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['Pterygium is a prevalent ocular surface disease with unknown pathogenesis. The authors investigated the role of nuclear factor kappa B (NF-κB) transcription factors in pterygium.', 'Surgically excised primary pterygia were studied compared with uninvolved conjunctiva tissues. NF-κB activation was evaluated using Western blot analysis, ELISA, and DNA-binding assays. Primary pterygium fibroblasts were treated with TNF-α (20 ng/mL), and NF-κB activation was evaluated using immunocytochemistry, Western blot analysis, phospho-IκBα ELISA, and DNA-binding assays. TNF-α stimulation of NF-κB target genes RelB, NFKB2, RANTES, MCP-1, ENA-78, MMP-1, MMP-2, and MMP-3 in pterygium fibroblasts was compared with that in primary tenon fibroblasts by real-time PCR.', 'Phosphorylation of IκBα (Ser32) was increased in pterygia tissues compared with uninvolved conjunctiva tissues, as determined by Western blot analysis and ELISA. IκBα expression was decreased, whereas nuclear RelA and p50 DNA-binding capacities were increased. Within 30 minutes of treatment with TNF-α, pterygium fibroblasts showed increased IκBα phosphorylation and nuclear translocation of RelA and p50. Treatment with TNF-α beyond 12 hours resulted in increased nuclear expression of RelB, p100, and p52. Furthermore, the upregulation of RANTES, MCP-1, ENA-78, MMP-1, MMP-2, and MMP-3 expression was more pronounced in TNF-α-treated pterygium fibroblasts than in tenon fibroblasts.'] Is the nuclear-factor kappaB pathway activated in pterygium?
qiaojin/PubMedQA
2
[ -2.317197561264038, -1.4732539653778076, 2.780156135559082 ]
['Familial hemophagocytic lymphohistiocytosis is a genetic disorder of lymphocyte cytotoxicity that usually presents in the first two years of life and has a poor prognosis unless treated by hematopoietic stem cell transplantation. Atypical courses with later onset and prolonged survival have been described, but no detailed analysis of immunological parameters associated with typical versus atypical forms of familial hemophagocytic lymphohistiocytosis has been performed.', 'We analyzed disease manifestations, NK-cell and T-cell cytotoxicity and degranulation, markers of T-cell activation and B-cell differentiation as well as Natural Killer T cells in 8 patients with atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2.', 'All but one patient with atypical familial hemophagocytic lymphohistiocytosis carried at least one splice-site mutation in UNC13D or STXBP2. In most patients episodes of hemophagocytic lymphohistiocytosis were preceded or followed by clinical features typically associated with immunodeficiency, such as chronic active Epstein Barr virus infection, increased susceptibility to bacterial infections, granulomatous lung or liver disease, encephalitis or lymphoma. Five of 8 patients had hypogammaglobulinemia and reduced memory B cells. Most patients had a predominance of activated CD8(+) T cells and low numbers of Natural Killer T cells. When compared to patients with typical familial hemophagocytic lymphohistiocytosis, NK-cell cytotoxicity and NK-cell and CTL degranulation were impaired to a similar extent. However, in patients with an atypical course NK-cell degranulation could be partially reconstituted by interleukin-2 and cytotoxic T-cell cytotoxicity in vitro was normal.'] Does atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlap with primary immunodeficiency diseases?
qiaojin/PubMedQA
2
[ -2.3808469772338867, -1.3974356651306152, 2.818218231201172 ]
['The characterization of the molecular changes that underlie the origin and diversification of morphological novelties is a key challenge in evolutionary developmental biology. The evolution of such traits is thought to rely largely on co-option of a toolkit of conserved developmental genes that typically perform multiple functions. Mutations that affect both a universal developmental process and the formation of a novelty might shed light onto the genetics of traits not represented in model systems. Here we describe three pleiotropic mutations with large effects on a novel trait, butterfly eyespots, and on a conserved stage of embryogenesis, segment polarity.', 'We show that three mutations affecting eyespot size and/or colour composition in Bicyclus anynana butterflies occurred in the same locus, and that two of them are embryonic recessive lethal. Using surgical manipulations and analysis of gene expression patterns in developing wings, we demonstrate that the effects on eyespot morphology are due to changes in the epidermal response component of eyespot induction. Our analysis of morphology and of gene expression in mutant embryos shows that they have a typical segment polarity phenotype, consistent with the mutant locus encoding a negative regulator of Wingless signalling.'] Does single locus affect embryonic segment polarity and multiple aspects of an adult evolutionary novelty?
qiaojin/PubMedQA
2
[ -2.8104374408721924, 0.5402563214302063, 1.2985799312591553 ]
['Multivitamin use is widespread in the United States, especially among patients with cancer. However, the influence of multivitamin supplementation on cancer recurrence and death after a curative resection of colon cancer is unknown.', 'We conducted a prospective, observational study of 1,038 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on multivitamin use during and 6 months after adjuvant chemotherapy. Patients were observed until March 2009 for disease recurrence and death. To minimize bias by occult recurrence, we excluded patients who recurred or died within 90 days of their multivitamin assessment.', 'Among 1,038 patients, 518 (49.9%) reported multivitamin use during adjuvant chemotherapy. Compared with nonusers, the multivariate hazard ratio (HR) for disease-free survival was 0.94 (95% CI, 0.77 to 1.15) for patients who used multivitamins. Similarly, multivitamin use during adjuvant chemotherapy was not significantly associated with recurrence-free survival (multivariate HR, 0.93; 95% CI, 0.75 to 1.15) or overall survival (multivariate HR 0.92; 95% CI, 0.74 to 1.16). Multivitamin use reported 6 months after completion of adjuvant chemotherapy was also not associated with improved patient outcome, and consistent use both during and following adjuvant therapy conferred no benefit. Neither an increasing number of tablets nor increasing duration of use before cancer diagnosis was associated with cancer recurrence or mortality. Multivitamin use also did not improve the rates of grade 3 and higher GI toxicity.'] Is multivitamin use associated with cancer recurrence or survival in patients with stage III colon cancer : findings from CALGB 89803?
qiaojin/PubMedQA
2
[ -1.8142184019088745, -1.4374804496765137, 2.248595952987671 ]
['Retinoid X receptors (RXRs) are members of the nuclear hormone receptor superfamily and are thought to be key regulators in differentiation, cellular growth, and gene expression. Although several experiments using pancreatic β-cell lines have shown that the ligands of nuclear hormone receptors modulate insulin secretion, it is not clear whether RXRs have any role in insulin secretion.', 'To elucidate the function of RXRs in pancreatic β-cells, we generated a double-transgenic mouse in which a dominant-negative form of RXRβ was inducibly expressed in pancreatic β-cells using the Tet-On system. We also established a pancreatic β-cell line from an insulinoma caused by the β-cell-specific expression of simian virus 40 T antigen in the above transgenic mouse.', 'In the transgenic mouse, expression of the dominant-negative RXR enhanced the insulin secretion with high glucose stimulation. In the pancreatic β-cell line, the suppression of RXRs also enhanced glucose-stimulated insulin secretion at a high glucose concentration, while 9-cis-retinoic acid, an RXR agonist, repressed it. High-density oligonucleotide microarray analysis showed that expression of the dominant-negative RXR affected the expression levels of a number of genes, some of which have been implicated in the function and/or differentiation of β-cells.'] Does nuclear hormone retinoid X receptor ( RXR ) negatively regulate the glucose-stimulated insulin secretion of pancreatic ß-cells?
qiaojin/PubMedQA
2
[ -2.5323598384857178, -1.0333662033081055, 2.6012866497039795 ]
['Recommendations promote a diversified and optimal but not excessive consumption of dairy products. Their efficiency may depend on sociodemographic and economic factors, for which little information is available. Links between these factors and dairy intake were investigated in a large sample of French adults.', 'Dietary intakes were assessed using at least six 24-h dietary records collected during a 2-year period from 4574 adults aged 45-60 years. The cost of each food item was estimated from national data. Sociodemographic and economic characteristics were assessed by self-administered questionnaires. Compliance with the current dairy recommendation, distribution of the dairy budget and calcium inadequacy were compared by logistic regression and covariance analyses.', 'Thirty-five percent of subjects complied with the three-per-day dairy recommendation, with more men than women exceeding this (36.2% versus 26.5%, P < 0.0001). The proportion of the dairy budget spent on milk increased with age in men (P = 0.002); in women, it was inversely associated with occupational category (P = 0.009) and residence in an urban area (P = 0.0001). The proportion of this budget spent on cheese increased with education level in women (P = 0.04) and decreased with age in men (P = 0.03). In men, the consumption of cream desserts decreased with age (P = 0.006) and education level (P = 0.002). Dietary calcium inadequacy was more prevalent in women than in men (32.7% versus 14.2%, P < 0.0001). Among women, this prevalence was higher in older subjects (P < 0.0001) and those who lived alone (P = 0.005).'] Do sociodemographic and economic characteristics associated with dairy intake vary across genders?
qiaojin/PubMedQA
0
[ 0.22227296233177185, -0.6106328368186951, -0.514683723449707 ]
['Mesenchymal stromal cells (MSC) are gaining in popularity as an experimental therapy for a number of conditions that often require expansion ex vivo prior to use. Data comparing clinical-grade MSC from various ages of donors are scant. We hypothesized that MSC from older donors may display differences in cellular fitness when expanded for clinical use.', 'We evaluated the expression of several markers of aging, oxidative stress and growth kinetics, and telomere length, in MSC obtained from a wide age range (8 months to 58 years).', 'To evaluate cellular fitness we compared MSC expanded from younger (8 months-6 years) versus older (38-58 years) donors in terms of selected cell-surface markers, lipofuscin, migration ability, telomere length and expression of iNOS, PGE₂, p16INK and SOD. Results did not differ between these groups. Neither SOD activity (0.025 versus 0.028 U/mL) nor death after oxidative challenge was significantly different (1% versus 1.5%, P = 0.14). We did find that, although MSC from older individuals produced slightly fewer cells over a 28-day culture period and had a slightly longer doubling time (54 h versus 42 hr, a satisfactory clinical product could still be obtained regardless of age cohort.'] Are mesenchymal stromal cells from donors varying widely in age of equal cellular fitness after in vitro expansion under hypoxic conditions?
qiaojin/PubMedQA
2
[ -1.9178606271743774, -1.2686614990234375, 2.2142527103424072 ]
['The chondrogenic differentiation potential of mesenchymal stromal cells (MSC), as well as their immunosuppressive properties, have been studied extensively. So far, only a few studies have addressed the question of whether MSC still retain their immunosuppressive qualities after transdifferentiation. In particular, the expression of immunogenic markers, such as human leukocyte antigen (HLA)-DR, after differentiation has never been investigated.', 'Chondrogenic transdifferentiation was induced in human adipose tissue-derived stem cell (ADSC) pellet cultures derived from 10 different patients, using 10 ng/mL transforming growth factor (TGF)-β3. Samples were harvested over a time-course of 28 days and analyzed by immunohistochemistry and reverse transcription (RT)-polymerase chain reaction (PCR). The cytokine levels in the supernatants of the samples were measured semi-quantitatively by dot-blots and quantitatively by enzyme-linked immunosorbant assays (ELISA).', 'Undifferentiated ADSC were negative for chondrogenic markers, as well as HLA-ABC and HLA-DR epitopes in immunofluorescence. In contrast, TGF-β3-induced pellet cultures showed both expression of chondrogenic differentiation markers, such as transcription factor 9 (Sox 9), collagen type IIa and aggrecan, and an up-regulation of HLA-DR, beginning at day 7 after induction. Interferon-γ (INF-γ) is known to up-regulate HLA-DR. Therefore we measured INF-γ levels in the supernatants of TGF-β3-induced pellets and, indeed, INF-γ was up-regulated during chondrogenesis in ADSC pellet cultures. However, both undifferentiated and TGF-β3-induced ADSC also showed expression of immunosuppressive HLA-G and interleukin (IL)-10 up-regulation.'] Do adipose tissue-derived stem cells show both immunogenic and immunosuppressive properties after chondrogenic differentiation?
qiaojin/PubMedQA
2
[ -2.3783042430877686, -1.3862190246582031, 2.844566822052002 ]
['To determine if posttraumatic nonconvulsive electrographic seizures result in long-term brain atrophy.', 'Prospective continuous EEG (cEEG) monitoring was done in 140 patients with moderate to severe traumatic brain injury (TBI) and in-depth study of 16 selected patients was done using serial volumetric MRI acutely and at 6 months after TBI. Fluorodeoxyglucose PET was done in the acute stage in 14/16 patients. These data were retrospectively analyzed after collection of data for 7 years.', 'cEEG detected seizures in 32/140 (23%) of the entire cohort. In the selected imaging subgroup, 6 patients with seizures were compared with a cohort of 10 age- and GCS-matched patients with TBI without seizures. In this subgroup, the seizures were repetitive and constituted status epilepticus in 4/6 patients. Patients with seizures had greater hippocampal atrophy as compared to those without seizures (21 +/- 9 vs 12 +/- 6%, p = 0.017). Hippocampi ipsilateral to the electrographic seizure focus demonstrated a greater degree of volumetric atrophy as compared with nonseizure hippocampi (28 +/- 5 vs 13 +/- 9%, p = 0.007). A single patient had an ictal PET scan which demonstrated increased hippocampal glucose uptake.'] Are nonconvulsive seizures after traumatic brain injury associated with hippocampal atrophy?
qiaojin/PubMedQA
2
[ -2.1508543491363525, -1.3288848400115967, 2.505922794342041 ]
['DNA methylation is an epigenetic mechanism with important regulatory functions in animals. While the mechanism itself is evolutionarily ancient, the distribution and function of DNA methylation is diverse both within and among phylogenetic groups. Although DNA methylation has been well studied in mammals, there are limited data on invertebrates, particularly molluscs. Here we characterize the distribution and investigate potential functions of DNA methylation in the Pacific oyster (Crassostrea gigas).', 'Methylation sensitive PCR and bisulfite sequencing PCR approaches were used to identify CpG methylation in C. gigas genes and demonstrated that this species possesses intragenic methylation. In silico analysis of CpGo/e ratios in publicly available sequence data suggests that DNA methylation is a common feature of the C. gigas genome, and that specific functional categories of genes have significantly different levels of methylation.'] Do dNA methylation patterns provide insight into epigenetic regulation in the Pacific oyster ( Crassostrea gigas )?
qiaojin/PubMedQA
2
[ -2.5477101802825928, -0.031711362302303314, 1.6779416799545288 ]
['The L1 cell adhesion molecule (L1CAM) was originally identified as a neural adhesion molecule involved in axon guidance. In many human epithelial carcinomas L1CAM is overexpressed and thereby augments cell motility, invasion and metastasis formation. L1CAM positive carcinomas are associated with bad prognosis. Recent data point out that L1CAM is regulated in a fashion similar to epithelial-mesenchymal transition (EMT). Previous studies have implied the transcription factors Slug and/or β-catenin in L1CAM transcriptional regulation. However, the regulation of human L1CAM expression at the transcriptional level is not well understood.', 'To better understand the molecular basis of L1CAM transcriptional regulation, we carried out a detailed characterization of the human L1CAM promoter. We identified two transcription start sites, the first in front of a non-translated exon 0 (promoter 1) and the other next to the first protein-coding exon 1 (promoter 2). Both sites could be verified in endometrial carcinoma (EC) cell lines and appear to be used in a cell-type specific manner. The two identified promoter regions showed activity in luciferase reporter assays. Chromatin-IP analyses confirmed the in silico predicted E-boxes, binding sites for transcription factors Snail and Slug, as well as Lef-1 sites, which are related to β-catenin-mediated transcriptional regulation, in both promoters. Overexpression of β-catenin exclusively augmented activity of promoter 1 whereas Slug enhanced promoter 1 and 2 activity suggesting that both promoters can be active. Overexpression of β-catenin or Slug could upregulate L1CAM expression in a cell-type specific manner.'] Is l1CAM expression in endometrial carcinomas regulated by usage of two different promoter regions?
qiaojin/PubMedQA
2
[ -2.2913572788238525, -1.2641663551330566, 2.567943572998047 ]
['This study aimed to investigate the educational needs of research ethics among nursing researchers.', 'Convenience sample of 161 nursing professors and 262 master or doctoral nursing students participated in the study. Data was collected with self-reported questionnaire from June to August 2009, and analyzed with descriptive statistics using SPSS WIN (version 14.0).', 'Among 161 nursing professors, about 31.7% has educated nursing ethics in the postgraduate course. The most common course was nursing research or methodology (62.7%), and median education time was 2 hr. Areas that showed difficulty in understanding was the conflict of interest and plagiarism for professors and falsification and fabrication for graduate students. Average knowledge on the research ethics was 75.4 points for professors and 61.6 points for students based on the 100 points.'] Does [ Educational need assessment on research ethics among nursing researchers ]?
qiaojin/PubMedQA
1
[ -0.18049606680870056, 1.5334888696670532, -1.8630530834197998 ]
['Postharvest losses of citrus fruit due to green mold decay, caused by the fungus Penicillium digitaum, have a considerable economic impact. However, little is known about the molecular processes underlying the response of citrus fruit to P. digitatum.', "Here we describe the construction of a subtracted cDNA library enriched in citrus genes preferentially expressed in response to pathogen infection followed by cDNA macroarray hybridization to investigate gene expression during the early stages of colonization of the fruit's peel by P. digitatum. Sequence annotation of clones from the subtracted cDNA library revealed that induction of secondary and amino acid metabolisms constitutes the major response of citrus fruits to P. digitatum infection. Macroarray hybridization analysis was conducted with RNA from either control, wounded, ethylene treated or P. digitatum infected fruit. Results indicate an extensive overlap in the response triggered by the three treatments, but also demonstrated specific patterns of gene expression in response to each stimulus. Collectively our data indicate a significant presence of isoprenoid, alkaloid and phenylpropanoid biosynthetic genes in the transcriptomic response of citrus fruits to P. digitatum infection. About half of the genes that are up-regulated in response to pathogen infection are also induced by ethylene, but many examples of ethylene-independent gene regulation were also found. Two notable examples of this regulation pattern are the genes showing homology to a caffeine synthase and a berberine bridge enzyme, two proteins involved in alkaloid biosynthesis, which are among the most induced genes upon P. digitatum infection but are not responsive to ethylene."] Does a transcriptomic approach highlight induction of secondary metabolism in citrus fruit in response to Penicillium digitatum infection?
qiaojin/PubMedQA
2
[ -2.6852848529815674, -0.8784927725791931, 2.6484334468841553 ]
['The enthesis, which attaches the tendon to the bone, naturally disappears with aging, thus limiting joint mobility. Surgery is frequently needed but the clinical outcome is often poor due to the decreased natural healing capacity of the elderly. This study explored the benefits of a treatment based on injecting chondrocyte and mesenchymal stem cells (MSC) in a new rat model of degenerative enthesis repair.', "The Achilles' tendon was cut and the enthesis destroyed. The damage was repaired by classical surgery without cell injection (group G1, n = 52) and with chondrocyte (group G2, n = 51) or MSC injection (group G3, n = 39). The healing rate was determined macroscopically 15, 30 and 45 days later. The production and organization of a new enthesis was assessed by histological scoring of collagen II immunostaining, glycoaminoglycan production and the presence of columnar chondrocytes. The biomechanical load required to rupture the bone-tendon junction was determined.", 'The spontaneous healing rate in the G1 control group was 40%, close to those observed in humans. Cell injection significantly improved healing (69%, p = 0.0028 for G2 and p = 0.006 for G3) and the load-to-failure after 45 days (p<0.05) over controls. A new enthesis was clearly produced in cell-injected G2 and G3 rats, but not in the controls. Only the MSC-injected G3 rats had an organized enthesis with columnar chondrocytes as in a native enthesis 45 days after surgery.'] Does mesenchymal stem cell therapy regenerate the native bone-tendon junction after surgical repair in a degenerative rat model?
qiaojin/PubMedQA
2
[ -2.186372756958008, -1.4579743146896362, 2.656527519226074 ]
['Matricellular proteins, including periostin, modulate cell-matrix interactions and cell functions by acting outside of cells.', 'In this study, however, we reported that periostin physically associates with the Notch1 precursor at its EGF repeats in the inside of cells. Moreover, by using the periodontal ligament of molar from periostin-deficient adult mice (Pn-/- molar PDL), which is a constitutively mechanically stressed tissue, we found that periostin maintained the site-1 cleaved 120-kDa transmembrane domain of Notch1 (N1) level without regulating Notch1 mRNA expression. N1 maintenance in vitro was also observed under such a stress condition as heat and H(2)O(2) treatment in periostin overexpressed cells. Furthermore, we found that the expression of a downstream effector of Notch signaling, Bcl-xL was decreased in the Pn-/- molar PDL, and in the molar movement, cell death was enhanced in the pressure side of Pn-/- molar PDL.'] Does periostin associate with Notch1 precursor to maintain Notch1 expression under a stress condition in mouse cells?
qiaojin/PubMedQA
2
[ -2.42439341545105, -1.1903016567230225, 2.6611897945404053 ]
['It is unclear what effect therapeutic hypothermia may have on renal function, because its effect has so far been primarily evaluated in settings in which there may be possible confounding perturbations in cardiovascular and renal physiology, such deep intraoperative hypothermia, general anesthesia, and post-cardiac arrest. We sought to determine if therapeutic hypothermia affects renal function in awake patients with normal renal function who were enrolled into a clinical trial of hypothermia plus intravenous thrombolysis for acute ischemic stroke.', 'Eleven patients with normal renal function were cooled to 33°C for 24 h using an endovascular catheter, and then re-warmed over 12 h to 36.5°C, while hourly temperature, blood pressure, and fluid status data was recorded. Blood samples for blood urea nitrogen (BUN), creatinine, and hematocrit were drawn prior to treatment (baseline), immediately after hypothermia and re-warming (day 2), and again at day 7 or discharge, and values compared.', 'On initiation of cooling, temperatures dropped from a median pre-treatment value of 36.1°C (IQR: 35.8-36.4°C) to 33.1°C (IQR: 33.1-33.4°C). Urine output decreased 5.1 ml/h for every 1°C decrease in body temperature (p-value=0.001), with no associated serious adverse events. There were no statistically significant changes in BUN, creatinine, or hematocrit in the hypothermia patients.'] Is therapeutic hypothermia associated with a decrease in urine output in acute stroke patients?
qiaojin/PubMedQA
2
[ -2.1871821880340576, -1.2340370416641235, 2.506840229034424 ]
['Both allergic and nonallergic rhinitis have been associated with increased prevalence of asthma.', 'To characterize asthma and intermediary asthma endpoints in young children with allergic and nonallergic rhinitis.', 'Thirty-eight 7-year-old children with allergic rhinitis, 67 with nonallergic rhinitis, and 185 without rhinitis from the Copenhagen Prospective Study on Asthma in Childhood birth cohort were compared for prevalence of asthma, eczema, food sensitization, filaggrin null-mutations, total IgE, blood eosinophil count, fractional exhaled nitric oxide (FeNO), lung function, and bronchial responsiveness.', 'Children with allergic rhinitis compared with asymptomatic controls had increased prevalence of asthma (21% vs 5%; P = .002), food sensitization (47% vs 13%; P < .001), and eczema (66% vs 43%; P = .01) and increased total IgE (155 kU/L vs 41 kU/L; P < .001), blood eosinophil count (0.46 x 10(9)/L vs 0.30 x 10(9)/L; P = .01), FeNO (15.9 ppb vs 6.6 ppb; P < .001), and bronchial hyperresponsiveness (23% vs 9%; P = .008). Filaggrin null-mutations were associated with allergic rhinitis (odds ratio, 3.3; 95% CI, 1.3-8.3) but did not modify these associations. Children with nonallergic rhinitis also had increased asthma prevalence (20% vs 5%; P = .001) but showed no association with filaggrin null-mutations, eczema, food sensitization, total IgE, blood eosinophil count, FeNO, or bronchial responsiveness.'] Do children with allergic and nonallergic rhinitis have a similar risk of asthma?
qiaojin/PubMedQA
2
[ -1.4522831439971924, -1.2015026807785034, 1.588770866394043 ]
['Purpose in life is thought to be associated with positive health outcomes in old age, but its association with disability is unknown.', 'Test the hypothesis that greater purpose in life is associated with a reduced risk of incident disability, including impairment in basic and instrumental activities of daily living and mobility disability, among community-based older persons free of dementia.', 'Participants were from the Rush Memory and Aging Project, a large longitudinal clinical-pathologic study of aging.', 'Retirement communities, senior housing facilities, and homes across the greater Chicago metropolitan area.', 'All participants underwent baseline assessment of purpose in life and detailed annual clinical evaluations to document incident disability.', 'The mean score on the purpose in life measure at baseline was 3.6 (standard deviation = 0.5, range: 2-5). In a series of proportional hazards models adjusted for age, sex, and education, greater purpose in life was associated with a reduced risk of disability in basic activities of daily living (hazard ratio [HR] = 0.60, 95% confidence interval [C1] = 0.45-0.81), instrumental activities of daily living (HR = 0.56, 95% CI = 0.40-0.78), and mobility disability (HR = 0.61, 95% CI = 0.44-0.84). These associations did not vary along demographic lines and persisted after the addition of terms to control for global cognition, depressive symptoms, social networks, neuroticism, income, physical frailty, vascular risk factors, and vascular diseases.'] Is purpose in life associated with a reduced risk of incident disability among community-dwelling older persons?
qiaojin/PubMedQA
2
[ -2.5178072452545166, 0.11545075476169586, 1.4976288080215454 ]
['In our earlier reports, we showed that downregulation of uPA and uPAR inhibited glioma tumor angiogenesis in SNB19 cells, and intraperitoneal injection of a hairpin shRNA expressing plasmid targeting uPA and uPAR inhibited angiogenesis in nude mice. The exact mechanism by which inhibition of angiogenesis takes place is not clearly understood.', 'In the present study, we have attempted to investigate the mechanism by which uPA/uPAR downregulation by shRNA inhibits angiogenesis in endothelial and glioblastoma cell lines. uPA/uPAR downregulation by shRNA in U87 MG and U87 SPARC co-cultures with endothelial cells inhibited angiogenesis as assessed by in vitro angiogenesis assay and in vivo dorsal skin-fold chamber model in nude mice. Protein antibody array analysis of co-cultures of U87 and U87 SPARC cells with endothelial cells treated with pU2 (shRNA against uPA and uPAR) showed decreased angiogenin secretion and angiopoietin-1 as well as several other pro-angiogenic molecules. Therefore, we investigated the role of angiogenin and found that nuclear translocation, ribonucleolytic and 45S rRNA synthesis, which are all critical for angiogenic function of angiogenin, were significantly inhibited in endothelial cells transfected with uPA, uPAR and uPA/uPAR when compared with controls. Moreover, uPA and uPAR downregulation significantly inhibited the phosphorylation of Tie-2 receptor and also down regulated FKHR activation in the nucleus of endothelial cells via the GRB2/AKT/BAD pathway. Treatment of endothelial cells with ruPA increased angiogenin secretion and angiogenin expression as determined by ELISA and western blotting in a dose-dependent manner. The amino terminal fragment of uPA down regulated ruPA-induced angiogenin in endothelial cells, thereby suggesting that uPA plays a critical role in positively regulating angiogenin in glioblastoma cells.'] Does suppression of uPA and uPAR attenuate angiogenin mediated angiogenesis in endothelial and glioblastoma cell lines?
qiaojin/PubMedQA
2
[ -2.423647165298462, -1.281860113143921, 2.7822349071502686 ]
['The short arm of chromosome 16 is rich in segmental duplications, predisposing this region of the genome to a number of recurrent rearrangements. Genomic imbalances of an approximately 600-kb region in 16p11.2 (29.5-30.1 Mb) have been associated with autism, intellectual disability, congenital anomalies, and schizophrenia. However, a separate, distal 200-kb region in 16p11.2 (28.7-28.9 Mb) that includes the SH2B1 gene has been recently associated with isolated obesity. The purpose of this study was to better define the phenotype of this recurrent SH2B1-containing microdeletion in a cohort of phenotypically abnormal patients not selected for obesity.', 'Array comparative hybridization was performed on a total of 23,084 patients in a clinical setting for a variety of indications, most commonly developmental delay.', 'Deletions of the SH2B1-containing region were identified in 31 patients. The deletion is enriched in the patient population when compared with controls (P = 0.003), with both inherited and de novo events. Detailed clinical information was available for six patients, who all had developmental delays of varying severity. Body mass index was ≥95th percentile in four of six patients, supporting the previously described association with obesity. The reciprocal duplication, found in 17 patients, does not seem to be significantly enriched in our patient population compared with controls.'] Do recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity?
qiaojin/PubMedQA
2
[ -2.017362356185913, -1.139568567276001, 2.1650967597961426 ]
['To evaluate targeting of a microbubble contrast agent to platelets under high shear flow using the natural selectin ligand sialyl Lewis.', 'Biotinylated polyacrylamide Sialyl Lewis or biotinylated carbohydrate-free polymer (used as a control) were attached to biotinylated microbubbles via a streptavidin linker. Activated human platelets were isolated and attached to fibrinogen-coated culture dishes. Fibrinogen-coated dishes without platelets or platelet dishes blocked by an anti-P-selectin antibody served as negative control substrates. Dishes coated by recombinant P-selectin served as a positive control substrate. Microbubble adhesion was assessed by microscopy in an inverted parallel plate flow chamber, with wall shear stress values of 40, 30, 20, 10, and 5 dynes/cm2. The ratio of binding and passing microbubbles was defined as capture efficiency.', 'There was no significant difference between the groups regarding the number of microbubbles in the fluid flow at each shear rate. Sialyl Lewis-targeted microbubbles were binding and slowly rolling on the surface of activated platelets and P-selectin-coated dishes at all the flow conditions including 40 dynes/cm2. Capture efficiency of targeted microbubbles to activated platelets and recombinant P-selectin decreased with increasing shear flow: at 5 dynes/cm2, capture efficiency was 16.11% on activated platelets versus 21.83% on P-selectin, and, at 40 dynes/cm2, adhesion efficiency was still 3.4% in both groups. There was neither significant adhesion of Sialyl Lewis-targeted microbubbles to control substrates, nor adhesion of control microbubbles to activated platelets or to recombinant P-selectin.'] Does an ultrasound contrast agent targeted to P-selectin detect activated platelets at supra-arterial shear flow conditions?
qiaojin/PubMedQA
2
[ -1.7849417924880981, -1.6055021286010742, 2.3823494911193848 ]
['The genetic factors associated with susceptibility to nonalcoholic fatty liver disease (NAFLD) in pediatric obesity remain largely unknown. Recently, a nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like phospholipase 3 gene (PNPLA3) has been associated with hepatic steatosis in adults. In a multiethnic group of 85 obese youths, we genotyped the PNLPA3 single-nucleotide polymorphism, measured hepatic fat content by magnetic resonance imaging and insulin sensitivity by the insulin clamp. Because PNPLA3 might affect adipogenesis/lipogenesis, we explored the putative association with the distribution of adipose cell size and the expression of some adipogenic/lipogenic genes in a subset of subjects who underwent a subcutaneous fat biopsy. Steatosis was present in 41% of Caucasians, 23% of African Americans, and 66% of Hispanics. The frequency of PNPLA3(rs738409) G allele was 0.324 in Caucasians, 0.183 in African Americans, and 0.483 in Hispanics. The prevalence of the G allele was higher in subjects showing hepatic steatosis. Surprisingly, subjects carrying the G allele showed comparable hepatic glucose production rates, peripheral glucose disposal rate, and glycerol turnover as the CC homozygotes. Carriers of the G allele showed smaller adipocytes than those with CC genotype (P = 0.005). Although the expression of PNPLA3, PNPLA2, PPARγ2(peroxisome proliferator-activated receptor gamma 2), SREBP1c(sterol regulatory element binding protein 1c), and ACACA(acetyl coenzyme A carboxylase) was not different between genotypes, carriers of the G allele showed lower leptin (LEP)(P = 0.03) and sirtuin 1 (SIRT1) expression (P = 0.04).'] Is a common variant in the patatin-like phospholipase 3 gene ( PNPLA3 ) associated with fatty liver disease in obese children and adolescents?
qiaojin/PubMedQA
2
[ -2.159872531890869, -1.4298362731933594, 2.5917630195617676 ]
['It is well known that oxidative stress is enhanced in patients with end-stage renal disease. However, little is known about the relationship between serum antioxidant capacity and clinical outcome in hemodialysis (HD) patients.', 'We examined the relationship between serum biomarkers of oxidative stress and clinical outcomes including all-cause mortality, hospitalization rate and incidence of cardiovascular events in HD patients. As biomarkers of oxidative stress, we measured serum levels of coenzyme Q10 (CoQ10) and biological antioxidant potential (BAP).', '108 patients were observed for 30 months as the follow-up periods. The survival group (n = 83) showed significantly higher BAP values compared with those in death groups (n = 25; p < 0.05). When serum BAP levels were divided into two groups by their median value, the group with higher BAP values had a better survival rate than that with lower BAP values on the Kaplan-Meier survival analysis (p = 0.05). Although serum levels of CoQ10 did not show any association with clinical outcomes, lower BAP was selected as an independent risk factor for all-cause mortality as well as the absence of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers therapy by age-adjusted Cox regression analysis.'] Does serum biological antioxidant potential predict the prognosis of hemodialysis patients?
qiaojin/PubMedQA
2
[ -2.2780401706695557, -1.2374662160873413, 2.599057674407959 ]
['Histological inflammation correlates with the degree of baseline olfactory dysfunction in patients with chronic rhinosinusitis (CRS); however, factors associated with improvement in olfactory status after endoscopic sinus surgery (ESS) remain elusive. Our purpose was to compare histopathological findings in CRS patients with olfactory loss and evaluate whether inflammatory markers can predict long-term olfactory improvement after ESS.', 'Adult (> or = 18 years) patients with CRS were prospectively enrolled after electing ESS due to failed medical management. Mucosal tissue specimens were collected at the time of surgery and underwent pathological review in a blinded fashion. Subjects completed the 40-item Smell Identification Test (SIT) preoperatively and at least 6 months postoperatively. Multivariate logistic regression was used to identify histological factors associated with postoperative improvement in SIT score.', 'The final cohort was comprised of 101 patients with a mean follow-up of 16.7 +/- 6.0 months. Mean mucosal eosinophil count was higher in patients with hyposmia and anosmia (p < 0.001). Patients with preoperative anosmia were more likely to have greater severity of basement membrane (BM) thickening compared with subjects with hyposmia or normosmia (p = 0.021). In patients with olfactory dysfunction, 54.7% reported olfactory improvement of at least 4 points on postoperative SIT scores. After controlling for nasal polyposis, histological variables were not associated with postoperative improvement in olfaction.'] Does ethmoid histopathology predict olfactory outcomes after endoscopic sinus surgery?
qiaojin/PubMedQA
2
[ -2.2650341987609863, -1.3185368776321411, 2.6326088905334473 ]
['HIV/hepatitis C virus (HCV) coinfection causes accelerated liver disease compared to HCV monoinfection, and only 30-60% of HIV/HCV-coinfected individuals respond to HCV therapy with pegylated interferon and ribavirin. There are currently no biomarkers that predict treatment response in these coinfected patients.', 'We investigated whether there is an association between HCV treatment response and SNPs of apoptosis-related genes during HIV/HCV coinfection.', 'Genomic DNA from 53 HIV/HCV-coinfected individuals was analyzed for 82 SNPs of 10 apoptosis-related genes.', 'We found that the presence of the rs4242392 SNP in tumor necrosis factor receptor superfamily, member 10a (TNFRSF10A), which encodes for tumor necrosis factor-related apoptosis-inducing ligand receptor 1, predicts poor outcome to HCV therapy, in HIV/HCV-co-infected patients [odds ratio 5.91 (95% confidence interval 1.63-21.38, P = 0.007)].'] Is polymorphism in tumor necrosis factor-related apoptosis-inducing ligand receptor 1 associated with poor viral response to interferon-based hepatitis C virus therapy in HIV/hepatitis C virus-coinfected individuals?
qiaojin/PubMedQA
2
[ -2.2171785831451416, -1.2967705726623535, 2.65098237991333 ]
['Oral antifungal terbinafine has been reported to cause liver injury with inflammatory responses in a small percentage of patients. However the underlying mechanism remains unknown. To examine the inflammatory reactions, we investigated whether terbinafine and other antifungal drugs increase the release of pro-inflammatory cytokines using human monocytic cells.', 'Dose- and time-dependent changes in the mRNA expression levels and the release of interleukin (IL)-8 and tumor necrosis factor (TNF)α from human monocytic THP-1 and HL-60 cells with antifungal drugs were measured. Effects of terbinafine on the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK)1/2 were investigated.', 'The release of IL-8 and TNFα from THP-1 and HL-60 cells was significantly increased by treatment with terbinafine but not by fluconazole, suggesting that terbinafine can stimulate monocytes and increase the pro-inflammatory cytokine release. Terbinafine also significantly increased the phosphorylation of ERK1/2 and p38 MAP kinase in THP-1 cells. Pretreatment with a MAP kinase/ERK kinase (MEK)1/2 inhibitor U0126 significantly suppressed the increase of IL-8 and TNFα levels by terbinafine treatment in THP-1 cells, but p38 MAPK inhibitor SB203580 did not. These results suggested that an ERK1/2 pathway plays an important role in the release of IL-8 and TNFα in THP-1 cells treated with terbinafine.'] Does terbinafine stimulate the pro-inflammatory responses in human monocytic THP-1 cells through an ERK signaling pathway?
qiaojin/PubMedQA
2
[ -2.3472330570220947, -1.2996509075164795, 2.7061519622802734 ]
['The Mycobacterium tuberculosis genome encodes two peptide transporters encoded by Rv3665c-Rv3662c and Rv1280c-Rv1283c. Both belong to the family of ABC transporters containing two nucleotide-binding subunits, two integral membrane proteins and one substrate-binding polypeptide. However, little is known about their functions in M. tuberculosis. Here we report functional characterization of the Rv1280c-Rv1283c-encoded transporter and its substrate-binding polypeptide OppA(MTB).', 'OppA(MTB) was capable of binding the tripeptide glutathione and the nonapeptide bradykinin, indicative of a somewhat broad substrate specificity. Amino acid residues G109, N110, N230, D494 and F496, situated at the interface between domains I and III of OppA, were required for optimal peptide binding. Complementaton of an oppA knockout mutant of M. smegmatis with OppA(MTB) confirmed the role of this transporter in importing glutathione and the importance of the aforesaid amino acid residues in peptide transport. Interestingly, this transporter regulated the ability of M. tuberculosis to lower glutathione levels in infected compared to uninfected macrophages. This ability was partly offset by inactivation of oppD. Concomitantly, inactivation of oppD was associated with lowered levels of methyl glyoxal in infected macrophages and reduced apoptosis-inducing ability of the mutant. The ability to induce the production of the cytokines IL-1beta, IL-6 and TNF-alpha was also compromised after inactivation of oppD.'] Does an oligopeptide transporter of Mycobacterium tuberculosis regulate cytokine release and apoptosis of infected macrophages?
qiaojin/PubMedQA
2
[ -2.3929288387298584, -1.304395079612732, 2.7357263565063477 ]
['the aim of the study was to assess whether myocardial contrast echocardiography (MCE) can predict mortality in patients with heart failure. Myocardial viability, ischaemia, and coronary flow reserve (CFR) are predictors of mortality in patients with heart failure. MCE can assess myocardial viability, ischaemia, and CFR at the bedside. However, its prognostic value is unknown in patients with heart failure.', 'eighty-seven patients (age: 68 ± 10 years, 62% male) with heart failure [left ventricular ejection fraction (LVEF): 35% ± 13] underwent low-power intermittent MCE at rest and 2 min after dipyridamole infusion. Resting and stress perfusion score index were derived qualitatively. CFR (MBF at stress/MBF at rest) was calculated by a quantitative method. All patients underwent coronary arteriography. Patients were followed up for mortality. Of the 87 patients, 43 (49%) patients had coronary artery disease. There were 28 (32%) deaths during a mean follow-up of 4.1 ± 1.7 years. Type 2 diabetes [P = 0.02, hazard ratios (HR) 2.43, confidence interval (CI) 1.13-5.22] and CFR (P = 0.001, HR 0.15, CI 0.05-0.45) were independent predictors of mortality. A CFR ≤ 1.5 had a significantly (P < 0.0001) higher mortality of 49 vs. 10% in patients with CFR > 1.5 over the 4 year follow-up period.'] Does coronary flow reserve assessed by myocardial contrast echocardiography predict mortality in patients with heart failure?
qiaojin/PubMedQA
2
[ -0.630260705947876, -1.8185926675796509, 1.4602609872817993 ]
['Hypomagnesemia with secondary hypocalcemia is due to disturbed renal and intestinal magnesium (Mg(2+)) (re)absorption. The underlying defect is a mutation in the transient receptor potential melastatin type 6 (TRPM6), a Mg(2+)-permeable ion channel expressed in the kidney and intestine. Our aim was to characterize homozygous (-/-) and heterozygous (+/-) TRPM6 knockout mice with respect to Mg(2+) homeostasis.', 'TRPM6(+/-) mice were bred on a normal (0.19% wt/wt Mg(2+)) and high (0.48% wt/wt Mg(2+)) Mg(2+) diet. In the offspring, 24-hour urinary Mg(2+) and calcium excretion as well as serum concentrations of both were determined. TRPM6 mRNA expression in the kidney and colon was measured.', 'On the regular diet, 30% of the offspring were TRPM6 wild-type ((+/+)), 70% were TRPM6(+/-), and none were TRPM6(-/-). The genotypic distribution of the litters remained the same on the 0.48% Mg(2+) diet. In TRPM6(+/-) mice on both diets, serum Mg(2+) levels were significantly lower, and renal and intestinal TRPM6 mRNA expression was reduced. Urinary Mg(2+) excretion was unaffected.'] Are transient receptor potential melastatin 6 knockout mice lethal whereas heterozygous deletion results in mild hypomagnesemia?
qiaojin/PubMedQA
2
[ -1.871871829032898, -1.5140994787216187, 2.3895440101623535 ]
['We investigated the long-term efficacy and renal safety of tenofovir disoproxil fumarate (TDF), administered to patients co-infected with human immunodeficiency virus and hepatitis B virus (HBV) as part of an antiretroviral therapy.', 'We performed a multicenter, prospective cohort study of 102 patients co-infected with human immunodeficiency virus and HBV who were treated with TDF.', 'At baseline, 80% of patients had a detectable viral load (HBV DNA >20 IU/mL). Among patients positive for hepatitis B e antigen (HBeAg) (n = 67), 92% had a virologic response (HBV DNA <20 IU/mL) after 5 years of treatment. There was no difference between patients with or without lamivudine resistance at baseline (P = .39). Loss rates of HBeAg and hepatitis B s antigen (HBsAg) were 46% and 12%, respectively. Among HBeAg-negative patients (n = 15), 100% had a virologic response after 4 years of treatment and 2 (13%) lost HBsAg. Twenty subjects (20%, all HBeAg-negative) had undetectable HBV DNA at baseline; during a median follow-up period of 52 months (interquartile range, 41-63 mo), 19 (95%) maintained a virologic response and 2 (10%) lost HBsAg. Overall, one patient acquired a combination of resistance mutations for anti-HBV drugs and experienced a virologic breakthrough. Three (3%) patients discontinued TDF because of increased serum creatinine levels. The estimated decrease in renal function after 5 years of TDF therapy was 9.8 mL/min/1.73 m(2), which was most pronounced shortly after TDF therapy was initiated.'] Is long-term therapy with tenofovir effective for patients co-infected with human immunodeficiency virus and hepatitis B virus?
qiaojin/PubMedQA
2
[ -1.7642452716827393, -1.5828945636749268, 2.3499464988708496 ]
['Cytologic examination of specimens obtained from the respiratory tract is a lung cancer diagnostic procedure with high specificity but moderate sensitivity. The use of molecular biomarkers may enhance the sensitivity of cytologic examination in the detection of lung cancer.', 'Complement factor H, a protein secreted by lung cancer cells, was quantified in a series of bronchoalveolar lavage supernatants from lung cancer patients and patients with nonmalignant respiratory diseases. Albumin, total protein content, and hemoglobin were also analyzed. Results were validated in independent sets of bronchoalveolar lavage and sputum supernatants.', 'There was a significantly higher concentration of factor H in bronchoalveolar lavage samples from lung cancer patients. The sensitivity and specificity of the factor H test was 82% and 77%, respectively. These results were validated in an independent set of patients with nearly identical results. Furthermore, 70% and 45% of bronchoalveolar lavage fluids from central and peripheral tumors, respectively, reported as cytologically negative, were classified as positive using this marker. Finally, the test was evaluated in a series of sputum supernatants from lung cancer patients and controls. The sensitivity and specificity of the factor H test in this series was 80% and 88%, respectively.'] Is complement factor H elevated in bronchoalveolar lavage fluid and sputum from patients with lung cancer?
qiaojin/PubMedQA
2
[ -2.2221362590789795, -1.3777134418487549, 2.6772608757019043 ]
['While there is significant interest in combining anti-angiogenesis therapy with conventional anti-cancer treatment, clinical trials have as of yet yielded limited therapeutic gain, mainly because mechanisms of anti-angiogenic therapy remain to a large extent unknown. Currently, anti-angiogenic tumor therapy is conceptualized to either "normalize" dysfunctional tumor vasculature, or to prevent recruitment of circulating endothelial precursors into the tumor. An alternative biology, restricted to delivery of anti-angiogenics immediately prior to single dose radiotherapy (radiosurgery), is provided in the present study.', 'Genetic data indicate an acute wave of ceramide-mediated endothelial apoptosis, initiated by acid sphingomyelinase (ASMase), regulates tumor stem cell response to single dose radiotherapy, obligatory for tumor cure. Here we show VEGF prevented radiation-induced ASMase activation in cultured endothelium, occurring within minutes after radiation exposure, consequently repressing apoptosis, an event reversible with exogenous C(16)-ceramide. Anti-VEGFR2 acts conversely, enhancing ceramide generation and apoptosis. In vivo, MCA/129 fibrosarcoma tumors were implanted in asmase(+/+) mice or asmase(-/-) littermates and irradiated in the presence or absence of anti-VEGFR2 DC101 or anti-VEGF G6-31 antibodies. These anti-angiogenic agents, only if delivered immediately prior to single dose radiotherapy, de-repressed radiation-induced ASMase activation, synergistically increasing the endothelial apoptotic component of tumor response and tumor cure. Anti-angiogenic radiosensitization was abrogated in tumors implanted in asmase(-/-) mice that provide apoptosis-resistant vasculature, or in wild-type littermates pre-treated with anti-ceramide antibody, indicating that ceramide is necessary for this effect.'] Is endothelial membrane remodeling obligate for anti-angiogenic radiosensitization during tumor radiosurgery?
qiaojin/PubMedQA
2
[ -2.449556589126587, -1.3644318580627441, 2.8977866172790527 ]
['Visceral pleural invasion, which is defined as tumor extension beyond the elastic lamina, is one of the most important prognostic factors in patients who have undergone curative resection for non-small cell lung cancer. However, in pathologic slides, pleural elastic lamina could not be found in the hilar region in which the pleura is reflected. Till date, when cancer cells are seen in this region, a basical agreement dealing with T factor is controversial among pathologists. The purpose of this study is to evaluate the significance of tumor invasion of that region as a prognostic factor.', 'We reviewed 91 cases of surgically resected lung cancer in which invasion of the hilar region was visible macroscopically. By microscopic examination, we divided them into three groups: a group in which no cancer cells are seen in the soft tissue beyond the hilar region (group A), a group in which cancer cells are seen in the soft tissue beyond the hilar region (group B), and a group in which cancer cells could not be seen in the soft tissue beyond the hilar region but invade into the mediastinal visceral pleura at some other site (group C). We then evaluated the clinicopathologic characteristics of the patients and their outcome.', 'There was no statistically significant difference in the 5-year overall survival rate or disease-free survival rate between group A and group B (overall: 55 versus 48%; disease free: 43 versus 42%), but disease-free survival of group C was significantly lesser than that of group A and group B (A versus C: p = 0.022; B versus C: p = 0.040).'] Does tumor invasion of extralobar soft tissue beyond the hilar region affect the prognosis of surgically resected lung cancer patients?
qiaojin/PubMedQA
2
[ -1.8541179895401, -1.3389923572540283, 2.2299256324768066 ]
['Tumor tissue is composed of variable numbers of cancer cells and stromal cells, and tumor-associated macrophages are recruited into cancer-induced stroma and produce a specific microenvironment. Alternatively, activated macrophages (M2 phenotype) are known to be related to tumor progression and outcome, and CD204 has been reported to be expressed in M2 macrophages in some tumors.', 'To investigate whether CD204-positive macrophages reflect tumor aggressiveness in adenocarcinoma of the lung, we investigated the relationships between the numbers of CD204-positive stromal macrophages and both clinicopathological features and outcome in 170 consecutive resected cases. We also examined the relationships between the numbers of CD204-positive macrophages and the expression levels of cytokines involved in the migration and differentiation of M2 macrophages.', 'The numbers of CD204-positive macrophages were significantly correlated with several prognostic factors. The log-rank test showed a significant association between the numbers of CD204-positive macrophages and a poor outcome (p = 0.0073), whereas the numbers of macrophages expressing CD68, a pan-macrophage/monocyte marker, were of marginal prognostic significance (p = 0.0789). We evaluated associations between the levels of expression of the cytokines IL-6, IL-10, IL-12a, IL-12b, M-colony-stimulating factor, IFN-gamma-., and monocyte chemoattractant protein-1 in cancer tissue and the numbers of CD204-positive macrophages. The expression levels of IL-10 and monocyte chemoattractant protein-1, which are involved in differentiation, accumulation, and migration of M2 macrophages, were significantly correlated with the numbers of CD204-positive macrophages (p = 0.031 and p = 0.031, respectively).'] Is stromal macrophage expressing CD204 associated with tumor aggressiveness in lung adenocarcinoma?
qiaojin/PubMedQA
2
[ -2.1842305660247803, -1.161874532699585, 2.453033685684204 ]
['Fatty liver disease (FLD), of either alcoholic (AFLD) or non-alcoholic (NAFLD) aetiologies, is characterised histologically by features that are lobulocentric that typically affect zone 3, in contrast with portal-based inflammation characteristics of other forms of chronic liver disease.', 'The authors aimed to determine the prevalence and significance of portal inflammation in a cohort of adults diagnosed as having AFLD and NAFLD.', 'From a histology database, the authors identified 160 patients with biopsy proven AFLD and 214 with NAFLD diagnosed between 1991 and 2001. All liver biopsies were reviewed by one pathologist to evaluate various histological features.', 'More than a mild degree of portal inflammation was found in 47% of AFLD compared with 30% in NAFLD subgroup. A higher degree of portal inflammation in AFLD was associated with a higher mean corpuscular volume, gamma glutamyl transferase (GGT) and alkaline phosphatase, and a lower platelet count and albumin, whereas in NAFLD this was associated with age, presence of diabetes, hypertension, body mass index (BMI), higher fasting blood glucose, cholesterol, alanine transaminase, GGT and ferritin. On regression analysis, portal inflammation was associated with the severity of steatosis (p=0.005), presence of ballooning (p=0.030) in NAFLD and severity of fibrosis in both AFLD and NAFLD (p<0.001).'] Is portal inflammation associated with advanced histological changes in alcoholic and non-alcoholic fatty liver disease?
qiaojin/PubMedQA
2
[ -2.2911975383758545, -1.382203221321106, 2.7063863277435303 ]
['The possible therapeutic benefits of using steroids to enhance muscle strength and slow disease progression in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) has been examined previously. In this investigation, it was hypothesised that steroid therapy is associated with morphological changes in the dystrophic muscle.', 'To test this hypothesis, two muscle biopsies were obtained (one biopsy before treatment, and the second 6 months following prednisone therapy) from 24 patients with dystrophies (18 DMD, 6 BMD). The participants were categorised into: control (6 specimens, normal muscle), untreated and treated groups. The muscle was evaluated for ultrastructural changes using transmission electron microscopy (TEM).', 'In the untreated group, the muscle fibres were degenerated and of variable sizes. The myofibrils were thin with either complete loss of bands and/or abnormal banding patterns. The Z-lines were irregularly spaced and loosely registered. The mitochondria of the myofibrils were small, few, spherical and irregularly distributed. Numerous dendritic cells (DCs) with euchromatic nuclei, and multiple and long dendrites, were seen among the myofibrils. The collagen fibres among the muscle fibres (endomysium) were numerous and large. The satellite cells had euchromatic nuclei with clumps of heterochromatin. In the treated group, the muscle fibres had a relatively uniform size with occasional fibres showing partial degeneration. The myofibrils had a relatively similar diameter comparable to that of normal muscle .The degenerated areas were small in size with occasional foci showing loss of banding pattern, and abnormal short bands with thick and hazy Z-lines. The mitochondria of the myofibrils were numerous, spherical, small in size and regularly arranged between the myofibrils. Few DCs, with heterochromatic nuclei, and few and short dendrites appeared between the myofibrils. The collagen fibres between the muscle fibres (endomysium) were numerous and large. As compared with the treated group, there was a statistically significant increase (p<0.05) in the numbers of DCs (0.7+/-0.2 vs 1.6+/-0.3) and fibroblasts (1.9+/-0.2 vs 2.9 +/-0.3) in the untreated group. Alternatively, there was a statistically significant decrease (p<0.05) in the numbers of satellite cells (1.2+/-0.2 vs 0.6+/-0.1).'] Is steroid therapy associated with decreased numbers of dendritic cells and fibroblasts , and increased numbers of satellite cells , in the dystrophic skeletal muscle?
qiaojin/PubMedQA
2
[ -2.1914994716644287, -1.4630433320999146, 2.688312530517578 ]
['Both childhood trauma and violent behavior are important risk factors for suicidal behavior. The aim of the present study was to construct and validate a clinical rating scale that could measure both the exposure to and the expression of violence in childhood and during adult life and to study the ability of the Karolinska Interpersonal Violence Scale (KIVS) to predict ultimate suicide in suicide attempters.', 'A total of 161 suicide attempters and 95 healthy volunteers were assessed with the KIVS measuring exposure to violence and expressed violent behavior in childhood (between 6-14 years of age) and during adult life (15 years or older). The Buss-Durkee Hostility Inventory (BDHI), "Urge to act out hostility" subscale from the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Early Experience Questionnaire (EEQ) were used for validation. All patients were followed up for cause of death and a minimum of 4 years from entering in the study.', 'Five patients who committed suicide within 4 years had significantly higher scores in exposure to violence as a child, in expressed violent behavior as an adult, and in KIVS total score compared to survivors. Suicide attempters scored significantly higher compared to healthy volunteers in 3 of the 4 KIVS subscales. There were significant correlations between the subscales measuring exposure to and expression of violent behavior during the life cycle. BDHI, Urge to act out hostility, and EEQ validated the KIVS.'] Does karolinska Interpersonal Violence Scale predict suicide in suicide attempters?
qiaojin/PubMedQA
2
[ -1.3465980291366577, -0.378001868724823, 0.9116898775100708 ]
['Women with gestational diabetes mellitus (GDM) maintain a higher risk for recurrent GDM and overt diabetes. Overt diabetes is a risk factor for development of chronic kidney disease (CKD), but GDM alone, without subsequent development of overt diabetes, may also pose a risk for CKD.', 'This cross-sectional analysis included Kidney Early Evaluation Program (KEEP) participants from 2000 to 2009. Patient characteristics and kidney function among three categories (GDM alone, overt diabetes, and no history of diabetes) were compared. The prevalence of microalbuminuria, macroalbuminuria, and CKD stages 1-2 and 3-5 was assessed using logistic regression.', 'Of 37,716 KEEP female participants, 571 (1.5%) had GDM alone and 12,100 (32.1%) had overt diabetes. Women with GDM had a higher rate of microalbuminuria but not macroalbuminuria than their nondiabetic peers (10.0 vs. 7.7%) that was substantially lower than the 13.6% prevalence in diabetic women. In multivariate analysis, women with GDM alone, compared with nondiabetic women, demonstrated increased odds of CKD stages 1-2 (multivariate odds ratio 1.54 [95% CI 1.16-2.05]) similar to the odds for women with overt diabetes (1.68 [1.55-1.82]). In stratified analyses, age, race, BMI, and hypertension modified the odds for CKD stages 1-2 but not CKD stages 3-5 among women with GDM.'] Is gestational diabetes mellitus alone in the absence of subsequent diabetes associated with microalbuminuria : results from the Kidney Early Evaluation Program ( KEEP )?
qiaojin/PubMedQA
2
[ -1.1926829814910889, -1.3923485279083252, 1.6537935733795166 ]
['To determine whether plasma triglyceride levels in adult Glycosylphosphatidylinositol HDL-binding protein 1 (GPIHBP1)-deficient (Gpihbp1(-/-)) mice would be sensitive to cholesterol intake.', 'Gpihbp1(-/-) mice were fed a Western diet containing 0.15% cholesterol. After 4 to 8 weeks, their plasma triglyceride levels were 113 to 135 mmol/L. When 0.005% ezetimibe was added to the diet to block cholesterol absorption, Lpl expression in the liver was reduced significantly, and the plasma triglyceride levels were significantly higher (>170 mmol/L). We also assessed plasma triglyceride levels in Gpihbp1(-/-) mice fed Western diets containing either high (1.3%) or low (0.05%) amounts of cholesterol. The high-cholesterol diet significantly increased Lpl expression in the liver and lowered plasma triglyceride levels.'] Does cholesterol intake modulate plasma triglyceride levels in glycosylphosphatidylinositol HDL-binding protein 1-deficient mice?
qiaojin/PubMedQA
2
[ -1.9274877309799194, -1.0732994079589844, 1.9793477058410645 ]
['The expression of BCL11B was reported in T-cells, neurons and keratinocytes. Aberrations of BCL11B locus leading to abnormal gene transcription were identified in human hematological disorders and corresponding animal models. Recently, the elevated levels of Bcl11b protein have been described in a subset of squameous cell carcinoma cases. Despite the rapidly accumulating knowledge concerning Bcl11b biology, the contribution of this protein to normal or transformed cell homeostasis remains open.', 'Here, by employing an overexpression strategy we revealed formerly unidentified features of Bcl11b. Two different T-cell lines were forced to express BCL11B at levels similar to those observed in primary T-cell leukemias. This resulted in markedly increased resistance to radiomimetic drugs while no influence on death-receptor apoptotic pathway was observed. Apoptosis resistance triggered by BCL11B overexpression was accompanied by a cell cycle delay caused by accumulation of cells at G1. This cell cycle restriction was associated with upregulation of CDKN1C (p57) and CDKN2C (p18) cyclin dependent kinase inhibitors. Moreover, p27 and p130 proteins accumulated and the SKP2 gene encoding a protein of the ubiquitin-binding complex responsible for their degradation was repressed. Furthermore, the expression of the MYCN oncogene was silenced which resulted in significant depletion of the protein in cells expressing high BCL11B levels. Both cell cycle restriction and resistance to DNA-damage-induced apoptosis coincided and required the histone deacetylase binding N-terminal domain of Bcl11b. The sensitivity to genotoxic stress could be restored by the histone deacetylase inhibitor trichostatine A.'] Does increased expression of bcl11b lead to chemoresistance accompanied by G1 accumulation?
qiaojin/PubMedQA
2
[ -2.512357473373413, -1.1923539638519287, 2.7223939895629883 ]
['The birth of a boy is significantly more common than a girl prior to secondary recurrent miscarriage (SRM) and is associated with a poorer chance of a subsequent live birth. Children born after SRM are more likely to be girls. High-titer antisera specific for male antigens (H-Y) have been shown to arrest development of male bovine embryos efficiently. We consequently questioned the role of H-Y antibodies in women with SRM.', 'Serum samples from patients with unexplained SRM (n = 84), unexplained primary recurrent miscarriage (PRM) (n = 12) and healthy women (n = 37) were obtained. The samples were taken during pregnancy (gestational weeks 4-5) for 77 (80%) of the patients. Enzyme-linked immunosorbent assay was used to detect immunoglobulin G antibodies that specifically recognized any of the five recombinant H-Y proteins (EIF1AY, RPS4Y1, ZFY, DDX3Y and UTY) and their H-X homologs.', 'H-Y-specific antibodies were more frequent in SRM patients (46%) compared with female controls (19%, P = 0.004) and PRM patients (8%, P = 0.01). The presence of H-Y antibodies in early pregnancy was associated with a low male: female birth ratio among the subsequent live births, as only 12% of children born to H-Y antibody-positive patients were boys compared with 44% boys born to H-Y antibody negative patients (P = 0.03).'] Are h-Y antibody titers increased in unexplained secondary recurrent miscarriage patients and associated with low male : female ratio in subsequent live births?
qiaojin/PubMedQA
2
[ -1.7891550064086914, -1.4370675086975098, 2.278977155685425 ]
['Cigarette smoking during pregnancy is associated with negative reproductive consequences for male fetuses in adult life such as reduced testicular volume and sperm concentration. The present study evaluates the number of germ and somatic cells present in human embryonic first-trimester gonads in relation to maternal smoking.', 'The study includes 24 human first-trimester testes, aged 37-68 days post-conception, obtained from women undergoing legal termination of pregnancy. A questionnaire was used to obtain information about smoking and drinking habits during pregnancy. Validated stereological methods were used to estimate gonadal cell numbers in histological sections. Results were also evaluated in the context of previously published data on ovaries from our laboratory.', 'A significant reduction in the number of germ cells by 55% [95% confidence interval (CI) 74-21% reduction, P = 0.004] and somatic cells by 37% (95% CI 59-3%, P = 0.023) was observed in testes prenatally exposed to maternal cigarette smoking, compared with unexposed. The effect of maternal smoking was dose-dependent being higher in the heavy smokers and remained consistent after adjusting for possible confounders such as alcohol and coffee consumption (P = 0.002). The number of germ cells in embryonic gonads, irrespective of gender, was also significantly reduced by 41% (95% CI 58-19%, P = 0.001) in exposed versus non-exposed embryonic gonads.'] Does cigarette smoking during early pregnancy reduce the number of embryonic germ and somatic cells?
qiaojin/PubMedQA
2
[ -1.8717368841171265, -0.6301195025444031, 1.4812499284744263 ]
['To assess the efficacy of moderate aerobic physical activity with sleep hygiene education to improve sleep, mood and quality of life in older adults with chronic insomnia.', 'Seventeen sedentary adults aged >or=55 years with insomnia (mean age 61.6 [SD±4.3] years; 16 female) participated in a randomized controlled trial comparing 16 weeks of aerobic physical activity plus sleep hygiene to non-physical activity plus sleep hygiene. Eligibility included primary insomnia for at least 3 months, habitual sleep duration <6.5h and a Pittsburgh Sleep Quality Index (PSQI) score >5. Outcomes included sleep quality, mood and quality of life questionnaires (PSQI, Epworth Sleepiness Scale [ESS], Short-form 36 [SF-36], Center for Epidemiological Studies Depression Scale [CES-D]).', 'The physical activity group improved in sleep quality on the global PSQI (p<.0001), sleep latency (p=.049), sleep duration (p=.04), daytime dysfunction (p=.027), and sleep efficiency (p=.036) PSQI sub-scores compared to the control group. The physical activity group also had reductions in depressive symptoms (p=.044), daytime sleepiness (p=.02) and improvements in vitality (p=.017) compared to baseline scores.'] Does aerobic exercise improve self-reported sleep and quality of life in older adults with insomnia?
qiaojin/PubMedQA
2
[ -2.1892309188842773, -0.38887396454811096, 1.7140636444091797 ]
['to evaluate specialist geriatric input and medication review in patients in high-dependency continuing care.', 'prospective, randomised, controlled trial.', 'two residential continuing care hospitals.', 'two hundred and twenty-five permanent patients.', 'patients were randomised to either specialist geriatric input or regular input. The specialist group had a medical assessment by a geriatrician and medication review by a multidisciplinary expert panel. Regular input consisted of review as required by a medical officer attached to each ward. Reassessment occurred after 6 months.', 'one hundred and ten patients were randomised to specialist input and 115 to regular input. These were comparable for age, gender, dependency levels and cognition. After 6 months, the total number of medications per patient per day fell from 11.64 to 11.09 in the specialist group (P = 0.0364) and increased from 11.07 to 11.5 in the regular group (P = 0.094). There was no significant difference in mortality or frequency of acute hospital transfers (11 versus 6 in the specialist versus regular group, P = 0.213).'] Does specialist medication review benefit short-term outcomes and net costs in continuing-care patients?
qiaojin/PubMedQA
2
[ -0.607146143913269, -0.5013135075569153, 0.2509503662586212 ]
['This study examined whether some of the age-associated decrements in basic cognitive resources (information-processing speed and working memory) result from anticholinergic medication use (as measured by serum anticholinergic activity [SAA]) and whether such decrements are lessened by caffeine.', 'Cross-sectional observational study.', 'University medical center.', 'One hundred fifty-two normal-elderly community volunteers.', 'Two tests each of information-processing speed and of working memory were administered, and blood samples were drawn before and after cognitive testing to determine serum levels of anticholinergic activity and of paraxanthine-a caffeine metabolite.', 'Elevated SAA was associated with a significant but modest slowing in information-processing time but only in those individuals who had low levels of serum paraxanthine. SAA did not correlate with performance on tests of working memory.'] Is cognitive slowing associated with elevated serum anticholinergic activity in older individuals decreased by caffeine use?
qiaojin/PubMedQA
2
[ -2.436119556427002, -0.7855214476585388, 2.329516649246216 ]
["The c-myb proto-oncogene is the founding member of a family of transcription factors involved principally in haematopoiesis, in diverse organisms, from zebrafish to mammals. Its deregulation has been implicated in human leukaemogenesis and other cancers. The expression of c-myb is tightly regulated by post-transcriptional mechanisms involving microRNAs. MicroRNAs are small, highly conserved non-coding RNAs that inhibit translation and decrease mRNA stability by binding to regulatory motifs mostly located in the 3'UTR of target mRNAs conserved throughout evolution. MYB is an evolutionarily conserved miR-150 target experimentally validated in mice, humans and zebrafish. However, the functional miR-150 sites of humans and mice are orthologous, whereas that of zebrafish is different.", "We identified the avian mature miRNA-150-5P, Gallus gallus gga-miR-150 from chicken leukocyte small-RNA libraries and showed that, as expected, the gga-miR-150 sequence was highly conserved, including the seed region sequence present in the other miR-150 sequences listed in miRBase. Reporter assays showed that gga-miR-150 acted on the avian MYB 3'UTR and identified the avian MYB target site involved in gga-miR-150 binding. A comparative in silico analysis of the miR-150 target sites of MYB 3'UTRs from different species led to the identification of a single set of putative target sites in amphibians and zebrafish, whereas two sets of putative target sites were identified in chicken and mammals. However, only the target site present in the chicken MYB 3'UTR that was identical to that in zebrafish was functional, despite the additional presence of mammalian target sites in chicken. This specific miR-150 site usage was not cell-type specific and persisted when the chicken c-myb 3'UTR was used in the cell system to identify mammalian target sites, showing that this miR-150 target site usage was intrinsic to the chicken c-myb 3'UTR."] Does the chicken miR-150 target the avian orthologue of the functional zebrafish MYB 3'UTR target site?
qiaojin/PubMedQA
2
[ -1.9697167873382568, -1.0046112537384033, 1.9297683238983154 ]
['Polycystic Kidney Disease is characterized by the formation of large fluid-filled cysts that eventually destroy the renal parenchyma leading to end-stage renal failure. Although remarkable progress has been made in understanding the pathologic mechanism of the disease, the precise orchestration of the early events leading to cyst formation is still unclear. Abnormal cellular proliferation was traditionally considered to be one of the primary irregularities leading to cyst initiation and growth. Consequently, many therapeutic interventions have focused on targeting this abnormal proliferation, and some have even progressed to clinical trials. However, the role of proliferation in cyst development was primarily examined at stages where cysts are already visible in the kidneys and therefore at later stages of disease development.', 'In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0-60 days after birth) we performed gene expression profiling and phenotype analysis by measuring various kidney parameters.', 'Phenotype analysis demonstrated that renal cysts appear immediately after birth in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal proliferation occurs at later stages of the disease as identified by gene expression profiling. Interestingly, other pathways appear to be deregulated at early stages of the disease in this PKD model. Specifically, gene expression analysis demonstrated that at day 0 the RAS system is involved. This is altered at day 6, when Wnt signaling and focal adhesion pathways are affected. However, at and after 24 days, proliferation, apoptosis, altered ECM signaling and many other factors become involved.'] Does cyst formation in the PKD2 ( 1-703 ) transgenic rat precede deregulation of proliferation-related pathways?
qiaojin/PubMedQA
2
[ -2.4935004711151123, -0.9238408207893372, 2.4886019229888916 ]
['This study evaluated the cytotoxicity of five prostaglandin analog ophthalmic solutions on four ocular surface cell lines, ie, Chang (human conjunctiva), SIRC (rabbit cornea), RC-1 (rabbit cornea), and BCE C/D-1b (bovine cornea).', 'Cell viability was measured by neutral red and MTT assays in cells treated for 10, 30, or 60 minutes with various doses of prostaglandins (undiluted, and 2- and 10-fold dilutions). The number of cell lines with viability >/=50% in the presence of selected dilution of the drug (CVS(50)) was used for comparison. In addition, 24 cell viability comparisons (four cell lines, two assays, and three exposure times) were made between latanoprost (Xalatan((R))) and each other solution at each dose. A comparison between the newly introduced tafluprost (Tapros((R))) with 0.01% benzalkonium chloride was also made.', 'The order of cell viability determined by CVS(50) was Travatan Z((R)) (travoprost with the SofZia system) > Tapros >/= Travatan((R)) (travoprost) = Xalatan > Rescula((R)) (unoproston). This was consistent with the results of direct comparisons between Xalatan and the other drugs. There was no clear difference in cell viability between Tapros and benzalkonium chloride.'] Does cytotoxicity of prostaglandin analog eye drop preserved with benzalkonium chloride in multiple corneoconjunctival cell lines?
qiaojin/PubMedQA
2
[ -2.0284206867218018, -1.4436168670654297, 2.5438404083251953 ]
['Slow nerve conduction velocity and reduction in response amplitude are objective hallmarks of diabetic sensorimotor polyneuropathy. Because subjective or clinical indicators of neuropathy do not always match well with the presence of abnormal nerve physiology tests, we evaluated associations to nerve conduction in patients with type 1 diabetes.', 'Nerve conduction studies were performed in the distal sural and ulnar sensory nerves and the peroneal motor nerve in 456 individuals with type 1 diabetes who participated in the follow-up visit of the EURODIAB Prospective Complications Study (EPCS). We used multivariate regression models to describe associations to decreased nerve conduction measures.', 'In addition to an effect of duration of diabetes and A1C, which were both associated with low nerve conduction velocity and response amplitude, we found that the presence of nephropathy, retinopathy, or a clinical diagnosis of neuropathy was associated with low nerve conduction velocity and amplitude. In the case of nonproliferative retinopathy, the odds ratio (OR) for being in lowest tertile was 2.30 (95% CI 1.13-4.67) for nerve conduction velocity. A similar OR was found for each 2% difference in A1C (2.39 [1.68-3.41]).'] Are low peripheral nerve conduction velocities and amplitudes strongly related to diabetic microvascular complications in type 1 diabetes : the EURODIAB Prospective Complications Study?
qiaojin/PubMedQA
2
[ -2.1212856769561768, -1.4131312370300293, 2.5522868633270264 ]
["Insulin directly changes the sheep pleural electrophysiology. The aim of this study was to investigate whether insulin induces similar effects in human pleura, to clarify insulin receptor's involvement, and to demonstrate if glibenclamide (hypoglycemic agent) reverses this effect.", 'Human parietal pleural specimens were mounted in Ussing chambers. Solutions containing insulin or glibenclamide and insulin with anti-insulin antibody, anti-insulin receptor antibody, and glibenclamide were used. The transmesothelial resistance (R(TM)) was determined. Immunohistochemistry for the presence of Insulin Receptors (IRa, IRb) was also performed.', 'Insulin increased R(TM) within 1st min (P = .016), when added mesothelially which was inhibited by the anti-insulin and anti-insulin receptor antibodies. Glibenclamide also eliminated the insulin-induced changes. Immunohistochemistry verified the presence of IRa and IRb.'] Are insulin-induced electrophysiology changes in human pleura mediated via its receptor?
qiaojin/PubMedQA
2
[ -2.466386079788208, -1.3220089673995972, 2.8575587272644043 ]
['The Surgical Care Improvement Project (SCIP) has benchmarked 6:00 AM blood sugars on postoperative days (PODs) 1 and 2 at <200 mg/dL as an indicator of overall glycemic control (GC) in postoperative cardiac surgery patients. However, even in demonstration hospitals that publicly report for incentive payments, only 10% are compliant with this benchmark. The objectives of this study were to validate that the SCIP indicator correlates with overall GC, and relate the intensity of implementation of an insulin infusion protocol (IIP) (goal, blood sugar 100 to 140 mg/dL) to effective GC.', 'All postoperative cardiac surgery patients for 12 consecutive months on the IIP were divided into 2 groups: group 1 included patients who were SCIP compliant (n = 98), and group 2 were patients who were not SCIP compliant (n = 10). For each patient, we determined average blood sugar, duration of hyperglycemia (percent of time with blood sugar >200mg/dL), and intensity of implementation of the IIP, defined as (number of blood sugar checks/hours on IIP), with 0.5 = minimum intensity of implementation dictated by the IIP, ie, an insulin adjustment every 2 hours.', 'The average blood sugar for each of the 110 patients was no different than the SCIP 6:00 AM blood sugar: 146 versus 154 mg/dL, p = 0.18. SCIP noncompliance correlated with more intense implementation of the IIP, 0.72 ± 0.03 versus 0.83 ± 0.06 blood sugar checks/hour.'] Does intense implementation of a strict insulin infusion protocol guarantee postoperative glycemic control?
qiaojin/PubMedQA
2
[ 0.289760559797287, -1.7959420680999756, 0.562766432762146 ]
['Fast-track (FT) postoperative protocols have been shown to be highly beneficial in open colectomy. Some have questioned the necessity of an FT protocol in the setting of laparoscopic colectomy because hospital stays are short and morbidity is low compared with open surgery. We set out to determine whether an FT protocol has any utility in the setting of elective laparoscopic colectomy.', 'A retrospective review was conducted on a cohort of 334 patients who underwent elective laparoscopic sigmoid resection for diverticulitis from 1998 to 2008, at Mayo Clinic, a tertiary care center in Rochester, MN. There were 235 patients who were managed with traditional postoperative care, and 99 who were managed with an FT protocol initiated in 2006. The main outcomes measures were time to soft diet, length of stay, overall morbidity, and readmission rate.', 'Times to soft diet (mean 2.3 vs 3.6 days), and first bowel movement (mean 2.6 vs 3.5 days) were shorter in the FT group (p < 0.001). The median lengths of stay were 3 days (interquartile range 3 to 4 days) and 5 days (interquartile range 4 to 6 days) for the FT and non-FT groups, respectively (p < 0.001). Morbidity was significantly lower in the FT group compared with the non-FT group (15.2% vs 25.5%, p < 0.03). The 30-day readmission rate was 2.9% for the FT group and 7.6% for the non-FT group (p = NS). There were no deaths in either group.'] Does a fast-track recovery protocol improve outcomes in elective laparoscopic colectomy for diverticulitis?
qiaojin/PubMedQA
2
[ -1.3264139890670776, -1.5474934577941895, 1.8274414539337158 ]
['Mutations in the thyroid hormone receptor beta (TR-beta) gene result in resistance to thyroid hormone (RTH). Mutation Delta337T in the TR-beta gene has been shown to have the characteristics of RTH syndrome in mice. The aim of this work was to study the possible involvement of TR-beta receptor in thyroid modulation of ClC-2 in mouse kidney.', 'Expression of mouse (Delta337T and normal C57BL/6) renal RNA and protein expression were studied by reverse transcriptase-polymerase chain reaction and Western blot, respectively, in mice with hyper- or hypothyroidism. Renal function was studied by analysis of urinary electrolyte excretion. Studies of the ClC-2 promoter region were performed in immortalized renal proximal tubule (IRPT) cells.', 'In RTH syndrome mice (Delta337T), renal dysfunction was found to be associated with changes in the fractional excretion of sodium (FE(Na)) and chloride (FE(Cl)). ClC-2 chloride channel mRNA and protein expression were found to be decreased by 40% in heterozygous and homozygous mutant mouse kidneys and high levels of plasma thyroid hormone were detected in both groups. Hypothyroidism induced by methimazole decreased the renal expression of ClC-2 in normal mice but not in Delta337T mutant mice. In in vitro studies performed on IRPT cells subjected to thyroid hormone treatment, the promoter region of the ClC-2 chloride channel was stimulated in a dose-dependent manner.'] Does thyroid hormone beta receptor mutation cause renal dysfunction and impairment of ClC-2 chloride channel expression in mouse kidney?
qiaojin/PubMedQA
2
[ -2.4168572425842285, -1.3228330612182617, 2.7441296577453613 ]
['Attine ants live in an intensely studied tripartite mutualism with the fungus Leucoagaricus gongylophorus, which provides food to the ants, and with antibiotic-producing actinomycete bacteria. One hypothesis suggests that bacteria from the genus Pseudonocardia are the sole, co-evolved mutualists of attine ants and are transmitted vertically by the queens. A recent study identified a Pseudonocardia-produced antifungal, named dentigerumycin, associated with the lower attine Apterostigma dentigerum consistent with the idea that co-evolved Pseudonocardia make novel antibiotics. An alternative possibility is that attine ants sample actinomycete bacteria from the soil, selecting and maintaining those species that make useful antibiotics. Consistent with this idea, a Streptomyces species associated with the higher attine Acromyrmex octospinosus was recently shown to produce the well-known antifungal candicidin. Candicidin production is widespread in environmental isolates of Streptomyces, so this could either be an environmental contaminant or evidence of recruitment of useful actinomycetes from the environment. It should be noted that the two possibilities for actinomycete acquisition are not necessarily mutually exclusive.', 'In order to test these possibilities we isolated bacteria from a geographically distinct population of A. octospinosus and identified a candicidin-producing Streptomyces species, which suggests that they are common mutualists of attine ants, most probably recruited from the environment. We also identified a Pseudonocardia species in the same ant colony that produces an unusual polyene antifungal, providing evidence for co-evolution of Pseudonocardia with A. octospinosus.'] Do a mixed community of actinomycetes produce multiple antibiotics for the fungus farming ant Acromyrmex octospinosus?
qiaojin/PubMedQA
2
[ -2.7525956630706787, 0.25310570001602173, 1.6024740934371948 ]
['To determine the inter-observer reliability in localization of recorded stridor sounds in children.', 'The stridor sounds of 28 children programmed for laryngobronchoscopy were recorded with a high quality digital recorder. Nineteen of these recordings with a diagnosis confirmed by endoscopy, were presented to otorhinolaryngology residents, academic specialists and non-academic consultants (n=38) in different situations with and without additional information about the subject. The participants were requested to score the sounds as pharyngeal, supraglottic, glottic, subglottic or tracheal in both situations. The scores were analyzed per group of participants, per location of obstruction and per diagnosis in the different situations.', 'The performance of the total group was just above chance level with an average score of 29.6%. The total results improved slightly with the additional information present, although not significantly. No significant difference was found between the three categories of participants. The supraglottic sounds were significantly better differentiated from the other locations in both assessment types (p<0.001). The tracheal region (p<0.01) and the supraglottic region (p<0.05) received significantly higher scores when the additional information was present. Laryngomalacia was significantly better differentiated (p<0.001) from the other diagnoses. The improvement in assessment with and without additional information present was significant for laryngomalacia (p=0.002) and tracheomalacia (p<0.035).'] Does inter-observer reliability of localization of recorded stridor sound in children?
qiaojin/PubMedQA
2
[ -1.627147912979126, -1.3219020366668701, 2.0503454208374023 ]
["Although ''Do not resuscitate'' (DNR) orders are among the most commonly discussed patient preference treatment measures, few studies have assessed internal medicine residents' views on this complex topic. Our objective was to assess resident practices in establishing code status. We also examined resident training and experiences in pronouncing death.", 'An 18-question survey addressing DNR discussions and pronouncing death was emailed to internal medicine residents in the state of Illinois. Each question had multiple-choice options.', 'A total of 175 residents completed the questionnaire (22% response rate). Seventy-eight percent of the residents had discussed DNR status with patients or their families at least 9 times. However, only one third of the residents felt very comfortable in such discussions. Only 26% of the residents had been observed by a faculty member during a code status discussion and fewer (16%) while pronouncing death. Do not resuscitate discussions rarely occurred in an outpatient clinic (27%). Most residents (90%) thought they would benefit from formal training in DNR discussion.'] Do residents ' practices and perceptions about resuscitate orders and pronouncing death : an opportunity for clinical training?
qiaojin/PubMedQA
1
[ -1.706102728843689, 2.406222105026245, -1.3266127109527588 ]
['Beta-catenin, as a major effector molecule in the canonical Wnt signaling pathway, could regulate adult neurogenesis. Here, the role of Wnt/β-catenin signaling pathway in the proliferation of hippocampal neural stem cells (NSCs) induced by hypoxia was investigated.', 'The hippocampal NSCs of neonatal green fluorescent protein transgenic mice on day 0 were cultured in hypoxia (5% O(2)) and traditional O(2) (20% O(2)). The expression of β-catenin, p-GSK-3β, and cyclinD1 in NSCs was measured under hypoxia or traditional O(2) by western blotting. NSCs were electroporated with pTOPFLASH reporter in different conditions and the LEF/TCF-dependent luciferase activity was assayed.', 'Hypoxia increased the proliferation and reduced the apoptosis of hippocampal NSCs. NSCs proliferation was inhibited by transfecting with pAxin, whereas promoted by transfecting with pβ-catenin.'] Is wnt/beta-catenin involved in the proliferation of hippocampal neural stem cells induced by hypoxia?
qiaojin/PubMedQA
2
[ -2.4578850269317627, -1.1610665321350098, 2.6601240634918213 ]
['Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination.', 'This was a prospective single-blinded trial involving 50 patients who were undergoing elective nontherapeutic colonoscopy. During colonoscopy, endoscopists removed the biopsy forceps first without and then with suctioning following contact with the sigmoid mucosa. A total of 50 L of air was collected continuously for 30 seconds at 30-cm distance from the biopsy channel valve of the colonoscope, with time starting at forceps removal. Airborne bacteria were collected by an impactor air sampler (MAS-100). Standard Petri dishes with CNA blood agar were used to culture Gram-positive bacteria. Main outcome measure was the bacterial load in endoscopy room air.', 'At the beginning and end of the daily colonoscopy program, the median (and interquartile [IQR] range) bioaerosol burden was 4 colony forming units (CFU)/m (3) (IQR 3 - 6) and 16 CFU/m (3) (IQR 13 - 18), respectively. Air suctioning during removal of the biopsy forceps reduced the bioaerosol burden from a median of 14 CFU/m (3) (IQR 11 - 29) to a median of 7 CFU/m (3) (IQR 4 - 16) ( P = 0.0001). Predominantly enterococci were identified on the agar plates.'] Does air suctioning during colon biopsy forceps removal reduce bacterial air contamination in the endoscopy suite?
qiaojin/PubMedQA
2
[ -1.808645486831665, -1.622302532196045, 2.477841854095459 ]
['the β-adrenergic and 5-HT(1A) receptor antagonist pindolol has been used in combination with antidepressant drugs, to shorten the time of onset of clinical efficacy and/or increase the proportion of responders in depressive and anxiety disorders. The aim of this study was to examine the interaction between pindolol and the selective serotonin reuptake inhibitor (SSRI), paroxetine in rats submitted to the elevated T-maze (ETM).', 'for assessing the drug combination effect, rats were administered with pindolol before paroxetine, using oral or intraperitoneal (i.p.) routes of acute administration, and were submitted to the ETM model.', 'the highest dose of pindolol used (15.0mg/kg, i.p.) increased both inhibitory avoidance and escape latencies in the ETM, probably due to nonspecific motor deficit, since locomotion in a circular arena was also significantly decreased. The highest dose of paroxetine (3.0mg/kg, i.p.) selectively impaired escape, considered a panicolytic effect. Combination of pindolol (5.0mg/kg, i.p.) with an ineffective dose of paroxetine (1.5mg/kg, i.p.) impaired escape, indicating a potentiation of the panicolytic effect of paroxetine. By the oral route, neither paroxetine (3.0mg/kg) nor pindolol (5.0mg/kg) alone were effective, but the combination treatment had a marked panicolytic effect, again indicating drug potentiation.'] Does pindolol potentiate the panicolytic effect of paroxetine in the elevated T-maze?
qiaojin/PubMedQA
2
[ -2.0178868770599365, -1.416542649269104, 2.482449769973755 ]
['Growing evidence indicates that glia atrophy contributes to the pathophysiology and possibly the pathogenesis of major depressive disorder. Electroacupuncture (EA), one of Chinese traditional therapy, has potent antidepressant-like effect in many clinical studies. The mechanism by which EA improves behavioral deficits is still unclear.', "Chronic unpredictable stress (CUS)-induced depression model rats were used to study the effect of EA treatment. EA was performed on acupoints 'Bai-Hui' (Du 20) and unilateral 'An-Mian' (EX 17) once daily for three consecutive weeks, two weeks post CUS procedure. The antidepressant-like effect of EA treatment was analyzed by physical state (PS) and open field test (OFT). Astrocytic marker glial fibrillary acidic protein (GFAP) level in the hippocampus was detected by immunohistochemistry, Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR).", 'Exposure to CUS resulted in a decrease of behavioral activity, whereas a daily session of EA treatment significantly reversed the behavioral deficit of these depression model rats. Moreover, the levels of GFAP mRNA and protein were decreased in the hippocampus of depression model rats. Intriguingly, EA treatment blocked effectively the decreased GFAP level.'] Is glia atrophy in the hippocampus of chronic unpredictable stress-induced depression model rats reversed by electroacupuncture treatment?
qiaojin/PubMedQA
2
[ -2.5618340969085693, -1.1991112232208252, 2.7720816135406494 ]
['Standardization of surgical and pathologic techniques is crucial to the interpretation of studies evaluating adjuvant therapies for pancreatic cancer (PC).', 'To assess the degree to which treatment administered prior to enrollment of patients in trials of adjuvant therapy is quality controlled, the operative and pathology reports of patients in American College of Surgeons Oncology Group (ACOSOG) Z5031-a national trial of chemoradiation following pancreaticoduodenectomy (PD)-were rigorously evaluated. We analyzed variables with the potential to influence staging or outcome.', '80 patients reported to have undergone R0 (75%) or R1 (25%) pylorus-preserving (38%) or standard (62%) PD were evaluated. A search for metastases was documented in 96% of cases. The proximity of the tumor to the superior mesenteric vein was reported in 69%; vein resection was required in 9% and lateral venorrhaphy in 14%. The method of dissection along the superior mesenteric artery (SMA) was described in 68%, being ultrasonic dissection (17%), stapler (24%), and clamp and cut (59%). SMA skeletonization was described in 25%, and absence of disease following resection was documented in 24%. The surgeon reported marking the critical SMA margin in 25%; inking was documented in 65% of cases and evaluation of the SMA margin was reported in 47%. A range of 1-49 lymph nodes was evaluated. Only 34% of pathology reports met College of American Pathologists criteria.'] Is standardization of surgical and pathologic variables needed in multicenter trials of adjuvant therapy for pancreatic cancer : results from the ACOSOG Z5031 trial?
qiaojin/PubMedQA
2
[ -2.077446937561035, -1.4987058639526367, 2.6420507431030273 ]
['In this report, we explored the role of PKCalpha and PKCe as mediators of phorbol 12-myristate13-acetate (PMA)-induced proliferation in pituitary tumor GH3B6 cells, and determined if the ERK1/2 and Akt pathways were activated.', 'The GH3B6 cell proliferation was estimated by BrdU incorporation and the cell cycle progression by flow cytometric cell cycle analysis. We determined the expression of PKCalpha and PKCe in membrane and cytosolic fractions by western blotting. The subcellular redistribution of both PKC isozymes was analyzed by confocal microscopy.', 'Incubation with PMA for 15 min stimulated PKCalpha and PKCe activation, which was correlated with the phosphorylation of ERK1/2 but not Akt. The activation of both these PKC isozymes was closely associated with the stimulation of proliferation and the cell cycle progression induced by PMA in GH3B6 cells, an effect that was blocked by the inhibitors of PKCalpha (Gö6976) and PKCe (eV1-2). In addition, the pretreatment with the inhibitor of ERK1/2 (PD98059) prevented the mitogenic activity induced by treatment with PMA for 15 min.'] Is gH3B6 pituitary tumor cell proliferation mediated by PKCalpha and PKCepsilon via ERK 1/2-dependent pathway?
qiaojin/PubMedQA
2
[ -2.372180700302124, -1.3375244140625, 2.785830497741699 ]
['Living donor liver transplantation (LDLT) patients run the risk of developing acute kidney injury (AKI) and subsequent chronic kidney disease, affecting morbidity and mortality. Sevoflurane has anti-inflammation properties, and renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic improvements in renal function. Extrahepatic metabolism of sevoflurane has been reported in patients undergoing liver transplantation, and might lead to nephrotoxicity. However, whether sevoflurane anesthesia is safe with regard to renal function in small-size liver transplantation needs further investigation. As neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of AKI, we looked at the renal effects of sevoflurane in a rat liver transplantation model using small-for-size grafts to investigate the changes of NGAL level and kidney histology.', 'Sixty male Sprague-Dawley rats were randomly divided into 2 groups after 50% size liver transplantation. Rats were anesthetized with chloral hydrate or with sevoflurane and subjected to liver transplantation. Twelve rats in each group were used for the survival study and 6 rats were used for the hemodynamic study. Six rats in each group were sacrificed 2 or 24 h after reperfusion. We harvested kidneys and serum for further analysis, including histological and functional parameters; TNF-α, IL-6 and NGAL immunoassay; expressions of myeloperoxidase (MPO) activity; and NF-κB in renal tissues.', 'Rats in the sevoflurane group had significantly lower Scr 24 h after reperfusion compared with those in the chloral hydrate group. Rats in the sevoflurane group demonstrated significantly reduced NGAL concentrations compared with rats in the chloral hydrate group 2 h after reperfusion. Epithelial necrosis in the chloral hydrate group (3.2 ± 0.8) was greater than that in the sevoflurane group (1.5 ± 1.1; p < 0.05). Sevoflurane anesthesia resulted in significantly lower plasma TNF-α and IL-6 concentrations and reduced MPO concentrations 2 h after reperfusion (p < 0.05). NF-κB protein levels 2 h after reperfusion increased by at least 110% in the chloral hydrate group relative to the sevoflurane group 2 h after reperfusion (p < 0.05). However, the urine inorganic fluoride concentrations increased significantly (p < 0.001) 2 h after reperfusion in the sevoflurane group (6.1 ± 1.5 μmol·l⁻¹) compared with the chloral hydrate group.'] Does sevoflurane protect against acute kidney injury in a small-size liver transplantation model?
qiaojin/PubMedQA
2
[ -2.1791841983795166, -1.4483044147491455, 2.6329221725463867 ]
['Osteoporosis is common in advanced COPD and worsens rapidly after transplantation, potentially impairing quality of life. Increased high density lipoprotein cholesterol (HDLc) has been observed in COPD and linked with osteoporosis in the general population. This association has not been previously examined in COPD.', 'We reviewed the records of 245 COPD patients referred for lung transplant evaluation. Osteoporosis was defined by either dual energy X-ray absorptiometry scan or use of osteoporosis medications. The presence or absence of osteoporosis could be ascertained in 152 subjects. Cholesterol values and other clinical variables were assessed for their association with osteoporosis.', 'Clinical factors associated with osteoporosis included lower BMI [OR 0.81, 95% CI 0.73-0.90], higher HDLc [OR 1.04, 95% CI 1.02 to 1.07], and worse lung function. HDLc was an independent predictor of OP and demonstrated an inverse linear correlation with T-scores (r\xa0=\xa0-0.21, p\xa0=\xa00.05), which was stronger amongst males (r\xa0=\xa0-0.45, p\xa0=\xa00.004).'] Are elevated HDL cholesterol levels associated with osteoporosis in lung transplant candidates with chronic obstructive pulmonary disease?
qiaojin/PubMedQA
2
[ -1.936816930770874, -1.549206256866455, 2.4620466232299805 ]
['Oxygen consumption is a key indicator of metabolic activity within embryos. Increased oxidative activity and REDOX changes at the time of fertilization have been suggested to signal Ca(2+) oscillations after sperm penetration. The objective of the present study was to determine the oxygen consumption and the REDOX status of zygotes and early embryos at the time of sperm penetration and cell cleavage and to investigate how metabolism relates to key temporal events and developmental competence.', 'Individual oxygen-consumption rates of bovine in vitro matured oocytes and presumptive zygotes (n = 101) were measured using the Nanorespirometer at 0, 7, 12, 17 and 24 h after IVF. Using the Embryoscope, oxygen-consumption profiles of individual oocytes and embryos (n = 75) were recorded repeatedly from 6 h until 30 h after IVF and time-lapse images were acquired, at intervals of ∼36 min. Oocytes and embryos were stained with Hoechst 33342 and visualization of nuclear stage was performed by fluorescence microscopy. To determine the REDOX status, cohorts of oocytes and zygotes (n = 55) were individually stained with REDOX-Sensor Red CC-1 and Hoechst 33342 at 0, 7, 12, 17 and 24 h after IVF and subsequently imaged by confocal microscopy.', 'A peak of oxygen consumption was observed at the time of fertilization and a smaller rise and fall in oxygen consumption could be detected prior to the first cell cleavage. Increased reactive oxygen species production was also observed at 7 h and then at 24 h after IVF, just preceding the first embryonic cleavage.'] Are oxygen consumption and ROS production increased at the time of fertilization and cell cleavage in bovine zygotes?
qiaojin/PubMedQA
2
[ -2.207149028778076, -1.2201554775238037, 2.5829832553863525 ]
['The clinical effectiveness of parenterally-administered glucagon-like peptide-1 (GLP-1) mimetics to improve glucose control in patients suffering from type 2 diabetes strongly supports discovery pursuits aimed at identifying and developing orally active, small molecule GLP-1 receptor agonists. The purpose of these studies was to identify and characterize novel nonpeptide agonists of the GLP-1 receptor.', 'Screening using cells expressing the GLP-1 receptor and insulin secretion assays with rodent and human islets were used to identify novel molecules. The intravenous glucose tolerance test (IVGTT) and hyperglycemic clamp characterized the insulinotropic effects of compounds in vivo.', 'Novel low molecular weight pyrimidine-based compounds that activate the GLP-1 receptor and stimulate glucose-dependent insulin secretion are described. These molecules induce GLP-1 receptor-mediated cAMP signaling in HEK293 cells expressing the GLP-1 receptor and increase insulin secretion from rodent islets in a dose-dependent manner. The compounds activate GLP-1 receptor signaling, both alone or in an additive fashion when combined with the endogenous GLP-1 peptide; however, these agonists do not compete with radiolabeled GLP-1 in receptor-binding assays. In vivo studies using the IVGTT and the hyperglycemic clamp in Sprague Dawley rats demonstrate increased insulin secretion in compound-treated animals. Further, perifusion assays with human islets isolated from a donor with type 2 diabetes show near-normalization of insulin secretion upon compound treatment.'] Does novel small molecule glucagon-like peptide-1 receptor agonist stimulate insulin secretion in rodents and from human islets?
qiaojin/PubMedQA
2
[ -2.535156011581421, -1.1816881895065308, 2.7528605461120605 ]
['Hormones are critical for early gonadal development in nonmammalian vertebrates, and oestrogen is required for normal ovarian development. In contrast, mammals determine sex by the presence or absence of the SRY gene, and hormones are not thought to play a role in early gonadal development. Despite an XY sex-determining system in marsupial mammals, exposure to oestrogen can override SRY and induce ovarian development of XY gonads if administered early enough. Here we assess the effect of exogenous oestrogen on the molecular pathways of mammalian gonadal development.', 'We examined the expression of key testicular (SRY, SOX9, AMH and FGF9) and ovarian (WNT4, RSPO1, FOXL2 and FST) markers during gonadal development in the marsupial tammar wallaby (Macropus eugenii) and used these data to determine the effect of oestrogen exposure on gonadal fate. During normal development, we observed male specific upregulation of AMH and SOX9 as in the mouse and human testis, but this upregulation was initiated before the peak in SRY expression and 4 days before testicular cord formation. Similarly, key genes for ovarian development in mouse and human were also upregulated during ovarian differentiation in the tammar. In particular, there was early sexually dimorphic expression of FOXL2 and WNT4, suggesting that these genes are key regulators of ovarian development in all therian mammals. We next examined the effect of exogenous oestrogen on the development of the mammalian XY gonad. Despite the presence of SRY, exogenous oestrogen blocked the key male transcription factor SOX9 from entering the nuclei of male somatic cells, preventing activation of the testicular pathway and permitting upregulation of key female genes, resulting in ovarian development of the XY gonad.'] Does oestrogen block the nuclear entry of SOX9 in the developing gonad of a marsupial mammal?
qiaojin/PubMedQA
2
[ -2.543649435043335, -0.28467991948127747, 1.905989170074463 ]
['Insulin resistance is a central feature of the metabolic syndrome and progressively increases with age, resulting in excessively high incidence of type II diabetes in the elderly population. Peroxisome proliferator-activated receptor-alpha (PPARalpha) is widely expressed in insulin target tissues, including those of the liver, kidney, and muscle, where it mediates expression of genes promoting fatty acid beta-oxidation. The aim of this study was to evaluate the potential role of PPARalpha in insulin resistance in aging mice induced by a high-fat diet.', 'We used male PPARalpha knockout (KO) mice and wild-type (WT) littermates that were 18 months old. Animals were fed with a high-fat diet (HFD) for 4 weeks, and metabolic parameters associated with insulin sensitivity were assessed.', 'Following HFD treatment, WT mice showed more severe insulin resistance than did mice lacking the PPARalpha gene, as assessed by both the glucose tolerance test (GTT) and insulin tolerance test (ITT). In addition, WT mice exhibited significantly higher HOMA-IR, plasma total cholesterol levels and urinary albumin-creatinine ratio but less liver weight than did PPARalpha KO mice.'] Does peroxisome proliferator-activated receptor-alpha deficiency protect aged mice from insulin resistance induced by high-fat diet?
qiaojin/PubMedQA
2
[ -2.307765245437622, -1.076791763305664, 2.386672019958496 ]
["The Israel Defense Force (IDF) conducts screening examinations of military personnel aimed at early detection of morbidities, including erectile dysfunction (ED) and other sexual disorders (SDs). Men with SDs are referred to the IDF's sex clinic for consultation.", 'We present the long-term compliance of military men with SDs to the screening program.', "We investigated how many men screened for ED and other SDs turned to the IDF's sex clinic for consultation.", "Subjects 25-50 years old performed screening examinations at the Staff Periodic Examination Center. The Sexual Health Inventory for Men (SHIM) questionnaire was used to categorize ED. The IDF's sex clinic records were investigated.", "During 2001-2003, 5,836 men completed the SHIM questionnaire. Overall, 1,570 (26.9%) men had low SHIM scores suggesting ED and other SDs. Although only 76 (4.8%) of these men turned to the IDF's sex clinic over these years, more men conferred with the IDF's sexologist every year, and more men were referred by their primary-care physicians to the IDF's sex clinic regardless of their SHIM score."] Do the minority of young adult men with sexual disorders seek medical treatment?
qiaojin/PubMedQA
1
[ -0.005224814638495445, 1.2673649787902832, -2.125453472137451 ]
["A phase II study was conducted to evaluate the activity and safety of topotecan in pediatric patients with recurrent Wilms' tumor.", "Patients with favorable histology Wilms' tumor (FHWT) and recurrence after at least one salvage chemotherapy regimen or with anaplastic histology Wilms' tumor (AHWT) in first or subsequent recurrence were eligible. Patients were stratified according to histology, with statistical considerations based on the FHWT stratum. Topotecan was administered intravenously over 30 minutes for 5 days on 2 consecutive weeks. Treatment dosages were adjusted to achieve a target area under the curve (AUC) of 80 +/- 10 ng/mL*h. Tumor responses were measured after two cycles of treatment.", 'Thirty-seven patients (26 patients with FHWT) were enrolled and received a total of 94 cycles of topotecan (range, one to six cycles). The median topotecan dosage required to achieve the target AUC was 1.8 mg/m2 (range, 0.7 to 3.2 mg/m2). Of 25 assessable patients with FHWT, 12 had partial response (PR), six had stable disease (SD), and seven had progressive disease (PD), for an overall response rate of 48% (95% CI, 27.8% to 68.7%). Of 11 assessable patients with AHWT, two had PR, one had SD, and eight had PD. The main toxicities were grade 3 and 4 neutropenia (median duration, 13 days) and thrombocytopenia (median duration, 7.5 days).'] Is topotecan active against Wilms ' tumor : results of a multi-institutional phase II study?
qiaojin/PubMedQA
2
[ -1.6537114381790161, -1.637311577796936, 2.260026693344116 ]
['A synergistic cytotoxic effect has been hypothesized for taxanes and capecitabine, a prodrug of 5-fluorouracil. Based on preclinical studies, this synergism has been attributed to an up-regulation of the enzyme thymidine phosphorylase (TP). Beside tumour tissue, TP is highly expressed in white blood cells, possibly causing increased hematotoxicity, when taxanes are combined with capecitabine. So far, this hypothesis has not been investigated in humans.', 'A total of 128 consecutive blood samples were collected from eight patients with advanced breast cancer receiving paclitaxel weekly at a dose of 80 mg/m2. To assess the expression of TP in blood cells, samples were collected prior to first therapy, at the end of infusion, and up to 15 days thereafter. This procedure was repeated during the sixth application of paclitaxel. After isolation of the peripheral mononuclear blood cells, the expression of TP was assessed by ELISA. In parallel, paclitaxel level in plasma was evaluated at three selected time points as pharmacokinetic control parameter.', 'Paclitaxel concentrations at the end of infusion did not change significantly from week 1 to week 6. The expression of TP in peripheral mononuclear blood cells decreased significantly after infusion below pretherapeutic values (p = 0.023; n = 8). After the nadir on day 3, the expression of TP increased moderately returning to baseline levels within one week. The overall picture in week 6 was similar to week 1. Using a trend analysis, neither a short-term nor a long-term induction of TP was observed.'] Is expression of thymidine phosphorylase in peripheral blood cells of breast cancer patients increased by paclitaxel?
qiaojin/PubMedQA
2
[ -2.165661096572876, -1.4885740280151367, 2.6907076835632324 ]
['To present and compare population-based and antenatal-care (ANC) sentinel surveillance HIV prevalence estimates among women in a rural South African population where both provision of ANC services and family planning is prevalent and fertility is declining. With a need, in such settings, to understand how to appropriately adjust ANC sentinel surveillance estimates to represent HIV prevalence in general populations, and with evidence of possible biases inherent to both surveillance systems, we explore differences between the two systems. There is particular emphasis on unrepresentative selection of ANC clinics and unrepresentative testing in the population.', 'HIV sero-prevalence amongst blood samples collected from women consenting to test during the 2005 annual longitudinal population-based serological survey was compared to anonymous unlinked HIV sero-prevalence amongst women attending antenatal care (ANC) first visits in six clinics (January to May 2005). Both surveillance systems were conducted as part of the Africa Centre Demographic Information System.', 'Population-based HIV prevalence estimates for all women (25.2%) and pregnant women (23.7%) were significantly lower than that for ANC attendees (37.7%). A large proportion of women attending urban or peri-urban clinics would be predicted to be resident within rural areas. Although overall estimates remained significantly different, presenting and standardising estimates by age and location (clinic for ANC-based estimates and individual-residence for population-based estimates) made some group-specific estimates from the two surveillance systems more predictive of one another.'] Does population and antenatal-based HIV prevalence estimate in a high contracepting female population in rural South Africa?
qiaojin/PubMedQA
1
[ -1.376517415046692, 0.9118248224258423, -0.3009181618690491 ]
["The loudness dependence of the auditory evoked Potential (LDAEP) has been suggested to be a putative marker of central serotonin function, with reported abnormalities in clinical disorders presumed to reflect serotonin dysfunction. Despite considerable research, very little is known about the LDAEP's sensitivity to other neurotransmitter systems.", 'Given the role of N-methyl-D-aspartate (NMDA) receptors in modulating pyramidal cell activity in cortico-cortico and thalamo-cortical loops, we examined the effect of targeting the glycine modulatory site of the NMDA receptor with high-dose glycine on the LDAEP in healthy subjects.', 'The study was a double-blind, placebo-controlled repeated-measures design in which 14 healthy participants were tested under two acute treatment conditions, placebo and oral glycine (0.8 g/kg). Changes in the amplitude of the N1/P2 at varying intensities (60, 70, 80, 90, 100 dB) were examined at C(Z).', 'Compared to placebo, high-dose glycine induced a weaker LDAEP (a pronounced decrease in the slope of the N1/P2 with increasing tone loudness; p < 0.02).'] Does high-dose glycine inhibit the loudness dependence of the auditory evoked potential ( LDAEP ) in healthy humans?
qiaojin/PubMedQA
2
[ -2.3061158657073975, -1.2992868423461914, 2.607729196548462 ]
['To investigate the effects of tanshinone IIA (Tan IIA) on the regulation of the production of endothelin (ET)-1 (including large ET-1), mRNA levels of ET-1, endothelin-converting enzyme-1 (ECE-1), endothelin-A receptor (ETA) and endothelin-B receptor (ETB) induced by TNF-alpha in rat brain microvascular endothelial cells (BMVEC).', 'The ET-1 release (including large ET-1) into the culture medium was determined by enzyme immunoassay. The levels of ET-1, ECE-1, ETA, and ETB mRNA were measured by RT-PCR. Endothelin receptor binding was also tested.', 'The induction of ET-1 release by TNF-alpha from cultured BMVEC was dose-dependently reduced by Tan IIA, but large ET-1 levels progressively increased in response to Tan IIA; the mRNA expression of ET-1 was unaffected. Tan IIA also caused a decrease in ETA receptor mRNA and ECE-1 expression in a dose-dependent manner. Endothelin receptor binding was unaltered in BMVEC stimulated with TNF-alpha alone or a combination of TNF-alpha and Tan IIA.'] Does tanshinone IIA inhibit endothelin-1 production in TNF-alpha-induced brain microvascular endothelial cells through suppression of endothelin-converting enzyme-1 synthesis?
qiaojin/PubMedQA
2
[ -2.434857130050659, -1.187223196029663, 2.6828103065490723 ]
['In general, opioids that induce the recycling of mu-opioid receptors (MORs) promote little desensitization, although morphine is one exception to this rule. While morphine fails to provoke significant internalization of MORs in cultured cells, it does stimulate profound desensitization. In contrast, morphine does promote some internalization of MORs in neurons although this does not prevent this opioid from inducing strong antinociceptive tolerance.', 'In neurons, morphine stimulates the long-lasting transfer of MOR-activated Galpha subunits to proteins of the RGS-R7 and RGS-Rz subfamilies. We investigated the influence of this regulatory process on the capacity of morphine to promote desensitization and its association with MOR recycling in the mature nervous system. In parallel, we also studied the effects of [D-Ala2, N-MePhe4, Gly-ol5] encephalin (DAMGO), a potent inducer of MOR internalization that promotes little tolerance. We observed that the initial exposure to icv morphine caused no significant internalization of MORs but rather, a fraction of the Galpha subunits was stably transferred to RGS proteins in a time-dependent manner. As a result, the antinociception produced by a second dose of morphine administered 6 h after the first was weaker. However, this opioid now stimulated the phosphorylation, internalization and recycling of MORs, and further exposure to morphine promoted little tolerance to this moderate antinociception. In contrast, the initial dose of DAMGO stimulated intense phosphorylation and internalization of the MORs associated with a transient transfer of Galpha subunits to the RGS proteins, recovering MOR control shortly after the effects of the opioid had ceased. Accordingly, the recycled MORs re-established their association with G proteins and the neurons were rapidly resensitized to DAMGO.'] Does morphine induce endocytosis of neuronal mu-opioid receptors through the sustained transfer of Galpha subunits to RGSZ2 proteins?
qiaojin/PubMedQA
2
[ -2.4894890785217285, -1.0609593391418457, 2.6082324981689453 ]
['Precise connections of neural circuits can be specified by genetic programming. In the Drosophila olfactory system, projection neurons (PNs) send dendrites to single glomeruli in the antenna lobe (AL) based upon lineage and birth order and send axons with stereotyped terminations to higher olfactory centers. These decisions are likely specified by a PN-intrinsic transcriptional code that regulates the expression of cell-surface molecules to instruct wiring specificity.', 'We find that the loss of longitudinals lacking (lola), which encodes a BTB-Zn-finger transcription factor with 20 predicted splice isoforms, results in wiring defects in both axons and dendrites of all lineages of PNs. RNA in situ hybridization and quantitative RT-PCR suggest that most if not all lola isoforms are expressed in all PNs, but different isoforms are expressed at widely varying levels. Overexpression of individual lola isoforms fails to rescue the lola null phenotypes and causes additional phenotypes. Loss of lola also results in ectopic expression of Gal4 drivers in multiple cell types and in the loss of transcription factor gene lim1 expression in ventral PNs.'] Does lola regulate Drosophila olfactory projection neuron identity and targeting specificity?
qiaojin/PubMedQA
2
[ -2.6774721145629883, -0.6933957934379578, 2.444875955581665 ]
['Cryptic species are two or more distinct but morphologically similar species that were classified as a single species. During the past two decades we observed an exponential growth of publications on cryptic species. Recently published reviews have demonstrated cryptic species have profound consequences on many biological disciplines. It has been proposed that their distribution is non-random across taxa and biomes.', 'We analysed a literature database for the taxonomic and biogeographical distribution of cryptic animal species reports. Results from regression analysis indicate that cryptic species are almost evenly distributed among major metazoan taxa and biogeographical regions when corrected for species richness and study intensity.'] Are cryptic animal species homogeneously distributed among taxa and biogeographical regions?
qiaojin/PubMedQA
1
[ -2.095418691635132, 2.3875086307525635, -0.8801802396774292 ]
["Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinson's disease.", "We analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinson's disease.", "We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects > or =65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700,000 subjects taking simvastatin and over 50,000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44-0.48, p < 0.0001) and 0.91 (CI 0.80-1.02, p = 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4-0.55, p < 0.0001)."] Is simvastatin associated with a reduced incidence of dementia and Parkinson 's disease?
qiaojin/PubMedQA
2
[ -1.4686232805252075, -1.3671319484710693, 1.8492511510849 ]
['Prolactin promotes proliferation of several cells. Prolactin receptor exists as two isoforms: long and short, which activate different transduction pathways including the Ca2+-dependent PKC-signaling. No information exists on the role of prolactin in the regulation of the growth of female cholangiocytes. The rationale for using cholangiocytes from female rats is based on the fact that women are preferentially affected by specific cholangiopathies including primary biliary cirrhosis. We propose to evaluate the role and mechanisms of action by which prolactin regulates the growth of female cholangiocytes.', 'Normal cholangiocytes express both isoforms (long and short) of prolactin receptors, whose expression increased following BDL. The administration of prolactin to normal female rats increased cholangiocyte proliferation. In purified normal female cholangiocytes, prolactin stimulated cholangiocyte proliferation, which was associated with increased [Ca2+]i levels and PKCbeta-I phosphorylation but decreased PKCalpha phosphorylation. Administration of an anti-prolactin antibody to BDL female rats decreased cholangiocyte proliferation. Normal female cholangiocytes express and secrete prolactin, which was increased in BDL rats. The data show that prolactin stimulates normal cholangiocyte growth by an autocrine mechanism involving phosphorylation of PKCbeta-I and dephosphorylation of PKCalpha.'] Does prolactin stimulate the proliferation of normal female cholangiocytes by differential regulation of Ca2+-dependent PKC isoforms?
qiaojin/PubMedQA
2
[ -2.4264914989471436, -1.1672221422195435, 2.5980324745178223 ]
['Adipocyte-fatty acid binding protein (A-FABP) is a circulating protein expressed in adipocytes and macrophages. Several recent studies demonstrated that A-FABP might be involved in the pathogenesis of metabolic syndrome, particularly in dyslipidaemia, insulin resistance and atherosclerosis. The aim of this study was to investigate the influence of atorvastatin treatment (20 mg day(-1) for 3 months) on serum A-FABP value in subjects with hyperlipidaemia.', 'Anthropometric and serum analyses were performed for body mass index, A-FABP, triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), high sensitive C-reactive protein (hs-CRP), creatine kinase (CK) and glucose on 26 subjects (BMI 30.3 +/- 6.0, mean age 62 +/- 10 years) with hyperlipidaemia who met the criteria: total cholesterol > 5.2 mmol L(-1), LDL cholesterol > 3.3 mmol L(-1) and triglycerides < 3 mmol L(-1).', 'After the 3-month therapy, a significant reduction in total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), glucose (P < 0.001), A-FABP (from 44.6 +/- 26.2 to 38.6 +/- 19.3 g L(-1), P < 0.01), uric acid (P < 0.05), AST (P < 0.05) and triglycerides (P < 0.05) values was observed. No difference was found in BMI, CK, ALT, hs-CRP, or HDL cholesterol values. A significant difference in the serum A-FABP value before and after the therapy remains after the correction for total cholesterol value (P < 0.001). A positive correlation between serum A-FABP and glucose was found (P < 0.05).'] Does treatment with atorvastatin reduce serum adipocyte-fatty acid binding protein value in patients with hyperlipidaemia?
qiaojin/PubMedQA
2
[ -1.8182690143585205, -1.6000189781188965, 2.409576177597046 ]
["Although endothelial cells express insulin receptors, it is controversially discussed whether the endothelium represents an insulin-responsive tissue. Since available data are primarily restricted to animal endothelial cells, this study tested (i) whether insulin affects glucose metabolism in human endothelium; (ii) whether insulin sensitivity is different in micro- versus macrovascular endothelial cells; and (iii) whether glucose concentration in the incubation medium affects the cells' response to insulin.", 'Human umbilical vein endothelial cells (HUVECs), human adult saphenous vein endothelial cells (HAVECs), human aortic endothelial cells (HAEC), and human retinal endothelial cells (HRECs) as well as human smooth muscle cells were incubated with/without insulin (0.3 nmol L(-1) or 1 micromol L(-1)). Glucose transport, glycogen synthesis, glycogen content, lactate release, and expression of phospho-Akt, Akt, and endothelial nitric oxide synthase (eNOS) were determined.', 'In HUVECs and HRECs, insulin (1 micromol L(-1)) increased (P < 0.05) eNOS expression by ~70% and doubled Akt phosphorylation, but the latter was by far more pronounced in human smooth muscle cells (+1093 +/- 500%, P < 0.05). In human smooth muscle cells, insulin (1 micromol L(-1)) stimulated glycogen synthesis by 67 +/- 11% (P < 0.01). In human micro- (HRECs) and macrovascular endothelial cells (HUVECs, HAVECs and HAECs), insulin, however, failed to stimulate glucose transport, glycogen synthesis, glycogen content, or lactate release under various conditions, i.e. after glucose deprivation or in medium with normal (5.5 mmol L(-1)) or high glucose (30 mmol L(-1)).'] Does insulin regulate glucose transport and metabolism in human endothelium?
qiaojin/PubMedQA
2
[ -2.2176637649536133, -1.14590585231781, 2.4463205337524414 ]
['Diabetic teratogenicity relates, partly, to embryonic oxidative stress and the extent of the embryonic damage can apparently be reduced by antioxidants. We investigated the effects of superoxide dismutase-mimics nitroxides, 2,2,6,6-tetramethyl piperidine-N-oxyl (TPL) as an effective antioxidant, on diabetes-induced embryopathy.', 'Embryos (10.5 day old) and their yolk sacs from Sabra female rats were cultured for 28 h in the absence or in the presence of nitroxides at 0.05-0.4 mM in control, diabetic subteratogenic, or diabetic teratogenic media, and monitored for growth retardation and congenital anomalies. The oxidant/antioxidant status was examined by oxygen radical absorbance capacity and lipid peroxidation assays, whereas the yolk sac function was evaluated by endocytosis assay.', 'Diabetic culture medium inhibited embryonic and yolk sac growth, induced a high rate of NTDs, reduced yolk sac endocytosis and embryonic antioxidant capacity, and increased lipid peroxidation. These effects were more prominent in the embryos with NTD compared to those without NTD. TPL added to diabetic teratogenic medium improved embryonic and yolk sac growth, reduced the rate of NTDs, and improved yolk sac function. The oxidant/antioxidant status of embryos was also improved. TPL at 1 mM did not damage the embryos cultured in control medium.'] Do nitroxide radicals protect cultured rat embryos and yolk sacs from diabetic-induced damage?
qiaojin/PubMedQA
2
[ -2.4181458950042725, -1.3142386674880981, 2.8116157054901123 ]
['Walking and cycling to school could be an important regular source of physical activity in growing children. The aim of this 12 months prospective observational study was thus to evaluate the effect of self-transportation to school on bone mineral accrual and gain in bone width in pre-pubertal children, both traits independently contributing to bone strength.', "Ninety-seven girls and 133 boys aged 7-9 years were recruited as a part of the Malmö Pediatric Osteoporosis Prevention (POP) Study in order to evaluate the influence of self-selected school transportation for the accrual of bone mineral and bone width. Children who walked or cycled to school were compared with children who went by bus or car. Bone mineral content (BMC) was measured by dual energy X-ray absorptiometry (DXA) in the lumbar spine (L2-L4), third lumbar vertebra (L3) and hip, and bone width was calculated at L3 and femoral neck (FN). Changes during the first 12 months were compared between the groups. Subjective duration of physical activity was estimated by a questionnaire and objective level of everyday physical activity at follow-up by accelerometers worn for four consecutive days. All children remained in Tanner stage 1 throughout the study. Comparisons were made by independent student's t-tests between means, ANCOVA and Fisher's exact tests.", 'There were no differences in baseline or annual changes in BMC or bone width when the transportation groups were compared. No differences were detected in objectively measured daily level of physical activity by accelerometer. All children reached above 60 minutes of moderate to intense daily physical activity per day, the international recommended level of daily physical activity according to the United Kingdom Expert Consensus Group.'] Is bone mineral accrual and gain in skeletal width in pre-pubertal school children independent of the mode of school transportation -- one-year data from the prospective observational pediatric osteoporosis prevention ( POP ) study?
qiaojin/PubMedQA
2
[ -1.586666464805603, -1.2890121936798096, 1.959093689918518 ]
['Interleukin-7 (IL-7) has been studied for its possible immunorestorative capacities following stem cell transplantation and has been shown to enhance post-transplant immune recovery predominantly by peripheral T-cell expansion. A major concern of IL-7 is its possible aggravating effect on graft-versus-host and host-versus-graft reactivity.', 'To study the effect of IL-7 on host-versus-graft reactivity, we applied IL-7 in an experimental transplantation model using RAG-1-/- mice supplied with B6 CD45.1 congenic T cells as recipients of T-cell depleted allogeneic bone marrow grafts.', 'Rejection of minor antigen-mismatched bone marrow was significantly reduced in IL-7 treated recipients compared with PBS treated control mice. Rejection was observed in 2 out of 18 IL-7 treated mice compared with 9 out of 17 PBS treated mice (11% vs. 53%; p=0.012). IL-7 administration resulted in enhanced recovery of peripheral blood CD4+CD25+ regulatory T cells (Treg) with a concomitant increase in peripheral blood Foxp3 mRNA expression. IL-7Ra (CD127) was expressed by the vast majority of CD4+Foxp3+ T cells. The incidence of graft rejection following fully MHC mismatched bone marrow transplantation was not reduced nor enhanced by IL-7 administration.'] Is iL-7-mediated protection against minor-antigen-mismatched allograft rejection associated with enhanced recovery of regulatory T cells?
qiaojin/PubMedQA
2
[ -2.308687448501587, -1.3971229791641235, 2.7056078910827637 ]
['Treatment with the anti-tumour necrosis factor alpha monoclonal antibody infliximab has been shown to be effective in moderate-to-severe ulcerative colitis. However, its effect on the mucosal histopathological abnormalities of this disease is largely unknown. This study aimed to assess the immunohistological effect of infliximab in ulcerative colitis.', 'Nine patients with moderate-to-severe ulcerative colitis received infliximab (5mg/kg) at weeks 0, 2 and 6, respectively. Colonic biopsies were collected before therapy and at week 10, when the Mayo score (including the endoscopic subscore) was also assessed. Severity of inflammation was evaluated by histologic score and histomorphometry. Immunohistochemical staining with antibody against tumour necrosis factor alpha was performed on all biopsies and expressed as percentage of positive stromal cells/1000 counted (tumour necrosis factor alpha score).', "A profound down-regulation of mucosal tumour necrosis factor alpha occurred in all the six patients who achieved a clinical response, but not in the three who did not respond. Median tumour necrosis factor alpha score dropped from 44.8 (range 35-58.3) to 12.8 (range 5.3-15.3) in the responders (p=0.03), whilst it remained unchanged in the non-responders. Such effect was related with a dramatic regression of the median histologic score, which dropped from 2.7 (range 2-3) to 0.5 (range 0.0-1.5) in responder patients (p=0.002). This was related to a virtual disappearance of neutrophils in responders (r=0.72; p=0.002; Spearman's test), but not in those who did not improve. Tumour necrosis factor alpha score appeared to be correlated with the histologic, endoscopic and clinical activity."] Does tumour necrosis factor alpha down-regulation parallel inflammatory regression in ulcerative colitis patients treated with infliximab?
qiaojin/PubMedQA
2
[ -2.176623821258545, -1.4678559303283691, 2.7045786380767822 ]
['To compare the ability of an amorphous first aid topical gel containing vinegar, citric acid and EDTA (RescuDerm(TM); RESC) and various derivative formulations to eradicate Pseudomonas aeruginosa (PSEUD) and Staphylococcus epidermidis (STAPH) biofilms.', '24-h biofilms prepared using the Minimum Biofilm Elimination Concentration (MBEC) Assay System were exposed for 4 or 24 h to the different gel formulations. Citric acid-free, acetic acid-free or acetic acid-free/sodium acetate-supplemented RESC gels reduced PSEUD and STAPH biofilm formation as effectively as RESC. Substituting the weak organic acids with equivalent concentrations of glacial acetic acid reduced the effectiveness of gel against PSEUD and STAPH biofilms by half, but viable bacterial counts still remained below 4 log(10) CFU/peg. Removal of gelling agent and/or EDTA enhanced efficacy against PSEUD but not STAPH biofilms. An acidified placebo gel formulation generated an only marginal bactericidal effect compared to that of RESC.'] Do biofilm reduction by a new burn gel that targets nociception?
qiaojin/PubMedQA
2
[ -2.315372943878174, -1.3731777667999268, 2.822523593902588 ]
['The purpose of the study was to compare the effectiveness of GnRH antagonist with luteal phase estradiol administration to GnRH agonist cycles, long protocol.', '55 IVF-ICSI patients received oestradiol in the luteal phase of the cycle, before a cycle with GnRH antagonist. Fifty-five patients submitted to IVF-ICSI with the use of agonist were allocated, age matched, as a control group (historical control). The primary outcome was the number of retrieved oocytes.', 'Patients were similar in terms of clinical characteristics. No differences were found in the number of oocytes retrieved (study group, 8.1 +/- 4.7; control group, 7.4 +/- 4.5) or in oocyte quality.'] Is luteal phase oestradiol administration in ovarian stimulation cycles with GnRH antagonist comparable to the GnRH agonist ( long ) protocol?
qiaojin/PubMedQA
2
[ -2.067110776901245, -1.4513440132141113, 2.5612945556640625 ]
['Accidental cannulation of an epidural vein is a common complication associated with epidural anesthesia or analgesia. On the basis of a pilot study and previous reports, we tested the hypothesis that predistention of the epidural space with saline before epidural catheterization would ease catheter insertion and decrease the incidence of this complication.', 'Two-hundred-three laboring women were randomly assigned to receive an epidural with loss of resistance technique with 2 mL (nondistention) or 5 mL saline (distention). In the distention group, the syringe plunger was held closed before epidural catheter insertion. Then in both groups, a test dose of 3 mL of 1.5% lidocaine was injected through the epidural catheter.', 'There were fewer accidental intravascular catheter placements (2% vs 16%, P = 0.0001) in the distention group, and 91% of patients in this group did not have any unblocked segments versus 67% in the nondistension group (P = 0.0001). The difference in onset time of analgesia was small (5.0 +/- 2 min vs 6 +/- 3 min, P = 0.0001) and not clinically important. The quality of analgesia (visual analog scores and ropivacaine consumption) was similar between groups.'] Does predistention of the epidural space before catheter insertion reduce the incidence of intravascular epidural catheter insertion?
qiaojin/PubMedQA
2
[ -1.9587572813034058, -1.5035053491592407, 2.4797492027282715 ]
['This study investigated sustained abdominal compression as a means to improve coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) and compared the resulting CPP augmentation with that achieved using vasopressor drugs.', 'During electrically induced ventricular fibrillation in anesthetized, 30kg juvenile pigs, Thumper CPR was supplemented at intervals either by constant abdominal compression at 100-500mmHg using an inflated contoured cuff or by the administration of vasopressor drugs (epinephrine, vasopressin, or glibenclamide). CPP before and after cuff inflation or drug administration was the end point.', 'Sustained abdominal compression at >200mmHg increases CPP during VF and otherwise standard CPR by 8-18mmHg. The effect persists over practical ranges of chest compression force and duty cycle and is similar to that achieved with vasopressor drugs. Constant abdominal compression also augments CPP after prior administration of epinephrine or vasopressin.'] Does sustained abdominal compression during CPR raise coronary perfusion pressures as much as vasopressor drugs?
qiaojin/PubMedQA
2
[ -2.450517416000366, -1.0496459007263184, 2.5679540634155273 ]
['Selenite-induced cataractogenesis is mediated by oxidative stress, accumulation of calcium and activation of lenticular calpains. Calpains are a super family of Ca2+ dependent proteases, which are involved in lens protein proteolysis and insolubilization. Many inhibitors could prevent calpain-induced proteolysis of alpha- and beta-crystallins in rodent cataracts. Evaluating natural sources with antioxidant property and subsequent prevention of calpain activation may lead to the development of safer and more effective agents against cataractogenesis. There are no reports on the protective role of bioactive components against calpain-mediated proteolysis and subsequent cataractogenesis. The purpose of the study was to evaluate the role of Drevogenin D, a triterpenoid aglycone, isolated from Dregea volubilis in preventing selenite-induced, calcium-activated, calpain-mediated proteolysis in cultured rat lenses.', 'Lenses were extracted from Sprague-Dawley strain rats at the age of one month and were organ cultured in M-199 medium with HEPES buffer. The lenses were divided into three groups with eight lenses in each group as follows: lenses cultured in a normal medium (GI), lenses cultured in a sodium selenite supplemented medium (GII), and lenses cultured in a medium supplemented with sodium selenite and Drevogenin D-treated (GIII). Changes to transparency and opacity formation of lenses were monitored under microscopic observation. At the end of the experiment, biochemical parameters such as activity of lens superoxide dismutase (SOD), lens Ca2+ ATPase, concentration of Ca2+, levels of sulfhydryl content, and thiobarbituric acid reacting substances (TBARS) were determined. Changes to casein zymography for calpains, immunoblot for Lp82, and SDS-PAGE of lens water soluble protein fraction (WSF) were also done.', 'Microscopic evaluation of lens morphology showed that Drevogenin D prevented the opacification in G-III. Drevogenin D inhibited the accumulation of calcium, the activation of calpain system, and lipid peroxidation. Activity of Ca2+ ATPase, SOD, and SDS-PAGE profile of water soluble proteins was normalized following treatment with Drevogenin D.'] Does drevogenin D prevent selenite-induced oxidative stress and calpain activation in cultured rat lens?
qiaojin/PubMedQA
2
[ -2.4627625942230225, -1.3700940608978271, 2.847069263458252 ]
['Neural retina leucine-zipper (NRL), a member of the basic motif leucine zipper family of transcription factors, is preferentially expressed in rod photoreceptors of the mammalian retina. Mutations in NRL are associated with retinopathies; many of these are suggested to change phosphorylation status and alter NRL-mediated transactivation of rhodopsin promoter. The purpose of this study was to identify potential kinases responsible for the phosphorylation of NRL and determine if such kinase-dependent phosphorylation is altered in disease-associated NRL mutations.', 'Metabolic labeling with 33P-orthophosphate was used to study phosphorylation of NRL in transfected COS-1 cells. NRL or NRL mutants were expressed as glutathione S-transferase (GST)-fusion proteins and used as substrate to screen various kinases by in vitro phosphorylation assays. CV-1 cells were co-transfected with rhodopsin promoter-reporter construct and expression plasmids, with or without specific mitogen-activated protein kinase (MAPK) inhibitors, to examine their effect on NRL-mediated transactivation. Expression of activated MAPKs in postnatal mice retina was determined by immunoblot analysis.', 'Metabolic labeling of NRL produces multiple phosphorylated protein bands in transfected COS-1 cells. Fewer but more intense radiolabeled bands are observed for NRL-S50T, -S50A, and -P51L mutants compared to wild-type NRL. We show that MAPK2 and p38 induce specific phosphorylation of NRL, but this pattern is altered in NRL mutants. Immunoblot analysis of extracts from developing mouse retina reveals enhanced expression of activated MAPK2 at postnatal day 0-3, concordant with the reported phosphorylation pattern of NRL in vivo. Inhibition of MAPK signaling pathways decreases NRL and CRX-mediated synergistic activation of rhodopsin promoter in transfected CV-1 cells.'] Do mutations associated with retinopathies alter mitogen-activated protein kinase-induced phosphorylation of neural retina leucine-zipper?
qiaojin/PubMedQA
2
[ -2.365253210067749, -1.2902297973632812, 2.68898868560791 ]
['To investigate the role of over-expression of Math5 on the retinal ganglion cell (RGC) expression patterns in retinal progenitor cells (RPCs).', 'RPCs were cultured and then transfected by recombinant Math5 plasmid with internal ribosome entry site and enhanced green fluorescent protein (pIRES2-EGFP-Math5; group A), with pIRES2-EGFP transfected (group B) and no plasmid transfected (group C) as control. RGCs were identified by Thy1.1 immunocytochemistry methods and analyzed by Leica Qwin V3.1 system. Real-time polymerase chain reaction was used to examine the expression of Math5-associated genes at different time points during the differentiation of RPCs.', 'It was determined that pIRES2-EGFP-Math5 could transfect RPCs, and the transfection rate was 24.68%. After plating, it was found that three different groups of RPCs could differentiate and express retina-specific markers, including RGC marker Thy1.1. The percentage breakdown of Thy1.1-positive cells was 30.85+/-6.28% in group A, 15.84+/-3.55% in group B, and 16.22+/-3.60% in group C. The differences between the three groups were statistically significant (p<0.001). Transfection by pIRES2-EGFP-Math5 could change the expression of Delta-1, Hes1, and Brn-3b.'] Does math5 promote retinal ganglion cell expression patterns in retinal progenitor cells?
qiaojin/PubMedQA
2
[ -1.7197697162628174, -1.5084760189056396, 2.2094669342041016 ]
['Despite the use of vitamin D analogues and oral calcium supplements, hypocalcaemia following surgical parathyroidectomy is a common problem, because of the so-called hungry bone syndrome.', 'The aim of this audit was to determine whether the change in clinical practice by the administration of pamidronate before parathyroidectomy, in addition to standard perioperative management, could prevent severe postoperative hypocalcaemia.', 'The postoperative course of 37 end-stage renal failure patients on regular dialysis referred for total parathyroidectomy were reviewed. Twenty-seven patients had been given pamidronate 24-48 h before surgery. Pamidronate reduced corrected serum calcium from 2.54 +/- 0.18 mmol/L (mean +/- SD) to 2.36 +/- 0.18 before surgery (P < 0.05). Following surgery, serum calcium in the 10 patients given standard therapy alone fell to a nadir of 2.08 mmol/L (1.75-2.19) (median (interquartile range) by the first postoperative day, and all 10 patients required additional support with multiple boluses of intravenous calcium. In the pamidronate group, the lowest median postoperative calcium was 2.3 mmol/L (2.2-2.46), P < 0.05, and only two patients required additional support with intravenous calcium, chi(2) = 27, P < 0.001). However, in the longer term the annual percentage increase in bone mineral density following parathyroidectomy was non-statistically lower in the pamidronate group compared with the controls (lumbar spine (L1-L4), 0.041 +/- 0.04 vs 0.058 +/- 0.41, P = 0.23 and femoral neck, 0.03 +/- 0.03 vs 0.107 +/- 0.1, P = 0.15, respectively).'] Does administration of pamidronate help prevent immediate postparathyroidectomy hungry bone syndrome?
qiaojin/PubMedQA
2
[ -1.8846179246902466, -1.588132619857788, 2.4627013206481934 ]
['This European Group for Blood and Marrow Transplantation (EBMT) multicentre randomized phase III study was designed to assess the safety and efficacy of CD34+ selection in newly diagnosed myeloma patients undergoing autologous transplantation.', 'One hundred and eleven patients responsive to initial chemotherapy were randomized to receive CD34+ selected (arm A) or unselected PBPC (arm B) after conditioning with high-dose melphalan and TBI. ASO-PCR was used to assess purging efficacy and reinfused tumor load. Tumor load could be assessed in 59 patients.', 'CD34+ selection gave a median tumor cell depletion of 2.2 logs (0.77-5.96). No tumor cells were detected in products infused in 17/26 (A) and 5/33 (B) patients. The five year overall survival (OS), event free survival (EFS) and relapse rate (RR) were 51%, 20% and 80% in arm A and 45%, 18% and 80% in arm B respectively with no significant difference between the two groups. Thirteen patients in arm A and 2 in arm B experienced episodes of serious early infection (p=0.02). There were 3 early transplant related deaths in A but none in B.'] Is relapse risk after autologous transplantation in patients with newly diagnosed myeloma related with infused tumor cell load and the outcome is not improved by CD34+ cell selection : long term follow-up of an EBMT phase III randomized study?
qiaojin/PubMedQA
2
[ -2.0746448040008545, -1.3911868333816528, 2.497189521789551 ]
['The efficacy control for the treatment of bone metastases in breast cancer is difficult and usually initiated later and with longer time between treatment cycles than the restaging of visceral or soft tissue metastases. The amino-terminal propeptide (PINP) of type I collagen as a biochemical indicator of bone turnover might facilitate early and valid disease surveillance. The utility of total PINP was investigated in metastatic breast cancer patients, with or without bone metastases (for monitoring of therapy). The results were compared to the established markers, osteocalcin and beta-carboxyterminal telopeptide (CTX) or crosslaps concentration.', 'Baseline serum samples of 51 patients with metastastic breast cancer under chemotherapy were investigated. In total, 38 patients had been diagnosed with bone metastases while 13 had no evidence of metastastic spread to the bone. All the patients with bone spread received bisphosphonates in addition to systemic chemotherapy and/or antibody therapy or hormonal treatment. Osteocalcin, CTX and PINP levels were measured on an Elecsys 2010 analyzer (electrochemiluminescence immunoassay--ECLIA). The normal cut-off values were: osteocalcin < 41.3 pg/ml, CTX < 1008 pg/ml and PINP < 95 ng/ml. Based on overall treatment outcome, the patients were grouped as responders (CR/PR), with stable disease (SD) or displaying primary progression (PD).', 'The baseline levels of PINP were significantly higher in patients with bone metastases (median: 92.8 ng/ml) than in those without (median: 63.2 ng/ml, p = 0.044). Patients with more than seven bone metastases had significantly higher PINP levels (median: 149.7 ng/ml) than those with fewer than seven (median: 67.6 ng/ml, p = 0.04). Significant differences were also found for osteocalcin and CTX, at p = 0.02 and p = 0.04, respectively, although the median levels remained under the normal cut-off levels. In terms of response assessment of bone spread, the PINP concentrations decreased in responders from 194.3 ng/ml to 100.4 ng/ml (p = 0.23). In patients with SD, PINP remained at the same level of approximately 70 ng/ml (p = 0.16), but increased in patients with PD from 83.4 ng/ml to 176.5 ng/ml (p = 0.14). These trends rather than statistical difference were probably due to the limited patient cohort. No differences were found for the serum concentrations of PINP, CTX and osteocalcin between post- and pre-menopausal women.'] Is the amino-terminal propeptide ( PINP ) of type I collagen a clinically valid indicator of bone turnover and extent of metastatic spread in osseous metastatic breast cancer?
qiaojin/PubMedQA
2
[ -1.8410561084747314, -1.603363275527954, 2.456540107727051 ]
['Chronic muscle pain is a major clinical problem that is often associated with fatigue. Conversely, chronic fatigue conditions are commonly associated with muscle pain. We tested the hypothesis that muscle fatigue enhances hyperalgesia associated with injection of acidic saline into muscle. We evaluated mechanical sensitivity of the paw (von Frey) in mice after 2 intramuscular injections of saline (20 microL; pH 4, pH 5, pH 6, pH 7.2) in a fatigue and a control group. To induce fatigue, mice were run for 2 h/day for 2 days prior to the first injection and 2 h/day for 2 days prior to the second injection. Muscle lactate, pCO(2), pO(2), creatinine kinase, phosphate, and histology were examined after the fatigue task and compared to a control group. Grip force was significantly decreased after 2 h of running indicating fatigue. The fatigue task did not induce muscle damage as there was no difference in muscle lactate, pCO(2), pO(2), creatinine kinase, phosphate, or histology. The fatigue task altered the dose-response relationship to intramuscular acidic saline injections. Mechanical hyperalgesia was observed in both fatigue and control groups after intramuscular injection of pH 4.0, but only the fatigue group after injection of pH 5. Neither the fatigue nor the control group developed hyperalgesia in response to intramuscular injection of pH 6 or pH 7.2. In conclusion, fatigue modified the susceptibility of mice to acid injection of pH 5.0 to result in mechanical hyperalgesia after 2 injections of pH 5.0. The fatigue task did not produce measurable changes in the muscle tissue suggesting a central mechanism mediating the enhancement of hyperalgesia.'] Does muscle fatigue increase the probability of developing hyperalgesia in mice?
qiaojin/PubMedQA
2
[ -2.3488175868988037, -1.3016862869262695, 2.6760029792785645 ]
['Proper development of plastids in embryo and seedling tissues is critical for plant development. During germination, plastids develop to perform many critical functions that are necessary to establish the seedling for further growth. A growing body of work has demonstrated that components of the plastid transcription and translation machinery must be present and functional to establish the organelle upon germination.', 'We have identified Arabidopsis thaliana mutants in a gene that encodes a plastid-targeted elongation factor G (SCO1) that is essential for plastid development during embryogenesis since two T-DNA insertion mutations in the coding sequence (sco1-2 and sco1-3) result in an embryo-lethal phenotype. In addition, a point mutation allele (sco1-1) and an allele with a T-DNA insertion in the promoter (sco1-4) of SCO1 display conditional seedling-lethal phenotypes. Seedlings of these alleles exhibit cotyledon and hypocotyl albinism due to improper chloroplast development, and normally die shortly after germination. However, when germinated on media supplemented with sucrose, the mutant plants can produce photosynthetically-active green leaves from the apical meristem.'] Do mutations in a plastid-localized elongation factor G alter early stages of plastid development in Arabidopsis thaliana?
qiaojin/PubMedQA
2
[ -2.6375532150268555, -0.7436707019805908, 2.373985528945923 ]
['There are some limitations associated with conventional clustering methods for short time-course gene expression data. The current algorithms require prior domain knowledge and do not incorporate information from replicates. Moreover, the results are not always easy to interpret biologically.', 'We propose a novel algorithm for identifying a subset of genes sharing a significant temporal expression pattern when replicates are used. Our algorithm requires no prior knowledge, instead relying on an observed statistic which is based on the first and second order differences between adjacent time-points. Here, a pattern is predefined as the sequence of symbols indicating direction and the rate of change between time-points, and each gene is assigned to a cluster whose members share a similar pattern. We evaluated the performance of our algorithm to those of K-means, Self-Organizing Map and the Short Time-series Expression Miner methods.'] Does difference-based clustering of short time-course microarray data with replicate?
qiaojin/PubMedQA
1
[ -1.8200141191482544, 0.8202670216560364, 0.23283007740974426 ]
['Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were -4.25 and -0.48 log(10) copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log(10) reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well-maintained during the post-treatment follow-up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment.'] Is clevudine highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression?
qiaojin/PubMedQA
2
[ -1.6562389135360718, -1.616776466369629, 2.313500165939331 ]
['EUS is the preferred modality for local staging of esophageal cancer. The presence of a long-lasting fluoroscopically visible marker of malignant lymph nodes would facilitate subsequent radiation and surgical therapy.', 'To assess the feasibility of EUS-guided implantation of a radiopaque marker (tantalum) into mediastinal and celiac lymph nodes in a porcine model.', 'Survival experiments on six 50-kg pigs.', 'A linear-array echoendoscope was advanced into the esophagus and the stomach. Mediastinal and celiac lymph nodes were identified and injected with 1 mL tantalum suspension by using 19- and 22-gauge FNA needles under fluoroscopy. The pigs were recovered. Fluoroscopy was repeated after 1, 2, and 4 weeks, then a postmortem examination was performed.', 'Long-term opacification of lymph nodes.', 'It was not possible to inject tantalum through the 22-gauge FNA needle because of its rapid precipitation inside the needle, which caused needle occlusion. Intranodal injection with the 19-gauge FNA needle was easily accomplished and resulted in excellent fluoroscopic opacification of injected lymph nodes. Repeat fluoroscopy at 1, 2, and 4 weeks demonstrated stable tantalum deposition at the injection site. There were no complications. Histologic examination of harvested lymph nodes revealed intranodal tantalum depositions without signs of infection, inflammation, tissue damage, or necrosis.'] Is eUS-guided implantation of radiopaque marker into mediastinal and celiac lymph nodes safe and effective?
qiaojin/PubMedQA
2
[ -2.34277081489563, -1.422917127609253, 2.830003261566162 ]