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['The triggering receptor expressed on myeloid cells-1 (TREM-1) is known to be expressed during bacterial infections. We investigated whether TREM-1 is also expressed in non-infectious inflammation following traumatic lung contusion.', 'In a study population of 45 adult patients with multiple trauma and lung contusion, we obtained bronchoalveolar lavage (BAL) (blind suctioning of 20 ml NaCl (0.9%) via jet catheter) and collected blood samples at two time points (16 hours and 40 hours) after trauma. Post hoc patients were assigned to one of four groups radiologically classified according to the severity of lung contusion based on the initial chest tomography. Concentration of soluble TREM-1 (sTREM-1) and bacterial growth were determined in the BAL. sTREM-1, IL-6, IL-10, lipopolysaccharide binding protein, procalcitonin, C-reactive protein and leukocyte count were assessed in blood samples. Pulmonary function was evaluated by the paO2/FiO2 ratio.', 'Three patients were excluded due to positive bacterial growth in the initial BAL. In 42 patients the severity of lung contusion correlated with the levels of sTREM-1 16 hours and 40 hours after trauma. sTREM-1 levels were significantly (P < 0.01) elevated in patients with severe contusion (2,184 pg/ml (620 to 4,000 pg/ml)) in comparison with patients with mild (339 pg/ml (135 to 731 pg/ml)) or no (217 pg/ml (97 to 701 pg/ml)) contusion 40 hours following trauma. At both time points the paO2/FiO2 ratio correlated negatively with sTREM-1 levels (Spearman correlation coefficient = -0.446, P < 0.01).'] Is soluble triggering receptor on myeloid cells-1 expressed in the course of non-infectious inflammation after traumatic lung contusion : a prospective cohort study?
qiaojin/PubMedQA
2
[ -1.5481475591659546, -1.6521626710891724, 2.2095165252685547 ]
['Recent evidence suggests that the quantity of intra-abdominal fat may be a more important predictor of postoperative complications than body mass index (BMI). We hypothesized that increased intra-abdominal fat would be associated with longer operations, increased blood loss, more complications, and prolonged length of stay after pancreatic resection.', 'Retrospective cohort study. Intra-abdominal fat was quantified using CT imaging, and patients were divided into three groups (low, moderate, high). Unconditional multiple logistic regression was used to evaluate the relationship between obesity measures and complications.', 'Between 2002 and 2010, 255 patients underwent pancreaticoduodenectomy or distal pancreatectomy, and 201 had preoperative CT imaging available for review. Operative time was significantly prolonged in patients with high quantities of intra-abdominal fat compared with those with low fat quantity (median 438 versus 354 min, P < 0.05), while BMI was not associated with changes in duration of surgery. Neither obesity defined by BMI (OR 0.90, 95% CI 0.36-2.21) nor visceral fat (OR 1.20, 95% CI 0.46-3.16) significantly predicted risk of complications. Median length of stay was similar in patients who were obese by BMI (7 versus 7.5 d) or amount of intra-abdominal fat (7 d).'] Does obesity increase complications following pancreatic surgery?
qiaojin/PubMedQA
2
[ -1.094903826713562, -1.3619349002838135, 1.4696722030639648 ]
['Lower limb ischemia-reperfusion (I/R) elicits oxidative stress and causes inflammation in lung tissues that may lead to lung injury. Magnesium sulfate (MgSO(4)) possesses potent anti-oxidation and anti-inflammation capacity. We sought to elucidate whether MgSO(4) could mitigate I/R-induced lung injury. As MgSO(4) is an L-type calcium channel inhibitor, the role of the L-type calcium channels was elucidated.', 'Adult male rats were allocated to receive I/R, I/R plus MgSO(4) (10, 50, or 100 mg/kg), or I/R plus MgSO(4) (100 mg/kg) plus the L-type calcium channels activator BAY-K8644 (20 μg/kg) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After euthanization, degrees of lung injury, oxidative stress, and inflammation were determined.', 'Arterial blood gas and histologic assays, including histopathology, leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity), and lung water content, confirmed that I/R caused significant lung injury. Significant increases in inflammatory molecules (chemokine, cytokine, and prostaglandin E(2) concentrations) and lipid peroxidation (malondialdehyde concentration) confirmed that I/R caused significant inflammation and oxidative stress in rat lungs. MgSO(4), at the dosages of 50 and 100 mg/kg but not 10 mg/kg, attenuated the oxidative stress, inflammation, and lung injury induced by I/R. Moreover, BAY-K8644 reversed the protective effects of MgSO(4).'] Does magnesium sulfate mitigate lung injury induced by bilateral lower limb ischemia-reperfusion in rats?
qiaojin/PubMedQA
2
[ -2.289698362350464, -1.4143333435058594, 2.7150344848632812 ]
['Instillation of chemotherapy after transurethral resection (TUR) has been considered as an optimal treatment for non-muscle invasive bladder cancer (NMIBC). However, controversy remains regarding the role of chemotherapy instillation. We therefore evaluated the usefulness of continuous saline bladder irrigation (CSBI) after TUR.', 'Patients with intermediate risk NMIBC were treated by TUR followed by either CSBI (123 patients) or intravesical instillation of mitomycin C (115 patients). Recurrence-free rates were estimated using the Kaplan-Meier method.', 'No significant differences were observed in the recurrence-free rate, period to first recurrence, nor in frequency of recurrence between the CSBI and intravesical chemotherapy groups. Tumor progression rate and local toxicities were significantly higher in the intravesical chemotherapy group.'] Is continuous saline bladder irrigation after transurethral resection a prophylactic treatment choice for non-muscle invasive bladder tumor?
qiaojin/PubMedQA
2
[ -2.5675110816955566, -1.1079610586166382, 2.743497371673584 ]
['Easily assessable clinical predictors of response to chemotherapy in advanced castration-resistant prostate cancer (CRPC) are few. The objective of this retrospective study was to search for and identify such candidate predictors of outcome.', "A retrospective analysis of clinical data of CRPC patients entered in the Clinical Therapeutics' departmental prostate cancer database from 1996-2009 was performed. Univariate and multivariate analyses for progression-free survival and overall survival included patients receiving both docetaxel- and non-docetaxel-containing regimens.", 'From 1996 until June 2009, 286 out of 313 patients in our database were treated with chemotherapy. Prostate-specific antigen (PSA) reduction >30% correlated with improved survival irrespective of treatment. Beyond previously reported predictors, i.e. baseline PSA >30 ng/dl, hemoglobin below 10 mg/dl, weight loss, poor performance status, elevated lactic dehydrogenase and alkaline phosphatase, and time to CRPC of less than or equal to two years was associated with a poor overall survival and shorter progression-free survival upon univariate analysis. Pain was associated with shorter survival. Multivariate analysis confirmed time to CRPC, lactate dehydrogenase and alkaline phosphatase as independent predictors of overall and progression-free survival.'] Is time to castration resistance an independent predictor of castration-resistant prostate cancer survival?
qiaojin/PubMedQA
2
[ -2.3343005180358887, -1.3562997579574585, 2.7268786430358887 ]
['To investigate whether Thai HIV-1-infected pregnant women require a dose increase of lopinavir/ritonavir (LPV/r) and to assess the safety and efficacy of the generic tablets during pregnancy.', 'Prospective, single-center pharmacokinetic study.', 'HIV-infected pregnant, antiretroviral therapy-naive or experienced women started HAART containing generic LPV/r 400/100 mg tablets twice daily. The 12-h pharmacokinetic curves were recorded at gestational age 20 weeks (GA20, optional), 33 weeks (GA33) and 12 weeks postpartum (12PP, optional).', 'Twenty women were included. Median [interquartile range (IQR)] age was 28 (25-33) years and mean (SD) weight at GA33 was 59.9 (4.2) kg. Mean (SD) values for LPV area under the curve(0-12 h), C(max), C(min), and T(half) were 72.9 (19.2) mg/l h, 9.3 (2.2) mg/l, 3.2 (1.3) mg/l and 4.8 (2.4) h, respectively, on GA33 and 98.0 (24.1) mg/l h, 11.7 (2.2) mg/l, 4.7 (2.2) mg/l and 5.9 (2.7) h, respectively on 12PP. Twelve women recorded both GA33 and 12PP curves; mean LPV AUC(0-12) was significantly lower at GA33 [-24.1 (95% confidence interval -44.4 to -3.7) mg/l h]. At GA33, 19 of 20 women had sufficient LPV trough concentrations (>1.0 mg/l) and at 12PP, all had sufficient LPV trough concentrations. None of the women stopped LPV/r before planned discontinuation due to side-effects. At delivery, 19 of 20 women had a viral load below 50 copies/ml. One woman had a viral load of 60 copies/ml, but was undetectable at 12PP.'] Do thai HIV-1-infected women require a dose increase of lopinavir/ritonavir during the third trimester of pregnancy?
qiaojin/PubMedQA
2
[ -0.6467188596725464, -1.7874804735183716, 1.4998323917388916 ]
['Most HIV-infected individuals develop HIV-specific antibodies (Abs) exhibiting a common idiotype designated as 1F7. Expression of this idiotype establishes idiotypic-driven repertoire freeze, maintaining antibody responses ineffective at controlling autologous contemporaneous viruses. As such, this study investigated the temporal dynamics of 1F7-idiotype expression, as well as the role of this idiotype in the selection of HIV-specific broadly neutralizing antibodies (BnAbs).', 'This study investigated the timing of appearance and persistence of 1F7-idiotypic HIV-specific Abs by screening plasma samples from individuals followed longitudinally starting in primary HIV infection. The expression of 1F7 on HIV-specific BnAbs was also investigated to determine whether their development occurs within the context of 1F7-idiotypic repertoire freeze.', 'The 1F7 idiotype was detected on gp120, gp41 and membrane proximal external region (MPER) peptide-specific Abs using an enzyme-linked immunosorbent assay (ELISA). HIV-specific Abs in longitudinal plasma samples from six patients and six BnAbs were tested for the presence of the 1F7 idiotype.', 'The idiotype was expressed on HIV-specific Abs within 3 months of infection, with the magnitude of 1F7 detection increasing with time from infection. The 1F7 idiotype was also expressed on all BnAbs tested.'] Does selection of human anti-HIV broadly neutralizing antibodies occur within the context of frozen 1F7-idiotypic repertoire?
qiaojin/PubMedQA
2
[ -2.3552117347717285, -1.2394359111785889, 2.6639373302459717 ]
['Increased levels of small dense low-density lipoproteins (sd-LDL) have been reported more atherogenic compared to total low-density lipoprotein (LDL); however, no definitive experiments using macrophages have examined this concept in vitro.', 'In this study, we isolated fractions of total LDL (density 1.019-1.063 g/ml) and sd-LDL (density 1.044-1.063 g/ml) from the plasma of subjects with modest hypertriglycidemia. Oxidizabilty as assessed by copper-induced generation (1.6 µmol/L CuSO(4),12 h) of thiobarbituric acid reactive substances (TBARS) was significantly greater (7-fold higher, p < 0.01) for sd-LDL (4.3 ± 1.1 nmol/mg) than for total LDL (0.6 ± 0.2 nmol/mg) at the same cholesterol concentrations. Moreover, oxidized sd-LDL induced more lipid staining in macrophages than oxidized total LDL. When non-oxidized sd-LDL were incubated with THP1 macrophages, there was much greater lipid accumulation as assessed by oil red O staining, and more than a 2-fold increase (p < 0.05) in intracellular triglyceride content as compared to non-oxidized total LDL. Furthermore, non-oxidized sd-LDL in contrast to non-oxidized total LDL enhanced macrophage lectin-like oxidized LDL receptor-1 (LOX-1) protein expression and significantly LOX-1 mRNA levels (+158%, p < 0.05), with no effect on scavenger receptor A or CD36 gene expression. These effects of non-oxidized sd-LDL on LOX-1 gene expression were suppressed when Toll-like receptor 4 was inactivated either by RNAi or antibody.'] Does small dense LDL enhance THP-1 macrophage foam cell formation?
qiaojin/PubMedQA
2
[ -1.94465970993042, -1.5455584526062012, 2.5177671909332275 ]
['Studies indicate that the change from closed to open eyes in a resting condition results in an increase in skin conductance level (SCL) and a global decrease in EEG alpha activity, both indicative of increased arousal. Other studies show that ingestion of caffeine also produces SCL increase and alpha reduction. This study investigated the additivity of the effects of these two independent arousing variables.', 'EEG activity and SCL were recorded from 22 university students during both eyes-closed and eyes-open resting conditions, under the action of both caffeine and placebo, in a counterbalanced randomised double-blind study.', 'SCL increased significantly from eyes-closed to eyes-open conditions, and from placebo to caffeine, with no interaction. Global reductions in EEG alpha amplitude were apparent with opening of the eyes and caffeine ingestion; again, there was no interaction. Caffeine had a larger effect than opening the eyes on SCL, but their relative effect sizes were reversed in alpha. The two dependent measures showed the predicted negative correlation in both eyes-closed placebo and eyes-open caffeine conditions, with the latter substantially reduced relative to the former.'] Do caffeine and opening the eyes have additive effects on resting arousal measures?
qiaojin/PubMedQA
2
[ -2.223184823989868, -0.6846885681152344, 1.918582558631897 ]
['The transcription factor HOXC9 belongs to the homeobox gene family acting as developmental morphogen in several species. HOXC9 is EXPRESSED in different vascular beds in vivo. Yet vascular functions of HOXC9 have not been studied.', 'This study was aimed at characterizing HOXC9 functions in human vascular endothelial cells and in zebrafish vascular development.', 'HOXC9 was abundantly expressed in resting human umbilical vein endothelial cells and was downregulated by hypoxia. Overexpression of HOXC9 inhibited endothelial cell proliferation, migration, and tube formation in vitro. Expression profiling and chromatin immunoprecipitation experiments in human umbilical vein endothelial cells identified interleukin 8 as the major HOXC9 target and demonstrated the direct binding of HOXC9 to the interleukin 8 promotor. HOXC9 overexpression led to reduced endothelial interleukin 8 production, whereas HOXC9 silencing increased interleukin 8. The antimigratory and antiangiogenic effect of HOXC9 overexpression could be rescued by external interleukin 8 administration. Corresponding to the cellular experiments, endothelial-specific overexpression of HOXC9 and morpholino-based interleukin 8 loss-of-function experiments inhibited zebrafish vascular development.'] Does the transcription factor HOXC9 regulate endothelial cell quiescence and vascular morphogenesis in zebrafish via inhibition of interleukin 8?
qiaojin/PubMedQA
2
[ -2.489349603652954, -1.1977200508117676, 2.709432363510132 ]
['The aim of this study was to investigate the effect of three different climates on age at menopause and metabolic factors in postmenopausal women.', "Study population consisted of 232 postmenopausal women with natural menopause who admitted to Dr. Sami Ulus Maternity and Women's Health Teaching and Research Hospital Menopause outpatient clinic for routine check up. Participants were divided into three groups according to climate where they had lived during reproductive span. Black Sea, Mediterranean, and continental climate effects on age at menopause and metabolic factors were investigated.", 'Postmenopausal women living in three different climates were significantly different according to body mass index, gravidity, age at menopause, menarche, and high-density lipoprotein (HDL) (p < 0.05). The lowest mean age at menopause and HDL levels were observed in women living in Mediterranean climate. Adjusted mean age at menopause remained significant (p < 0.05).'] Is mediterranean climate associated with early age at menopause and low high-density lipoprotein in postmenopausal women?
qiaojin/PubMedQA
2
[ -1.586694598197937, 0.3443168103694916, 0.5255753993988037 ]
['Randomized trials demonstrating decreased locoregional recurrence (LRR) and improved overall survival (OS) in women receiving postmastectomy radiation therapy (PMRT) used up to 50 Gy to the chest wall (CW), but in practice, many centers boost the CW dose to ≥60 Gy, despite lack of data supporting this approach. We evaluated the relationship between CW dose and clinical outcome.', 'We retrospectively reviewed medical records of 582 consecutively treated patients who received PMRT between January 1999 and December 2009. We collected data on patient, disease, treatment characteristics, and outcomes of LRR, progression-free survival (PFS) and OS.', 'Median follow-up from the date of diagnosis was 44.7 months. The cumulative 5-year incidence of LRR as first site of failure was 6.2%. CW dose for 7% (43 patients) was ≤50.4 Gy (range, 41.4-50.4 Gy) and 93% received >50.4 Gy (range, 52.4-74.4 Gy). A CW dose of >50.4 Gy vs. ≤50.4 Gy was associated with lower incidence of LRR, a 60-month rate of 5.7% (95% confidence interval [CI], 3.7-8.2) vs. 12.7% (95% CI, 4.5-25.3; p = 0.054). Multivariate hazard ratio (HR) for LRR controlling for race, receptor status, and stage was 2.62 (95% CI, 1.02-7.13; p = 0.042). All LRR in the low-dose group occurred in patients receiving 50 to 50.4 Gy. Lower CW dose was associated with worse PFS (multivariate HR, 2.73; 95% CI, 1.64-4.56; p < 0.001) and OS (multivariate HR, 3.88; 95% CI, 2.16-6.99; p < 0.001).'] Does higher chest wall dose result in improved locoregional outcome in patients receiving postmastectomy radiation?
qiaojin/PubMedQA
2
[ -1.013015866279602, -1.7490665912628174, 1.7802972793579102 ]
['Acquired Von Willebrand syndrome (AVWS) can contribute to bleeding complications in patients with ventricular assist devices (VADs). AVWS results from shear stress, which causes unfolding of the high-molecular-weight (HMW) multimers of Von Willebrand factor (VWF) with subsequent cleavage. Loss of the HMW multimers of VWF is the leading finding in AVWS. In consequence, binding of VWF to collagen and to platelets is impaired. The onset of AVWS after VAD implantation is not yet determined. We examined VAD patients for presence of an AVWS in the early, intermediate, and late phase after VAD implantation.', 'Patients with a biventricular Thoratec-PVAD(®) (BVAD, n = 6) or a left-ventricular HeartMateII(®) (HMII, n = 11) were analyzed prior to VAD implantation and after 1, 3, 14, 30, and 60 days. Diagnosis of AVWS based on VWF:ristocetin cofactor activity/VWF:VWF antigen (VWF:RCo/VWF:Ag), collagen-binding capacity:VWF antigen (VWF:CB/VWF:Ag), and multimeric analysis. In addition, we analyzed the number of bleeding episodes, which required surgical intervention.', 'No patient had an AVWS prior to VAD implantation. An AVWS was identified already in the very early postoperative period, that is, in almost all patients on the first day and in all patients on the third day. The AVWS was also detected in the majority of patients in the further course. Nine of all 17 patients suffered bleeding complications and required a total of 25 interventions due to hemorrhages. Forty percent of re-interventions were carried out within the first 10 days after implantation; five of these were necessary within the first 24h.'] Is acquired Von Willebrand syndrome an early-onset problem in ventricular assist device patients?
qiaojin/PubMedQA
2
[ -2.3003170490264893, -1.3985316753387451, 2.834627628326416 ]
['Data comparing the effectiveness of high-frequency oscillatory ventilation and of conventional mechanical ventilation in the treatment of respiratory distress syndrome of very low birth weight infants are, to date, still matter of debate. We investigated the effects of first intention high-frequency oscillatory ventilation or conventional mechanical ventilation support on selected primary and secondary outcomes in very low birth weight infants complicated by respiratory distress syndrome in which antenatal glucocorticoid prophylaxis was not performed.', 'Multicenter randomized control trial.', 'Three tertiary centers of neonatal intensive care units from December 2004 to December 2007.', 'Eighty-eight very low birth weight infants complicated by respiratory distress syndrome, without antenatal glucocorticoids, supported by first intention high-frequency oscillatory ventilation (n = 44) or conventional mechanical ventilation (n = 44).', 'All newborns were monitored by standard monitoring procedure, including routine laboratory variables, neurologic patterns, and ultrasound imaging. Primary outcomes were: the length of ventilatory support, the need of reintubation, and the length of nasal continuous positive airway pressure support in the postextubation period. Secondary outcomes were: the length of stay in neonatal intensive care unit and in hospital, death before discharge, adverse short- and long-term pulmonary and neonatal outcomes, and the need for a second dose of surfactant and of postnatal glucocorticoid treatment.', 'High-frequency oscillatory ventilation infants showed a significant lower duration (p < .001 for all) of ventilator dependency, lower need of reintubation and of duration of nasal continuous positive airway pressure support in the postextubation period. Among secondary outcomes in the high-frequency oscillatory ventilation infants, the need of a second dose of surfactant administration, and the length of stay in the neonatal intensive care unit and in hospital were significantly lower (p < .05 for all).'] Do first intention high-frequency oscillatory and conventional mechanical ventilation in premature infants without antenatal glucocorticoid prophylaxis?
qiaojin/PubMedQA
2
[ -2.363107681274414, -1.0599538087844849, 2.5135929584503174 ]
['Probiotics may alter immune regulation. Recently, we showed that the probiotic bacteria Lactobacillus acidophilus NCFM™ influenced the activity of regulatory T cells (Tregs) in vitro. The aim of the present work was to demonstrate if L. acidophilus NCFM™ also affects the function of Tregs in vivo.', 'Development of colitis after transfer of CD4+CD25- T cells and protection from colitis by Tregs was studied in immunodeficient SCID mice which were simultaneously tube-fed with L. acidophilus NCFM™ or L. salivarius Ls-33 for 5 weeks.', 'Probiotic-fed SCID mice transplanted with low numbers of Tregs in addition to the disease-inducing T cells were completely protected from colitis. This was in contrast to the control group, which showed intermediate levels of inflammation. In addition, feeding with probiotics lowered serum levels of inflammatory cytokines in both colitic mice and in mice protected from colitis by Tregs. Gene expression patterns of rectum samples of protected mice that receive either one of the probiotics showed a closer resemblance to naïve SCID mice than did patterns of the control group. The mechanism of action of the probiotics appears to be an indirect effect by inducing a Treg-favorable environment rather than a direct effect on the Tregs.'] Does consumption of probiotics increase the effect of regulatory T cells in transfer colitis?
qiaojin/PubMedQA
2
[ -2.6165125370025635, -0.9454888701438904, 2.5846028327941895 ]
['In order to develop non-invasive and effective nose-to-brain delivery of drugs, we synthesized Tat analog-modified methoxy poly(ethylene glycol) (MPEG)/poly(ε-caprolactone) (PCL) amphiphilic block copolymers through the ester bond.', 'We evaluated the brain distribution of coumarin, acting as a model chemical, after intravenous or intranasal administration of MPEG-PCL. In addition, cellular uptake of coumarin by rat glioma cells transfected with coumarin-loaded MPEG-PCL or MPEG-PCL-Tat was determined. Finally, we determined the brain distribution and biodistribution after intranasal administration of coumarin-loaded MPEG-PCL-Tat.', 'The amount of coumarin in the brain after intranasal administration was significantly higher than that after intravenous administration. In addition, cellular uptake of coumarin using MPEG-PCL was the lowest, while cellular uptake of coumarin using Tat-modified MPEG-PCL (MPEG-PCL-Tat) was higher than that of MPEG-PCL. Therefore, the brain distribution of coumarin administered using MPEG-PCL-Tat was significantly greater than that using MPEG-PCL. Then, the coumarin distribution after MPEG-PCL-Tat administration in non-targeted tissues (lung, liver, heart, kidney and spleen) was lower than that after coumarin administration without nanomicelles.'] Do cell-penetrating peptide-modified block copolymer micelles promote direct brain delivery via intranasal administration?
qiaojin/PubMedQA
2
[ -2.2385385036468506, -1.4390029907226562, 2.735201358795166 ]
['In isolated rabbit hearts, repetitive endocardial focal discharges (REFDs) were consistently observed during ventricular fibrillation (VF) with prolonged (>5 minutes) global ischemia (GI). We hypothesized that BAPTA-AM, a calcium chelator, can suppress these REFDs.', "Using a two-camera optical mapping system, we simultaneously mapped endocardial (left ventricle, LV) and epicardial (both ventricles) activations during ventricular arrhythmia with GI. In 5 hearts (protocol I), we infused Tyrode's solution (no BAPTA-AM) for ≥30 minutes before the onset of no-flow GI. In 7 additional hearts (protocol II), BAPTA-AM (20 μmol/L) was infused for ≥30 minutes before the initiation of GI. In protocol I, sustained VF (>30 seconds) was successfully induced in all 5 hearts with prolonged GI. REFDs were present in >85 % of recording time. In protocol II, however, ventricular arrhythmia was not inducible and REFDs were not observed after 5-minute GI in 5 hearts. Effects of BAPTA-AM on intracellular calcium (Ca(i) ) at the LV endocardium were also evaluated in 5 hearts (protocol III) using dual Ca(i) /membrane potential mapping. GI, both without and with BAPTA-AM pretreatment, caused a decrease of Ca(i) amplitude during S(1) pacing. However, this effect was more pronounced in the hearts with BAPTA-AM pretreatment (P < 0.001). GI, without BAPTA-AM pretreatment, caused broadening of Ca(i) transient. In contrast, GI, with BAPTA-AM pretreatment, caused narrowing of Ca(i) transient."] Does pretreatment of BAPTA-AM suppress the genesis of repetitive endocardial focal discharges and pacing-induced ventricular arrhythmia during global ischemia?
qiaojin/PubMedQA
2
[ -2.002864122390747, -1.5367003679275513, 2.557753562927246 ]
['It is unclear why some patients, who undergo complete repair or palliative surgery for congenital heart disease (CHD), still develop irreversible pulmonary artery hypertension (PAH). There is no consensus to preoperationally assess the reversible and irreversible pulmonary vasculopathy seen in PAH.', 'The peri-operative pulmonary hemodynamic data of 16 CHD patients (reversible PAH, n = 6; irreversible PAH, n = 10) were analyzed. The lung biopsies were also performed during surgery for defining histopathological characteristics as well as immunohistochemical expression of endothelin-1 (ET-1), endothelin-1 receptors (ETR), and its downstream signaling markers in the small pulmonary arteries and arterioles. Neointimal formation and neoangiogenesis was characterized by increased intimal layer immunoreactivity for α-SMA, Factor VIII, CD34, and VEGF. Neointimal formation was found in 90% of patients and neoangiogenesis was found in 80% of patients with irreversible PAH. Neither was present in the reversible PAH group and the control group. Expression of ET-1 and ETR in the neointimal layer of the pulmonary arterioles was upregulated in irreversible PAH, and immunoreactivity of phospho-Akt, phospho-ERK1/2, and phospho-mTOR was also increased in irreversible PAH.'] Is activation of endothelin-1 receptor signaling pathways associated with neointima formation , neoangiogenesis and irreversible pulmonary artery hypertension in patients with congenital heart disease?
qiaojin/PubMedQA
2
[ -2.3999013900756836, -1.3399983644485474, 2.778999090194702 ]
['Inflammation might contribute to the development of stent thrombosis (ST). The association between inflammatory cytokine concentrations and drug-eluting ST were evaluated.', "Among the 123 ST patients enrolled in the multicenter Korea Stent Thrombosis registry, plasma samples were available in 41 patients. The patients' clinical characteristics and plasma concentrations of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and interleukin (IL)-6 were compared with 81 matched controls. Although the concentrations of 3 cytokines were higher in the ST group, they did not have significant differences. When divided into quartiles, the proportion of patients with the highest quartile of IL-6 was higher in the ST group than in the control group (44% vs. 16%, P = 0.001), and the highest IL-6 quartile was an independent predictor of ST for both early (adjusted hazard ratio [HR] 6.96; 95% confidence interval [CI] 1.75-27.66) and late ST (adjusted HR 4.71; 95%CI 1.06-20.92). In addition, the highest IL-6 quartile was an independent predictor of ST in those on clopidogrel (adjusted HR 7.70; 95%CI 1.97-30.13) but not in those who were off clopidogrel."] Is high plasma interleukin-6 associated with drug-eluting stent thrombosis : possible role of inflammatory cytokines in the development of stent thrombosis from the Korea Stent Thrombosis Registry?
qiaojin/PubMedQA
2
[ -2.218174934387207, -1.365541696548462, 2.6611533164978027 ]
['The proximal region of murine Chr 2 has long been known to harbour one or more imprinted genes from classic genetic studies involving reciprocal translocations. No imprinted gene had been identified from this region until our study demonstrated that the PcG gene Sfmbt2 is expressed from the paternally inherited allele in early embryos and extraembryonic tissues. Imprinted genes generally reside in clusters near elements termed Imprinting Control Regions (ICRs), suggesting that Sfmbt2 might represent an anchor for a new imprinted domain.', 'We analyzed allelic expression of approximately 20 genes within a 3.9 Mb domain and found that Sfmbt2 and an overlapping non-coding antisense transcript are the only imprinted genes in this region. These transcripts represent a very narrow imprinted gene locus. We also demonstrate that rat Sfmbt2 is imprinted in extraembryonic tissues. An interesting feature of both mouse and rat Sfmbt2 genes is the presence of a large block of miRNAs in intron 10. Other mammals, including the bovine, lack this block of miRNAs. Consistent with this association, we show that human and bovine Sfmbt2 are biallelic. Other evidence indicates that pig Sfmbt2 is also not imprinted. Further strengthening the argument for recent evolution of Sfmbt2 is our demonstration that a more distant muroid rodent, Peromyscus also lacks imprinting and the block of miRNAs.'] Does recent acquisition of imprinting at the rodent Sfmbt2 locus correlate with insertion of a large block of miRNAs?
qiaojin/PubMedQA
2
[ -2.555870771408081, -0.6336426138877869, 2.278519630432129 ]
['Neuroblastoma (NB) tumors are well known for their pronounced clinical and molecular heterogeneity. The global gene expression and DNA copy number alterations have been shown to have profound differences in tumors of low or high stage and those with or without MYCN amplification. RNA splicing is an important regulatory mechanism of gene expression, and differential RNA splicing may be associated with the clinical behavior of a tumor.', 'In this study, we used exon array profiling to investigate global alternative splicing pattern of 47 neuroblastoma samples in stage 1 and stage 4 with normal or amplified MYCN copy number (stage 1-, 4- and 4+). The ratio of exon-level expression to gene-level expression was used to detect alternative splicing events, while the gene-level expression was applied to characterize whole gene expression change.', 'Principal component analysis (PCA) demonstrated distinct splicing pattern in three groups of samples. Pairwise comparison identified genes with splicing changes and/or whole gene expression changes in high stage tumors. In stage 4- compared with stage 1- tumors, alternatively spliced candidate genes had little overlap with genes showing whole gene expression changes, and most of them were involved in different biological processes. In contrast, a larger number of genes exhibited either exon-level splicing, gene-level expression or both changes in stage 4+ versus stage 1- tumors. Those biological processes involved in stage 4- tumors were disrupted to a greater extent by both splicing and transcription regulations in stage 4+ tumors.'] Does exon array analysis reveal neuroblastoma tumors have distinct alternative splicing patterns according to stage and MYCN amplification status?
qiaojin/PubMedQA
2
[ -2.2330145835876465, -1.0337135791778564, 2.4410340785980225 ]
['Traditionally, the administration of aspirin is stopped seven days before coronary artery bypass surgery to reduce the risk of postoperative bleeding. The aim of this study was to evaluate the effect of preoperative aspirin on bleeding in these patients.', 'A prospective nonrandomized unblinded study was carried out at the King Abdullah University Hospital in Jordan/Irbid from June 2005 to December 2009 in 756 patients. Patients were divided into 2 groups: Group 1 (n\u2009=\u2009400) consisted of patients on aspirin, 100\u2009mg/day, until the day of surgery; Group 2 (n\u2009=\u2009356) consisted of patients who stopped taking aspirin seven days before surgery. The groups were compared to evaluate the effect of preoperative aspirin on bleeding in patients undergoing elective coronary artery bypass surgery. Data were collected and compared and included total amount of postoperative chest tube drainage, number of transfused units of blood and blood products, and numbers of patients who required reexploration for bleeding. Results were considered significant when P\u2009<\u20090.05.', 'There was no significant increase in the amount of blood loss, units of transfused blood products, or the incidence of reexploration between the two groups ( P\u2009>\u20090.05).'] Does aspirin increase bleeding and allogeneic blood transfusion in coronary artery surgery?
qiaojin/PubMedQA
2
[ -0.6834810972213745, -1.5708913803100586, 1.2204539775848389 ]
['A significant number of young people start smoking at an age of 13-15, which means that serious smoking-evoked changes may have been occurred by their twenties. Surfactant proteins (SP) and matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to cigarette smoke induced lung remodelling and chronic obstructive pulmonary disease (COPD). However, the level of these proteins has not been examined during ageing or in young individuals with short smoking histories.', 'Plasma levels of SP-A, SP-D, MMP-9, and TIMP-1 were measured by EIA/ELISA from young (18-23 years) non-smoking controls (YNS) (n = 36), smokers (YS) (n = 51), middle aged/elderly (37-77 years) non-smoking controls (ONS) (n = 40), smokers (OS) (n = 64) (FEV1/FVC >0.7 in all subjects) and patients with COPD (n = 44, 35-79 years).', 'Plasma levels of SP-A increased with age and in the older group in relation to smoking and COPD. Plasma SP-D and MMP-9 levels did not change with age but were elevated in OS and COPD as compared to ONS. The TIMP-1 level declined with age but increased in chronic smokers when compared to ONS. The clearest correlations could be detected between plasma SP-A vs. age, pack years and FEV1/FVC. The receiver operating characteristic (ROC) curve analysis revealed SP-A to be the best marker for discriminating between patients with COPD and the controls (area under ROC curve of 0.842; 95% confidence interval, 0.785-0.899; p < 0.001).'] Do ageing and smoking contribute to plasma surfactant proteins and protease imbalance with correlations to airway obstruction?
qiaojin/PubMedQA
2
[ -1.9897041320800781, -1.3630568981170654, 2.4238548278808594 ]
['The stress-activated mitogen-activated protein kinases (MAPKs), c-Jun NH2-terminal kinase (JNK), and p38 have been implicated in hepatocarcinogenesis. Although the many interrelated functions of JNK and p38 are precisely regulated by upstream signaling molecules, little is known about upstream regulators. We investigated the role of apoptosis signal-regulating kinase 1 (ASK1), a major player in the regulation of JNK and p38 activities, in hepatocarcinogenesis using a mouse hepatocellular carcinoma (HCC) model. ASK1-deficient (ASK1(-/-) ) and wildtype (WT) mice were treated with diethylnitrosamine on postnatal day 14. Strikingly, after 7 months, approximately three times as many tumors developed in ASK1(-/-) mice as in WT mice. Although JNK and p38 activation were attenuated in ASK1(-/-) HCCs relative to WT HCCs, cell proliferation was comparable in HCCs from both types of mice. On the other hand, both cancer cell apoptosis and hyperphosphorylation of BimEL, a proapoptotic Bcl-2 family member, were suppressed in the ASK1(-/-) HCCs. ASK1(-/-) mice showed remarkable resistance to Fas-induced hepatocyte apoptosis in vivo, probably because of attenuated JNK-mediated BimEL phosphorylation and mitochondrial apoptotic pathway activation. The reintroduction of ASK1 to ASK1(-/-) mouse liver using an adenoviral vector restored Fas-induced hepatocyte death and phosphorylation of JNK and BimEL. Similar findings were obtained in tumor necrosis factor alpha-induced hepatocyte apoptosis. Furthermore, ASK1 was involved in DNA damage-induced p21 up-regulation through a p38 pathway.'] Does apoptosis signal-regulating kinase 1 inhibit hepatocarcinogenesis by controlling the tumor-suppressing function of stress-activated mitogen-activated protein kinase?
qiaojin/PubMedQA
2
[ -2.396897077560425, -1.2337435483932495, 2.670891284942627 ]
['The substitution of plastics based on fossil raw material by biodegradable plastics produced from renewable resources is of crucial importance in a context of oil scarcity and overflowing plastic landfills. One of the most promising organisms for the manufacturing of medium-chain-length polyhydroxyalkanoates (mcl-PHA) is Pseudomonas putida KT2440 which can accumulate large amounts of polymer from cheap substrates such as glucose. Current research focuses on enhancing the strain production capacity and synthesizing polymers with novel material properties. Many of the corresponding protocols for strain engineering rely on the rifampicin-resistant variant, P. putida KT2442. However, it remains unclear whether these two strains can be treated as equivalent in terms of mcl-PHA production, as the underlying antibiotic resistance mechanism involves a modification in the RNA polymerase and thus has ample potential for interfering with global transcription.', 'To assess PHA production in P. putida KT2440 and KT2442, we characterized the growth and PHA accumulation on three categories of substrate: PHA-related (octanoate), PHA-unrelated (gluconate) and poor PHA substrate (citrate). The strains showed clear differences of growth rate on gluconate and citrate (reduction for KT2442 > 3-fold and > 1.5-fold, respectively) but not on octanoate. In addition, P. putida KT2442 PHA-free biomass significantly decreased after nitrogen depletion on gluconate. In an attempt to narrow down the range of possible reasons for this different behavior, the uptake of gluconate and extracellular release of the oxidized product 2-ketogluconate were measured. The results suggested that the reason has to be an inefficient transport or metabolization of 2-ketogluconate while an alteration of gluconate uptake and conversion to 2-ketogluconate could be excluded.'] Does a reduction in growth rate of Pseudomonas putida KT2442 counteract productivity advances in medium-chain-length polyhydroxyalkanoate production from gluconate?
qiaojin/PubMedQA
2
[ -2.5277609825134277, -1.0142145156860352, 2.6767821311950684 ]
['Chromatin binding plays a central role in the molecular mechanism of LEDGF/p75 in HIV-1 DNA integration. Conflicting results have been reported in regards to the relevance of the LEDGF/p75 chromatin binding element PWWP domain in its HIV-1 cofactor activity.', 'Here we present evidence that re-expression of a LEDGF/p75 mutant lacking the PWWP domain (ΔPWWP) rescued HIV-1 infection in cells verified to express background levels of endogenous LEDGF/p75 that do not support efficient HIV-1 infection. The HIV-1 cofactor activity of LEDGF/p75 ΔPWWP was similar to that of LEDGF/p75 wild type (WT). A possible molecular explanation for the nonessential role of PWWP domain in the HIV-1 cofactor activity of LEDGF/p75 comes from the fact that coexpression of HIV-1 integrase significantly restored the impaired chromatin binding activity of LEDGF/p75 ΔPWWP. However, integrase failed to promote chromatin binding of a non-chromatin bound LEDGF/p75 mutant that lacks both the PWWP domain and the AT hook motifs (ΔPWWP/AT) and that exhibits negligible HIV-1 cofactor activity. The effect of integrase on the chromatin binding of LEDGF/p75 requires the direct interaction of these two proteins. An HIV-1 integrase mutant, unable to interact with LEDGF/p75, failed to enhance chromatin binding, whereas integrase wild type did not increase the chromatin binding strength of a LEDGF/p75 mutant lacking the integrase binding domain (ΔIBD).'] Does hIV-1 integrase modulate the interaction of the HIV-1 cellular cofactor LEDGF/p75 with chromatin?
qiaojin/PubMedQA
2
[ -2.23465633392334, -1.1457680463790894, 2.3780369758605957 ]
['According to the cognitive model of depression, depression entails certain cognitive biases. These occur when explaining life events: depressive patients tend to attribute negative life events to internal, stable and global reasons. Moreover depressive patients presumably experience themselves as passive sufferers rather than active agents of events.', 'The study explored some typical cognitive biases of depressive patients as appearing in their personal narratives. Specifically, it focused on the explanatory style and the sense of agency. As both narrative methods are unknown in Hungary so far, the study describes them in detail as well.', 'Altogether 108 narratives of 16 depressive patients and 15 healthy people were analyzed. The attribution style was analyzed by the CAVE (Content Analysis of Verbatim Expressions) method, which explores the attribution style of the narratives in three dimensions: locus (internal-external), stability (stable-instable) and pervasiveness (global-specific). The sense of agency was assessed by using a self-developed narrative method.', 'It was found that when explaining positive life events, depressive patients referred to external reasons significantly more frequently than to internal reasons, and they tended to explain negative life events with global reasons. There was no difference between the two groups in any other attribution. Furthermore, depressive patients tended to describe themselves as being only passive sufferers or recipients of events, in contrast with members of the control group who appeared more as active agents in their narratives.'] Do [ Pessimistic explanatory style and lack of agency characterise the narratives of depressive patients ]?
qiaojin/PubMedQA
1
[ -2.3553168773651123, 2.102898120880127, -0.5745428800582886 ]
['B-cell receptors (BCRs) and their recognition of specific epitopes may play a pivotal role in the development and progression of chronic lymphocytic leukemia (CLL). In this study, the authors set up a model system to explore epitope reactivity and its clinical relevance in CLL.', 'Epitope-mimicking peptides were selected from phage display libraries on 6 CLL BCRs from randomly chosen patients. The binding of the 6 index epitope mimics was evaluated in a set of 100 unrelated CLL samples. Epitope recognition patterns were correlated with the clinical course of the disease.', 'Surprisingly, all CLL samples recognized 1 or several index epitopes, and some revealed marked polyreactivity. Patients with CLL who expressed BCRs that reacted with ≥5 epitope mimics had a significantly worse clinical course than less polyreactive patients (median time to first treatment, 24 months vs 102 months). This effect was independent of otherwise known prognostic markers.'] Does b-cell receptor epitope recognition correlate with the clinical course of chronic lymphocytic leukemia?
qiaojin/PubMedQA
2
[ -2.3130598068237305, -1.1990183591842651, 2.5548105239868164 ]
['Oncoproteins encoded by the early region of adenoviruses have been shown to be powerful tools to study gene regulatory mechanisms, which affect major cellular events such as proliferation, differentiation, apoptosis and oncogenic transformation. They are possesing a key role to favor viral replication via their interaction with multiple cellular proteins. In a yeast two-hybrid screen we have identified Sprouty1 (Spry1) as a target of adenoviral E1A Oncoproteins. Spry proteins are central and complex regulators of the receptor tyrosine kinase (RTK) signalling pathway. The deregulation of Spry family members is often associated with alterations of the RTK signalling and its downstream effectors, leading to the ERK pathway.', 'Here, we confirm our yeast two-hybrid data, showing the interaction between Spry1 and E1A in GST pull-down and immunoprecipitation assays. We also demonstrated the interaction of E1A with two further Spry isoforms. Using deletion mutants we identified the N-terminus and the CR conserved region (CR) 3 of E1A- and the C-terminal half of Spry1, which contains the highly conserved Spry domain, as the essential sites for direct interaction between Spry and E1A. Immunofluorescent microscopy data revealed a co-localization of E1A(13S) with Spry1 in the cytoplasm. SRE and TRE reporter assays demonstrated that co-expression of Spry1 with E1A(13S) abolishes the inhibitory function of Spry1 in RTK signalling, which is consequently accompanied with a decrease of E1A13S-induced gene expression.'] Is sprouty a cytoplasmic target of adenoviral E1A oncoproteins to regulate the receptor tyrosine kinase signalling pathway?
qiaojin/PubMedQA
2
[ -2.3275744915008545, -1.2264676094055176, 2.6133828163146973 ]
['PMP22, a member of the GAS3 family of tetraspan proteins, is associated with a variety of neurological diseases. Previous studies have shown that PMP22 is expressed in proliferative endometrium, but its function within this tissue is poorly understood. In this study, we first characterized the expression of PMP22 in the human menstrual cycle and began to characterize its function in the endometrium.', 'Using a combination of immunohistochemistry and quantitative PCR, we characterized the expression of PMP22 in both proliferative and secretory endometrium. Differences in PMP22 expression between proliferative and secretory endometrium were determined using a Mann-Whitney U test. In order to investigate the influence of PMP22 on α6 integrin expression, cells were created that ectopically overexpressed PMP22 or expressed a siRNA to inhibit its expression. These cells were analyzed for changes in integrins and binding to extracellular matrices.', 'In this study, we show that PMP22 expression is higher in proliferative phase than secretory phase. Functionally, we have begun to characterize the functional significance of this expression. Previous studies have suggested a link between PMP22 and α6 integrin, and therefore we asked whether PMP22 could associate or potentially modulate the expression of α6 integrin. Expression of both PMP22 and α6 integrin were detectable in endometrial epithelial and stromal cells, and we show that both proteins can associate and colocalize with each other. To understand if PMP22 directly altered the expression of a6 integrin, we examined cell lines with modulated levels of the protein. Overexpression of PMP22 was sufficient to increase α6 integrin surface expression with a concominant increase in binding to the extracellular matrix laminin, while a reduction in PMP22 suppressed α6 integrin surface expression.'] Does peripheral myelin protein-22 ( PMP22 ) modulate alpha 6 integrin expression in the human endometrium?
qiaojin/PubMedQA
2
[ -2.3866350650787354, -1.1674184799194336, 2.6194663047790527 ]
['Despite progress in surgical techniques and perioperative care, gastrectomy remains a procedure of significant morbidity. Several scoring systems and clinical measures have been adopted to predict postoperative complications in gastric cancer patients. The aim of this study was to investigate whether high serum levels of interleukin 6 (IL-6) in the early postoperative period may be a prognostic factor of postoperative morbidity.', 'A group of 99 consecutive patients with resectable gastric cancer were enrolled. The mean age was 62.9 years and the male/female ratio was 72:27. Subtotal gastric resection was performed in 22 patients and total gastric resection in 77. The IL-6 serum level was measured on the 1st postoperative day (POD).', 'Complications were recorded in 28 patients (28.3%). The observed case-fatality rate was 3.03%. An IL-6 serum level of >288.7 pg/ml on the 1st POD in univariate and multivariate Cox proportional hazard models was an independent prognostic factor for overall complications and infective complications.'] Do iL-6 serum levels predict postoperative morbidity in gastric cancer patients?
qiaojin/PubMedQA
2
[ -1.994247317314148, -1.2811357975006104, 2.3199634552001953 ]
['To investigate the association between the programmed death-1(PD-1) polymorphisms and genetic susceptibility of chronic hepatitis B virus (HBV) infection in Chinese patients.', 'Two single nucleotide polymorphisms (SNPs), PD-1.1 G > A and PD-1.2 G > A, were genotyped in 539 patients with chronic HBV infection and 353 other family members (HbsAg-) from 256 nuclear families using polymerase chain reactiorestriction fragment length polymorphisms assay. The associations between PD-1 polymorphisms and genetic susceptibility of chronic HBV infection were analyzed usng the family-based association analysis method.', 'No association or linkage was detected among 539 patients. Univariate (single-marker) family-based association tests demonstrated that PD-1 genotypes, alleles and transmitted haplotypes are not associated with chronic HBV infection (all with P value more than 0.05). Transmission/disequilibrium test and sibship disequilibrium test analysis showed no excess of the alleles from heterozygous parents to affected offspring (P = 0.688880, P = 1.000000 respectively).'] Are polymorphisms in programmed death-1 gene associated with chronic HBV infection in Chinese patients?
qiaojin/PubMedQA
2
[ -1.9186817407608032, -1.4170993566513062, 2.374255895614624 ]
['The decline noticed in several fertility traits of dairy cattle over the past few decades is of major concern. Understanding of the genomic factors underlying fertility, which could have potential applications to improve fertility, is very limited. Here, we aimed to identify and study those genes that associated with a key fertility trait namely estrous behavior, among genes expressed in four bovine brain areas (hippocampus, amygdala, dorsal hypothalamus and ventral hypothalamus), either at the start of estrous cycle, or at mid cycle, or regardless of the phase of cycle.', 'An average heat score was calculated for each of 28 primiparous cows in which estrous behavior was recorded for at least two consecutive estrous cycles starting from 30 days post-partum. Gene expression was then measured in brain tissue samples collected from these cows, 14 of which were sacrificed at the start of estrus and 14 around mid cycle. For each brain area, gene expression was modeled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model. Genes whose expression patterns showed significant linear or quadratic relationships with heat scores were identified. These included genes expected to be related to estrous behavior as they influence states like socio-sexual behavior, anxiety, stress and feeding motivation (OXT, AVP, POMC, MCHR1), but also genes whose association with estrous behavior is novel and warrants further investigation.'] Do gene expression patterns in four brain areas associate with quantitative measure of estrous behavior in dairy cows?
qiaojin/PubMedQA
2
[ -1.9645658731460571, 0.5596363544464111, 0.6364943981170654 ]
['Over-the-counter (OTC) medications, benzodiazepines, and barbiturates are not covered under many Medicare drug benefit plans; hence, their use by homebound older adults is largely unreported. Furthermore, the tiered design of Medicare drug formularies may in fact promote the use of older but potentially inappropriate medications. Little is known about the use of these medications in the homebound older adult population.', 'To determine the prevalence of the use by homebound older adults of OTC drugs, dietary supplements (vitamins, minerals, and herbal products), Part D-excluded medications (benzodiazepines and barbiturates), and potentially inappropriate medications (according to Beers criteria).', "Patients were enrollees in a home and community-based Medicaid waiver provider. All clients were older than 65 and were dually eligible for Medicare and Medicaid. All clients met Florida Medicaid's medical and financial criteria for nursing home placement. The medication list was obtained by geriatric care managers during a home assessment.", 'A total of 3911 older adults (mean [SD] age 83.6 [8.0] years) were taking an average of 9.9 [4.8] drugs. Of these individuals, 74.5% were using an OTC medication, 41.9% were using a dietary supplement, 29.6% were using a benzodiazepine or barbiturate, and 25.2% were using at least 1 potentially inappropriate medication.'] Do medication assessments by care managers reveal potential safety issues in homebound older adults?
qiaojin/PubMedQA
2
[ -1.5494459867477417, 0.051276348531246185, 0.6903527975082397 ]
['We previously reported a higher expression of protease-activated receptor-2 (PAR(2)) together with higher interleukin (IL)-1α, IL-6, IL-8, and tumor necrosis factor-α levels, total proteolytic activity, Porphyromonas gingivalis (Pg) prevalence, and neutrophil-protease 3 messenger RNA (mRNA) expression in patients with chronic periodontitis compared to healthy control patients. The aim of the present study is to expand this observation by considering the site level according to the presence of Pg.', 'Microbiologic and gingival crevicular fluid samples were collected from patients with chronic periodontitis. Pg presence was evaluated by polymerase chain reaction and PAR(2) mRNA expression was evaluated by reverse-transcription polymerase chain reaction. Total proteolytic activity in the crevicular fluid was analyzed by using a specific substrate benzoylarginine nitroanilide, and the proinflammatory mediators IL-1α, IL-6, IL-8, and tumor necrosis factor-α were analyzed by enzyme-linked immunosorbent assay.', 'In Pg-positive periodontal sites, the mean probing depth and clinical attachment level, the prevalence of bleeding on probing sites, and crevicular fluid volume were higher (P <0.05) compared to Pg-negative sites. In addition, with the exception of IL-8, all other inflammatory mediators were positively (P <0.05) associated with Pg presence. Pg presence was also positively associated with a higher proteolytic activity (P = 0.0037) and higher PAR(2) mRNA expression (P = 0.0271).'] Is porphyromonas gingivalis associated with protease-activated receptor-2 upregulation in chronic periodontitis?
qiaojin/PubMedQA
2
[ -2.3053362369537354, -1.4527753591537476, 2.800339698791504 ]
['Rac small GTPases play important roles in cytoskeleton and many cell functions including cell cycle, cell growth, cell adhesion and gene transcription. Here, we investigated the roles of Rac including Rac1 and Rac2 in lipopolysaccharide (LPS)-induced pulmonary injury.', 'After LPS was intratracheally instilled to lungs in mice, Rac, CDC42 and RhoA activation assay by pull-down and West blot, inflammatory cell infiltration assay by counting cell numbers and lung histological examination, pro-inflammatory mediator mRNA expression assay by quantitative RT-PCR, measurement of myeloperoxidase (MPO) activity, Evans Blue and albumin accumulation by spectrophotometry were performed to evaluate the roles of Rac in pulmonary injury by using its specific inhibitor, NSC23766.', 'LPS challenge led to increases of both Rac1 and Rac2, but not CDC42 or RhoA activities in lungs, and intraperitoneal administration with NSC23766 inhibited both Rac1 and Rac2, but not CDC42 or RhoA activities. Treatment with NSC23766 at 1 or 3mg/kg not only reduced the inflammatory cells infiltration and MPO activities, but also inhibited pro-inflammatory mediators, tumor necrosis factor-α and interleukin-1β, mRNA expression. Moreover, in vitro neutrophil migration assay and in vivo microvascular permeability assay indicated that NSC23766 not only inhibited neutrophil transwell migration toward a chemoattractant, fMLP, but also reduced Evans Blue and albumin accumulation in LPS-challenged lungs. LPS activated both Rac1 and Rac2, but not CDC42 or RhoA activities in lungs, and specific inhibition of Rac activities by NSC23766 effectively alleviated LPS-induced injury.'] Does inhibition of Rac activity alleviate lipopolysaccharide-induced acute pulmonary injury in mice?
qiaojin/PubMedQA
2
[ -2.3480520248413086, -1.3706743717193604, 2.7296392917633057 ]
['Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for proteasomal degradation. The Nrf2/Keap1 system is dysregulated in lung, head and neck, and breast cancers and this affects cellular proliferation and response to therapy. Here, we have investigated the integrity of the Nrf2/Keap1 system in pancreatic cancer.', 'Keap1, Nrf2 and the Nrf2 target genes AKR1c1 and GCLC were detected in a panel of five pancreatic cancer cell lines. Mutation analysis of NRF2 exon 2 and KEAP1 exons 2-6 in these cell lines identified no mutations in NRF2 and only synonomous mutations in KEAP1. RNAi depletion of Nrf2 caused a decrease in the proliferation of Suit-2, MiaPaca-2 and FAMPAC cells and enhanced sensitivity to gemcitabine (Suit-2), 5-flurouracil (FAMPAC), cisplatin (Suit-2 and FAMPAC) and gamma radiation (Suit-2). The expression of Nrf2 and Keap1 was also analysed in pancreatic ductal adenocarcinomas (n = 66 and 57, respectively) and matching normal benign epithelium (n = 21 cases). Whilst no significant correlation was seen between the expression levels of Keap1 and Nrf2 in the tumors, interestingly, Nrf2 staining was significantly greater in the cytoplasm of tumors compared to benign ducts (P < 0.001).'] Is nrf2 overexpressed in pancreatic cancer : implications for cell proliferation and therapy?
qiaojin/PubMedQA
2
[ -2.189178943634033, -1.3832874298095703, 2.581604480743408 ]
['To investigate the effects of transcorneal electrical stimulation (TES) on eyes that have a branch retinal artery occlusion (BRAO).', 'We studied two eyes having a BRAO, with an interval between the onset of symptoms and the beginning of treatment of >16 weeks (longstanding cases), and in three eyes with an interval of <16 weeks (fresh cases). The visual functions of the eyes were assessed by the best-corrected visual acuity (BCVA), multifocal electroretinograms (mfERGs), and automated static perimetry with the Humphrey field analyzer (HFA). The mfERGs were recorded before and 1 month after the TES, and perimetry with the HFA was done before and at 1 and 3 months after the TES. The amplitudes and implicit times of the N1, P1, and N2 components of the mfERGs were analyzed.', 'TES did not alter the BCVA significantly in all eyes, but it led to a significant increase in the amplitude of the N2 wave of the mfERGs (P < 0.01). The amplitude of the N1-P1 was also increased but not significantly. The implicit times of N1 (P < 0.01) and P1 (P < 0.05) were significantly shorter than that before the TES. The mean deviation of the HFA was increased after the TES but only in the longstanding cases.'] Does transcorneal electrical stimulation improve visual function in eyes with branch retinal artery occlusion?
qiaojin/PubMedQA
2
[ -2.0862112045288086, -1.2329299449920654, 2.336798906326294 ]
['To assess whether dihydrofolate reductase (DHFR) expression is correlated with the concentration of methotrexate (MTX) exposure and the resistance index during the establishment of MTX-resistant human choriocarcinoma JeG-3 cell line.', 'Two series of different MTX-resistant JeG-3 sublines were established by intermittent- and consecutive-inducing methods. Quantitative real-time reverse transcription polymerase chain reaction was used to measure DHFR messenger RNA expression in the sublines during different concentrations of MTX exposure. [beta]-Human chorionic gonadotropin ([beta]-HCG) secretion in these cell lines were detected by using chemoluminescence method.', 'In the 2 series of MTX-resistant cell lines, the same dynamic profiling of [beta]-HCG secretion and DHFR transcript level were found: At a certain range of concentration, the upward [beta]-HCG secretion and the messenger RNA level of DHFR were correlated with the dose of MTX exposing. However, once the concentration of MTX exceeded this range, the expression would not increase but decrease sharply. According to the concentration of MTX exposure from low to high, the multiples of [beta]-HCG increases were 1.86-, 5.15-, 8.38-, 64.17-, 2.6-, and 0.78-fold for intermittent induction and 22.05-, 6.12-, 5.80-, and 1.77-fold for continuous induction; the multiples of DHFR gene expression increases were 12.84-, 99.02-, 129.01-, 177.63-, 420.78-, and 86.09-fold for intermittent induction and 9.59-, 20.56-, 96.05-, and 58.72-fold for continuous induction.'] Is dihydrofolate reductase transcript level suitable for methotrexate-resistance prediction in choriocarcinoma cell line?
qiaojin/PubMedQA
2
[ -1.7160992622375488, -1.5229370594024658, 2.21626353263855 ]
['Elevated plantar loading has been implicated in the etiology of plantar ulceration in individuals with diabetes mellitus and peripheral neuropathy. Total contact casts and cast walker boots are common off-loading strategies to facilitate ulcer healing and prevent re-ulceration. The purpose of this study was to compare off-loading capabilities of these strategies with respect to plantar loading during barefoot walking.', 'Twenty-three individuals with diabetes, peripheral neuropathy, and plantar ulceration were randomly assigned to total contact cast (n=11) or removable cast walker boot (n=12). Each subject underwent plantar loading assessment walking barefoot and wearing the off-loading device. Analysis of covariance was used to compare loading patterns in the off-loading devices for the whole foot, hindfoot, midfoot, and forefoot while accounting for walking speed and barefoot loading.', 'For the foot as a whole, there were no differences in off-loading between the two techniques. Subjects wearing cast walker boots had greater reductions in forefoot peak pressure, pressure-time integral, maximum force, and force-time integral with respect to barefoot walking. Healing times were similar between groups, but a greater proportion of ulcers healed in total contact casting compared to cast walker boots.'] Do removable cast walker boots yield greater forefoot off-loading than total contact casts?
qiaojin/PubMedQA
2
[ -1.346153974533081, -0.6935663819313049, 1.079193353652954 ]
['It is well documented that transient acidosis during reperfusion is protective. The aim of this study was to evaluate the cardioprotection of acidic buffer or plus cyclosporine A in isolated rat hearts after cardioplegic arrest.', 'Langendorff-perfused Sprague-Dawley rat hearts were perfused for 20 min with Krebs-Henseleit (K-H) buffer followed by 30 min of crystalloid cardioplegia and 60 min of reperfusion. Control hearts were perfused with Krebs-Henseleit buffer. Acidic buffer post-conditioning hearts were perfused with acidic K-H buffer (pH 6.8) for the first 3 min of reperfusion. Acidic buffer plus cyclosporine A hearts were perfused with K-H acidic buffer (pH 6.8) containing cyclosporine A (0.2 μmol/L) for the first 3 min of reperfusion.', 'Compared with the control group, acidic buffer or plus cyclosporine A post-conditioning significantly improved myocardial performance, decreased cytochrome C release into the cytosol, increased Bcl-2 expression and decreased Bax expression, decreased sensitivity of mPTP-opening to [Ca2+] and the rate of apoptosis after reperfusion.'] Does acidic buffer or plus cyclosporine A post-conditioning protect isolated rat hearts against ischemia-reperfusion injury?
qiaojin/PubMedQA
2
[ -2.3954150676727295, -1.3063578605651855, 2.7382960319519043 ]
['Long-term exposure to morphine leads to analgesic tolerance. In addition to an opioid receptor conformational change, enhancing the glutamatergic signal transmission is also involved in morphine tolerance. Tumor necrosis factor-α has been demonstrated to correlate with neuronal plasticity via activation of glutamatergic transmission. We examined the effect of etanercept, a tumor necrosis factor-α inhibitor on morphine tolerance in rats.', 'Male Wistar rats were implanted with 2 intrathecal (IT) catheters, and 1 IT catheter was connected to a mini-osmotic pump, used for either morphine infusion (15 μg/h) or saline (1 μL/h) infusion for 5 days. On day 5, either etanercept (50 μg) or saline (10 μL) was injected after discontinued morphine infusion. Three hours later, acute morphine (15 μg/10 μL, IT) treatment was given and all rats received a nociceptive tail-flick test.', 'The results showed that acute etanercept (50 μg) treatment caused a significant antinociceptive effect of morphine in morphine-tolerant rats. Western blotting indicated that etanercept attenuated the downregulation of membrane glutamate transporters GLT-1 and GLAST in morphine-tolerant rats. Etanercept also inhibited the upregulation of surface AMPA-receptor and N-methyl-d-aspartate-receptor subunits, including GluR1/GluR2 and NR1/NR2A.'] Does intrathecal etanercept partially restore morphine 's antinociception in morphine-tolerant rats via attenuation of the glutamatergic transmission?
qiaojin/PubMedQA
2
[ -2.318225622177124, -1.40130615234375, 2.7485947608947754 ]
['The objective of our study was to evaluate the accuracy of MDCT enteroclysis with a split-bolus technique in detecting ureteral compression caused by endometriosis in women with suspected bowel endometriosis.', 'This prospective study included 103 patients with suspected bowel endometriosis. Examinations were performed on a 16-MDCT scanner; 20% of the IV contrast material was administered during colonic distention and intestinal hypotonization (i.e., 7-8 minutes before starting volumetric acquisition). After injection of the remaining quantity of contrast material, the volumetric acquisition was performed during the portal phase of contrast enhancement.', 'The sensitivity of MDCT enteroclysis urography in identifying bowel nodules was 95.5%; specificity, 97.2%; positive predictive value (PPV), 98.5%; negative predictive value (NPV), 92.1%; accuracy, 96.1%; positive likelihood ratio, 34.39; and negative likelihood ratio, 0.05. The opacification was poor in 8.2% of the ureters, sufficient in 17.4%, and good in 74.4%. One hundred ninety-one ureters (92.3%) were opacified between the crossing of the iliac vessels and the bladder. Compression was observed at MDCT enteroclysis urography in 36 ureters (17.4%); surgery confirmed the presence of ureteral compression in 34 ureters (16.4%). The sensitivity of MDCT enteroclysis urography in identifying ureteral compression was 97.1%; specificity, 98.8%; PPV, 94.4%; NPV, 99.4%; accuracy, 99.0%; positive likelihood ratio, 83.54; and negative likelihood ratio, 0.03.'] Does mDCT enteroclysis urography with split-bolus technique provide information on ureteral involvement in patients with suspected bowel endometriosis?
qiaojin/PubMedQA
2
[ -1.8832578659057617, -1.591280221939087, 2.5398292541503906 ]
['To determine the contribution of B- and T-cell-mediated inflammation in a murine airway granulation model.', 'Pilot study in a modified murine model.', 'Philadelphia VA Medical Center Research Building.', 'Laryngotracheal complexes (LTCs) from 54 donor C57BL/6 mice were harvested and divided into 3 groups: (1) uninjured, (2) mechanically injured using a wire brush, and (3) chemically injured using hydrochloric acid. One donor LTC from each group was placed in deep dorsal subcutaneous pockets of either severe combined immunodeficiency (SCID)- or C57BL-recipient mice, for a total of 3 transplanted tracheas per recipient mouse. After 3 weeks, the transplanted LTCs were harvested from both C57BL- and SCID-recipient mice. Tissues were fixed, sectioned, and stained with hematoxylin and eosin. Representative slides were reviewed by a blinded pathologist to determine the formation of granulation tissue and graded as to the degree of formation of granulation tissue.', 'Despite significant granulation formation in C57BL-recipient mice, direct airway injury did not induce the formation of granulation tissue under the disrupted epithelium of airway mucosa in SCID mice 3 weeks after injury.'] Does cellular adaptive inflammation mediate airway granulation in a murine model of subglottic stenosis?
qiaojin/PubMedQA
2
[ -2.543658494949341, -1.2050514221191406, 2.7735953330993652 ]
['Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC to identify novel therapeutic targets.', 'DNA was extracted from 32 CC samples. Bacterial artificial chromosome (BAC) array comparative genomic hybridization was performed using microarray slides containing 3400 BAC clones covering the whole human genome at distances of 1 Mb. Data were analysed within the R statistical environment.', 'DNA CN gains (89 regions) occurred more frequently than DNA CN losses (55 regions). Six regions of gain were identified in all cases on chromosomes 16, 17, 19 and 22. Twenty regions were frequently gained on chromosomes 1, 5, 7, 9, 11, 12, 16, 17, 19, 20 and 21. The BAC clones covering ERBB2, MEK2 and PDGFB genes were gained in all cases. Regions covering MTOR, VEGFR 3, PDGFA, RAF1, VEGFA and EGFR genes were frequently gained.'] Does array comparative genomic hybridization identify novel potential therapeutic targets in cholangiocarcinoma?
qiaojin/PubMedQA
2
[ -2.1447629928588867, -1.1312901973724365, 2.397934913635254 ]
['Hilar cholangiocarcinoma presents both diagnostic and therapeutic challenges. While establishing a diagnosis is important for patients considering aggressive treatment, a transperitoneal fine needle aspiration (FNA) may lead to seeding of the tumour. The aim of the present study was to determine whether patients who have undergone transperitoneal FNA of the primary tumour have a higher incidence of metastases.', 'Outcomes of 191 patients enrolled in a neoadjuvant chemoradiotherapy followed by liver transplantation (LT) from 1 October 1992 to 1 January 2010 were analysed. The incidence of metastases was compared between those who did or did not undergo a transperitoneal FNA biopsy of the primary tumour.', 'A total of 16 patients underwent FNA biopsy. There were six patients with biopsies positive for adenocarcinoma and 5/6 (83%) had peritoneal metastases at operative staging. Nine patients had biopsies, which did not demonstrate a tumour, and had no evidence of metastasis. One patient had an equivocal biopsy. Of those who did not undergo a transperitoneal biopsy, the incidence of peritoneal metastasis was 8% (14/175), P= 0.0097 vs. positive staging (83%) in those with a diagnostic transperitoneal FNA. Survival at 5 years for those who underwent LT was 74%.'] Is trans-peritoneal fine needle aspiration biopsy of hilar cholangiocarcinoma associated with disease dissemination?
qiaojin/PubMedQA
2
[ -1.8908261060714722, -1.5195947885513306, 2.420910358428955 ]
['To characterize hyperosmolarity-responsive genes in leiomyoma cells and determine whether gonadotropin-releasing hormone (GnRH) agonist treatment altered their expression.', 'Laboratory study.', 'University hospital.', 'None.', 'Cell culture under hypertonic conditions and with GnRH agonist treatment, RNA isolation, and real-time reverse-transcriptase polymerase chain reaction (RT-PCR).', 'Expression of nuclear factor of activated T cells 5 (NFAT5), aldose reductase (AR), and sodium myo-inositol transporter 1 (SMIT) messenger RNA (mRNA) in immortalized leiomyoma and patient-matched myometrial cells.', 'Leiomyoma cells had increased basal expression of NFAT5 mRNA (1.7±0.08-fold) compared with myometrial cells. The NFAT5 increased further in leiomyoma cells cultured under hyperosmolar conditions (3.0±0.46-fold at 50 mM NaCl and 3.3±0.48-fold at 100 mM NaCl). The NFAT5-regulated mRNA transcripts for AR and SMIT were increased in untreated leiomyoma cells compared with myometrial cells and further increased in leiomyoma cells exposed to osmotic stress. The NFAT5 transcripts were decreased with low-dose GnRH agonist treatment but increased with supraphysiologic doses.'] Does gonadotropin-releasing hormone agonist increase expression of osmotic response genes in leiomyoma cells?
qiaojin/PubMedQA
2
[ -2.466632127761841, -1.2458112239837646, 2.767819404602051 ]
['Soft-tissue swelling and increased extracellular volume, two features of acromegaly, are related to the antinatriuretic effects of excess GH/IGF-I, but the precise pathophysiological mechanism is unclear.', 'Our objective was to determine the effect of the GH excess on renal and extrarenal epithelial sodium channel (ENaC) activity.', 'We conducted a prospective randomized open-label blinded-endpoint (PROBE) crossover study (www.ClinicalTrials.gov Identifier: NCT00531908) at a tertiary referral medical center and clinical investigation center.', 'Sixteen patients (five females, 11 males) with acromegaly were randomly assigned to receive 20 mg amiloride (an ENaC blocker) and 25 mg furosemide (a Na-K-2Cl cotransporter blocker) under a high-sodium diet to suppress endogenous renin and aldosterone.', 'Diuretic-induced changes in the urinary Na/K ratio (reflecting coupling between ENaC-mediated Na reabsorption and distal K secretion) and the intranasal amiloride-sensitive potential (reflecting extrarenal ENaC activity) were measured before and 6 months after (range, 1-12 months) treatment of acromegaly.', 'Serum IGF-I concentrations normalized in all the patients after treatment of acromegaly. Baseline plasma renin and aldosterone concentrations remained unchanged after treatment. Active acromegaly, compared with controlled disease, was associated with an enhanced response [median (interquartile range)] to amiloride [urinary Na/K, 13.9 (9.8-19.5) vs. 6.3 (4.3-8.4) mmol/mmol, P = 0.0003], a reduced response to furosemide [urinary Na/K, 5.2 (4.6-7.2) vs. 7.1 (5.4-8.8) mmol/mmol, P =0.0151], and an increased intranasal amiloride-sensitive potential [5.8 (11.9-3.8) vs. 4.2 (6.4-2.1) mV, P = 0.031], respectively.'] Is body fluid expansion in acromegaly related to enhanced epithelial sodium channel ( ENaC ) activity?
qiaojin/PubMedQA
2
[ -2.349428176879883, -1.4373071193695068, 2.844073534011841 ]
['Chronic high levels of PTH may be associated with up-regulation of proteases and cytokines. Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory cytokine, produced predominantly by macrophages and endothelial cells, and is expressed in adipose tissue. More recently it has been shown that PTH administration increases MCP-1 expression in osteoblasts.', 'Because both PTH and MCP-1 levels are higher in obesity, the goal was to determine whether the high MCP-1 occurs only in the presence of high serum PTH and is independent of adiposity and examine its relationship with bone mineral density (BMD) and turnover.', 'In this case-control clinical design, 111 eligible women were categorized into four groups: leaner women [body mass index (BMI) 23 ± 2 kg/m(2)] with normal or higher PTH and obese (BMI 44 ± 7 kg/m(2)) with normal or higher PTH.', 'Serum MCP-1 levels were higher (P < 0.01) in the high (PTH = 74.9 ± 27.0 pg/ml, MCP-1 = 421.5 ± 157.0 pg/ml) compared with normal PTH (PTH = 32.5 ± 10.4 pg/ml, MCP-1 = 322.5 ± 97.8 pg/ml) group, independent of BMI. C-reactive protein and adiponectin were influenced only by BMI and not PTH. MCP-1 was positively associated with osteocalcin and propeptide of type 1 collagen in the leaner (r > 0.3, P < 0.05) but not the obese women and was not associated with BMD in either group.'] Is the high serum monocyte chemoattractant protein-1 in obesity influenced by high parathyroid hormone and not adiposity?
qiaojin/PubMedQA
2
[ -1.6996076107025146, -1.5440640449523926, 2.237553596496582 ]
['Myocardial failure, leading to inotrope-unresponsive shock, is the predominant cause of death in meningococcal and other forms of septic shock. Proinflammatory cytokines released in septic shock are known to have myocardial depressant effects. We previously showed that interleukin 6 is a major myocardial depressant factor in children with meningococcal septicemia. In the current study, we aimed to investigate the mechanisms by which interleukin 6 induces myocardial failure in meningococcal sepsis and to identify potential novel therapeutic targets.', 'Laboratory-based study.', 'University hospital and laboratories.', 'Children with a clinical diagnosis of meningococcal septic shock.', 'We studied interleukin 6-induced signaling events, both in vitro using isolated rat ventricular cardiac myocytes as a model of myocardial contractility and in whole blood from children with meningococcal sepsis.', 'None.', 'We demonstrated involvement of Janus kinase 2, phosphatidylinositol 3-kinase, Akt, and p38 mitogen-activated protein kinase in interleukin 6-induced negative inotropy in isolated cardiac myocytes. Inhibition of p38 mitogen-activated protein kinase not only reversed interleukin 6-induced myocardial depression in both rat and human myocytes, but restored inotrope responsiveness. Cardiomyocytes transduced with dominant-negative p38 mitogen-activated protein kinase showed no interleukin 6-induced myocardial depression. To investigate p38 mitogen-activated protein kinase in vivo, we profiled global RNA expression patterns in peripheral blood of children with meningococcal septicemia. Transcripts for genes mapping to the p38 mitogen-activated protein kinase pathway showed significantly altered levels of abundance with a high proportion of genes of this pathway affected.'] Are myocardial depressant effects of interleukin 6 in meningococcal sepsis regulated by p38 mitogen-activated protein kinase?
qiaojin/PubMedQA
2
[ -2.512519598007202, -1.2164937257766724, 2.748034715652466 ]
['Septic shock is characterized by hypotension and multiple organ failure after infection of microorganisms. Septic shock patients display high levels of circulating microparticles. These are small vesicles released from the plasma membrane of activated or apoptotic cells. Here, we have investigated the effects of in vivo injection of microparticles from nonseptic or septic subjects on protein expression in mouse tissues.', 'Prospective, controlled experiments.', 'Animal basic science laboratory.', 'Male Swiss mice were randomly assigned to one of two groups: 11 animals injected with microparticles isolated from healthy subjects and 15 animals injected with microparticles isolated from septic patients.', 'Microparticles were extracted from whole blood of septic and nonseptic subjects and were intravenously injected in mice. After 24 hrs, mice were killed and heart, lungs, liver, and kidneys were isolated for Western blot assays. Organs were also used for direct measurements of nitric oxide and superoxide anion production by electron paramagnetic resonance.', 'In heart and lungs, microparticles from septic shock patients increased the expression of endothelial and inducible nitric oxide synthases, cyclooxygenase-2, and nuclear factor-κB. However, extracellular superoxide dismutase was only increased in the heart. These effects were associated either with a greater oxidative or nitrative stress in heart and lungs, without affecting nitric oxide production. The liver exhibited an increase in oxidative stress linked to decreased endothelial nitric oxide synthase and manganese superoxide dismutase expression. However, cyclooxygenase-2 expression and IκBα phosphorylation were decreased. Septic microparticles did not change superoxide anion and nitric oxide productions in kidneys.'] Do circulating microparticles from septic shock patients exert differential tissue expression of enzymes related to inflammation and oxidative stress?
qiaojin/PubMedQA
2
[ -2.6132149696350098, -1.1220123767852783, 2.8367631435394287 ]
['Characterization of sudden cardiac death (SCD) risk remains a challenge in the application of implantable cardioverter-defibrillator (ICD) therapy. Late gadolinium enhancement cardiac MRI (LGE-CMR) can accurately identify myocardial scar. We performed a retrospective, single-center observational study to evaluate the association between the extent and distribution of left ventricular scar, quantified using LGE-CMR, and the burden of ventricular arrhythmias in patients with coronary artery disease and ICDs.', 'All patients included (2006 to 2009) had undergone LGE-CMR before ICD implantation. Scar (defined as myocardium with a signal intensity ≥50% of the maximum in scar tissue) was characterized in terms of percent scar, scar surface area, and number of transmural left ventricular scar segments. The end point was appropriate ICD therapy. Sixty-four patients (mean age, 66±11 years; male sex, 51) were included. During 19±10 months follow-up, appropriate ICD therapy occurred in 19 (30%) patients. In Cox regression analyses, both percent scar (hazard ratio per 10%, 1.75; 95% CI, 1.09 to 2.81; P=0.02) and number of transmural scar segments (hazard ratio per segment, 1.40; 95% CI, 1.15 to 1.70; P=0.001) were significantly associated with the occurrence of appropriate ICD therapy.'] Is the extent of left ventricular scar quantified by late gadolinium enhancement MRI associated with spontaneous ventricular arrhythmias in patients with coronary artery disease and implantable cardioverter-defibrillators?
qiaojin/PubMedQA
2
[ -1.630832314491272, -1.6224576234817505, 2.3110251426696777 ]
['Brugada syndrome (BrS) has a significantly higher incidence among the male sex. Among genes coding ion channels and their modulatory proteins, KCNE5 (KCNE1L) is located in the X chromosome and encodes an auxiliary β-subunit for K channels. KCNE5 has been shown to modify the transient outward current (I(to)), which plays a key role in determining the repolarization process in the myocardium. This study investigated whether KCNE5 mutations could be responsible for BrS and other idiopathic ventricular fibrillation (IVF).', 'In 205 Japanese patients with BrS or IVF who tested negative for SCN5A mutation, we conducted a genetic screen for KCNE5 variants. We identified 2 novel KCNE5 variants: p.Y81H in 3 probands and p.[D92E;E93X] in 1 proband from 4 unrelated families. Y81H was identified in 1 man and 2 women; D92E;E93X was found in a 59-year-old man. All probands received implantable cardioverter-defibrillators. Functional consequences of the KCNE5 variants were determined through biophysical assay using cotransfection with KCND3 or KCNQ1. In the experiments with KCND3, which encodes Kv4.3, I(to) was significantly increased for both KCNE5 variants compared to wild type. In contrast, there were no significant changes in current properties reconstructed by KCNQ1+ wild type KCNE5 and the 2 variants. With the simulation model, both variants demonstrated notch-and-dome or loss-of-dome patterns.'] Are kCNE5 ( KCNE1L ) variants novel modulators of Brugada syndrome and idiopathic ventricular fibrillation?
qiaojin/PubMedQA
2
[ -2.1054015159606934, -1.4897863864898682, 2.5357666015625 ]
['Chronic obstructive pulmonary disease (COPD) is characterized by inflammation and remodeling of the lungs. This results in alterations in extracellular matrix (ECM) and structural changes leading to airflow obstruction. We studied the expression of tenascin-C (Tn-C) and alpha smooth muscle actin (α-SMA), which act as a marker of myofibroblasts, in large airways from COPD patients. Our aim was to elucidate whether this expression correlated with smoking or with disease development.', 'Bronchoscopy was performed on 20 COPD patients (mean age 56 years; range 39-61; FEV1/FVC < 70% and FEV1 median 53% (range 33-69) of predicted). Age and smoking matched smokers (S) without COPD (n = 13) and age matched non-smokers (NS) (n = 14) served as controls. Bronchial mucosal biopsies were analyzed by immunohistochemistry. The distribution of Tn-C expression was assessed and graded in three levels, and the number of spindle shaped cells staining positive for α-SMA were counted.', 'Biopsies from COPD patients had more (P < 0.001) Tn-C expression than the two control groups. A significantly (P < 0.05) increased number of spindle shaped cells expressing α-SMA was observed in COPD patients compared with the controls. Smokers and nonsmokers did not differ in this respect. The expression of Tn-C correlated positively (P < 0.001) to the number of α-SMA positive cells.'] Are tenascin-C and alpha-smooth muscle actin positive cells increased in the large airways in patients with COPD?
qiaojin/PubMedQA
2
[ -1.8955310583114624, -1.5332682132720947, 2.3589749336242676 ]
['Our purpose in conducting this study was to determine whether administration of high-dose tranexamic acid (TA) at the time of diagnosis of postpartum haemorrhage (PPH) could reduce blood loss.', 'This was a randomised, controlled, multicentred, open-label trial. Women with PPH >800 mL following vaginal delivery were randomly assigned to receive TA (loading dose 4 g over 1 hour, then infusion of 1 g/hour over 6 hours) or not. In both groups, packed red blood cells (PRBCs) and colloids could be used according to French guidelines. The use of additional procoagulant treatments was permitted only in cases involving intractable bleeding. The primary objective was to assess the efficacy of TA in the reduction of blood loss in women with PPH, and the secondary objectives were the effect of TA on PPH duration, anaemia, transfusion and the need for invasive procedures.', 'A total of 144 women fully completed the protocol (72 in each group). Blood loss between enrolment and 6 hours later was significantly lower in the TA group than in the control group (median, 173 mL; first to third quartiles, 59 to 377) than in controls (221 mL; first to third quartiles 105 to 564) (P = 0.041). In the TA group, bleeding duration was shorter and progression to severe PPH and PRBC transfusion was less frequent than in controls (P < 0.03). Invasive procedures were performed in four women in the TA group and in seven controls (P = NS). PPH stopped after only uterotonics and PRBC transfusion in 93% of women in the TA group versus 79% of controls (P = 0.016). Mild, transient adverse manifestations occurred more often in the TA group than in the control group (P = 0.03).'] Does high-dose tranexamic acid reduce blood loss in postpartum haemorrhage?
qiaojin/PubMedQA
2
[ -1.4669030904769897, -1.601001501083374, 2.0716192722320557 ]
['JAK2V617F mutation occurs in 90% of polycythemia vera (PV) and in 50% of essential thrombocythemia (ET) patients.', '253 consecutive patients affected by myeloproliferative disorders (MPD, 121 PV, 132 ET) were evaluated and stratified in 4 age groups: 18-39, 40-59, 60-75 and over 75 years (>75). The JAK2V617F mutation was searched and its allele burden was evaluated.', 'The percentage of mutated patients increased progressively with age mainly in patients >75 (p=0.0015 vs 18-39, p=0.0021 vs 40-59 and p=0.012 vs 60-75). We also found a progressive increase in allele burden with age (R2=0.042). Thrombotic events were more common in patients carrying the mutation in comparison with wild type (WT) (p=0.006, coefficient risk 1.94). No differences in the percentage of patients carrying the JAK2V617F mutation were found, in spite of different follow-up durations (<5 yrs, 5-10 yrs, 10-15 yrs, >15 yrs). The JAK2V617F allele burden was similar in patients with (57 ± 31%) and without (45 ± 26%) long-term hydroxyurea treatment.'] Is jAK2V617F mutation common in old patients with polycythemia vera and essential thrombocythemia?
qiaojin/PubMedQA
2
[ -1.2611099481582642, -1.3316972255706787, 1.6551767587661743 ]
['We evaluated the respective influence of the causative pathogen and infection site on hospital mortality from severe sepsis related to community-, hospital-, and intensive care unit-acquired infections.', 'We used a prospective observational cohort 10-yr database. We built a subdistribution hazards model with corrections for competing risks and adjustment for potential confounders including early appropriate antimicrobial therapy.', 'Twelve intensive care units.', 'We included 4,006 first episodes of acquisition-site-specific severe sepsis in 3,588 patients. INTEVENTIONS: None.', 'We included 1562 community-acquired, 1432 hospital-acquired, and 1012 intensive care unit-acquired episodes of severe sepsis. After adjustment, we found no independent associations of the causative organism, multidrug resistance of the causative organism, infection site, or presence of bacteremia with mortality. Early appropriate antimicrobial therapy was consistently associated with better survival in the community-acquired (0.64 [0.51-0.8], p = .0001), hospital-acquired (0.72 [0.58-0.88], p = .0011), and intensive care unit-acquired (0.79 [0.64-0.97], p = .0272) groups.'] Are outcomes in severe sepsis and patients with septic shock : pathogen species and infection sites associated with mortality?
qiaojin/PubMedQA
2
[ -2.1349432468414307, -1.2086436748504639, 2.4515576362609863 ]
['To test the hypothesis that red blood cell (RBC) transfusions in preterm infants are associated with increased intra-hospital mortality.', 'Variables associated with death were studied with Cox regression analysis in a prospective cohort of preterm infants with birth weight <1500 g in the Brazilian Network on Neonatal Research. Intra-hospital death and death after 28 days of life were analyzed as dependent variables. Independent variables were infant demographic and clinical characteristics and RBC transfusions.', 'Of 1077 infants, 574 (53.3%) received at least one RBC transfusion during the hospital stay. The mean number of transfusions per infant was 3.3 ± 3.4, with 2.1 ± 2.1 in the first 28 days of life. Intra-hospital death occurred in 299 neonates (27.8%), and 60 infants (5.6%) died after 28 days of life. After adjusting for confounders, the relative risk of death during hospital stay was 1.49 in infants who received at least one RBC transfusion in the first 28 days of life, compared with infants who did not receive a transfusion. The risk of death after 28 days of life was 1.89 times higher in infants who received more than two RBC transfusions during their hospital stay, compared with infants who received one or two transfusions.'] Are red blood cell transfusions independently associated with intra-hospital mortality in very low birth weight preterm infants?
qiaojin/PubMedQA
2
[ -0.9339985847473145, 0.011486323550343513, 0.039265893399715424 ]
['Genetic variants in TRAF1C5 and PTPN22 genes have been shown to be significantly associated with arthritis rheumatoid in Caucasian populations. This study investigated the association between single nucleotide polymorphisms (SNPs) in TRAF1/C5 and PTPN22 genes and rheumatoid arthritis (RA) in a Han Chinese population. We genotyped SNPs rs3761847 and rs7021206 at the TRAF1/C5 locus and rs2476601 SNP in the PTPN22 gene in a Han Chinese cohort composed of 576 patients with RA and 689 controls. The concentrations of anti-cyclic citrullinated peptide antibodies (CCP) and rheumatoid factor (RF) were determined for all affected patients. The difference between the cases and the controls was compared using χ2 analysis.', 'Significant differences in SNPs rs3761847 and rs7021206 at TRAF1/C5 were observed between the case and control groups in this cohort; the allelic p-value was 0.0018 with an odds ratio of 1.28 for rs3761847 and 0.005 with an odds ratio of 1.27 for rs7021206. This significant association between rs3761847 and RA was independent of the concentrations of anti-CCP and RF. No polymorphism of rs2476601 was observed in this cohort.'] Are single nucleotide polymorphisms at the TRAF1/C5 locus associated with rheumatoid arthritis in a Han Chinese population?
qiaojin/PubMedQA
2
[ -1.7153788805007935, -1.2746086120605469, 2.0504112243652344 ]
['To generate a prognostic index using recursive partitioning analysis (RPA) for patients undergoing spine stereotactic body radiation therapy (sSBRT) for spinal metastases (sMet).', 'From an institutional review board-approved database, 174 patients were treated for sMet with sSBRT between February 2006 and August 2009. Median dose was 14 Gy (range, 8-24 Gy), typically in a single fraction (range, 1-5). Kaplan-Meier analysis was performed to detect any correlation between survival and histology. Histologies were divided into favorable (breast and prostate), radioresistant (renal cell, melanoma and sarcoma), and other (all other histologies). RPA was performed to identify any association of the following variables with overall survival (OS) following sSBRT: histology, gender, age, Karnofsky performance status (KPS), control of primary, extraosseous metastases, time from primary diagnosis (TPD), dose of sSBRT (≤14 Gy vs. >14 Gy), extent of spine disease (epidural only, bone and epidural, bone only), upfront or salvage treatment, presence of paraspinal extension, and previous surgery.', 'Median follow-up was 8.9 months. Median OS time from sSBRT was 10.7 months. Median OS intervals for favorable histologies were 14 months, 11.2 months for radioresistant histologies, and 7.3 months for other histologies (p = 0.02). RPA analysis resulted in three classes (p < 0.0001). Class 1 was defined as TPD of >30 months and KPS of >70; Class 2 was TPD of >30 months and KPS of ≤70 or a TPD of ≤30 months and age <70 years old; Class 3 was TPD of ≤30 months and age ≥70 years old. Median OS was 21.1 months for Class 1 (n = 59), 8.7 months for Class 2 (n = 104), and 2.4 months for Class 3 (n = 11).'] Is recursive partitioning analysis index predictive for overall survival in patients undergoing spine stereotactic body radiation therapy for spinal metastases?
qiaojin/PubMedQA
2
[ -1.7218550443649292, -1.6337674856185913, 2.32961368560791 ]
['High serum copeptin levels are associated with injury severity after traumatic brain injury (TBI). However, not much is known regarding its relation with mortality. Thus, we sought to evaluate its relation with disease mortality.', 'Fifty healthy controls and 94 patients with acute severe TBI were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7. Its concentration was measured by enzyme-linked immunosorbent assay.', 'Twenty-six patients (27.7%) died from TBI in a month. After brain injury, plasma copeptin level in patients increased during the 6-hour period immediately, peaked in 24 hours, plateaued at day 2, decreased gradually thereafter, and was substantially higher than that in healthy controls during the 7-day period. A forward stepwise logistic regression selected plasma copeptin level (odds ratio, 1.008; 95% confidence interval, 1.002-1.014; p = 0.010) as an independent predictor for 1-month mortality of patients. A multivariate linear regression showed that plasma copeptin level was negatively associated with Glasgow Coma Scale (GCS) score (t = -7.161; p < 0.001). A receiver operating characteristic curve identified plasma copeptin cutoff level (451.8 pg/mL) that predicted 1-month mortality with the optimal sensitivity (88.5%) and specificity (75.0%) values (area under curve, 0.874; 95% confidence interval, 0.789-0.933; p < 0.001). The area under curve of plasma copeptin level was similar to that of GCS score (p = 0.299). However, copeptin did not statistically significantly improve the area under curve of GCS score (p = 0.413).'] Is copeptin associated with mortality in patients with traumatic brain injury?
qiaojin/PubMedQA
2
[ -1.0470175743103027, -1.706400990486145, 1.7980108261108398 ]
['Appropriateness of the vitamin doses in Japanese commercial multi-vitamin preparations for parenteral nutrition therapy was investigated in patients with gastrointestinal tract disorder by evaluating the vitamin status (blood concentrations and urinary excretions of vitamins B1, B2, B6, and C) of them.', 'Commercial multivitamin preparations were administered continuously with a commercial PN solution over 5 days to 10 patients with gastrointestinal tract disorder. Blood concentrations of vitamins B1, B2, B6, and C were measured on the mornings of day 1, day 4, and day 6. Urinary excretions were measured in 24-h urine collections collected after day 3 and after day 5.', 'Blood concentrations of vitamins B1, B2, and B6 increased but remained within or slightly above the normal throughout the study, and urinary excretion values were normal in all patients. However, blood vitamin C concentration surpassed the lower limit of normal (5.5 microg/mL) only on day 6. Urinary vitamin C excretion was below normal (20.0 mg/day) in all and 7 patients on days 3 and 5, respectively.'] Do patients with gastrointestinal tract disorders receiving parenteral nutrition need a higher dose of vitamin C?
qiaojin/PubMedQA
2
[ -1.4189790487289429, -1.1732597351074219, 1.5996685028076172 ]
['GH has positive cognitive effects when given to GH-IGF-I-deficient patients. GH and IGF-I exert both neuroprotective and regenerative effects on experimental stroke. We investigated whether the endogenous serum IGF-I (s-IGF-I) levels correlated with recovery of functional independence in patients who had suffered an ischemic stroke.', 'The s-IGF-I levels were measured in 407 patients (260 males, 147 females) with mean age of 55 (range, 18-69) yr and 40 randomly selected matched controls who were previously included in the Sahlgrenska Academy Study on Ischemic Stroke. Serum samples were collected on two occasions: acutely at 1-10 d (median, 4 d) after stroke and 3 months after the stroke. Recovery after ischemic stroke was evaluated using the modified Rankin scale 3 and 24 months after the stroke, and the Scandinavian Stroke Scale was used for assessments during the acute stage and 3 months after the stroke.', 'The s-IGF-I levels were higher in the acute stage than after 3 months and compared with the controls (P < 0.001 and P < 0.01, respectively), and the s-IGF-I levels were progressively lower in the elderly patients. The levels of s-IGF-I in the acute phase and after 3 months both positively correlated with improvement in the modified Rankin scale scores between 3 and 24 months (P = 0.001; r = 0.174, and P < 0.001; r = 0.24, respectively).'] Do serum IGF-I levels correlate to improvement of functional outcome after ischemic stroke?
qiaojin/PubMedQA
2
[ -0.9722331166267395, -1.3978865146636963, 1.3793259859085083 ]
['Slit-lamp beam measurements of a pterygium can be difficult to reproduce accurately.', 'To compare standard slit-lamp beam measurements of pterygia to computer caliper measurements of Anterior Segment Optical Coherence Tomography (OCT)images.', 'Thirteen pterygia often patients were evaluated. Two physicians independently measured each pterygium using the slit lamp beam. Caliper measurements of two different OCT images of each pterygium were obtained. All measurements determined the distance from the limbus to the pterygium apex.', 'The difference in the slit lamp beam measurements of each pterygium was calculated and the mean of the differences was 0.3 and the standard deviation was 0.32.The difference in the two OCT measurements of each pterygium was also calculated and the mean of the differences was 0.1 and the standard deviation was 0.12. A two-tailed t-test demonstrated a statistically significant difference in these measurements (p = 0.0256).'] Are pterygia measurements more accurate with anterior segment optical coherence tomography - a pilot study?
qiaojin/PubMedQA
2
[ -1.4924644231796265, -1.2140921354293823, 1.8110343217849731 ]
['It has recently been reported that unilateral fatiguing exercise affects not only the motor area innervating the exercising muscle but also the ipsilateral motor area innervating homologous nonexercised muscle.', 'This study was designed to clarify the effects of fatiguing intermittent lower limb exercise on the excitability of the motor cortex representation of nonexercised muscles in the arm.', 'Eight subjects performed an intermittent leg press exercise composed of three bouts of 5-minute leg press (T1, T2, and T3) at 50% of maximal voluntary contraction separated by a 2-minute rest. Motor-evoked potentials (MEP), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF), using paired-pulse transcranial magnetic stimulation, were assessed in two nonexercised arm muscles (first dorsal interosseous muscle: FDI, n = 8; biceps brachii muscle: BB, n = 6) and one exercised leg muscle (quadriceps femoris muscle: QF, n = 6) before and immediately after each bout of exercise and for 30 minutes during recovery after the end of the third exercise bout (Experiment 1). Experiment 2 was the same as Experiment 1, except that the test pulse intensity was adjusted to produce a given amplitude of MEP(TEST) at each time point.', 'MEPs and SICI in the exercised QF muscle were depressed at all time points during and after fatigue. In contrast, MEPs in nonexercised arm muscles were facilitated from T1-T3 (T3, only FDI), but were then depressed for up to 20 minutes in the recovery period. SICI was reduced in both muscles during T1-T3 and remained depressed until 20 minutes into recovery. ICF was unchanged in arm muscles but depressed in QF over T1-T3.'] Does fatiguing intermittent lower limb exercise influence corticospinal and corticocortical excitability in the nonexercised upper limb?
qiaojin/PubMedQA
2
[ -2.00028133392334, -1.2029998302459717, 2.2422022819519043 ]
['Hepatocellular carcinoma (HCC) usually has a dismal prognosis because of its limited response to current pharmacotherapy and high metastatic rate. Sulfated oligosaccharide has been confirmed as having potent antitumor activities against solid tumors. Here, we explored the preclinical effects and molecular mechanisms of isomalto oligosaccharide sulfate (IMOS), another novel sulfated oligosaccharide, in HCC cell lines and a xenograft model.', 'The effects of IMOS on HCC proliferation, apoptosis, adhesion, migration, and invasiveness in vitro were assessed by cell counting, flow cytometry, adhesion, wound healing, and transwell assays, respectively. The roles of IMOS on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. Total and phosphorylated protein levels of AKT, ERK, and JNK as well as total levels of c-MET were detected by Western blotting. IMOS-regulated genes were screened by quantitative reverse-transcription PCR (qRT-PCR) array in HCCLM3-red fluorescent protein (RFP) xenograft tissues and then confirmed by qRT-PCR in HepG2 and Hep3B cells.', 'IMOS markedly inhibited cell proliferation and induced cell apoptosis of HCCLM3, HepG2, and Bel-7402 cells and also significantly suppressed cell adhesion, migration, and invasion of HCCLM3 in vitro. At doses of 60 and 90 mg/kg/d, IMOS displayed robust inhibitory effects on HCC growth and metastasis without obvious side effects in vivo. The levels of pERK, tERK, and pJNK as well as c-MET were significantly down-regulated after treatment with 16 mg/mL IMOS. No obvious changes were found in the levels of pAkt, tAkt, and tJNK. Ten differentially expressed genes were screened from HCCLM3-RFP xenograft tissues after treatment with IMOS at a dose of 90 mg/kg/d. Similar gene expression profiles were confirmed in HepG2 and Hep3B cells after treatment with 16 mg/mL IMOS.'] Does isomalto oligosaccharide sulfate inhibit tumor growth and metastasis of hepatocellular carcinoma in nude mice?
qiaojin/PubMedQA
2
[ -2.301142454147339, -1.4135148525238037, 2.749035120010376 ]
['Our aim was to determine the influence of prenatal tobacco exposure on regional cerebral tissue oxygen saturation (r(c)SO(2)) and fractional tissue oxygen extraction (FTOE) in preterm infants. We hypothesized that as a result of vasoconstriction caused by prenatal tobacco exposure r(c)SO(2) would be lower and FTOE would be higher during the first days after birth in infants exposed to tobacco during pregnancy.', 'Sixty preterms were included in this prospective, observational cohort study (median gestational age 29.9 weeks, range 26.0-31.8, median birth weight 1248 g, range 615-2250). Fourteen infants had been exposed to tobacco during pregnancy. All mothers smoked more than five cigarettes a day till delivery. We measured r(c)SO(2) and transcutaneous arterial oxygen saturation (tcSaO(2)) in all infants on days 1-5, 8, and 15. FTOE was calculated: FTOE=(tcSaO(2)-r(c)SO(2))/tcSaO(2).', 'In preterm infants exposed to tobacco during pregnancy, r(c)SO(2) was lower during days 1, 2, and 8 after birth, median 73% versus 81%, 73% versus 80% and 71% versus 78% respectively. FTOE was higher during days 1 and 8 after birth, median 0.24 versus 0.15 and 0.26 versus 0.19 respectively. On the second day, FTOE tended to be higher, 0.18 versus 0.14.'] Does prenatal tobacco exposure influence cerebral oxygenation in preterm infants?
qiaojin/PubMedQA
0
[ 0.556139349937439, -1.7881290912628174, 0.3275187611579895 ]
['Hantaviruses are important human pathogens that cause clinical diseases characterized by renal and cardiopulmonary manifestations. Their pathogenesis is currently poorly understood. We have studied the role of the complement system in the pathogenesis of Puumala (PUUV) hantavirus infection.', 'We studied the activation of complement by measuring the terminal complement complex SC5b-9 and complement component C3 and C4 levels in patients with acute PUUV infection. Several laboratory parameters and clinical findings reflecting the severity of PUUV-HFRS were evaluated with regard to complement activation.', 'The levels of SC5b-9 were significantly increased and C3 decreased in the acute stage as compared to the levels at full recovery (P < 0.001). We found that SC5b-9 levels were higher in patients with chest X-ray abnormalities than in patients with a normal X-ray during the acute stage (P = 0.028). Furthermore, SC5b-9 and C3 levels showed significant correlation with several clinical and laboratory parameters that reflect the severity of the acute PUUV infection.'] Does complement activation in Puumala hantavirus infection correlate with disease severity?
qiaojin/PubMedQA
2
[ -2.4053337574005127, -0.8498710989952087, 2.318765163421631 ]
['To examine the hypothesis that vitamin D deficiency (VDD) is associated with an increased prevalence of microvascular complications in young people with type 1 diabetes.', 'In a cross-sectional study of 517 patients, 25-hydroxyvitamin D was measured. Retinopathy was assessed by 7-field stereoscopic retinal photography, peripheral neuropathy by thermal and vibration threshold testing, and microalbuminuria by albumin excretion rate or albumin-to-creatinine ratio.', 'Retinopathy prevalence was higher in cases with VDD versus sufficiency (18 vs. 9%, P = 0.02); deficiency was not associated with microalbuminuria or neuropathy. In logistic regression, retinopathy was associated with VDD (odds ratio 2.12 [95% CI 1.03-4.33]), diabetes duration (1.13, 1.05-1.23), and HbA(1c) (1.24, 1.02-1.50).'] Is vitamin D deficiency associated with retinopathy in children and adolescents with type 1 diabetes?
qiaojin/PubMedQA
2
[ -2.214751958847046, -1.3677361011505127, 2.6418488025665283 ]
['Pulmonary hypertension (PH) in COPD carries a poor prognosis. Statin therapy has been associated with numerous beneficial clinical effects in COPD, including a possible improvement in PH. We examined the association between statin use and pulmonary hemodynamics in a well-characterized cohort of patients undergoing evaluation for lung transplantation.', 'We conducted a cross-sectional analysis of 112 subjects evaluated for lung transplant with a diagnosis of COPD. Clinical characteristics, pulmonary function, cardiac catheterization findings and medical comorbidities were compared between statins users and non-users.', 'Thirty-four (30%) subjects were receiving statin therapy. Statin users were older and had an increased prevalence of systemic hypertension and coronary artery disease (CAD). Mean pulmonary arterial pressure (mPAP) in the statin group was lower [26 ± 7 vs 29 ± 7 mmHg, p = 0.02], as was pulmonary artery wedge pressure (PAWP) [12 ± 5 vs. 15 ± 6 mmHg, p = 0.02]. Pulmonary vascular resistance did not differ between the groups. In multiple regression analysis, statin use was associated with a 4.2 mmHg (95% CI: 2 to 6.4, p = <0.001) lower PAWP and a 2.6 mmHg (95% CI: 0.3 to 4.9, p = 0.03) reduction in mPAP independent of PAWP.'] Is statin therapy associated with decreased pulmonary vascular pressures in severe COPD?
qiaojin/PubMedQA
2
[ -1.8798956871032715, -1.478140115737915, 2.4085493087768555 ]
['The docosahexaenoic acid (DHA) intake of pregnant women is lower than estimates of the DHA accretion by the fetus, and recommendations were made to increase the DHA intake of pregnant women.', 'The objective of this study was to determine whether the supplementation of pregnant women with DHA improved the visual acuity of infants at 4 mo.', 'We conducted a blinded assessment of a subset of healthy, full-term infants born to women enrolled in a double-blind, randomized controlled trial called the DHA for Maternal and Infant Outcomes (DOMInO) trial. Women were randomly assigned to consume DHA-rich fish-oil capsules (≈800 mg DHA/d in the treatment group) or vegetable oil capsules (control group) from midpregnancy to delivery. The primary outcome was the sweep visual evoked potential (VEP) acuity at 4 mo. The VEP latency at 4 mo was a secondary outcome.', 'Mean (±SD) VEP acuity did not differ between treatment and control groups [treatment group: 8.37 ± 2.11 cycles per degree (cpd), n = 89; control group: 8.55 ± 1.86 cpd, n = 93; P = 0.55]. VEP latencies also did not differ between groups. Irrespective of the group, maternal smoking in pregnancy was independently associated with poorer VEP acuity in the infant.'] Does maternal supplementation with docosahexaenoic acid during pregnancy affect early visual development in the infant : a randomized controlled trial?
qiaojin/PubMedQA
2
[ -2.038421869277954, -1.2080512046813965, 2.274796724319458 ]
['It remains incompletely understood whether patients with transfusion related cardiac iron overload without signs of heart failure exhibit already subclinical alterations of systolic left ventricular (LV) dysfunction. Therefore we performed a comprehensive evaluation of systolic and diastolic cardiac function in such patients using tagged and phase-contrast CMR.', "19 patients requiring regular blood transfusions for chronic anemia and 8 healthy volunteers were investigated using cine, tagged, and phase-contrast and T2* CMR. LV ejection fraction, peak filling rate, end-systolic global midventricular systolic Eulerian radial thickening and shortening strains as well as left ventricular rotation and twist, mitral E and A wave velocity, and tissue e' wave and E/e' wave velocity ratio, as well as isovolumic relaxation time and E wave deceleration time were computed and compared to cardiac T2*.", 'Patients without significant iron overload (T2* > 20 ms, n = 9) had similar parameters of systolic and diastolic function as normal controls, whereas patients with severe iron overload (T2* < 10 ms, n = 5), had significant reduction of LV ejection fraction (54 ± 2% vs. 62 ± 6% and 65 ± 6% respectively p < 0.05), of end-systolic radial thickening (+6 ± 4% vs. +11 ± 2 and +11 ± 4% respectively p < 0.05) and of rotational twist (1.6 ± 0.2 degrees vs. 3.0 ± 1.2 and 3.5 ± 0.7 degrees respectively, p < 0.05) than patients without iron overload (T2* > 20 ms) or normal controls. Patients with moderate iron overload (T2* 10-20 ms, n = 5), had preserved ejection fraction (59 ± 6%, p = NS vs. pts. with T2* > 20 ms and controls), but showed reduced maximal LV rotational twist (1.8 ± 0.4 degrees). The magnitude of reduction of LV twist (r = 0.64, p < 0.001), of LV ejection fraction (r = 0.44, p < 0.001), of peak radial thickening (r = 0.58, p < 0.001) and of systolic (r = 0.50, p < 0.05) and diastolic twist and untwist rate (r = -0.53, p < 0.001) in patients were directly correlated to the logarithm of cardiac T2*.'] Is iron overload in polytransfused patients without heart failure associated with subclinical alterations of systolic left ventricular function using cardiovascular magnetic resonance tagging?
qiaojin/PubMedQA
2
[ -1.327264666557312, -1.7270150184631348, 2.0473697185516357 ]
['Endothelial dysfunction is known to be associated with atherosclerosis progression and cardiovascular events. Limited information exists regarding the importance of this topic in hypertensive postmenopausal women. In this particular population the influence of endothelial dysfunction on cardio-vascular end cerebro-vascular events is well demonstrated. Therefore, we investigated, in a prospective study, the influence of endothelial-dependent vasodilation on carotid intima-media thickness (IMT) progression in our population of hypertensive postmenopausal women.', 'In addition to common risk factors and pharmacological therapy, we measured carotid IMT and flow-mediated dilation (FMD) of the brachial artery at baseline and after 1 year of follow-up.', 'Baseline and follow-up data were available for 618 hypertensive postmenopausal women with an age of 55 ± 8 years. The mean IMT at baseline was 754 ± 161 μm [interquartile range (IQR) from 600 to 838 μm]. The mean FMD at baseline was 5.8 ± 3.9% (IQR from 3.2 to 8.2%). There was a significant correlation between baseline FMD and carotid IMT (r = -0.16; P = 0.003). Mean IMT progression resulted in 103 μm (range from -250 to 567 μm; IQR from 0 to 200 μm) per year. Baseline FMD, FMD change and the amount of SBP reduction during follow-up remained the independent predictors of IMT progression in multivariable analysis.'] Does endothelial function affect early carotid atherosclerosis progression in hypertensive postmenopausal women?
qiaojin/PubMedQA
2
[ -2.0046777725219727, -1.484223484992981, 2.4907851219177246 ]
['Lifestyle intervention is not always effective for improving arterial hypertension and other cardiovascular risk factors, and the parameters determining the outcome are not known. Because high cardiorespiratory fitness (CRF) protects from cardiovascular disease and mortality, we determined whether CRF at baseline predicts the improvement of blood pressure and other cardiovascular risk factors during a lifestyle intervention.', 'A total of 219 patients at risk for type 2 diabetes, who underwent a 9-month lifestyle intervention with diet modification and increase in physical activity, and had measurement of CRF, were studied. Insulin sensitivity was estimated during a 75-g oral glucose tolerance test. Total body, visceral and liver fat were measured by magnetic resonance (MR) tomography and H-MR spectroscopy. CRF was estimated using two different methods, an incremental cycle exercise (maximal aerobic capacity-VO2max) test and a motorized treadmill (individual anaerobic threshold) test.', 'After 9 months of intervention adiposity, glycemia, CRF, insulin sensitivity, SBP and serum lipids (except high-density lipoprotein cholesterol, P = 0.65) improved (all other P ≤ 0.006). DBP did not change significantly (P = 0.06). High CRF at baseline predicted decreases in SBP (P ≤ 0.0002) and DBP (P ≤ 0.004), and increase in insulin sensitivity (P ≤ 0.04), but not change in serum lipids (all P ≥ 0.06). For 1 SD increase in baseline CRF the odds ratio for resolution of hypertension or prehypertension was 2.26 (individual anaerobic threshold; 95% CI 1.40-3.80) and 1.75 (VO2max; 95% CI 1.08-2.89).'] Does cardiorespiratory fitness determine the reduction in blood pressure and insulin resistance during lifestyle intervention?
qiaojin/PubMedQA
2
[ -0.877162754535675, -1.7985315322875977, 1.6803994178771973 ]
['The oral contraceptive pill (OCP) is widely prescribed throughout the world. Although it is associated with a small but significant increase in blood pressure, the influence of the OCP on large artery stiffness and wave reflection is unclear. The aim of this study was to determine the relationship between use of the OCP and aortic stiffness and wave reflections in a young, healthy cohort of women.', 'Participants were drawn from the ENIGMA study, which examines the natural history of blood pressure in young adults. A detailed medical history and lifestyle questionnaire, including OCP details were taken. Blood pressure was measured according to the British Hypertension Society guidelines. Aortic pulse wave velocity (aPWV) was measured together with augmentation index (AIx). Stroke volume (SV) and cardiac output (CO) were also assessed.', 'Women taking the OCP (n = 225) had a higher SBP and pulse pressure compared with nonusers (n = 660; 112 ± 12 vs. 110 ± 11 and 43 ± 8 vs. 42 ± 8 mmHg, respectively, P < 0.05 for both). CO and SV were also higher (6.6 ± 1.5 vs. 6.3 ± 1.5 l/min, P < 0.01 and 81 ± 16 vs. 78 ± 19 ml, P < 0.05) as was aPWV (5.5 ± 0.7 vs. 5.4 ± 0.7 m/s, P < 0.05). However, there was no difference in DBP (68 ± 9 vs. 69 ± 9 mmHg), mean arterial pressure (81 ± 10 vs. 81 ± 10 mmHg) or AIx (2 ± 12 vs. 3 ± 13%) between the groups.'] Is use of the oral contraceptive pill associated with increased large artery stiffness in young women : the ENIGMA study?
qiaojin/PubMedQA
2
[ -0.7332178354263306, -1.6048038005828857, 1.4353621006011963 ]
['Excessive reactive oxygen species (ROS) activate the inflammatory transcription factor nuclear factor-kappa B (NF-κB). ROS-induced inflammation appears to be an early event in the development of hypertension in different models. In the spontaneously hypertensive rat (SHR) we investigated whether perinatal inhibition of NF-κB persistently decreases blood pressure. To probe antihypertensive mechanisms we studied natriuresis and sensitivity of blood pressure and renal hemodynamics to the superoxide dismutase mimetic Tempol.', 'Perinatal pyrrolidine di thio carbamate (PDTC) (a NF-κB inhibitor), administered during pregnancy and lactation to SHR dams, persistently ameliorated hypertension up to 28 weeks of age in their offspring. Furthermore, after perinatal treatment with PDTC natriuresis was temporarily doubled at 4 weeks of age in both females and males. Urinary excretion of thiobarbituric acid reactive substances (an indirect measure of oxidative stress) was decreased by perinatal PDTC, persistently in females and temporarily in males. At 28 weeks, Tempol reduced arterial pressure in all groups, but had opposite effects in control and perinatal PDTC rats on renal vascular resistance (RVR), namely decreased RVR in controls and increased RVR in perinatal PDTC rats.'] Does perinatal inhibition of NF-kappaB have long-term antihypertensive effects in spontaneously hypertensive rats?
qiaojin/PubMedQA
2
[ -2.510082960128784, -1.2906941175460815, 2.8219730854034424 ]
['The RET/GDNF signalling pathway plays a crucial role during development of the kidneys and the enteric nervous system. In humans, RET activating mutations cause multiple endocrine neoplasia, whereas inactivating mutations are responsible for Hirschsprung disease. RET mutations have also been reported in fetuses with renal agenesis, based on analysis of a small series of samples.', "To characterise better the involvement of RET and GDNF in kidney development defects, a series of 105 fetuses with bilateral defects, including renal agenesis, severe hypodysplasia or multicystic dysplastic kidney, was studied. RET and GDNF coding sequences, evolutionary conserved non-coding regions (ECRs) in promoters, 3'UTRs, and RET intron 1 were analysed. Copy number variations at these loci were also investigated.", "The study identified: (1) a low frequency (<7%) of potential mutations in the RET coding sequence, with inheritance from the healthy father for four of them; (2) no GDNF mutation; (3) similar allele frequencies in patients and controls for most single nucleotide polymorphism variants, except for RET intron 1 variant rs2506012 that was significantly more frequent in affected fetuses than in controls (6% vs 2%, p=0.01); (4) distribution of the few rare RET variants unidentified in controls into the various 5'-ECRs; (5) absence of copy number variations."] Are rET and GDNF mutations rare in fetuses with renal agenesis or other severe kidney development defects?
qiaojin/PubMedQA
2
[ -2.007192373275757, -1.2987607717514038, 2.354828119277954 ]
['The King Island Emu (Dromaius ater) of Australia is one of several extinct emu taxa whose taxonomic relationship to the modern Emu (D. novaehollandiae) is unclear. King Island Emu were mainly distinguished by their much smaller size and a reported darker colour compared to modern Emu.', 'We investigated the evolutionary relationships between the King Island and modern Emu by the recovery of both nuclear and mitochondrial DNA sequences from sub-fossil remains. The complete mitochondrial control (1,094 bp) and cytochrome c oxidase subunit I (COI) region (1,544 bp), as well as a region of the melanocortin 1 receptor gene (57 bp) were sequenced using a multiplex PCR approach. The results show that haplotypes for King Island Emu fall within the diversity of modern Emu.'] Does ancient DNA suggest dwarf and 'giant ' emu are conspecific?
qiaojin/PubMedQA
2
[ -2.3117835521698, 0.6877841949462891, 0.7522221803665161 ]
["Increasing evidence has demonstrated that the senescence of vascular endothelial cells has critical roles in the pathogenesis of vascular dysfunction such as atherosclerosis and thrombosis. MicroRNA (miR) are small non-coding RNAs that inhibit gene expression by binding to complementary sequences in the 3'UTR of their target mRNAs. MiRs modulate a variety of biological functions such as cell development, cell differentiation, and apoptosis. Moreover, several miRs involved in endothelial cell function have been identified.", 'Through a microarray approach, we have identified a miR-146a that is progressively modulated in endothelial cells with aging. In young human umbilical vein endothelial cells, this miR is involved in a premature senescence-like phenotype through direct targeting of the NOX4 protein, implicated in cell senescence and aging.'] Is miR-146a modulated in human endothelial cell with aging?
qiaojin/PubMedQA
2
[ -2.402879238128662, -0.81707364320755, 2.308450698852539 ]
['Delirium is an acute, reversible and fluctuating central nervous system dysfunction with an organic cause, and is associated with substantial morbidity and mortality. Many recent studies have shown that delirium is highly prevalent in the Intensive Care Unit (ICU) population. Despite its seriousness; delirium in the ICU is under recognized by bedside nurses.', 'To determine if routine bedside nurse-patient interactions enable the detection of delirium.', 'We performed a single center observational study, in a 12 bed general Intensive Care Unit. Bedside nurses were asked to assess patients for delirium during routine patient care throughout their shift. This assessment was then compared to an independent assessment using the Confusion Assessment Method - ICU (CAM-ICU) performed by a nurse trained in this delirium detection tool.', 'We analysed the results of 35 matched assessments performed on 35 patients. The presence of delirium was identified by the bedside nurse in 27% of CAM-ICU delirium positive assessments, whereas the absence of delirium was identified by the bedside nurse in 92% of CAM-ICU delirium negative assessments.'] Do bedside nurse-patient interactions reliably detect delirium : an observational study?
qiaojin/PubMedQA
2
[ -2.475072145462036, -0.5040927529335022, 2.1165096759796143 ]
['The present study describes the spasmogenic and spasmolytic activities of Daphne oleoides Schreb. (Thymelaeaceae), exploring the possible underlying pharmacological mechanisms.', 'Pharmacological investigation of Daphne oleoides to provide evidence for its therapeutic application in gastrointestinal motility disorders.', 'Methanol crude extract of Daphne oleoides (Do.Cr) was studied in gastrointestinal isolated tissues.', 'In spontaneously contracting rabbit jejunum preparations, Do.Cr at 0.3-3.0 mg/mL caused moderate stimulation, followed by relaxant effect at the next higher concentrations (5.0-10\u2009mg/mL). In presence of atropine, spasmogenic effect was blocked and the relaxation was emerged, suggesting that the spasmogenic effect of Daphne oleoides is mediated through activation of muscarinic receptors. When tested against the high K+ (80\u2009mM)-induced contractions, Do.Cr (0.3-5.0\u2009mg/mL), like verapamil, inhibited the induced contractions, suggesting Ca++ channel blockade (CCB) effect. The CCB effect was further confirmed when pre-treatment of the tissue with Do.Cr shifted the Ca++ concentration-response curves to the right, similar to that caused by verapamil.'] Are gut modulatory effects of Daphne oleoides mediated through cholinergic and Ca++ antagonist mechanisms?
qiaojin/PubMedQA
2
[ -2.4862518310546875, -1.2479238510131836, 2.8213424682617188 ]
['Caner-initiating cells (CICs or cancer stem cells) have been shown both experimentally and clinically to be resistant to radiation. The mechanism underlying radioresistance remains unclear.', 'In the present study, we screened 51 genes which are potentially important in mediating radioresistance of breast CICs.', 'The expression of AKT1 and AKT2 at protein and mRNA levels was dramatically increased among the screened genes by 8\xa0Gy radiation treatment in MCF-7 mammosphere cells (predominantly CD24(-/low)/CD44(+) CICs), but not in the bulk population of MCF-7 cells (predominantly CD24(+)/CD44(+)). Using apoptosis and clonogenic survival assays, we found pharmacological inhibition of AKT with selective inhibitors of AKT sensitized MCF-7 mammosphere cells, but not MCF-7 monolayer cells to radiation.'] Does pharmacological inhibition of AKT sensitize MCF-7 human breast cancer-initiating cells to radiation?
qiaojin/PubMedQA
2
[ -2.450634717941284, -1.1368012428283691, 2.612058162689209 ]
['To investigate biological differences and prognostic indicators of different ampullary cancer (AC) subtypes.', 'AC is associated with a favorable prognosis compared with other periampullary carcinomas. Aside from other prognostic factors, the histological origin of AC may determine survival. Specifically, the pancreatobiliary subtype of AC displays worse prognosis compared with the intestinal subtype. However, knowledge of inherent molecular characteristics of different periampullary tumors and their effects on prognosis has been limited.', 'Gene expression profiling was used to screen for differential gene expression between 6 PDAC cases and 12 AC cases. Among others, hepatocyte nuclear factor 4α (HNF4α) mRNA overexpression was observed in AC cases. Nuclear HNF4α protein expression was assessed using tissue microarrays consisting of 99 individual AC samples. The correlation of HNF4α expression with clinicopathological data (n = 99) and survival (n = 84) was assessed.', 'HNF4α mRNA is 7.61-fold up-regulated in AC compared with that in PDAC. Bioinformatics analyses indicated its key role in dysregulated signaling pathways. Nuclear HNF4α expression correlates with histological subtype, grading, CDX2 positivity, MUC1 negativity and presence of adenomatous components in the carcinoma. The presence of HNF4α is a univariate predictor of survival in AC mean survival (50 months versus 119 months, P = 0.002). Multivariate analysis revealed that HNF4α negativity (HR = 17.95, 95% CI: 2.35-136.93, P = 0.005) and lymph node positivity (HR = 3.33, 95% CI: 1.36-8.18, P = 0.009) are independent negative predictors of survival.'] Does hepatocyte nuclear factor ( HNF ) 4α expression distinguish ampullary cancer subtypes and prognosis after resection?
qiaojin/PubMedQA
2
[ -2.1376330852508545, -1.4966497421264648, 2.635626792907715 ]
['Heavy smokers exhibit greater levels of impulsive choice and behavioural disinhibition than non-smokers. To date, however, the relationship between nicotine use and differing dimensions of impulsivity has not been systematically assessed.', 'A series of studies was designed to assess the acute dose-response effects of nicotine and the nicotinic receptor antagonist mecamylamine alone, and in combination with nicotine, on impulsive choice and behavioural disinhibition in rats.', 'Separate groups of rats were trained on a symmetrically reinforced go/no-go task to measure levels of disinhibition and a systematic delayed reward task to measure levels of impulsive choice. Once trained, all animals in each task were treated acutely with nicotine (0.125, 0.25, 0.5 and 1.0 mg/kg), mecamylamine (0.1, 0.3 and 1.0 mg/kg) and varying doses of mecamylamine (0.1, 0.3 and 1.0 mg/kg) prior to nicotine (0.5 mg/kg). An additional experiment assessed the effects of alterations in primary motivation (presatiation and fasting) on performance in both tasks.', 'Acute nicotine increased both impulsive choice and behavioural disinhibition, effects that were blocked by pre-treatment with mecamylamine. Mecamylamine when administered alone did not alter impulsive behaviour. The lack of effect of presatiation on performance measures suggests that the observed nicotine-induced impulsivity cannot be attributed to the anorectic activity of the compound.'] Does acute nicotine increase both impulsive choice and behavioural disinhibition in rats?
qiaojin/PubMedQA
2
[ -2.544745922088623, -0.9061927199363708, 2.529891014099121 ]
['Although abuse of benzodiazepines alone is uncommon, it is high in polydrug abusers, including those who primarily use opioids or stimulants.', 'This study investigated whether drugs that are abused (e.g., amphetamine) or drugs that have mechanisms of action similar to abused drugs (e.g., morphine) alter the discriminative stimulus effects of the benzodiazepine midazolam.', 'Three rhesus monkeys discriminated 0.56 mg/kg of midazolam while responding under a fixed-ratio 10 schedule of food presentation. Dose-effect curves were determined for midazolam alone and in the presence of morphine (opioid receptor agonist), amphetamine (dopamine receptor indirect agonist), dizocilpine (N-methyl-D: -aspartic acid receptor antagonist), or γ-butyrolactone (prodrug of γ-hydroxybutyrate, which acts primarily at GABA(B) receptors).', 'Doses of midazolam larger than 0.32 mg/kg produced ≥80% midazolam-lever responding. When administered alone, morphine, amphetamine, dizocilpine, and γ-butyrolactone did not produce midazolam-lever responding, although large doses of each drug eliminated responding; when administered in combination with midazolam, they did not alter the discriminative stimulus effects of midazolam up to doses that markedly decreased response rates.'] Are the discriminative stimulus effects of midazolam resistant to modulation by morphine , amphetamine , dizocilpine , and γ-butyrolactone in rhesus monkeys?
qiaojin/PubMedQA
2
[ -2.2859256267547607, -1.1901342868804932, 2.52531099319458 ]
["Clarification of alcohol's effect on stress response during threat is critical to understand motivation for alcohol use and related alcohol-use disorders. Evaluation of stress response dampening (SRD) effects of alcohol has been limited by nonsystematic use of varied experimental methods and measures.", 'This experiment parametrically varied alcohol dose and shock threat intensity among social drinkers to examine their effects on startle potentiation, a physiological measure of the affective component of the stress response.', 'Ninety-six participants were assigned to one of four beverage groups: placebo and target blood alcohol concentration (BAC) groups of 0.04%, 0.075%, and 0.11%. Participants viewed colored cues presented in shock and no-shock blocks. Distinct colored cues predicted imminent low, moderate, or high intensity electric shock administration. Startle potentiation during shock threat relative to no-shock cues indexed affective response.', 'High threat increased startle potentiation relative to moderate/low intensity threat. Startle potentiation decreased as BAC increased. Threat intensity moderated this BAC effect with the strongest BAC effect observed during high threat. Analysis of individual difference moderators revealed reduced effect of BAC among heavier, more problematic drinkers.'] Do alcohol dose effects on stress response to cued threat vary by threat intensity?
qiaojin/PubMedQA
2
[ -2.3244926929473877, -0.5213265419006348, 1.895846962928772 ]
['The response of colorectal tumours to chemotherapy is highly variable. Preclinical work has shown that the Kirsten ras (KRAS) oncogene sensitizes colorectal tumour cells to oxaliplatin and capecitabine in a wild-type tumour suppressor p53 (TP53)-dependent manner. Therefore, whether or not the combined mutation status of KRAS and TP53 could predict response to chemotherapy in metastatic colorectal cancer was tested.', 'A subgroup of patients from the CAIRO2 study (randomized phase III study on capecitabine, oxaliplatin, bevacizumab with or without cetuximab in first-line advanced colorectal cancer) that received capecitabine plus oxaliplatin (CAPOX) treatment in combination with bevacizumab was selected. The tumours were analyzed for KRAS and TP53 mutations by PCR/sequencing. The relationship between tumour response and genotype was analyzed.', 'The following KRAS/TP53 genotypes were identified: KRASmut/TP53mut n=21, KRASmut/TP53wt n=20, KRASwt/TP53mut n=25, KRASwt/TP53wt n=15. No genotype was associated with a significantly better or worse progression-free or overall survival.'] Is combined KRAS and TP53 mutation status predictive in CAPOX-treated metastatic colorectal cancer?
qiaojin/PubMedQA
2
[ -1.9776332378387451, -1.5483037233352661, 2.546370506286621 ]
['Integrins influence tumourigenesis, tumor progression and development of metastases. The impact of polymorphisms in integrin genes on relapse-free survival (RFS) and overall survival (OS) for 433 Caucasian patients with colorectal cancer was analysed in this retrospective study.', 'A Cox regression model including integrin genotype, age, grading, tumour size, number of lymph nodes examined, number of metastatic lymph nodes, stage and application of fluorouracil-based adjuvant chemotherapy was used to estimate their effect.', 'After a median follow-up of 41 months for RFS and 55 months for OS, no significant correlation between the ITGA2 1648A allele (RFS p=0.618, OS p=0.604), the ITGA2 807T allele (RFS p=0.603, OS p=0.807) and the ITGB3 176C allele (RFS p=0.719, OS p=0.261) and survival was detectable.'] Are single nucleotide polymorphisms of integrin alpha-2 and beta-3 genes associated with relapse-free and overall survival in colorectal cancer patients?
qiaojin/PubMedQA
2
[ -2.2489473819732666, -1.3694982528686523, 2.7036495208740234 ]
['Greater social cohesion is related to lower rates of coronary heart disease, but its relation to stroke risk is unstudied. This study examined whether neighborhood social cohesion was protective against stroke mortality and incidence.', 'Data come from 5789 participants (60% female; 62% black; mean age, 74.7 years) in a longitudinal study of chronic diseases in the elderly. Stroke mortality, ascertained through December 31, 2007, was verified through the National Death Index; 186 stroke deaths were identified in 11 years of follow-up. Stroke incidence was determined in a subset (N=3816) with linkage to Medicare claims files; 701 first-ever strokes were identified. Cohesion was measured by 6 items assessing frequency of contact and social interactions with neighbors; items were z-scored and averaged. Individual scores were averaged across 82 census block groups, forming a neighborhood-level measure of social cohesion. Marginal Cox proportional hazard models tested the association of neighborhood-level cohesion with stroke mortality and incidence.', 'Each 1-point increase in cohesion related to a 53% reduced risk of stroke mortality (hazard ratio, 0.47; 95% CI, 0.24 to 0.90), adjusting for relevant covariates, including sociodemographics, known stroke risk factors, and neighborhood-level socioeconomic status. A race×cohesion interaction (P=0.04) revealed cohesion was protective in whites (hazard ratio, 0.34; 95% CI, 0.17 to 0.67) but not blacks (hazard ratio, 1.17; 95% CI, 0.35 to 3.86). Cohesion was unrelated to stroke incidence (P>0.5).'] Is neighborhood cohesion associated with reduced risk of stroke mortality?
qiaojin/PubMedQA
2
[ -0.8124226331710815, -1.29793119430542, 1.1294702291488647 ]
['The purpose of this study was to follow the natural course of spontaneous passage (SP) of ingested foreign bodies (FBs) in children.', 'The medical records of 249 patients who ingested FBs were reviewed. In addition, they were studied by telephone questionnaires to follow up spontaneously passed FB. The factors associated with SP such as age, the type, size, and initial location of the FBs were analyzed.', 'Foreign bodies were spontaneously passed in 145 patients (58.2%), endoscopic removal was performed in 100 patients (40.2%), and operative removal was performed in 4 patients (1.6%). Most SP FBs were passed within 5 days. The SP rates (SPRs) according to the initial location were the following: 12.2% for the esophagus (P<0.0001), 71.4% for the stomach, 85.7% for the small bowel, and 96.4% for the colon. There was no significant difference in the SPR according to age. When coins and disk batteries that required early endoscopic removal were excluded, the SPR was 63.4% for FBs less than 10 mm, 80.4% for FBs 10 to 20 mm, 72.8% for FBs 20 to 30 mm, and 50.0% for FBs more than 30 mm (P=0.091). The initial location of the FB (odds ratio, 33.7; 95% confidence interval, 14.4-79.0) and the size of the FB (odds ratio, 3.5; 95% confidence interval, 1.0-11.6) were independent predictors of SP by multivariate analysis.'] Does initial location determine spontaneous passage of foreign bodies from the gastrointestinal tract in children?
qiaojin/PubMedQA
2
[ -0.03134192153811455, -1.661581039428711, 0.7908756732940674 ]
['The aim of the study was to conduct a meta-analysis of epidemiological and case control studies to determine whether arterial hypertension is specifically associated with an increased risk of vascular dementia (VaD).', 'Longitudinal and cross-sectional prospective studies using operationalised criteria to define VaD and hypertension, with a normal control comparison group were systematically reviewed. Cochrane Library, Embase, Medline, and PsycInfo data sources were searched along with reference lists of included articles and reviews. Original, prevalence or incidence studies were included if operationalised criteria for hypertension and VaD as well as number of cases with and without hypertension in VaD and non-demented groups were provided. Intervention studies and post-stroke and CADASIL studies were excluded.', 'Eleven studies recruiting either volunteers or clinical patients, or which were population-based, examined a total of 768 people with VaD and 9857 control cases. A meta-analysis of the six longitudinal studies showed that hypertension was significantly associated with increased risk of incident VaD (odds ratio, OR: 1.59, CI: 1.29-1.95, p\u2009<\u20090.0001). A similar association between hypertension and the risk of prevalent VaD was found in the five cross-sectional studies (OR: 4.84, CI: 3.52-6.67, p\u2009<\u20090.00001).'] Is hypertension a potential risk factor for vascular dementia : systematic review?
qiaojin/PubMedQA
2
[ -2.2121970653533936, -1.1345545053482056, 2.4446144104003906 ]
['Endothelial dysfunction and atherosclerosis are chronic inflammatory diseases characterized by activation of the innate and acquired immune system. Specialized protein receptors of the innate immune system recognize products of microorganisms and endogenous ligands such as nucleic acids. Toll-like receptor 3 (TLR3), for example, detects long double-stranded RNA and is abundantly expressed in endothelial cells. Whether innate immunity contributes to atherogenic mechanisms in endothelial cells is poorly understood.', 'We sought to determine the effects of TLR3 activation in endothelial cells.', 'We first investigated whether stimulation of TLR3 influences endothelial biology in mice. Intravenous injection of polyinosine polycytidylic acid, a synthetic double-stranded RNA analog and TLR3 ligand, impaired endothelium-dependent vasodilation, increased vascular production of reactive oxygen species, and reduced reendothelialization after carotid artery injury in wild-type mice compared with controls but had no effect in TLR3(-/-) animals. TLR3 stimulation not only induced endothelial dysfunction but also enhanced the formation of atherosclerotic plaques in apolipoprotein E-deficient mice. In vitro incubation of endothelial cells with polyinosine polycytidylic acid induced production of the proinflammatory cytokines interleukin-8 and interferon-γ-induced protein 10, increased formation of reactive oxygen species, diminished proliferation, and increased apoptosis, which suggests that endothelial cells are able to directly detect and respond to TLR3 ligands. Neutralization of interleukin-8 and interferon-γ-induced protein 10 antagonizes the observed negative effects of polyinosine polycytidylic acid. We found elevated levels of circulating endothelial progenitor cells in polyinosine polycytidylic acid-treated mice, although they displayed increased endothelial dysfunction. Stimulation of TLR3 in cultured endothelial progenitor cells, however, led to increased formation of reactive oxygen species, increased apoptosis, and reduced migration. Injection of endothelial progenitor cells that had been incubated with polyinosine polycytidylic acid ex vivo hindered reendothelialization after carotid artery injury. Therefore, endothelial progenitor cell function was affected by TLR3 stimulation. Finally, apolipoprotein E-deficient/TLR3-deficient mice exhibited improved endothelial function compared with apolipoprotein E-deficient/TLR3(+/+) littermates.'] Does activation of endothelial toll-like receptor 3 impair endothelial function?
qiaojin/PubMedQA
2
[ -2.514524221420288, -1.2801434993743896, 2.8275389671325684 ]
['Mast cells (MCs) contribute to the formation of abdominal aortic aneurysms (AAAs) by producing biologically active mediators. Tryptase is the most abundant MC granule protein and participates in MC activation, protease maturation, leukocyte recruitment, and angiogenesis-all processes critical to AAA pathogenesis.', 'To test the hypothesis that tryptase participates directly in AAA formation.', 'Immunohistochemistry demonstrated enhanced tryptase staining in media and adventitia of human and mouse AAA lesions. Serum tryptase levels correlated significantly with the annual expansion rate of AAA before (r = 0.30, P = 0.003) and after (r = 0.29, P = 0.005) adjustment for common AAA risk factors in a patient follow-up study, and associated with risks for later surgical repair or overall mortality before (P = 0.009, P = 0.065) and after (P = 0.004, P = 0.001) the adjustment. Using MC protease-6-deficient mice (Mcpt6(-/-)) and aortic elastase perfusion-induced experimental AAAs, we proved a direct role of this tryptase in AAA pathogenesis. Whereas all wild-type (WT) mice developed AAA at 14 or 56 days postperfusion, Mcpt6(-/-) mice were fully protected. AAA lesions from Mcpt6(-/-) mice had fewer inflammatory and apoptotic cells, and lower chemokine levels, than did those from WT mice. MC from WT mice restored reduced AAA lesions and lesion inflammatory cell content in MC-deficient Kit(W-sh/W-sh) mice, but those prepared from Mcpt6(-/-) mice did not. Mechanistic studies demonstrated that tryptase deficiency affected endothelial cell (EC) chemokine and cytokine expression, monocyte transmigration, smooth-muscle cell apoptosis, and MC and AAA lesion cysteinyl cathepsin expression and activities.'] Does mast cell tryptase deficiency attenuate mouse abdominal aortic aneurysm formation?
qiaojin/PubMedQA
2
[ -2.338080406188965, -1.392661452293396, 2.736682415008545 ]
['The objective of this study was to identify the role of dimethylarginine dimethylaminohydrolase-1 (DDAH1) in degrading the endogenous nitric oxide synthase inhibitors asymmetrical dimethylarginine (ADMA) and N(g)-monomethyl-L-arginine (L-NMMA).', 'We generated a global-DDAH1 gene-deficient (DDAH1(-/-)) mouse strain to examine the role of DDAH1 in ADMA and l-NMMA degradation and the physiological consequences of loss of DDAH1. Plasma and tissue ADMA and L-NMMA levels in DDAH1(-/-) mice were several folds higher than in wild-type mice, but growth and development of these DDAH1(-/-) mice were similar to those of their wild-type littermates. Although the expression of DDAH2 was unaffected, DDAH activity was undetectable in all tissues tested. These findings indicate that DDAH1 is the critical enzyme for ADMA and L-NMMA degradation. Blood pressure was ≈ 20 mm Hg higher in the DDAH1(-/-) mice than in wild-type mice, but no other cardiovascular phenotype was found under unstressed conditions. Crossing DDAH1(+/-) male with DDAH1(+/-) female mice yielded DDAH1(+/+), DDAH1(+/-), and DDAH1(-/-) mice at the anticipated ratio of 1:2:1, indicating that DDAH1 is not required for embryonic development in this strain.'] Is dimethylarginine dimethylaminohydrolase-1 the critical enzyme for degrading the cardiovascular risk factor asymmetrical dimethylarginine?
qiaojin/PubMedQA
2
[ -2.0975563526153564, -1.4735517501831055, 2.565410614013672 ]
['Syndecan-4 (Syn4), a cell-surface heparan sulfate proteoglycan, has been detected in the infarct region after myocardial infarction (MI), but its functional significance has not been elucidated.', 'We examined whether and how Syn4 regulates the cardiac healing process after MI.', 'Although the heart in Syn4-deficient (Syn4(-/-)) mice was morphologically and functionally normal, Syn4(-/-) mice exhibited impaired heart function and increased mortality rate as a result of cardiac ruptures after MI. Cardiac ruptures in Syn4(-/-) mice were associated with reduced inflammatory reaction and impaired granulation tissue formation during the early phase of MI, as evidenced by reduced numbers of leukocytes, fibroblasts, myofibroblasts, macrophages, and capillary vessels, along with reduced extracellular matrix protein deposition in the infarct region after MI. Transforming growth factor-β1-dependent cell signaling was preserved, whereas cell migration, fibronectin-induced cell signaling, and differentiation into myofibroblasts were defective in Syn4(-/-) cardiac fibroblasts. We also found that Syn4 was involved in basic fibroblast growth factor-dependent endothelial cell signaling, cell proliferation, and tube formation. Finally, overexpression of the shed form of Syn4 before MI creation led to an increase in mortality due to cardiac rupture via its action as a dominant-negative inhibitor of endogenous Syn4 signaling, which suggested a protective role of Syn4 signaling in MI.'] Does syndecan-4 prevent cardiac rupture and dysfunction after myocardial infarction?
qiaojin/PubMedQA
2
[ -2.3788647651672363, -1.2160544395446777, 2.6405014991760254 ]
['Congenital diaphragmatic hernia (CDH) is the costliest noncardiac congenital defect. Extracorporeal membrane oxygenation (ECMO) is a treatment strategy offered to those babies with CDH who would not otherwise survive on conventional therapy. The primary objective of our study was to identify the leading source of expenditures in CDH care.', "All patients surviving CDH repair were identified in the Kids' Inpatient Database (KID) from 1997 to 2006, with costs converted to 2006 US dollars. Patients were categorized into groups based on severity of disease for comparison including CDH repair only, prolonged ventilator dependence, and ECMO use. Factors associated with greater expenditures in CDH management were analyzed using a regression model.", 'Eight hundred thirty-nine patients from 213 hospitals were studied. Extracorporeal membrane oxygenation use decreased from 18.2% in 1997 to 11.4% in 2006 (P = .002). Congenital diaphragmatic hernia survivors managed with ECMO cost more than 2.4 times as much as CDH survivors requiring only prolonged ventilation postrepair and 3.5 times as much as those with CDH repair only (both P < .001). Age, multiplicity of diagnoses, patient transfer, inhaled nitric oxide use, prolonged ventilation, and ECMO use were all associated with higher costs. Extracorporeal membrane oxygenation use was the single most important factor associated with higher costs, increasing expenditures 2.4-fold (95% confidence interval, 2.1-2.8). Though the CDH repair with ECMO group constituted 12.2% of patients, this group has the highest median costs ($156,499.90/patient) and constitutes 28.5% of national costs based on CDH survivors in the KID. Annual national cost for CDH survivors is $158 million based on the KID, and projected burden for all CDH patients exceeds $250 million/year.'] Does costs of congenital diaphragmatic hernia repair in the United States-extracorporeal membrane oxygenation foot the bill?
qiaojin/PubMedQA
2
[ -0.07032709568738937, -1.7994837760925293, 0.7702884674072266 ]
['The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers.', 'Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome.', 'High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients.'] Is lPL the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia?
qiaojin/PubMedQA
2
[ -2.3318698406219482, -1.1309075355529785, 2.5615949630737305 ]
['An effect of insulin that is crucial for stimulating glucose uptake is its ability to increase the number of perfused capillaries, and thereby enhance its own delivery, and that of glucose, to muscle cells. To unravel possible mechanisms involved in the insulin-sensitizing effects of angiotensin II receptor blockers (ARBs) in hypertensive individuals we investigated the effect of single-dose ARB administration on insulin-mediated microvascular perfusion in hypertensive individuals.', 'We examined the effects of ARB administration on hyperinsulinemia-associated capillary density by measuring baseline skin capillary density, capillary density during reactive hyperemia (hyperemic capillary recruitment), and capillary density during venous congestion in 17 hypertensive individuals in the basal state, during a hyperinsulinemic euglycemic clamp, and during a hyperinsulinemic clamp with acute ARB administration (600 mg irbesartan), acute calcium channel blockade (CCB; 10mg felodipine ER), as a control for the reduction in blood pressure, or placebo. In addition, insulin sensitivity and blood pressure were measured.', 'Compared to the basal state, hyperinsulinemia increased baseline capillary density (57.3 ± 6.8 vs. 60.3 ± 7.9 n/mm(2), P<0.01), but not hyperemic capillary recruitment. ARB and CCB treatment induced similar blood pressure reductions. Compared to placebo, ARB, but not CCB, increased hyperinsulinemia-associated baseline capillary density (+2.3 ± 3.4 (P=0.02) and -0.4 ± 4.4n/mm(2), respectively). Hyperinsulinemia-associated hyperemic capillary recruitment was not altered by either treatment. Compared to placebo, neither ARB nor CCB treatment enhanced insulin sensitivity.'] Does acute angiotensin II receptor blockade improve insulin-induced microvascular function in hypertensive individuals?
qiaojin/PubMedQA
2
[ -2.1136279106140137, -1.419472336769104, 2.5613110065460205 ]
['Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment.', 'The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures.', 'BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls.', 'Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (P=0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels ≤-2.0 s.d. Furthermore, 75% of those with a Z-score ≤-2.0 s.d. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only.'] Are hypothalamic involvement and insufficient sex steroid supplementation associated with low bone mineral density in women with childhood onset craniopharyngioma?
qiaojin/PubMedQA
2
[ -1.754696249961853, -1.4776878356933594, 2.221412181854248 ]
['Accumulating evidence from a relatively small number of prospective studies indicates that exposure to prenatal stress profoundly influences the developing human fetus with consequences that persist into childhood and very likely forever.', 'Maternal/fetal dyads are assessed at ∼20, ∼25, ∼31 and ∼36 weeks of gestation. Infant assessments begin 24 h after delivery with the collection of cortisol and behavioral responses to the painful stress of the heel-stick procedure and measures of neonatal neuromuscular maturity. Infant cognitive, neuromotor development, stress and emotional regulation are evaluated at 3, 6 12 and 24 months of age. Maternal psychosocial stress and demographic information is collected in parallel with infant assessments. Child neurodevelopment is assessed with cognitive tests, measures of adjustment and brain imaging between 5 and 8 years of age.', 'Psychobiological markers of stress during pregnancy, especially early in gestation, result in delayed fetal maturation, disrupted emotional regulation and impaired cognitive performance during infancy and decreased brain volume in areas associated with learning and memory in 6- to 8-year-old children. We review findings from our projects that maternal endocrine alterations that accompany pregnancy and influence fetal/infant/child development are associated with decreased affective responses to stress, altered memory function and increased risk for postpartum depression.'] Does exposure to prenatal psychobiological stress exert programming influences on the mother and her fetus?
qiaojin/PubMedQA
2
[ -2.7982895374298096, -0.30608513951301575, 2.223214864730835 ]