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['Nicotine plays an important role in cigarette-smoke-associated airway disease. The present study was designed to examine if nicotine could induce airway hyperresponsiveness through kinin receptors, and if so, explore the underlying mechanisms involved.', 'Murine tracheal segments were cultured for 1, 2 or 4 days in serum-free DMEM medium in presence of nicotine (1 and 10 microM) or vehicle (DMSO). Contractile responses induced by kinin B1 receptor agonist, des-Arg9-bradykinin, and B2 receptor agonist, bradykinin, were monitored with myographs. The B1 and B2 receptor mRNA expressions were semi-quantified using real-time PCR and their corresponding protein expressions assessed with confocal-microscopy-based immunohistochemistry. Various pharmacological inhibitors were used for studying intracellular signaling pathways.', 'Four days of organ culture with nicotine concentration-dependently increased kinin B1 and B2 receptor-mediated airway contractions, without altering the kinin receptor-mediated relaxations. No such increase was seen at day 1 or day 2. The airway contractile responses to 5-HT, acetylcholine and endothelin receptor agonists remained unaffected by nicotine. Two different neuronal nicotinic receptor antagonists MG624 and hexamethonium blocked the nicotine-induced effects. The enhanced contractile responses were accompanied by increased mRNA and protein expression for both kinin receptors, suggesting the involvement of transcriptional mechanisms. Confocal-microscopy-based immunohistochemistry showed that 4 days of nicotine treatment induced activation (phosphorylation) of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38. Inhibition of JNK with its specific inhibitor SP600125 abolished the nicotine-induced effects on kinin receptor-mediated contractions and reverted the enhanced receptor mRNA expression. Administration of phosphodiesterase inhibitors (YM976 and theophylline), glucocorticoid (dexamethasone) or adenylcyclase activator (forskolin) suppressed the nicotine-enhanced airway contractile response to des-Arg9-bradykinin and bradykinin.'] Does nicotine enhance murine airway contractile responses to kinin receptor agonists via activation of JNK- and PDE4-related intracellular pathways?
qiaojin/PubMedQA
2
[ -2.4376914501190186, -1.391127586364746, 2.862360954284668 ]
['The involvement of p38 MAPK in mediating factors that may produce aortic valve disease is unknown. Angiotensin II (Ang II) has been implicated in the development of aortic stenosis through either the generation of free radicals and/or the modulation of inflammatory responses. A variety of proinflammatory factors utilize Toll-like receptors, and these may also play a role in the development of aortic valve disease.', 'Valve interstitial cells (VICs) were cultured from porcine aortic valves. Cells were treated with Ang II, 3-morpholinosydnonimine (SIN-1), which liberates NO and superoxide anion generating peroxynitrite, or the lipopetide Toll-like receptor-2 (TLR-2) agonist Pam3CSK4.', 'In response to Ang II (1 microM), MAPK phosphorylation levels were increased by 3.5-fold after 15 min, peaked at 4.6-fold after 60 min, and decreased to 1.9-fold greater than control after 120 min of treatment. In response to SIN-1, phosphorylation levels were increased progressively throughout the 90 min of treatment and were significantly (p < 0.05) twofold (1.9 +/- 0.3) greater than control or native p38 MAPK (2.3 +/- 0.4) after 90 min. SB202190, a relatively selective inhibitor of the p38a MAPK isoform, reduced SIN-1-induced p38 MAPK phosphorylation. In contrast, there was a rapid and marked decline in phosphorylated p38 MAPK, in response to Pam3CSK4 that was evident at 30 min; after 90 min, the p38 MAPK level was 85% lower than baseline.'] Is p38 MAP kinase in valve interstitial cells activated by angiotensin II or nitric oxide/peroxynitrite , but reduced by Toll-like receptor-2 stimulation?
qiaojin/PubMedQA
2
[ -2.227283239364624, -1.4352158308029175, 2.6833534240722656 ]
['To investigate whether alanine aminotransferase (ALT), even within the reference range, is associated with atherosclerotic burden in apparently healthy adults.', 'This was an observational study performed on 830 healthy individuals with normal ALT concentration (<or=40U/L). Atherosclerotic burden was assessed by carotid arterial intima-media thickness (IMT). All subjects were divided according to the quartile based on their ALT concentrations.', 'Despite all subjects having a normal ALT concentration, ultrasonographic liver steatosis was observed in 48.4% and 36.7% of men and women, respectively. In both genders, subjects in the highest quartile of ALT concentration had a significantly higher waist circumference, triglyceride concentration, HOMA-IR, a higher prevalence of metabolic syndrome, and a greater severity of ultrasonographic liver steatosis than did those in the lower quartiles. In women, the carotid IMT increased significantly with increasing quartiles of ALT concentration (0.62+/-0.14mm, 0.66+/-0.15mm, 0.69+/-0.15mm, vs. 0.72+/-0.24mm; P for trend<0.001). Based on multivariate regression analysis, the serum ALT, even within the normal range, was associated with the carotid IMT in both men and women, and independently of traditional cardiovascular risk factors.'] Is normal range of alanine aminotransferase concentration associated with carotid atherosclerosis?
qiaojin/PubMedQA
2
[ -1.8314319849014282, -1.4951785802841187, 2.374706506729126 ]
['Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of brain CDP-diacylglycerol synthase - the enzyme that catalyzes the physiological synthesis of CDP-diacylglycerol.', 'Imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of CDP-diacylglycerol and phosphatidylinositides in PC12 cells. Rat forebrain tissues depleted of serotonin by pretreatment with p-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. With fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. Each drug significantly increased the enzymatic activity of CDP-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues.'] Does antidepressant stimulation of CDP-diacylglycerol synthesis require monoamine reuptake inhibition?
qiaojin/PubMedQA
2
[ -2.4962000846862793, -1.1749956607818604, 2.7069783210754395 ]
['Although alopecia is a commonly recognized problem affecting many captive Rhesus macaque colonies, there is no consensus as to the underlying etiology or appropriate course of management.', 'We performed skin biopsies to assess underlying pathology in alopecic Rhesus macaques and performed immunohistochemical and metachromatic staining of these biopsies to assess the cellular infiltrates.', 'Alopecia is associated with superficial dermal perivascular mononuclear cell infiltrates and skin pathology consistent with chronic hypersensitivity dermatitis. The inflammation is primarily composed of CD4+ cells admixed with histiocytes and mast cells. Inflammation is correlated with degree of alopecia. Further analysis in different groups of macaques revealed that animals born outdoors or infected with lung mites had reduced dermal inflammatory cell infiltrates and a lower incidence of alopecia.'] Does alopecia in Rhesus macaques correlate with immunophenotypic alterations in dermal inflammatory infiltrates consistent with hypersensitivity etiology?
qiaojin/PubMedQA
2
[ -2.6790273189544678, -1.0270428657531738, 2.8028674125671387 ]
['To analyse, in a population-based study, the association between parental fear of hypoglycaemia and (i) the prevalence of hypoglycaemia and diabetes treatment factors in children with Type 1 diabetes and (ii) emotional distress in mothers and fathers.', 'Mothers (n = 103) and fathers (n = 97) of 115 children with Type 1 diabetes (1-15 years old) participated in the study. In addition to demographic and disease-specific data, the participants completed the Hypoglycaemia Fear Survey-Parent version (HFS-P) (worry and behaviour subscales) and the Hopkins Symptom Checklist-25 items (HSCL-25) to measure emotional distress.', "A higher HFS-P worry score was associated with higher glycated haemoglobin (HbA(1c)), a higher frequency (>or= 7) of what parents experienced as problematic hypoglycaemic events during the past year and co-morbid disease in the child. A higher HFS-P behaviour score was associated with children receiving insulin injections compared with using an insulin pump and a higher frequency (>or= 7 per day) of blood glucose measurements. The mothers had higher scores than the fathers in both the worry and behaviour subscales. The mothers' and the fathers' HFS-P worry scores correlated significantly with their HSCL-25 scores."] Is fear of hypoglycaemia in mothers and fathers of children with Type 1 diabetes associated with poor glycaemic control and parental emotional distress : a population-based study?
qiaojin/PubMedQA
2
[ -2.261420965194702, -0.3978867828845978, 1.8463258743286133 ]
['We studied the signal transduction of atrial structural remodeling that contributes to the pathogenesis of atrial fibrillation (AF).', 'Fibrosis is a hallmark of arrhythmogenic structural remodeling, but the underlying molecular mechanisms are incompletely understood.', 'We performed transcriptional profiling of left atrial myocardium from patients with AF and sinus rhythm and applied cultured primary cardiac cells and transgenic mice with overexpression of constitutively active V12Rac1 (RacET) in which AF develops at old age to characterize mediators of the signal transduction of atrial remodeling.', 'Left atrial myocardium from patients with AF showed a marked up-regulation of connective tissue growth factor (CTGF) expression compared with sinus rhythm patients. This was associated with increased fibrosis, nicotinamide adenine dinucleotide phosphate oxidase, Rac1 and RhoA activity, up-regulation of N-cadherin and connexin 43 (Cx43) expression, and increased angiotensin II tissue concentration. In neonatal rat cardiomyocytes and fibroblasts, a specific small molecule inhibitor of Rac1 or simvastatin completely prevented the angiotensin II-induced up-regulation of CTGF, Cx43, and N-cadherin expression. Transfection with small-inhibiting CTGF ribonucleic acid blocked Cx43 and N-cadherin expression. RacET mice showed up-regulation of CTGF, Cx43, and N-cadherin protein expression. Inhibition of Rac1 by oral statin treatment prevented these effects, identifying Rac1 as a key regulator of CTGF in vivo.'] Does rac1-induced connective tissue growth factor regulate connexin 43 and N-cadherin expression in atrial fibrillation?
qiaojin/PubMedQA
2
[ -2.4655110836029053, -1.3538060188293457, 2.839144706726074 ]
['Coeliac disease is frequently diagnosed after a long delay resulting in increased morbidity and mortality.', 'To define the parameters which have the highest impact on the cost-effectiveness of mass screening for coeliac disease.', 'A Markov model examined a coeliac disease screening programme of the healthy young-adult general population compared with a no-screening strategy. The main outcome measures were quality adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). Effects of variables were examined using sensitivity analyses.', 'The screening strategy resulted in a gain of 0.0027 QALYs. The ICER of screening vs. no-screening strategy was US$48,960/QALYs. The variables with the largest impact on cost effectiveness were: the time delay from symptom onset to diagnosis, the utility of adherence to a gluten-free diet (GFD) and the prevalence of coeliac disease. Screening would be cost-effective if the time delay to diagnosis is longer than 6 years and utility of GFD adherence is greater than 0.978.'] Is cost effectiveness of mass screening for coeliac disease determined by time-delay to diagnosis and quality of life on a gluten-free diet?
qiaojin/PubMedQA
2
[ -1.3593865633010864, -1.3317676782608032, 1.6558313369750977 ]
['To verify whether chromosomes 1, 4, and 6 have a role in determining oocyte viability.', 'Retrospective study.', 'Reproductive Medicine Unit, Società Italiana Studi Medicina della Riproduzione, Bologna, Italy.', 'Eighty-five patients with a normal karyotype who had undergone an assisted conception cycle with chromosomal analysis of first polar bodies for chromosomes 13, 15, 16, 18, 21, and 22 (first panel). A clinical pregnancy was obtained in 43 patients, whereas 42 patients were not pregnant.', 'After conclusion of clinical pregnancies to delivery or abortion, first polar bodies from 85 patients were reanalyzed for chromosomes 1, 4, and 6 (second panel).', 'Aneuploidy frequency, clinical pregnancy outcome.', 'The aneuploidy rate contributed by chromosome 1, 4, and 6 to the oocytes that were normal for the first panel was significantly higher in the nonpregnant patients (28%) versus the pregnant patients (11%), whereas no difference resulted between term pregnancies (11%) and abortions (10%). This trend was also observed when studying the first polar bodies from the oocytes that originated the transferred embryos. The frequency of aneuploidy for chromosomes 1 and 4 was comparable with that of chromosomes 15, 16, 21, and 22.'] Are aneuploidies of chromosomes 1 , 4 , and 6 compatible with human embryos ' implantation?
qiaojin/PubMedQA
2
[ -2.0522029399871826, -0.4738066494464874, 1.687666654586792 ]
['Cell-cell adhesion and intracellular trafficking are regulated by signaling pathways from small GTPases of the Rho, Arf, and Rab subfamilies. How signaling from distinct small GTPases are integrated in a given process is poorly understood.', 'We find that a TBC/RabGAP protein, Armus, integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Armus binds specifically to activated Rac1 and its C-terminal TBC/RabGAP domain inactivates Rab7. Thus, Armus is a novel Rac1 effector and a bona fide GAP for Rab7 in vitro and in vivo, a unique and previously unreported combination. Arf6 activation efficiently disrupts cell-cell contacts and is known to activate Rac1 and Rab7. Arf6-induced E-cadherin degradation is efficiently blocked by expression of Armus C-terminal domain or after Armus RNAi. Coexpression of Arf6 with dominant-negative Rab7 or Rac1 also inhibits junction disassembly. Importantly, Armus RabGAP expression also prevents EGF-induced scattering in keratinocytes, a process shown here to require Arf6, Rac1, and Rab7 function. To our knowledge, this is the first report to demonstrate a molecular and functional link between Rac1 and Rab7.'] Is armus a Rac1 effector that inactivates Rab7 and regulates E-cadherin degradation?
qiaojin/PubMedQA
2
[ -2.471954584121704, -0.9709513783454895, 2.5022566318511963 ]
['Studies assessing the efficacy of azathioprine (AZA) in steroid-dependent ulcerative colitis (UC) are scarce. The aim of this study was to assess the long-term efficacy and safety of AZA in patients with steroid-dependent UC, as well as factors associated with sustained response.', 'In this prospective observational study 46 adult subjects with steroid-dependent UC were included for AZA therapy during a 12-month period. AZA dosage was adjusted according to clinical response and occurrence of adverse events. Steroid therapy was tapered according to protocol. The primary endpoint was the rate of steroid-free remission to AZA at the end of 12 months. Secondary endpoints included clinical relapse, cumulative steroid dose and safety of treatment.', 'On an intention-to-treat basis, the proportion of patients remaining in steroid-free remission at the end of 12 months was 0.54. The median time until complete steroid withdrawal was 5 months. A significant decrease in the relapse rate and in requirement for steroids were observed during 12 months on AZA compared with the prior year (P=0.000). Demographic, dose of AZA, steroid use, and disease-related data did not correlate with remission. Only disease duration <24 months was associated to steroid-free remission (P=0.03, OR 3.60 95% CI 1.95-9.74). Serious adverse events related to AZA were uncommon.'] Is early onset steroid-dependent ulcerative colitis a predictor of azathioprine response : a longitudinal 12-month follow-up study?
qiaojin/PubMedQA
2
[ -1.967764139175415, -1.3840985298156738, 2.4195995330810547 ]
['The transcriptional regulatory network involved in low temperature response leading to acclimation has been established in Arabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10 degrees C), an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach.', 'Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10 degrees C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters.Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2 spikes within the initial 6 to 12 hours. Oxidative-independent responses involve DREB/CBF, RAP2 and RAV1 factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters.'] Does transcriptional regulatory network triggered by oxidative signals configure the early response mechanisms of japonica rice to chilling stress?
qiaojin/PubMedQA
2
[ -2.7153704166412354, -0.7193232774734497, 2.4776039123535156 ]
['Biallelic MUTYH exon 7 and 13 mutations are associated with a high frequency of somatic K-ras gene guanine to thymine transversion mutations at codon 12 position 1 in MUTYH-associated polyposis patients who have increased risk of colon cancer. The purpose of this study was to determine if a similar association exists between exon 7 and 13 MUTYH mutations and pancreatic cancer.', 'Genomic DNA samples from 140 patients with pancreatic cancer and 107 controls were sequenced and analyzed for mutations in each of MUTYH exons 7 and 13.', 'Two patients with pancreatic cancer were identified as heterozygous for a MUTYH Y165C germline mutation. One pancreatic cancer patient was heterozygous for a G382D mutation and an additional patient was heterozygous for a novel missense mutation, L406M. No biallelic mutations were identified in pancreatic cancer or control subjects.'] Are mUTYH exon 7 and 13 mutations associated with colorectal cancer ( MAP syndrome ) commonly associated with sporadic pancreatic cancer?
qiaojin/PubMedQA
2
[ -2.3640005588531494, -1.0916887521743774, 2.502854585647583 ]
['We evaluated the impact of the initial intravenous fluid resuscitation rate within the first 24 h of presentation to the emergency room on important outcomes in severe acute pancreatitis.', "Patients presenting directly with a diagnosis of severe acute pancreatitis were identified retrospectively. Patients were divided into two groups - those who received >or=33% ('early resuscitation') and <33% ('late resuscitation') of their cumulative 72-hour intravenous fluid volume within the first 24 h of presentation. The primary clinical outcomes were in-hospital mortality, development of persistent organ failure, and duration of hospitalization.", "17 patients were identified in the 'early resuscitation' group and 28 in the 'late resuscitation' group and there were no baseline differences in clinical characteristics between groups. Patients in the 'late resuscitation' group experienced greater mortality than those in the 'early resuscitation' group (18 vs. 0%, p < 0.04) and demonstrated a trend toward greater rates of persistent organ failure (43 vs. 35%, p = 0.31). There was no difference in the total amount of fluid given during the first 72 h."] Does faster rate of initial fluid resuscitation in severe acute pancreatitis diminish in-hospital mortality?
qiaojin/PubMedQA
2
[ -0.6406601667404175, -0.8765296339988708, 0.5972877740859985 ]
['Tinnitus is a common and disturbing condition, reported by 10% to 20% of the general population.', 'The authors sought to determine personality characteristics associated with tinnitus patients versus a control group of ear-nose-throat (ENT) patients without tinnitus.', 'Adult chronic tinnitus sufferers (N=265) and ENT patients without tinnitus (N=265) participated in a cross-sectional study. The authors evaluated personality characteristics with tests for distressed personality (Type D), neuroticism, extraversion, and emotional stability.', 'As compared with control subjects, tinnitus patients had statistically significant and clinically relevant higher levels of neuroticism, negative affectivity, and social inhibition, on one hand, and lower levels of extraversion and emotional stability on the other hand. Also, tinnitus patients were more likely to have a type D personality.'] Is the distressed ( Type D ) personality independently associated with tinnitus : a case-control study?
qiaojin/PubMedQA
2
[ -2.6660072803497314, -0.26658210158348083, 2.0856404304504395 ]
['Myotonic dystrophy type 2 (DM2) is caused by a [CCTG]n intronic expansion in the zinc finger protein 9 (ZNF9) gene. As for DM1, sharing with DM2 a similar phenotype, the pathogenic mutation involves a transcribed but untranslated genomic region, suggesting that RNA toxicity may have a role in the pathogenesis of these multisystem disorders by interfering with common cellular mechanisms. However, haploinsufficiency has been described in DM1 and DM2 animal models, and might contribute to pathogenesis. The aim of the present work was therefore to assess ZNF9 protein expression in rat tissues and in human muscle, and ZNF9 subcellular distribution in normal and DM2 human muscles.', 'Polyclonal anti-ZNF9 antibodies were obtained in rabbit, high pressure liquid chromatography-purified, and used for Western blot, standard and confocal immunofluorescence and immunogold labelling electron microscopy on a panel of normal rat tissues and on normal and DM2 human muscles.', 'Western blot analysis showed that ZNF9 is ubiquitously expressed in mammalian tissues, and that its signal is not substantially modified in DM2 muscles. Immunofluorescence studies showed a myofibrillar distribution of ZNF9, and double staining with two non-repetitive epitopes of titin located it in the I bands. This finding was confirmed by the visualization of ZNF9 in close relation with sarcomeric thin filaments by immunogold labelling electron microscopy. ZNF9 distribution was unaltered in DM2 muscle fibres.'] Is the myotonic dystrophy type 2 ( DM2 ) gene product zinc finger protein 9 ( ZNF9 ) associated with sarcomeres and normally localized in DM2 patients ' muscles?
qiaojin/PubMedQA
2
[ -2.3834402561187744, -1.392201542854309, 2.858595848083496 ]
['The clinical and MRI presentation differs between earlier- and later-onset pediatric multiple sclerosis (MS), whereas the effect of age on the CSF inflammatory profile is unknown and may contribute to delayed diagnosis.', 'To compare the CSF cellular and immunoglobulin G (IgG) profiles between earlier- and later-onset pediatric MS.', 'We queried the databases of 6 pediatric MS centers for earlier-onset (onset <11 years) and later-onset (> or = 11 and <18 years) patients with MS or clinically isolated syndrome who underwent CSF analysis within the first 3 months of presentation (observational study). We compared CSF white blood cell (WBC) differential count, IgG index, and IgG oligoclonal bands between age groups.', 'We identified 40 earlier-onset (mean age at onset = 7.2 +/- 2.7 years, 60% females) and 67 later-onset pediatric MS patients (15.1 +/- 1.7 years, 63% females). Although WBC count tended to be higher in earlier-onset patients (median = 9/mm(3) [0-343] vs 6 [0-140], p = 0.15), they had a lower proportion of lymphocytes (70% [0-100] vs 93% [0-100] of WBCs, p = 0.0085; difference = +3% per 1-year increase of age, p = 0.0011) and higher proportion of neutrophils than later-onset patients (0.5% [0-75] vs 0% [0-50] of WBCs, p = 0.16; difference = -1% per 1-year increase of age, p = 0.033). In earlier-onset disease, fewer patients had an elevated IgG index than in the later-onset group (35% vs 68% of patients, p = 0.031).'] Do younger children with MS have a distinct CSF inflammatory profile at disease onset?
qiaojin/PubMedQA
2
[ -0.6167154312133789, -1.6025381088256836, 1.2837324142456055 ]
['To clarify whether a three-dimensional-gradient echo (3D-GRE) or spin echo (SE) sequence is more useful for evaluating sellar lesions on contrast-enhanced T1-weighted MR imaging at 3.0Tesla (T).', 'We retrospectively assessed contrast-enhanced T1-weighted images using 3D-GRE and SE sequences at 3.0T obtained from 33 consecutive patients with clinically suspected sellar lesions. Two experienced neuroradiologists evaluated the images qualitatively in terms of the following criteria: boundary edge of the cavernous sinus and pituitary gland, border of sellar lesions, delineation of the optic nerve and cranial nerves within the cavernous sinus, susceptibility and flow artifacts, and overall image quality.', 'At 3.0T, 3D-GRE provided significantly better images than the SE sequence in terms of the border of sellar lesions, delineation of cranial nerves, and overall image quality; there was no significant difference regarding the boundary edge of the cavernous sinus and pituitary gland. In addition, the 3D-GRE sequence showed fewer pulsation artifacts but more susceptibility artifacts.'] Do three-dimensional gradient echo versus spin echo sequence in contrast-enhanced imaging of the pituitary gland at 3T?
qiaojin/PubMedQA
2
[ -1.9200960397720337, -1.44032883644104, 2.3765268325805664 ]
['Renal insufficiency (RI) seems to be a source of complications after carotid endarterectomy (CEA). However, published studies do not use a common definition of RI. Our objective was to analyze the effects of RI on carotid surgery using three classifications of renal function.', 'Using a prospective database, we studied renal function and postoperative complications in patients operated on between January 1, 2003 and December 31, 2008. Renal function was studied using the level of plasma creatinine, creatinine clearance calculated according to the Cockcroft formula, and to the Modification of Diet in Renal Disease (MDRD) equation. For each method, the patients were divided into three groups: normal renal function, moderate RI, and severe RI. The principal judgment criterion was the 30-day non-fatal stroke and death rate.', 'The analysis concerned 961 CEAs carried out in 901 patients. The 30-day non-fatal stroke and death rate was 2%. In the analysis of renal function using the level of creatinine, there was no statistical difference between the groups in the 30-day stroke and death rate (normal renal function: 1.8%, moderate: 2.7%, severe: 8.3%, P = .21). The analysis of renal function according to creatinine clearance calculated using the Cockcroft formula showed that in the severe RI group, the stroke and death rate was higher than in the other two groups (normal renal function: 1.7%, moderate RI: 1.4%, severe RI: 7.5%, P = .004). Analysis using the MDRD formula showed similar differences between the severe RI group and the other two with a higher rate of 30-day stroke and death (normal renal function: 1.4%, moderate RI: 1.7%, severe RI: 12.5%, P < .001). Subgroup analysis showed that among patients with severe RI according to the creatinine clearance, those with symptomatic carotid stenosis had the highest incidences of non-fatal stroke and death (Cockcroft, n = 19: 21.1%, MDRD, n = 10: 40%).'] Is the impact of renal insufficiency on the outcome of carotid surgery influenced by the definition used?
qiaojin/PubMedQA
2
[ -1.585710883140564, -1.3938655853271484, 1.9652817249298096 ]
['In chronic thromboembolic pulmonary hypertension (CTEPH), dyspnea is considered to be related to increased dead space ventilation caused by vascular obstruction. Pulmonary endarterectomy releases the thromboembolic obstruction, thereby improving regional pulmonary blood flow. We hypothesized that pulmonary endarterectomy reduces dead space ventilation and that this reduction contributes to attenuation of dyspnea symptoms.', 'In this follow-up study we assessed dead space ventilation, hemodynamic severity of disease, and symptomatic dyspnea in 54 consecutive CTEPH patients, before and 1 year after pulmonary endarterectomy. Dead space ventilation was calculated using the Bohr-Enghoff equation. Dyspnea was assessed by Borg scores and the New York Heart Association functional classification.', 'Preoperatively, dead space ventilation was increased (0.40 +/- 0.07) and correlated with severity of disease (mean pulmonary artery pressure: r = 0.49, p < 0.001; total pulmonary resistance: r = 0.53, p < 0.001), and resting (r = 0.35, p < 0.05) and post-exercise Borg dyspnea scores (r = 0.44, p < 0.01). Postoperatively, dead space ventilation (0.33 +/- 0.08, p < 0.001) and dyspnea symptoms decreased significantly. Changes in symptomatic dyspnea were independently associated with changes in pulmonary hemodynamics and absolute dead space.'] Does pulmonary endarterectomy improve dyspnea by the relief of dead space ventilation?
qiaojin/PubMedQA
2
[ -2.2118642330169678, -1.2304039001464844, 2.4624857902526855 ]
['To find out the mechanisms of HBx gene inducing oval cell malignant transformation into hepatoma carcinoma cell.', 'The changes of morphology, cell cycle, differentiated markers, c-myc and TGF-alpha in pEGFP-HBx oval cells strain, which stably expressed HBx gene, were studied by inversion phase contrast microscope and transmission electron microscopy, flow cytometry, periodic acid-schiff (PAS) staining, soft agar growth assay, real-time PCR, immunocytochemistry. pEGFP-oval cells and LE/6 oval cells were used as control groups.', '(1) The pEGFP-HBx oval cells showed bigger in size with malformed nucleus as compared with control groups. (2) Flow cytometry showed that, in contrast with the control groups, the proportion of pEGFP-HBx oval cells arrested in G0/G1 phase decreased but in S or G2/M phase rose. Moreover, the population of aneuploid cells increased obviously. (3) PAS staining showed that there were many glycogen granules in the cytoplasm of pEGFP-HBx oval cell. (4) The pEGFP-HBx oval cell formed colonies in the soft agar. (5) Compared with the control groups, the expression of HNF-4 alpha, AFP, c-myc and TGF-alpha rose obviously, whereas the expression of CK-7 and CK-19 decreased. And the expression of cps1 mRNA was not in the extent of detection.'] Does [ The studies of hepatitis B virus X gene induce oval cell malignant transformation ]?
qiaojin/PubMedQA
2
[ -2.3263885974884033, -1.2733964920043945, 2.687162399291992 ]
['Aneurysmal subarachnoid haemorrhage (SAH) has recently been reported as a common cause of chronic hypopituitarism, and introduction of routine neuroendocrine screening has been advocated. We aimed at estimating the risk of hypopituitarism after SAH using strict criteria including confirmatory testing in case of suggested insufficiency.', 'Cross-sectional evaluation with a nested prospective subgroup. Patients and measurements Endocrine evaluation was performed at a median of 14 months (range 11-26) post-SAH in 62 patients with SAH and 30 healthy controls. Twenty-six patients were followed prospectively (median 7 days, and 12 months post-SAH). Endocrine evaluation included baseline evaluation, which was combined with an insulin tolerance test (ITT) or, if contraindicated, GHRH + arginine tests and a standard ACTH test at evaluation 1-2 years post-SAH. Pituitary insufficiencies were confirmed by re-evaluation.', 'Early post-SAH hormone alterations mimicking central hypogonadism were present in 58% of the patients and associated with a worse clinical state (P < 0.05). One to 2 years post-SAH, initial neuroendocrine evaluation identified seven patients (11%) with abnormal results; three had free T4 and TSH suggestive of central hypothyroidism, three men had testosterone below 10 nm, and one had an insufficient GH and cortisol response to the ITT. None of these abnormalities was confirmed upon confirmatory testing.'] Is hypopituitarism uncommon after aneurysmal subarachnoid haemorrhage?
qiaojin/PubMedQA
2
[ -2.290515422821045, -1.4125699996948242, 2.7631258964538574 ]
["Chronic pain is associated with depression. Self-treatment of depression with herbal over-the-counter medicine St John's wort makes pain patients prone to drug interactions.", "The aim of this study was to assess the potential of St John's wort to alter the CYP3A-mediated metabolism of a mu-opioid receptor agonist, oxycodone.", "The study design was placebo-controlled, randomized, cross-over with two phases at intervals of 4 weeks and was conducted with 12 healthy participants. St John's wort (Jarsin) or placebo was administered t.i.d. for 15 days and oral oxycodone hydrochloride 15 mg on day 14. Oxycodone pharmacokinetics and pharmacodynamics were compared after St John's wort or placebo. Behavioural and analgesic effects were assessed with subjective visual analogue scales and cold pressor test. Plasma drug concentrations were measured from 0 to 48 h, behavioural and analgesic effects from 0 to 12 h.", "Following St John's wort administration the oxycodone AUC decreased 50% (p<0.001). Oxycodone elimination half-life shortened from a mean+/-SD 3.8+/-0.7 to 3.0+/-0.4h (p<0.001). The self-reported drug effect of oxycodone as measured by AUEC(0-12) decreased significantly (p=0.004). Differences between St John's wort and placebo phases in cold pain threshold and intensity AUEC(0-12) were not observed."] Does st John 's wort greatly reduce the concentrations of oral oxycodone?
qiaojin/PubMedQA
2
[ -1.9264098405838013, -1.5158920288085938, 2.4325931072235107 ]
['Cough is an essential innate protective behavior, which is experienced by even healthy individuals. The mechanism of cough triggered by bronchoconstriction is not yet clear. The aim of this study was to investigate the relation between bronchoconstriction and cough caused by methacholine (Mch) inhalation in typical asthmatics and normal healthy subjects.', 'We measured bronchial responsiveness to Mch and counted the number of coughs induced by Mch inhalation in 15 typical asthmatics and 20 normal subjects.', 'After inhalation of Mch at the concentration causing 20% or more decrease in forced expiratory volume in 1 second (FEV(1)) (PC(20)-FEV(1)), coughs were provoked in normal subjects (number of cough: 22.5/32 min, range: 3.3-45). Conversely, coughs were hardly provoked in typical asthmatics (median number of cough: 2/32 min, range: 0-4).'] Is bronchoconstriction-triggered cough impaired in typical asthmatics?
qiaojin/PubMedQA
2
[ -1.2654327154159546, -0.6988133788108826, 1.1006784439086914 ]
['Airway hyperresponsiveness (AHR) is the characteristic functional abnormality of asthma, and previous studies have shown the potential for AHR to be influenced by psychological factors, yet the relationship between anxiety and/or depression and AHR remains unclear in patients with asthma.', 'To explore the relationship between psychological status and AHR in asthma patients.', 'In a cross-sectional study, 168 adult subjects were recruited with physician-diagnosed uncontrolled asthma and a positive result for AHR in methacholine (Mch) challenge test. Psychological status, asthma control, and asthma quality of life were assessed using Zung self-rating anxiety/depression scale, asthma control test (ACT), and asthma quality of life questionnaire (AQLQ), respectively. AHR severity was evaluated and quantified by the provocative concentration of Mch, which evoked a given decrease of 20% in FEV(1).', 'A total of 70.23% of recruited patients (n = 118) met the diagnostic criteria for anxiety and/or depression. There was a trend between negative psychological status and AHR in asthma patients that did not reach statistical significance, but no independent effects of negative mood states (anxiety, depression, or both) on AHR were established. Further, analyses revealed that only anxiety is associated with worse asthma control (p = 0.029), and a significant interaction effect of depression and anxiety accounted for lower asthma-related quality-of-life scores (p < 0.001).'] Is psychological status in uncontrolled asthma related to airway hyperresponsiveness?
qiaojin/PubMedQA
2
[ -2.0547754764556885, -0.8329143524169922, 1.9868614673614502 ]
['Diet-induced obesity (DIO) in mice causes vascular inflammation and insulin resistance that are accompanied by decreased endothelial-derived NO production. We sought to determine whether reduced NO-cGMP signaling contributes to the deleterious effects of DIO on the vasculature and, if so, whether these effects can be blocked by increased vascular NO-cGMP signaling.', 'By using an established endothelial cell culture model of insulin resistance, exposure to palmitate, 100 micromol/L, for 3 hours induced both cellular inflammation (activation of IKK beta-nuclear factor-kappaB) and impaired insulin signaling via the insulin receptor substrate-phosphatidylinositol 3-kinase pathway. Sensitivity to palmitate-induced endothelial inflammation and insulin resistance was increased when NO signaling was reduced using an endothelial NO synthase inhibitor, whereas endothelial responses to palmitate were blocked by pretreatment with either an NO donor or a cGMP analogue. To investigate whether endogenous NO-cGMP signaling protects against vascular responses to nutrient excess in vivo, adult male mice lacking endothelial NO synthase were studied. As predicted, both vascular inflammation (phosphorylated I kappaB alpha and intercellular adhesion molecule levels) and insulin resistance (phosphorylated Akt [pAkt] and phosphorylated eNOS [peNOS] levels) were increased in endothelial NO synthase(-/-) (eNOS(-/-)) mice, reminiscent of the effect of DIO in wild-type controls. Next, we asked whether the vascular response to DIO in wild-type mice can be reversed by a pharmacological increase of cGMP signaling. C57BL6 mice were either fed a high-fat diet or remained on a low-fat diet for 8 weeks. During the final 2 weeks of the study, mice on each diet received either placebo or the phosphodiesterase-5 inhibitor sildenafil, 10 mg/kg per day orally. In high-fat diet-fed mice, vascular inflammation and insulin resistance were completely prevented by sildenafil administration at a dose that had no effect in mice fed the low-fat diet.'] Does reduced NO-cGMP signaling contribute to vascular inflammation and insulin resistance induced by high-fat feeding?
qiaojin/PubMedQA
2
[ -2.409022092819214, -1.2547919750213623, 2.6995110511779785 ]
['Animal and clinical studies have suggested that polyphenols in fruits, red wine, and tea may delay the development of atherosclerosis through their antioxidant and anti-inflammatory properties. We investigated whether individual dietary polyphenols representing different polyphenolic classes, namely quercetin (flavonol), (-)-epicatechin (flavan-3-ol), theaflavin (dimeric catechin), sesamin (lignan), or chlorogenic acid (phenolic acid), reduce atherosclerotic lesion formation in the apolipoprotein E (ApoE)(-/-) gene-knockout mouse.', 'Quercetin and theaflavin (64-mg/kg body mass daily) significantly attenuated atherosclerotic lesion size in the aortic sinus and thoracic aorta (P<0.05 versus ApoE(-/-) control mice). Quercetin significantly reduced aortic F(2)-isoprostane, vascular superoxide, vascular leukotriene B(4), and plasma-sP-selectin concentrations; and augmented vascular endothelial NO synthase activity, heme oxygenase-1 protein, and urinary nitrate excretion (P<0.05 versus control ApoE(-/-) mice). Theaflavin showed similar, although less extensive, significant effects. Although (-)-epicatechin significantly reduced F(2)-isoprostane, superoxide, and endothelin-1 production (P<0.05 versus control ApoE(-/-) mice), it had no significant effect on lesion size. Sesamin and chlorogenic acid treatments exerted no significant effects. Quercetin, but not (-)-epicatechin, significantly increased the expression of heme oxygenase-1 protein in lesions versus ApoE(-/-) controls.'] Do specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction?
qiaojin/PubMedQA
2
[ -2.3798410892486572, -1.3708608150482178, 2.794858455657959 ]
['Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein beta3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up.', 'Subjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables.', 'The GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91).'] Is the G-protein beta3 subunit 825 TT genotype associated with epigastric pain syndrome-like dyspepsia?
qiaojin/PubMedQA
2
[ -1.5491678714752197, -1.5476311445236206, 2.060222625732422 ]
['To determine the effects of corneal epithelial membrane-type 1 matrix metalloproteinase (MT1-MMP) on vascular endothelial migration and proliferation.', 'We generated immortalized wild-type, MT1-MMP knockout and MT1-MMP knock-in corneal epithelial cells. Calf pulmonary arterial endothelial (CPAE) cell proliferation and Boyden chamber migration were assayed.', "Conditioned media from MT1-MMP epithelial knockout cells significantly increased CPAE proliferation 5-bromo-2'-deoxy-uridine (BrdU) incorporation, and CPAE migration as compared with wild-type epithelial cells. Conditioned media from knock-in cells reversed the increase in CPAE proliferation, BrdU incorporation and CPAE migration. Knock-in cells transfected with mutant MT1-MMP (E240A) did not abrogate the reversal effect."] Does corneal epithelial MT1-MMP inhibit vascular endothelial cell proliferation and migration?
qiaojin/PubMedQA
2
[ -2.518890380859375, -1.1444451808929443, 2.7379279136657715 ]
['Limited data are available on the association between the severity of emphysema or airway narrowing, and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD), which has been seen to be more prevalent among elderly subjects. The aim of this study was to examine the association between HRQOL, physical parameters and structural alterations in lung of COPD patients.', 'Stable COPD patients (n = 125; mean age 71.0) were studied. Both the severity of emphysema, which was expressed as the extent of the low-attenuation area (LAA%), and percentage of the large airway wall area (WA%) on high-resolution computed tomography (HRCT) were compared with various parameters of the generic and HRQOL, respectively, together with pulmonary function tests and exercise capacity.', 'The predicted value of forced expiratory volume in 1 s was significantly associated with both LAA% and WA%, but the diffusion capacity was strongly correlated with LAA% alone. Parameters of the generic and HRQOL, and almost all other parameters appeared to be significantly associated with LAA% alone, whereas no association was observed between WA% and QOL.'] Is emphysema on imaging associated with quality of life in elderly patients with chronic obstructive pulmonary disease?
qiaojin/PubMedQA
2
[ -1.858811855316162, -1.3063933849334717, 2.2461609840393066 ]
['We evaluated proton magnetic resonance spectroscopic imaging (MRSI) findings for children with traumatic brain injury attributable to nonaccidental trauma (NAT) early after injury, to determine whether brain metabolite changes predicted outcomes.', 'Proton MRSI (1.5 T) was performed (mean: 5 days after injury [range: 1-30 days]) through the level of the corpus callosum for 90 children with confirmed NAT. Regional N-acetylaspartate/total creatine, N-acetylaspartate/total choline, and choline/creatine ratios and the presence of lactate were measured. Data on long-term outcomes defined at > or =6 months were collected for 44 of 90 infants. We grouped patients into good (normal, mild disability, or moderate disability; n = 32) and poor (severe disability, vegetative state, or dead; n = 12) outcome groups.', 'We found that N-acetylaspartate/creatine and N-acetylaspartate/choline ratios (mean total, corpus callosum, and frontal white matter) were significantly decreased in patients with poor outcomes (P < .001). A logistic regression model using age, initial Glasgow Coma Scale score, presence of retinal hemorrhage, lactate on MRSI scans, and mean total N-acetylaspartate/creatine ratio predicted outcomes accurately in 100% of cases.'] Does magnetic resonance spectroscopy predict outcomes for children with nonaccidental trauma?
qiaojin/PubMedQA
2
[ -1.9791966676712036, -1.3610126972198486, 2.424776554107666 ]
['Knowledge of the effect of topically applied calcineurin antagonists such as tacrolimus on the sensitization phase of allergic contact dermatitis is currently limited.', 'To investigate tacrolimus-dependent immunomodulation on gene expression alterations in human antigen-presenting cells which are stimulated with small-molecular-weight contact allergens.', 'Monocyte-derived dendritic cells (moDC) and THP-1 cells were stimulated with the contact sensitizer cinnamic aldehyde (CAld) and compared with the very strong experimental sensitizer 2,4,6-trinitrobenzene sulfonic acid (TNBS) in vitro. Quantitative PCR analysis was used to detect gene expression changes, particularly of interleukin (IL) 8, as an indicator of differential dendritic cell (DC) gene expression after sensitizer stimulation in the absence or presence of tacrolimus and betamethasone at two different concentrations.', 'DC activation was clearly demonstrated by a significant IL-8 upregulation after 24 h, whereas tacrolimus or betamethasone alone did not affect IL-8 baseline expression. Betamethasone and, to a lesser extent, tacrolimus led to a marked reduction of chemical-induced IL-8 expression by TNBS and CAld.'] Does tacrolimus modulate dendritic cell activation in the sensitization phase of allergic contact dermatitis?
qiaojin/PubMedQA
2
[ -2.5700700283050537, -1.268916368484497, 2.9066271781921387 ]
['To investigate the potential anti-Helicobacter pylori (H. pylori) and anti-inflammation in vivo effects of two lactobacillus strains from human stomach.', 'Forty H. pylori infected Balb/c mice were randomly divided into 4 groups: proton pump inhibitor and antibiotics triple treated group, Lactobacillus fermenti (L. fermenti) treated group, Lactobacillus acidophilus treated group and normal saline control group. Ten uninfected mice were also included as blank control group. The infection of H. pylori was detected by rapid urease tests, Giemsa staining and bacterial culture. The colonization of H. pylori was assessed in bacterial density score and gastric inflammation was assessed in histological score. The colonization of L. fermenti was performed by fluorescent probe.', 'Histopathologic evaluation showed significant release of mucosal inflammation in gastric antrum and gastric body in lactobacillus treated groups and triple treated group. H. pylori eradication rate in both lactobacillus treated groups and triple treated group were higher than normal saline control group. Lactobacillus treated groups and triple treated group showed significant decrease of H. pylori bacterial density.'] Do two stomach-originated Lactobacillus strains improve Helicobacter pylori infected murine gastritis?
qiaojin/PubMedQA
2
[ -2.4302890300750732, -1.374480128288269, 2.882561683654785 ]
['Activation of MET, either by increased gene copy number (GCN) or mutation, has been detected in various cancers. We investigate the clinicopathologic features of MET gene copy in nonsmall cell lung cancer (NSCLC).', 'Tumor tissues were obtained from 180 resected NSCLCs, including 97 squamous cell carcinomas (SCCs) and 72 adenocarcinomas. No patient received epidermal growth factor receptor (EGFR)-targeted therapy. EGFR and MET GCNs were studied using fluorescence in situ hybridization (FISH) and were estimated according to the University of Colorado Cancer Center (UCCC) criteria. For MET, we also assessed GCNs using the Cappuzzo system.', 'FISH-positive MET was observed in 16.7% using the UCCC criteria; specifically, amplification was seen in 3.9% and high polysomy in 12.8%. FISH-positive MET status was significantly correlated with FISH-positive EGFR (p = 0.003). In the Cappuzzo system, high MET GCN (mean, >/=5 copies/cell) was found in 6.7% and also associated with FISH-positive EGFR (p = 0.031). MET gene copy status was not associated with gender, smoking history, histology, or stage. However, true MET amplification was more frequent in patients with SCC than in those with adenocarcinoma. FISH-positive MET status predicted worse survival in patients with NSCLC at advanced stages (p = 0.034) and in patients with SCC (p = 0.028). In multivariate analyses, increased MET GCN was significantly associated with shorter survival in patients with SCC, as analyzed using both the UCCC and Cappuzzo criteria (p = 0.019 and 0.008).'] Does high MET gene copy number lead to shorter survival in patients with non-small cell lung cancer?
qiaojin/PubMedQA
2
[ -2.0066583156585693, -1.5120573043823242, 2.5100715160369873 ]
['Allergic asthma is characterized by reversible airway obstruction, lung inflammation, and airway hyperresponsiveness (AHR). Previous studies using leukotriene B(4) (LTB(4)) receptor 1-deficient mice and adoptive transfer experiments have suggested that LTB(4) plays a role in lung inflammation and AHR.', 'In this study, we used a leukotriene A(4) hydrolase (LTA(4)H) inhibitor as a pharmacological tool to directly examine the role of LTB(4) in a mast cell-dependent murine model of allergic airway inflammation.', 'We used the forced oscillation technique to test the effects of an LTA(4)H inhibitor dosed during the challenge phase on AHR. Lung tissue and lavage were collected for analysis.', 'Treatment with an LTA(4)H inhibitor improved multiple parameters encompassing AHR and lung function. Significant decreases in inflammatory leukocytes, cytokines, and mucin were observed in the lung lumen. Serum levels of antigen-specific IgE and IgG1 were also decreased. Labeled antigen uptake by lung dendritic cells and subsequent trafficking to draining lymph nodes and the lung were decreased on LTA(4)H inhibitor treatment. Provocatively, inhibition of LTA(4)H increased lipoxin A(4) levels in lung lavage fluid.'] Does leukotriene A ( 4 ) hydrolase inhibition attenuate allergic airway inflammation and hyperresponsiveness?
qiaojin/PubMedQA
2
[ -2.5167953968048096, -1.2534304857254028, 2.808408498764038 ]
['Polysaccharide from fuzi (FPS), a Chinese herbal medicine extract, has been demonstrated to exert lipid lowering affects. In this study we examined potential mechanisms underlying this affect, specifically alterations in expression of the LDL-receptor (LDL-R), 3-hydroxy-3-methyl glutaryl (HMG)-CoA reductase and cytochrome P450 7alpha-1 (CYP7alpha-1), using a rat model of hypercholesterolemia.', 'Male rats were fed either a normal or high cholesterol (HC) diet for two-weeks. Half of the rats on the HC diet were orally gavaged with FPS (224 mg/kg, 448 mg/kg or 896 mg/kg diet) daily. Serum lipid levels were quantified at end of the study period as were liver levels of LDL-R protein and mRNA expression of CYP7alpha-1 and HMG-CoA. Serum cholesterol and LDL-C concentrations were significantly elevated from control in HC rats, but not in those treated with FPS (P < 0.05). LDL-R expression was significantly decreased in the HC group compared to control (P < 0.05), but significantly increased in the FPS group (P < 0.05). HMG-CoA mRNA levels were significantly increased in the HC group compared both other groups (P < 0.05), while CYP7alpha-1 expression was significantly higher in the FPS group compared to both other groups (P < 0.05).'] Does polysaccharide from fuzi ( FPS ) prevent hypercholesterolemia in rats?
qiaojin/PubMedQA
2
[ -1.6811453104019165, -1.4503861665725708, 2.0781726837158203 ]
['Nonischemic right ventricular dysfunction and cardiac failure is a source of considerable morbidity in children with congenital heart disease. Cell transplantation has not previously been studied in the pediatric setting in which enhancing ventricular function in response to supraphysiologic workloads might be beneficial.', 'Engraftment and differentiation of human cord blood stem cells were studied in an immunosuppressed neonatal ovine model of right ventricular training. Week-old sheep underwent pulmonary artery banding and epicardial injection of cord blood stem cells (n=8) or pulmonary artery banding and placebo injection (n=8). Control groups received cord blood stem cells (n=6) or placebo (n=6) injection without pulmonary artery banding. Right ventricular function was measured at baseline and 1 month later using conductance catheter.', 'Cord blood stem cells were detected in the myocardium, spleen, kidney, and bone marrow up to 6 weeks after transplantation and expressed the hematopoietic markers CD45 and CD23. We identified neither differentiation nor fusion of transplanted human cells. In the groups undergoing pulmonary artery banding, cord blood stem cell transplantation was accompanied by functional benefits compared with placebo injection: end-systolic elastance increased by a mean of 1.4 +/- 0.2 mm Hg/mL compared with 0.9 +/- 0.1 mm Hg/mL, and the slope of preload recruitable stroke work increased by 21.1 +/- 2.9 mm Hg compared with 15.8 +/- 2.5 mm Hg. Cord blood stem cell transplantation had no significant effect on right ventricular function in the absence of pulmonary artery banding.'] Do human cord blood stem cells enhance neonatal right ventricular function in an ovine model of right ventricular training?
qiaojin/PubMedQA
2
[ -2.0643131732940674, -1.4706337451934814, 2.5506372451782227 ]
['Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections.', 'Serum samples of 134 patients with untreated mycobacterium infections (122 TB, 12 nontuberculous mycobacterium) were tested for antibodies against both the citrullinated (Cit) and the non-citrullinated (Arg) form of 2 cyclic synthetic peptides. In 33 patients, a follow-up sample was tested six months after starting anti-mycobacterial drugs.', 'A substantial proportion of patients with mycobacterial infections demonstrated antibodies against 0401Cit, 0401Arg, 0722Cit and 0722Arg. Fourteen patients demonstrated anti-0401Cit, 83 anti-0401Arg, 22 anti-0722Cit and 61 anti-0722Arg, while none of these antibodies were detected in the 20 healthy controls. All the patients but one, who were anti-0401Cit and anti-0722Cit positive, demonstrated reactivity against the respective Arg peptide. In the subset of 33 patients with a follow-up test six months after starting treatment, the mean levels of antibodies to 0401Cit, 0401Arg, 0722Cit and 0722Arg significantly decreased after treatment. All the patients who were anti-0401Cit and anti-0722Cit positive turned negative after treatment. The presence of anti-0401Cit/Arg and anti-0722Cit/Arg was found to be significantly correlated with the presence of HIV.'] Is the anti-cyclic citrullinated peptide response in tuberculosis patients citrulline-dependent and sensitive to treatment?
qiaojin/PubMedQA
2
[ -1.8254441022872925, -1.5056196451187134, 2.354496479034424 ]
['Anandamide (AEA) is an endogenous lipid mediator that exerts several effects in the brain as well as in peripheral tissues. These effects are mediated mainly by two types of cannabinoid receptors, named CB(1)R and CB(2)R, making AEA a prominent member of the "endocannabinoid" family. Also immune cells express CB(1) and CB(2) receptors, and possess the whole machinery responsible for endocannabinoid metabolism. Not surprisingly, evidence has been accumulated showing manifold roles of endocannabinoids in the modulation of the immune system. However, details of such a modulation have not yet been disclosed in primary human T-cells.', 'In this investigation we used flow cytometry and ELISA tests, in order to show that AEA suppresses proliferation and release of cytokines like IL-2, TNF-alpha and INF-gamma from activated human peripheral T-lymphocytes. However, AEA did not exert any cytotoxic effect on T-cells. The immunosuppression induced by AEA was mainly dependent on CB(2)R, since it could be mimicked by the CB(2)R selective agonist JWH-015, and could be blocked by the specific CB(2)R antagonist SR144528. Instead the selective CB(1)R agonist ACEA, or the selective CB(1)R antagonist SR141716, were ineffective. Furthermore, we demonstrated an unprecedented immunosuppressive effect of AEA on IL-17 production, a typical cytokine that is released from the unique CD4+ T-cell subset T-helper 17.'] Does anandamide suppress proliferation and cytokine release from primary human T-lymphocytes mainly via CB2 receptors?
qiaojin/PubMedQA
2
[ -2.407794713973999, -1.2875114679336548, 2.7486586570739746 ]
['Improved outcome measures in systemic sclerosis (SSc) are critical to finding active therapeutics for this disease. The modified Rodnan skin thickness score (MRSS) is the current standard for evaluating skin disease in SSc, but it is not commonly used in the clinical setting, in part because it requires specialized training to perform accurately and consistently. The purpose of this study was to investigate whether skin gene expression might serve as a more objective surrogate outcome measure to supplement skin score evaluations.', 'Skin RNAs from a group of patients with diffuse cutaneous SSc were studied for expression levels of genes known to be regulated by transforming growth factor beta (TGFbeta) and interferon (IFN). These levels were correlated with the MRSS, using multiple regression analyses to obtain best-fit models.', 'Skin expression of the TGFbeta-regulated genes cartilage oligomeric matrix protein (COMP) and thrombospondin 1 (TSP-1) correlated moderately well with the MRSS, but the addition of other TGFbeta-regulated genes failed to significantly improve best-fit models. IFN-regulated genes were also found to correlate with the MRSS, and the addition of interferon-inducible 44 (IFI44) and sialoadhesin (Siglec-1) to COMP and TSP-1 in multiple regression analyses significantly improved best-fit models, achieving an R(2) value of 0.89. These results were validated using an independent group of skin biopsy samples. Longitudinal scores using this 4-gene biomarker indicated that it detects change over time that corresponds to changes in the MRSS.'] Does a four-gene biomarker predict skin disease in patients with diffuse cutaneous systemic sclerosis?
qiaojin/PubMedQA
2
[ -2.3126027584075928, -1.3191654682159424, 2.694307327270508 ]
['To determine whether elevated serum lipid levels resulting from feeding animals a high-fat diet can affect the inflammatory process in C57BL/6 (B6) wild-type (WT) and B6 ApoE(-/-) mouse models of collagen-induced arthritis (CIA).', "Male B6 WT or ApoE(-/-) mice were fed either a normal chow diet or a high-fat diet. CIA was induced in mice at 12 weeks of age using type II chicken collagen, Freund's complete adjuvant, and, on occasion, a lipopolysaccharide boost. Expression levels of autoantibodies and cytokines were measured using enzyme-linked immunosorbent assay and multiplex assay, respectively.", 'Whereas B6 WT mice developed severe articular inflammation after collagen immunization, ApoE(-/-) mice developed no clinical or histologic evidence of disease regardless of whether they had been fed a high-fat diet or a normal chow diet. The fact that arthritis was not present in ApoE(-/-) mice did not result from inadequate production of serum IgG2a collagen antibodies, since levels observed in ApoE(-/-) mice were similar to those observed in arthritic B6 WT control mice. Critically, development of atherosclerosis in ApoE(-/-) mice was not affected by the CIA protocol.'] Are apolipoprotein E-deficient mice resistant to the development of collagen-induced arthritis?
qiaojin/PubMedQA
2
[ -2.4324071407318115, -1.2087897062301636, 2.6781094074249268 ]
['There are limited data suggesting that methotrexate polyglutamate (MTXGlu) concentrations can guide MTX dosing in patients with rheumatoid arthritis (RA). The aim of this study was to define a therapeutic range of red blood cell (RBC) MTXGlu(n) concentrations (where n refers to the number of glutamate groups), including threshold values for efficacy and adverse effects in patients receiving long-term oral MTX treatment.', 'A cross-sectional study of 192 patients receiving oral MTX was undertaken. Disease activity was assessed by the swollen and tender joint counts, the C-reactive protein level, and the Disease Activity Score in 28 joints (DAS28). High disease activity was defined as a DAS28 of >3.2. A standardized questionnaire regarding common MTX adverse effects was completed.', 'The MTX dosage was significantly higher in patients in whom the swollen joint count and DAS28 were higher. The MTXGlu(4), MTXGlu(5), MTXGlu(3-5), and MTXGlu(1-5) concentrations were significantly higher in patients with high disease activity. After correction for age, the estimated glomerular filtration rate, and the MTX dosage, the association remained significant for MTXGlu(5). RBC folate concentrations were significantly higher in the group with high disease activity. There was no association between any MTXGlu(n) concentration and adverse effects.'] Are methotrexate polyglutamate concentrations associated with disease control in rheumatoid arthritis patients receiving long-term methotrexate therapy?
qiaojin/PubMedQA
2
[ -2.264723300933838, -1.3276293277740479, 2.647324562072754 ]
['To evaluate the accuracy of clinical assessment of adenoidal obstruction based on a standardized score of the degree of mouth breathing and speech hyponasality (nasal obstruction index [NOI]) in comparison to nasal fiberoptic endoscopy.', 'Cross-sectional study with planned data collection.', 'Outpatient clinics of the Departments of Maternal and Pediatric Sciences and Specialized Surgical Sciences, University of Milan, Italy.', 'Children aged three to 12 years with adenoidal obstruction suspected on the grounds of persistent/recurrent otitis media or perceived obstructive nasal breathing were eligible. Ear, nose, and throat examination, allergy testing, NOI measurement, and nasal fiberoptic endoscopy to assess the degree of adenoidal hypertrophy were performed. Agreement between the NOI and adenoidal hypertrophy grade was assessed in the patients as a whole and by clinical subgroups.', 'A total of 202 children were enrolled: 54.9 percent had otological diseases and 45.1 percent had perceived obstructive nasal breathing. Most of the children (79.2%) showed mild or moderate clinical nasal obstruction. Adenoidal hypertrophy ranged from no obstruction (18%) to severe obstruction (38%). There was no substantial agreement between the NOI and the degree of adenoidal obstruction in the population as a whole and in all the clinical subgroups. False positive findings were significantly more frequent among allergic children (50%) than non-allergic children (22.4%, P = 0.009).'] Is clinical assessment of adenoidal obstruction based on the nasal obstruction index no longer useful in children?
qiaojin/PubMedQA
2
[ -1.86868417263031, -1.0415867567062378, 2.002575397491455 ]
['Earlier work has demonstrated that serum autoantibodies from coeliac patients targeted against transglutaminase 2 (TG2) inhibit in vitro angiogenesis. The aim of this study was to establish whether coeliac patient-derived monoclonal TG2-targeted antibodies produced by recombination technology exert similar anti-angiogenic effects to serum-derived coeliac autoantibodies. In addition, we studied whether the monoclonal patient autoantibodies modulate endothelial cell TG2 activity and whether such modulation is related to the anti-angiogenic effects.', 'The influence of coeliac patient-derived monoclonal TG2-targeted antibodies on endothelial cell tubule formation was studied using a three-dimensional angiogenic cell culture model. Endothelial cell TG2 enzymatic activity was determined by means of a live-cell enzyme-linked immunosorbent assay.', 'Coeliac patient-derived monoclonal TG2-targeted antibodies produced by recombination technology inhibited endothelial tubule formation and enhanced the crosslinking activity of TG2. When this enzymatic activity was inhibited using site-directed irreversible TG2 inhibitors in the presence of autoantibodies, in vitro angiogenesis reverted to the control level.'] Does inhibition of transglutaminase 2 enzymatic activity ameliorate the anti-angiogenic effects of coeliac disease autoantibodies?
qiaojin/PubMedQA
2
[ -2.483654260635376, -1.199115514755249, 2.762251615524292 ]
['Uterine myomas may change the concentrations of the screening serum markers and therefore alter the risk calculation of the fetal chromosomal abnormalities. An increased risk leads to invasive diagnostics procedures which in these cases can often be technically difficult due to the presence of myomas.', 'The aim of this study was to assess the influence of uterine myomas on the first and second trimester serum markers concentrations and, possibly on the test results.', 'The study group consisted of 127 women between 11 and 20 weeks of normal singleton pregnancy. In each case uterine myomas were diagnosed--over 20 mm in the diameter and located in the uterine wall. 77 patients underwent the first trimester screening (PAPP-A & free beta-hCG) and 50 patients had the second trimester screening (triple test). The control group consisted of 1020 women between 11 and 20 weeks of normal singleton pregnancy without uterine myomas. Delfia Xpress analyser was used for the serum markers estimations. All pregnant women delivered normal healthy babies.', 'In the first trimester group the PAPP-A serum concentrations were not different from the controls while the mean median concentration of free beta-hCG were significant higher--1.43 MoM. In the second trimester group the following mean median values were observed: no significance for the AFP--1.18 MoM and estriol--1.29 MoM and significantly higher mean median value for the free beta-hCG--2.01 MoM.'] Does [ Connection between uterine myomas and biochemical screening result in the first and second trimester of pregnancy ]?
qiaojin/PubMedQA
2
[ -2.131892204284668, -1.1501851081848145, 2.4235401153564453 ]
['Various lines of evidence demonstrate the involvement of mitochondrial dysfunction in the pathogenesis of glaucoma. Therefore, mitochondrial DNA is a promising candidate for genetic susceptibility studies on glaucoma. To test the hypothesis that mitochondrial haplogroups influence the risk to develop glaucoma, we genotyped 12 single-nucleotide polymorphisms that define the European mitochondrial DNA haplogroups in healthy controls and two German patient cohorts with either exfoliation glaucoma or the normal tension subgroup of primary open angle glaucoma.', 'Mitochondrial haplogroup U was significantly under-represented in patients with exfoliation glaucoma (8.3% compared with 18.9% in controls; p = 0.004).'] Is mitochondrial haplogroup U associated with a reduced risk to develop exfoliation glaucoma in the German population?
qiaojin/PubMedQA
2
[ -1.9346379041671753, -0.7506822943687439, 1.7489404678344727 ]
['The aim of this study is to determine the prevalence and prognostic value of elevated cardiac troponin (cTnT) and its association with clinical characteristics according to renal function status in patients with stable heart failure.', 'In a prospective observational study, 152 consecutive patients from the Heart Failure Clinic of the INCMNSZ were followed for a period of 42 months. All underwent clinical evaluation, echocardiography, and determination of body composition by electric bioimpedance to identify hypervolemia. Concentrations of cTnT were quantified by immunoassay with electrochemoluminescence and > or = 0.02 ng/mL levels were considered elevated. Also glomerular filtration rate (eGFR) was estimated using the Cockcroft-Gault equation.', 'Elevated cTnT was significantly associated with increased all-cause mortality in the observational period even after adjusting for eGFR < 60 mL/min/1.73 m2 and clinical findings such as hypertension, functional class, loop diuretics, angiotensin converting enzyme inhibitors, pulmonary pressure and hypervolemia in Cox regression analysis with a hazard ratio of 4.58 (95% confidence interval: 1.84-11.45).'] Is prognostic value of cardiac troponin T elevation independent of renal function and clinical findings in heart failure patients?
qiaojin/PubMedQA
2
[ -2.202988386154175, -1.4484610557556152, 2.759791374206543 ]
['Prevalence of microalbuminuria is increased in patients with HIV. Microalbuminuria is associated with increased mortality in other populations, including diabetics, for whom microalbuminuria testing is standard of care. We investigated whether microalbuminuria is associated with mortality in HIV-infected women not receiving antiretroviral therapy.', "Urinalysis for proteinuria and semiquantitative testing for microalbuminuria were performed in specimens from 2 consecutive visits in 1547 HIV-infected women enrolled in the Women's Interagency HIV Study in 1994-1995. Time to death was modeled using proportional hazards analysis.", 'Compared with women without albuminuria, the hazard ratio (HR) for all-cause mortality was increased in women with 1 (HR: 3.4; 95% CI: 2.2 to 5.2) or 2 specimens positive for either proteinuria or microalbuminuria (HR: 3.9; 95% CI: 2.1 to 7.0). The highest risk was observed in women with both specimens positive for proteinuria (HR: 5.8; 95% CI: 3.4 to 9.8). The association between albuminuria and all-cause mortality risk remained significant after adjustment for demographics, HIV disease severity, and related comorbidities. Similar results were obtained for AIDS death.'] Is microalbuminuria associated with all-cause and AIDS mortality in women with HIV infection?
qiaojin/PubMedQA
2
[ -2.2396018505096436, -1.0622607469558716, 2.4205737113952637 ]
['To investigate the effect of vitamin C (VC) on visceral lipid oxidative injury during oral fluid resuscitation of burn shock.', 'Twelve male Beagle dogs were surgically prepared for arterial and venous cannulation, and 24 hours later they were subjected to a 50% TBSA full-thickness flame injury. In the first 24 hours after burn dogs were resuscitated with gastric infusion of either glucose-electrolyte solution (GES group, n = 6) or GES containing 250 mg/kg of VC (GES/VC group, n = 6). The delivery rate and volume of GES was in accordance with that of Parkland formula (4 ml x kg(-1) x 1% TBSA(-1) in the first 24 hours). In the second 24 hours all animals received delayed i.v. fluid resuscitation. At end of 72 hours after injury, animals were sacrificed, and specimens of heart, lung, liver, kidney and jejunum were harvested for evaluation of xanthine oxidase (XOD), malondialdehyde (MDA) and assessment of the tissue water content (ratio of dry to wet weight) of organs. The plasma levels of alanine aminotransferase (ALT), creatinine (Cr), MB isoenzyme of creatine kinase (CK-MB) and diamine oxidase (DAO) were determined at same time.', 'At 72 hours after burn it was showed significant higher activities of XOD in GES/CAR than GES group in heart, kidney and jejunum, and lower contents of MDA in heart, lung, liver, kidney and jejunum (P all < 0.01). Tissue water contents were significantly lower in GES/CAR than GES group in heart [(75.4 +/-1.1)% vs (78.5 +/- 0.8)%], lung [(68.1 +/- 0.9)% vs (73.9 +/- 1.0)%], liver [ (75.2 +/- 0.8)% vs (78.3 +/- 1.2)%], kidney [(73.8 +/- 1.1)% vs (78.1 +/- 0.8)%] and jejunum [(76.3 +/- 0.8)% vs ( 80.4 +/- 0.6)] respectively, all P < 0.01. The levels of ALT, CK-MB, Cr and DAO in GES/CAR group were (46.6 +/- 2.49) U/L, (43.4 +/- 7.05) mol/L, (7156 +/- 596) U/L and (1.86 +/- 0.45) U/L respectively, all significantly lower than those of the GES group [(86.9 +/- 7.89) U/L, (95.2 +/- 1.23) mol/L, (8023 +/- 384) U/L and (2.68 +/- 0.61) U/L respectively, all P < 0.05].'] Does [ Vitamin alleviate visceral lipid peroxidative injury in dogs during oral fluid resuscitation of burn shock ]?
qiaojin/PubMedQA
2
[ -1.904109239578247, -1.5648479461669922, 2.468175172805786 ]
['The impact of active surveillance, comprising annual computed tomography scanning and bone marrow biopsies, in the follow-up of patients after high-dose therapy with autologous stem cell rescue for recurrent follicular lymphoma was analyzed.', 'Seventy-one of 99 patients who received high-dose therapy commenced the surveillance program. Response duration, time to next treatment and overall survival were compared according to whether disease progression had been diagnosed on the basis of surveillance investigations or on clinical grounds.', 'After a median follow-up of 16 years, progression was documented by surveillance in 16 patients and clinically in 18, the median response duration being 2.4 and 2.3 years, respectively (P=NS). Ten patients with a relapse detected clinically started treatment immediately, contrasting with one patient whose relapse was detected by surveillance investigations. Five patients with relapses detected by surveillance investigations have not required treatment after a median follow-up of 18 years, whereas all but two patients with a relapse detected clinically have been treated. The median time to next treatment was 7 years for patients with a relapse identified by surveillance investigations and 4 years for those whose relapse was manifested clinically (P=0.03). Overall survival was not significantly different between the two groups.'] Do surveillance investigations after high-dose therapy with stem cell rescue for recurrent follicular lymphoma have no impact on management?
qiaojin/PubMedQA
2
[ -1.7467478513717651, -1.1034207344055176, 1.9075288772583008 ]
['The clinical use of chromatin-modulating drugs, such as histone deacetylase inhibitors, for the treatment of bone marrow failure and hematopoietic malignancies has increased dramatically over the last few years. Nonetheless, little is currently known concerning their effects on myelopoiesis.', 'We utilized an ex vivo differentiation system in which umbilical cord blood-derived CD34(+) cells were treated with trichostatin A, sodium butyrate and valproic acid to evaluate the effect of histone deacetylase inhibitor treatment on myeloid lineage development, colony-forming potential, proliferation, and terminal neutrophil differentiation.', 'Trichostatin A treatment modestly reduced progenitor proliferation, while sodium butyrate and valproic acid resulted in concentration-dependent effects on proliferation and apoptosis. Addition of valproic acid uniquely stimulated CD34(+) proliferation. Sodium butyrate treatment inhibited terminal neutrophil differentiation both quantitatively and qualitatively. Addition of 100 microM valproic acid resulted in increased numbers of mature neutrophils with a block in differentiation at increasing concentrations. Sodium butyrate and valproic acid treatment resulted in increased acetylation of histones 3 and 4 while trichostatin A, sodium butyrate and valproic acid had differential effects on the acetylation of non-histone proteins.'] Does histone deacetylase inhibition modulate cell fate decisions during myeloid differentiation?
qiaojin/PubMedQA
2
[ -2.5981032848358154, -1.1725540161132812, 2.7983996868133545 ]
['Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis.', 'We first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04).'] Is infection with Helicobacter pylori associated with protection against tuberculosis?
qiaojin/PubMedQA
2
[ -1.9877429008483887, -1.452292799949646, 2.4603607654571533 ]
['Asthma typically originates in early-life, and the impact of infection during immunologic maturation is a critical factor in disease pathogenesis. The progression of aberrant T(H)2 cell responses and disease development has been attributed to a lack of infections. However, exposure to specific pathogens such as Chlamydia may alter immunologic programming and predispose to asthma.', 'To investigate the effects of chlamydial infection at different ages on allergic airways disease in later life.', 'Neonatal, infant, or adult BALB/c mice were infected and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Hallmark features of allergic airways disease were compared with uninfected allergic and nonallergic controls.', 'Early-life (neonatal and infant) but not adult chlamydial infection enhanced the development of hallmark features of asthma in ovalbumin-induced allergic airways disease. Notably early-life infection increased mucus-secreting cell numbers, IL-13 expression, and airway hyperresponsiveness. Neonatal infection attenuated eosinophil influx and ovalbumin-specific T(H)2 cytokine release and numbers of activated myeloid dendritic cells (DCs) in lymph nodes. By contrast, infant infection augmented features of allergic inflammation with increased airway eosinophils, T(H)2 cytokine, and DC responses. Both neonatal and infant infection increased systemic DC-induced IL-13 release from CD4(+) T cells. The timing of infection had significant effects on lung structure because neonatal but not infant or adult infection induced increases in alveolar diameter.'] Does early-life chlamydial lung infection enhance allergic airways disease through age-dependent differences in immunopathology?
qiaojin/PubMedQA
2
[ -2.7538068294525146, -0.9112640619277954, 2.761829137802124 ]
['The potent anti-cancer capability of a novel CPT derivarate, 10-methoxy-9-nitrocamptothecin (MONCPT), has been demonstrated in our previous studies. The present study focuses on the in vitro and in vivo anti-cancer activities, the cell cycle arrest- and apoptosis-induction abilities of MONCPT on human bladder uroepithelial carcinoma 5637 cell line.', 'MTT assay and flow cytometric analyses were employed to evaluate the cell proliferation, cell cycle distribution and apoptosis of MONCPT-treated 5637 cells. Using 5637 xenografted nuce mice models, the in vivo anti-cancer capability of MONCPT were examined, as indicated by the decreased tumor volume and tumor weight. The effect of MONCPT on some of the key regulators of G2/M checkpoint and apoptosis, including CDKI-CDK-cyclin cascade, Kip1/p27 and Cip1/p21, PARP were examined using western blotting.', 'The more potent anti-tumor activities of MONCPT than SN-38 against 5637 cells were indicated by the IC50 value (48 h) of 226.7 +/- 0.5 nM and 2031.0 +/- 0.5 nM, respectively. MONCPT treatment (0.1 microM) for 24 h caused the increment of G2/M population from 7.94% to 75.52%, indicating that MONCPT significantly triggered G2/M arrest. Moreover, MONCPT exposure (0.1 microM, 24 h) caused down-regulation of CDK7, p-Cdc2, and cyclinB1. Treatment with MONCPT (0.1 microM) for 48 h obviously induced apoptosis of 5637 cells, which was revealed by the accumulation of Annexin V-positive cells. The superior anti-tumor capabilities of MONCPT were further demonstrated in the human 5637 xenograft-bearing mice model. The administration of MONCPT at the dosages of 5, 10, 20 mg/kg for 15 days significantly inhibited the tumor growth with the inhibition rates of 64.8%, 86.2% and 96.5%, respectively.'] Does mONCPT exert anti-cancer activities via inducing G2/M arrest and apoptosis in human bladder cancer?
qiaojin/PubMedQA
2
[ -1.944092869758606, -1.5475783348083496, 2.5362749099731445 ]
['A proportion of small diameter primary sensory neurones innervating human skin are chemosensitive. They respond in a receptor dependent manner to chemical mediators of inflammation as well as naturally occurring algogens, thermogens and pruritogens. The neurotransmitter GABA is interesting in this respect because in animal models of neuropathic pain GABA pre-synaptically regulates nociceptive input to the spinal cord. However, the effect of GABA on human peripheral unmyelinated axons has not been established.', 'Electrical stimulation was used to assess the effect of GABA on the electrical excitability of unmyelinated axons in isolated fascicles of human sural nerve. GABA (0.1-100 microM) increased electrical excitability in a subset (ca. 40%) of C-fibres in human sural nerve fascicles suggesting that axonal GABA sensitivity is selectively restricted to a sub-population of human unmyelinated axons. The effects of GABA were mediated by GABA(A) receptors, being mimicked by bath application of the GABA(A) agonist muscimol (0.1-30 microM) while the GABA(B) agonist baclofen (10-30 microM) was without effect. Increases in excitability produced by GABA (10-30 microM) were blocked by the GABA(A) antagonists gabazine (10-20 microM), bicuculline (10-20 microM) and picrotoxin (10-20 microM).'] Does gABA increase electrical excitability in a subset of human unmyelinated peripheral axons?
qiaojin/PubMedQA
2
[ -2.2550487518310547, -1.3321460485458374, 2.585872173309326 ]
["Women who received irradiation for Hodgkin's lymphoma have a strong increased risk for developing breast cancer. Approximately 90% of the breast cancers in these patients can be attributed to their radiation treatment, rendering such series extremely useful to determine whether a common radiation-associated cause underlies the carcinogenic process.", "In this study we used gene expression profiling technology to assess gene expression changes in radiation-associated breast tumors compared with a set of control breast tumors of women unexposed to radiation, diagnosed at the same age. RNA was obtained from fresh frozen tissue samples from 22 patients who developed breast cancer after Hodgkin's lymphoma (BfHL) and from 20 control breast tumors.", 'Unsupervised hierarchical clustering of the profile data resulted in a clustering of the radiation-associated tumors separate from the control tumors (p < 0.001). Using a supervised class prediction tool, a nearest centroid classifier of 198 probes was identified. The BfHL tumors were often of the intrinsic basal breast tumor subtype, and they showed a chromosomal instability profile and a higher expression of the proliferation marker Ki-67.'] Do radiation-associated breast tumors display a distinct gene expression profile?
qiaojin/PubMedQA
2
[ -2.3552074432373047, -0.961687445640564, 2.44541335105896 ]
['Regulatory T (Treg) cells suppress the sensitization phase of experimental contact hypersensitivity (CHS) reactions when injected before hapten application.', 'Our aim was to analyze the mechanisms by which Treg cells suppress the sensitization phase of CHS reactions.', 'Treg cells were labeled with different fluorescent dyes and injected into naive mice directly before sensitization with the hapten 2,4,6-trinitro-1-chlorobenzene. Two days after sensitization, the lymphoid organs were analyzed for the presence of Treg cells and engagement of gap junctions with other cells. Dendritic cells (DCs) and effector CD8(+)T cells were isolated from the draining lymph nodes (LNs) of the differently treated groups, analyzed by using FACS for activation markers, and assessed for the T-cell stimulatory capacity of the DCs and the priming of effector T cells.', 'Only the LN-homing Treg cells suppressed the sensitization phase in CHS reactions by means of establishing gap junctions with DCs in the dLNs. This gap junctional intercellular communication led to downregulation of T-cell costimulatory molecules on the surface of the DCs, abrogating the priming, activation, and proliferation of hapten-specific CD8(+)T cells. Consequently, the ear-swelling response induced by challenge with the respective hapten was prevented.'] Do gap junctions between regulatory T cells and dendritic cells prevent sensitization of CD8 ( + ) T cells?
qiaojin/PubMedQA
2
[ -2.6517117023468018, -1.0741569995880127, 2.7662878036499023 ]
['To study the demographic and clinical parameters of three different categories of obesity, with particular focus on a cohort of individuals with BMI > or = 50 kg/m2, the fastest growing category of obesity.', 'Over 700 obese individuals were studied (186 with BMI = 30-39 kg/m2, 316 with BMI = 40-49 kg/m2 and 290 with BMI > or = 50 kg/m2).', 'Median BMI was 51 kg/m2 for patients who reported onset of overweight before 15 years of age, 47 kg/m2 for patients who reported onset between 15 and 30 years, and 42 kg/m2 for patients who became overweight after 30 years of age. The BMI > or = 50 kg/m2 group was notably younger than the group with BMI = 30-39 kg/m2 (44 (SD 11) years v. 50 (SD 15) years; P < 0.0001). Eighteen per cent of obese patients studied were considered metabolically healthy according to standard cut-off points for blood pressure, fasting glucose and lipid profiles. However, the proportion of metabolically healthy individuals was significantly higher in the BMI = 30-39 kg/m2 group than in the BMI = 40-49 kg/m2 and BMI > or = 50 kg/m2 groups (31% v. 17% and 12% respectively; P < 0.05 and P < 0.005). When compared with people of similar age in the general population, individuals with BMI > or = 50 kg/m2 had lower rates of marriage (51% v. 72%) and a higher prevalence of unemployment (14% v. 5%).'] Is bMI > or = 50 kg/m2 associated with a younger age of onset of overweight and a high prevalence of adverse metabolic profiles?
qiaojin/PubMedQA
0
[ 2.6638224124908447, -1.6273854970932007, -1.7217686176300049 ]
['Endomyocardial biopsy (EMB) remains the gold standard for acute cellular rejection (ACR) diagnosis in cardiac transplantation yet is subject to interobserver variability. A method that could avoid discordant EMB analysis would be desirable. The apoptosis rate in EMB correlates with ACR severity. Apollon inhibits apoptosis, and RNF41 catalyzes its degradation. Whether tissue Apollon/RNF41 could diagnose ACR is not known. This study addressed this issue.', 'Apollon/RNF41 messenger RNA (mRNA) was measured by real time reverse-transcriptase polymerase chain reaction and apoptosis was quantified with TUNEL assays in EMBs of 268 transplant recipients. EMBs were obtained at 1, 2, 3, 4, 7, 12, 24, and 52 posttransplant weeks.', 'At all time points posttransplant, Apollon mRNA decreased significantly in EMBs with ACR grades 2R/3R combined (P<or=0.0010) compared with 0/1R combined, although RNF41 mRNA significantly increased in EMBs with ACR grade 1R (P<0.0001) or 2R/3R combined (P<0.0001) compared with 0. At the identified cut-off level of less than or equal to 168.2 arbitrary units, Apollon mRNA identified ACR grades 2R/3R with 100% sensitivity and 84% specificity, whereas RNF41 mRNA at the cut-off level of more than or equal to 51.8 identified ACR grades 1R-3R with 99% sensitivity and 95% specificity. Increased RNF41 (rs, 0.728; P<0.0001) and decreased Apollon (rs, -0.562; P<0.0001) expression correlated significantly with the degree of apoptosis in EMBs.'] Does apollon/RNF41 myocardial messenger RNA diagnose cardiac allograft apoptosis in rejection?
qiaojin/PubMedQA
2
[ -1.0300523042678833, -1.7837156057357788, 1.741194248199463 ]
['Plants engineered for abiotic stress tolerance may soon be commercialized. The engineering of these plants typically involves the manipulation of complex multigene networks and may therefore have a greater potential to introduce pleiotropic effects than the simple monogenic traits that currently dominate the plant biotechnology market. While research on unintended effects in transgenic plant systems has been instrumental in demonstrating the substantial equivalence of many transgenic plant systems, it is essential that such analyses be extended to transgenic plants engineered for stress tolerance. Drought-tolerant Arabidopsis thaliana were engineered through overexpression of the transcription factor ABF3 in order to investigate unintended pleiotropic effects. In order to eliminate position effects, the Cre/lox recombination system was used to create control plant lines that contain identical T-DNA insertion sites but with the ABF3 transgene excised. This additionally allowed us to determine if Cre recombinase can cause unintended effects that impact the transcriptome.', 'Microarray analysis of control plant lines that underwent Cre-mediated excision of the ABF3 transgene revealed only two genes that were differentially expressed in more than one plant line, suggesting that the impact of Cre recombinase on the transcriptome was minimal. In the absence of drought stress, overexpression of ABF3 had no effect on the transcriptome, but following drought stress, differences were observed in the gene expression patterns of plants overexpressing ABF3 relative to control plants. Examination of the functional distribution of the differentially expressed genes revealed strong similarity indicating that unintended pathways were not activated.'] Does transcriptome analysis reveal absence of unintended effects in drought-tolerant transgenic plants overexpressing the transcription factor ABF3?
qiaojin/PubMedQA
2
[ -2.401634931564331, -0.8036066889762878, 2.325676441192627 ]
['Oral Cancer Overexpressed 1 (ORAOV1) is a candidate protooncogene locating on 11q13. Recent studies show that ORAOV1 acts as a primary driving force behind 11q13 gene amplification and plays a functional role in the tumorigenesis in a variety of human squamous cell carcinomas (SCCs). According to the results of molecular cytogenetic methods, 11q13 was characterized to be a high-level and recurrent amplification chromosomal site in cervical cancers. Up till now, the role of ORAOV1 in cervical cancer is unknown. The purpose of this study is to elucidate the function of ORAOV1 in cervical cancer cell growth by studying its roles in HeLa cells using small interfering RNA.', 'Functional analyses revealed that ORAOV1 was involved in the regulation of HeLa cell growth through its effect on cell cycle and apoptosis. Silence of ORAOV1 in HeLa cells downregulated the expression of Cyclin A, Cyclin B1 and Cdc2, and led to a distinct S cell cycle arrest. Moreover, knockdown of ORAOV1 expression activated both extrinsic and intrinsic apoptotic pathways and led to apoptosis in HeLa cells through its effect on the expression of several apoptosis related proteins such as P53, Bcl-2, Caspase-3, Caspase-8, Caspase-9 and cytochrome c. Interestingly, the expression of Cyclin D1, a pivotal gene for cervical cancer tumorigenesis, was also found to be reduced in ORAOV1 silenced HeLa cells.'] Does oral cancer overexpressed 1 ( ORAOV1 ) regulate cell cycle and apoptosis in cervical cancer HeLa cells?
qiaojin/PubMedQA
2
[ -2.4762637615203857, -1.1971750259399414, 2.7220821380615234 ]
['Histological examination of pre-transplant renal biopsy specimens can be used to select grafts from older donors after cardiac death (DCD) with a satisfactory transplant outcome. The aim was to determine whether such biopsy specimens can be reproducibly scored between pathologists and are representative of the whole kidney.', 'In renal biopsy specimens from DCD aged >or=60 years (n = 44), globally sclerosed glomeruli, vascular narrowing, tubular atrophy and interstitial fibrosis were scored by three independent pathologists according to the Pirani scoring system. Interobserver agreement on the sum of scores improved considerably with the introduction of a combined tubulo-interstitial scoring system (intraclass correlation coefficient increased from 0.38 to 0.64). In small needle biopsy specimens (n = 144) obtained at autopsy, estimates of the proportion of globally sclerosed glomeruli were more precise with increasing sample size. Reasonably precise estimates may be obtained from specimens with at least seven glomeruli.'] Is histological assessment of pre-transplant kidney biopsies reproducible and representative?
qiaojin/PubMedQA
2
[ -1.9429391622543335, -1.3345251083374023, 2.3696444034576416 ]
['In kidney cancer, new anti-angiogenic therapies have emerged requiring parameters of effectiveness. The aim was to analyse the expression of endocan or endothelial cell-specific molecule-1, which is a proteoglycan up-regulated in presence of pro-angiogenic factors.', 'We investigated 44 renal clear cell carcinomas (RCC) and 25 papillary carcinomas (PC). Circulating endocan was detected by enzyme-linked immunosorbent assays (ELISA) in 14 patients with RCC, in eight with PC and in 15 healthy volunteers. Endocan was detected by immunohistochemistry in endothelial cells in almost all the cases of RCC without immunoreactivity in tumour cells. In PC, only 5/25 tumours exhibited weak immunoreactivity. Reverse transcriptase-polymerase chain reaction study confirmed that endocan levels were strongly increased in RCC. Endocan was also detected by ELISA at levels from 3- to 10-fold higher in the sera of patients with RCC. In vitro, addition of sunitinib prevented the release of endocan in human umbilical vascular endothelial cells when induced by vascular endothelial growth factor.'] Is vascular endocan ( ESM-1 ) markedly overexpressed in clear cell renal cell carcinoma?
qiaojin/PubMedQA
2
[ -2.4025022983551025, -1.3959219455718994, 2.852679491043091 ]
['Resistin was thought to link the obesity to type 2 diabetes. This study aimed to investigate the effect of resistin on insulinoma cell proliferation.', 'pcDNA3.1-resistin was transfected into rat insulinoma cells RINm5F. Cell proliferation was assessed by the MTT assay. The resistin and SOCS3 mRNA levels were assessed by RT-PCR. The total Akt level and the phosphorylation status were assessed by Western blot.', 'The over-expressed resistin inhibited the RINm5F cell proliferation (p<0.05). SOCS-3 expression was up-regulated by resistin over-expression (3.2 folds over the control; p<0.05). Akt phosphorylation was down-regulated by resistin over-expression (0.6 fold over the control; p<0.05).'] Does [ Resistin inhibit rat insulinoma cell RINm5F proliferation ]?
qiaojin/PubMedQA
2
[ -1.881511926651001, -1.2076733112335205, 2.171055555343628 ]
['Cardiac dyssynchrony is common in advanced heart failure (HF), but the changes in cardiac synchrony after myocardial infarction (MI) have not been adequately descríbed.', 'To study the relationship between cardiac synchrony and left ventricular remodeling after acute myocardial infarction.', 'Forty nine patients aged 59+/-10 years (77% men) with a first episode of a ST segment elevation MI, were studied. Scintigraphic left ventricular function and synchrony analyses were performed at baseline and after a six months follow-up. Determinations were compared with 33 healthy subjects.', 'At baseline, patients with MIhad a decreased left ventricular ejection fraction (LVEF) and significant dyssynchrony, when compared with controls. LVEF was 36.4%+/-10%, left ventricular end-diastolic volume (LVEDV) 127+/-38 mL, interventricular delay (IEV) 29+/-35 miliseconds (ms), and intraventricular delay (IAV), 234+/-89 ms. After 6 months, LVEF significantly improved (38%+/-10%, p =0.042) without significant changes in LVEDV (129+/-32 mL, p =0.97), IEV (24+/-17, p =0.96) or IAV (231+/-97, p =0.34). At baseline there were significant correlations between IAV and LVEF, and between IAV and LVEDV (r =0.48, p =0.001 and r =0.41, p =0.004, respectively). These correlations remained significant after 6 months. There was a positive correlation between IAV and LVEDV changes at six months (r =0.403, p =0.04).'] Does [ Cardiac dyssynchrony correlate with left ventricular remodeling after myocardial Infarction ]?
qiaojin/PubMedQA
2
[ -1.0244110822677612, -1.6620028018951416, 1.6778059005737305 ]
['When substituted for carbohydrate in a meal, dietary protein enhances glycaemic control in subjects with type 2 diabetes (DM2). It is unknown whether the effect is a result of increased protein or reduced carbohydrate. The present study aimed to compare the effects of two meals differing in protein to fat ratios on post-prandial glucose and insulin responses.', 'This was a crossover, blind study in which obese subjects with (n = 23) and without (n = 26) DM2 consumed two meals in random order with equal amounts of energy (3.1 MJ, 741 kcal), fibre and carbohydrates and a 1-week washout period. Meals were a high protein, low fat (30% protein, 51% carbohydrates, 19% fat) meal and a low protein, high fat (15% protein, 51% carbohydrates, 34% fat) meal. Subjects were matched for age and body mass index. Plasma glucose and insulin were measured at fasting, 30, 60, 90, 120 min post-prandially. Insulin resistance and insulin sensitivity were assessed.', 'There was no significant meal effect on glucose and insulin responses within groups. Glucose response was higher in diabetic (120 min 11 +/- 0.7 mmol L(-1)) compared to nondiabetic (120 min 5 +/- 0.2; P < 0.001) subjects. Diabetic subjects had significantly higher insulin resistance (P < 0.001) and lower insulin sensitivity (P < 0.001) than nondiabetics. Although peak insulin levels, 60 min post-prandially, did not differ between groups (81 +/- 9 pmol L(-1) for diabetic versus 79 +/- 7 pmol L(-1) for nondiabetic subjects), they were achieved much later, 90 min post-prandially, in diabetic, (99 +/- 8 pmol L(-1)) compared to nondiabetic (63 +/- 7 pmol L(-1), P = 0.002) subjects.'] Does a high protein low fat meal influence glucose and insulin responses in obese individuals with or without type 2 diabetes?
qiaojin/PubMedQA
2
[ -1.048032283782959, -1.4650548696517944, 1.5524320602416992 ]
['The accumulation and aggregation of alpha-synuclein in nerve cells and glia are characteristic features of a number of neurodegenerative diseases termed synucleinopathies. alpha-Synuclein is a highly soluble protein which in a nucleation dependent process is capable of self-aggregation. The causes underlying aggregate formation are not yet understood, impairment of the proteolytic degradation systems might be involved.', 'In the present study the possible aggregate clearing effects of the geldanamycin analogue 17-AAG (17-(Allylamino)-17-demethoxygeldanamycin) was investigated. Towards this, an oligodendroglial cell line (OLN-93 cells), stably expressing human alpha-synuclein (A53T mutation) was used. In these cells small punctate aggregates, not staining with thioflavine S, representing prefibrillary aggregates, occur characteristically. Our data demonstrate that 17-AAG attenuated the formation of alpha-synuclein aggregates by stimulating macroautophagy. By blocking the lysosomal compartment with NH(4)Cl the aggregate clearing effects of 17-AAG were abolished and alpha-synuclein deposits were enlarged. Analysis of LC3-II immunoreactivity, which is an indicator of autophagosome formation, further revealed that 17-AAG led to the recruitment of LC3-II and to the formation of LC3 positive puncta. This effect was also observed in cultured oligodendrocytes derived from the brains of newborn rats. Inhibition of macroautophagy by 3-methyladenine prevented 17-AAG induced occurrence of LC3 positive puncta as well as the removal of alpha-synuclein aggregates in OLN-A53T cells.'] Does 17-AAG induce cytoplasmic alpha-synuclein aggregate clearance by induction of autophagy?
qiaojin/PubMedQA
2
[ -2.4432122707366943, -1.3321646451950073, 2.7985665798187256 ]
['Patients reproduce symptoms of primary open-angle glaucoma (POAG) when treated with glucocorticoids (GCs) topically on the eyes. Here we investigated the effects of GCs on junctional protein expression and cytoskeleton organization in primary human trabecular meshwork (TM) cultures to understand the molecular pathologies of POAG.', 'Human TM cells from POAG (GTM) and age-matched nondiseased (NTM) individuals were obtained by standard surgical trabeculectomy. Some of the cultures were treated with dexamethasone (DEX), a synthetic GC, at 1-5 x 10(-7) mol/l for 1-7 days. The expression levels of zonula occluden-1 (ZO-1) and connexin43 (Cx43) in TM cells with or without DEX treatment were measured using reverse transcription (RT)-PCR, immunocytochemistry, and western blot analysis.', 'mRNA and proteins of ZO-1 and Cx43 were found in both NTM and GTM cells. ZO-1 and Cx43 were located on the plasma membrane, especially along the border of adjacent cells. ZO-1 had no marked changes in localization in NTM and GTM cells after treatment with 10(-7) mol/l DEX for 48 h, whereas Cx43 appeared to increase in the cytoplasm. mRNA of two ZO-1 isoforms, alpha+ and alpha-, were present in TM cells, and the former was expressed less than the latter. Only ZO-1 alpha- isoform protein was expressed in NTM cells, whereas proteins of both isoforms were found in GTM cells. DEX increased the protein levels of ZO-1 and Cx43 in both NTM and GTM cells. DEX also altered the F-actin architecture and promoted cross-linked actin network formation, the effects of which were more pronounced in GTM cells.'] Does dexamethasone disrupt intercellular junction formation and cytoskeleton organization in human trabecular meshwork cells?
qiaojin/PubMedQA
2
[ -2.3267364501953125, -1.442348837852478, 2.790228843688965 ]
['The efficacy of tight glycemic control for the prevention of death and renal failure in the general diabetic population is well established. However, in diabetic renal-allograft recipients, the effect of different treatment strategies on outcomes is undetermined.', 'We conducted a cohort study of 798 diabetic, renal-allograft recipients transplanted at the Medical University of Vienna between 1990 and 2004. We studied the influence of glucose parameters and diabetes treatment on mortality and graft loss. Marginal-structural models and multivariable Cox regression analysis were used to control for confounding.', 'Maximal glucose levels but not HbA1c were independently associated with mortality. Being in the highest quartile of maximal glucose increased the adjusted risk of death by a factor of 2.2 (P value for trend 0.009). Furthermore, in patients receiving insulin, the risk of death was increased 1.7-fold (95% confidence interval 0.9-3.1) compared with diet and 2.0-fold (95% confidence interval 1.1-3.7) compared with oral medication. Maximal glucose, HbA1c, or diabetes treatment did not influence death-censored functional graft survival.'] Is glucose control associated with patient survival in diabetic patients after renal transplantation?
qiaojin/PubMedQA
2
[ -2.0901010036468506, -1.061092495918274, 2.219012498855591 ]
['Phosphatidylinositol 3-phosphate is involved in regulation of several key cellular processes, mainly endocytosis, signaling, nuclear processes, cytoskeletal remodelling, cell survival, membrane trafficking, phagosome maturation and autophagy. In most cases effector proteins bind to this lipid, using either FYVE or PX domain. These two domains are distributed amongst varied life forms such as virus, protists, fungi, viridiplantae and metazoa. As the binding ligand is identical for both domains, the goal of this study was to understand if there is any selectivity for either of these domains in different taxa. Further, to understand the different cellular functions that these domains may be involved in, we analyzed the taxonomic distribution of additional domains that associate with FYVE and PX.', 'There is selectivity for either FYVE or PX in individual genomes where both domains are present. Fungi and metazoa encode more PX, whereas streptophytes in viridiplantae encode more FYVE. Excess of FYVE in streptophytes results from proteins containing RCC1and DZC domains and FYVE domains in these proteins have a non-canonical ligand-binding site. Within a taxonomic group the selected domain associates with a higher number of other domains and is thus expected to discharge a larger number of cellular functions. Also, while certain associated domains are present in all taxonomic groups, most of them are unique to a specific group indicating that while certain common functions are discharged by these domains in all taxonomic groups, some functions appear to be group specific.'] Does comparative genomics reveal selective distribution and domain organization of FYVE and PX domain proteins across eukaryotic lineages?
qiaojin/PubMedQA
2
[ -2.5212996006011963, -0.9061387777328491, 2.5641350746154785 ]
['Insulin resistance is intrinsically related to intramyocellular (IMCL) rather than extramyocellular (EMCL) triglyceride content. Conflicting results have been reported on the ability of insulin sensitizer agents, such as thiazolidinediones, to modify muscle fat distribution. The aim of this study was to investigate the role of rosiglitazone on muscle fat compartment distribution in an adult population of obese non-diabetic metabolic syndrome patients.', 'Fifteen obese, non-diabetic, metabolic syndrome patients were studied by means of proton nuclear magnetic resonance ((1)H-NMR) spectroscopy before and after treatment with rosiglitazone 8 mg/day for 6 months. Anthropometrical and metabolic variables were assessed.', 'After rosiglitazone, body weight and hip circumference increased [100.9 (91.12-138.7) vs. 107.0 (79.6-142.8) kg and 118 (107-126) vs. 122 (110-131) cm]; while waist-hip ratio (WHR) decreased from 0.93 (0.87-1.00) to 0.89 (0.82-0.97) (P < 0.001 for all). Additionally, fasting plasma glucose, insulin and homeostatis model assessment of insulin resistance (HOMA-IR) significantly decreased while adiponectin increased over threefold [9.7 (3.7-17.7) vs. 38.0 (19.3-42.4) microg/ml] without any changes in resistin. Finally, the IMCL did not change [267.54 (213.94-297.94) vs. 305.75 (230.80-424.75) arbitrary units (AU), P = 0.15] while the EMCL increased [275.53 (210.39-436.66) vs. 411.39 (279.92-556.59) AU; P < 0.01] therefore decreasing the IMCL-to-EMCL (IMCL/EMCL) ratio [1.07 (0.78-1.23) vs. 0.71 (0.53-0.96); P < 0.01].'] Does rosiglitazone decrease intra- to extramyocellular fat ratio in obese non-diabetic adults with metabolic syndrome?
qiaojin/PubMedQA
2
[ -1.6491554975509644, -1.6325522661209106, 2.2721686363220215 ]
['Although the limitations of the Friedewald-calculated serum low-density lipoprotein cholesterol (LDL-C) are well recognized, many diabetes and lipid guidelines propose LDL-C as a therapeutic target. The validity of calculated LDL-C in people with Type 1 diabetes (T1DM) is uncertain and the use of alternatives such as non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein measurement unexplored. We have therefore measured LDL-C with the designated reference method and examined some of the potential sources of such bias, including plasma concentrations of other lipids and apolipoproteins.', 'Seventy-four people with T1DM and 80 healthy control subjects were recruited. Fasting samples were collected for analysis of lipid profiles by a beta-quantification (BQ) reference method and by routine laboratory methods including direct HDL-C and calculation of LDL-C using the Friedewald formula.', 'Overall, Friedewald LDL-C was 0.29 +/- 0.02 (mean +/- SE) mmol/l (P < 0.001) lower in the two groups than by the BQ method. This resulted in misclassification of approximately 50% of people with a calculated LDL-C < 2.0 mmol/l. Overestimation of HDL-C by the routine assay [0.08 +/- 0.01 mmol/l (P < 0.001)] accounted for approximately 28% of the error in calculation of LDL-C and the remainder appeared to be as a result of triglyceride in lipoprotein particles other than very-low-density lipoprotein (VLDL). Correlation of non-HDL-C with apolipoprotein B was better than LDL-C with apolipoprotein B for both assays in both diabetic and non-diabetic populations.'] Does friedewald equation underestimate low-density lipoprotein cholesterol at low concentrations in young people with and without Type 1 diabetes?
qiaojin/PubMedQA
2
[ -0.9917682409286499, -1.7580065727233887, 1.7166118621826172 ]
['To determine the difference in the levels of nitrites in induced sputum of children with cystic fibrosis (CF) and controls. Furthermore, to evaluate the association between induced sputum nitrites and lung function in children with CF.', 'Nitrites, cell differentials, white blood cell count, were estimated in induced sputum of 20 children with CF and 10 age-matched healthy controls. Nitrites in induced sputum samples were measured using the Greiss assay. Lung function was ascertained by spirometry.', 'We observed high levels of nitrites in CF (184.8 +/- 11.07 microM/L) versus controls (56.4 +/- 5.7 microM/L) (p < 0.01). A positive correlation between neturophil percent and nitrites, white blood cell count and nitrites (p < 0.05) in children with CF was observed. Sputum nitrites correlated negatively with FEV(1) (p < 0.05) in children with CF.'] Do induced sputum nitrites correlate with FEV1 in children with cystic fibrosis?
qiaojin/PubMedQA
2
[ -1.7396461963653564, -1.307881236076355, 2.082242727279663 ]
['Cross-regulation between TNF and type I IFN has been postulated to play an important role in autoimmune diseases. Therefore, we determined the effect of TNF blockade in rheumatoid arthritis (RA) on the type I IFN response gene activity in relation to clinical response.', 'Peripheral blood from 33 RA patients was collected in PAXgene tubes before and after the start of infliximab treatment. In a first group of 15 patients the baseline expression of type I IFN-regulated genes was determined using cDNA microarrays and compared to levels one month after treatment. The remaining 18 patients were studied as an independent group for validation using quantitative polymerase chain reaction (qPCR).', 'Gene expression analysis revealed that anti-TNF antibody treatment induced a significant increase in type I IFN response gene activity in a subset of RA patients, whereas expression levels remained similar or were slightly decreased in others. The findings appear clinically relevant since patients with an increased IFN response gene activity after anti-TNF therapy had a poor clinical outcome. This association was confirmed and extended for an IFN response gene set consisting of OAS1, LGALS3BP, Mx2, OAS2 and SERPING1 in five EULAR good and five EULAR poor responders, by qPCR.'] Is regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis associated with clinical response to treatment?
qiaojin/PubMedQA
2
[ -2.3992879390716553, -1.3459224700927734, 2.8315653800964355 ]
['Gene therapy in the hematopoietic system remains promising, though certain aspects of vector design, such as transcriptional control elements, continue to be studied. Our group has developed a retroviral vector where transgene expression is controlled by p53 with the intention of harnessing the dynamic and inducible nature of this tumor suppressor and transcription factor. We present here a test of in vivo expression provided by the p53-responsive vector, pCLPG. For this, we used a model of serial transplantation of transduced bone marrow cells.', 'We observed, by flow cytometry, that the eGFP transgene was expressed at higher levels when the pCLPG vector was used as compared to the parental pCL retrovirus, where expression is directed by the native MoMLV LTR. Expression from the pCLPG vector was longer lasting, but did decay along with each sequential transplant. The detection of eGFP-positive cells containing either vector was successful only in the bone marrow compartment and was not observed in peripheral blood, spleen or thymus.'] Does serial bone marrow transplantation reveal in vivo expression of the pCLPG retroviral vector?
qiaojin/PubMedQA
2
[ -2.437069892883301, -1.166029930114746, 2.745079517364502 ]
['Low-grade serous carcinoma (LGSC) is a chemoresistant ovarian neoplasm thought to potentially arise in a background of low malignant potential tumors (LMP), which are typically non-aggressive. However, LMP with micropapillary features (LMP-MP) have more aggressive clinical behavior and may represent an intermediate in progression to LGSC. The objective of this study was to obtain and compare gene expression profiles of LMP, LMP-MP and LGSC to determine if LMP-MP more closely resembles LGSC, and to identify genes involved in LGSC carcinogenesis.', 'Epithelial cells from LMP (n=17), LMP-MP (n=9) and LGSC (n=11) were isolated by laser capture microdissection. RNA was extracted, reverse transcribed to cDNA, amplified and hybridized to Affymetrix U133 Plus2 genechip arrays. Gene expression data were checked for quality, filtered and significantly altered genes between subgroups were identified. Differential expression of selected genes was verified by RT-qPCR and immunohistochemistry.', 'Gene expression analysis identified differential expression between LMP and LMP-MP, LMP and LGSC but not LMP-MP and LGSC. Integration of differentially expressed genes into the protein interaction database CytoScape highlighted gene products in the MAPK pathway as differentially regulated between LMP and LGSC. Four genes were selected and validated by RT-qPCR performed on microarray samples (n=15) and immunohistochemistry on a representative microarray (n=57).'] Are low malignant potential tumors with micropapillary features molecularly similar to low-grade serous carcinoma of the ovary?
qiaojin/PubMedQA
2
[ -2.2689154148101807, -1.3875916004180908, 2.732272148132324 ]
['We aimed to report 3-year survival and causes of death of first-ever ischemic stroke stratified by initial stroke severity.', "From September 1998 to October 1999, 360 acute first-ever ischemic stroke patients consecutively admitted were followed up prospectively. Patients' vital status and causes of death were identified from the National Death Registry, till December 31, 2002. Potential prognostic factors available at admission were evaluated using Cox proportional hazards regression analysis with bootstrap validation.", 'Three hundred and sixty patients, 58% males with age 64.9 years on average, were followed up for 43.4 months with no lost follow-up. Ninety-two (25.6%) patients died, 25 in the first month. The cumulative case-fatality rates were 12.2%, 15.8%, 20.5% and 25.6% for years 1-4. The proportion of vascular deaths was 84% during the first 30 days and 71% for the subsequent 5 months. The hazard ratio (95% CI) was 1.08 (1.05-1.11) for age (1-year increment), 335.90 (20.72-5446.23) for NIHSS 16-38, 2.48 (1.39-4.42) for NIHSS 7-15, and 0.95 (0.91-0.99) for an interaction term of age and NIHSS 16-38.'] Is three-year survival after first-ever ischemic stroke predicted by initial stroke severity : A hospital-based study?
qiaojin/PubMedQA
2
[ -1.3838313817977905, -0.8849624991416931, 1.535745620727539 ]
['Despite its role as a generator of haplotypic variation, little is known about how the rates of recombination evolve across taxa. Recombination is a very labile force, susceptible to evolutionary and life trait related processes, which have also been correlated with general levels of genetic diversity. For example, in plants, it has been shown that long-lived outcrossing taxa, such as trees, have higher heterozygosity (He) at SSRs and allozymes than selfing or annual species. However, some of these tree taxa have surprisingly low levels of nucleotide diversity at the DNA sequence level, which points to recombination as a potential generator of genetic diversity in these organisms. In this study, we examine how genome-wide and within-gene rates of recombination evolve across plant taxa, determine whether such rates are influenced by the life-form adopted by species, and evaluate if higher genome-wide rates of recombination translate into higher He values, especially in trees.', 'Estimates of genome-wide (cM/Mb) recombination rates from 81 higher plants showed a significant phylogenetic signal. The use of different comparative phylogenetic models demonstrated that there is a positive correlation between recombination rate and He (0.83 +/- 0.29), and that trees have higher rates of genome-wide recombination than short-lived herbs and shrubs. A significant taxonomic component was further made evident by our models, as conifers exhibited lower recombination rates than angiosperms. This trend was also found at the within-gene level.'] Does the contribution of recombination to heterozygosity differ among plant evolutionary lineages and life-forms?
qiaojin/PubMedQA
2
[ -1.884167194366455, 0.4593023955821991, 0.5682908296585083 ]
['The immune response to trauma has traditionally been modeled to consist of the systemic inflammatory response syndrome (SIRS) followed by the compensatory anti-inflammatory response syndrome (CARS). We investigated these responses in a homogenous cohort of male, severe blunt trauma patients admitted to a University Hospital surgical intensive care unit (SICU). After obtaining consent, peripheral blood was drawn up to 96 hours following injury. The enumeration and functionality of both myeloid and lymphocyte cell populations were determined.', 'Neutrophil numbers were observed to be elevated in trauma patients as compared to healthy controls. Further, neutrophils isolated from trauma patients had increased raft formation and phospho-Akt. Consistent with this, the neutrophils had increased oxidative burst compared to healthy controls. In direct contrast, blood from trauma patients contained decreased naïve T cell numbers. Upon activation with a T cell specific mitogen, trauma patient T cells produced less IFN-gamma as compared to those from healthy controls. Consistent with these results, upon activation, trauma patient T cells were observed to have decreased T cell receptor mediated signaling.'] Are divergent adaptive and innate immunological responses observed in humans following blunt trauma?
qiaojin/PubMedQA
2
[ -2.6614301204681396, -1.0299708843231201, 2.7671821117401123 ]
['An increase in carotid intima-media thickness (CIMT) represents an early phase of the atherosclerotic process. The aim of our study was to evaluate whether a reduction in CIMT could be seen with 1-year treatment with rosuvastatin (10 mg/day).', 'Forty-five patients with hypercholesterolemia and asymptomatic carotid atherosclerosis on baseline carotid ultrasound investigation (CUI) were examined with repeat CUI after 1 year of treatment (rosuvastatin 10 mg/day). Demographic and lifestyle data were collected. A physical examination was performed, and fasting venous blood samples were obtained. Total cholesterol, low-density lipoprotein cholesterol and triglycerides decreased significantly (p < 0.001), while high-density lipoprotein cholesterol increased significantly (p < 0.001) during the intervention. The mean decreases in the IMT of the right and left common carotid arteries (CCAs) were 0.29 and 0.26 mm, respectively (p < 0.05 for each). Age and lipid profile parameters were significant predictors of change in CIMT in linear regression analyses after adjustment for established atherosclerosis risk factors.'] Does one-year treatment with rosuvastatin reduce intima-media thickness in 45 hypercholesterolemic subjects with asymptomatic carotid artery disease?
qiaojin/PubMedQA
2
[ -2.1638331413269043, -1.4378020763397217, 2.658999443054199 ]
['The aim of the study was to evaluate whether the "Quantitative Blush Evaluator" (QuBE) score is associated with measures of myocardial reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated in two hospitals with 24/7 coronary intervention facilities.', 'QuBE is an open source computer program to quantify myocardial perfusion. Although QuBE has shown to be practical and feasible in the patients enrolled in the Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS), QuBE has not yet been verified on reperfusion outcomes of primary percutaneous coronary intervention (PCI) patients treated in other catheterization laboratories.', 'Core lab adjudicated angiographic outcomes and QuBE values were assessed on angiograms of patients who were enrolled in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-Elevation (PREPARE) trial. ST-segment resolution immediately after PCI measured by continuous ST Holter monitoring was calculated by a blinded core lab.', 'The QuBE score could be assessed on 229 of the 284 angiograms (81%) and was significantly associated with visually assessed myocardial blush grade (P < 0.0001). Patients with improved postprocedural Thrombolysis in Myocardial Infarction-graded flow, myocardial blush grade, ST-segment resolution immediately after PCI, or a small infarct size measured by peak CK-MB had a significant better QuBE score.'] Do feasibility and applicability of computer-assisted myocardial blush quantification after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction?
qiaojin/PubMedQA
2
[ -2.234649181365967, -1.4191443920135498, 2.7103424072265625 ]
['Definitive practice guidelines regarding the utility of chest x-ray (CXR) following chest tube removal in trauma patients have not been established. The authors hypothesized that the selective use of CXR following chest tube removal is safe and cost effective.', 'A retrospective review of chest tube insertions performed at a level I trauma center was conducted.', 'Patients who underwent chest tube removal without subsequent CXR had a lower mean Injury Severity Score and were less likely to have suffered penetrating thoracic injuries. These patients received fewer total CXRs and had shorter durations of chest tube therapy and shorter lengths of stay following tube removal. Subsequent reinterventions were performed more frequently in the CXR group. The annual decrease in hospital charges by foregoing a CXR was $16,280.'] Is omission of routine chest x-ray after chest tube removal safe in selected trauma patients?
qiaojin/PubMedQA
2
[ -2.4102232456207275, -0.6486198306083679, 2.1237406730651855 ]
['Oxidative stress (OS) is enhanced in hemodialysis (HD) patients. Lipid peroxidation and oxidative damage to glycids, proteins and nucleic acids are the main consequences of OS and are associated with increased cardiovascular risk. Vitamin E and glutathione peroxidase (GSH-Px) represent the main antioxidant systems in human cells. Selenium (Se), bound to the active sites of GSH-Pxs, plays a critical role in this antioxidant defence system. Statins are widely used and extensively investigated in the prevention of cardiovascular disease, notably in high-risk subjects. Several studies show antioxidant effects of statins not related to their lipid-lowering action. Our study aimed to compare serum Se concentration in ESRD patients on maintenance HD and in homogeneous healthy subjects and to investigate whether chronic treatment with statins may interfere with serum Se concentration in HD patients.', 'A total of 103 HD patients and 69 healthy subjects were enrolled; HD patients were divided into patients who were not treated with statins (group A) and patients who assumed statins since 6 months at least (group B). Serum Se was determined by atomic absorption spectrometry.', 'Serum Se was significantly lower in HD patients of group A compared with healthy subjects (81.65+/-19.66 Vs. 96.47+/-15.62 mcg/L, p<0.0040). However, in HD patients who assumed statins serum, Se was significantly higher than in HD patients who did not (111.83+/-18.82 vs. 81.65+/-19.66 mcg/L, p<0.0001).'] Does chronic treatment with statins increase the availability of selenium in the antioxidant defence systems of hemodialysis patients?
qiaojin/PubMedQA
2
[ -1.2182108163833618, -1.646784782409668, 1.8233624696731567 ]
['To investigate whether chronic vigorous exercising is related to improved sleep and psychological functioning, and whether this association varies with gender. Both lay and scientific opinions hold that physical activity is an efficient remedy and preventative measure for poor sleep. However, empirical evidence on adolescents is very limited.', 'A total of 434 adolescents (258 athletes, 176 controls; mean age 17.2 years) took part in the study. Weekly hours spent exercising were 17.69 hours and 4.69 hours, respectively. To assess sleep patterns and psychological functioning, participants completed a sleep log for 7 consecutive days and several self-rating questionnaires.', 'Compared with controls, athletes reported better sleep patterns including higher sleep quality, shortened sleep onset latency, and fewer awakenings after sleep onset, as well as less tiredness and increased concentration during the day. Athletes reported significantly lower anxiety and fewer depressive symptoms. Compared with males, females reported fewer variations in sleep. Male controls had particularly unfavorable scores related to sleep and psychological functioning.'] Are high exercise levels related to favorable sleep patterns and psychological functioning in adolescents : a comparison of athletes and controls?
qiaojin/PubMedQA
1
[ -1.712623953819275, 2.6020054817199707, -1.2996203899383545 ]
['Before ovulation, sperm-oviduct interaction mechanisms may act as checkpoint for the selection of fertilizing spermatozoa in mammals. Postovulatory mating does not allow the sperm to attach to the oviduct, and spermatozoa may only undergo some selection processes during the transport through the female reproductive tract and/or during the zona pellucida (ZP) binding/penetration.', 'We have induced DNA damage in spermatozoa by two treatments, (a) a scrotal heat treatment (42 degrees C, 30 min) and (b) irradiation with 137Cs gamma-rays (4 Gy, 1.25 Gy/min). The effects of the treatments were analyzed 21-25 days post heat stress or gamma-radiation. Postovulatory females mated either with treated or control males were sacrificed at Day 14 of pregnancy, and numbers of fetuses and resorptions were recorded.', 'Both treatments decreased significantly implantation rates however, the proportion of fetuses/resorptions was only reduced in those females mated to males exposed to radiation, indicating a selection favoring fertilization of sperm with unfragmented DNA on the heat treatment group. To determine if DNA integrity is one of the keys of spermatozoa selection after postovulatory mating, we analyzed sperm DNA fragmentation by COMET assay in: a) sperm recovered from mouse epididymides; b) sperm recovered from three different regions of female uterine horns after mating; and c) sperm attached to the ZP after in vitro fertilization (IVF). Similar results were found for control and both treatments, COMET values decreased significantly during the transit from the uterine section close to the uterotubal junction to the oviduct, and in the spermatozoa attached to ZP. However, fertilization by IVF and intracytoplasmatic sperm injection (ICSI) showed that during sperm ZP-penetration, a stringent selection against fragmented-DNA sperm is carried out when the damage was induced by heat stress, but not when DNA fragmentation was induced by radiation.'] Does selection against spermatozoa with fragmented DNA after postovulatory mating depend on the type of damage?
qiaojin/PubMedQA
2
[ -2.3832695484161377, -0.9344722032546997, 2.3795766830444336 ]
['Currently platelet concentrates (PC) are collected using different synthetic materials and different centrifugation/leucocyte-removal processes. Upon exposure to artificial surfaces and high centrifugation forces, blood cells can undergo various levels of stress-induced, cellular activation/fragmentation and release reactions which may not only influence the extent of the platelet storage lesion but may also contribute to poor clinical effectiveness of the PC and transfusion reactions.', 'An array of assays, used for quality control of PC, was performed in two different groups of PC prepared from random donor plasma on days 1, 3 and 5 of storage. The group 1 PC were not leucoreduced while the group 2 PC underwent prestorage leucoreduction using a PL50E filter. As current recommendations for the evaluation of PC include the measurement of platelet activation, in this study CD62P on platelet membrane was measured. Furthermore, in vitro studies indicate that sHLA antigens may modulate immune competent cell function so, the presence of sHLA-1 in blood components is considered a marker of immunological reactivity and this, too, was measured.', 'The levels of CD62P and sHLA-1 were significantly lower in leucoreduced PC than in non-leucoreduced ones. However, the overall rate of increase of sHLA-1 during storage was faster in the leucoreduced group of PC. No significant differences were detected regarding other assays of quality.'] Does in vitro assessment of platelet storage lesion in leucoreduced random donor platelet concentrate?
qiaojin/PubMedQA
2
[ -2.3604722023010254, -1.2649691104888916, 2.747647285461426 ]
['To investigate whether aerobic fitness and obesity in school children are associated with standardized test performance.', 'Ethnically diverse (n = 1989) 5th, 7th, and 9th graders attending California schools comprised the sample. Aerobic fitness was determined by a 1-mile run/walk test; body mass index (BMI) was obtained from state-mandated measurements. California standardized test scores were obtained from the school district.', 'Students whose mile run/walk times exceeded California Fitnessgram standards or whose BMI exceeded Centers for Disease Control sex- and age-specific body weight standards scored lower on California standardized math, reading, and language tests than students with desirable BMI status or fitness level, even after controlling for parent education among other covariates. Ethnic differences in standardized test scores were consistent with ethnic differences in obesity status and aerobic fitness. BMI-for-age was no longer a significant multivariate predictor when covariates included fitness level.'] Are low aerobic fitness and obesity associated with lower standardized test scores in children?
qiaojin/PubMedQA
1
[ -1.883853554725647, 2.2589123249053955, -1.0325772762298584 ]
['To test the hypothesis that frequent participation in cognitive activities can moderate the effects of limited education on cognitive functioning.', 'A national study of adult development and aging, Midlife in the United States, with assessments conducted at the second wave of measurement in 2004-2006.', 'Assessments were made over the telephone (cognitive measures) and in a mail questionnaire (demographic variables, measures of cognitive and physical activity, and self-rated health).', 'A total of 3,343 men and women between the ages of 32 and 84 with a mean age of 55.99 years.', 'The dependent variables were Episodic Memory (Immediate and Delayed Word List Recall) and Executive Functioning (Category Fluency, Backward Digit Span, Backward Counting Speed, Reasoning, and Attention Switching Speed). The independent variables were years of education and frequency of cognitive activity (reading, writing, doing word games or puzzles, and attending lectures). The covariates were age, sex, self-rated health, income, and frequency of physical activity.', 'The two cognitive measures were regressed on education, cognitive activity frequency, and their interaction, while controlling for the covariates. Education and cognitive activity were significantly correlated with both cognitive abilities. The interaction of education and cognitive activity was significant for episodic memory but not for executive functioning.'] Does frequent cognitive activity compensate for education differences in episodic memory?
qiaojin/PubMedQA
2
[ -2.1971852779388428, 0.34061965346336365, 0.9959001541137695 ]
['CRISP-3 was previously shown to be bound to alpha(1)B-glycoprotein (A1BG) in human serum/plasma. All mammalian sera are supposed to contain A1BG, although its presence in rodent sera is not well-documented. Since animal sera are often used to supplement buffers in experiments, in particular such that involve cell cultures, binding proteins present in sera might interfere in the experiments.', 'We examined sera from five different animal species for CRISP-3 binding proteins using gel filtration and ligand blotting. We developed a rapid method for isolation of proteins that bind to human CRISP-3 and identified the isolated proteins by mass spectrometry and N-terminal sequencing.', 'We identified A1BG as a CRISP-3 binding protein in sera from cow, horse and rabbit. CRISP-3 bound kininogen 1 in mouse serum, whereas rat serum showed no CRISP-3 binding activity. In equine serum, we furthermore detected a possible CRISP, already bound to A1BG.'] Does human CRISP-3 bound serum alpha ( 1 ) B-glycoprotein across species?
qiaojin/PubMedQA
2
[ -2.1830098628997803, -0.7234472632408142, 2.0538856983184814 ]
['Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. These ligands can determine the ultimate fate of target cells by stimulating or repressing gene expression directly, or indirectly through crosstalking with other signal transducers.', 'Using different breast cancer cell models, we show here that depending on the cellular context retinoids can signal either towards cell death or cell survival. Indeed, retinoids can induce the expression of pro-apoptotic (i.e. TRAIL, TNF-Related Apoptosis-Inducing Ligand, Apo2L/TNFSF10) and anti-apoptotic (i.e. cIAP2, inhibitor of apoptosis protein-2) genes. Promoter mapping, gel retardation and chromatin immunoprecipitation assays revealed that retinoids induce the expression of this gene mainly through crosstalk with NF-kappaB. Supporting this crosstalk, the activation of NF-kappaB by retinoids in T47D cells antagonizes the apoptosis triggered by the chemotherapeutic drugs etoposide, camptothecin or doxorubicin. Notably apoptosis induced by death ligands (i.e. TRAIL or antiFAS) is not antagonized by retinoids. That knockdown of cIAP2 expression by small interfering RNA does not alter the inhibition of etoposide-induced apoptosis by retinoids in T47D cells reveals that stimulation of cIAP2 expression is not the cause of their anti-apoptotic action. However, ectopic overexpression of a NF-kappaB repressor increases apoptosis by retinoids moderately and abrogates almost completely the retinoid-dependent inhibition of etoposide-induced apoptosis. Our data exclude cIAP2 and suggest that retinoids target other regulator(s) of the NF-kappaB signaling pathway to induce resistance to etoposide on certain breast cancer cells.'] Does retinoic acid protect human breast cancer cells against etoposide-induced apoptosis by NF-kappaB-dependent but cIAP2-independent mechanisms?
qiaojin/PubMedQA
2
[ -2.5020394325256348, -1.1719045639038086, 2.719616413116455 ]
["The safety and efficacy of maintenance therapy with the anti-tumor necrosis factor certolizumab pegol has not been reported beyond 6 months. We assessed the long-term efficacy, safety, and immunogenicity of continuous versus interrupted maintenance therapy with subcutaneous certolizumab pegol in patients with Crohn's disease.", "Patients who responded to induction therapy at week 6 of the PEGylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECiSE) 2 trial were assigned randomly to groups given certolizumab pegol (continuous) or placebo (drug-interruption) during weeks 6 to 26. Patients who completed PRECiSE 2 were eligible to enter PRECiSE 3, an ongoing, prospective, open-label extension trial in which patients have received certolizumab pegol (400 mg) every 4 weeks for 54 weeks to date, and were not offered the option to increase their dose. Disease activity was measured by the Harvey-Bradshaw Index.", 'Harvey-Bradshaw Index responses at week 26 for the continuous and drug-interruption groups were 56.3% and 37.6%, respectively; corresponding remission rates were 47.9% and 32.4%, respectively. Of patients responding at week 26, response rates at week 80 after the start of PRECiSE 2 in the continuous and drug-interruption groups were 66.1% and 63.3%, respectively; among patients in remission at week 26, week 80 remission rates were 62.1% and 63.2%, respectively. More patients in the drug-interruption group developed antibodies against certolizumab pegol (and had lower plasma concentrations of certolizumab pegol) than the continuously treated group.'] Does continuous therapy with certolizumab pegol maintain remission of patients with Crohn 's disease for up to 18 months?
qiaojin/PubMedQA
2
[ -1.7672908306121826, -1.5185998678207397, 2.303284168243408 ]
['The actual risk factors that drive hepatic inflammation during the transition from steatosis to steatohepatitis are unknown. We recently demonstrated that hyperlipidemia-prone apolipoprotein E-deficient (ApoE(-/-)) mice exhibit hepatic steatosis and increased susceptibility to hepatic inflammation and advanced fibrosis. Because the proinflammatory 5-lipoxygenase (5-LO) pathway was found to be up-regulated in these mice and given that 5-LO deficiency confers cardiovascular protection to ApoE(-/-) mice, we determined the extent to which the absence of 5-LO would alter liver injury in these mice. Compared with ApoE(-/-) mice, which showed expected hepatic steatosis and inflammation, ApoE/5-LO double-deficient (ApoE(-/-)/5-LO(-/-)) mice exhibited reduced hepatic inflammation, macrophage infiltration, tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-18 expression, caspase-3 and nuclear factor-kappaB (NF-kappaB) activities, and serum alanine aminotransferase levels in the absence of changes in hepatic steatosis. The lack of 5-LO produced a remarkable insulin-sensitizing effect in the adipose tissue because peroxisome proliferator-activated receptor gamma, insulin receptor substrate-1, and adiponectin were up-regulated, whereas c-Jun amino-terminal kinase phosphorylation and MCP-1 and IL-6 expression were down-regulated. On the other hand, hepatocytes isolated from ApoE(-/-)/5-LO(-/-) mice were more resistant to TNF-alpha-induced apoptosis. The 5-LO products leukotriene (LT) B(4), LTD(4), and 5-HETE consistently triggered TNF-alpha-induced apoptosis and compromised hepatocyte survival by suppressing NF-kappaB activity in the presence of actinomycin D. Moreover, ApoE(-/-)/5-LO(-/-) mice were protected against sustained high-fat diet (HFD)-induced liver injury and hepatic inflammation, macrophage infiltration and insulin resistance were significantly milder than those of ApoE(-/-) mice. Finally, pharmacological inhibition of 5-LO significantly reduced hepatic inflammatory infiltrate in the HFD and ob/ob models of fatty liver disease.'] Does 5-lipoxygenase deficiency reduce hepatic inflammation and tumor necrosis factor alpha-induced hepatocyte damage in hyperlipidemia-prone ApoE-null mice?
qiaojin/PubMedQA
2
[ -2.3682868480682373, -1.3535466194152832, 2.700428009033203 ]
['Stroke remains an important complication after coronary artery bypass graft surgery (CABG). We sought to determine the frequency and death-related incidence of stroke after on-pump and off-pump CABG.', 'We analyzed 4,869 consecutive isolated CABG performed in our institution. Of these, 3,490 (71.7%) were off-pump and 1,379 (28.3%) were on-pump. Propensity matched samples of 1,379 off-pump and 1,379 on-pump were compared on clinical presentation and The Society of Thoracic Surgeons (STS) predicted scores for risk of postoperative mortality and stroke. Univariate analyses were used to compare the relationship of off-pump and on-pump groups to postoperative mortality and stroke. Multivariate logistic regression was used to determine the unique association between all variables and occurrence of mortality after stroke.', 'No differences were found for sex, diabetes mellitus, history of renal failure, prior stroke, or timing of surgery. Postoperative mortality occurred in 75 patients (2.7%) and stroke in 47 (1.7%). The off-pump patients had a lower rate of stroke (1.0% versus 2.4%; p < 0.01) compared with on-pump patients. Mortality after stroke occurred in 14 patients, with a lower rate occurring in the off-pump group (14.3% versus 36.4%; p = 0.07). Multivariate analyses controlling for the effect of preoperative risk factors and STS mortality risk demonstrated that off-pump status was independently associated with an 84% decrease in the risk of death after stroke (adjusted odds ratio 0.157, 95% confidence interval: 0.035 to 0.711, p = 0.016).'] Is stroke-related mortality in coronary surgery reduced by the off-pump approach?
qiaojin/PubMedQA
2
[ -1.696885347366333, -1.2779796123504639, 2.0556323528289795 ]
['Cerebrovascular disease (CVD) is a major determinant of the prognosis in end-stage renal diseases (ESRD). The purpose of this study was to examine whether factors associated with arterial stiffness contributed to the development of CVD in patients with ESRD.', 'CVD (lacunes and carotid/intracranial artery stenosis) was evaluated with brain magnetic resonance imaging (MRI), and carotid/intracranial artery magnetic resonance angiography (MRA) in 44 pre-dialytic patients. The severity of CVD was evaluated by the number of lacunes and the degree of stenosis, respectively. The association between CVD and atherosclerotic parameters was evaluated.', 'Patients with severe lacunes (n=18) manifested older age, lower diastolic blood pressure, serum creatinine and albumin, and higher CRP and serum calcium than those with absent-moderate lacunes (n=26). When assessed by multivariate analysis, only baPWV was adopted as an independent risk factor for severe lacunes. Furthermore, baPWV and i-PTH were associated with the severity of carotid/intracranial artery stenosis, both of which were independent of other risk factors, including age and diabetes.'] Does brachial-ankle pulse wave velocity predict silent cerebrovascular diseases in patients with end-stage renal diseases?
qiaojin/PubMedQA
2
[ -2.4199469089508057, -1.2944915294647217, 2.819140911102295 ]
['Transcriptional control of hematopoietic lineage fate relies on the integration of many intra- and extracellular signals. To test whether the microenvironment impacts on leukemic phenotype, we exploited the MN1 model of acute myeloid leukemia under defined genetically modified microenvironmental conditions.', 'The requirement of both FLT3 and c-Kit signaling for MN1 leukemias was investigated using retroviral infection of bone marrow cells from wild-type, c-Kit-mutated (W41), and Flt3-ligand knockout cells, and bone marrow transplantation into wild-type, c-Kit-mutated, or Flt3-ligand knockout mice.', 'Genetic disruption of both FLT3 and c-Kit signaling in the MN1-leukemia model was dispensable for MN1-induced leukemogenesis. However, it induced a switch from myeloid to erythroid phenotype that was preserved, when FLT3 signaling was restored by secondary transplantation of leukemic cells into wild-type recipients.'] Do extrinsic signals determine myeloid-erythroid lineage switch in MN1 leukemia?
qiaojin/PubMedQA
2
[ -2.626939535140991, -0.9502226710319519, 2.6651861667633057 ]
['The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I.', 'Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-I(N)), lipid-free apoA-I nonenzymatically glycated by incubation with methylglyoxal (apoA-I(Glyc in vitro)), nonenzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I(Glyc in vivo)), discoidal reconstituted high-density lipoproteins (rHDL) containing phosphatidylcholine and apoA-I(N), (A-I(N))rHDL, or apoA-I(Glyc in vitro), (A-I(Glyc in vitro))rHDL. At 24 hours postinfusion, acute vascular inflammation was induced by inserting a nonocclusive, periarterial carotid collar. The animals were euthanized 24 hours after the insertion of the collar. The collars caused intima/media neutrophil infiltration and increased endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). ApoA-I(N) infusion decreased neutrophil infiltration and VCAM-1 and ICAM-1 expression by 89%, 90%, and 66%, respectively. The apoA-I(Glyc in vitro) infusion decreased neutrophil infiltration by 53% but did not reduce VCAM-1 or ICAM-1 expression. ApoA-I(Glyc in vivo) did not inhibit neutrophil infiltration or adhesion molecule expression. (A-I(Glyc in vitro))rHDL also inhibited vascular inflammation less effectively than (A-I(N))rHDL. The reduced antiinflammatory properties of nonenzymatically glycated apoA-I were attributed to a reduced ability to inhibit nuclear factor-kappaB activation and reactive oxygen species formation.'] Does nonenzymatic glycation impair the antiinflammatory properties of apolipoprotein A-I?
qiaojin/PubMedQA
2
[ -2.3842036724090576, -1.4158047437667847, 2.8024468421936035 ]
['Naringenin is a citrus flavonoid that potently inhibits the assembly and secretion of apolipoprotein B100-containing lipoproteins in cultured hepatocytes and improves the dyslipidemia and insulin resistance in a mouse model of the metabolic syndrome. In the present study, we used low-density lipoprotein receptor-null mice fed a high-fat diet (Western, TD96125) to test the hypothesis that naringenin prevents atherosclerosis.', 'Three groups (chow, Western, and Western plus naringenin) were fed ad libitum for 6 months. The Western diet increased fasting plasma triglyceride (TG) (5-fold) and cholesterol (8-fold) levels compared with chow, whereas the addition of naringenin significantly decreased both lipids by 50%. The Western-fed mice developed extensive atherosclerosis in the aortic sinus because plaque area was increased by 10-fold compared with chow-fed animals. Quantitation of fat-soluble dye (Sudan IV)-stained aortas, prepared en face, revealed that Western-fed mice also had a 10-fold increase in plaque deposits throughout the arch and in the abdominal sections of the aorta, compared with chow. Atherosclerosis in both areas was significantly decreased by more than 70% in naringenin-treated mice. Consistent with quantitation of aortic lesions, the Western-fed mice had a significant 6-fold increase in cholesterol and a 4-fold increase in TG deposition in the aorta compared with chow-fed mice. Both were reduced more than 50% by naringenin. The Western diet induced extensive hepatic steatosis, with a 10-fold increase in both TG and cholesteryl ester mass compared with chow. The addition of naringenin decreased both liver TG and cholesteryl ester mass by 80%. The hyperinsulinemia and obesity that developed in Western-fed mice was normalized by naringenin to levels observed in chow-fed mice.'] Does naringenin decrease progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice?
qiaojin/PubMedQA
2
[ -2.112732172012329, -1.4523451328277588, 2.5018558502197266 ]
['Circulating progenitor cells (CPC) have emerged as potential mediators of vascular repair. In experimental models, CPC mobilization is critically dependent on nitric oxide (NO). South Asian ethnicity is associated with reduced CPC. We assessed CPC mobilization in response to exercise in Asian men and examined the role of NO in CPC mobilization per se.', 'In 15 healthy, white European men and 15 matched South Asian men, CPC mobilization was assessed during moderate-intensity exercise. Brachial artery flow-mediated vasodilatation was used to assess NO bioavailability. To determine the role of NO in CPC mobilization, identical exercise studies were performed during intravenous separate infusions of saline, the NO synthase inhibitor L-NMMA, and norepinephrine. Flow-mediated vasodilatation (5.8%+/-0.4% vs 7.9%+/-0.5%; P=0.002) and CPC mobilization (CD34(+)/KDR(+) 53.2% vs 85.4%; P=0.001; CD133(+)/CD34(+)/KDR(+) 48.4% vs 73.9%; P=0.05; and CD34(+)/CD45(-) 49.3% vs 78.4; P=0.006) was blunted in the South Asian group. CPC mobilization correlated with flow-mediated vasodilatation and l-NMMA significantly reduced exercise-induced CPC mobilization (CD34(+)/KDR(+) -3.3% vs 68.4%; CD133(+)/CD34(+)/KDR(+) 0.7% vs 71.4%; and CD34(+)/CD45(-) -30.5% vs 77.8%; all P<0.001).'] Is human exercise-induced circulating progenitor cell mobilization nitric oxide-dependent and is blunted in South Asian men?
qiaojin/PubMedQA
2
[ -1.7984524965286255, -1.5642125606536865, 2.347781181335449 ]
['Activated endothelium and increased monocyte-endothelial interactions in the vessel wall are key early events in atherogenesis. ATP binding cassette (ABC) transporters play important roles in regulating sterol homeostasis in many cell types. Endothelial cells (EC) have a high capacity to efflux sterols and express the ABC transporter, ABCG1. Here, we define the role of ABCG1 in the regulation of lipid homeostasis and inflammation in aortic EC.', 'Using EC isolated from ABCG1-deficient mice (ABCG1 KO), we observed reduced cholesterol efflux to high-density lipoprotein compared to C57BL/6 (B6) EC. However, total cholesteryl ester levels were not changed in ABCG1 KO EC. Secretions of KC, MCP-1, and IL-6 by ABCG1 KO EC were significantly increased, and surface expressions of intercellular adhesion molecule-1 and E-selectin were increased several-fold on ABCG1 KO EC. Concomitant with these findings, we observed a 4-fold increase in monocyte adhesion to the intact aortic endothelium of ABCG1 KO mice ex vivo and to isolated aortic EC from these mice in vitro. In a gain-of-function study in vitro, restoration of ABCG1 expression in ABCG1 KO EC reduced monocyte-endothelial interactions. Utilizing pharmacological inhibitors for STAT3 and the IL-6 receptor, we found that blockade of STAT3 and IL-6 receptor signaling in ABCG1 KO EC completely abrogated monocyte adhesion to ABCG1 KO endothelium.'] Does aBCG1 deficiency in mice promote endothelial activation and monocyte-endothelial interactions?
qiaojin/PubMedQA
2
[ -2.40352463722229, -1.2719218730926514, 2.6887600421905518 ]
['The objective of this cross-sectional study was to determine the prevalence of migraine headache among depressed Latino adults of Mexican American origin meeting the criteria for bipolar disorder (BPD) or major depressive disorder (MDD) relative to patients in a psychiatric comparison group.', 'In a mental health clinic for the indigent, consecutively and systematically evaluated acutely depressed Latino adults received structured diagnostic psychiatric interviews based on modules extracted from the Structured Clinical Interview for DSM-IV. All were asked as part of routine assessment whether they had headaches "in the last week." Patients with unilateral, pounding, pulsating headache were classified as having migraine headache. The prevalence of migraine headache among the patients with BPD and MDD was contrasted with that of patients in a psychiatric comparison group composed of patients with disorders other than schizophrenia or schizoaffective disorder. Logistic regression was used to test for associations and control for confounding effects. The data were collected between August 2001 and November 2004.', 'Eighty-seven patients had BPD and 123 had MDD. Bipolar patients were 2.9 times more likely to have migraine headaches than patients with MDD (P < .0001). There was a trend for patients with MDD to have a higher prevalence of migraine than patients in the psychiatric comparison group.'] Is migraine headache in affectively ill latino adults of mexican american origin associated with bipolarity?
qiaojin/PubMedQA
2
[ -1.620017647743225, 0.3447420597076416, 0.44032353162765503 ]