300, D3S1289, D3S1266, and D3S2338 on chromosome 3p was performed by radiolabeled PCR. p53 Mutations (exons 5, 6, 7, and 8) were detected by PCR-single-strand conformational polymorphism assay.', 'There were 76 patients, 65 men; median age was 68 years (range, 42-86), 20 had stage I, 40 stage II, and 16 stage III, the majority of pts (48.7%) had squamous-cell histology. Sixty-nine (91%) were smokers and most had good Eastern Cooperative Oncology Group performance status (0/1:72/4). Mean circulating DNA of all pts was 60 ng/ml versus 5 ng/ml in smoker-matched controls (p < 0.0001). In pts without recurrence, mean circulating DNA was 48.5 ng/ml at baseline, 32.8 ng/ml at 3 month, and 20.6 ng/ml at 12 month after surgery. In pts with recurrence, mean circulating DNA at baseline was 97.1 ng/ml. At 3 month after surgery, mean DNA concentration was significantly lower in disease-free pts than in patients with recurrent disease (32.8 versus 292.7 ng/ml; p = 0.0016). MA in at least one locus was found in 39.5% of NSCLC tumors. p53 Genomic mutations were observed in 54.0% of tumor samples. Statistically significant associations were observed between MA and squamous-cell histotype (p = 0.007) and between p53 mutations and lymph node involvement (p = 0.012). MA and p53 mutations were found to be significantly associated with recurrence of disease (p = 0.033 and 0.026, respectively).'] Are plasma DNA , microsatellite alterations , and p53 tumor mutations associated with disease-free survival in radically resected non-small cell lung cancer patients : a study of the perugia multidisciplinary team for thoracic oncology? | qiaojin/PubMedQA | 2 | [
-1.4121171236038208,
-1.7179126739501953,
2.073763608932495
] |
['This study was designed to ascertain the optimal therapy and diagnostics for children with pancreatic injury.', 'From January 1, 2001 to January 1, 2007, all children (newborn to 17 years) who presented to this Level I trauma center with demonstrated pancreatic injury were prospectively entered into the TRACS IV system and reviewed for injury type, diagnostics, therapy, demographics, and outcome.', 'Fourteen children sustained grade II or higher pancreatic injury during this period. CT scan was performed for diagnosis in all cases. There were 11 boys and 3 girls, and mean age was 6.9 (range, 2-16) years. There were five grade II injuries, four grade III injuries, four grade IV injuries, and one grade V injury. All grade II injuries were treated successfully nonoperatively with observation. The nine grade III-IV injuries all underwent operative external drainage without pancreatectomy or stent placement. The single grade V injury died of multiple associated injuries after operative intervention. No pseudocysts developed in these children. All children have normal pancreatic function, and all except one have normal anatomy on follow-up scans. Early exploration and drainage directly reduces length of stay.'] Is initial resection of potentially viable tissue optimal treatment for grades II-IV pancreatic injuries? | qiaojin/PubMedQA | 2 | [
-2.5686020851135254,
-0.5994755029678345,
2.30010986328125
] |
['While searching by microarray for sugar-responsive genes, we inadvertently discovered that sodium-phosphate cotransporter 2B (NaPi-2b) mRNA concentrations were much lower in fructose-perfused than in glucose-perfused intestines of neonatal rats. Changes in NaPi-2b mRNA abundance by sugars were accompanied by similar changes in NaPi-2b protein abundance and in rates of inorganic phosphate (Pi) uptake.', 'We tested the hypothesis that luminal fructose regulates NaPi-2b.', 'We perfused into the intestine fructose, glucose, and nonmetabolizable or poorly transported glucose analogs as well as phlorizin.', 'NaPi-2b mRNA concentrations and Pi uptake rates in fructose-perfused intestines were approximately 30% of those in glucose and its analogs. NaPi-2b inhibition by fructose is specific because the mRNA abundance and activity of the fructose transporter GLUT5 (glucose transporter 5) increased with fructose perfusion, whereas those of other transporters were independent of the perfusate. Plasma Pi after 4 h of perfusion was independent of the perfusate, probably because normal kidneys can maintain normophosphatemia. Inhibiting glucose-6-phosphatase, another fructose-responsive gene, with tungstate or vanadate nonspecifically inhibited NaPi-2b mRNA expression and Pi uptake in both glucose- or fructose-perfused intestines. The AMP kinase (AMPK)-activator AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside) enhanced and the fatty acid synthase-AMPK inhibitor C75 (3-carboxy-4-octyl-2-methylenebutyrolactone trans-4-carboxy-5-octyl-3-methylenebutyrolactone) prevented fructose inhibition of NaPi-2b but had no effect on expression of other transporters. NaPi-2b expression decreased markedly with age and was inhibited by fructose in all age groups.'] Does luminal fructose inhibit rat intestinal sodium-phosphate cotransporter gene expression and phosphate uptake? | qiaojin/PubMedQA | 2 | [
-2.4382808208465576,
-1.2098422050476074,
2.6569275856018066
] |
['The effects of subclinical vitamin D deficiency on bone mineral density (BMD) and bone turnover in adolescents, especially in boys, are unclear.', 'We aimed to investigate the relations of different stages of vitamin D status and BMD and bone turnover in a representative sample of adolescent boys and girls.', 'BMD was measured by dual-energy X-ray absorptiometry at the nondominant forearm and dominant heel in a random sample of 12- (n = 260) and 15-y-old (n = 239) boys and 12- (n = 266) and 15-y-old (n = 250) girls. Serum 25-hydroxyvitamin D, parathyroid hormone, osteocalcin, and type I collagen cross-linked C-telopeptide were assessed by using enzyme-linked immunoassays. Relations between vitamin D status and bone health indexes were assessed by using regression modeling.', 'Using multivariate regression to adjust for potential physical, lifestyle, and dietary confounding factors, we observed that 12- and 15-y-old girls with high vitamin D status (>/=74.1 nmol/L) had significantly greater forearm (but not heel) BMD (beta = 0.018; SE = 0.008; P < 0.05 for each age group) and lower serum parathyroid hormone concentrations and bone turnover markers than did those with low vitamin D status. These associations were evident in subjects sampled throughout the year and in winter only. There was no significant relation between vitamin D status and BMD in boys.'] Does low vitamin D status adversely affect bone health parameters in adolescents? | qiaojin/PubMedQA | 2 | [
-2.233997344970703,
-1.2740895748138428,
2.5931334495544434
] |
['Severe asthma may involve an irreversible obstructive pattern, and structural changes in bronchial airways are believed to play a key role in this context. The aim of the present study was to compare airway remodeling in severe asthmatic children with or without obstructive pattern.', 'Two groups of children with severe asthma and persistent symptoms, 5-14 years old were included, 15 with persistent obstructive pattern (group O) and 10 without obstructive pattern (group N). Persistent obstructive pattern was defined as a forced expiratory volume in 1 s (FEV(1)) less than 80% of the predicted value after a course of systemic corticosteroids and no significant improvement after bronchodilator. We examined bronchial biopsies by pathological and immunochemical methods and quantified airway smooth muscle (ASM) and mucus gland areas, reticular basement membrane (RBM) thickening, distance between ASM and RBM, muscle light chain kinase (MLCK) expression and number of vessels (CD31 expression).', 'Surface area of ASM (P = 0.009), MLCK expression (P = 0.03) and number of vessels (P = 0.0008) were increased in group O compared with group N. Distance of RBM-ASM was shorter in group O (P = 0.007). FEV(1) negatively correlated with ASM area (r = -0.6; P = 0.002), MLCK expression (r = -0.45; P = 0.02) and CD31 expression (r = -0.7; P = 0.0003), and positively correlated with the distance of RBM-ASM (r = 0.5; P = 0.007).'] Is airway remodeling correlated with obstruction in children with severe asthma? | qiaojin/PubMedQA | 2 | [
-1.6664952039718628,
-1.4487643241882324,
2.1702122688293457
] |
['Low cellular uptake and endosomal escape are regarded as major limitations for nonviral gene delivery. In the present study, we use cationic liposomes incorporating fusogenic peptides from glycoprotein H of herpes simplex virus to improve cellular internalization and endosomal release of cationic liposome-DNA complexes.', 'A synthetic analogue of a fusogenic peptide domain in glycoprotein H from herpes simplex virus was evaluated for in vitro gene delivery. The fusogenicity of the peptide was evaluated by a lipid mixing assay in neutral and acidic environments. The influence of the peptide on cellular internalization and subcellular distribution of Lipofectamine-pGL3 complexes were evaluated by flow cytometry, fluorescence microscopy, and confocal laser scanning microscopy. The effect of the peptide on transfection efficiency of cationic liposomes was also evaluated by luciferase assay in human cell lines.', 'A pH-sensitive fusogenicity of the wild-type peptide was observed. In the lipid mixing assay, the peptide mediated 80% membrane fusion at pH 7.4 at a 0.05 : 1 (peptide : lipid) mole ratio. At pH 4.5, 100% of membrane fusion was observed at a 0.005 : 1 ratio. Adding the peptide to Lipofectamine-pGL3 complexes significantly increased cellular uptake and, thus, increased transgene expression up to 30-fold in human cell lines. Nuclear localization of the DNA complex by the fusogenic peptide was observed by confocal microscopy.'] Does a fusogenic segment of glycoprotein H from herpes simplex virus enhance transfection efficiency of cationic liposomes? | qiaojin/PubMedQA | 2 | [
-2.3015758991241455,
-1.3522536754608154,
2.756924629211426
] |
['The reduced folate carrier (RFC1) is a ubiquitously expressed integral membrane protein that mediates delivery of 5-methyltetrahydrofolate into mammalian cells. In this study, embryonic/fetal development is characterized in an RFC1 knockout mouse model in which pregnant dams receive different levels of folate supplementation.', 'RFC1(+/-) males were mated to RFC1(+/-) females, and pregnant dams were treated with vehicle (control) or folic acid (25 or 50 mg/kg) by daily subcutaneous injection (0.1 mL/10 g bwt), beginning on E0.5 and continuing throughout gestation until the time of sacrifice.', 'Without maternal folate supplementation, RFC1 nullizygous embryos die shortly postimplantation. Supplementation of pregnant dams with 25 mg/kg/day folic acid prolongs survival of mutant embryos until E9.5-E10.5, but they are developmentally delayed relative to wild-type littermates, display a marked absence of erythropoiesis, severe neural tube and limb bud defects, and failure of chorioallantoic fusion. Fgfr2 protein levels are significantly reduced or absent in the extraembryonic membranes of RFC1 nullizygous embryos. Maternal folate supplementation with 50 mg/kg/day results in survival of 22% of RFC1 mutants to E18.5, but they develop with multiple malformations of the eyelids, lungs, heart, and skin.'] Is embryonic development in the reduced folate carrier knockout mouse modulated by maternal folate supplementation? | qiaojin/PubMedQA | 2 | [
-2.304675579071045,
-1.2290358543395996,
2.579735517501831
] |
['Cat ownership is inversely associated with atopy and asthma in some areas of the world, but the relevance of cat ownership to allergic disease in the inner city is less known.', 'We sought to evaluate the relationship between cat ownership and the development of early sensitization and wheeze.', 'By using a prospective birth cohort study, Dominican and African American mothers living in New York City underwent repeated questionnaires about their child from birth to age 5 years. Sera collected from children at ages 2 (n = 323), 3 (n = 336), and 5 (n = 242) years were assayed for anti-cat IgE and anti-Fel d 1 IgG antibodies.', 'Cat ownership was a significant risk factor for the development of anti-cat IgE by age 2 years (risk ratio [RR], 6.4; 95% CI, 1.9-22) but not for anti-cat IgE development between the ages of 2 and 5 years (RR, 0.88; 95% CI, 0.24-2.3). Current wheeze was significantly more common among those children with anti-cat IgE at ages 3 (RR, 3.5; 95% CI, 2.1-6.0) and 5 (RR, 3.4; 95% CI, 2.3-4.9) years. Cat ownership was inversely associated with current wheeze at age 5 years among children without anti-cat IgE (RR, 0.26; 95% CI, 0.083-0.81). Among children with anti-cat IgE, a similar trend was observed (RR, 0.57; P = .044, Fisher exact test), although one with borderline statistical significance.'] Is cat ownership a risk factor for the development of anti-cat IgE but not current wheeze at age 5 years in an inner-city cohort? | qiaojin/PubMedQA | 2 | [
-1.3131195306777954,
-1.3724884986877441,
1.7377326488494873
] |
['The specific genetic contributions to childhood asthma have been difficult to elucidate. A recent whole-genome association study suggested that single nucleotide polymorphisms at loci controlling the expression of the ORMDL3 gene and others in the neighborhood of the NRG1 and ERO1LB genes might be important.', 'We sought to replicate the associations of these genetic markers with asthma in a large population of asthmatic patients from Scotland and to assess the effect of these variants on asthma outcomes.', 'Using mouthwash-derived DNA and clinical interviews and measurements, we investigated the association of 3 single nucleotide polymorphisms in the candidate genes with susceptibility to asthma in a case-control study and also exacerbations in a group of 1054 patients aged 3 to 22 years.', 'A common C/T polymorphism at a locus controlling ORMDL3 gene expression (rs7216389) was significantly associated with the risk of childhood asthma (P = 1.73 x 10(-12)), with a single copy of the T allele conferring an odds ratio of 1.50 (95% CI, 1.24-1.81) and 2 copies of the T allele conferring an odds ratio of 2.11 (95% CI, 1.71-2.61), respectively. In asthmatic patients the T allele was associated with exacerbations of the condition (P = .008). Polymorphisms at the loci of nearby genes for NRG1 (rs4512342) and ERO1LB (rs10924993) were associated with neither the occurrence of nor exacerbations of asthma.'] Is a polymorphism controlling ORMDL3 expression associated with asthma that is poorly controlled by current medications? | qiaojin/PubMedQA | 2 | [
-2.0346179008483887,
-1.238356113433838,
2.3245201110839844
] |
['Leukotriene B4 (LTB4) is a potent inflammatory lipid mediator that binds to LTB4 receptor 1 (BLT1). Ligation of BLT1 by LTB4 plays an important role in the recruitment of effector memory CD8+ T cells into the airways of sensitized and challenged mice.', 'The effects of the corticosteroid dexamethasone (DEX) on BLT1-expressing effector memory CD8+ T cells and effector memory CD8+ T cell-mediated airway hyperresponsiveness (AHR) and allergic inflammation were determined.', 'Effector memory CD8+ T cells were generated from ovalbumin(257-264)-primed mononuclear cells from OT-1 mice in the presence of IL-2. In some cultures DEX was added. The effects of DEX on BLT1 expression, LTB4-induced Ca2+ influx, phosphorylation of extracellular signal-regulated kinase 1/2, chemotaxis, and effector memory CD8+ T cell-mediated AHR were examined.', 'DEX-treated effector memory CD8+ T cells showed significant increases in surface expression of BLT1, LTB4-induced intracellular Ca2+ influx, phosphorylation of extracellular signal-regulated kinase 1/2, and chemotaxis. Upregulation of BLT1 by DEX was accompanied by increased IL-2 receptor expression. Adoptive transfer of DEX-treated effector memory CD8+ T cells into ovalbumin-sensitized and ovalbumin-challenged CD8-/- mice resulted in significant increases in AHR, allergic inflammation, goblet cell metaplasia, and numbers of both CD8+ and CD4+ T cells in the bronchoalveolar lavage fluid and lungs.'] Do corticosteroids enhance CD8+ T cell-mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1? | qiaojin/PubMedQA | 2 | [
-2.4562394618988037,
-1.3173165321350098,
2.7464916706085205
] |
['Studies have demonstrated that selenium supplementation reduces the incidence of cancer, particularly prostate cancer. Evidence from experimental studies suggests that apoptosis is a key event in cancer chemoprevention by selenium and reactive oxygen species play a role in induction of apoptosis by selenium compounds. The current study was designed to investigate the role of superoxide and mitochondria in selenite-induced apoptosis in human prostate cancer cells.', 'LNCaP cells were transduced with adenoviral constructs to overexpress four primary antioxidant enzymes: manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), or glutathione peroxidase 1 (GPx1). Cell viability, apoptosis, and superoxide production induced by sodium selenite were analyzed by the MTT assay, chemiluminescence, flow cytometry, western blot analysis, and Hoechst 33342 staining following overexpression of these antioxidant enzymes.', 'Our study shows the following results: (1) selenite induced cancer cell death and apoptosis by producing superoxide radicals; (2) selenite-induced superoxide production, cell death, and apoptosis were inhibited by overexpression of MnSOD, but not by CuZnSOD, CAT, or GPx1; and (3) selenite treatment resulted in a decrease in mitochondrial membrane potential, release of cytochrome c into the cytosol, and activation of caspases 9 and 3, events that were suppressed by overexpression of MnSOD.'] Does sodium selenite induce apoptosis by generation of superoxide via the mitochondrial-dependent pathway in human prostate cancer cells? | qiaojin/PubMedQA | 2 | [
-2.581731081008911,
-1.1951885223388672,
2.820357084274292
] |
['Several studies suggested that genetic factors play a role in cluster headache (CH) susceptibility. We found a significant association between the 1246 G>A polymorphism of the hypocretin receptor-2 (HCRTR2) gene and the disease. This association was confirmed in a large study from Germany but was not replicated in a dataset of CH patients from Northern Europe.', 'The purpose of this study was to further evaluate the association between CH and the HCRTR2 gene using new polymorphisms, estimating the frequency of different gene haplotypes, searching for gene mutations, and evaluating the effects of the examined polymorphisms on hypocretin binding sites.', 'We genotyped 109 CH patients and 211 healthy controls for 5 new polymorphisms of the HCRTR2 gene and we inferred different gene haplotypes. Complete HCRTR2 sequencing was undertaken for 11 independent CH patients, 5 of whom had a positive family history. The effects of the 1246 G>A polymorphism on the hypocretin binding sites were evaluated using different computer-assisted analyses.', 'Three new polymorphisms of the HCRTR2 gene resulted significantly associated with CH. The GTAAGG haplotype resulted more frequent in cases than in controls (OR: 3.68; 95% CI: 1.85-7.67). No point mutation of the HCRTR2 gene was found. Binding analyses showed that the 1246 G>A polymorphism (substitution of valine at position 308 by isoleucine) has no effect on the hypocretin binding sites but could influence the dimerization process of the receptor.'] Does haplotype analysis confirm the association between the HCRTR2 gene and cluster headache? | qiaojin/PubMedQA | 2 | [
-2.143721342086792,
-1.2277216911315918,
2.3651657104492188
] |
['Tumour angiogenesis is the result of an inbalance between anti- and pro-angiogenic factors. CD105 (endoglin) is a component of the receptor complex of transforming growth factor (TGF-beta1). Vascular endothelial growth factor receptor 2 (VEGFR2 or Flk-1/KDR) belongs to the high-affinity VEGF receptors. The aim of the study was to investigate the expression, cellular localization and role of CD105 and VEGFR2 in laryngeal carcinoma.', 'Sections of 62 laryngeal carcinomas were stained with CD105 and VEGFR2/Flk-1/KDR antibodies.', 'A significant association between CD105 expression and locoregional recurrence was found (p = 0.009). Interestingly, in N0 patients CD105 expression was significantly associated with locoregional recurrence of the carcinoma (p = 0.03). The log-rank test showed a significant difference in the disease-free interval in patients stratified according to CD105 expression (p = 0.02). Statistical analysis showed no significant associations between vessel endothelial cell or laryngeal carcinoma cell VEGFR2 expressions and recurrence of disease or disease-free intervals.'] Are laryngeal carcinoma recurrence rate and disease-free interval related to CD105 expression but not to vascular endothelial growth factor 2 ( Flk-1/Kdr ) expression? | qiaojin/PubMedQA | 2 | [
-2.1486594676971436,
-1.4424126148223877,
2.602680206298828
] |
['Non-alcoholic-steatohepatitis (NASH) leading to fibrosis, end-stage cirrhosis and hepatocellular carcinoma is an increasing health problem in the Western world. Thus, the need for new therapeutic approaches is increasing. IKK2 plays a key role in the development of NASH by mediating inflammation and insulin resistance.', 'Here the beneficial effects of a pharmacological IKK2 inhibitor (AS602868) on initial stages of NASH progression were tested.', 'Mice were fed with a high sucrose diet (HSD) and daily-administered AS602868 and vehicle. The impact of AS602868 on NASH progression was studied using biochemical, histological and molecular markers.', 'AS602868 treatment prevented HSD-induced weight gain and visceral fat accumulation. In adipose tissue, AS602868-treated mice exhibited a lower degree of infiltrated macrophages along with reduced proinflammatory cytokine production. Further analysis demonstrated that AS602868 treatment efficiently inhibited nuclear factor (NF)-kappaB activation in liver non-parenchymal cells and as a consequence attenuated the inflammatory response in the liver. Accordingly, in HSD/AS602868 mice, liver and adipose tissue adiponectin levels remained at levels comparable with those of control chow-fed mice, while they were decreased in HSD/vehicle animals. Additionally, AS602868 improved lipid beta-oxidation mediated by peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma. Systemic pharmacological IKK2 inhibition by AS602868 treatment efficiently prevented liver steatosis and inflammation, and improved antioxidant response. All this contributed to attenuation of NASH progression as evidenced by lower hepatocyte apoptosis and early stages of liver fibrosis.'] Does pharmacological IKK2 inhibition block liver steatosis and initiation of non-alcoholic steatohepatitis? | qiaojin/PubMedQA | 2 | [
-2.3827507495880127,
-1.3492201566696167,
2.736865520477295
] |
['Lung involvement is the leading cause of morbidity and mortality in systemic sclerosis (SSc; scleroderma), and interstitial lung disease (ILD) is the most common pulmonary manifestation. An abnormal profibrotic Th2/Tc2-polarized T cell response is postulated to mediate tissue damage and fibrosis. The aim of this study was to investigate whether a polarized T cell phenotype in SSc is associated with lung disease or other clinical manifestations of SSc.', 'Circulating T cells were characterized by flow cytometry in 62 patients with SSc and 36 healthy control subjects, using antibodies against CD3, CD4, CD8, chemokine receptor CCR5 (Th1/Tc1-specific), and prostaglandin D2 receptor CRTH2 (Th2/Tc2-specific). The ratio between CCR5 and CRTH2 T cell frequencies was used to quantify type 1 (high-ratio) or type 2 (low-ratio) immune polarization.', 'Patients with SSc exhibited lower CCR5/CRTH2 T cell ratios than those exhibited by control subjects (P<0.0001), indicating a Th2/Tc2-polarized phenotype. Markedly reduced CCR5/CRTH2 T cell ratios were observed in SSc patients with ILD compared with SSc patients without ILD (P<0.0001), particularly in patients with active ILD (P<0.0001) compared with those with stable lung function. Lower CCR5/CRTH2 ratios were strongly associated with a lower value for the percent predicted forced vital capacity (P<0.0001). In patients with an estimated right ventricular systolic pressure>35 mm Hg, suggestive of pulmonary vascular disease, a lower value for the percent predicted diffusing capacity (DLCO) was associated with higher CCR5/CRTH2 T cell ratios (Th1/Tc1) (P=0.009), while in those with right ventricular systolic pressure<35 mm Hg, a lower value for the percent predicted DLCO correlated with lower ratios (Th2/Tc2) (P<0.0001), as observed for ILD.'] Does t cell polarization identify distinct clinical phenotypes in scleroderma lung disease? | qiaojin/PubMedQA | 2 | [
-1.9392756223678589,
-1.531548261642456,
2.42169189453125
] |
['This study was undertaken to test the hypothesis that abnormalities of the subchondral bone can result in osteoarthritis (OA).', 'We used a knockin model of human osteogenesis imperfecta, the Brittle IV (Brtl) mouse, in which defective type I collagen is expressed in bone. OA in individual mice was documented by micro-magnetic resonance imaging (micro-MRI) and micro-computed tomography (micro-CT). Alterations in the knee joints were confirmed by histopathologic and immunohistochemical analysis. In addition, atomic force microscopy (AFM) was used to assess the ultrastructure of the articular cartilage and subchondral bone matrix.', 'Brtl mice had decreased integrity of bone but initially normal articular cartilage. However, by the second month of life, Brtl mice developed alterations of the cartilage that were characteristic of OA, as documented by micro-CT, micro-MRI, and histologic evaluation. In addition, chondrocyte loss and breakdown of the collagen matrix in the residual cartilage were demonstrated using AFM.'] Does a type I collagen defect lead to rapidly progressive osteoarthritis in a mouse model? | qiaojin/PubMedQA | 2 | [
-2.433314085006714,
-1.2620271444320679,
2.7946810722351074
] |
['Type I interferon (IFN) plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE) and is therefore considered a potential therapeutic target. This study was undertaken to establish a feasible biomarker for IFN effects with respect to disease activity and effectiveness of IFN-suppressive therapy in SLE patients.', 'Transcriptomes of purified monocytes from 9 SLE patients and 7 healthy controls were analyzed by Affymetrix GeneChip technology. Levels of sialic acid-binding Ig-like lectin 1 (Siglec-1) (sialoadhesin, CD169) in inflammatory and resident monocytes were determined at the protein level in 38 healthy controls and 52 SLE patients, using multicolor flow cytometry.', 'Transcriptomes of peripheral monocytes from SLE patients revealed a dominant type I IFN signature. Siglec-1 was identified as one of the most prominent type I IFN-regulated candidate genes. At the protein level, the frequency of Siglec-1-expressing monocyte subsets was correlated with disease activity (as measured by the SLE Disease Activity Index) and was inversely correlated with levels of complement factors. Most interestingly, levels of anti-double-stranded DNA (anti-dsDNA) antibodies were highly correlated with the percentage of resident monocytes, but not inflammatory monocytes, expressing Siglec-1. High-dose glucocorticoid treatment resulted in a dramatic reduction of Siglec-1 expression in cells from patients with active SLE.'] Is sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus? | qiaojin/PubMedQA | 2 | [
-2.3749396800994873,
-1.3652534484863281,
2.7952704429626465
] |
['The aim of this study was to explore the predictive value of longitudinal self-reported adherence data on viral rebound.', 'Individuals in the Swiss HIV Cohort Study on combined antiretroviral therapy (cART) with RNA <50 copies/ml over the previous 3 months and who were interviewed about adherence at least once prior to 1 March 2007 were eligible. Adherence was defined in terms of missed doses of cART (0, 1, 2 or >2) in the previous 28 days. Viral rebound was defined as RNA >500 copies/ml. Cox regression models with time-independent and -dependent covariates were used to evaluate time to viral rebound.', 'A total of 2,664 individuals and 15,530 visits were included. Across all visits, missing doses were reported as follows: 1 dose 14.7%, 2 doses 5.1%, >2 doses 3.8% taking <95% of doses 4.5% and missing > or =2 consecutive doses 3.2%. In total, 308 (11.6%) patients experienced viral rebound. After controlling for confounding variables, self-reported non-adherence remained significantly associated with the rate of occurrence of viral rebound (compared with zero missed doses: 1 dose, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.72-1.48; 2 doses, HR 2.17, 95% CI 1.46-3.25; >2 doses, HR 3.66, 95% CI 2.50-5.34). Several variables significantly associated with an increased risk of viral rebound irrespective of adherence were identified: being on a protease inhibitor or triple nucleoside regimen (compared with a non-nucleoside reverse transcriptase inhibitor), >5 previous cART regimens, seeing a less-experienced physician, taking co-medication, and a shorter time virally suppressed.'] Does self-reported non-adherence to antiretroviral therapy repeatedly assessed by two questions predict treatment failure in virologically suppressed patients? | qiaojin/PubMedQA | 2 | [
-1.6745002269744873,
-1.4224767684936523,
2.049177646636963
] |
['Patients with right iliac fossa pain present a diagnostic challenge to emergency room doctors when equivocal signs are present.', 'To evaluate Alvarado score as an admission criterion in patients with suspected diagnosis of acute appendicitis.', "This was a prospective study of 100 consecutive patients who presented to the an emergency department with right iliac fossa pain and suspected diagnosis of acute appendicitis between January 2004 and December 2004. They were assessed usingAlvarado score. Main outcome measures in relation to these scores were, patient's admission, patient's discharge, and whether patient had appendicitis or not.", 'The range of scores was 1-10. Seventy-four patients were admitted while 26 were discharged. Thirty-four patients with confirmed diagnosis of acute appendicitis had scores ranging from 5-10. No patient with score less than 5 had appendicitis. The sensitivity and negative predictive value reached 100% at scores below five, while specificity and positive predictive value reached 100% at the score of 10.'] Do evaluation of Alvarado score as an admission criterion in patients with suspected diagnosis of acute appendicitis? | qiaojin/PubMedQA | 2 | [
-1.1904631853103638,
-0.6832830309867859,
1.0087554454803467
] |
['Without specific strategies to address tracheostomy care on the wards, patients discharged from the intensive care unit (ICU) with a tracheostomy may receive suboptimal care. We formed an intensivist-led multidisciplinary team to oversee ward management of such patients. To evaluate the service, we compared outcomes for the first 3 years of the service with those in the year preceding the service.', 'Data were prospectively collected over the course of 3 years on ICU patients not under the care of the ear, nose, and throat unit who were discharged to the ward with a tracheostomy and compared with outcomes in the year preceding the introduction of the service. Principal outcomes were decannulation time, length of stay after ICU discharge, and stay of less than 43 days (upper trim point for the disease-related group [DRG] for tracheostomy). Analysis included trend by year and multivariable analysis using a Cox proportional hazards model. P values of less than 0.05 were assumed to indicate statistical significance. As this was a quality assurance project, ethics approval was not required.', 'Two hundred eighty patients were discharged with a tracheostomy over the course of a 4-year period: 41 in 2003, 60 in 2004, 95 in 2005, and 84 in 2006. Mean age was 61.8 (13.1) years, 176 (62.9%) were male, and mean APACHE (Acute Physiology and Chronic Health Evaluation) II score was 20.4 (6.4). Length of stay after ICU decreased over time (30 [13 to 52] versus 19 [10 to 34] days; P < 0.05 for trend), and a higher proportion of decannulated patients were discharged under the upper DRG trim point of 43 days (48% versus 66%; P < 0.05). Time to decannulation after ICU discharge decreased (14 [7 to 31] versus 7 [3 to 17] days; P < 0.01 for trend). Multivariate analysis showed that the hazard for decannulation increased by 24% (3% to 49%) per year.'] Is an intensivist-led tracheostomy review team associated with shorter decannulation time and length of stay : a prospective cohort study? | qiaojin/PubMedQA | 2 | [
-1.6519039869308472,
-1.2445104122161865,
2.0268590450286865
] |
['Performing a motor task after a period of training has been associated with reduced cortical activity and changes in oscillatory brain activity. Little is known about whether learning also affects the neural network associated with motor preparation and post movement processes. Here we investigate how short-term motor learning affects oscillatory brain activity during the preparation, execution, and post-movement stage of a force-feedback task.', 'Participants performed a visually guided power-grip tracking task. EEG was recorded from 64 scalp electrodes. Power and coherence data for the early and late stages of the task were compared.', 'Performance improved with practice. During the preparation for the task alpha power was reduced for late experimental blocks. A movement execution-related decrease in beta power was attenuated with increasing task practice. A post-movement increase in alpha and lower beta activity was observed that decreased with learning. Coherence analysis revealed changes in cortico-cortical coupling with regard to the stage of the visuomotor task and with regard to learning. Learning was variably associated with increased coherence between contralateral and/or ipsilateral frontal and parietal, fronto-central, and occipital brain regions.'] Is short-term learning of a visually guided power-grip task associated with dynamic changes in EEG oscillatory activity? | qiaojin/PubMedQA | 2 | [
-2.690962076187134,
-0.6832484602928162,
2.453777313232422
] |
['The aim of this study was to use the glycogen depletion technique to determine whether reinnervated muscle fibers could be distinguished from denervated muscle fibers by their size or by neural cell adhesion molecule (NCAM) expression.', 'Medial gastrocnemius muscles of five adult Fischer rats were reinnervated from embryonic neurons transplanted into the distal stump of the tibial nerve. Ten weeks later, the transplants were stimulated repeatedly to deplete reinnervated muscle fibers of glycogen. Areas of reinnervated (glycogen-depleted) muscle fibers were measured and assessed for NCAM expression. The areas of muscle fibers from reinnervated, denervated (n=5) and unoperated control muscles (n=5) were compared.', 'Mean reinnervated muscle fiber area was significantly larger than the mean for denervated fibers (mean +/- SE: 40 +/- 6 and 10 +/- 1% of unoperated control fibers, respectively). NCAM was expressed in 55 +/- 7% of reinnervated fibers (mean +/- SE; range: 42-77%). The mean areas of reinnervated fibers that did or did not express NCAM were similar. NCAM was only expressed in some fibers in completely denervated muscles.'] Does embryonic neurons transplanted into the tibial nerve reinnervate muscle and reduce atrophy but NCAM expression persist? | qiaojin/PubMedQA | 2 | [
-1.2108901739120483,
-1.248881459236145,
1.4588922262191772
] |
['Severe periodontal breakdown is often associated with Down syndrome (DS); however, the etiology of this condition is not understood fully. Cellular motility of gingival fibroblasts is a critical event for wound healing and regeneration of periodontal tissues. Porphyromonas gingivalis is known to be a periodontal pathogen that invades host cells, contributing to periodontal destruction. In this study, we examined the influence of P. gingivalis infection on the motility of DS gingival fibroblasts (DGFs).', 'DGFs and normal gingival fibroblasts (NGFs) were infected with P. gingivalis with type II fimbriae, and cellular motility was evaluated using an in vitro wounding assay. Protein degradation of alpha5beta1-integrin subunits and a migration-regulating signaling molecule, paxillin, were investigated using specific antibodies. The adhesion to and invasion of fibroblasts by P. gingivalis were determined with a colony forming assay. The gene expressions of alpha5beta1-integrin subunits were also quantified using a reverse transcription-polymerase chain reaction method.', 'The cellular motility of DGFs was impaired significantly by P. gingivalis compared to NGFs, and the former were invaded readily by P. gingivalis. Further, cellular paxillin from DGFs was degraded markedly by the pathogen. Although protein degradation of alpha5beta1 integrin was induced, its mRNA expression was not affected significantly.'] Is cellular motility of Down syndrome gingival fibroblasts susceptible to impairment by Porphyromonas gingivalis invasion? | qiaojin/PubMedQA | 2 | [
-2.4423601627349854,
-1.302061676979065,
2.8222854137420654
] |
['The melatonin receptor subfamily contains three members Mel1a, Mel1b and Mel1c, found in all vertebrates except for Mel1c which is found only in fish, Xenopus species and the chicken. Another receptor, the melatonin related receptor known as GPR50, found exclusively in mammals and later identified as a member of the melatonin receptor subfamily because of its identity to the three melatonin receptors despite its absence of affinity for melatonin. The aim of this study was to describe the evolutionary relationships between GPR50 and the three other members of the melatonin receptor subfamily.', 'Using an in silico approach, we demonstrated that GPR50 is the ortholog of the high affinity Mel1c receptor. It was necessary to also study the synteny of this gene to reach this conclusion because classical mathematical models that estimate orthology and build phylogenetic trees were not sufficient. The receptor has been deeply remodelled through evolution by the mutation of numerous amino acids and by the addition of a long C-terminal tail. These alterations have modified its affinity for melatonin and probably affected its interactions with the other two known melatonin receptors MT1 and MT2 that are encoded by Mel1a and Mel1b genes respectively. Evolutionary studies provided evidence that the GPR50 group evolved under different selective pressure as compared to the orthologous groups Me11 a, b, and c.'] Is gPR50 the mammalian ortholog of Mel1c : evidence of rapid evolution in mammals? | qiaojin/PubMedQA | 2 | [
-2.3768904209136963,
-0.6699784398078918,
2.0848312377929688
] |
['Hepatocyte growth factor (HGF) and transforming growth factor-beta (TGF-beta) regulate diversified cellular functions and often act antagonistically against each other. For example, TGF-beta is the most potent factor accelerating liver fibrosis, whereas HGF treatment prevents its progression. Here, we propose a novel molecular mechanism by which HGF counter represses TGF-beta-stimulated profibrogenic signal transduction.', 'Effects of HGF on TGF-beta-responsive gene transcription of type I collagen, the major matrix component of fibrotic liver, were examined by using cultured hepatic stellate cells (HSC) and transgenic mice harboring alpha2(I) collagen gene (COL1A2) promoter. Expression and subcellular localization of Smad3 were determined by Western blot analyses and immunofluorescence staining, respectively. A mass spectrometric analysis was employed to identify immunoprecipitated proteins with antiphospho-Smad2/3 antibodies.', 'Over expression of HGF inhibited COL1A2 transcription in cultured HSC and suppressed activation of COL1A2 promoter in liver tissue induced by carbon tetrachloride administration. A mass spectrometric analysis identified galectin-7 as one of the immunoprecipitated proteins with antiphospho-Smad2/3 antibodies following HGF treatment. HGF accelerated nuclear export of Smad3 by enhancing its interaction with galectin-7. Transfection of cells with galectin-7 small interfering RNA inhibited nuclear export of Smad3 and abolished suppressive effect of HGF on expression of TGF-beta-responsive genes such as COL1A2 and plasminogen activator inhibitor-1. On the other hand, over expression of galectin-7 suppressed TGF-beta-stimulated expression of those target genes.'] Does hepatocyte growth factor suppress profibrogenic signal transduction via nuclear export of Smad3 with galectin-7? | qiaojin/PubMedQA | 2 | [
-2.4449462890625,
-1.2925169467926025,
2.8027963638305664
] |
['Cartilage degradation in osteoarthritis (OA) generates the type II collagen fragments, Helix-II and CTX-II that can be used as clinical biological markers. Helix-II and C-telopeptide of type II collagen (CTX-II) levels are associated independently with progression of OA suggesting that they may be generated through different collagenolytic pathways. In this study we analyzed the release of Helix-II and CTX-II from human cartilage collagen by the proteinases reported to play a role in cartilage degradation.', 'In vitro, human articular cartilage extract was incubated with activated human recombinant cathepsins (Cats) and matrix-metalloproteases (MMPs). Next, we analyzed the spontaneous release of Helix-II and CTX-II from cartilage sections of patients with knee OA who were immediately deep frozen after joint replacement to preserve endogenous enzyme activity until assay. Cartilage sections were then incubated for up to 84 h in the presence or absence of E-64 and GM6001, inhibitors of cysteine proteases and MMPs, respectively.', 'In vitro, Cats K, L and S generated large amount of Helix-II, but not CTX-II. Cat B generated CTX-II fragment, but destroyed Helix-II immunoreactivity. Cat D was unable to digest intact cartilage. MMPs-1, -3, -7, -9, and -13 efficiently released CTX-II, but only small amount of Helix-II. Neither CTX-II nor Helix-II alone was able to reflect accurately the collagenolytic activity of Cats and MMPs as reflected by the release of hydroxyproline. In OA cartilage explants, E-64 blunted the release of Helix-II whereas the release of CTX-II could be completely abrogated by GM6001 and only partly by E-64.'] Do the type II collagen fragments Helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation? | qiaojin/PubMedQA | 2 | [
-2.243824005126953,
-1.4011578559875488,
2.6340842247009277
] |
['Inflammation is an important feature of biliary atresia, and recent studies suggest that its occurs in a genetically susceptible host. The intercellular adhesion molecule-1 (ICAM-1) is of paramount importance for the initiation and propagation of various inflammatory conditions.', 'To determine whether the Glu241Arg polymorphism in the ICAM-1 gene, which impairs inflammatory responses, is associated with biliary atresia.', "Between February 2002 and November 2004, 19 patients (mean age 1 +/- 0.4 years) diagnosed as biliary atresia were included in the study. Thirty-eight children with chronic liver disease and a group of unrelated healthy controls (n = 123) included in this study. After informed consent, blood was collected and genomic DNA was obtained. Genotyping was performed by amplification-refractory mutation system polymerase chain reaction (ARMSPCR). Associations were assessed by using Fischer's exact test.", 'ICAM G242R A allele frequency was significantly higher in the BA group than in both the CLD and healthy control groups (OR = 4.4, 95 CI% 1.3-15.1, P = 0.03 and OR = 4.8 CI% 1.5-15.6, P = 0.01, respectively). Univariate analysis showed that polymorphism of ICAM G241R polymorphism was significantly related to biliary atresia. There was not significant correlation between PELD score and ICAM-1 genotypes both in BA and CLD groups.'] Are polymorphisms of the ICAM-1 gene associated with biliary atresia? | qiaojin/PubMedQA | 2 | [
-2.1031458377838135,
-1.4425429105758667,
2.5777788162231445
] |
['Postprandial consumption of alcoholic beverages with high ethanol concentration (so-called digestifs) is a widespread custom to alleviate dyspeptic symptoms after comprehensive meals. Alcoholic beverages preprandially ingested inhibit gastric emptying rate of solid meals. However, the effect of a postprandial intake has never been studied in a controlled manner.', 'In 10 healthy male subjects gastric emptying was repeatedly studied by ultrasonography after the intake of a 576 kcal meal. Immediately after the meal subjects received in a randomized order 40 ml of the following liquids: brandy, herb flavored liqueur, Williams pear brandy, aquavit (each 40 % (v/v) ethanol concentration), espresso, water, 40% (v/v) ethanol and 70% (w/v) glucose. Postprandial satiety, fullness and bloating were determined on a visual analogue scale every 10 minutes. On another occasion subjects received 40 ml of water and walked afterwards slowly (4 km/h) on a treadmill.', 'Gastric half emptying time (t 1/2) of the meal with water was 123 +/- 5 min, while with brandy (119 +/- 9 min), herb flavored liqueur (123 +/- 10 min), aquavit (125 +/- 9 min), Williams pear brandy (126 +/- 6 min) or espresso (125 +/- 9 min) t(1/2) it was not significantly different. Postprandial walking accelerated t(1/2) significantly (107 +/- 5 min, p=0.02). Dyspeptic symptoms were unchanged. Blood ethanol concentrations were under the level of detection (< 5 mg/dl).'] Does postprandial walking but not consumption of alcoholic digestifs or espresso accelerate gastric emptying in healthy volunteers? | qiaojin/PubMedQA | 2 | [
-0.3471434712409973,
-1.7089344263076782,
1.0473096370697021
] |
['Lysosomal carboxypeptidase, cathepsin A (protective protein, CathA), is a component of the lysosomal multienzyme complex along with beta-galactosidase (GAL) and sialidase Neu1, where it activates Neu1 and protects GAL and Neu1 against the rapid proteolytic degradation. On the cell surface, CathA, Neu1, and the enzymatically inactive splice variant of GAL form the elastin-binding protein complex. In humans, genetic defects of CathA cause galactosialidosis, a metabolic disease characterized by combined deficiency of CathA, GAL, and Neu1 and a lysosomal storage of sialylated glycoconjugates. However, several phenotypic features of galactosialidosis patients, including hypertension and cardiomyopathies, cannot be explained by the lysosomal storage. These observations suggest that CathA may be involved in hemodynamic functions that go beyond its protective activity in the lysosome.', 'We generated a gene-targeted mouse in which the active CathA was replaced with a mutant enzyme carrying a Ser190Ala substitution in the active site. These animals expressed physiological amounts of catalytically inactive CathA protein, capable of forming lysosomal multienzyme complex, and did not develop secondary deficiency of Neu1 and GAL. Conversely, the mice showed a reduced degradation rate of the vasoconstrictor peptide, endothelin-1, and significantly increased arterial blood pressure. CathA-deficient mice also displayed scarcity of elastic fibers in lungs, aortic adventitia, and skin.'] Is enzymatic activity of lysosomal carboxypeptidase ( cathepsin ) A required for proper elastic fiber formation and inactivation of endothelin-1? | qiaojin/PubMedQA | 2 | [
-2.4017727375030518,
-1.2744698524475098,
2.696981430053711
] |
["Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). Two tightly linked polymorphisms (PvuII and XbaI) in the first intron of estrogen receptor 1 (ESR1), the gene for ER-alpha, have been reported to influence estrogen receptor expression and may influence the risk of AD.", 'We examined the relation of polymorphisms in ESR1 to the risk of AD in women with Down syndrome. The subjects (181 women with DS, 41-78 years of age) were followed at 14- to 18-month intervals. Information from cognitive assessments, caregiver interviews, medical record reviews and neurological examinations was used to classify dementia. Genomic DNA was genotyped for 5 single-nucleotide polymorphisms in the upstream region and the first exon/intron of the ESR1 gene. Their association with dementia risk was evaluated, adjusting for covariates.', 'Women with at least 1 copy of the C allele at rs2234693 (PvuII) and those homozygous for the C allele at rs2077647 had an almost 3-fold increase in the risk of AD, compared with women without the C allele. The increased risks were independent of the apolipoprotein E genotype.'] Do estrogen receptor-alpha variants increase risk of Alzheimer 's disease in women with Down syndrome? | qiaojin/PubMedQA | 2 | [
-2.266268491744995,
-1.059688925743103,
2.273024082183838
] |
['Over a hundred years ago, Wolff originally observed that bone growth and remodeling are exquisitely sensitive to mechanical forces acting on the skeleton. Clinical studies have noted that the size and the strength of bone increase with weight bearing and muscular activity and decrease with bed rest and disuse. Although the processes of mechanotransduction and functional response of bone to mechanical strain have been extensively studied, the molecular signaling mechanisms that mediate the response of bone cells to mechanical stimulation remain unclear.', 'Here, we identify a novel germline mutation at the mouse Bone morphogenetic protein 5 (Bmp5) locus. Genetic analysis shows that the mutation occurs at a site encoding the proteolytic processing sequence of the BMP5 protein and blocks proper processing of BMP5. Anatomic studies reveal that this mutation affects the formation of multiple skeletal features including several muscle-induced skeletal sites in vivo. Biomechanical studies of osteoblasts from these anatomic sites show that the mutation inhibits the proper response of bone cells to mechanical stimulation.'] Does dominant negative Bmp5 mutation reveal key role of BMPs in skeletal response to mechanical stimulation? | qiaojin/PubMedQA | 2 | [
-2.534820079803467,
-1.041651964187622,
2.7154812812805176
] |
['Our previous studies showed that arthritic Lewis (LEW) rats produced the highest levels of tumour necrosis factor (TNF)alpha in the recovery phase of adjuvant arthritis (AA), suggesting a correlation between high TNFalpha levels and reduced severity of arthritis. To further explore this correlation, we compared the TNFalpha secretion profile of the AA-resistant Wistar Kyoto (WKY) rats with that of LEW rats, determined the effect of exogenous TNFalpha on the course of AA in LEW rats, and examined various mechanisms involved in TNFalpha-induced disease modulation.', 'A cohort each of LEW and WKY rats was immunised subcutaneously with heat-killed Mycobacterium tuberculosis H37Ra (Mtb). At different time points thereafter, subgroups of rats were killed and their draining lymph node cells were tested for cytokine production. Another group of LEW rats was injected with TNFalpha intraperitoneally daily for a total of 10 injections, 3 before and 6 after Mtb challenge, and then observed for signs of AA. In parallel, TNFalpha-treated rats were examined for changes in other cytokines, in CD4+CD25+ T cell frequency, and in indoleamine 2,3-dioxygenase (IDO) mRNA expression levels.', 'LEW rats displayed a TNFalpha secretion profile that was opposite to that of the WKY rats. Furthermore, TNFalpha treatment significantly down modulated the severity of AA in LEW rats, and decreased the interferon (IFN)-gamma secretion in response to the pathogenic determinant of the disease-related antigen. No significant alterations were observed in other parameters tested.'] Does exogenous tumour necrosis factor alpha induce suppression of autoimmune arthritis? | qiaojin/PubMedQA | 2 | [
-2.3635222911834717,
-1.2941763401031494,
2.6784825325012207
] |
['Epidermal Growth Factor Receptor (EGFR) is a key target molecule in current treatment of several neoplastic diseases. Hence, in order to develop and improve current drugs targeting EGFR signalling, an accurate understanding of how this signalling pathway is regulated is required. It has recently been demonstrated that inhibition of cAMP-dependent protein kinase (PKA) induces a ligand-independent internalization of EGFR. Cyclic-AMP-dependent protein kinase consists of a regulatory dimer bound to two catalytic subunits.', 'We have investigated the effect on EGFR levels after ablating the two catalytic subunits, Calpha and Cbeta in two different models. The first model used targeted disruption of either Calpha or Cbeta in mice whereas the second model used Calpha and Cbeta RNA interference in HeLa cells. In both models we observed a significant reduction of EGFR expression at the protein but not mRNA level.'] Are epidermal growth factor receptor levels reduced in mice with targeted disruption of the protein kinase A catalytic subunit? | qiaojin/PubMedQA | 2 | [
-2.4966068267822266,
-0.8567790389060974,
2.353511333465576
] |
['An interaction between ghrelin, which is implicated in the regulation of short- and long-term energy balance, and thyroid function has been reported in hyperthyroidism in which ghrelin levels are reversibly suppressed. We measured serum ghrelin levels and metabolic indices in hypothyroid patients before and after L-thyroxine replacement.', 'Eleven patients were examined twice: 1) in the hypothyroid state and 2) after at least 2 months of euthyroidism. Ten healthy subjects served as a control group. Ghrelin was measured in conjunction with indirect calorimetry and a hyperinsulinemic euglycemic clamp.', 'Serum ghrelin levels were increased by 32% under basal conditions in the hypothyroid state (PRE) as compared with posttreatment (POST) (picograms per milliliter): 976.4 +/- 80.8 vs. 736.8 +/- 67.1 (P < 0.001). This difference prevailed during the clamp, but a decline was observed in both states: 641.4 +/- 82.2 vs. 444.3 +/- 66.8 microg/ml (P = 0.005). The hypothyroid state was associated with decreased resting energy expenditure, increased respiratory quotient, and insulin resistance. Serum ghrelin levels as well as the metabolic aberrations became normalized after L-thyroxine replacement as compared with the control subjects.'] Are serum ghrelin levels increased in hypothyroid patients and become normalized by L-thyroxine treatment? | qiaojin/PubMedQA | 2 | [
-2.049062490463257,
-1.3220133781433105,
2.345491409301758
] |
['The implementation of bowel cancer screening in the UK requires the maintenance of high standards in colonoscopy. Part of this quality control requires the reliable documentation of complete colonoscopy that can be externally audited and assessed. It has been suggested that terminal ileal biopsy is the only definitive and reliable method of confirming caecal intubation, but it is not cost-effective and may now be contraindicated because of potential prion infection.', "To determine how reliable routine terminal ileal images were as an independent predictor of complete colonoscopy and whether their interpretation was aided with water insufflation or indigo-carmine dye-spraying. Method Forty-nine histologically confirmed terminal ileal images were obtained from a single endoscopist's database; 19 were conventional white-light images, 15 were taken with water insufflation and 15 were taken using chromoscopy enhancement. The images were transferred onto CD-ROM and sent as a questionnaire to 42 colonoscopists who were asked to identify the images as terminal ileum or not.", 'Twenty questionnaires were returned resulting in a total of 980 responses. Overall, the accuracy of positive identification was 53.4%. Water insufflation and chromoscopy improved the accuracy to 68.3% and 63% respectively. Experience of (> 1000 colonoscopies) did not increase overall accuracy. Less experienced endoscopists had an increased accuracy rate with dye-spraying (76.7%vs 59.3%, P < 0.05) but experienced endoscopists had an increased accuracy rate with water insufflation (67.4%vs 63.3%, P > .05).'] Is direct photographic documentation of ileal mucosa in routine colonoscopy an independent valid or reliable proof of completion : quality assurance issues for the national colorectal cancer-screening programme? | qiaojin/PubMedQA | 2 | [
-1.7891472578048706,
-1.6039658784866333,
2.4334237575531006
] |
["Exon skipping oligonucleotides (ESOs) of 2'O-Methyl (2'OMe) and morpholino chemistry have been shown to restore dystrophin expression in muscle fibers from the mdx mouse, and are currently being tested in phase I clinical trials for Duchenne Muscular Dystrophy (DMD). However, ESOs remain limited in their effectiveness because of an inadequate delivery profile. Synthetic cationic copolymers of poly(ethylene imine) (PEI) and poly(ethylene glycol) (PEG) are regarded as effective agents for enhanced delivery of nucleic acids in various applications.", "We examined whether PEG-PEI copolymers can facilitate ESO-mediated dystrophin expression after intramuscular injections into tibialis anterior (TA) muscles of mdx mice. We utilized a set of PEG-PEI copolymers containing 2 kDa PEI and either 550 Da or 5 kDa PEG, both of which bind 2'OMe ESOs with high affinity and form stable nanoparticulates with a relatively low surface charge. Three weekly intramuscular injections of 5 microg of ESO complexed with PEI2K-PEG550 copolymers resulted in about 500 dystrophin-positive fibers and about 12% of normal levels of dystrophin expression at 3 weeks after the initial injection, which is significantly greater than for injections of ESO alone, which are known to be almost completely ineffective. In an effort to enhance biocompatibility and cellular uptake, the PEI2K-PEG550 and PEI2K-PEG5K copolymers were functionalized by covalent conjugation with nanogold (NG) or adsorbtion of colloidal gold (CG), respectively. Surprisingly, using the same injection and dosing regimen, we found no significant difference in dystrophin expression by Western blot between the NG-PEI2K-PEG550, CG-PEI2K-PEG5K, and non-functionalized PEI2K-PEG550 copolymers. Dose-response experiments using the CG-PEI2K-PEG5K copolymer with total ESO ranging from 3-60 microg yielded a maximum of about 15% dystrophin expression. Further improvements in dystrophin expression up to 20% of normal levels were found at 6 weeks after 10 twice-weekly injections of the NG-PEI2K-PEG550 copolymer complexed with 5 microg of ESO per injection. This injection and dosing regimen showed over 1000 dystrophin-positive fibers. H&E staining of all treated muscle groups revealed no overt signs of cytotoxicity."] Do nanopolymers improve delivery of exon skipping oligonucleotides and concomitant dystrophin expression in skeletal muscle of mdx mice? | qiaojin/PubMedQA | 2 | [
-2.182626485824585,
-1.4847769737243652,
2.640165328979492
] |
['Low-dose, long-term macrolide therapy has been shown to be effective for the treatment of diffuse panbronchiolitis (DPB) and similar disorders in terms of the presence of airway mucus hypersecretion such as bronchiectasis, chronic bronchitis and sinobronchial syndrome. However, there are some patients, especially advanced cases, whose volume of sputum does not decrease sufficiently with macrolide therapy. These patients suffer from copious expectoration. There is currently no effective treatment, and an effective therapy is therefore urgently required. The aim of this study was to clarify whether or not the inhalation of tiotropium improves the symptoms in these cases.', 'Tiotropium (18 microg/day) was administered to patients with DPB and similar disorders with airway mucus hypersecretion who did not respond to macrolide. The symptoms were evaluated by a visual analog scale (VAS) prior to and at 1 and 3 months after tiotropium administration. Radiological and pulmonary function tests were also performed to evaluate the effects of tiotropium.', 'Thirteen patients (DPB 5, sinobronchial syndrome 5, bronchiectasis 3) were enrolled. The VAS scores were dramatically improved after the introduction of tiotropium. FEV(1) was significantly improved after 3 months of treatment with tiotropium. In contrast, the radiological findings remained unchanged.'] Does tiotropium ameliorate symptoms in patients with chronic airway mucus hypersecretion which is resistant to macrolide therapy? | qiaojin/PubMedQA | 2 | [
-2.4424636363983154,
-1.1752607822418213,
2.7359166145324707
] |
['Interleukin (IL)-17 is involved in autoimmune inflammatory disorders and naturally occurring CD25pos regulatory T cells were shown to promote IL-17 synthesis. Because IL-17 is overproduced in certain types of allograft rejection, it is important to characterize the cells responsible for IL-17 synthesis and to define how IL-17 is regulated during alloimmune responses.', 'Splenic CD4pos T cells were isolated from C57BL/6 mice and fractionated according to CD25 expression. T cells were stimulated by major histocompatibility complex class II-mismatched bone marrow-derived dendritic cells from bm12 mice, either immature or made mature by exposure to lipopolysaccharide. To track T cell populations, CD25negCD4pos and CD25posCD4pos were isolated from Thy1.1 and congenic Thy1.2 mice, respectively. Cell proliferation was quantified by CFSE dilution. IL-17-producing cells and FOXP3pos cells were enumerated by intracytoplasmic staining and cytokine levels in culture supernatants were measured by ELISA.', 'Addition of CD25posCD4pos T cells to CD25negCD4pos T cells inhibited IL-2, interferon-[gamma], and IL-13 production but promoted IL-17 synthesis on stimulation by allogenic immature DC. In this setting, IL-17 originated from CD25intCD4posFOXP3neg memory T cells, which depend on IL-2 to produce IL-17. Alloreactive CD25negCD4pos T cells were also induced to produce IL-17 when stimulated by mature DC in the presence of CD25highCD4posFOXP3pos T cells.'] Does iL-17 production elicited by allo-major histocompatibility complex class II recognition depend on CD25posCD4pos T cells? | qiaojin/PubMedQA | 2 | [
-2.3571512699127197,
-1.3486247062683105,
2.7312660217285156
] |
['In our experience, correction of coagulation defects with plasma transfusion does not decrease the need for intraoperative red blood cell (RBC) transfusions during liver transplantation. On the contrary, it leads to a hypervolemic state that result in increased blood loss. A previous study has shown that plasma transfusion has been associated with a decreased 1-year survival rate. The aim of this prospective study was to evaluate whether anesthesiologists could reduce RBC transfusion requirements during liver transplantation by eliminating plasma transfusion.', 'Two hundred consecutive liver transplantations were prospectively studied over a 3-year period. Patients were divided into two groups: low starting international normalized ratio (INR) value <1.5 and high INR > or =1.5. Low central venous pressure was maintained in all patients before the anhepatic phase. Coagulation parameters were not corrected preoperatively or intraoperatively in the absence of uncontrollable bleeding. Phlebotomy and auto transfusion of blood salvaged were used following our protocol. Independent variables were analyzed in both univariate and multivariate fashion to find a link with RBC transfusions or decreased survival rate.', "The mean number of intraoperative RBC units transfused was 0.3+/-0.8. Plasma, platelet, albumin, and cryoprecipitate were not transfused. In 81.5% of the patients, no blood product was used during their transplantation. The average final hemoglobin (Hb) value was 91.2+/-15.0 g/L. There were no differences in transfusional rate, final Hb, or bleeding between two groups (low or high INR values). The overall 1-year survival rate was 85.6%. Logistic regression showed that avoidance of plasma transfusion, phlebotomy, and starting Hb value were significantly linked to liver transplantation without RBC transfusion. The need for intraoperative RBC transfusion and Pugh's score were linked to the decreased 1-year survival rate."] Do coagulation defects predict blood product requirements during liver transplantation? | qiaojin/PubMedQA | 2 | [
-1.77904212474823,
-1.529358148574829,
2.2899985313415527
] |
['Oxidized low-density lipoprotein (oxLDL) promotes expression and secretion of endothelin-1 (ET-1), however, the precise mechanism involved is unclear. This study was designed to identify the regulatory mechanism of oxLDL-induced ET-1 expression in endothelial cells.', 'ET-1 mRNA expression, secretion and promoter activity were evaluated by reverse transcriptase-PCR (RT-PCR), enzyme immunometric and luciferase assays, respectively.', "oxLDL (35 microg/ml) significantly enhanced reactive oxygen species (ROS), mRNA expression, secretion and promoter activity of ET-1 in human umbilical vein endothelial cells (HUVECs), all of which were nullified by the antioxidant N-acetyl cysteine (NAC). oxLDL stimulated the extracellular signal-regulated kinase (ERK) phosphorylation in HUVECs, which was blocked by NAC and the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD98059. NAC and PD98059 stopped oxLDL-elicited increase in mRNA expression, secretion and promoter activity of ET-1. Fusion plasmids with decreasing length of 5'-flanking sequence of ET-1 from -566 bpLuc to -250 bpLuc displayed increased luciferase activity after 24 h of oxLDL treatment. Interestingly, fusion plasmid from -233 and -185 bpLuc significantly reduced the luciferase activity in control and oxLDL-treated HUVECs. In addition, transfection of the reporter construct -250Luc, which contains a 2 bp mutation at activator protein-1 site, abolished both basal and oxLDL-stimulated ET-1 promoter activities."] Do reactive oxygen species mediate oxidized low-density lipoprotein-induced endothelin-1 gene expression via extracellular signal-regulated kinase in vascular endothelial cells? | qiaojin/PubMedQA | 2 | [
-2.279092311859131,
-1.4072902202606201,
2.72332763671875
] |
['Oxidative stress causes endothelial dysfunction and plays a major role in the pathogenesis of cardiovascular disease. Increased vascular stiffness is an intermediate phenotype in the development of cardiovascular disease. We hypothesized that vascular stiffness is partially determined by oxidative stress.', 'We examined 163 participants out of whom 80 had coronary artery disease. Vascular stiffness was assessed by pulse wave analysis, pulse wave velocity and measurement of aortic compliance by cardiac MRI. Circulating markers of oxidative stress and vascular superoxide generation in saphenous vein were measured.', 'After adjustment for age, sex, BMI, heart rate, blood pressure and lipids only carotid-femoral pulse wave velocity and aortic compliance were different between patients and control group. Aortic compliance was reduced (11.4 +/- 6.3 vs. 13.9 +/- 7.3 ml x 10(-3) per mmHg; P = 0.035) and vascular superoxide generation increased (1.01 +/- 0.45 vs. 0.76 +/- 0.44 nmol/mg per min; P = 0.035) in patients with coronary artery disease compared with those without. In a multiple stepwise regression analysis, aortic compliance was determined by age (P < 0.001) and vascular superoxide production (P = 0.033). CYBA C242T and NOS3 G894T polymorphisms had additive effects on vascular superoxide generation (P = 0.026) and xanthine oxidase activity was increased in patients with CAD (P = 0.043). Genetic factors (P = 0.033) and xanthine oxidase activity (P < 0.001) were also related to aortic compliance.'] Is vascular stiffness related to superoxide generation in the vessel wall? | qiaojin/PubMedQA | 2 | [
-2.198498487472534,
-1.4134962558746338,
2.628700017929077
] |
['Obstruction of the urinary tract has marked effects on renal blood flow, glomerular filtration rate (GFR), and tubular function. Moreover, ureteral obstruction results in an injury response that can progress to irreversible renal fibrosis and tubular atrophy by apoptosis.', 'We examined the effect of a calcium channel blocker (verapamil) on renal functions and the abundance of apoptotic (p53, Fas, proliferating cell nuclear antigen [PCNA]) markers 1 week after Unilateral Ureteral Obstruction (UUO).', 'Immunohistochemistry studies revealed that UUO was markedly associated with up-regulation in the expression of p53 (1550 +/- 82 vs 100 +/- 23%), Fas (657 +/- 48 vs 100 +/- 31%), and proliferating cell nuclear antigen (945 +/- 70 vs 100 +/- 17% of sham levels). Administration of verapamil normalized the up-regulation of apoptotic markers p53 (724 +/- 116 vs 1550 +/- 82%); Fas (162 +/- 38 vs 657 +/- 48%) and PCNA (353 +/- 54 vs 945 +/- 70%). Furthermore, tubular diameter, as an important marker for detecting tubular atrophy was significantly decreased compared to those in UUO rabbits. The percent area of interstitial fibrosis in UUO kidneys was significantly greater than that in Verapamil-treated kidneys. Importantly, Verapamil reduced the development of interstitial fibrosis in UUO rabbits. We measured the GFR and renal blood flow in UUO. Short-term Verapamil challenge partially prevented the decrease in GFR (non-treated UUO: 62 +/- 14; Verapamil + UUO: 119 +/- 7; Sham: 127 +/- 23 microL x min(-1) x kg body wt(-1), P < 0.05) and renal blood flow (non-treated UUO: 1.1 +/- 0.4; Verapamil + UUO: 5.0 +/- 0.2; sham: 6.3 +/- 0.2 mL x min(-1) x kg body wt(-1), P < 0.05).'] Does verapamil prevent the apoptotic and hemodynamic changes in response to unilateral ureteral obstruction? | qiaojin/PubMedQA | 2 | [
-1.9431164264678955,
-1.6022709608078003,
2.525076150894165
] |
['To assess the use of lipid-lowering therapy in patients with known coronary heart disease (CHD), cerebrovascular disease or diabetes in a community-based population in Sweden considering expert recommendations.', 'A random sample of individuals aged > or =40 years who were surveyed in 1993-1994 were revisited 10 years later during 2003-2004 (n = 724). A clinical investigation focused on cardiovascular risk including serum total cholesterol. Information on medical history and current medication was collected in structured interviews.', 'Eighty-two patients (11.3%) reported a history of CHD, including 51 men and 31 women. Fifty-three patients fulfilled criteria for treatment and most of them (85%) were on lipid-lowering therapy. A higher fraction of women were treated; however only 13% of them reached target cholesterol levels compared to 37% of the men (P < 0.001). Sixty-five subjects (9.0%) had diabetes and/or a previous stroke (29 men, 36 women) but no previous CHD. Patients with CHD were more likely to be treated compared to patients with diabetes and/or stroke but no CHD (85.0 vs. 28.5%, OR 6.0, 95% CI 2.2-16.9, P = 0.01). In a total of 79 participants (10.9%) who were on lipid-lowering therapy, women reached a total serum cholesterol level below 5.0 mmol/L less often than men (26.3 vs. 63.4%, P < 0.001).'] Is cholesterol in women at high cardiovascular risk less successfully treated than in corresponding men . The Skaraborg Hypertension and Diabetes Project? | qiaojin/PubMedQA | 2 | [
-0.07310550659894943,
-1.2942253351211548,
0.4563180208206177
] |
['We investigated whether or not, in type 2 diabetic (T2D) patients, an individualized training effect on whole-body lipid oxidation would be associated with changes in muscle oxidative capacity.', 'Eleven T2D patients participated in the study. Whole-body lipid oxidation during exercise was assessed by indirect calorimetry during graded exercise. Blood samples for measuring blood glucose and free fatty acids during exercise, and muscle oxidative capacity measured from skeletal muscle biopsy (mitochondrial respiration and citrate synthase activity), were investigated in the patients before and after a 10-week individualized training program targeted at LIPOXmax, corresponding to the power at which the highest rate of lipids is oxidized (lipid oxidation at LIPOXmax).', 'Training induced both a shift to a higher-power intensity of LIPOXmax (+9.1+/-4.2W; P<0.05) and an improvement of lipid oxidation at LIPOXmax (+51.27+/-17.93 mg min(-1); P<0.05). The improvement in lipid oxidation was correlated with training-induced improvement in mitochondrial respiration (r=0.78; P<0.01) and citrate synthase activity (r=0.63; P<0.05).'] Is training-induced improvement in lipid oxidation in type 2 diabetes mellitus related to alterations in muscle mitochondrial activity . Effect of endurance training in type 2 diabetes? | qiaojin/PubMedQA | 2 | [
-2.33447003364563,
-1.2313156127929688,
2.651838541030884
] |
['Annexin-1 (Anx-A1) has been recently shown to play a key role in T-cell activation and to be highly expressed in T cells from RA patients. Here, we investigated the effects of glucocorticoids (GCs) on Anx-A1 expression in T cells in vitro and in vivo.', 'To evaluate the effects of dexamethasone (Dex) on Anx-A1 expression, human peripheral blood T cells were incubated with Dex and then analysed by real-time PCR and western blotting. Similar experiments were carried out in vivo by measuring Anx-A1 levels in T cells from patients with RA before and after administration of steroids.', 'Incubation of T cells with Dex decreased Anx-A1 levels in a time-dependent fashion and almost abolished its expression after 12 h. Stimulation of T cells pre-incubated with Dex for 12 h with anti-CD3/CD28 led to significant reduction of IL-2 production. Addition of human recombinant Anx-A1 to Dex-treated cells reversed the inhibitory effects of the steroids on anti-CD3/CD28-induced IL-2 production. Treatment of RA patients with steroid decreased Anx-A1 expression in T cells.'] Does glucocorticoid treatment inhibit annexin-1 expression in rheumatoid arthritis CD4+ T cells? | qiaojin/PubMedQA | 2 | [
-2.584458589553833,
-1.1300604343414307,
2.7101786136627197
] |
['Antiplatelet therapy is important in secondary prophylaxis in patients with ischemic heart, brain and vascular diseases. The aim of this study was to investigate the number of patients in Vejle County admitted to hospital in the second half of 2003 with acute and chronic heart, brain and vascular diseases to evaluate the kind of secondary prophylaxis and its duration. Moreover, the study registered the number of patients with diabetes mellitus treated with antiplatelet therapy.', "The study included 2345 patients with ischemic heart, brain and vascular diseases, and patients with diabetes mellitus. Patients' data and information about medication were obtained from the hospital electronic database and public health insurance of Vejle County. Antiplatelet therapy was registered up to one year after onset of the disease.", '1121 patients were admitted with cardiac diseases (including patients with angina pectoris), 624 patients had cerebral diseases, and 600 had diabetes mellitus. Acetylsalicylic acid (ASA) and a combination of ASA and clopidogrel were the most frequent forms of antiplatelet medication. Patients with diabetes and ischemic brain diseases made up 75% of those for whom medication was not registered.'] Is [ Antiplatelet treatment after acute and chronic ischemic heart and brain events insufficient according to recommendations ]? | qiaojin/PubMedQA | 2 | [
-1.999672293663025,
-0.48460397124290466,
1.4988172054290771
] |
['TGFbeta (transforming growth factor beta) is a multifunctional cytokine and a potent regulator of cell growth, migration and differentiation in many cell types. In the vascular system, TGFbeta plays crucial roles in vascular remodelling, but the signalling pathways involved remain poorly characterized.', 'Using the model of porcine aortic endothelial cells, we demonstrated that TGFbeta stimulates cellular spreading when cells are on collagen I. TGFbeta-stimulated Rac1-GTP accumulation, which was associated with increased MAPK (mitogen-activated protein kinase) p38 phosphorylation. Furthermore, ectopic expression of a dominant-negative Rac mutant, or treatment of the cells with the p38 pharmacological inhibitor SB203580, abrogated TGFbeta-induced cell spreading. Our results demonstrate for the first time that prolonged exposure to TGFbeta stimulates endothelial cell hypertrophy and flattening. Collectively, these data indicate that TGFbeta-induced cell spreading and increase in cell surface areas occurs via a Rac-p38-dependent pathway.'] Does tGFbeta1 regulate endothelial cell spreading and hypertrophy through a Rac-p38-mediated pathway? | qiaojin/PubMedQA | 2 | [
-2.47129225730896,
-1.1142501831054688,
2.6402335166931152
] |
['The bestrophin family of proteins has been demonstrated to generate or regulate Ca2+-activated Cl(-) conductances. Mutations in bestrophin-1 (Best1) cause several blinding eye diseases, but little is known about other bestrophin family members. This study involved disruption of the Best2 gene in mice.', 'The mouse Best2 gene was disrupted by replacing exons 1, 2, and part of exon 3 with a Lac Z. The expression profile of Bestrophin-2 (Best2) was examined using RT-PCR, X-gal staining, and immunohistochemistry. Intraocular pressure (IOP) was measured by anterior chamber cannulation.', 'RT-PCR of mouse tissues revealed Best2 mRNA in eye, colon, nasal epithelia, trachea, brain, lung, and kidney. X-gal staining, confirmed expression in colon epithelia and in the eye, in the nonpigmented epithelia (NPE). Best2 was not expressed in RPE cells. Best2 protein was observed only in NPE and colon epithelia. The absence of Best2 had no obvious deleterious effect on the mice. However, the Best2-/- mice were found to have significantly (P < 0.02) diminished IOP with respect to the Best2+/+ and Best2+/- littermates. The Best2-/- and Best2+/- mice responded better to the carbonic anhydrase inhibitor brinzolamide than did their Best2+/+ littermates, although the beta-blocker timolol brought IOP to the same level, regardless of genotype.'] Is bestrophin-2 involved in the generation of intraocular pressure? | qiaojin/PubMedQA | 2 | [
-2.2138707637786865,
-1.40302312374115,
2.5826289653778076
] |
['Fibromyalgia (FM) and chronic fatigue syndrome (CFS) frequently overlap clinically and have been considered variants of one common disorder. We have recently shown that CFS is associated with a short corrected electrocardiographic QT interval (QTc). In the present study, we evaluated whether FM and CFS can be distinguished by QTc.', "The study groups were comprised of women with FM (n=30) and with CFS (n=28). The patients were evaluated with a 10 min supine-30 min head-up tilt test. The electrocardiographic QT interval was corrected for heart rate (HR) according to Fridericia's equation (QTc). In addition, cardiovascular reactivity was assessed based on blood pressure and HR changes and was expressed as the 'hemodynamic instability score' (HIS).", 'The average supine QTc in FM was 417 ms (SD 25) versus 372 ms (SD 22) in CFS (p<0.0001); the supine QTc cut-off <385.7 ms was 79% sensitive and 87% specific for CFS vs. FM. The average QTc at the 10th minute of tilt was 409 ms (SD 18) in FM versus 367 ms (SD 21) in CFS (p<0.0001); the tilt QTc cut-off <383.3 ms was 71% sensitive and 91% specific for CFS vs. FM. The average HIS in FM patients was -3.52 (SD 1.96) versus +3.21 (SD 2.43) in CFS (p<0.0001).'] Do electrocardiographic QT interval and cardiovascular reactivity in fibromyalgia differ from chronic fatigue syndrome? | qiaojin/PubMedQA | 2 | [
-0.858336329460144,
-1.8104463815689087,
1.6047922372817993
] |
['The aim of this study was to evaluate the suppression effect of survivin shRNA on the expression of the survivin gene in the human laryngeal cancer cell line Hep-2.', '60 cases of laryngeal squamous-cell carcinoma (LSCC) and 10 cases of normal laryngeal mucosa were examined using immunohistochemistry to determine whether the expression of survivin correlated with tumorigenesis. Three plasmid vectors of short hairpin RNA (shRNA) specific for survivin were designed and generated. Western blot and real-time PCR analysis of survivin expression in Hep-2 cells was performed 48 h after transfection. The growth curve was used to determine the cell proliferation. Propidium iodide (PI) single staining was applied to detect the cell cycle. The apoptosis of the cells was analyzed by flow cytometry with the FITC-annexin-V/PI double staining and PI single staining.', '68.33% (41 out of 60) of tumors were positive for survivin expression and significantly associated with lymph node metastasis and advanced stage. In contrast, no expression of survivin in normal mucosa was detected. Transfection of Hep-2 cells with survivin shRNA significantly inhibited survivin expression at both the mRNA and the protein level in Hep-2 cells. Downregulation of survivin resulted in increasing the apoptosis index, but the results showed no obvious influence on cell cycle.'] Does suppression of survivin expression by short hairpin RNA induce apoptosis in human laryngeal carcinoma cells? | qiaojin/PubMedQA | 2 | [
-2.3303632736206055,
-1.365870714187622,
2.7254483699798584
] |
['Human tumors differ from normal tissues in their capacity to present Hsp70, the major stress-inducible member of the HSP70 family, on their plasma membrane. Membrane Hsp70 has been found to serve as a prognostic indicator of overall patient survival in leukemia, lower rectal and non small cell lung carcinomas. Why tumors, but not normal cells, present Hsp70 on their cell surface and the impact of membrane Hsp70 on cancer progression remains to be elucidated.', 'Although Hsp70 has been reported to be associated with cholesterol rich microdomains (CRMs), the partner in the plasma membrane with which Hsp70 interacts has yet to be identified. Herein, global lipid profiling demonstrates that Hsp70 membrane-positive tumors differ from their membrane-negative counterparts by containing significantly higher amounts of globotriaoslyceramide (Gb3), but not of other lipids such as lactosylceramide (LacCer), dodecasaccharideceramide (DoCer), galactosylceramide (GalCer), ceramide (Cer), or the ganglioside GM1. Apart from germinal center B cells, normal tissues are Gb3 membrane-negative. Co-localization of Hsp70 and Gb3 was selectively determined in Gb3 membrane-positive tumor cells, and these cells were also shown to bind soluble Hsp70-FITC protein from outside in a concentration-dependent manner. Given that the latter interaction can be blocked by a Gb3-specific antibody, and that the depletion of globotriaosides from tumors reduces the amount of membrane-bound Hsp70, we propose that Gb3 is a binding partner for Hsp70. The in vitro finding that Hsp70 predominantly binds to artificial liposomes containing Gb3 (PC/SM/Chol/Gb3, 17/45/33/5) confirms that Gb3 is an interaction partner for Hsp70.'] Is tumor-specific Hsp70 plasma membrane localization enabled by the glycosphingolipid Gb3? | qiaojin/PubMedQA | 2 | [
-2.399500608444214,
-1.2544186115264893,
2.7371015548706055
] |
['Metabolic syndrome (MS) is a clustering of cardiovascular disease risk factors that identifies individuals with the highest risk for heart disease. Two factors that may influence the MS are physical activity and aerobic fitness. This study determined if adolescent with the MS had low levels of aerobic fitness and physical activity as children.', 'This longitudinal, exploratory study had 389 participants: 51% girls, 84% Caucasian, 12% African American, 1% Hispanic, and 3% other races, from the State of North Carolina. Habitual physical activity (PA survey), aerobic fitness (VO2max), body mass index (BMI), blood pressure, and lipids obtained at 7-10 y of age were compared to their results obtained 7 y later at ages 14-17 y.', 'Eighteen adolescents (4.6%) developed 3 or more characteristics of the MS. Logistic regression, adjusting for BMI percentile, blood pressure, and cholesterol levels, found that adolescents with the MS were 6.08 (95%CI = 1.18-60.08) times more likely to have low aerobic fitness as children and 5.16 (95%CI = 1.06-49.66) times more likely to have low PA levels.'] Do adolescents with metabolic syndrome have a history of low aerobic fitness and physical activity levels? | qiaojin/PubMedQA | 1 | [
-1.2429180145263672,
0.27299389243125916,
0.22642509639263153
] |
['Protein membrane transduction domains that are able to cross the plasma membrane are present in several transcription factors, such as the homeodomain proteins and the viral proteins such as Tat of HIV-1. Their discovery resulted in both new concepts on the cell communication during development, and the conception of cell penetrating peptide vectors for internalisation of active molecules into cells. A promising cell penetrating peptide is Penetratin, which crosses the cell membranes by a receptor and metabolic energy-independent mechanism. Recent works have claimed that Penetratin and similar peptides are internalized by endocytosis, but other endocytosis-independent mechanisms have been proposed. Endosomes or plasma membranes crossing mechanisms are not well understood. Previously, we have shown that basic peptides induce membrane invaginations suggesting a new mechanism for uptake, "physical endocytosis".', 'Herein, we investigate the role of membrane lipid phases on Penetratin induced membrane deformations (liquid ordered such as in "raft" microdomains versus disordered fluid "non-raft" domains) in membrane models. Experimental data show that zwitterionic lipid headgroups take part in the interaction with Penetratin suggesting that the external leaflet lipids of cells plasma membrane are competent for peptide interaction in the absence of net negative charges. NMR and X-ray diffraction data show that the membrane perturbations (tubulation and vesiculation) are associated with an increase in membrane negative curvature. These effects on curvature were observed in the liquid disordered but not in the liquid ordered (raft-like) membrane domains.'] Does the homeodomain derived peptide Penetratin induce curvature of fluid membrane domains? | qiaojin/PubMedQA | 2 | [
-2.5797994136810303,
-1.1175342798233032,
2.793822765350342
] |
['The molecular mechanisms of oncogenesis in mesothelioma involve the loss of negative regulators of cell growth including p16INK4a. Absence of expression of the p16INK4a gene product is exhibited in virtually all mesothelioma tumors and cell lines examined to date. Loss of p16INK4a expression has also been frequently observed in more common neoplasms such as lung cancer as well. In a wide variety of these malignancies, including lung cancer, p16INK4a expression is known to be inactivated by hypermethylation of the first exon. This project (CALGB 159904) intended to test the hypothesis that in mesothelioma loss of p16INK4a via methylation would correlate with response to the cytidine analog and methylation inhibitor dihydro-5-azacytidine (DHAC).', 'Using tissue samples from CALGB 8833 and 9031, two clinical studies which used DHAC based therapy in mesothelioma, this study tested the hypothesis that tumors possessing methylation of p16INK4a would have a better response and survival following DHAC treatment than their nonmethylated counterparts.', 'Methylation of p16INK4a was identified in 4 of the 20 specimens. Although there was a trend towards improved survival the result was not statistically significant.'] Is response to the methylation inhibitor dihydro-5-azacytidine in mesothelioma associated with methylation of p16INK4a : results of cancer and leukemia group B 159904? | qiaojin/PubMedQA | 2 | [
-2.435472249984741,
-1.1937217712402344,
2.673029899597168
] |
['There is substantial evidence to consider both heart rate (HR) at rest and pulse pressure (PP) as significant markers of cardiovascular prognosis in the general population. Despite this, neither of these two parameters has been taken into consideration in the design of modern coronary artery bypass risk prediction scores, and little data on their early postoperative prognostic value are currently available. We aimed to assess the predictive value of preoperative HR and PP in the 30-day postoperative period.', 'We prospectively enrolled all patients referred to our institution for non-urgent coronary artery bypass grafting. We measured HR on ECG at admittance. Preoperative pulse pressure was obtained by the difference of the mean of three consecutive systolic and diastolic blood pressures. The primary outcome combined the 30-day postoperative mortality, myocardial infarction (new Q-waves on ECG or Troponin-I >20 microg/l) and stroke or transient ischemic attack. The secondary outcome corresponded to clinical events only (stroke or death). Statistical analysis was performed by usual methods.', 'We enrolled 1022 patients (age 66.9+/-9.2 years). Those meeting the primary outcome (n=146) had a significantly higher HR (69.9+/-14.3 bpm vs 64.9+/-13.2 bpm, p<0.0001) and a higher proportion presented a PP >70 mmHg (17.1% vs 10.2%, p<0.03). After adjustments for age, gender, systolic blood pressure, preoperative beta-blocker therapy, left ventricular ejection fraction <0.40, unstable cardiac status, redo surgery, peripheral arterial disease, renal failure, and combined vascular surgery, both HR (OR=1.17 per 10 bpm, p<0.03) and PP >70 mmHg (OR=1.99, p=0.03) remained significant risk predictors. Similar results were found when considering only clinical events.'] Are heart rate and pulse pressure at rest major prognostic markers of early postoperative complications after coronary bypass surgery? | qiaojin/PubMedQA | 2 | [
-1.5285061597824097,
-1.565246343612671,
2.103853225708008
] |
['Regeneration of the myocardium and improved ventricular function have been demonstrated in patients with acute myocardial infarction (MI) treated by intracoronary delivery of autologous bone marrow mononuclear cells (BMC) a few days after successful myocardial reperfusion by percutaneous coronary intervention (PCI); however, the effects of intracoronary cell infusion in chronic MI patients are still unknown.', 'To investigate whether intracoronary infusion of BMC into the infarct-related artery in patients with healed MI could lead to improvement in left ventricular (LV) function.', 'Among 47 patients with stable ischaemic heart disease due to a previous MI (13 (SD 8) months previously), 24 were randomised to intracoronary infusion of BMC (BMC group) and 23 to a saline infusion (control group) into the target vessel after successful PCI within 12 hours after chest pain occurred. LV systolic and diastolic function, infarct size and myocardial perfusion defect were assessed with the use of echocardiography, magnetic resonance imaging (MRI) or (201)Tl single-photon-emission computed tomography (SPECT) at baseline and repeated at the 6-month follow-up examination.', 'BMC treatment did not result in a significant increase in LV ejection fraction in any of the groups by any of the methods used, and the apparent tendency of an improvement was not statistically different between the two groups. The two groups also did not differ significantly in changes of LV end-diastolic and systolic volume, infarct size or myocardial perfusion. However, there was an overall effect of BMC transfer compared with the control group with respect to early/late (E/A) (p<0.001), early diastolic velocity/late diastolic (Aa) velocity (Ea/Aa) ratio (p = 0.002) and isovolumetric relaxation time (p = 0.038) after 6 months, as evaluated by tissue Doppler echocardiography. We noted no complications associated with BMS transfer.'] Does administration of intracoronary bone marrow mononuclear cells on chronic myocardial infarction improve diastolic function? | qiaojin/PubMedQA | 2 | [
-2.2802698612213135,
-1.4347057342529297,
2.772137403488159
] |
['Two strategies are clinically available to induce selective hypertrophy of the liver: portal vein embolization (PVE) and portal vein ligation (PVL). The aim of this study was to compare the impact of PVE and PVL on liver regeneration. Rats were subjected to 70% PVL, 70% PVE, 70% partial hepatectomy (PH) (positive control), or sham operation (negative control). PVL and PVE of liver segments were validated by portography and histology, demonstrating obstruction of the involved portal branches. Liver weight and markers of regeneration were assessed at 24, 48, and 72 hours, and 7 days after surgery (n = 5). Sinusoidal perfusion was examined by intravital microscopy. The weight of the regenerating liver segments increased continuously in all groups, with the highest weight gain after PH, which also disclosed the strongest proliferative activity. In Ki-67 and PCNA stainings, hepatocyte proliferation after PVL was more pronounced than after PVE (P = 0.01). Volumetric blood flow and functional sinusoidal density were lower after PVE than after PVL (P = 0.006, P = 0.02, respectively). The accumulation of Kupffer cells 24 hours after the intervention was highest after PH. Transcript levels of cytokines (interleukin-1beta, tumor necrosis factor-alpha, interleukin-6) peaked at 24 hours and were highest after PH. The embolized part of the liver after PVE showed prominent foreign body reaction in the portal triad with accumulation of macrophages.'] Do selective portal vein embolization and ligation trigger different regenerative responses in the rat liver? | qiaojin/PubMedQA | 2 | [
-2.337761640548706,
-1.4340758323669434,
2.8291568756103516
] |
['Orthotopic liver transplantation is the only proven effective treatment for fulminant hepatic failure (FHF), but its use is limited because of organ donor shortage, associated high costs, and the requirement for lifelong immunosuppression. FHF is usually accompanied by massive hepatocellular death with compensatory liver regeneration that fails to meet the cellular losses. Therefore, therapy aimed at inhibiting cell death and stimulating endogenous repair pathways could offer major benefits in the treatment of FHF. Recent studies have demonstrated that mesenchymal stem cell (MSC) therapy can prevent parenchymal cell loss and promote tissue repair in models of myocardial infarction, acute kidney failure, and stroke through the action of trophic secreted molecules. In this study, we investigated whether MSC therapy can protect the acutely injured liver and stimulate regeneration. In a D-galactosamine-induced rat model of acute liver injury, we show that systemic infusion of MSC-conditioned medium (MSC-CM) provides a significant survival benefit and prevents the release of liver injury biomarkers. Furthermore, MSC-CM therapy resulted in a 90% reduction of apoptotic hepatocellular death and a three-fold increment in the number of proliferating hepatocytes. This was accompanied by a dramatic increase in the expression levels of 10 genes known to be up-regulated during hepatocyte replication. Direct antiapoptotic and promitotic effects of MSC-CM on hepatocytes were demonstrated using in vitro assays.'] Do mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo? | qiaojin/PubMedQA | 2 | [
-2.463874340057373,
-1.3109779357910156,
2.834244728088379
] |
['We wanted to determine whether routine postoperative chest radiography is needed after surgery with eleventh rib resection.', 'Data on 80 patients who underwent radical or partial nephrectomy, nephroureterectomy or adrenalectomy through 82 flank incisions with eleventh rib resection were collected and analyzed retrospectively.', 'Radical and partial nephrectomies, nephroureterectomies and adrenalectomies were done through 47, 20, 6 and 9 flank incisions in 80 patients, respectively. Among these, one patient underwent a partial nephrectomy and subsequent contralateral radical nephrectomy, and another patient underwent simultaneous bilateral adrenalectomies. The intrapleural space was entered accidentally in 16 flank incisions (19.51%). Repair was performed with a simple evacuation technique at the time of surgery, and a chest tube was needed in only three patients (18.75%) according to postoperative chest x-ray evaluation after pleural repair. Of the remaining patients who had no evidence of pleural opening on the water seal test before wound closure, none developed respiratory distress postoperatively and no chest x-rays were ordered, except for one patient who developed subcutaneous emphysema on the day of surgery where no evidence of pneumothorax was detected.'] Is routine postoperative chest radiography needed after flank incisions with eleventh rib resection? | qiaojin/PubMedQA | 2 | [
-2.2033205032348633,
-1.1996644735336304,
2.511657476425171
] |
['Provision of adequate patient information may contribute to a "satisfying" surgical treatment. The patient\'s views on successful transfer of information concerning operative characteristics may not be in concert with the surgeon\'s. The aim of the present study was to determine opinions of both surgeons and patients about issues of surgical information.', "A group of surgeons (n = 24) and surgical patients (n = 125) responded to a questionnaire that included 80 topics involving domains of information on disease, physical examination, preoperative period, anesthesia, operation, postoperative period, self care, and general hospital issues. Both groups were asked for their opinion on what they considered important and useful preoperative information for patients. Questions were scored with a visual analog scale. The reliability of the questionnaire was calculated with Cronbach's alpha. Differences in opinions between surgeons and patients were analyzed with Student's t-test.", "The Cronbach's alpha of the questionnaire was high (0.91), indicating its high reliability. Patients scored significantly higher (p < 0.001) in most domains, including preoperative period, anaesthesia, operation, postoperative period, self care, and general hospital information. Women demonstrated a significantly higher need for information than men did. These findings were independent of patient age or complexity of operation. In contrast, surgeons thought that their patients desired more extensive information on cause, effect, and prognosis of the disease itself (p < 0.001)."] Do surgeons underestimate their patients ' desire for preoperative information? | qiaojin/PubMedQA | 2 | [
-1.843721866607666,
-0.14597436785697937,
1.113908052444458
] |
['Some patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) improve rapidly from anti-tumor necrosis factor (anti-TNF) therapy. No sensitive markers are available that might predict outcome of anti-TNF therapy. We undertook this study to investigate the predictive value of hypothalamic-pituitary-adrenal (HPA) axis hormones for clinical improvement during anti-TNF therapy.', 'An observational study in 23 RA patients was followed by a validation study in 38 RA patients. The patients receiving anti-TNF antibodies had no glucocorticoid treatment, and we measured baseline serum levels of adrenocorticotropic hormone (ACTH) and cortisol. Improvement during anti-TNF antibody treatment was judged by the Disease Activity Score in 28 joints (DAS28), and serum levels of cortisol were measured at followup.', 'The observational study demonstrated that improvement in the DAS28 correlated negatively with baseline serum levels of cortisol (R=-0.520, P=0.011) and the cortisol:ACTH ratio (R=-0.700, P=0.0002). In the longitudinal part of the study at followup, those patients with good improvement and initially low serum levels of cortisol demonstrated an increase of serum cortisol, in contrast to patients with little or no improvement. Findings in the observational study were supported by those in the validation study in a group of RA patients with less inflammation (correlation of improvement in the DAS28 with cortisol:ACTH ratio: R=-0.320, P=0.025).'] Does increased cortisol relative to adrenocorticotropic hormone predict improvement during anti-tumor necrosis factor therapy in rheumatoid arthritis? | qiaojin/PubMedQA | 2 | [
-2.0666182041168213,
-1.361541748046875,
2.4006752967834473
] |
['To compare the outcomes of out-of hospital cardiac arrest (OHCA) victims treated with monophasic truncated exponential (MTE) versus biphasic truncated exponential (BTE) defibrillation in an urban EMS system.', 'We conducted a retrospective review of electronic prehospital and hospital records for victims of OHCA between August 2000 and July 2004, including two years before and after implementation of biphasic defibrillators by the Fresno County EMS agency. Main outcome measures included: return of spontaneous circulation (ROSC), number of defibrillations required for ROSC, survival to hospital discharge, and discharge to home versus an extended care facility.', 'There were 485 cases of cardiac arrest included. Baseline characteristics between the monophasic and biphasic groups were similar. ROSC was achieved in 77 (30.6%, 95% CI 25.2-36.5%) of 252 patients in the monophasic group, and in 70 (30.0% 95% CI 24.5-36.2%) of 233 in the biphasic group (p= .92). Survival to hospital discharge was 12.3% (95% CI 8.8-17%) for monophasic and 10.3% (95% CI 7.0-14.9%) for biphasic (p= .57). Discharge to home was accomplished in 20 (7.9%, 95% CI 5.1-12.0%) of the monophasic, and in 15 (6.4%, 95% CI 3.9-10.4%) of the biphasic group (p= .60). More defibrillations were required to achieve ROSC (3.5 vs. 2.6, p= .015) in the monophasic group.'] Does biphasic defibrillation improve outcomes compared to monophasic defibrillation in out-of-hospital cardiac arrest? | qiaojin/PubMedQA | 2 | [
-0.6914198994636536,
-1.6102619171142578,
1.2681777477264404
] |
['Liver fibrosis with any aetiology, induced by the transdifferentiation and proliferation of hepatic stellate cells (HSCs) to produce collagen, is characterized by progressive worsening in liver function, leading to a high incidence of death. We have recently reported that all-trans-retinoic acid (ATRA) suppresses the transdifferentiation and proliferation of lung fibroblasts and prevents radiation- or bleomycin-induced lung fibrosis.', 'We examined the impact of ATRA on carbon tetrachloride (CCl(4))-induced liver fibrosis. We performed histological examinations and quantitative measurements of transforming growth factor (TGF)-beta1 and interleukin (IL)-6 in CCl(4)-treated mouse liver tissues with or without the administration of ATRA, and investigated the effect of ATRA on the production of the cytokines in quiescent and activated HSCs.', 'CCl(4)-induced liver fibrosis was attenuated in histology by intraperitoneal administration of ATRA, and the overall survival rate at 12 weeks was 26.5% without ATRA (n=25), whereas it was 75.0% (n=24) in the treatment group (P=0.0187). In vitro studies disclosed that the administration of ATRA reduced (i) the production of TGF-beta1, IL-6 and collagen from HSCs, (ii) TGF-beta-dependent transdifferentiation of the cells and IL-6-dependent cell proliferation and (iii) the activities of nuclear factor-kappaB p65 and p38mitogen-activated protein kinase, which stimulate the production of TGF-beta1 and IL-6, which could be the mechanism underlying the preventive effect of ATRA on liver fibrosis.'] Does all-trans-retinoic acid ameliorate carbon tetrachloride-induced liver fibrosis in mice through modulating cytokine production? | qiaojin/PubMedQA | 2 | [
-2.405081033706665,
-1.3794360160827637,
2.8207430839538574
] |
['In cardiac arrest due to prolonged ventricular fibrillation (VF), defibrillation is more likely to result in a perfusing rhythm if chest compressions are performed first. Furthermore, the VF waveform can predict the shockability of VF and thus automated external defibrillators (AEDs) are being designed to analyze the VF waveform to direct therapies. However, it is unknown whether the VF waveform is dependent on recording direction, which could be altered by incorrect placement of AED patches.', 'VF was induced in 26 patients with ischemic cardiomyopathy and 19 patients with dilated cardiomyopathy and recorded in six limb leads. Frequency characteristics (mean, median, dominant frequency, and bandwidth) were computed as well as amplitude-based measures: amplitude spectral area (AMSA), slope, signal amplitude, and slope divide by signal amplitude (slope-amp).', 'Frequency characteristics were similar in all leads. However, AMSA, slope, and signal amplitude were significantly affected (P<0.001) by lead. In particular, for ischemic cardiomyopathy patients, between leads I and II, AMSA varied from 29.4+/-3.2 to 49.3+/-4.6 mV Hz (mean+/-SEM, P<0.001) and slope varied from 1.5+/-0.2 to 2.4+/-0.3 mV/s (P<0.001). Slope-amp was similar in all leads. There were no significant differences between ischemic and dilated cardiomyopathy patients.'] Does direction of signal recording affect waveform characteristics of ventricular fibrillation in humans undergoing defibrillation testing during ICD implantation? | qiaojin/PubMedQA | 2 | [
-1.7699815034866333,
-1.568312644958496,
2.3265891075134277
] |
['The objective of this study was to examine the ultrastructural changes in cell organelles such as mitochondria, endoplasmic reticulum (ER) and Golgi apparatus in inflamed colon and uninflamed ileum in colitic rats.', 'Colitis was induced in rats by intracolonic administration of trinitrobenzenesulfonic acid (TNBS). The animals were sacrificed on day 5 after TNBS administration and colonic and ileal samples were used for estimation of myeloperoxidase (MPO) activity, malondialdehyde (MDA) concentration, histologic examination and transmission electron microscopy.', 'TNBS caused a significant reduction in body weight and an increase in MPO activity in colonic, but not in the ileal samples in animals with colitis. MDA levels were increased both in inflamed colon and the uninflamed ileal segments in colitis. Electron microscopy revealed swelling of mitochondria with broken cristae and disruption of the inner membrane. Colitis also caused fragmentation of the ER with loss of ribosomes and swelling of the Golgi apparatus with distended vesicles in both smooth muscle and epithelial cells in the ileal and colonic segments. These changes were absent in the control rats without colitis.'] Is experimental colitis associated with ultrastructural changes in inflamed and uninflamed regions of the gastrointestinal tract? | qiaojin/PubMedQA | 2 | [
-2.6443912982940674,
-1.1194987297058105,
2.869558572769165
] |
['Cachexia, a debilitating syndrome characterized by skeletal muscle wasting, is associated to many chronic diseases and diminishes the quality of life and survival of patients. Tumor-derived factors and proinflammatory cytokines, including TNF-alpha, IL-6 and IL-1 beta, mediate cachexia. In response to elevated cytokine levels, increased proteasome-mediated proteolysis and auto-phagocytosis result in muscle wasting. The histologic features of muscle cachexia are not fully elucidated. Therefore, we analysed alterations of different cell populations in cachectic muscle.', 'By immunohistochemical and cytological approaches, we characterized changes in the abundance of cellular populations in the musculature of a murine model of cancer cachexia (C26-bearing mice).', 'Cachectic muscle displayed a decreased DNA content proportional to muscle mass wastage. A decrease in the number of nuclei occurred in the muscular but not in the stromal compartment. Cachectic muscle showed: mild modulation of myeloperoxidase activity, a neutrophil marker; reduction of macrophages in the endomysium; decrease in CD3(+) lymphocyte number. Conversely, a statistically significant enrichment in Sca-1(+) CD45(+) hematopoietic stem cells (HSCs) occurred in cachectic muscle.'] Is skeletal muscle enriched in hematopoietic stem cells and not inflammatory cells in cachectic mice? | qiaojin/PubMedQA | 2 | [
-2.554155111312866,
-1.189516305923462,
2.8491129875183105
] |
['In patients with untreated metastatic renal cell carcinoma (mRCC), progression-free survival (PFS) was longer with bevacizumab + interferon (IFN)-alpha than IFN + placebo (AVOREN trial). In this hypothesis-generating study, subgroup analysis was carried out to determine the effect of IFN dose reduction.', 'A total of 649 patients received IFN 9 MIU s.c. three times weekly plus bevacizumab 10 mg/kg or placebo every 2 weeks until disease progression. The IFN dose was reduced to 6 or 3 MIU with the development of IFN-attributed toxicity. Differences between treatment arms in PFS, response rate and tolerability were analysed in the reduced-dose group.', 'IFN dose was reduced in 131 patients in the bevacizumab + IFN arm and 97 patients in the IFN + placebo arm during the trial. PFS rates in the bevacizumab + reduced-dose IFN group were comparable with the total population (Kaplan-Meier estimates of event-free rate at 1 year: 0.524 versus 0.427). Bevacizumab + reduced-dose IFN was well tolerated, with substantial decreases in the rate of adverse events following dose reduction.'] Is first-line bevacizumab combined with reduced dose interferon-alpha2a active in patients with metastatic renal cell carcinoma? | qiaojin/PubMedQA | 2 | [
-1.824872374534607,
-1.514766812324524,
2.424668312072754
] |
["Preterm infants are at an increased risk for abnormalities of general movements, which predict subsequent poor neurodevelopmental outcome. The cerebral lesion that predisposes the preterm infant to abnormal general movements remains unknown. The objective of this study was to determine the association between MRI-defined cerebral abnormalities and general movements at 1 and 3 months' corrected age in infants who were born very preterm.", "Eighty-six preterm infants (<30 weeks' gestation) were prospectively recruited and underwent brain MRI at term-equivalent age to investigate the relationship between qualitative white and gray matter pathology and abnormality of general movements. Standardized videotaped recordings of general movements were obtained at 1 and 3 months postterm (+/-1 week) and scored without knowledge of the MRI findings. At 1 month corrected age, general movements of a writhing character were classified as normal or abnormal (poor repertoire, cramped synchronized, or chaotic). At 3 months' corrected age, fidgety general movements were classified as present or absent.", 'At 1 month, 53 (62%) infants had abnormal general movements, 46 of whom had poor repertoire general movements and 7 of whom had cramped synchronized general movements. At 3 months, 23 (25%) infants had absent fidgety movements. At both 1 and 3 months of age, consistently abnormal general movement classifications were related to increasing white matter abnormality on MRI. In contrast, there were no significant relationships between general movement classifications and gray matter abnormalities, either individually or in total.'] Is quality of general movements related to white matter pathology in very preterm infants? | qiaojin/PubMedQA | 2 | [
-2.048191547393799,
-0.29629069566726685,
1.5049526691436768
] |
['Acute liver failure (ALF) has various causes and is characterized by rapid hepatocyte dysfunction with development of encephalopathy in the absence of preexisting liver disease. Whereas most patients require liver transplantation to prevent the high mortality, some patients recover spontaneously and show complete liver regeneration. Because of the low incidence of ALF, however, the molecular mechanisms of liver dysfunction and regeneration are largely unknown. In this study, we investigated the role of apoptosis and caspases in 70 ALF patients using novel biomarkers that allow the detection of caspase activation in serum samples. Compared with healthy individuals, activation of caspases was strongly enhanced in ALF patients. Interestingly, patients with spontaneous recovery from ALF revealed a significantly higher activation of caspases than patients that required transplantation or died, although in the latter patients extensive DNA fragmentation and signs of nonapoptotic cell death were observed. In the spontaneous survivors, increased caspase activation was accompanied by elevated levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), important cytokines involved in liver regeneration.'] Is caspase activation associated with spontaneous recovery from acute liver failure? | qiaojin/PubMedQA | 2 | [
-2.5313808917999268,
-1.0287047624588013,
2.600921630859375
] |
['Response to chemotherapy may be determined by gene polymorphisms involved in metabolism of cytotoxic drugs. A plausible candidate is the gene for bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, an essential component of chemotherapy regimens for disseminated testicular germ-cell cancer (TC). We investigated whether the single nucleotide polymorphism (SNP) A1450G of the BLMH gene (rs1050565) is associated with survival.', 'Data were collected on survival and BLMH genotype of 304 patients with TC treated with bleomycin-containing chemotherapy at the University Medical Center Groningen, the Netherlands, between 1977 and 2003. Survival according to genotype was analyzed using Kaplan-Meier curves with log-rank testing and Cox regression analysis with adjustment for confounders.', 'BLMH gene SNP A1450G has a significant effect on TC-related survival (log-rank P = .001). The homozygous variant (G/G) genotype (n = 31) is associated with decreased TC related survival compared with the heterozygous variant (A/G; n = 133) and the wild-type (A/A; n = 140). With Cox regression the G/G genotype proves to be an unfavorable prognostic factor, in addition to the commonly used International Germ Cell Consensus Classification prognosis group, with a hazard ratio of 4.97 (95% CI, 2.17 to 11.39) for TC-related death. Furthermore, the G/G genotype shows a higher prevalence of early relapses.'] Is variation in bleomycin hydrolase gene associated with reduced survival after chemotherapy for testicular germ cell cancer? | qiaojin/PubMedQA | 2 | [
-2.103630304336548,
-1.5113898515701294,
2.671687602996826
] |
["The variable penetrance of ovarian cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify disease risk. The C to T transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring BRCA1 mutations.", "To investigate whether the PHB 3'UTR polymorphism also modifies hereditary ovarian cancer risk, we performed a case-control study among Polish women carrying one of the three common founder mutations (5382insC, 300 T > G, 4154delA) including 127 ovarian cases and 127 unaffected controls who had both breasts and ovaries intact. Controls were matched to cases by year of birth and BRCA1 mutation. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using conditional and penalized univariable and multivariable logistic regression.", "A comparison of the genotype frequencies between cases and controls revealed no association of the PHB 3'UTR _CT+TT genotypes with ovarian cancer risk (ORadj 1.34; 95% CI, 0.59-3.11)."] Is ovarian cancer risk in Polish BRCA1 mutation carriers associated with the prohibitin 3 ' untranslated region polymorphism? | qiaojin/PubMedQA | 2 | [
-2.0060720443725586,
-1.3300180435180664,
2.3763678073883057
] |
['The aim of this study was to investigate the effects of frequency modulated electromagnetic neural stimulation (FREMS), a recently developed safe and effective treatment of painful diabetic neuropathy, on cutaneous microvascular function.', 'Thirty-one patients with painful neuropathy were enrolled in a randomised, double-blind, crossover FREMS vs. placebo study; each received two series of 10 treatments of either FREMS or placebo in random sequence within no more than 3 weeks. Patients were studied at baseline, end of FREMS and placebo series, and after 4 months of follow-up. Cutaneous blood flow was measured by laser doppler flowmetry and partial tissue tension of oxygen (TcPO2) and carbonic anhydride (TcPCO2) by oxymetry at the lower extremities in basal resting conditions and as incremental response after thermal stimulation.', 'Crossover analysis showed no consistent differences between FREMS and placebo. After 4-month follow-up, a 52% increase of cutaneous blood flow was observed in resting conditions (P=.0086 vs. baseline), while no differences were observed as incremental flow after warming; compared with baseline, no significant differences were observed for TcPO2 and TcPCO2, both in resting conditions and as incremental response to warm.'] Does frequency-modulated electromagnetic neural stimulation enhance cutaneous microvascular flow in patients with diabetic neuropathy? | qiaojin/PubMedQA | 2 | [
-2.225160837173462,
-1.3283419609069824,
2.5921578407287598
] |
['Scale invariance is a property of scientific laws or objects that change in a prescribed fashion if measurements are scaled, and is often represented by a power-law relationship. Power laws suggest that events of a large magnitude will be rare, while small events will be much more common, and that a simple mathematical law relates "severity" with frequency. Scale invariance has been demonstrated in scientific fields including physics, social science, and economics. The authors use the complication of a posttonsillectomy hemorrhage to test whether this property is a feature of surgical complications.', 'Non-identifiable data were obtained regarding posttonsillectomy hemorrhage and subcategorized by calendar month, and the percentage rate of posttonsillectomy hemorrhage was calculated. The data were then transformed using a logarithmic function. This transformed data were plotted and a linear regression analysis was performed.', 'The 13-year period studied included 6,381 tonsillectomy procedures. The logarithm of the frequency of a given rate range of posttonsillectomy hemorrhage (y) was linearly related to the logarithm of the geometric mean of the rate range (x). The best-fit straight line was y = -1.3996x + 2.0624 with R2 = 0.851, n = 10, r = 0.922, and P < .001.'] Are variations in posttonsillectomy hemorrhage rates scale invariant? | qiaojin/PubMedQA | 2 | [
-0.8918591737747192,
-1.5542594194412231,
1.444903016090393
] |
['Arterial stiffness is a strong predictor of cardiovascular events and particularly of stroke. A likely explanation is the development of atherosclerotic lesions at the carotid level, favored by increased local stiffness. Another possibility involves cardiac consequences of aortic stiffness and particularly left atrial dilatation with its subsequent risk of atrial fibrillation (AF) and cerebral embolism.', 'The present study investigated the link between arterial stiffness, pulse pressure and left atrial size, a determinant of AF risk.', 'Arterial stiffness was determined from pulse wave velocity (PWV) and pulse pressure (PP). Left atrial size was also measured. Several potential confounders were taken into account including indices of ventricular remodeling and diastolic function (estimated by NT-Pro brain natriuretic peptide (NT-proBNP) levels).', 'Three-hundred and ten hypertensive patients, aged 53 +/- 13 years, were included. Mean 24-h blood pressure (BP) was 154 +/- 20 over 93 +/- 13 mmHg. Significant relationships were found between left atrial diameter (LAD) and PWV (r=0.27, P<0.001) and between LAD and 24-h PP (r=0.32, P<0.001). LAD was also correlated significantly, although not always tightly, with left ventricular dimensions, geometry and NT-proBNP. In two different multivariate models, LAD remained significantly correlated with PWV or with 24-h PP, independently of classical determinants like age, gender, body mass index, ventricular remodeling (i.e. dimensions and geometry) and filling pressure.'] Is arterial stiffness associated with left atrial size in hypertensive patients? | qiaojin/PubMedQA | 2 | [
-1.8074895143508911,
-1.4706498384475708,
2.306436538696289
] |
['Injury to the brain and spinal cord is one of the most catastrophic and costly occurrences in the Ontario health system. The objective of the present study was to evaluate the impact of past Ontario Neurotrauma Foundation (ONF) studentships and fellowships in terms of capacity building in the neurotrauma field in Ontario.', 'An online, cross sectional survey amongst past recipients of studentships and fellowships that terminated prior to July 2005. Explicit data were collected on various aspects of career development including current activity, awards and publications.', 'Thirty-six out of 42 (86%) eligible past trainees responded; 12 (33%) were Masters students, 12 (33%) were PhD students and 12 (33%) were Post-Doctoral students. A majority of the recipients (61%) are currently involved in neurotrauma-related activities (clinical, research and teaching) in more than 20% of their time, with no substantial differences between the degree groups. Half the recipients are currently involved in neurotrauma-related research in more than 20% of their time. The awardees published 1.5 peer-review manuscripts/person-year and received multiple awards. A high majority of our recipients (86%) feel that the ONF award had a substantial impact on their career.'] Do oNF trainee awards contribute to capacity building in neurotrauma? | qiaojin/PubMedQA | 1 | [
-1.5187342166900635,
1.5532927513122559,
-0.7017248868942261
] |
['Colorectal cancer (CRC) arising in patients under age 30 is a rare disease, and few cases have been reported within Li-Fraumeni kindreds. To determine how often alterations in the p53 pathway genes contribute to disease susceptibility, we have evaluated patients with early onset CRC for the presence of germline variants in the p53 gene and MDM2 SNP309.', 'Thirty-five patients with CRC diagnosed before age 30 were included in this study-based on tissue availability. DNA samples from peripheral blood leukocytes were analyzed for constitutional mutations and polymorphisms in p53 as well as polymorphisms in MDM2 SNP309.', 'No mutations were found in exons 4-10 of the p53 gene. The frequencies of polymorphisms in p53 and in MDM2 SNP309 did not differ from rates previously reported for normal control populations, and no polymorphism in either gene could be associated with early onset CRC.'] Are genetic variants in germline TP53 and MDM2 SNP309 associated with early onset colorectal cancer? | qiaojin/PubMedQA | 2 | [
-2.3015220165252686,
-0.9308252930641174,
2.285416603088379
] |
['Falls are the most frequently reported adverse event among frail nursing home residents and are an important resident safety issue. Incident reporting systems have been successfully used to improve quality and safety in healthcare. The purpose of this study was to test the effect of a systematically guided menu-driven incident reporting system (MDIRS) on documentation of post-fall evaluation processes in nursing homes.', 'Six for-profit nursing homes in southeastern USA participated in the study. Over a 4-month period, MDIRS was used in three nursing homes matched with another three nursing homes which continued using their existing narrative incident report to document falls. Trained geriatric nurse practitioner auditors used a data collection audit tool to collect medical record documentation of the processes of care for residents who fell. Multivariate analysis of covariance was used to compare the post-fall nursing care processes documented in the medical records.', '207 medical records of resident who fell were examined. Over 75% of the sample triggered at high risk for falls by the minimum data set. An adequate neurological assessment was documented for only 18.4% of residents who had experienced a fall. Although two-thirds of the sample had a diagnosis of incontinence, less than 20% of the records had incontinence-related interventions in the nursing care plan. Overall, there was more complete documentation of the post-fall evaluation process in the medical records in nursing homes using the MDIRS than in nursing homes using standard narrative incident reports (p<0.001).'] Does use of a fall incident reporting system to improve care process documentation in nursing homes? | qiaojin/PubMedQA | 1 | [
-1.3007383346557617,
0.23912516236305237,
0.15977612137794495
] |
['Comparative sequencing studies among a wide range of taxonomic groups, including fungi, have led to the discovery that reproductive genes evolve more rapidly than other genes. However, for fungal reproductive genes the question has remained whether the rapid evolution is a result of stochastic or deterministic processes. The mating-type (mat) genes constitute the master regulators of sexual reproduction in filamentous ascomycetes and here we present a study of the molecular evolution of the four mat-genes (mat a-1, mat A-1, mat A-2 and mat A-3) of 20 Neurospora taxa.', 'We estimated nonsynonymous and synonymous substitution rates of genes to infer their evolutionary rate, and confirmed that the mat-genes evolve rapidly. Furthermore, the evolutionary trajectories are related to the reproductive modes of the taxa; likelihood methods revealed that positive selection acting on specific codons drives the diversity in heterothallic taxa, while among homothallic taxa the rapid evolution is due to a lack of selective constraint. The latter finding is supported by presence of stop codons and frame shift mutations disrupting the open reading frames of mat a-1, mat A-2 and mat A-3 in homothallic taxa. Lower selective constraints of mat-genes was found among homothallic than heterothallic taxa, and comparisons with non-reproductive genes argue that this disparity is not a nonspecific, genome-wide phenomenon.'] Does the evolutionary trajectory of the mating-type ( mat ) genes in Neurospora relate to reproductive behavior of taxa? | qiaojin/PubMedQA | 1 | [
-2.7257418632507324,
1.021809458732605,
0.8494085669517517
] |
['The majority of our bones develop through the process of endochondral ossification that involves chondrocyte proliferation and hypertrophic differentiation in the cartilage growth plate. A large number of growth factors and hormones have been implicated in the regulation of growth plate biology, however, less is known about the intracellular signaling pathways involved. PI3K/Akt has been identified as a major regulator of cellular proliferation, differentiation and death in multiple cell types.'] Does the PI3K pathway regulate endochondral bone growth through control of hypertrophic chondrocyte differentiation? | qiaojin/PubMedQA | 2 | [
-2.6568899154663086,
-0.08154857903718948,
1.7639100551605225
] |
['Measurements of range of motion play a key role in shoulder research. The purpose of this study is to investigate intra-observer reproducibility of measurements of active and passive range of motion in patients with adhesive capsulitis.', 'The study was carried out in a population consisting of 32 patients with clinical signs of adhesive capsulitis. A specified measurement protocol was used, and range of motion in affected and non-affected shoulders was measured twice for each patient with a one-week interval.', 'For most of the investigated individual movements, test-retest differences in range of motion score of more than approximately 15 degrees are not likely to occur as a result of measurement error only. Point-estimates for the intraclass correlation coefficient ranged from 0.61 to 0.93.'] Is range of shoulder motion in patients with adhesive capsulitis ; intra-tester reproducibility acceptable for group comparisons? | qiaojin/PubMedQA | 2 | [
-1.4874082803726196,
-1.2513806819915771,
1.8782994747161865
] |
['Clostridial collagenase A (CCA) has been shown effective in degrading collagen in eschar tissue and promoting healing in partial-thickness burns. As there are also reports of fever, leukocytosis, increased C-reactive protein (CRP) levels and septic complications during treatment with CCA, we aimed to determine in rats whether CCA aggravates the systemic inflammatory response.', 'Rats with partial-thickness burns were randomly divided into groups with either no dressing (ND), povidone-iodine dressing (PID) or CCA dressing (CCAD). Body weights and temperatures, blood leukocyte counts, and serum levels of CRP, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), were measured at 0, 3, and 24h and days 3 and 7 from burn. Wounds were cultured on days 1, 3 and 7 and burn depth was evaluated on day 1.', 'Body weights for all groups were significantly lower after burn, with highest loss (25.5%) in the CCAD group. At 3h a significant drop in rectal temperature was noted in all groups. The CCAD group had higher rectal temperature levels than the PID group on days 3 and 7 (p<0.05). Changes in serum levels of CRP, IL-1 beta, IL-6 and TNF-alpha were not significant in the ND and PID groups; the CCAD group showed a significant rise in serum levels of CRP on day 1, of IL-6 on day 3 and of TNF-alpha on day 7. Wound infection was more common in CCAD group and increased on days 3 and 7, but this was insignificant.'] Does clostridial collagenase aggravate the systemic inflammatory response in rats with partial-thickness burns? | qiaojin/PubMedQA | 2 | [
-2.0683517456054688,
-1.4772248268127441,
2.529966354370117
] |
['Experimental models show that apolipoprotein CI (apoCI) binds and enhances the inflammatory response to endotoxin. We studied in patients undergoing cardiopulmonary bypass surgery (CPB) and experiencing endotoxemia during reperfusion whether plasma apoCI levels correlate with the inflammatory response and perioperative cytokine release.', 'Prospective, observational, clinical cohort study.', 'Operating room (OR) and intensive care unit (ICU) of a university hospital.', 'One hundred fifty-nine consecutive patients > 18 years of age (66% males =105), median age 65 and 67 years for males and females, respectively) undergoing elective cardiothoracic surgery with cardiopulmonary bypass.', 'None.', 'Baseline apoCI, apoCIII, total cholesterol and triglyceride levels, and perioperative endotoxin and TNF-alpha levels were determined.', 'High preoperative plasma apoCI, but not apoCIII, levels were associated (p < 0.05) with increased perioperative levels of TNF-alpha in patients experiencing endotoxemia. This association was not observed in patients without endotoxemia.'] Do preoperative apolipoprotein CI levels correlate positively with the proinflammatory response in patients experiencing endotoxemia following elective cardiac surgery? | qiaojin/PubMedQA | 2 | [
-2.368152618408203,
-1.3147408962249756,
2.7506749629974365
] |
['We discuss very recent studies that address the critical role of extracellular matrix in controlling the balance between vascular morphogenesis and regression. Much of this work suggests that a balance mechanism exists for controlling the extent of tissue vascularization involving downstream signaling events regulating endothelial cell behaviors in relation to their interactions with extracellular matrix molecules.', 'Endothelial gene expression changes and signaling lead to events that not only stimulate vascular morphogenesis but also suppress mechanisms mediated through pro-regression factors such as Rho kinase. At the same time, vascular networks are susceptible to regression mediated by factors such as matrix metalloproteinase-1, matrix metalloproteinase-10, thrombospondin-1, extracellular matrix matricryptic fragments and angiopoietin-2. Pericyte recruitment to such vascular tubes can prevent regression events by delivering molecules such as tissue inhibitor of metalloproteinase-3 and angiopoietin-1 that promote vascular stabilization by decreasing tube susceptibility to these regression stimuli.'] Does extracellular matrix mediate a molecular balance between vascular morphogenesis and regression? | qiaojin/PubMedQA | 2 | [
-2.907912254333496,
-0.3375098407268524,
2.371163845062256
] |
['In an effort to evaluate pharmacologic agents for optimal anticoagulant prophylaxis in patients undergoing free tissue transfer, we evaluated the efficacy of desirudin (Canyon Pharmaceuticals, Hunt Valley, MD), a recombinant hirudin that acts as a direct thrombin inhibitor, using a rat model of microvenous thrombosis.', 'Randomized, blinded study using an in vivo rat model of microvenous failure.', 'Thirty-two rats received either desirudin or saline in a randomized, blinded fashion 30 minutes prior to performance of a standardized thrombogenic procedure on rat femoral veins. Bleeding time, vessel patency, and presence of clot within the anastomosis were subsequently assessed. Appropriate statistical analyses were then performed.', 'There was a significant increase in vessel patency in rats treated preoperatively with desirudin compared to controls receiving saline (96.9% vs. 53.1%, P < .001). In evaluating patent vessels for non-occluding clot, 41.2% of control rats had non-obstructive clot at the site of anastomosis, versus 3.2% of rats treated with desirudin (P = .002). Bleeding times were longer in desirudin-treated rats than those that received saline (7.17 +/- 3 minutes vs. 5.15 +/- 1.2 minutes, P = .027).'] Does desirudin reduce the rate of microvenous thrombosis in a rat model? | qiaojin/PubMedQA | 2 | [
-1.857934832572937,
-1.48323655128479,
2.3314011096954346
] |
['To systematically review the account of center and provider effects in large surgical and interventional randomized controlled trials.', 'A systematic review of multicenter interventional randomized trials of 200+ patients. The search included Medline from 1 January 2000 through 11 October 2005 and a hand search of the bibliographies of retrieved articles. One author abstracted all data using standardized abstraction forms; a second reviewer assessed a random sample of reports as quality-assurance procedure.', 'Sixty-eight reports met inclusion criteria. The trials predominantly reported on cardiology (n=23, 34%). The number of participating providers was reported in 11 trials (16%). Both the performed control and performed interventional procedures were described in 43 trials (63%). The use of stratified random allocation on center was reported in 26 trials (38%) and on provider in 6 trials (9%). The analysis was adjusted for center in four trials (6%) and for provider in three trials (4%).'] Is the account for provider and center effects in multicenter interventional and surgical randomized controlled trials in need of improvement : a review? | qiaojin/PubMedQA | 2 | [
-2.3899190425872803,
-0.3899476230144501,
2.018651247024536
] |
['To evaluate the frequencies of T-lymphocytes expressing CC chemokine receptor-5 (CCR5(+) T-cells) and their relationship with frailty in older adults.', 'Case-control study with an age-, race-, and sex-matched design.', 'General Clinical Research Center.', 'Community-dwelling adults aged 72 and older from Baltimore, Maryland.', 'Frailty was determined using five validated criteria: weakness, slow walking speed, fatigue, low physical activity, and weight loss. Those meeting three or more of these five criteria were defined as frail and those with none as nonfrail. Complete blood counts were performed to obtain peripheral lymphocyte counts using an automated (Coulter) counter. Peripheral blood was collected for surface immunofluorescent staining of CCR5 and other T-cell markers.', 'Twenty-six frail and matched nonfrail participants (mean age+/-standard deviation 83.8+/-5.3, range 72-94) completed the study. Frail participants had higher CCR5(+), CCR5(+)CD8(+), and CCR5(+)CD45RO(-) T-cell counts than matched nonfrail controls (349+/-160/mm(3) vs 194+/-168/mm(3), P=.02; 208+/-98/mm(3) vs 105+/-62/mm(3), P=.02; and 189+/-149/mm(3) vs 52+/-36/mm(3), P=.01; respectively). Furthermore, there was a trend toward graded increase in these T-cell counts across the frailty scores in frail participants (e.g., CCR5(+)CD8(+) counts of 123+/-52/mm(3), 248+/-115/mm(3), and 360+/-215/mm(3) for those with frailty scores of 3, 4, and 5, respectively).'] Are t-lymphocytes expressing CC chemokine receptor-5 increased in frail older adults? | qiaojin/PubMedQA | 2 | [
-1.3796387910842896,
-1.5239393711090088,
1.893467903137207
] |
['Evidence for the dietary determinants of obesity in children is limited.', 'The objective was to identify a dietary pattern that explained dietary energy density (DED), fiber density (FD), and percentage of energy intake from fat and analyze its relation to fatness in children.', 'The subjects were 521 (at ages 5 and 9 y) and 682 (at ages 7 and 9 y) children participating in the Avon Longitudinal Study of Parents and Children. Diet was assessed with the use of 3-d diet diaries at ages 5 and 7 y. Reduced rank regression derived a dietary pattern with the use of DED, fiber, and fat intake as intermediate variables. Fat mass was measured at age 9 y with the use of dual-energy X-ray absorptiometry. Fat mass index (FMI) was calculated, and excess adiposity was defined (as the top quintile of logFMI).', 'Pattern score at ages 5 and 7 y was correlated with DED (r = 0.8), FD (r = -0.7), and percentage of energy intake from fat (r = 0.5). An increase of 1 SD of pattern score at ages 5 and 7 y, respectively, was associated with a 0.15-kg (95% CI: -0.1, 0.45 kg) and a 0.28-kg (95% CI: 0.05, 0.53 kg) higher fat mass at age 9 y, after controlling for confounders. The adjusted odds of excess adiposity at age 9 y for children in quintile 5 compared with quintile 1 of dietary pattern score at ages 5 and 7 y, respectively, were 2.52 (95% CI: 1.13, 6.08) and 4.18 (95% CI: 2.07, 9.38).'] Is energy-dense , low-fiber , high-fat dietary pattern associated with increased fatness in childhood? | qiaojin/PubMedQA | 2 | [
0.13627810776233673,
-1.5103907585144043,
0.4929794669151306
] |
['Physical activity is an essential component of diabetes management; however, exercise is associated with the risk for metabolic decompensation. The aim of the study was to analyze insulin response to the short-term intense exercise in middle-aged Type 2 diabetic patients treated with gliclazide.', 'Fourteen Type 2 diabetic patients (47.9+/-1.6 years, mean+/-S.E.M.), treated with gliclazide, and 14 healthy controls (45.1+/-1.0 years) were submitted to standard graduated submaximal (90% HR(max)) exercise treadmill testing at 2 h after standardized breakfast. Serum glucose, insulin, proinsulin, C peptide, growth hormone, insulin-like growth factor-1, and cortisol concentrations; and plasma lactate, glucagon, epinephrine, and norepinephrine concentrations were measured during the periexercise period up to the 60th min of the recovery period.', 'Significant hemodynamic (heart rate, systolic, and diastolic blood pressure), metabolic (lactate concentration), and hormonal (epinephrine and norepinephrine levels) responses to the exercise were similar in patients and healthy subjects. Glucose, insulin, and proinsulin levels were higher in the diabetic group at the preexercise and at all the next analyzed time points. The insulin concentration increased during the postprandial period in both groups and decreased subsequently during the exercise only in the control group, without concurrent C peptide decline. The C peptide-to-insulin ratio increased during the exercise and decreased immediately postexercise only in the control group.'] Is normal insulin response to short-term intense exercise abolished in Type 2 diabetic patients treated with gliclazide? | qiaojin/PubMedQA | 2 | [
-2.3420588970184326,
-1.2841753959655762,
2.70383882522583
] |
['To determine whether there is an association between transfusion of fresh frozen plasma and infection in critically ill surgical patients.', 'Retrospective study.', 'A 24-bed surgical intensive care unit in a university hospital.', 'A total of 380 non-trauma patients who received fresh frozen plasma from 2004 to 2005 were compared with 2,058 nontrauma patients who did not receive fresh frozen plasma.', 'None.', 'We calculated the relative risk of infectious complication for patients receiving and not receiving fresh frozen plasma. T-test allowed comparison of average units of fresh frozen plasma transfused to patients with and without infectious complications to describe a dose-response relationship. We used multivariate logistic regression analysis to evaluate the association between fresh frozen plasma and infectious complication, controlling for the effect of red blood cell transfusion, Acute Physiology and Chronic Health Evaluation II, and patient age. A significant association was found between transfusion of fresh frozen plasma and ventilator-associated pneumonia with shock (relative risk 5.42, 2.73-10.74), ventilator-associated pneumonia without shock (relative risk 1.97, 1.03-3.78), bloodstream infection with shock (relative risk 3.35, 1.69-6.64), and undifferentiated septic shock (relative risk 3.22, 1.84-5.61). The relative risk for transfusion of fresh frozen plasma and all infections was 2.99 (2.28-3.93). The t-test revealed a significant dose-response relationship between fresh frozen plasma and infectious complications (p = .02). Chi-square analysis showed a significant association between infection and transfusion of fresh frozen plasma in patients who did not receive concomitant red blood cell transfusion (p < .01), but this association was not significant in those who did receive red blood cells in addition to fresh frozen plasma. The association between fresh frozen plasma and infectious complications remained significant in the multivariate model, with an odds ratio of infection per unit of fresh frozen plasma transfused equal to 1.039 (1.013-1.067). This odds ratio resembled that noted for each unit of packed red blood cells, 1.074 (1.043-1.106).'] Is transfusion of fresh frozen plasma in critically ill surgical patients associated with an increased risk of infection? | qiaojin/PubMedQA | 2 | [
-1.6729912757873535,
-1.4069228172302246,
2.1107795238494873
] |
['Apoptosis appears to have an essential role in the control of testis germ cell number and Fas expression has been reported in apoptotic spermatocytes and spermatids. We investigated if Fas (CD95) was present on ejaculated human sperm and any relationship between Fas on sperm and the apoptotic marker Syto16.', 'Semen samples from 77 male partners of infertile couples were evaluated. Each sample was analysed both before and after semen preparation by conventional microscopical procedures and by flow cytometry (FC). A multiparameter FC analysis to assess simultaneously sperm concentration, sperm viability, sperm apoptosis, CD45 positive (leukocyte) and CD95 (Fas) positive cell concentration was carried out. A further 10 samples were studied by indirect immunofluorescence to confirm results.', 'The mean concentration of CD95 positive cells was very low (<1%), with no significant difference between normozoospermic and non-normozoospermic men. There was no correlation between apoptotic sperm and CD95 positive cell concentration. A linear correlation was found between CD95 positive cell and leukocyte (CD45 positive) concentration (r = 0.9946, P < 0.0001). CD95 mean fluorescence intensity of leukocytes was 10-fold greater than that of sperm and of isotypic control. Both incubation with activating anti-Fas antibody and betulinic acid induced apoptosis in leukocytes. Incubation with betulinic acid, but not with activating anti-Fas antibody, induced apoptosis in sperm. Pre-incubation with neutralizing anti-Fas antibody suppressed CD95 expression on leukocytes, whereas it did not change sperm CD95 peak fluorescence.'] Is fas receptor present on ejaculated human sperm? | qiaojin/PubMedQA | 2 | [
-2.066636800765991,
-1.4547302722930908,
2.5803608894348145
] |
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