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['Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow microenvironment plays a critical role in sustaining the growth and survival of myeloma cells during tumor progression. Identification and functional analysis of the (adhesion) molecules involved in this interaction will provide important insights into the pathogenesis of multiple myeloma.', "Multiple myeloma cell lines and patients' samples were analyzed for expression of the adhesion molecule N-cadherin by immunoblotting, flow cytometry, immunofluorescence microscopy, immunohistochemistry and expression microarray. In addition, by means of blocking antibodies and inducible RNA interference we studied the functional consequence of N-cadherin expression for the myeloma cells, by analysis of adhesion, migration and growth, and for the bone marrow microenvironment, by analysis of osteogenic differentiation.", 'The malignant plasma cells in approximately half of the multiple myeloma patients, belonging to specific genetic subgroups, aberrantly expressed the homophilic adhesion molecule N-cad-herin. N-cadherin-mediated cell-substrate or homotypic cell-cell adhesion did not contribute to myeloma cell growth in vitro. However, N-cadherin directly mediated the bone marrow localization/retention of myeloma cells in vivo, and facilitated a close interaction between myeloma cells and N-cadherin-positive osteoblasts. Furthermore, this N-cadherin-mediated interaction contributed to the ability of myeloma cells to inhibit osteoblastogenesis.'] Does n-cadherin-mediated interaction with multiple myeloma cells inhibit osteoblast differentiation? | qiaojin/PubMedQA | 2 | [
-2.487323045730591,
-1.2287354469299316,
2.829651117324829
] |
['Resistance to therapy and subsequent relapse remain major challenges in the clinical management of relapsed childhood acute lymphoblastic leukemia. As the bone marrow environment plays an important role in survival and chemotherapy resistance of leukemia cells by activating different signaling pathways, such as the VLA-4 and PI3K/Akt pathways, we studied the prognostic and biological impact of VLA-4 expression in leukemia cells from children with relapsed B-cell precursor acute lymphoblastic leukemia and its influence on the sensitivity of the leukemia cells to drugs.', 'VLA-4 expression was quantified by real-time polymerase chain reaction in leukemia cells from 56 patients with relapsed acute lymphoblastic leukemia enrolled in the ALL-REZ BFM 2002 trial of the Berlin-Frankfurt-Münster study group. Gene expression changes related to VLA-4 expression were investigated by microarray-based mRNA profiling. The effect of VLA-4 signaling on proliferation and drug resistance was studied in co-cultures of leukemia and stromal cells.', 'High expression of VLA-4 at first relapse was associated with adverse prognostic factors, poor molecular response to therapy and significantly worse probabilities of event-free and overall survival. VLA-4 expression was an independent prognostic parameter. Comparing gene expression profiles of leukemia cells with high versus low VLA-4 expression, we identified 27 differentially expressed genes primarily involved in the PI3K/Akt, ephrin and Rho GTPase pathways. Blocking of VLA-4 signaling in combination with cytarabine treatment abolished the growth supportive effect of stromal cells.'] Is high VLA-4 expression associated with adverse outcome and distinct gene expression changes in childhood B-cell precursor acute lymphoblastic leukemia at first relapse? | qiaojin/PubMedQA | 2 | [
-2.3691489696502686,
-1.2717280387878418,
2.694995880126953
] |
['Follow-up of patients undergoing dextranomer/hyaluronic acid injection for vesico-ureteral reflux (VUR) is controversial. The purpose of our study was to test the hypothesis that patients undergoing the double hydrodistention-implantation technique (Double HIT) have a higher clinical and radiographic success rate.', 'Patients undergoing Double HIT endoscopic injection for VUR were prospectively identified. Patients underwent an ultrasound at 6 weeks to assess the implants, and, if visible, prophylactic antibiotics were discontinued and patients were scheduled for a 1-year voiding cystourethrogram (VCUG). Radiographic success was defined as a negative VCUG and clinical success as no febrile urinary tract infections at 1 year.', 'A total of 54 patients underwent endoscopic injection for VUR. Twenty-five (51%) were compliant with the 1 year follow-up; 18 non-compliant patients were contacted and their clinical status assessed. Thirty patients eventually completed the 1-year VCUG at a mean of 12.2 months (range 10-20). Among the 60% of patients with 1-year radiographic follow-up, 2 had persistent VUR for a radiologic success rate of 93%. All radiographic failures were infection-free. Of the 80% (43/54) of patients with available clinical data, 3 (7%) had afebrile UTI for a clinical success rate of 93%.'] Does intermediate to long-term follow-up indicate low risk of recurrence after Double HIT endoscopic treatment for primary vesico-ureteral reflux? | qiaojin/PubMedQA | 2 | [
-1.9127330780029297,
-1.472771406173706,
2.424154281616211
] |
['The relationship between clinical judgment and indications of the CURB-65 score in deciding the site-of-care for patients with community-acquired pneumonia (CAP) has not been fully investigated. The aim of this study was to evaluate reasons for hospitalization of CAP patients with CURB-65 score of 0 and 1.', 'An observational, retrospective study of consecutive CAP patients was performed at the Fondazione Cà Granda, Milan, Italy, between January 2005 and December 2006. The medical records of hospitalized patients with CAP having a CURB-65 score of 0 and 1 were identified and reviewed to determine whether there existed a clinical basis to justify hospitalization.', 'Among the 580 patients included in the study, 218 were classified with a CURB-65 score of 0 or 1. Among those, 127 were hospitalized, and reasons that justified hospitalization were found in 104 (83%) patients. Main reasons for hospitalization included the presence of hypoxemia on admission (35%), failure of outpatient therapy (14%) and the presence of cardiovascular events on admission (9.7%). Used as the sole indicator for inappropriate hospitalization, the CURB-65 score had a poor positive predictive value of 52%.'] Is low CURB-65 of limited value in deciding discharge of patients with community-acquired pneumonia? | qiaojin/PubMedQA | 2 | [
-1.0716708898544312,
-1.072427749633789,
1.1835808753967285
] |
['To identify circumstances and characteristics of suicidal behavior among early (aged 10-14 years) and late (aged 15-18 years) adolescents from a cohort of youth who were prescribed antidepressant medication.', 'In-depth reviews of all available medical records were performed for 250 randomly chosen confirmed episodes of suicidal behavior identified as part of a large retrospective cohort study of antidepressant users and suicidal behavior. Study data were obtained from Tennessee Medicaid records and death certificates from January 1, 1995, to December 31, 2006. Medical records and autopsy reports for cases identified from electronic data were adjudicated by 2 investigators blinded to exposure status and classified by using a validated scale.', 'Of the 250 cases reviewed, 65.6% were female and 26.4% were aged 10 to 14 years. Medication ingestion was the most frequent method of suicidal behavior for both early and late adolescents; however, early adolescents were significantly more likely to use hanging as a method of suicide. Nearly one-half of the adolescents had previously attempted suicide. Early adolescents were significantly more likely to have a history of sexual abuse and significantly less likely to have a history of substance abuse. Early adolescents were also significantly more likely than older adolescents to have a history of a psychotic disorder and to report hallucinations before the suicide attempt.'] Does suicidal behavior differ among early and late adolescents treated with antidepressant agents? | qiaojin/PubMedQA | 1 | [
-1.6097341775894165,
1.180518388748169,
-0.24835596978664398
] |
['To use quality-improvement (QI) methods to develop and test a multimodal intervention to improve hand-hygiene compliance among health care workers (HCWs) to >90%.', "We used a quasi-experimental staggered intervention that was conducted on 2 similar general pediatric units within a 475-bed tertiary children's hospital. Compliance was defined as acceptable hand hygiene both before and after contact with the patient or the patient's care environment. Measurement of HCW hand-hygiene compliance was performed by covert observations made during routine patient care. Twelve months of preintervention data were collected. QI methods were used to test and implement interventions sequentially in each unit. Interventions addressed leadership support, improving HCW knowledge, hand-hygiene supply availability, and HCW behavior.", 'Interventions began on unit A on November 10, 2008. Similar interventions were later tested on unit B starting March 23, 2009. By April 1, 2009, compliance increased on unit A (from 65% to 91%) and unit B (from 74% to 92%). Improvement on each unit occurred only after the interventions were introduced. Identifying HCWs who failed to perform hand hygiene and offering alcohol-based hand rub to them before patient contact resulted in the greatest improvement. Improvements were sustained on both units for 18 months.'] Does quality-improvement initiative sustain improvement in pediatric health care worker hand hygiene? | qiaojin/PubMedQA | 2 | [
-2.2774240970611572,
-0.20993772149085999,
1.5889546871185303
] |
['Reactive oxygen species (ROS) are highly diffusable and reactive molecules which modulate gene transcription, particularly of pro-inflammatory cytokines which play a crucial role in the nascency and progression of chronic inflammatory diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). Since thiols could be potent inhibitors of the production of cytokines, the effects of dimethyl sulphoxide (DMSO) and dimethyl sulphone (DMS) on constitutive and IL-1β-induced IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2 were evaluated.', 'C-28/I2 cells were incubated for 12h with different concentrations of DMSO or DMS. The secretion of IL-6 and IL-8 was quantified by enzyme-linked immunosorbent assays (ELISAs). The impact of DMSO and DMS on the regulation of p38 and ERK1/2 mitogen-activated protein kinases (MAPKs) was confirmed by Western blot experiments. Furthermore, C-28/I2 cells were stimulated with IL-1β in the absence or presence of DMSO and DMS and IL-6 and IL-8 expression was quantified by ELISAs and quantitative real-time polymerase chain reaction (qRT-PCR).', 'C-28/I2 cells constitutively expressed large quantities of IL-6 and IL-8. Long-term exposure of cells to DMSO (1%) or DMS (100mM) led to a dramatic downregulation of IL-6 and IL-8 expression which was accompanied by the deactivation of ERK1/2. Both substances also blocked IL-1β-induced IL-6 and IL-8 expression.'] Are dimethyl sulphoxide and dimethyl sulphone potent inhibitors of IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2? | qiaojin/PubMedQA | 2 | [
-2.3223297595977783,
-1.4069221019744873,
2.757430076599121
] |
['Hepatic failure has been treated successfully with clinical extracorporeal perfusions of porcine livers. However, dog-to-pig and pig-to-baboon liver xenotransplant models have resulted in severe bleeding secondary to liver xenograft-induced thrombocytopenia. Kupffer cells (KC) are abundant phagocytic cells in the liver. KC express the CD11b/CD18 receptor, which has been implicated in chilled platelet binding and phagocytosis through interaction with platelet surface proteins and carbohydrates. We sought to identify the role of KC CD18 in liver xenograft-induced thrombocytopenia.', 'Primary pig KC were characterized by flow cytometry, immunoblots, and quantitative polymerase chain reaction. Pig KC were used in inhibition assays with fluorescently labeled human platelets. The CD18 receptor was targeted for siRNA knockdown.', 'Domestic and α1,3-galactosyltransferase double knockout porcine KC cultures were approximately 92% positive for CD18 as detected by quantitative polymerase chain reaction and flow cytometry. Use of CD18 blocking antibodies resulted in reduction of human platelet binding and phagocytosis. Additionally, asialofetuin, not fetuin, inhibited platelet phagocytosis suggesting the involvement of an oligosaccharide-binding site. Furthermore, reduced CD18 expression by siRNA resulted in decreased human platelet binding.'] Does primary porcine Kupffer cell phagocytosis of human platelets involve the CD18 receptor? | qiaojin/PubMedQA | 2 | [
-2.4333713054656982,
-1.3518480062484741,
2.8499152660369873
] |
['The transfemoral approach is an extensile surgical approach that is performed routinely to facilitate cement and implant removal and improve exposure for revision stem implantation. Previous studies have looked at clinical results of small patient groups. The factors associated with fixation failure of cementless revision stems when using this approach have not been examined.', 'We determined (1) the clinical results and (2) complications of the transfemoral approach and (3) factors associated with fixation failure of revision stems when using the transfemoral approach.', 'We retrospectively examined all our patients in whom femoral stem revision was performed through a transfemoral approach between December 1998 and April 2004 and for whom a minimal followup of 2 years was available. One hundred patients were available for this study. The mean (± SD) postoperative followup was 5 years (± 1.64 years).', 'The average Harris hip score improved from 45.2 (± 14.02) preoperatively to 83.4 (± 11.86) at final followup. Complete radiographic bony consolidation of the osteotomy site was observed in 95% of patients. Dislocations occurred in 9% of patients. Four revision stem fixation failures were observed, all occurring in patients with primary three-point fixation. Three-point fixation was associated with short osteotomy flaps and long revision stems.'] Are stem and osteotomy length critical for success of the transfemoral approach and cementless stem revision? | qiaojin/PubMedQA | 2 | [
-2.148277997970581,
-1.1940170526504517,
2.4124464988708496
] |
['The literature suggests lateral unicompartmental knee arthroplasties are associated with low revision rates. However, there are fewer reports describing techniques for lateral unicompartmental arthroplasty and whether technique influences ROM and function compared to reports for medial unicompartmental arthroplasty.', 'We report our indications for lateral unicompartmental arthroplasty, how we perform this procedure, and the subsequent Knee Society scores, ROM, and revision and reoperation rates.', 'From a retrospective review of electronic records from 2004 through 2008, we identified 93 patients who had 100 lateral unicompartmental arthroplasties. Indications were complete lateral bone-on-bone arthrosis with a correctible deformity and maintenance of the medial joint space on varus stress radiographs or isolated lateral disease by diagnostic arthroscopy. Average age was 68 years. Seventy percent of patients were women. At followup, we obtained Knee Society scores and ROM. Minimum followup was 24 months (average, 39 months; range, 24-81 months).', 'At followup, Knee Society scores averaged 46 for pain, 94 for clinical, and 89 for function, and ROM averaged 124°. Three patients had reoperations: one an open reduction and internal fixation for fracture at 2 years postoperatively, one an arthroscopy for a medial meniscal tear, and one a revision for pain.'] Does lateral unicompartmental knee arthroplasty through a lateral parapatellar approach have high early survivorship? | qiaojin/PubMedQA | 2 | [
-2.2250800132751465,
-1.1420494318008423,
2.4013538360595703
] |
['HIV/HCV co-infection is characterised by accelerated progression of liver disease. Recently, the rs12979860 C/T polymorphism in the IL28B gene has been linked to progression towards cirrhosis in HCV mono-infected patients and to treatment response of HCV-infection in HIV/HCV co-infected patients. Our aim was to clarify by non-invasive techniques if this polymorphism affects fibrosis progression in HIV/HCV co-infection.', 'In a cross-sectional design, liver stiffness (transient elastography), surrogate markers of liver fibrosis (APRI and FIB-4 scores) and rs12979860 genotypes were analysed in 84 HCV/HIV co-infected patients. IL28B genotypes were determined by real-time PCR using a light cycler. In 56 HIV/HCV co-infected patients we also studied progression of fibrosis in relation to rs12979860 C/T genotypes over two years.', '82% of the patients were on HAART (74% without detectable HI viremia) and 67% were haemophiliacs, respectively. HCV genotype 1 was present in 62%. Cross-sectional median liver stiffness was 7.4 kPa and correlated with APRI and FIB-4 scores (r = 0.6 each, p < 0.001). Frequencies of IL28B genotypes were: CC 50%, CT 43% and TT 7%. In the cross-sectional analysis liver stiffness values were not different between the various IL28B-genotypes. Upon follow-up under HAART carriers of a C allele did not show further progression, while liver stiffness significantly increased in HIV/HCV co-infected patients with the T allele (p = 0.047).'] Is progression of liver fibrosis in HIV/HCV genotype 1 co-infected patients related to the T allele of the rs12979860 polymorphism of the IL28B gene? | qiaojin/PubMedQA | 2 | [
-1.526900053024292,
-1.6609997749328613,
2.19783616065979
] |
['A number of studies have revealed that Francisella tularensis (FT) suppresses innate immune responses such as chemokine/cytokine production and neutrophil recruitment in the lungs following pulmonary infection via an unidentified mechanism. The ability of FT to evade early innate immune responses could be a very important virulence mechanism for this highly infectious bacterial pathogen.', 'Here we describe the characterization of a galU mutant strain of FT live vaccine strain (LVS). We show that the galU mutant was highly attenuated in a murine model of tularemia and elicited more robust innate immune responses than the wild-type (WT) strain. These studies document that the kinetics of chemokine expression and neutrophil recruitment into the lungs of mice challenged with the galU mutant strain are significantly more rapid than observed with WT FT, despite the fact that there were no observed differences in TLR2 or TLR4 signaling or replication/dissemination kinetics during the early stages of infection. We also show that the galU mutant had a hypercytotoxic phenotype and more rapidly induced the production of IL-1β following infection either in vitro or in vivo, indicating that attenuation of the galU mutant strain may be due (in part) to more rapid activation of the inflammasome and/or earlier death of FT infected cells. Furthermore, we show that infection of mice with the galU mutant strain elicits protective immunity to subsequent challenge with WT FT.'] Is a galU mutant of Francisella tularensis attenuated for virulence in a murine pulmonary model of tularemia? | qiaojin/PubMedQA | 2 | [
-2.5230953693389893,
-1.0217556953430176,
2.6740036010742188
] |
['Cluster differentiation 44 standard isoform (CD44s) is a transmembrane glycoprotein. CD44s is a known prognostic factor in various cancers, due to its involvement in tumor cell growth, invasion and metastasis. Its prognostic role, however, is debated because it can be a positive or negative prognostic factor depending on tumor type and is still an ambiguous prognostic indicator in other cancers, especially hepatocellular carcinoma (HCC). We investigated the relationship between CD44s expression and survival in HCC patients.', 'A total of 260 HCC samples were collected to generate a tissue microarray. Staining of the arrays with a primary mouse CD44s monoclonal antibody was followed by evaluation of the relationship between CD44s expression and tumor differentiation. The effect of CD44s expression on patient survival was analyzed.', 'CD44s protein expression correlated with histological grade (most and worst Edmondson grade) of the HCC (p=0.029 and p=0.039, respectively) and adversely affected the disease free survival period based on univariate and multivariate analyses (p=0.038 and p=0.077, respectively).'] Does expression of the Transmembrane Glycoprotein CD44s be Potentially an Independent Predictor of Recurrence in Hepatocellular Carcinoma? | qiaojin/PubMedQA | 2 | [
-2.174555540084839,
-1.352536678314209,
2.5887398719787598
] |
['Drug resistance presents a major obstacle for the treatment of some patients with chronic myeloid leukemia (CML). Pro-apoptotic ceramide mediates imatinib-induced apoptosis, and metabolism of ceramide by glucosylceramide synthase (GCS) activity, converting ceramide to glucosyl ceramide, might contribute to imatinib resistance. In this study, we investigated the role of ceramide metabolism by GCS in the regulation of imatinib-induced apoptosis in drug-sensitive and drug-resistant K562 and K562/IMA-0.2 and K562/IMA-1 human CML cells, which exhibit about 2.3- and 19-fold imatinib resistance, respectively.', 'Cytotoxic effects of PDMP and imatinib were determined by XTT cell proliferation assay. Expression levels of GCS were determined by RT-PCR and western blot. Intracellular ceramide levels were determined by LC-MS. Cell viability analyses was conducted by Trypan blue dye exclusion assay. Cell cycle and apoptosis analyses were examined by flow cytometry.', 'We first showed that mRNA and protein levels of GCS are increased in drug-resistant K562/IMA as compared to sensitive K562 cells. Next, forced expression of GCS in sensitive K562 cells conferred resistance to imatinib-induced apoptosis. In reciprocal experiments, targeting GCS using its known inhibitor, PDMP, enhanced ceramide accumulation and increased cell death in response to imatinib in K562/IMA cells.'] Does targeting glucosylceramide synthase sensitize imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation? | qiaojin/PubMedQA | 2 | [
-2.4436590671539307,
-1.3079580068588257,
2.816473960876465
] |
['Patients with atopic dermatitis (AD) are frequently colonized with α-toxin-producing Staphylococcus aureus which is in turn positively correlated with the severity of eczema.', 'IN this study we addressed T cell proliferation and T cell as well as monocyte cytokine secretion upon α-toxin stimulation in peripheral blood mononuclear cells (PBMCs) from AD patients compared to healthy controls.', 'We found that α-toxin stimulation of PBMCs markedly enhanced T cell proliferation both in patients with AD and healthy controls and was significantly increased in AD patients compared to healthy controls. PBMCs of AD patients secreted significantly more IL-31 compared to those of healthy controls upon α-toxin and SEB stimulation. Moreover, α-toxin stimulation yielded an increase in T cell (IL-2, IL-9, IL-10 and IFN-γ) as well as monocyte (IL-1β and TNF-α) cytokine secretion.'] Does staphylococcal α-toxin induce a higher T cell proliferation and interleukin-31 in atopic dermatitis? | qiaojin/PubMedQA | 2 | [
-2.5220301151275635,
-1.1097946166992188,
2.6469807624816895
] |
['Describe the clinical and molecular epidemiology of incident Clostridium difficile infection (CDI) cases in Chicago area acute healthcare facilities (HCFs).', 'Laboratory, clinical, and epidemiologic information was collected for patients with incident CDI who were admitted to acute HCFs in February 2009. Stool cultures and restriction endonuclease analysis typing of the recovered C. difficile isolates was performed.', 'Two hundred sixty-three patients from 25 acute HCFs.', 'Acute HCF rates ranged from 2 to 7 patients with CDI per 10,000 patient-days. The crude mortality rate was 8%, with 20 deaths occurring in patients with CDI. Forty-two (16%) patients had complications from CDI, including 4 patients who required partial, subtotal, or total colectomy, 3 of whom died. C. difficile was isolated and typed from 129 of 178 available stool specimens. The BI strain was identified in 79 (61%) isolates. Of patients discharged to long-term care who had their isolate typed, 36 (67%) had BI-associated CDI.'] Is clostridium difficile outbreak strain BI highly endemic in Chicago area hospitals? | qiaojin/PubMedQA | 2 | [
-1.6649909019470215,
-1.1590009927749634,
1.9740216732025146
] |
['Patients on clinical trials often experience declining quality of life (QOL). Little is known about the psychosocial variables that buffer against decline.', 'This study aims to examine correlations between psychosocial variables and QOL over the course of a clinical trial in patients with metastatic renal cell cancer.', 'At baseline, 114 participants completed measures of treatment-related optimism, social support, and QOL (Functional Assessment of Cancer Therapy-General). QOL was also assessed 2, 4, and 8\xa0weeks after the start of treatment with low-dose or intermediate-dose interferon.', 'QOL decreased significantly in the intermediate-dose group but not in the low-dose group (p\u2009<\u2009.01). The decline was less severe for patients who had high rather than low treatment optimism (p\u2009=\u2009.03). A higher level of social support was significantly associated with higher baseline QOL (p\u2009<\u2009.05) but a more rapid decline in QOL over time (p\u2009<\u2009.01).'] Does treatment-related optimism protect quality of life in a phase II clinical trial for metastatic renal cell carcinoma? | qiaojin/PubMedQA | 2 | [
-1.9155900478363037,
-1.188664197921753,
2.1412267684936523
] |
['Hepatocyte growth factor (HGF) is a potent growth factor involved in liver regeneration that has various effects on epithelial and nonepithelial cells. Although it has been demonstrated that HGF can reduce liver inflammation or fibrosis caused by pharmaceutical or chemical insult, no examination of its effect on liver injury in nonalcoholic steatohepatitis (NASH) has been reported.', 'To examine the effect of HGF on liver injury in NASH, we generated a murine steatohepatitis model on an HGF overexpression transgenic (Tg) background, and fed the mice a methionine- and choline-deficient diet (MCD).', 'In mice fed the MCD diet, serum ALT levels and the inflammation score for the Tg mice were significantly lower than those for the wild-type (Wt) control mice (P\xa0<\xa00.01). The index of lipid peroxidation increased in the liver of the Wt mice as demonstrated by thiobarbituric acid-reactive substances. Furthermore, the liver fibrosis in Tg mice was dramatically suppressed in comparison to that in Wt mice. The gene expression of matrix metalloprotease-13 in the Tg mice was significantly increased in comparison to that of the Wt mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay showed the apoptotic cells to significantly decrease in number in the Tg mice in comparison to the Wt mice fed the MCD diet (P\xa0<\xa00.01).'] Does hepatocyte growth factor overexpression ameliorate liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis? | qiaojin/PubMedQA | 2 | [
-2.304825782775879,
-1.3826603889465332,
2.675251007080078
] |
['Hypocretin (orexin) signaling is involved in drug addiction. In this study, we investigated the role of these hypothalamic neuropeptides in nicotine withdrawal by using behavioral and neuroanatomical approaches.', 'Nicotine withdrawal syndrome was precipitated by mecamylamine (2 mg/kg, subcutaneous) in C57BL/6J nicotine-dependent mice (25 mg/kg/day for 14 days) pretreated with the hypocretin receptor 1 (Hcrtr-1) antagonist SB334867 (5 and 10 mg/kg, intraperitoneal), the hypocretin receptor 2 antagonist TCSOX229 (5 and 10 mg/kg, intraperitoneal), and in preprohypocretin knockout mice. c-Fos expression was analyzed in several brain areas related to nicotine dependence by immunofluorescence techniques. Retrograde tracing with rhodamine-labeled fluorescent latex microspheres was used to determine whether the hypocretin neurons project directly to the paraventricular nucleus of the hypothalamus (PVN), and SB334867 was locally administered intra-PVN (10 nmol/side) to test the specific involvement of Hcrtr-1 in this brain area during nicotine withdrawal.', 'Somatic signs of nicotine withdrawal were attenuated in mice pretreated with SB334867 and in preprohypocretin knockout mice. No changes were found in TCSOX229 pretreated animals. Nicotine withdrawal increased the percentage of hypocretin cells expressing c-Fos in the perifornical, dorsomedial, and lateral hypothalamus. In addition, the increased c-Fos expression in the PVN during withdrawal was dependent on hypocretin transmission through Hcrtr-1 activation. Hypocretin neurons directly innervate the PVN and the local infusion of SB334867 into the PVN decreased the expression of nicotine withdrawal.'] Is hypocretin/orexin signaling in the hypothalamic paraventricular nucleus essential for the expression of nicotine withdrawal? | qiaojin/PubMedQA | 2 | [
-2.336674451828003,
-1.4069018363952637,
2.7517101764678955
] |
['The aim of this study was to measure chest compression decay during simulated advanced life support (ALS) in a cardiac arrest manikin model.', '19 paramedic teams, each consisting of three paramedics, performed ALS for 12 minutes with the same paramedic providing all chest compressions. The patient was a resuscitation manikin found in ventricular fibrillation (VF). The first shock terminated the VF and the patient remained in pulseless electrical activity (PEA) throughout the scenario. Average chest compression depth and rate was measured each minute for 12 minutes and divided into three groups based on chest compression quality; good (compression depth ≥ 40 mm, compression rate 100-120/minute for each minute of CPR), bad (initial compression depth < 40 mm, initial compression rate < 100 or > 120/minute) or decay (change from good to bad during the 12 minutes). Changes in no-flow ratio (NFR, defined as the time without chest compressions divided by the total time of the ALS scenario) over time was also measured.', 'Based on compression depth, 5 (26%), 9 (47%) and 5 (26%) were good, bad and with decay, respectively. Only one paramedic experienced decay within the first two minutes. Based on compression rate, 6 (32%), 6 (32%) and 7 (37%) were good, bad and with decay, respectively. NFR was 22% in both the 1-3 and 4-6 minute periods, respectively, but decreased to 14% in the 7-9 minute period (P = 0.002) and to 10% in the 10-12 minute period (P < 0.001).'] Is decay in chest compression quality due to fatigue rare during prolonged advanced life support in a manikin model? | qiaojin/PubMedQA | 2 | [
0.12640680372714996,
-1.7353153228759766,
0.7137627601623535
] |
['Endometriosis is associated with chronic subclinical inflammation. C-reactive protein (CRP), a marker of inflammation, could serve as a biomarker of endometriosis. We tested the hypothesis that a high sensitivity CRP assay (hsCRP) is more accurate than a classical CRP assay in the detection of subclinical inflammation in plasma of women with endometriosis.', 'CRP levels were measured by hsCRP and classical CRP assays in plasma of 204 women with endometriosis and 91 women without endometriosis. Both assays were compared with respect to their value for the diagnosis of endometriosis.', 'The number of plasma samples with detectable CRP was significantly higher (100%) using the hsCRP assay when compared to the classical CRP assay (42.7%) (p < 0.0001). Significantly increased CRP plasma levels were found in women with endometriosis when compared with controls when the hsCRP assay was used in samples obtained during the luteal phase (p = 0.008). The highest discriminative ability for the diagnosis of endometriosis was also obtained using the hsCRP assay during the luteal phase, especially for moderate -severe endometriosis. At a cut-off level of hsCRP > 0.71 mg/L, moderate-severe stages were diagnosed with 80.7% sensitivity and 63.9% specificity during the luteal phase. Using a similar cut-off value for CRP analyzed by the classical method, moderate-severe endometriosis was diagnosed with lower sensitivity (67.7%, p = 0.06) and comparable specificity (63.9%).'] Is a high sensitivity assay more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis? | qiaojin/PubMedQA | 2 | [
-1.5293201208114624,
-1.5319534540176392,
2.041935443878174
] |
['Colonoscopy has been proven a valuable tool in preventing colorectal cancer in controlled studies; we conducted a longitudinal confirmation study in everyday clinical practice.', 'In a retrospective study, we monitored the outcome of patients with a total colonoscopy at our hospital between 1994 and 2007. We analysed the data of in-house follow-up colonoscopies, a national person registry and the morphological tumour registry centralizing all histopathological data at a national level. Patients with a particular colorectal cancer risk were excluded.', '8950 patients were included in our study. 2032 (22.7%) patients had at least one colorectal adenoma at index colonoscopy. Adenoma prevalence was significantly higher in men than in women (27.9% vs. 17.4%, p<0.001) and was increasing with age in both sexes. Patients were followed for a mean of 5.2 years and 19 had invasive colorectal cancer detected over 47,725 person years of follow-up. The incidence rate was 0.40 cases/1000 person years of follow-up (95% confidence interval, 0.25-0.62), and the standardized incidence ratio was 0.37 (95% confidence interval, 0.24-0.58).'] Is colorectal cancer incidence low in patients following a colonoscopy? | qiaojin/PubMedQA | 2 | [
-0.6802189350128174,
-1.3710331916809082,
1.132077932357788
] |
['Traumatic injury is a major global health problem, accounting for approximately 1 in 10 deaths worldwide. Hemorrhagic shock accounts for 30% to 40% of injury-associated deaths (2/3 of those patients surviving to reach the hospital) and is the leading cause of preventable and early in-hospital mortality. Excessive blood loss is an infrequent but important complication of both elective and emergency surgery, increasing the risk of morbidity and mortality and prolonging the duration of hospital stay.', 'The modified rapid deployment hemostat (mRDH) trauma bandage has been developed and tested during the past several years. The mRDH has a unique mechanism of action involving vasoconstriction, platelet activation, and red blood cell activation and is effective in the absence of clotting factors or platelets. The mRDH bandage has shown hemostatic efficacy in patients with severe visceral injuries and hepatic rupture.'] Does the mRDH bandage provide effective hemostasis in trauma and surgical hemorrhage? | qiaojin/PubMedQA | 2 | [
-2.614210605621338,
-0.783515453338623,
2.5035061836242676
] |
['Achieving hemostasis in anticoagulated patients is an increasingly important clinical issue. Poly-N-acetylglucosamine (pGlcNAc) nanofibers activate platelets by β3 subunit (CD61) and the von Willebrand receptor GP1b (CD42b) integrin signaling for generation of a prothrombotic surface membrane. Recombinant coagulation factor VIIa (rFVIIa) functions in hemophilia A and B by catalyzing formation of the Xa/Va complex on the surface of activated platelets. These observations suggest that pGlcNAc nanofibers may amplify the activity of rFVIIa in hemophilic blood.', 'The activity of rFVIIa on platelets was tested by performing thromboelastographic analysis with blood from hemophilia B dogs in the presence of pGlcNAc nanofibers and increasing concentrations of rFVIIa. Mechanisms for hemostatic system activation were investigated with inhibitors of tissue factor, factor XIIa, and platelet function.', 'Recombinant FVIIa was observed to partially restore the ability of the hemophiliac blood to form fibrin clots in a dose-dependent manner with thromboelastographic analysis. The addition of pGlcNAc nanofibers amplified the rFVIIa effect. The activity of rFVIIa and the amplification effect of pGlcNAc were dependent on platelet integrin function but independent of FXIIa and tissue factor activities.'] Do poly-N-acetylglucosamine fibers amplify the effectiveness of recombinant factor VIIA on clot formation in hemophilia B canine blood? | qiaojin/PubMedQA | 2 | [
-2.4778504371643066,
-1.3346900939941406,
2.832582950592041
] |
['It has been previously demonstrated that short-fiber poly-N-acetyl-glucosamine (sNAG) nanofibers specifically interact with platelets, are hemostatic, and stimulate diabetic wound healing by activating angiogenesis, cell proliferation, and reepithelialization. Platelets play a significant physiologic role in wound healing. The influence of altered platelet function by treatment with the ADP inhibitor Clopidogrel (CL) on wound healing and the ability of sNAG to repair wounds in diabetic mice treated with CL were studied.', 'Dorsal 1 cm2 skin wounds were excised on genetically diabetic 8-week to 12-week-old, Lep/r-db/db male mice, and wound healing kinetics were determined. Microscopic analysis was performed for angiogenesis (PECAM-1) and cell proliferation (Ki67). Mice were either treated with CL (P2Y12 ADP receptor antagonist, CL) or saline solution (NT). CL wounds were also treated with either a single application of topical sNAG (CL-sNAG) or were left untreated (CL-NT).', 'CL treatment did not alter wound healing kinetics, while sNAG induced faster wound closure in CL-treated mice compared with controls. CL treatment of diabetic mice caused an augmentation of cell proliferation and reduced angiogenesis compared with nontreated wounds. However, sNAG reversed the effects of CL on angiogenesis and partially reversed the effect on cell proliferation in the wound beds. The sNAG-treated wounds in CL-treated mice showed higher levels of cell proliferation and not did inhibit angiogenesis.'] Do poly-N-acetyl glucosamine fibers induce angiogenesis in ADP inhibitor-treated diabetic mice? | qiaojin/PubMedQA | 2 | [
-2.429490804672241,
-1.346086859703064,
2.78090500831604
] |
['Vacuum-assisted closure (VAC) has become the preferred modality to treat many complex wounds but could be further improved by methods that minimize bleeding and facilitate wound epithelialization. Short fiber poly-N-acetyl glucosamine nanofibers (sNAG) are effective hemostatic agents that activate platelets and facilitate wound epithelialization. We hypothesized that sNAG used in combination with the VAC device could be synergistic in promoting wound healing while minimizing the risk of bleeding.', 'Membranes consisting entirely of sNAG nanofibers were applied immediately to dorsal excisional wounds of db/db mice followed by application of the VAC device. Wound healing kinetics, angiogenesis, and wound-related growth factor expression were measured.', 'The application of sNAG membranes to wounds 24 hours before application of the VAC device was associated with a significant activation of wounds (expression of PDGF, TGFβ, EGF), superior granulation tissue formation rich in Collagen I as well as superior wound epithelialization (8.6% ± 0.3% vs. 1.8% ± 1.1% of initial wound size) and wound contraction.'] Are poly-N-acetyl glucosamine fibers synergistic with vacuum-assisted closure in augmenting the healing response of diabetic mice? | qiaojin/PubMedQA | 2 | [
-2.517272710800171,
-1.2316598892211914,
2.8360595703125
] |
['The purpose of this study was to evaluate the ability of a membrane material, consisting only of short poly-N-acetyl glucosamine (sNAG) nanofibers, to regenerate bone tissue after implantation into circular holes in the rabbit femur.', 'Three circular holes were created in the femurs of five male New Zealand white rabbits. The holes were ∼ 2.0 mm in diameter. Three holes in the left femur were implanted with the comparative control substance (Bone Wax; Ethicon, Inc.); three holes in the right femur were implanted with the sNAG membrane test article. Animals were killed 4 weeks after surgery, and macroscopic evaluation of the implant sites was made. Hematoxylin and eosin histology was performed on both control and test sites.', 'All control (bone wax) sites had visible holes (defects) at the 28-day end point of the study and showed no evidence of new bone formation. All the 15 sNAG test sites were found to have new bone tissue present in the bone hole defects. Hematoxylin and eosin histology of the sNAG-treated test sites showed the presence of osteoblasts, osteocytes, and trabecula of new bone formation at the 28-day end point of the study.'] Do poly-N-acetyl glucosamine fibers activate bone regeneration in a rabbit femur injury model? | qiaojin/PubMedQA | 2 | [
-2.4124410152435303,
-1.0978668928146362,
2.593733787536621
] |
['Incidence of hepatitis C virus (HCV) induced hepatocellular carcinoma (HCC) has been increasing in the United States and Europe during recent years. Although HCV-associated HCC shares many pathological characteristics with other types of HCC, its molecular mechanisms of progression remain elusive.', 'To investigate the underlying pathology, we developed a systematic approach to identify deregulated biological networks in HCC by integrating gene expression profiles with high-throughput protein-protein interaction data. We examined five stages including normal (control) liver, cirrhotic liver, dysplasia, early HCC and advanced HCC.', 'Among the five consecutive pathological stages, we identified four networks including precancerous networks (Normal-Cirrhosis and Cirrhosis-Dysplasia) and cancerous networks (Dysplasia-Early HCC, Early-Advanced HCC). We found little overlap between precancerous and cancerous networks, opposite to a substantial overlap within precancerous or cancerous networks. We further found that the hub proteins interacted with HCV proteins, suggesting direct interventions of these networks by the virus. The functional annotation of each network demonstrates a high degree of consistency with current knowledge in HCC. By assembling these functions into a module map, we could depict the stepwise biological functions that are deregulated in HCV-induced hepatocarcinogenesis. Additionally, these networks enable us to identify important genes and pathways by developmental stage, such as LCK signalling pathways in cirrhosis, MMP genes and TIMP genes in dysplastic liver, and CDC2-mediated cell cycle signalling in early and advanced HCC. CDC2 (alternative symbol CDK1), a cell cycle regulatory gene, is particularly interesting due to its topological position in temporally deregulated networks.'] Does integrative network analysis identify key genes and pathways in the progression of hepatitis C virus induced hepatocellular carcinoma? | qiaojin/PubMedQA | 2 | [
-2.586207866668701,
-0.8125340342521667,
2.5289227962493896
] |
['Chaga mushroom (Inonotus obliquus, IO) has been used as a folk remedy for cancer, digestive system diseases, and other illnesses in Russia and Eastern Europe.', 'In the present study, we investigated the immunomodulating effects of IO through in vivo and ex vivo studies.', 'Serum immunoglobulins (IgE, IgG(1), and IgG(2a)) and cytokines (interleukin (IL)-4, interferon (IFN)-γ, and IL-2) were measured in concanavalin A (ConA)-stimulated splenocytes and CD4(+) T cells. The nitric oxide (NO) secretion of lipopolysaccharide (LPS)-stimulated peritoneal macrophages was also measured after oral administration of 50, 100, or 200 mg kg(-1) d(-1) IO hot water extract (IOE) to ovalbumin (OVA)-sensitized BALB/c mice.', 'We found that the OVA-induced increase in serum IgE and IgG(2a) was significantly suppressed when IOE was orally administered after the second immunization with OVA. ConA stimulation in spleen cells isolated from OVA-sensitized mice treated with 100 mg kg(-1) IOE resulted in a 25.2% decrease in IL-4 production and a 102.4% increase in IFN-γ, compared to the controls. Moreover, IL-4, IFN-γ, and IL-2 were significantly reduced after ConA stimulation in isolated CD4(+)T cells. We also determined that IOE inhibits the secretion of NO from LPS-stimulated peritoneal macrophages ex vivo.'] Do inonotus obliquus extracts suppress antigen-specific IgE production through the modulation of Th1/Th2 cytokines in ovalbumin-sensitized mice? | qiaojin/PubMedQA | 2 | [
-2.295830726623535,
-1.3968563079833984,
2.720210075378418
] |
['Among human adolescents, drug use is substantially influenced by the attitudes and behaviors of peers. Social factors also affect the drug-seeking behaviors of laboratory animals. Conditioned place preference (CPP) experiments indicate that social context can influence the degree to which rodents derive a rewarding experience from drugs of abuse. However, the precise manner by which social factors alter drug reward in adolescent rodents remains unknown.', 'We employed the relatively asocial BALB/cJ (BALB) mouse strain and the more prosocial C57BL/6J (B6) strain to explore whether "low" or "high" motivation to be with peers influences the effects of social context on morphine CPP (MCPP).', 'Adolescent mice were conditioned by subcutaneous injections of morphine sulfate (0.25, 1.0, or 5.0 mg/kg). During the MCPP procedure, mice were housed in either isolation (Ih) or within a social group (Sh). Similarly, following injection, mice were conditioned either alone (Ic) or within a social group (Sc).', 'Adolescent B6 mice expressed a robust MCPP response except when subjected to Ih-Sc, which indicates that, following isolation, mice with high levels of social motivation are less susceptible to the rewarding properties of morphine when they are conditioned in a social group. By contrast, MCPP responses of BALB mice were most sensitive to morphine conditioning when subjects experienced a change in their social environment between housing and conditioning (Ih-Sc or Sh-Ic).'] Does social influence on morphine-conditioned place preference in adolescent BALB/cJ and C57BL/6J mice? | qiaojin/PubMedQA | 2 | [
-2.3894970417022705,
-0.03165445476770401,
1.4885958433151245
] |
['To assess the significance of Rac GTPase-activating protein 1 (RACGAP1) expression in identifying HBV-positive human hepatocellular carcinoma (HCC) patients who are at high risk for recurrent disease.', 'The prognostic significance of RACGAP1 was compared with clinicopathologic parameters available at diagnosis using multivariate and log-rank test. RACGAP1 expression and outcome in recurrence was compared between 35 patients with recurrence and 41 patients without recurrence using Kaplan-Meier analysis. RACGAP1-targeted molecules and pathways were identified and characterized by inhibition with siRNA duplexes.', 'Kaplan-Meier analysis showed that the level of RACGAP1 expression is sufficient to predict the early recurrence of HCC: high RACGAP1 expression correlates with high risk of postresection recurrent HCC (P < 0.0005). Silencing of RACGAP1 in Hep3B and MHCC97-H HCC cells with high endogenous RACGAP1 expression inhibited cell migration and invasion. Using Ingenuity Pathway Analysis, the target molecules silenced in the RACGAP1 interactome were mostly genes related to the mitotic roles of the polo-like kinases. These included PRC1, AURKB, CDC2, ECT2, KIF23, PAK1, and PPP2R5E. In providing clinical corroboration of these results, when expression of these transcripts was analyzed in an expression database that we have established previously for HBV-positive HCC patients, these genes was mostly upregulated in patients who exhibited early recurrent disease and hence provided important corroboration of these results.'] Is upregulation of Rac GTPase-activating protein 1 significantly associated with the early recurrence of human hepatocellular carcinoma? | qiaojin/PubMedQA | 2 | [
-2.3836467266082764,
-1.2806836366653442,
2.6911075115203857
] |
['To evaluate the nature of cyclin-dependent kinase 5 (CDK5) hyperactivity in pancreatic cancer progression.', 'We used genetic, biochemical, and molecular biology methods to investigate the nature and function of overexpression of CDK5 and its activators p35 and p39 during the progression of pancreatic cancer.', 'Amplification of the CDK5 gene or either of its main activators, p35 and p39, was observed in 67% of human pancreatic ductal adenocarcinoma (PDAC). CDK5, p35, and p39 were rarely expressed in pancreatic ducts whereas more than 90% of PDACs had increased levels of CDK5 and p35. Increased levels of CDK5, p35, and p39 protein were observed in several pancreatic cancer cell lines. Inhibition of CDK5 kinase activity using a CDK5 dominant-negative mutant or the drug roscovitine significantly decreased the migration and invasion of pancreatic cancer cells in vitro. Increased CDK5 kinase activity was also observed in immortalized human pancreatic nestin-expressing (HPNE) cells expressing a mutant form of K-Ras (G12D) compared with HPNE cells expressing native K-Ras. G12D K-Ras increased cleavage of p35 to p25, a stable and greater activator of CDK5, thus implicating a role for CDK5 in early progression of PDAC. Inhibition of the signaling cascade downstream of mutant K-Ras (G12D) that involves mitogen-activated protein/extracellular signal-regulated kinase, phosphoinositide 3-kinase, or CDK5 decreased p25 protein levels.'] Is cyclin-dependent kinase 5 amplified and overexpressed in pancreatic cancer and activated by mutant K-Ras? | qiaojin/PubMedQA | 2 | [
-2.4223902225494385,
-1.2369060516357422,
2.6694729328155518
] |
['The anti-inflammatory properties of the female sex hormone estrogen have been linked to a reduced incidence of cardiovascular disease. In the present study, we addressed whether estrogen could activate vasculoprotective mechanisms via annexin A1 (AnxA1) mobilization in human polymorphonuclear cells (PMNs).', 'Using whole-blood flow cytometry, we demonstrated that premenopausal women expressed higher levels of surface AnxA1 on circulating PMNs compared with males. This correlated with high plasma estrogen during the menstrual cycle. The addition of estrogen in vitro to male PMNs induced rapid mobilization of AnxA1, optimal at 5 ng/mL and a 30-minute incubation period; this effect was abolished in the presence of the estrogen receptor antagonist ICI182780. Estrogen addition to human PMNs induced a distinct AnxA1(hi) CD62L(lo) CD11b(lo) phenotype, and this was associated with lower cell activation as measured by microparticle formation. Treatment of human PMNs with E(2) inhibited cell adhesion to an endothelial cell monolayer under shear, which was absent when endogenous AnxA1 was neutralized. Of interest, addition of estrogen to PMNs flowed over the endothelial monolayer amplified its upregulation of AnxA1 localization on the cell surface. Finally, in a model of intravital microscopy, estrogen inhibition of white blood cell adhesion to the postcapillary venule was absent in mice nullified for AnxA1.'] Does activation of the annexin A1 pathway underlie the protective effects exerted by estrogen in polymorphonuclear leukocytes? | qiaojin/PubMedQA | 2 | [
-2.485609292984009,
-1.3072248697280884,
2.8376662731170654
] |
['Epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, TWIST and SNAI1, are fundamental in regulating EMT.', 'Immunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas.', 'Tumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively).'] Is twist and snai1 expression in pharyngeal squamous cell carcinoma stroma related to cancer progression? | qiaojin/PubMedQA | 2 | [
-2.1972622871398926,
-1.3875970840454102,
2.617018938064575
] |
['There is a national shortage of organs available for transplantation. Implementation of preset donor management goals (DMGs) to improve outcomes is recommended, but uniform practices and data are lacking. We hypothesized that meeting DMGs before organ procurement would result in more organs transplanted per donor (OTPD).', 'The eight organ procurement organization in United Network for Organ Sharing Region 5 selected 10 critical care end points as DMGs. Each organ procurement organization submitted retrospective data from 40 standard criteria donors. "DMGs met" was defined as achieving any eight DMGs before procurement. The primary outcome was ≥4 OTPD. Binary logistic regression was used to determine independent predictors of ≥4 OTPD with a p<0.05.', 'Three hundred twenty standard criteria donors had 3.6±1.6 OTPD. Donors with DMGs met had more OTPD (4.4 vs. 3.3, p<0.001) and were more likely to have ≥4 OTPD (70% vs. 39%, p<0.001). Independent predictors of ≥4 OTPD were age (odds ratio [OR]=0.94), serum creatinine (OR=0.65), thyroid hormone use (OR=2.0), "DMGs met" (OR=4.4), and achieving the following individual DMGs: central venous pressure 4 mm Hg to 10 mm Hg (OR=1.9), ejection fraction>50% (OR=4.0), Pao2:FIO2>300 (OR=4.6), and serum sodium 135 to 160 mEq/L (OR=3.4).'] Is achieving donor management goals before deceased donor procurement associated with more organs transplanted per donor? | qiaojin/PubMedQA | 2 | [
-0.37526804208755493,
-1.959338903427124,
1.29297935962677
] |
['Upper respiratory tract infection is a frequent cause of morbidity worldwide. Although the course of infection is usually mild, it is responsible for enormous social and economic costs. Immunostimulation with bacterial extracts consisting of ribosomal RNA and proteoglycans, such as Ribomunyl, was introduced into the clinic in the 1980s as a new treatment concept, but did not achieve widespread application. Ribomunyl has been proposed to activate innate immunity, but the contribution of its RNA content as well as its antiviral potential has not been studied.', 'Peripheral blood mononuclear cells from healthy donors and immune cells from adenoids were incubated with Ribomunyl either by itself or formulated in a complex with cationic polypeptides such as poly-l-arginine or protamine, and induction of cytokines was quantified by ELISA.', 'Ribomunyl in complex with either poly-l-arginine or protamine, but not on its own, was able to strongly induce interferon-α (P<0.01) and interleukin-12 (P<0.01) in peripheral blood mononuclear cells, whereas induced tumour necrosis factor-α and interleukin-6 levels were independent of the formulation. Comparable results were obtained in immune cells from adenoids, suggesting efficacy also in virus-affected tissue. Cell sorting, RNase digests and selective receptor expression show that the RNA in Ribomunyl acts as an agonist of Toll-like receptor (TLR)7 and TLR8.'] Does delivery with polycations extend the immunostimulant Ribomunyl into a potent antiviral Toll-like receptor 7/8 agonist? | qiaojin/PubMedQA | 2 | [
-2.479917526245117,
-1.2872653007507324,
2.855135440826416
] |
['The aim of this study was to examine the factors that influence soluble endothelial selectin (sE-selectin) levels in umbilical cord serum.', 'sE-selectin levels in umbilical cord serum were measured in 144 patients using enzyme-linked immunosorbent assay. We examined the association of sE-selectin levels with gestational age, pre-eclampsia (PE), histological chorioamnionitis (HCAM), preterm premature rupture of membranes, magnesium sulfate use, birthweight, and placental weight.', 'A significant positive correlation was observed between sE-selectin levels and gestational age in the patients who had neither PE nor HCAM (r = 0.559, P < 0.0001). This statistically positive correlation persisted in patients with PE without HCAM (n = 25, r = 0.644, P < 0.001), but not in patients with HCAM without PE (n = 58, r = 0.102, P = 0.448). In matched gestational age analysis, sE-selectin levels were increased in the presence of HCAM (P = 0.0006), but were not influenced by the presence of PE (P = 0.127), preterm premature rupture of membranes (P = 0.352) or magnesium sulfate use (P = 0.337).'] Are levels of soluble endothelial selectin in umbilical cord serum influenced by gestational age and histological chorioamnionitis , but not by pre-eclampsia? | qiaojin/PubMedQA | 2 | [
-2.071848154067993,
-1.3789069652557373,
2.505520820617676
] |
['Severe post-partum hemorrhage during cesarean section due to placenta previa is still one of the leading causes of maternal mortality. The aim of this study was to evaluate the efficiency of intrauterine tamponade with a Sengstaken-Blakemore tube (SB-tube) for the treatment of severe post-partum hemorrhage in cases of placenta previa.', 'Data were collected from our departmental clinical records on all patients who underwent caesarian section due to placenta previa between 2007 and 2009.', 'During the period analyzed, 37 patients underwent caesarian section due to placenta previa/low-lying placenta. Four (11%) underwent hysterectomy due to placenta accreta and 33 (89%) were treated conservatively. Of the 33 patients with conserved uterus, 10 (28%) patients required a SB-tube during the cesarean section because of continuous post-partum hemorrhage despite appropriate medical treatment. The median bleeding during the operation was 2030±860mL in the patients who used SB-tube. None of them presented severe complications related to these procedures or required any further invasive surgery.'] Is balloon tamponade during cesarean section useful for severe post-partum hemorrhage due to placenta previa? | qiaojin/PubMedQA | 2 | [
-1.8079591989517212,
-0.9940359592437744,
1.8902275562286377
] |
['The authors investigated whether an insulin protocol for parenteral nutrition (PN)-induced hyperglycemia is superior to conventional management relying primarily on sliding-scale insulin at a large county hospital.', 'A prospective cohort study with historical controls was completed. Adult patients receiving PN were managed with a protocol that determined insulin doses based on carbohydrate delivery and capillary blood glucose (CBG) if half or more of CBG measurements in the first 24 hours after initiation of PN exceeded 140 mg/dL. Control data were obtained from records of patients who met study eligibility criteria but had been managed before implementation of the insulin protocol.', 'Mean CBG after the start of insulin therapy was 138 ± 37 mg/dL for protocol patients and 159 ± 46 mg/dL for controls (P < .0001). Proportion of CBG values in the target range of 80-140 mg/dL was 60% in the protocol group and 35% in the control group (P < .0001). Hypoglycemia, defined as CBG <80 mg/dL, occurred infrequently but more often in the protocol group (3% vs 1%, P = .012). There was no difference in total daily insulin between groups, although protocol patients received mostly scheduled insulin (93% total daily dose), whereas control patients received predominantly supplemental insulin (66% total daily dose).'] Is an insulin protocol for management of hyperglycemia in patients receiving parenteral nutrition superior to ad hoc management? | qiaojin/PubMedQA | 2 | [
-1.5687288045883179,
-1.3013083934783936,
1.9302136898040771
] |
['This study aimed to determine whether relationships between obesity, as measured by waist-to-hip ratio (WHR), and cognition and brain structure were modified by the apolipoprotein epsilon 4 allele (apoE4).', 'The sample included 1969 stroke- and dementia-free participants from the Framingham Offspring Cohort who underwent neuropsychological (NP) testing and structural magnetic resonance imaging (MRI) between 1999 and 2002. WHR was categorized into sex-specific quartiles with those in Q4 representing central obesity. Multivariate linear regression estimated the relationships between Q4-WHR, cognitive, and MRI measures; interaction terms examined modification of these relationships by the presence of apoE4. All analyses were cross sectional.', 'ApoE4 status significantly modified a number of associations. Specifically, we observed a significant negative relationship between Q4-WHR and a measure of executive function in the apoE4(+) group but not in the apoE4(-) group. Similarly, we observed a stronger negative relationship between Q4-WHR and a measure of memory function for those in the apoE4(+) group compared to those in the apoE4(-) group. In addition, apoE4 status modified the relationship between Q4-WHR and 2 measures of structural brain integrity. First, a paradoxical finding of a negative association between WHR and frontal brain volume that was significant only for those in the apoE4(-) group, and a second finding that WHR was significantly associated with greater white matter hyperintensity volume only in the apoE4(+) group.'] Does apolipoprotein epsilon 4 allele modify waist-to-hip ratio effects on cognition and brain structure? | qiaojin/PubMedQA | 2 | [
-2.2296793460845947,
-1.054556965827942,
2.385810375213623
] |
['Liver X receptor (LXR) is a transcription factor of the nuclear receptor family, regulating genes involved in metabolism, inflammation, and apoptosis. In the present investigation, we examined the role of LXR in organ injury and systemic inflammation in rodent models of polymicrobial peritonitis caused by cecal ligation and puncture (CLP).', 'Rats were subjected to CLP sepsis or a sham operation. Some were treated with the synthetic LXR agonist GW3965 0.3 mg/kg 30 min prior to the CLP procedure, and organs and plasma were harvested at 3, 10, 18, or 24 h. Organs were analyzed for RNA expression by quantitative polymerase chain reaction or for morphologic differences by histologic review. Organ injury and inflammatory markers were measured in plasma.', 'Expression of the LXRα gene was decreased in the livers of CLP rats compared with sham-operated rats. Administration of a synthetic agonist of LXR (GW3965) reduced biochemical indices of liver injury in the blood of CLP rats. We also demonstrated that liver injury associated with CLP is aggravated in LXRα- and LXRαβ-deficient mice compared with wild-type and LXRβ-deficient mice, indicating a role for LXRα in protecting the liver. The enhanced liver injury in LXR-deficient mice was associated with elevated plasma concentrations of high mobility group box 1, a late mediator of inflammation and a known factor in the pathology of this model.'] Does liver X receptor protect against liver injury in sepsis caused by rodent cecal ligation and puncture? | qiaojin/PubMedQA | 2 | [
-2.395521402359009,
-1.320333480834961,
2.742966890335083
] |
['Relapse is an important problem in substance dependence treatment. When drug users try to abstain from drug use, they often report strong temptations to use drugs. Temptation episodes have commonalities with relapse episodes, and assessment of temptation episodes may help to identify individuals at risk of relapse.', 'This study aims to examine affect and cognition prior to and during temptation episodes by administering self-report and implicit cognitive assessments on a handheld computer (PDA) using Ecological Momentary Assessment.', 'Heroin-dependent patients (N\u2009=\u200968) attending a drug detoxification unit completed up to four random assessments (RAs) per day on a PDA for 1 week. They also completed an assessment when they experienced a temptation to use drugs (temptation assessment; TA).', 'Participants completed 1,482 assessments (353 TAs, 1,129 RAs). The rate of TAs was maximal during the first 2 days. Participants reported higher levels of negative affect, anxiety, and difficulty concentrating, and more positive explicit attitudes to drugs, at TAs compared to RAs. In addition, they exhibited elevated attentional bias to drug cues (assessed using the modified Stroop task) at TAs compared to RAs. Implicit affective associations with drug cues (assessed using the Implicit Association Test) were not different at TAs compared to RAs. Attentional bias was elevated in the 1 h prior to the entry of a temptation episode.'] Is attentional bias to drug cues elevated before and during temptations to use heroin and cocaine? | qiaojin/PubMedQA | 2 | [
-2.5828857421875,
-0.40459516644477844,
2.0606439113616943
] |
['Elevated blood pressure (BP) is a risk factor for stroke and dementia, but the effect of BP, and change in BP over time, on white matter hyperintensity volume (WMHV) is not fully understood. Few studies have included Hispanics, who are at greater risk of stroke and dementia than non-Hispanic whites. We examined BP in relation to WMHV in a stroke-free cohort.', 'The Northern Manhattan Study includes 1290 stroke-free participants who had brain MRI. We examined baseline systolic and diastolic (DBP) BP, and changes in BP from baseline to MRI, and WMHV.', 'There were 1281 participants with brain MRI and 2 BP measurements (mean age, 64 years; SD=8; range, 40 to 94 years). Baseline DBP was associated with greater WMHV (P<0.0001) independent of sociodemographic and vascular risk factors. Each 10 mm Hg above the mean baseline DBP (83±11 mm Hg) was associated with a 1.17% greater WMHV. Over 7 years average follow-up, participants with an increase >5 mm Hg DBP from baseline to MRI had 1.21% greater WMHV relative to those whose BP did not increase (P=0.02). The association between baseline DBP and WMHV was strongest for blacks compared with Hispanics and whites (interaction P=0.04).'] Are baseline and longitudinal increases in diastolic blood pressure associated with greater white matter hyperintensity volume : the northern Manhattan study? | qiaojin/PubMedQA | 2 | [
-1.6683284044265747,
-0.6586884260177612,
1.4322527647018433
] |
['Experimental and clinical evidence suggests that prolonged spreading depolarizations (SDs) are a promising target for therapeutic intervention in stroke because they recruit tissue at risk into necrosis by protracted intracellular calcium surge and massive glutamate release. Unfortunately, unlike SDs in healthy tissue, they are resistant to drugs such as N-methyl-d-aspartate-receptor antagonists. This drug resistance of SD in low perfusion areas may be due to the gradual rise of extracellular potassium before SD onset. Brain slices from patients undergoing surgery for intractable epilepsy allow for screening of drugs, targeting pharmacoresistant SDs under elevated potassium in human tissue. However, network changes associated with epilepsy may interfere with tissue susceptibility to SD. This could distort the results of pharmacological tests.', 'We investigated the threshold for SD, induced by a gradual rise of potassium, in neocortex slices of patients with intractable epilepsy and of chronically epileptic rats as well as age-matched and younger control rats using combined extracellular potassium/field recordings and intrinsic optical imaging.', 'Both age and epilepsy significantly increased the potassium threshold, which was similarly high in epileptic rat and human slices (23.6±2.4 mmol/L versus 22.3±2.8 mmol/L).'] Do chronically epileptic human and rat neocortex display a similar resistance against spreading depolarization in vitro? | qiaojin/PubMedQA | 2 | [
-2.390209197998047,
-1.3037056922912598,
2.7418453693389893
] |
['The formation of reactive astrocytes is common after central nervous system injuries such as stroke. However, the signaling pathway(s) that control astrocyte formation and functions are poorly defined. We assess the effects of Notch 1 signaling in peri-infarct-reactive astrocytes after stroke.', 'We examined reactive astrocyte formation in the peri-infarct area 3 days after distal middle cerebral artery occlusion with or without γ-secretase inhibitor treatment. To directly study the effects of inhibiting a γ-secretase cleavage target in reactive astrocytes, we generated glial fibrillary acidic protein-CreER™:Notch 1 conditional knockout mice.', 'Gamma-secretase inhibitor treatment after stroke decreased the number of proliferative glial fibrillary acidic protein-positive reactive astrocytes and RC2-positive reactive astrocytes directly adjacent to the infarct core. The decrease in reactive astrocytes correlated with an increased number of CD45-positive cells that invaded into the peri-infarct area. To study the influence of reactive astrocytes on immune cell invasion, ex vivo immune cell invasion assays were performed. We found that a γ-secretase-mediated pathway in astrocytes affected Jurkat cell invasion. After tamoxifen treatment, glial fibrillary acidic protein-CreER™:Notch 1 conditional knockout mice had a significantly decreased number of proliferating reactive astrocytes and RC2-positive reactive astrocytes. Tamoxifen treatment also led to an increased number of CD45-positive cells that invaded the peri-infarct area.'] Are proliferating reactive astrocytes regulated by Notch-1 in the peri-infarct area after stroke? | qiaojin/PubMedQA | 2 | [
-2.460557699203491,
-1.2676618099212646,
2.7544925212860107
] |
['Asthma, one major respiratory consequence, might be caused by a complex interaction between multiple candidate genes and environmental factors. Herein, we aimed to investigate whether Janus kinase (JAK)-1 gene polymorphisms are associated with asthma susceptibility.', 'Patients were divided into two groups: (1) asthma (n=117) and (2) nonasthma (n=60). The JAK-1 polymorphisms (rs2780895, rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277) were amplified by polymerase chain reaction and detected by electrophoresis after restriction enzyme (HpyCH4IV, Tsp45I, HpaII, XmnI, MspI, and HpaII) digestions. Genotypes, allelic frequencies, and association of haplotypes in both groups were compared.', 'JAK-1 rs2780895 gene polymorphism is associated with susceptibility to asthma. Distributions of JAK-1 rs2780895*CC/CT/TT and C/T allele in both groups are: (1) 80/4/16% and 82/18%; (2) 48/45/7% and 71/29%. Other 5 JAK-1 SNPs (rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277) are not associated with asthma susceptibilities. Distributions of JAK-1 rs10789166*AA/AG/GG, rs4916008*CC/CT/TT, rs2780885*CC/CT/TT, rs17127114*AA/AG/GG, rs3806277*AA/AG/GG in both groups are: (1) 50/40/10%, 42/49/9%, 50/40/10%, 9/37/54%, 8/35/57%; (2) 43/50/7%, 40/50/10%, 50/43/7%, 7/48/45%, 6/42/52%. Haplotype analyses for JAK-1 gene polymorphisms (rs2780895-rs10789166-rs4916008-rs2780885-rs17127114-rs3806277) revealed that JAK-1 haplotypes are not associated with asthma susceptibilities.'] Are jAK-1 rs2780895 C-related genotype and allele but not JAK-1 rs10789166 , rs4916008 , rs2780885 , rs17127114 , and rs3806277 associated with higher susceptibility to asthma? | qiaojin/PubMedQA | 2 | [
-0.8387837409973145,
-1.7152851819992065,
1.4989724159240723
] |
['Tpr is a large coiled-coil protein located in the nuclear basket of the nuclear pore complex for which many different functions were proposed from yeast to human.', 'Here we show that depletion of Tpr by RNA interference triggers G0-G1 arrest and ultimately induces a senescent-like phenotype dependent on the presence of p53. We also found that Tpr depletion impairs the NES [nuclear export sequence]-dependent nuclear export of proteins and causes partial co-depletion of Nup153. In addition Tpr depletion impacts on level and function of the SUMO-protease SENP2 thus affecting SUMOylation regulation at the nuclear pore and overall SUMOylation in the cell.'] Does silencing nuclear pore protein Tpr elicit a senescent-like phenotype in cancer cells? | qiaojin/PubMedQA | 2 | [
-2.6472928524017334,
-0.36497971415519714,
2.0074071884155273
] |
['Given high relapse rates and residual symptoms in depression, new strategies to increase treatment effectiveness are required. A promising avenue is to investigate how electronic momentary assessment technology may contribute to clinical assessment and interventions in depression.', 'A literature search was conducted focusing on the potential contribution of momentary assessments to clinical applications in depression.', 'Momentary assessments are able to reveal subtle, small but repetitive and relevant patterns of emotional expression that predict future course of depression. A momentary assessment tool may expose manageable pieces of daily life behaviour contributing to the depressive experience that patients can influence. The use of this explicit knowledge of daily life experience is understudied with regard to its contribution to diagnostic assessment, monitoring of treatment effects and feedback interventions in depressed patients. The clinical application of momentary assessments may stimulate a shift from passive consumption of treatment to an active role for patients in their recovery and increased patient ownership.'] Do momentary assessment technology as a tool to help patients with depression help themselves? | qiaojin/PubMedQA | 1 | [
-2.828960657119751,
1.0245492458343506,
0.9266920685768127
] |
['Management strategies after severe traumatic brain injury (TBI) target prevention and treatment of intracranial hypertension (ICH) and cerebral hypoperfusion (CH). We have previously established that continuous automated recordings of vital signs (VS) are more highly correlated with outcome than manual end-hour recordings. One potential benefit of automated vital sign data capture is the ability to detect brief episodes of ICH and CH. The purpose of this study was to establish whether a relationship exists between brief episodes of ICH and CH and outcome after severe TBI.', 'Patients at the R Adams Cowley Shock Trauma Center were prospectively enrolled over a 2-year period. Inclusion criteria were as follows: age >14 years, admission within the first 6 hours after injury, Glasgow Coma Scale score <9 on admission, and placement of a clinically indicated ICP monitor. From high-resolution automated VS data recording system, we calculated the 5-minute means of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Brain Trauma Index (BTI = CPP/ICP). Patients were stratified by mortality and 6-month Extended Glasgow Outcome Score (GOSE).', 'Sixty subjects were enrolled with a mean admission Glasgow Coma Scale score of 6.4 ± 3.1, a mean Head Abbreviated Injury Severity Scale score of 4.2 ± 0.7, and a mean Marshall CT score of 2.5 ± 0.9. Significant differences in the mean number of brief episodes of CPP <50 and BTI <2 in patients with a GOSE 1-4 versus GOSE 5-8 (9.4 vs. 4.7, p = 0.02 and 9.3 vs. 4.9, p = 0.03) were found. There were significantly more mean brief episodes per day of ICP >30 (0.52 vs. 0.29, p = 0.02), CPP <50 (0.65 vs. 0.28, p < 0.001), CPP <60 (1.09 vs. 0.7, p = 0.03), BTI <2 (0.66 vs. 0.31, p = 0.002), and BTI <3 (1.1 vs. 0.64, p = 0.01) in those patients with GOSE 1-4. Number of brief episodes of CPP <50, CPP <60, BTI <2, and BTI <3 all demonstrated high predictive power for unfavorable functional outcome (area under the curve = 0.65-0.75, p < 0.05).'] Are brief episodes of intracranial hypertension and cerebral hypoperfusion associated with poor functional outcome after severe traumatic brain injury? | qiaojin/PubMedQA | 2 | [
-1.0639601945877075,
-1.6587934494018555,
1.7506998777389526
] |
['Calcium removal from the medium promptly reduces human sperm motility and induces a Na(+)-dependent depolarization that is accompanied by an increase in intracellular sodium concentration ([Na(+)](i)) and a decrease in intracellular calcium concentration ([Ca(2+)](i)). Sodium loading activates a Na(+)/K(+)-ATPase.', 'Membrane potential (Vm) and [Ca(2+)](i) were simultaneously detected in human sperm populations with the fluorescent probes diSC(3)(5) and fura 2. [Na(+)](i) and was measured independently in a similar fashion using sodium-binding benzofuran isophthalate. Motility was determined in a CASA system, ATP was measured using the luciferin-luciferase assay, and cAMP was measured by radioimmunoassay.', 'Human sperm motility reduction after calcium removal is related to either Na(+)-loading or Na(+)-dependent depolarization, because, under conditions that inhibit the calcium removal-induced Na(+)-dependent depolarization and [Na(+)](i) increase, sperm motility was unaffected. By clamping sperm Vm with valinomycin, we found that the motility reduction associated with the calcium removal was related to sodium loading, and not to membrane potential depolarization. Mibefradil, a calcium channel blocker, markedly inhibited the Na(+)-dependent depolarization and sodium loading, and also preserved sperm motility. In the absence of calcium, both ATP and cAMP concentrations were decreased by 40%. However ATP levels were unchanged when calcium removal was performed under conditions that inhibit the calcium removal-induced Na(+)-dependent depolarization and [Na(+)](i) increase.'] Does sodium influx induced by external calcium chelation decrease human sperm motility? | qiaojin/PubMedQA | 2 | [
-2.343763589859009,
-1.3436408042907715,
2.744260311126709
] |
['Diabetic neuropathy, a long-term complication of type 2 diabetes (T2D), has a genetic inheritance component to its manifestation. We aimed at identifying whether the proteasome modulator 9 (PSMD9) gene responsible for linkage with T2D and maturity-onset diabetes of the young 3 in Italian families may play a role in the inheritance of diabetic neuropathy in T2D as well.', 'We characterized the Italian families with T2D for presence and/or absence of diabetic neuropathy. The diabetic neuropathy is reported as unknown in all cases in which either the diagnosis was unclear or the data were not available for the subject studied. Thus, in our 200 Italian families, the data presence was less than 100%. We tested in the 200 Italians families for the presence of the linkage of the PSMD9 single nucleotide polymorphisms (SNPs) with diabetic neuropathy. The nonparametric as well as the parametric linkage analysis was performed by using the Merlin software; the LOD score and correspondent P value were calculated. For the significance and/or trends toward significance linkage score, 1000 replicates were performed to determine the empirical P value.', 'We report the linkage study of the PSMD9 SNPs [intervening sequence IVS3+nt460A/G, IVS3+nt437C/T and E197G] in Italian families with T2D neuropathy.'] Is pSMD9 linked to type 2 diabetes neuropathy? | qiaojin/PubMedQA | 2 | [
-1.6941752433776855,
-1.3832188844680786,
2.1780974864959717
] |
['The purpose was to assess the activity of nuclear factor (NF)-κB and hypoxia inducible factor (HIF)-1α transcription factors and the expression levels of inflammation markers [interleukin (IL)-6 and IL-8] in the vitreous of patients suffering from proliferative diabetic retinopathy (PDR) scheduled for elective vitreous surgery in a single academic-based retina practice in a prospective clinical study.', 'Twenty-seven patients with PDR were enrolled in the study. The severity of retinopathy was classified (0, 1, 2, 3, 4) and the activity of neovascularization was graded (0, 1, 2, 3, 4) by the surgeon intraoperatively. Samples of the vitreous were collected during surgery, and the activity of NF-κB and HIF-1α transcription factors and the expression levels of IL-6 and IL-8 were measured.', "The majority of samples fell into the retinopathy class 3 (n = 12) or 4 (n = 13). The level of IL-6 increased from 68.9 ± 46.8 pg/ml to 102.7 ± 94.1 pg/ml, and IL-8 increased from 165.1 ± 136.0 pg/ml to 521.0 ± 870.9 pg/ml (mean ± S.D., nonsignificant change: normality test followed with Mann-Whitney Rank Sum Test). According to the neovascularization activity, the samples fell into grade 1 (n = 7), 2 (n = 12) or 3 (n = 7). In IL-6, there was a statistically significant increase (P < .05) from grade 2 to 3: 58.6 ± 40.3 pg/ml and 158.4 ± 102.5 pg/ml, respectively (Kruskal-Wallis One-Way Analysis of Variance on Ranks followed with Dunn's Method). The level of IL-8 was as follows: in grade 1: 118.0 ± 62.4 pg/ml, in grade 2: 192.3 ± 127.1 pg/ml and in grade 3: 884.3 ± 1161.0 pg/ml (statistically nonsignificant change). There was a statistically significant linear regression between IL-6 and IL-8 (P < .001): IL-6 = 51.88 pg/ml + (0.092*IL-8), r = 0.772. Increased activity of the NF-κB and HIF-1α transcription factors was not observed."] Are increased IL-6 levels related to NF-κB or HIF-1α transcription factors activity in the vitreous of proliferative diabetic retinopathy? | qiaojin/PubMedQA | 2 | [
-1.1871179342269897,
-1.7703114748001099,
1.9008500576019287
] |
['The authors have identified a recessive mutation causing progressive retinal degeneration, white fundus flecks, and eventual retinal pigment epithelium (RPE) atrophy. The goal of these studies was to characterize the retinal phenotype, to identify the causative locus, and to examine possible functions of the affected gene.', 'SNP mapping, DNA sequencing, and genetic complementation were used to identify the affected locus. Histology, electroretinography, immunohistochemistry, Western blot analysis, fundus photography, electron microscopy, and in vitro phagocytosis assays were used to characterize the phenotype of the mouse.', 'Gene mapping identified a single base pair deletion in membrane-type frizzled related protein (MFRP), designated Mfrp(174delG). MFRP is normally expressed in the RPE and ciliary body but was undetectable by Western blot in mutants. CTRP5, a binding partner of MFRP, was upregulated at the mRNA level and at the protein level in most patients. Assays designed to test the integrity of retinoid cycling and phagocytic pathways showed no deficits in Mfrp(174delG) or rd6 animals. However, the RPE of both Mfrp(174delG) and rd6 mice exhibited a dramatic increase in the number of apical microvilli. Furthermore, evidence of RPE atrophy was evident in Mfrp(174delG) mice by 21 months.'] Does 174delG mutation in mouse MFRP cause photoreceptor degeneration and RPE atrophy? | qiaojin/PubMedQA | 2 | [
-2.1858904361724854,
-1.4127599000930786,
2.6100618839263916
] |
['It has not been solved whether subjects carrying the minor alleles of the -455T>C or -482C>T single nucleotide polymorphisms (SNPs) in the apolipoprotein-C3-gene (APOC3) have an increased risk for developing fatty liver and insulin resistance. We investigated the relationships of the SNPs with hepatic APOC3 expression and hypothesized that visceral obesity may modulate the effects of these SNPs on liver fat and insulin sensitivity (IS).', 'APOC3 mRNA expression and triglyceride content were determined in liver biopsies from 50 subjects. In a separate group (N=330) liver fat was measured by (1)H-magnetic resonance spectroscopy. IS was estimated during an oral glucose tolerance test (OGTT) and the euglycemic, hyperinsulinemic clamp (N=222).', 'APOC3 mRNA correlated positively with triglyceride content in liver biopsies (r=0.29, P=0.036). Carriers of the minor alleles (-455C and -482T) tended to have higher hepatic APOC3 mRNA expression (1.80 (0.45-3.56) vs 0.77 (0.40-1.64), P=0.09), but not higher triglyceride content (P=0.76). In 330 subjects the genotype did not correlate with liver fat (P=0.97) or IS (OGTT: P=0.41; clamp: P=0.99). However, a significant interaction of the genotype with waist circumference in determining liver fat was detected (P=0.02) in which minor allele carriers had higher liver fat only in the lowest tertile of waist circumference (P=0.01). In agreement, during a 9-month lifestyle intervention the minor allele carriers of the SNP -482C>T in the lowest tertile also had less decrease in liver fat (P=0.04).'] Does visceral obesity modulate the impact of apolipoprotein C3 gene variants on liver fat content? | qiaojin/PubMedQA | 2 | [
-1.4306434392929077,
-1.5391738414764404,
1.9453072547912598
] |
['The rate-corrected QT interval (QTc) prolongation is a risk factor for sudden cardiac death and may be induced by antipsychotic drugs.', 'To determine the clinical characteristics associated with QTc prolongation (440\u2009msec or greater) in children and adolescents hospitalized for treatment of psychiatric disorders.', 'We determined the frequency of baseline prolongation of QTc in 811 psychiatric pediatric inpatients (15.5\u2009±\u20092.4 years of age). QTc duration was 440\u2009msec or greater (range 441-481\u2009msec) in 16 patients (1.97%). In a 1:5 nested case-control design, the 16 patients with prolonged QTc were age- and gender-matched with 80 patients with QTc of <421\u2009msec.', 'Patients with normal and prolonged QTc had similar utilization of antipsychotics (43.8% vs. 40.8%) and daily chlorpromazine equivalents (165\u2009±\u2009110 vs. 168\u2009±\u2009218\u2009mg). Hypokalemia (p\u2009=\u20090.009) and obesity (p\u2009=\u20090.032) were more common among patients with prolonged QTc. The correlation between obesity and QTc prolongation was confirmed in logistic regression analysis.'] Does antipsychotic drug administration correlate with prolonged rate-corrected QT interval in children and adolescents : results from a nested case-control study? | qiaojin/PubMedQA | 2 | [
-1.9335639476776123,
-1.4723669290542603,
2.434384346008301
] |
['Cadmium zinc telluride (CZT) detectors with linear counting rate response enable count subtraction in sequential scanning. We evaluated whether count subtraction eliminated the need for higher activity doses in the second part of the 1-d stress-rest myocardial perfusion imaging (MPI) protocol.', 'For 50 patients (mean age ± SD, 66 ± 12 y) with visually abnormal (n = 42) or equivocal (n = 8) adenosine-stress MPI (320 MBq of (99m)Tc-tetrofosmin) on a CZT camera, rest MPI was performed with a low dose (320 MBq) and repeated after injection of an additional 640 MBq of (99m)Tc-tetrofosmin to achieve a standard 3-fold increased dose at rest (960 MBq), compared with stress (320 MBq). Low-dose rest myocardial perfusion images were reconstructed after subtracting the background activity of the preceding stress scan. Segmental percentage tracer uptake of the 2 rest myocardial perfusion images (320 vs. 960 MBq) was compared using intraclass correlation and Bland-Altman limits of agreement. Patient- and coronary territory-based clinical agreement was assessed.', 'The standard protocol revealed ischemia in 34 (68%) and a fixed defect in 8 (16%) patients, of whom 33 (97%) and 8 (100%) were correctly identified by low-dose MPI (clinical agreement, 98%). Segmental uptake correlated well between low- and standard-dose rest scans (r = 0.94, P < 0.001; Bland-Altman limits of agreement, -11 to +11%). Defect extent was 14.4% (low-dose) versus 13.1% (standard-dose) at rest (P = not statistically significant) and 26.6% at stress (P < 0.001 vs. rest scans).'] Do semiconductor detectors allow low-dose-low-dose 1-day SPECT myocardial perfusion imaging? | qiaojin/PubMedQA | 2 | [
-1.7225784063339233,
-1.6431543827056885,
2.4247279167175293
] |
['Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the ingestion of aspirin. Although alterations in eicosanoid metabolites play a role in AERD, other immune or inflammatory mechanisms may be involved. We aimed to identify proteins that were differentially expressed in nasal polyps between patients with AERD and aspirin-tolerant asthma (ATA).', 'Two-dimensional electrophoresis was adopted for differential display proteomics. Proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS). Western blotting and immunohistochemical staining were performed to compare the amount of fatty acid-binding protein 1 (FABP1) in the nasal polyps of patients with AERD and ATA. Fifteen proteins were significantly up- (seven spots) or down-regulated in the nasal polyps of patients with AERD (n = 5) compared to those with ATA (n = 8). LC-MS revealed an increase in seven proteins expression and a decrease in eight proteins expression in patients with AERD compared to those with ATA (P = 0.003-0.045). FABP1-expression based on immunoblotting and immunohistochemical analysis was significantly higher in the nasal polyps of patients with AERD compared to that in patients with ATA. FABP1 was observed in epithelial, eosinophils, macrophages, and the smooth-muscle cells of blood vessels in the polyps.'] Is fatty acid binding protein 1 related with development of aspirin-exacerbated respiratory disease? | qiaojin/PubMedQA | 2 | [
-2.3638858795166016,
-1.3786656856536865,
2.8209567070007324
] |
['Identification of children at risk of developing asthma provides a window of opportunity for risk-reducing interventions. Allergen sensitization might identify high-risk children.', 'We sought to determine whether skin prick tests (SPTs) to individual allergens up to age 2 years predict wheeze at age 12 years.', 'In a birth cohort of 620 children oversampled for familial allergy, sensitization was assessed by using SPTs (monosensitized, polysensitized, or either) to 6 allergens at ages 6, 12, and 24 months. Wheeze and eczema were recorded 18 times during the first 2 years. Current wheeze was recorded at age 12 years. Adjusted associations were evaluated by multiple logistic regression.', 'A positive SPT to house dust mite (HDM) at age 1 or 2 years predicted wheeze at age 12 years (adjusted odds ratio: 1 year, 3.31 [95% CI 1.59-6.91]; 2 years, 6.37 [95% CI, 3.48-11.66]). Among wheezy 1-year-olds, those who were HDM sensitized had a 75% (95% CI, 51% to 91%) probability of wheeze at age 12 years compared with a 36% (95% CI, 23% to 50%) probability among those not sensitized. Among eczematous 1-year-olds, those who were HDM sensitized had a 67% (95% CI, 45% to 84%) probability of wheeze at age 12 years compared with a 35% (95% CI, 25% to 45%) probability among those not sensitized. Among 1-year-old children with both eczema and wheeze, the probability of wheeze at age 12 years was 64% (95% CI, 35% to 87%) if HDM sensitized and 50% (95% CI, 26% to 74%) if not.'] Does house dust mite sensitization in toddlers predict current wheeze at age 12 years? | qiaojin/PubMedQA | 2 | [
-1.2428330183029175,
-1.0860393047332764,
1.3807628154754639
] |
['Allergic diseases affect a large population. Pollen, an ubiquitous allergen, is the trigger of seasonal rhinitis, conjunctivitis, and asthma, as well as an exacerbating factor of atopic dermatitis. However, the underlying mechanism by which pollen induces thymic stromal lymphopoietin (TSLP)-triggered allergic inflammation through epithelial innate immunity is largely unknown.', 'We sought to explore whether short ragweed (SRW) pollen induces TSLP/OX40 ligand (OX40L)/OX40 signaling through Toll-like receptor (TLR) 4-dependent pathways in patients with allergic disease.', 'Three models were used for this study, a well-characterized murine model of allergic conjunctivitis induced by SRW pollen, a topical challenge model on the murine ocular surface, and a culture model of primary human corneal epithelium exposed to aqueous extract of defatted SRW pollen (SRWe).', 'The topical challenges with SRW pollen generated typical allergic conjunctivitis in BALB/c mice. Clinical signs, stimulated TSLP/OX40L/OX40 signaling, and T(H)2 cytokine levels in the ocular mucosa and draining cervical lymph nodes were significantly reduced or eliminated in TLR4-deficient (Tlr4-d) or myeloid differentiation primary response gene 88 (MyD88) knockout (MyD88(-/-)) mice compared with those seen in their wild-type littermates. SRWe stimulated TSLP production by ocular epithelia in wild-type but not Tlr4-d or MyD88(-/-) mice. SRWe-stimulated TSLP was blocked by TLR4 antibody and nuclear factor κB inhibitor in murine and human corneal epithelia.'] Does short ragweed pollen trigger allergic inflammation through Toll-like receptor 4-dependent thymic stromal lymphopoietin/OX40 ligand/OX40 signaling pathways? | qiaojin/PubMedQA | 2 | [
-2.466634511947632,
-1.26981782913208,
2.771068811416626
] |
['Karrikinolide (KAR(1)) is a smoke-derived chemical that can trigger seeds to germinate. A potential application for KAR(1) is for synchronizing the germination of weed seeds, thereby enhancing the efficiency of weed control efforts. Yet not all species germinate readily with KAR(1), and it is not known whether seemingly non-responsive species can be induced to respond. Here a major agronomic weed family, the Brassicaceae, is used to test the hypothesis that a stimulatory response to KAR(1) may be present in physiologically dormant seeds but may not be expressed under all circumstances.', 'Seeds of eight Brassicaceae weed species (Brassica tournefortii, Raphanus raphanistrum, Sisymbrium orientale, S. erysimoides, Rapistrum rugosum, Lepidium africanum, Heliophila pusilla and Carrichtera annua) were tested for their response to 1 µm KAR(1) when freshly collected and following simulated and natural dormancy alleviation, which included wet-dry cycling, dry after-ripening, cold and warm stratification and a 2 year seed burial trial.', 'Seven of the eight Brassicaceae species tested were stimulated to germinate with KAR(1) when the seeds were fresh, and the remaining species became responsive to KAR(1) following wet-dry cycling and dry after-ripening. Light influenced the germination response of seeds to KAR(1), with the majority of species germinating better in darkness. Germination with and without KAR(1) fluctuated seasonally throughout the seed burial trial.'] Do seeds of Brassicaceae weeds have an inherent or inducible response to the germination stimulant karrikinolide? | qiaojin/PubMedQA | 1 | [
-2.2936203479766846,
0.8886503577232361,
0.5264434218406677
] |
['Soy-based infant formula contains high levels of isoflavones. These estrogen-like compounds have been shown to induce changes in sexually dimorphic behaviors in animals exposed in early development.', 'We examined gender-role play behavior in relation to soy-based and non-soy-based infant feeding methods among children in the Avon Longitudinal Study of Parents and Children.', 'We studied 3,664 boys and 3,412 girls. Four exposure categories were created using data from questionnaires administered at 6 and 15 months postpartum: primarily breast, early formula (referent), early soy, and late soy. Gender-role play behavior was assessed using the Pre-School Activities Inventory (PSAI). Associations between infant feeding and PSAI scores at 42 months of age were assessed using linear regression. Post hoc analyses of PSAI scores at 30 and 57 months were also conducted.', 'Early-infancy soy use was reported for approximately 2% of participants. Mean [95% confidence interval (CI)] PSAI scores at 42 months were 62.3 (62.0, 62.6) and 36.9 (36.6, 37.2) for boys and girls, respectively. After adjustment, early soy (vs. early formula) feeding was associated with higher (less feminine) PSAI scores in girls (β = 2.66; 95% CI: 0.19, 5.12) but was not significantly associated with PSAI scores in boys. The association between soy exposure and PSAI scores in girls was substantially attenuated at 30 and 57 months.'] Do early-life soy exposure and gender-role play behavior in children? | qiaojin/PubMedQA | 2 | [
-1.5597343444824219,
-0.6764087677001953,
1.2794995307922363
] |
['Bisphenol A (BPA) is one of the most prevalent chemicals in daily-use materials; therefore, human exposure to BPA is ubiquitous. The estrogenicity of BPA is generally mediated by nuclear estrogen receptors (ERs). However, low concentrations of BPA stimulate seminoma cell proliferation by an uncertain mechanism that does not involve activation of ERs.', 'We investigated the possible promoting effects of low-concentration BPA and the possible mechanism(s) using the murine ER-β negative spermatogonial GC-1 cell line.', 'Using the specific signaling inhibitor, BPA at test concentrations ranging from 10-10 to 10-8 M markedly induced proliferation of GC-1 cells by activating both cGMP-dependent protein kinase (PKG) and epidermal growth factor receptor (EGFR) extracellular regulated kinase (ERK) pathways. BPA stimulated a rapid (15-min) phosphorylation of the transcription factor cAMP response element binding protein (CREB) and the cell cycle regulator retinoblastoma protein (Rb). Interestingly, ER-α phosphorylation is involved in the proliferation, whereas BPA does not directly transactivate ER-α in gene reporter assays. Using specific agonists and gene silencing, we further observed that BPA mediates the proliferation and fos gene expression of GC-1 cells by G protein-coupled receptor 30 (GPR30) and ER-α.'] Do low concentrations of bisphenol A induce mouse spermatogonial cell proliferation by G protein-coupled receptor 30 and estrogen receptor-α? | qiaojin/PubMedQA | 2 | [
-2.440081834793091,
-1.209744930267334,
2.694734573364258
] |
["To examine the efficacy of self-regulation of food marketing to children by comparing, during children's preferred viewing on television, the differences in food/beverage marketing between two groups of corporations: 17 corporations participating in the Canadian Children's Food and Beverage Advertising Initiative (CAI) and 35 corporations not participating (non-CAI) in this initiative.", "The food/beverage marketing activities of CAI and non-CAI corporations during 99.5 hours of children's preferred viewing on television were compared. First, the preferred television viewing of 272 children aged 10-12 years from Ontario and Quebec who completed TV viewing journals for a seven-day period was determined. A total of 32 television stations were simultaneously recorded, and a content analysis of children's preferred viewing was conducted and included coding all food/beverage promotions and their nutritional content. Each food/beverage promotion was classified by corporation type (i.e., CAI or non-CAI).", "The CAI was responsible for significantly more food/beverage promotions, and used media characters and repetition more frequently in their food/beverage promotions than the non-CAI group. Nutritionally, the CAI food/beverage promotions were higher in fats, sugar, sodium and energy per 100 grams. A significantly greater proportion of the CAI food/beverage promotions were considered 'less healthy' compared to the non-CAI promotions."] Is self-regulation by industry of food marketing having little impact during children 's preferred television? | qiaojin/PubMedQA | 1 | [
-1.4038827419281006,
2.073791265487671,
-1.4030168056488037
] |
['Toll-like receptors (TLRs) are expressed on cardiomyocytes and recognize pathogen-associated molecular patterns. Whether endogenous molecules produced by tissue injury (damage associated molecular patterns, DAMPs) can induce cardiomyocyte inflammation via TLR signalling pathways and/or reduce cardiomyocyte contractility is unknown.', 'Primary cardiomyocytes isolated from nuclear factor κ B (NFκB)-luciferase knock-in mice were used to assess NFκB signalling. DAMPs, HSP60, HSP70 and HMGB1, increased NFκB transcriptional activity compared to controls. HSP70 stood out compared to other DAMPs and even lipopolysaccharide (LPS). Subsequent experiments focused on HSP70. Cardiomyocytes exposed to HSP70 had a 58% decrease in contractility without a decrease in calcium flux. Exposure of cultured HL-1 cardiomyocytes to HSP70 resulted in increased expression of intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6) and keratinocyte-derived chemokine (KC) compared to controls. Knock-out mice for TLR2, TLR4 and MyD88, plus background strain controls (C57BL/6) were used to assess induction of cardiomyocyte inflammation by HSP70. The cardiomyocyte expression of ICAM-1 induced by HSP70 was significantly reduced in TLR2 and MyD88 knock-out mice but not TLR4 knock-out mice; implicating the TLR2 signalling pathway. Furthermore, blocking antibodies to TLR2 were able to abrogate HSP70-induced contractile dysfunction and cell death.'] Does extracellular heat shock protein 70 induce cardiomyocyte inflammation and contractile dysfunction via TLR2? | qiaojin/PubMedQA | 2 | [
-2.3841326236724854,
-1.3549758195877075,
2.7473480701446533
] |
['The surgical approach to benign goiter is becoming increasingly radical due to the risk of recurrent goiter. The aim of this prospective study was to evaluate the impact of surgery on health-related quality of life (HRQoL) of patients with benign goiter.', 'HRQoL data from 115 patients with benign goiter were analyzed. Thirty-three patients (group 1) had a hemithyroidectomy. Sixty-five patients (group 2) had a so-called Dunhill operation (hemithyroidectomy\u2009+\u2009near-total thyroidectomy of the opposite side), and in 17 patients, a total resection of the goiter was performed. The validated HRQoL instrument, the EuroQol-5D, was applied to measure the health-related quality of life.', 'With an overall complication rate of 10% and no permanent recurrent laryngeal nerve palsy, it was shown that surgery for benign goiter is safe. In the validated HRQoL questionnaire (EQ-5D), no significant variance could be found between different surgical procedures such as thyroidectomy, hemithyroidectomy, or Dunhill procedure. Further, no significant differences in QoL were found in EQ-5D questionnaire compared to normal population.'] Is quality of life influenced by the extent of surgery in patients with benign goiter? | qiaojin/PubMedQA | 2 | [
-1.7814173698425293,
-1.4413118362426758,
2.2669904232025146
] |
['Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by downregulating T cell activation. The most studied +49A>G polymorphism of the CTLA-4 gene has been associated with several autoimmune diseases. However, little is known about the association between this functional polymorphism of CTLA-4 and cancer prognosis.', 'To investigate the association between CTLA-4 +49A>G polymorphism and prognosis of advanced non-small cell lung cancer (NSCLC) patients in a Chinese population.', 'The CTLA-4 +49A>G polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 338 advanced NSCLC patients.', 'The frequencies of CTLA-4 +49 GG, GA and AA in advanced NSCLC patients were 44.4%, 42.0% and 13.6%, respectively. No significant association was observed between CTLA-4 +49A>G polymorphism and clinicopathologic features of advanced NSCLC including gender, histopathological type, clinical stage and tumor markers. Patients with the AA genotype had a survival time of 9.8 months, significantly shorter than those with the GG genotype (12.5 months) or the GA genotype (12.0 months) (p < 0.001; log-rank test). Multivariate Cox analysis further revealed that the CTLA-4 +49AA genotype is an independent adverse prognostic indicator for NSCLC patients.'] Does cTLA-4 +49A > G polymorphism is associate with advanced non-small cell lung cancer prognosis? | qiaojin/PubMedQA | 2 | [
-2.1272494792938232,
-1.5001165866851807,
2.6950035095214844
] |
['To date, there are no studies about the attachment of the articular capsule of the superior shoulder joint. The aim of this study was to measure the width of the attachment of the articular capsule on the humerus, and to clarify the anatomy and the relationship to the footprint of the rotator cuff.', 'The attachment of the articular capsule on the greater tuberosity was exposed. The width of the attachment of the capsule and the footprint of the rotator cuff were measured.', 'The maximum capsular width was located at the border between the infraspinatus and the teres minor, and measured 9.1 mm. The minimum capsular width was 3.5 mm, and it was located at 10.9 mm posterior to the anterior margin of the greater tuberosity and 1.5 mm anterior to the posterior margin of the supraspinatus.'] Does the superior capsule of the shoulder joint complement the insertion of the rotator cuff? | qiaojin/PubMedQA | 2 | [
-1.6978219747543335,
-0.8251731991767883,
1.6677827835083008
] |
['Animal and human brain imaging studies suggest that the cerebellum plays an important role in the control of swallowing. In this study, we probed the interaction between cerebellar and pharyngeal motor cortical activity with transcranial magnetic stimulation (TMS) to determine if the cerebellum can modulate cortical swallowing motor circuitry.', 'Healthy volunteers (n=16, eight men, mean age=32, range 19-57years) underwent TMS measurements of pharyngeal electromyography (EMG) recorded from a swallowed intraluminal catheter to assess cortical and cerebellar excitability. Subjects then underwent a paired pulse paradigm, where active or sham TMS conditioning pulses over the cerebellum and control sites were followed by suprathreshold TMS over the cortical pharyngeal area. Paired pulses were delivered at varying inter-stimulus intervals (ISIs) with the cortical response amplitudes being assessed.', 'Stimulation of the cerebellum over its midline or hemispheres evoked distinct pharyngeal EMG responses. There was no difference in EMG amplitudes following cerebellar hemispheric or midline stimulation (mean 55.5±6.9 vs 42.8±5.9μV, P=0.08). In contrast, after cerebellar preconditioning, the cortically evoked responses underwent maximal facilitation at ISIs of 50-200ms (P<0.05), an effect not seen with sham or trigeminal nerve preconditioning.'] Does non-invasive magnetic stimulation of the human cerebellum facilitate cortico-bulbar projections in the swallowing motor system? | qiaojin/PubMedQA | 2 | [
-2.272486925125122,
-1.3470957279205322,
2.6678590774536133
] |
['The soluble hematopoietin receptor Epstein-Barr virus-induced protein (EBI)-3 is an immune regulator that has been associated with the pathogenesis of inflammatory bowel disease. However, the concept that EBI3 is part of an interleukin (IL)-27 heterodimer that mediates chronic inflammatory and autoimmune diseases has been challenged by the description of IL-35, a bioactive cytokine comprising EBI3 and IL-12 p35. We investigated the roles of IL-27 and IL-35 in chronic inflammation of the intestine.', 'We analyzed EBI3-deficient mice and IL-27p28-deficient mice with spontaneous or T-cell transfer-induced colitis and compared outcomes with wild-type mice (controls). We constructed vectors that express EBI3 covalently linked to the IL-12p35 chain (recombinant [r]IL-35).', 'Intestines of EBI3-deficient mice had increased pathologic features of colitis, compared with IL-27p28-deficient or control mice; they also had shorter survival times, indicating that IL-35, rather than IL-27, protects the intestine from immune responses in mice. The mucosa of EBI3-deficient mice accumulated subsets of activated CD4+ T cells that produced T-helper (Th)1 and Th17 cytokines. Adoptive transfer of these T cells induced colitis in RAG-deficient mice. The rIL-35 significantly reduced the development of several forms of experimental colitis and reduced levels of markers of Th1 and Th17 cells.'] Does interleukin-35 mediate mucosal immune responses that protect against T-cell-dependent colitis? | qiaojin/PubMedQA | 2 | [
-2.4023871421813965,
-1.297311544418335,
2.7123050689697266
] |
['Hepatocellular carcinoma (HCC) can result from hepatitis C virus (HCV)-related liver disease and is the fastest-growing cause of cancer-related death in the United States. α-fetoprotein (AFP) has been used as a prognostic factor for HCC, but the value of AFP as a prognostic factor for HCV-related HCC in the United States is unknown. We investigated whether higher levels of AFP at the time of diagnosis are associated with increased mortality of patients with HCV-related HCC.', 'In a retrospective study, we collected data from a cohort of HCV-infected veterans, identifying incident HCC cases from October 1, 1998, to January 1, 2007 (n = 1480 patients). The mean serum levels of AFP, obtained within 60 days before to 30 days after HCC diagnosis, were determined for 1064 patients and categorized as less than 10 ng/mL (18%), 10 to less than 100 ng/mL (30%), 100 to less than 1000 ng/mL (22%), or 1000 ng/mL or more (29%). Cox proportional hazard models were used to associate serum levels of AFP with mortality, adjusting for demographic features, clinical factors, and treatment.', 'The median survival times were significantly lower among patients with higher levels of AFP: 709 days for patients with less than 10 ng/mL, 422 days for patients with 10 to less than 100 ng/mL, 208 days for patients with 100 to less than 1000 ng/mL, and 68 days for patients with 1000 ng/mL or more. In the multivariate analysis, increased levels of AFP (10 to <100, 100 to <1000, and ≥1000) were associated significantly with increased mortality, compared with a serum AFP level of less than 10; hazard ratios were 1.50, 2.23, and 4.35, respectively.'] Does level of α-fetoprotein predict mortality among patients with hepatitis C-related hepatocellular carcinoma? | qiaojin/PubMedQA | 2 | [
-0.8201214075088501,
-1.682729959487915,
1.5485997200012207
] |
['The purpose of this study was to assess myocardial blood flow (MBF) using positron emission tomography in patients with hypertrophic cardiomyopathy (HCM) according to genetic status.', 'Coronary microvascular dysfunction is an important feature of HCM, associated with ventricular remodeling and heart failure. We recently demonstrated the increased prevalence of systolic dysfunction in patients with HCM with sarcomere myofilament gene mutations and postulated an association between genetic status and coronary microvascular dysfunction.', 'Maximum MBF (intravenous dipyridamole, 0.56 mg/kg; Dip-MBF) was measured using (13)N-labeled ammonia in 61 patients with HCM (age 38 ± 14 years), genotyped by automatic DNA sequencing of 8 myofilament-encoding genes (myosin-binding protein C, beta-myosin heavy chain, regulatory and essential light chains, troponin T, troponin I, troponin C, alpha-tropomyosin, and alpha-actin). In 35 patients, cardiac magnetic resonance imaging was performed.', 'Fifty-three mutations were identified in 42 of the 61 patients (genotype positive; 69%). Despite similar clinical profiles, genotype-positive patients with HCM showed substantially lower Dip-MBF compared with that of genotype-negative patients (1.7 ± 0.6 ml/min/g vs. 2.4 ± 1.2 ml/min/g; p < 0.02). A Dip-MBF <1.5 ml/min/g had 81% positive predictive value for genotype-positive status and implied a 3.5-fold independent increase in likelihood of carrying myofilament gene mutations (hazard ratio: 3.52; 95% confidence interval: 1.05 to 11.7; p = 0.04). At cardiac magnetic resonance imaging, the prevalence of late gadolinium enhancement was greater in genotype-positive patients (22 of 23 [96%] compared with 8 of 12 [67%] genotype-negative patients; p = 0.038).'] Is microvascular function selectively impaired in patients with hypertrophic cardiomyopathy and sarcomere myofilament gene mutations? | qiaojin/PubMedQA | 2 | [
-1.7151128053665161,
-1.6886160373687744,
2.387894630432129
] |
['Chronic obstructive pulmonary disease (COPD) is thought to result in rapid and progressive loss of lung function usually expressed as mean values for whole cohorts.', 'Longitudinal studies evaluating individual lung function loss and other domains of COPD progression are needed.', 'We evaluated 1,198 stable, well-characterized patients with COPD (1,100 males) recruited in two centers (Florida and Tenerife, Spain) and annually monitored their multidomain progression from 1997 to 2009. Patients were followed for a median of 64 months and up to 10 years. Their individual FEV(1) (L) and BODE index slopes, expressed as annual change, were evaluated using regression models for repeated measures. A total of 751 patients with at least three measurements were used for the analyses.', 'Eighteen percent of patients had a statistically significant FEV(1) slope decline (-86 ml/yr; 95% confidence interval [CI], -32 to -278 ml/yr). Higher baseline FEV(1) (relative risk, 1.857; 95% CI, 1.322-2.610; P < 0.001) and low body mass index (relative risk, 1.071; 95% CI, 1.035-1.106; P < 0.001) were independently associated with FEV(1) decline. The BODE index had a statistically significant increase (0.55, 0.20-1.37 point/yr) in only 14% of patients and these had more severe baseline obstruction. Concordance between FEV1 and BODE change was low (κ Cohen, 16%). Interestingly, 73% of patients had no significant slope change in FEV1 or BODE. Only the BODE change was associated with mortality in patients without FEV(1) progression.'] Is the progression of chronic obstructive pulmonary disease heterogeneous : the experience of the BODE cohort? | qiaojin/PubMedQA | 2 | [
-0.5717587471008301,
-1.5657753944396973,
1.178470492362976
] |
['Longitudinal tears of the medial meniscus posterior horn (MMPH) are commonly associated with a chronic anterior cruciate ligament (ACL) deficiency. Many studies have demonstrated the importance of the medial meniscus in terms of limiting the amount of anterior-posterior tibial translation in response to anterior tibial loads in ACL-deficient knees.', 'An MMPH tear in an ACL-deficient knee increases the anterior-posterior tibial translation and rotatory instability. In addition, MMPH repair will restore the tibial translation to the level before the tear.', 'Controlled laboratory study.', 'Ten human cadaveric knees were tested sequentially using a custom testing system under 5 conditions: intact, ACL deficient, ACL deficient with an MMPH peripheral longitudinal tear, ACL deficient with an MMPH repair, and ACL deficient with a total medial meniscectomy. The knee kinematics were measured at 0°, 15°, 30°, 60°, and 90° of flexion in response to a 134-N anterior and 200-N axial compressive tibial load. The rotatory kinematics were also measured at 15° and 30° of flexion in a combined rotatory load of 5 N·m of internal tibial torque and 10 N·m of valgus torque.', 'Medial meniscus posterior horn longitudinal tears in ACL-deficient knees resulted in a significant increase in anterior-posterior tibial translation at all flexion angles except 90° (P < .05). An MMPH repair in an ACL-deficient knee showed a significant decrease in anterior-posterior tibial translation at all flexion angles except 60° compared with the ACL-deficient/MMPH tear state (P < .05). The total anterior-posterior translation of the ACL-deficient/MMPH repaired knee was not significantly increased compared with the ACL (only)-deficient knee but was increased compared with the ACL-intact knee (P > .05). A total medial meniscectomy in an ACL-deficient knee did not increase the anterior-posterior tibial translation significantly compared with MMPH tears in ACL-deficient knees at all flexion angles (P > .05). In a combined rotatory load, tibial rotation after MMPH tears or a total medial meniscectomy in an ACL-deficient knee were not affected significantly at all flexion angles.'] Does longitudinal tear of the medial meniscus posterior horn in the anterior cruciate ligament-deficient knee significantly influence anterior stability? | qiaojin/PubMedQA | 2 | [
-1.9187265634536743,
-1.5109049081802368,
2.407935857772827
] |
['Computer-based tests are widely used for the purpose of documenting baseline neurocognitive function, and athletes are often tested in groups. At present, there is limited research on the effects of administering these tests in a group versus individual setting.', 'Athletes assessed with neurocognitive tests in groups would show decreased performance compared with those assessed individually.', 'Cohort study; Level of evidence, 3.', 'High school athletes completed preseason baseline neurocognitive tests either in groups in their school or individually in a private neuropsychological clinic (with no significant between-group differences in sex, history of concussion, and attention deficit disorder/learning disability). All athletes completed the ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing) test battery on 1 occasion, which yielded scores in the area of verbal memory, visual memory, motor processing speed, reaction time, and symptom scores.', 'Athletes in the group setting scored significantly lower on verbal memory (mean 83.4 vs 86.5; P = .003), visual memory (mean 71.6 vs 76.7; P = .0001), motor processing speed (mean 35.6 vs 38.4; P = .0001), and reaction time (mean 0.61 vs 0.57; P = .001), but not symptom scores (mean 6.1 vs 4.4; P = .11), and exhibited a greater rate of invalid baselines. Similar results were obtained after excluding athletes with attention deficit disorder/learning disability and/or a history of concussion.'] Does group versus individual administration affect baseline neurocognitive test performance? | qiaojin/PubMedQA | 2 | [
-2.3561599254608154,
0.010952601209282875,
1.4905110597610474
] |
['Muscle contusions are common muscle injuries. Although these injuries are capable of healing, incomplete functional recovery often occurs. Muscle-derived stem cells (MDSCs) are likely derived from blood vessel cells and have a multilineage differentiation potential.', 'The aims of this study are (1) to find optimal timing of MDSC transplantation to enhance muscle healing by stimulating muscle regeneration and preventing scar tissue (fibrosis) formation after skeletal muscle contusion injury, and (2) to investigate the role of angiogenesis in the muscle-healing process after MDSC transplantation.', 'Controlled laboratory study.', 'Muscle-derived stem cells were injected directly into injured tibialis anterior muscles of mice at various time points (1, 4, and 7 days) after the muscle contusion injury. Muscle regeneration, angiogenesis, and fibrosis formation were evaluated by histology and real-time polymerase chain reaction analysis, and functional recovery was measured by physiologic testing.', 'Transplantation of MDSCs at 4 days after injury significantly promoted angiogenesis, which was induced by high levels of vascular endothelial growth factor expression at week 1, and significantly increased muscle regeneration and muscle strength by week 2, when compared with the other groups. A decrease in fibrosis formation was observed at week 4, when compared with the other groups, after the transplantation of MDSCs at 4 and 7 days after injury.'] Does intramuscular transplantation of muscle-derived stem cells accelerate skeletal muscle healing after contusion injury via enhancement of angiogenesis? | qiaojin/PubMedQA | 2 | [
-2.7801694869995117,
-0.52312171459198,
2.3529884815216064
] |
['The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic β-cell function by potentiating insulin secretion and β-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function.', 'Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies. Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of β-cell viability and proliferation.', 'The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells.'] Do pleiotropic effects of GIP on islet function involve osteopontin? | qiaojin/PubMedQA | 2 | [
-2.366497278213501,
-1.2328298091888428,
2.615215539932251
] |
['Cardiomyocyte calcium overloading has been implicated in the pathogenesis of Duchenne muscular dystrophy (DMD) heart disease. The cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) plays a major role in removing cytosolic calcium during heart muscle relaxation. Here, we tested the hypothesis that SERCA2a over-expression may mitigate electrocardiography (ECG) abnormalities in old female mdx mice, a murine model of DMD cardiomyopathy.', '1 × 10(12) viral genome particles/mouse of adeno-associated virus serotype-9 (AAV-9) SERCA2a vector was delivered to 12-m-old female mdx mice (N = 5) via a single bolus tail vein injection. AAV transduction and the ECG profile were examined eight months later.', 'The vector genome was detected in the hearts of all AAV-injected mdx mice. Immunofluorescence staining and western blot confirmed SERCA2a over-expression in the mdx heart. Untreated mdx mice showed characteristic tachycardia, PR interval reduction and QT interval prolongation. AAV-9 SERCA2a treatment corrected these ECG abnormalities.'] Does sERCA2a gene transfer improve electrocardiographic performance in aged mdx mice? | qiaojin/PubMedQA | 2 | [
-2.3186585903167725,
-1.4337835311889648,
2.795166015625
] |
['The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simple epithelium even across species and classes, and can partially restore features of differentiated tissue to mouse mammary tumours in co-culture experiments. Despite these exciting properties, the molecular identity of embryonic mammary cells remains to be fully characterised.', 'Here, we define the transcriptome of the mammary primordium and the two distinct cellular compartments that comprise it, the mammary primordial bud epithelium and mammary mesenchyme. Pathway and network analysis was performed and comparisons of embryonic mammary gene expression profiles to those of both postnatal mouse and human mammary epithelial cell sub-populations and stroma were made.', 'Several of the genes we have detected in our embryonic mammary cell signatures were previously shown to regulate mammary cell fate and development, but we also identified a large number of novel candidates. Additionally, we determined genes that were expressed by both embryonic and postnatal mammary cells, which represent candidate regulators of mammary cell fate, differentiation and progenitor cell function that could signal from mammary lineage inception during embryogenesis through postnatal development. Comparison of embryonic mammary cell signatures with those of human breast cells identified potential regulators of mammary progenitor cell functions conserved across species.'] Does transcriptome analysis of embryonic mammary cells reveal insights into mammary lineage establishment? | qiaojin/PubMedQA | 2 | [
-2.4814274311065674,
-0.709657609462738,
2.3489530086517334
] |
['Cerebral tissue oxygen level modifies crucial processes of neurogenesis, glial and neuronal development during physiological and hypoxic conditions. Whether hypoxia-sensitive factors such as doublecortin (DCX) and hypoxia-inducible transcription factor (HIF)-regulated CXCR4 and SDF-1 modify and activate adaptation to hypoxia in developing brain is not well understood. Present study investigated maturational regulation of oxygen-sensitive developmental genes and proteins in developing mouse brain in relation to the degree of hypoxia.', 'Physiological expression of HIF-1, CXCR4, SDF-1 and DCX were analyzed in the brain of C57/BL6 mice (P0-P60). In addition, mice (P0, P7) were exposed to normoxia, acute (8% O(2), 6 h) or chronic hypoxia (10% O(2), 7 d) followed by reoxygenation. Gene expression was analyzed by quantitative PCR, proteins were quantified by Western blot analysis and immunohistochemistry.', 'Cerebral HIF-1α protein, CXCR4 and DCX mRNA levels showed maturational stage-related peak levels at P0/P1, whereas SDF-1 mRNA levels were highest at P17. CXCR4 and SDF-1 mRNA levels were not altered in response to hypoxia. Whereas DCX mRNA levels significantly increased during acute hypoxia, down-regulation of DCX transcripts was found in response to chronic hypoxia compared to controls, and these changes were related to specifically vulnerable brain regions.'] Does systemic hypoxia differentially affect neurogenesis during early mouse brain maturation? | qiaojin/PubMedQA | 2 | [
-2.3565351963043213,
-1.1550408601760864,
2.574472427368164
] |
['Men who have a brother with prostate cancer have a 2-fold increased risk of being diagnosed with prostate cancer. Strategies employed by these men to reduce prostate cancer risk are not well understood. Preliminary studies have shown that men with a family history of prostate cancer have a high rate of vitamin and supplement usage aimed at the prevention of prostate cancer.', 'The authors analyzed data from a cross-sectional study of men with familial and hereditary prostate cancer and their unaffected brothers. A total of 542 unaffected men who had at least one brother who had been diagnosed with prostate cancer regarding their use of vitamins and supplements, as well as the motivation for use, were interviewed.', 'The associations between subject characteristics and vitamin and supplement use were evaluated using an unconditional logistic regression modeling approach.', 'Overall, 59.2% and 36.5% of men reported ever using and currently using, respectively, one or more vitamins or supplements (including multivitamins). One third of men took a vitamin or supplement that has been targeted for prostate health or cancer prevention, including green tea, magnesium, male hormones, saw palmetto, selenium, soy, vitamins A, C, E, and zinc. Increasing age at time of survey was associated with vitamin/supplement use (odds ratio [OR] = 1.03; 95% confidence interval [CI] = 1.01-1.05). After adjusting for age at time of survey, being younger than an affected brother was associated with vitamin and supplement use (OR = 1.51; 95% CI = 1.01-2.25). A total of 25% of men reported obtaining information from books or articles as the most common source of information.'] Does prevalence and correlate of vitamin and supplement usage among men with a family history of prostate cancer? | qiaojin/PubMedQA | 2 | [
0.09701631218194962,
-1.2296096086502075,
0.20735739171504974
] |
['Spinocerebellar ataxia (SCA) refers to a disease entity in which polyglutamine aggregates are over-produced in Purkinje cells (PCs) of the cerebellum as well as other neurons in the central nervous system, and the formation of intracellular polyglutamine aggregates result in the loss of neurons as well as deterioration of motor functions. So far there is no effective neuroprotective treatment for this debilitating disease although numerous efforts have been made. Mesenchymal stem cells (MSCs) possess multi-lineage differentiation potentials as well as immuno-modulatory properties, and are theoretically good candidates for SCA treatment. The purpose of this study is to investigate whether transplantation of human MSCs (hMSCs) can rescue cerebellar PCs and ameliorate motor function deterioration in SCA in a pre-clinical animal model.', 'Transgenic mice bearing poly-glutamine mutation in ataxin-2 gene (C57BL/6J SCA2 transgenic mice) were serially transplanted with hMSCs intravenously or intracranially before and after the onset of motor function loss. Motor function of mice was evaluated by an accelerating protocol of rotarod test every 8 weeks. Immunohistochemical stain of whole brain sections was adopted to demonstrate the neuroprotective effect of hMSC transplantation on cerebellar PCs and engraftment of hMSCs into mice brain.', 'Intravenous transplantation of hMSCs effectively improved rotarod performance of SCA2 transgenic mice and delayed the onset of motor function deterioration; while intracranial transplantation failed to achieve such neuroprotective effect. Immunohistochemistry revealed that intravenous transplantation was more effective in the preservation of the survival of cerebellar PCs and engraftment of hMSCs than intracranial injection, which was compatible to rotarod performance of transplanted mice.'] Does mesenchymal stem cell transplantation ameliorate motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells? | qiaojin/PubMedQA | 2 | [
-2.4788320064544678,
-1.3082420825958252,
2.8533921241760254
] |
['Prehospital cooling of acute stroke patients would be ideal when associated with minor or no side effects. Therefore, we evaluated a cooling cap for the surface of head and cervical regions in awake volunteers.', '10 healthy volunteers were treated by external cooling for 190 min using a gel-based cooling device. Vital signs, rectal temperature, tympanic temperature, the extent of shivering and individual perception of frostiness and discomfort were measured.', 'All participants (median age 35 years) successfully completed the treatment and experienced only mild to moderate discomfort. No serious adverse events and no shivering were noticed. There was a significant drop in the tympanic temperature to 34.68°C (difference from baseline: 1.7°C, 95% CI: 0.61-2.7°C, p = 0.001), in the rectal temperature to 36.65°C (difference from baseline: 0.65°C, 95% CI: 0.06-1.2°C, p = 0.019) and in the heart rate (difference from baseline: 15 beats/min, 95% CI: 0.63-30 beats/min, p = 0.035).'] Does local head and neck cooling lead to hypothermia in healthy volunteers? | qiaojin/PubMedQA | 2 | [
-1.353072166442871,
-1.2492008209228516,
1.6335041522979736
] |
['The number of HIV infections in Taiwan has been increasingly linear in recent years. At the close of April 2009, Taiwan registered 17, 979 AIDS infections. The average annual infection rate has grown an average 18% during the most recent five year period. Apart from medical problems, the social and psychological problems associated with AIDS are becoming increasingly complicated both in Taiwan and globally with the increasing number of HIV infections. Identifying the knowledge needs of nursing staff members for providing appropriate nursing care to HIV/AIDS patients is important to planning effective in-service nursing education programs. Quality of both patient care and professional development can be promoted.', 'This study investigated the HIV/AIDS educational needs of nursing staffs and variations in care knowledge needs by individual background. Results provide a reference for in-service education program planners.', 'This was a descriptive and correlational study design that used self-structured questionnaires to conduct a cross-sectional survey. A total of 556 structural questionnaires were distributed and 546 completed questionnaires were returned (response rate = 98.2%) and used in data analysis.', 'The average knowledge need score for nursing staffs with regard to HIV/AIDS patient care was > 4 points. The highest three mean scores were (in rank order): follow-up treatment for victims after sexual assault, prevention of injury (e.g., sharp objects, exposure to infected body fluids) and subsequent management, and nursing care of opportunistic infection. The lowest three mean scores were (in rank order): HIV epidemiology, Taiwan HIV policies and regulations, and HIV transmission routes. Nurses who were older, married, or held senior nurse positions had more knowledge needs.'] Does [ A needs assessment of nursing staff AIDS care knowledge need ]? | qiaojin/PubMedQA | 1 | [
-1.4843109846115112,
0.9581443667411804,
-0.3532901406288147
] |
['The challenge of resident education in urologic surgery programs is to overcome disparity imparted by diverse patient populations, limited training times, and inequalities in the availability of expert surgical educators. Specifically, in the area of prosthetic urology, only a small proportion of programs have full-time faculty available to train residents in this discipline.', 'To examine whether a new model using yearly training sessions from a recognized expert can establish a successful penile prosthetics program and result in better outcomes, higher case volumes, and willingness to perform more complex surgeries.', 'A recognized expert conducted one to two operative training sessions yearly to teach standardized technique for penile prosthetics to residents. Each session consisted of three to four operative cases performed under the direct supervision of the expert. Retrospective data were collected from all penile prosthetic operations before (February, 2000 to June, 2004: N = 44) and after (July, 2004 to October, 2007: N = 79) implementation of these sessions.', "Outcomes reviewed included patient age, race, medical comorbidities, operative time, estimated blood loss, type of prosthesis, operative approach, drain usage, length of stay, and complications including revision/explantation rates. Statistical analysis was performed using Student's t-tests, Fisher's tests, and survival curves using the Kaplan-Meier technique (P value ≤ 0.05 to define statistical significance).", 'Patient characteristics were not significantly different pre- vs. post-training. Operative time and estimated blood loss significantly decreased. Inflatable implants increased from 19/44 (43.2%, pre-training) to 69/79 (87.3%, post-training) (P < 0.01). Operations per year increased from 9.96 (pre-training) to 24 (post-training) (P < 0.01). Revision/explantation occurred in 11/44 patients (25%, pre-training) vs. 7/79 (8.9%, post-training) (P < 0.05).'] Does expert training with standardized operative technique help establish a successful penile prosthetics program for urologic resident education? | qiaojin/PubMedQA | 2 | [
-1.9398375749588013,
-0.990946352481842,
1.9721529483795166
] |
["Postpartum sexual health education was once routinely administered to postpartum women, but few interventions were specifically described or clearly based on theory, and few sexual interventions affected women's sexual behaviors.", "To evaluate the effectiveness of a refined theory-based interactive postpartum sexual health education program (IPSHEP) in enhancing postpartum women's sexual behavior and health.", 'For this prospective, randomized controlled trial, 250 participants were randomized to three groups. Experimental group A received our refined theory-based IPSHEP. Experimental group B received only an interactive, self-help pamphlet. The control group received routine education (a 10- to 15-minute educational talk and a sexual health pamphlet without an interactive design). Data were collected at baseline, 3 days, 2 months, and 3 months postpartum.', "Postpartum women's sexual self-efficacy (SSE), diversity of sexual activity (DSA), return to sexual activity, and sexual satisfaction (SS).", 'Women who received our theory-based postpartum sexual health education program had significantly greater SSE (P\u2003<\u20030.05) and greater DSA (P\u2003<\u20030.05), and tended to resume their sexual life earlier than women in the routine teaching and interactive pamphlet-only groups (P\u2003<\u20030.05). However, the SS levels of postpartum women who received our program did not differ significantly from those of women who received routine teaching or the interactive pamphlet only.'] Does transtheoretical model-based postpartum sexual health education program improve women 's sexual behaviors and sexual health? | qiaojin/PubMedQA | 2 | [
-2.2424912452697754,
-0.17513319849967957,
1.5043156147003174
] |
['Tumor cells can move as individual cells in two interconvertible modes: mesenchymal mode and amoeboid mode. Cytoskeleton rearrangement plays an important role in the interconversion. Previously, we reported that HAb18G/CD147 and annexin II are interacting proteins involved in cytoskeleton rearrangement, yet the role of their interaction is unclear. In this study we found that the depletion of HAb18G/CD147 produced a rounded morphology, which is associated with amoeboid movement, whereas the depletion of annexin II resulted in an elongated morphology, which is associated with mesenchymal movement. The extracellular portion of HAb18G/CD147 can interact with a phosphorylation-inactive mutant of annexin II and inhibit its phosphorylation. HAb18G/CD147 inhibits Rho signaling pathways and amoeboid movement by inhibiting annexin II phosphorylation, promotes membrane localization of WAVE2 and Rac1 activation by way of the integrin-FAK-PI3K/PIP3 signaling pathway, and promotes the formation of lamellipodia and mesenchymal movement.'] Does hAb18G/CD147 promote cell motility by regulating annexin II-activated RhoA and Rac1 signaling pathways in hepatocellular carcinoma cells? | qiaojin/PubMedQA | 2 | [
-2.401289701461792,
-1.086141586303711,
2.489673614501953
] |
['MiR-637 (microRNA-637) is a primate-specific miRNA belonging to the small noncoding RNA family, which represses gene regulation at the post-transcriptional expression level. Although it was discovered approximately 5 years ago, its biomedical significance and regulatory mechanism remain obscure. Our preliminary data showed that miR-637 was significantly suppressed in four HCC cell lines and, also, in most of the hepatocellular carcinoma (HCC) specimens, thereby suggesting that miR-637 would be a tumor suppressor in HCC. Simultaneously, the enforced overexpression of miR-637 dramatically inhibited cell growth and induced the apoptosis of HCC cells. The transcription factor, signal transducer and activator of transcription 3 (Stat3), is constitutively activated in multiple tumors, and aberrant Stat3 activation is linked to the promotion of growth and desensitization of apoptosis. Our study showed that Stat3 tyrosine 705 phosphorylation and several Stat3-regulated antiapoptotic genes were down-regulated in miR-637 mimics-transfected and Lv-miR637-infected HCC cells. In addition, miR-637 overexpression negatively regulated Stat3 phosphorylation by suppressing autocrine leukemia inhibitory factor (LIF) expression and exogenous LIF-triggered Stat3 activation and rescued cell growth in these cells. A nude mice model also demonstrated the above-described results, which were obtained from the cell model. Furthermore, we found that LIF was highly expressed in a large proportion of HCC specimens, and its expression was inversely associated with miR-637 expression.'] Does primate-specific microRNA-637 inhibit tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling? | qiaojin/PubMedQA | 2 | [
-2.1558098793029785,
-1.1523066759109497,
2.3044233322143555
] |
['Modified function of immune cells in nasal secretions may play a role in the enhanced susceptibility to respiratory viruses that is seen in smokers. Innate immune cells in nasal secretions have largely been characterized by cellular differentials using morphologic criteria alone, which have successfully identified neutrophils as a significant cell population within nasal lavage fluid (NLF) cells. However, flow cytometry may be a superior method to fully characterize NLF immune cells. We therefore characterized immune cells in NLF by flow cytometry, determined the effects of live attenuated influenza virus (LAIV) on NLF and peripheral blood immune cells, and compared responses in samples obtained from smokers and nonsmokers.', 'In a prospective observational study, we characterized immune cells in NLF of nonsmokers at baseline using flow cytometry and immunohistochemistry. Nonsmokers and smokers were inoculated with LAIV on day 0 and serial nasal lavages were collected on days 1-4 and day 9 post-LAIV. LAIV-induced changes of NLF cells were characterized using flow cytometry. Cell-free NLF was analyzed for immune mediators by bioassay. Peripheral blood natural killer (NK) cells from nonsmokers and smokers at baseline were stimulated in vitro with LAIV followed by flow cytometric and mediator analyses.', 'CD45(+)CD56(-)CD16(+) neutrophils and CD45(+)CD56(+) NK cells comprised median 4.62% (range 0.33-14.52) and 23.27% (18.29-33.97), respectively, of non-squamous NLF cells in nonsmokers at baseline. LAIV did not induce changes in total NK cell or neutrophil percentages in either nonsmokers or smokers. Following LAIV inoculation, CD16(+) NK cell percentages and granzyme B levels increased in nonsmokers, and these effects were suppressed in smokers. LAIV inoculation enhanced expression of activating receptor NKG2D and chemokine receptor CXCR3 on peripheral blood NK cells from both nonsmokers and smokers in vitro but did not induce changes in CD16(+) NK cells or granzyme B activity in either group.'] Is nasal lavage natural killer cell function suppressed in smokers after live attenuated influenza virus? | qiaojin/PubMedQA | 2 | [
-2.1203773021698,
-1.475644826889038,
2.6030116081237793
] |
['Fusobacterium nucleatum is a heterogeneous oral pathogen that is also a common resident of the human gut mucosa. Given that some strains of F. nucleatum are known to be invasive and proinflammatory in the oral mucosa, we compared strains isolated from patients with inflammatory bowel disease (IBD) with strains isolated from healthy controls to determine 1) whether this species was more commonly associated with IBD patients; and 2) whether gut-derived F. nucleatum strains from IBD patients showed an increased capacity for invasion.', 'Biopsy material was obtained from 56 adult patients undergoing colonoscopy for colon cancer screening purposes or assessment of irritable bowel syndrome status (34 patients), or to assess for presence of gastrointestinal disease (i.e., IBD or indeterminate colitis, 22 patients). We enumerated Fusobacterium spp. strains isolated from human gut biopsy material in a blinded fashion, and then compared the virulence potential of a subset of F. nucleatum strains using an invasion assay in a Caco-2 model system.', 'Fusobacterium spp. were isolated from 63.6% of patients with gastrointestinal disease compared to 26.5% of healthy controls (P = 0.01). In total, 69% of all Fusobacterium spp. recovered from patients were identified as F. nucleatum. F. nucleatum strains originating from inflamed biopsy tissue from IBD patients were significantly more invasive in a Caco-2 cell invasion assay than strains that were isolated from healthy tissue from either IBD patients or control patients (P < 0.05 to 0.001).'] Does invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlate with IBD status of the host? | qiaojin/PubMedQA | 2 | [
-2.193927764892578,
-1.2734988927841187,
2.537101984024048
] |
['The pregnane X receptor (PXR/NR1I2) is an important regulator of xenobiotic metabolism and intestinal integrity. However, there are controversial studies on the role of PXR/NR1I2 in inflammatory bowel disease (IBD). We therefore initiated the largest analysis to date on PXR/NR1I2 gene variants in IBD patients.', "Genomic DNA from 2823 individuals of Caucasian origin including 859 patients with Crohn's disease (CD), 464 patients with ulcerative colitis (UC), and 1500 healthy, unrelated controls was analyzed for eight PXR/NR1I2 single nucleotide polymorphisms (SNPs) (rs12721602 (-25564), rs3814055 (-25385), rs1523128 (-24756), rs1523127 (-24381), rs45610735 = p.Gly36Arg (+106), rs6785049 (+7635), rs2276707 (+8055), and rs3814057 (+11156)). In addition, detailed haplotype and genotype-phenotype analyses were performed.", 'The PXR/NR1I2 SNP rs2276707 was weakly associated with UC susceptibility (P = 0.01; odds ratio [OR] 1.27 [1.06-1.52]). None of the other PXR/NR1I2 SNPs were associated with UC or CD susceptibility. However, several rare PXR/NR1I2 haplotypes were highly associated with CD susceptibility. In CD, the strongest disease association was found for a haplotype consisting of the SNPs rs12721602-rs3814055-rs1523128-rs1523127-rs12721607-rs6785049-rs2276707-rs3814057 (omnibus P-value: 6.50 × 10(-15)) which was found in two separate cohorts (cohort I = discovery cohort: CD: n = 492, controls: n = 793; P = 4.51 × 10(-17); Bonferroni corrected: P = 1.27 × 10(-15); cohort II = replication cohort: CD: n = 367, controls: n = 707; P = 7.12 × 10(-4); P(corr) = 1.99 × 10(-2)).'] Do pregnane X receptor ( PXR/NR1I2 ) gene haplotypes modulate susceptibility to inflammatory bowel disease? | qiaojin/PubMedQA | 2 | [
-1.2350302934646606,
-1.6792761087417603,
1.8976759910583496
] |
['Very low-density lipoprotein (VLDL) secretion provides a mechanism to export triglycerides (TG) from the liver to peripheral tissues, maintaining lipid homeostasis. In nonalcoholic fatty liver disease (NAFLD), VLDL secretion disturbances are unclear. Methionine adenosyltransferase (MAT) is responsible for S-adenosylmethionine (SAMe) synthesis and MAT I and III are the products of the MAT1A gene. Deficient MAT I and III activities and SAMe content in the liver have been associated with NAFLD, but whether MAT1A is required for normal VLDL assembly remains unknown. We investigated the role of MAT1A on VLDL assembly in two metabolic contexts: in 3-month-old MAT1A-knockout mice (3-KO), with no signs of liver injury, and in 8-month-old MAT1A-knockout mice (8-KO), harboring nonalcoholic steatohepatitis. In 3-KO mouse liver, there is a potent effect of MAT1A deletion on lipid handling, decreasing mobilization of TG stores, TG secretion in VLDL and phosphatidylcholine synthesis via phosphatidylethanolamine N-methyltransferase. MAT1A deletion also increased VLDL-apolipoprotein B secretion, leading to small, lipid-poor VLDL particles. Administration of SAMe to 3-KO mice for 7 days recovered crucial altered processes in VLDL assembly and features of the secreted lipoproteins. The unfolded protein response was activated in 8-KO mouse liver, in which TG accumulated and the phosphatidylcholine-to-phosphatidylethanolamine ratio was reduced in the endoplasmic reticulum, whereas secretion of TG and apolipoprotein B in VLDL was increased and the VLDL physical characteristics resembled that in 3-KO mice. MAT1A deletion also altered plasma lipid homeostasis, with an increase in lipid transport in low-density lipoprotein subclasses and decrease in high-density lipoprotein subclasses.'] Does methionine adenosyltransferase 1A gene deletion disrupt hepatic very low-density lipoprotein assembly in mice? | qiaojin/PubMedQA | 2 | [
-2.3200509548187256,
-1.3837649822235107,
2.712620496749878
] |
['Many surgeons use absorbable packing materials after endoscopic sinus surgery (ESS). Despite their popularity, some of these agents have been shown to contribute to synechiae formation. Microporous polysaccharide hemospheres (MPH) is a plant-based hemostatic powder that does not interfere with regenerating sinus mucosa in the animal model. The goal of this study was to examine the impact of MPH on healing and synechiae formation after ESS in human subjects.', 'A prospective, randomized, controlled, double-blind study was performed. Forty consenting adult patients with chronic sinusitis requiring symmetric ESS were randomized to receive MPH unilaterally at the conclusion of surgery. The opposite side was untreated. Standard postoperative care was performed bilaterally. Outcomes measured included blinded observer ratings for synechiae formation, edema, and infection. Each side was examined endoscopically and scored at postoperative days 7, 14, and 30.', 'Twenty men and 20 women with an average age of 48.2 years were included. There were no complications and all patients were discharged home the same day. There was no significant difference in synechiae formation at any point postoperatively. The rate of synechiae formation was determined to be 10% (4/40) on the MPH-treated side versus 7.5% (3/40) on the untreated side (p = 0.7639). In addition, there were no significant differences observed in edema (p = 0.7480) or infection (p = 0.5533).'] Do microporous polysaccharide hemospheres increase synechiae after sinus surgery : randomized controlled study? | qiaojin/PubMedQA | 2 | [
-1.6278443336486816,
-1.5703610181808472,
2.164207935333252
] |
['Mortality rates for advanced lung cancer have not declined for decades, even with the implementation of novel chemotherapeutic regimens or the use of tyrosine kinase inhibitors. Cancer Stem Cells (CSCs) are thought to be responsible for resistance to chemo/radiotherapy. Therefore, targeting CSCs with novel compounds may be an effective approach to reduce lung tumor growth and metastasis. We have isolated and characterized CSCs from non-small cell lung cancer (NSCLC) cell lines and measured their telomerase activity, telomere length, and sensitivity to the novel telomerase inhibitor MST312.', 'The aldehyde dehydrogenase (ALDH) positive lung cancer cell fraction is enriched in markers of stemness and endowed with stem cell properties. ALDH+ CSCs display longer telomeres than the non-CSC population. Interestingly, MST312 has a strong antiproliferative effect on lung CSCs and induces p21, p27 and apoptosis in the whole tumor population. MST312 acts through activation of the ATM/pH2AX DNA damage pathway (short-term effect) and through decrease in telomere length (long-term effect). Administration of this telomerase inhibitor (40 mg/kg) in the H460 xenograft model results in significant tumor shrinkage (70% reduction, compared to controls). Combination therapy consisting of irradiation (10Gy) plus administration of MST312 did not improve the therapeutic efficacy of the telomerase inhibitor alone. Treatment with MST312 reduces significantly the number of ALDH+ CSCs and their telomeric length in vivo.'] Does inhibition of telomerase activity preferentially target aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer? | qiaojin/PubMedQA | 2 | [
-2.2860381603240967,
-1.3422842025756836,
2.642305850982666
] |
['The impact of walking and bicycling on insulin resistance (IR) in women with abdominal obesity is unclear.', 'Pooled analysis of data from a randomized trial on physically active commuting (bicycling + walking vs walking only) in women with abdominal obesity [n = 98; age:47.3 ± 7.6 yrs; waist circumference (WC):103.1 ± 7.8 cm]. Bicycling and walking data were collected during 7 consecutive days by trip meters (Trelock FC-410) and pedometers (Yamax digiwalker SW-200) at baseline, 2, 4, and 6 months. Owing to a skew distribution we analyzed bicycling as a binary dummy variable with a 10 km/week cut-off. Fasting serum insulin and homeostatic model assessment - insulin resistance (HOMA-IR) were assessed at baseline and 6 months, as were body mass index (BMI), WC, and dual x-ray absorptiometry (DXA)-assessed % whole-body fat.', 'Increased bicycling by 10 km/wk was associated with reductions in fasting serum insulin at follow-up independent of age, treatment allocation, baseline phenotype, Δ walking, and Δ % body fat (β = -10.9, P = .042), but not HOMA-IR (β = -2.0, P = .13). Increased walking was not associated with fasting serum insulin (P = .33) or HOMA-IR (P = .44) at follow-up, after adjustment for the same covariates and Δ bicycling.'] Is bicycling but not walking independently associated with fasting insulin in abdominally obese women? | qiaojin/PubMedQA | 2 | [
-1.732646107673645,
-1.544698715209961,
2.3052825927734375
] |
['Recognition of trauma-induced coagulopathy by conventional coagulation testing (CCT) is limited by their slow results, incomplete characterization, and their poor predictive nature. Rapid thrombelastography (r-TEG) delivers a more comprehensive assessment of the coagulation system but has not been prospectively validated in trauma patients. The purpose of this pilot study was to evaluate the timeliness of r-TEG results, their correlation with CCTs, and the ability of r-TEG to predict early blood transfusion.', 'Over a 5-month period, 583 consecutive major trauma activations were prospectively entered into a database, of which 272 met entry criteria. r-TEG and CCTs (prothrombin time, international normalized ratio, partial thromboplastin time, and platelet count) were obtained on all patients. Graphical results for r-TEG were displayed "real time" in the trauma bay. Spearman\'s correlation and regression models were used to compare r-TEG and CCTs.', 'Early r-TEG values (activated clotting time [ACT], k-time, and r-value) were available within 5 minutes, late r-TEG values (maximal amplitude and α-angle) within 15 minutes, and CCTs within 48 minutes (p < 0.001). ACT, r-value, and k-time showed strong correlation with prothrombin time, international normalized ratio, and partial thromboplastin time (all r >0.70; p < 0.001), whereas maximal amplitude (r = -0.49) and α-angle (r = 0.40) correlated with platelet count (both p < 0.001). Linear regression demonstrated ACT predicted red blood cells (coef. 0.05; 95% confidence interval [CI], 0.04-0.06; p < 0.001), plasma (coef. 0.03; 95% CI, 0.02-0.04; p < 0.001), and platelet (coef. 0.06; 95% CI, 0.04-0.07; p < 0.001) transfusions within the first 2 hours of arrival. Controlling for all demographics and Emergency Department vitals, ACT >128 predicted massive transfusion (≥10 U) in the first 6 hours (odds ratio, 5.15; 95% CI, 1.36-19.49; p = 0.01). In addition, ACT <105 predicted patients who did not receive any transfusions in the first 24 hours (odds ratio, 2.80; CI, 1.02-7.07; p = 0.04).'] Does rapid thrombelastography deliver real-time results that predict transfusion within 1 hour of admission? | qiaojin/PubMedQA | 2 | [
-1.675923228263855,
-1.6363904476165771,
2.258044719696045
] |
['We examined the effect of thrombomodulin (TM) domains 2 and 3 (TMD23) on human early endothelial progenitor cells (EPCs).', 'TM was expressed and released by human EPCs cultured from peripheral blood mononuclear cells (PBMCs). Addition of TMD23 (100 ng/mL) to the cultured PBMCs increased the colony-forming units, chemotactic motility, matrix metalloproteinase activity, and interleukin-8 secretion but decreased tumor necrosis factor-α (TNF-α) release. Analysis of the signal pathway showed that TMD23 activated Akt. Inhibition of phosphatidylinositol-3 kinase-Akt blocked the effects of TMD23 on chemotactic motility, matrix metalloproteinase-9, interleukin-8, and TNF-α. In hindlimb ischemia mice, laser Doppler perfusion imaging of the ischemic limb during the 21 days after arterial ligation showed that the perfusion recovered best with intraperitoneal infusion of TMD23 plus local injection of early EPCs, followed by either infusion of TMD23 or injection of the cells. Animals without either treatment had the worst results. Animals treated with TMD23 also had lower circulating and tissue levels of TNF-α.'] Is therapeutic angiogenesis of human early endothelial progenitor cells enhanced by thrombomodulin? | qiaojin/PubMedQA | 2 | [
-2.40510630607605,
-1.413212776184082,
2.863010883331299
] |
['Scavenger receptor BI (SR-BI) is a high-density lipoprotein (HDL) receptor. Recent studies revealed that SR-BI protects against sepsis via modulating innate immunity. However, its role in adaptive immunity is unclear.', 'SR-BI-null mice exhibited impaired lymphocyte homeostasis as shown by splenomegaly and imbalanced expansion of T and B lymphocytes in the spleens. Importantly, the activated T and B lymphocytes were increased 3- to 4-fold, indicating a heightened active status of T and B lymphocytes. More importantly, in line with the accumulation of the activated T and B lymphocytes, SR-BI-null mice developed systemic autoimmune disorders characterized by the presence of autoantibodies in circulation, the deposition of immune complexes in glomeruli, and the leukocyte infiltration in kidney. Further analyses revealed that SR-BI deficiency enhanced lymphocyte proliferation, caused imbalanced interferon-γ and interleukin-4 production in lymphocytes, and caused elevated inflammatory cytokine production in macrophages. Furthermore, HDL from SR-BI-null mice exhibited less capability of suppressing lymphocyte proliferation.'] Does deficiency of scavenger receptor BI lead to impaired lymphocyte homeostasis and autoimmune disorders in mice? | qiaojin/PubMedQA | 2 | [
-2.339993715286255,
-1.2479901313781738,
2.6176393032073975
] |
['Chronic infection has long been postulated as a stimulus for atherogenesis. Pseudomonas aeruginosa infection has been associated with increased atherosclerosis in rats, and these bacteria produce a quorum-sensing molecule 3-oxo-dodecynoyl-homoserine lactone (3OC12-HSL) that is critical for colonization and virulence. Paraoxonase 2 (PON2) hydrolyzes 3OC12-HSL and also protects against the effects of oxidized phospholipids thought to contribute to atherosclerosis. We now report the response of human aortic endothelial cells (HAECs) to 3OC12-HSL and oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (Ox-PAPC) in relation to PON2 expression.', 'Using expression profiling and network modeling, we identified the unfolded protein response (UPR), cell cycle genes, and the mitogen-activated protein kinase signaling pathway to be heavily involved in the HAEC response to 3OC12-HSL. The network also showed striking similarities to a network created based on HAEC response to Ox-PAPC, a major component of minimally modified low-density lipoprotein. HAECs in which PON2 was silenced by small interfering RNA showed increased proinflammatory response and UPR when treated with 3OC12-HSL or Ox-PAPC.'] Does paraoxonase-2 modulate stress response of endothelial cells to oxidized phospholipids and a bacterial quorum-sensing molecule? | qiaojin/PubMedQA | 2 | [
-2.463590383529663,
-1.249767780303955,
2.7575764656066895
] |
['Vascular smooth muscle cell (SMC) proliferation has an indispensable role in the pathogenesis of vascular disease, but the mechanism is not fully elucidated. The epigenetic enzyme histone deacetylase 7 (HDAC7) is involved in endothelial homeostasis and SMC differentiation and could have a role in SMC proliferation. In this study, we sought to examine the effect of 2 HDAC7 isoforms on SMC proliferation and neointima formation.', 'We demonstrated that overexpression of unspliced HDAC7 (HDAC7u) could suppress SMC proliferation through downregulation of cyclin D1 and cell cycle arrest, whereas spliced HDAC7 (HDAC7s) could not. Small interfering RNA (siRNA)-mediated knockdown of HDAC7 increased SMC proliferation and induced nuclear translocation of β-catenin. Additional experiments showed that only HDAC7u could bind to β-catenin and retain it in the cytoplasm. Reporter gene assay and reverse transcription polymerase chain reaction revealed a reduction of β-catenin activity in cells overexpressing HDAC7u but not HDAC7s. Deletion studies indicated that the C-terminal region of HDAC7u is responsible for the interaction with β-catenin. However, the addition of amino acids to the N terminus of HDAC7u disrupted the binding, further strengthening our hypothesis that HDAC7s does not interact with β-catenin. The growth factor platelet-derived growth factor-BB increased the splicing of HDAC7 while simultaneously decreasing the expression of HDAC7u. Importantly, in an animal model of femoral artery wire injury, we demonstrated that knockdown of HDAC7 by siRNA aggravates neointima formation in comparison with control siRNA.'] Does splicing of histone deacetylase 7 modulate smooth muscle cell proliferation and neointima formation through nuclear β-catenin translocation? | qiaojin/PubMedQA | 2 | [
-2.36982798576355,
-1.2779291868209839,
2.6488561630249023
] |
['Nitric oxide (NO) and protein S-nitrosylation (SNO) play important roles in ischemic preconditioning (IPC)-induced cardioprotection. Mitochondria are key regulators of preconditioning, and most proteins showing an increase in SNO with IPC are mitochondrial. The aim of this study was to address how IPC transduces NO/SNO signaling to mitochondria in the heart.', 'In this study using Langendorff perfused mouse hearts, we found that IPC-induced cardioprotection was blocked by treatment with either N-nitro-L-arginine methyl ester (L-NAME, a constitutive NO synthase inhibitor), ascorbic acid (a reducing agent to decompose SNO), or methyl-?-cyclodextrin (M?CD, a cholesterol sequestering agent to disrupt caveolae). IPC not only activated AKT/eNOS signaling but also led to translocation of eNOS to mitochondria. M?CD treatment disrupted caveolar structure, leading to dissociation of eNOS from caveolin-3 and blockade of IPC-induced activation of the AKT/eNOS signaling pathway. A significant increase in mitochondrial SNO was found in IPC hearts compared to perfusion control, and the disruption of caveolae by M?CD treatment not only abolished IPC-induced cardioprotection, but also blocked the IPC-induced increase in SNO.', 'These results provide mechanistic insight into how caveolae/eNOS/NO/SNO signaling mediates cardioprotection induced by IPC.'] Does disruption of caveolae block ischemic preconditioning-mediated S-nitrosylation of mitochondrial proteins? | qiaojin/PubMedQA | 2 | [
-2.4563376903533936,
-1.2695435285568237,
2.751507520675659
] |
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