pubid
int32 113k
27.9M
| question
stringlengths 17
664
| context
sequence | long_answer
stringlengths 1
3.12k
| final_decision
stringclasses 2
values | claim
stringlengths 17
394
|
---|---|---|---|---|---|
22,555,057 | Does systemic up-regulation of TLR4 cause lipopolysaccharide-induced augmentation of nasal cytokine release in allergic rhinitis? | {
"contexts": [
"Allergic rhinitis is a systemic disorder, and it is clinically well recognized that it can be aggravated by infection. Activation of the innate immune system constitutes a critical element in the process. Toll-like receptors (TLRs) comprise a part of the innate immune system, and lipopolysaccharide (LPS)-induced activation of TLR4 represents bacterial-induced interactions in various model systems. The present study examines how TLR2 and TLR4 expression is affected by symptomatic allergic rhinitis, and if LPS added upon allergen affects nasal cytokine release.",
"In patients with pollen-induced allergic rhinitis and healthy non-allergic volunteers, nasal lavage (NAL), peripheral blood and bone marrow were sampled before and during the pollen season. TLR2 and TLR4 expression was determined flow cytometrically. Changes in the TLR receptor expression pattern were evaluated by a nasal challenge with allergen followed by LPS, or vice versa. Symptoms along with cells and cytokines in NAL were analyzed.",
"TLR4 expression increased in leukocytes in NAL, peripheral blood and bone marrow during symptomatic allergic rhinitis. A similar increase was seen for TLR2 in neutrophils in blood. Nasal challenge with allergen followed by LPS augmented the release of IL-4, IL-5, IL-10, IL-13, IFN-γ and TNF-α."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Allergens",
"Betula",
"Bone Marrow",
"Cytokines",
"Humans",
"Leukocytes",
"Lipopolysaccharides",
"Nasal Lavage Fluid",
"Nasal Mucosa",
"Phleum",
"Pollen",
"Rhinitis, Allergic, Seasonal",
"Toll-Like Receptor 2",
"Toll-Like Receptor 4",
"Up-Regulation"
]
} | A systemic up-regulation of TLR4 in symptomatic allergic rhinitis may explain why LPS preceded by allergen increases nasal cytokine release. | yes | Systemic up-regulation of TLR4 causes lipopolysaccharide-induced augmentation of nasal cytokine release in allergic rhinitis. |
15,197,093 | Does endotoxin have an indirect vasodilatory effect on isolated human skeletal muscle arterioles? | {
"contexts": [
"Septic shock and its effects are a major cause of mortality in the intensive care environment. The exact effect and mechanism of endotoxin has yet to be fully described. With a better understanding of this process, better clinical tools could be developed to treat these patients.",
"Endotoxin has no direct effect on human skeletal muscle microvasculature and requires the release of an endothelial-derived factor to produce the vasodilation seen in gram-negative sepsis.",
"Benchtop research using an isolated arteriole model with controlled exposure to endotoxin.",
"University medical center.",
"First-order arterioles (approximately 150- micro m diameter) were isolated from human cremasteric muscles and pressurized to physiologic levels before exposure to an endotoxin-rich effluent with and without an upstream conduit vessel (superficial epigastric vein). The vasodilatory effect was measured with videomicroscopy and compared with control samples.",
"Mean vessel diameter and percentage of loss in tone.",
"When compared with controls, the isolated arteriole had no significant response when exposed to endotoxin alone (3.5% change in basal tone). When the endotoxin was allowed to pass over an upstream conduit vessel, the arteriole showed marked dilation (14.2% loss of basal tone)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Arterioles",
"Bacterial Toxins",
"Endotoxins",
"Humans",
"In Vitro Techniques",
"Muscle, Skeletal",
"Vasodilation",
"Vasodilator Agents"
]
} | This study demonstrates that endotoxin has no direct vasodilatory effect on human skeletal muscle arterioles, but it is the release of an endothelial factor from the upstream conduit vessels that produces the loss of tone in the microvasculature. Further research is ongoing to characterize the factors involved (nuclear factor-kappaB, tumor necrosis factor alpha, and interleuklin 6) for possible clinical intervention (antioxidants, cyclosporine, and nitric oxdide synthase inhibitors). | yes | Endotoxin has an indirect vasodilatory effect on isolated human skeletal muscle arterioles. |
20,236,256 | Does nationwide linkage analysis in Scotland implicate age as the critical overall determinant of mortality in ulcerative colitis? | {
"contexts": [
"Recent data associated higher mortality with medical rather than surgical intervention in patients with ulcerative colitis who require hospitalization.",
"To examine factors influencing UC-related mortality in Scotland.",
"Using the national record linkage database 1998-2000, 3-year mortality was determined after four admission types: colectomy-elective or emergency; no colectomy-elective or emergency.",
"Of 1078 patients, crude 3-year mortality rates were: colectomy elective 5.6% (n = 177) and emergency 9.0% (100); no colectomy elective 9.8% (244) and emergency 16.0% (557). Using elective colectomy as reference, multivariate analysis [OR (95% CI)] showed that admission age >50 years [OR 5.46 (2.29-11.95)], male gender [OR 1.92 (1.23-3.02)], comorbidity [OR 2.2 (1.38-3.51)], length of stay >15 days [OR 2.04 (1.08-3.84)] and prior IBD admission [OR 1.66 (1.06-2.61)] were independently related to mortality. Age was the strongest determinant. No patient <30 years died. Mortality of patients aged <50 years [10/587 (1.7%)] was significantly lower than mortality of those aged 50-64 years [26/246 (10.6%)] (chi(2) = 32.91; P < 0.0000001) and >65 [96/245 (39.2%)] (chi(2) = 218.2; P < 0.0000001). For those patients aged more than 65 years, mortality in the four groups was 29.4%, 33.3%, 28.1% and 44.7%- all greater than expected in the Scottish population on assessment of standardized mortality ratios."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Age Factors",
"Colectomy",
"Colitis, Ulcerative",
"Comorbidity",
"Female",
"Hospitalization",
"Humans",
"Male",
"Middle Aged",
"Multivariate Analysis",
"Risk Factors",
"Scotland"
]
} | Hospital admission in UC patients >65 is associated with high mortality. Management strategies should consider this by treatment in specialist units, early investigation, focused medical treatment and earlier surgical referral. | yes | Nationwide linkage analysis in Scotland implicates age as the critical overall determinant of mortality in ulcerative colitis. |
16,146,459 | Does post-operative myocardial dysfunction affect the physiological response to early mobilization after coronary artery bypass grafting? | {
"contexts": [
"An acute increase in oxygen demand can be compensated for either by increased cardiac index (CI) or increased oxygen extraction, resulting in reduced mixed venous oxygen saturation (SvO2). We tested the hypothesis that post-operative cardiac dysfunction may explain why oxygen extraction alone is increased during early mobilization after cardiac surgery.",
"Twenty patients with a pre-operative ejection fraction > 50% were included in an open prospective observational study comparing the changes in SvO2 and hemodynamics during mobilizations immediately prior to surgery and on the first post-operative morning.",
"Mobilization induced an absolute reduction in SvO2 of 17.7 +/- 7.4% pre- and 19.0 +/- 5.5% post-operatively (NS). ANOVA for a series of measurements throughout the mobilization sequence identified no different effect on SvO2 between pre- and post-operative mobilizations (P = 0.567). The SvO2 level was reduced post-operatively resulting in a SvO2 during standing exercise of 55% before and 49% after the surgery (P < 0.01). Mobilization increased the heart rate (HR) and decreased the stroke volume index (SVI), leaving CI unchanged. This response was similar pre- and post-operatively (NS). Compared with pre-operative measurements, CI and HR increased post-operatively while SVI remained unchanged despite elevated cardiac filling pressures and reduced systemic vascular resistance. The left ventricular stroke work index was reduced, indicating reduced myocardial performance."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aortic Valve",
"Cardiomyopathies",
"Chlorides",
"Coronary Artery Bypass",
"Early Ambulation",
"Electrocardiography",
"Female",
"Heart Function Tests",
"Heart Valve Prosthesis Implantation",
"Hemodynamics",
"Humans",
"Lactic Acid",
"Male",
"Middle Aged",
"Oximetry",
"Oxygen",
"Point-of-Care Systems",
"Postoperative Complications",
"Posture",
"Stroke Volume"
]
} | Myocardial function was reduced on the first morning after coronary artery bypass grafting (CABG), but during post-operative mobilization this reduction did not significantly influence the changes in CI or SvO2. | no | Post-operative myocardial dysfunction affects the physiological response to early mobilization after coronary artery bypass grafting. |
25,619,396 | Does artemisinin analogue SM934 ameliorate the proteinuria and renal fibrosis in rat experimental membranous nephropathy? | {
"contexts": [
"SM934 is a novel water-soluble artemisinin derivative with immunoregulatory activities that has been used to treat murine lupus nephritis. In the current study, we investigated the effects of SM934 on rat experimental membranous nephropathy.",
"Passive Heymann nephritis (PHN) was induced in SD rats by intraperitoneal injection of anti-Fx1A serum. The rats were orally administered SM934 (12.5 and 25 mg·kg(-1)·d(-1)) or prednisolone (5 mg·kg(-1)·d(-1)) for 28 d. Blood and urine sample, and kidney tissue were collected for analyses. Human complement C3a-induced injury of HK-2 cells was used for in vitro experiments.",
"Treatment of PHN rats with SM934 or prednisolone attenuated the progression of glomerulonephritis and renal fibrosis, as evidenced by the reduced level of proteinuria and circulating antibodies, as well as by the reduced immune complex deposition, reversed podocyte injuries, and attenuated tubulointerstitial fibrosis in the kidneys. Furthermore, the two drugs suppressed TGF-β1 expression and Smad2/3 phosphorylation, and increased Smad7 expression in the kidneys. The two doses of SM934 produced almost identical therapeutic effects on PHN rats. Pretreatment with SM934 or a C3a receptor antagonist blocked the C3a-induced epithelial-mesenchymal transition in HK-2 cells in vitro."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Artemisinins",
"Fibrosis",
"Glomerulonephritis, Membranous",
"Kidney",
"Kidney Diseases",
"Male",
"Models, Animal",
"Proteinuria",
"Rats",
"Rats, Sprague-Dawley"
]
} | SM934 ameliorates kidney injury and attenuates the tubulointerstitial fibrosis in PHN rats by down-regulation of the TGF-β1/Smad signaling pathway. | yes | Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy. |
16,600,035 | Is the PLAC1-homology region of the ZP domain sufficient for protein polymerisation? | {
"contexts": [
"Hundreds of extracellular proteins polymerise into filaments and matrices by using zona pellucida (ZP) domains. ZP domain proteins perform highly diverse functions, ranging from structural to receptorial, and mutations in their genes are responsible for a number of severe human diseases. Recently, PLAC1, Oosp1-3, Papillote and CG16798 proteins were identified that share sequence homology with the N-terminal half of the ZP domain (ZP-N), but not with its C-terminal half (ZP-C). The functional significance of this partial conservation is unknown.",
"By exploiting a highly engineered bacterial strain, we expressed in soluble form the PLAC1-homology region of mammalian sperm receptor ZP3 as a fusion to maltose binding protein. Mass spectrometry showed that the 4 conserved Cys residues within the ZP-N moiety of the fusion protein adopt the same disulfide bond connectivity as in full-length native ZP3, indicating that it is correctly folded, and electron microscopy and biochemical analyses revealed that it assembles into filaments."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Cloning, Molecular",
"Dimerization",
"Egg Proteins",
"Membrane Glycoproteins",
"Polymers",
"Pregnancy Proteins",
"Receptors, Cell Surface",
"Recombinant Proteins",
"Zona Pellucida",
"Zona Pellucida Glycoproteins"
]
} | These findings provide a function for PLAC1-like proteins and, by showing that ZP-N is a biologically active folding unit, prompt a re-evaluation of the architecture of the ZP domain and its polymers. Furthermore, they suggest that ZP-C might play a regulatory role in the assembly of ZP domain protein complexes. | yes | The PLAC1-homology region of the ZP domain is sufficient for protein polymerisation. |
17,412,579 | Does ascorbic acid supplementation attenuate exercise-induced bronchoconstriction in patients with asthma? | {
"contexts": [
"Previous research has shown that diet can modify the bronchoconstrictor response to exercise in asthmatic subjects.",
"Determine the effect of ascorbic acid supplementation on pulmonary function and several urinary markers of airway inflammation in asthmatic subjects with exercise-induced bronchoconstriction (EIB).",
"Eight asthmatic subjects with documented EIB participated in a randomized, placebo controlled double-blind crossover trial. Subjects entered the study on their usual diet and were placed on either 2 weeks of ascorbic acid supplementation (1500 mg/day) or placebo, followed by a 1-week washout period, before crossing over to the alternative diet. Pre- and post-exercise pulmonary function, asthma symptom scores, fraction of exhaled nitric oxide (FENO), and urinary leukotriene (LT) C4-E4 and 9alpha, 11beta-prostagladin (PG) F2] were assessed at the beginning of the trial (usual diet) and at the end of each treatment period.",
"The ascorbic acid diet significantly reduced (p < 0.05) the maximum fall in post-exercise FEV1 (-6.4 +/- 2.4%) compared to usual (-14.3 +/- 1.6%) and placebo diet (-12.9 +/- 2.4%). Asthma symptoms scores significantly improved (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. Post-exercise FENO, LTC4-E4 and 9alpha, 11beta-PGF2 concentration was significantly lower (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Anti-Asthmatic Agents",
"Ascorbic Acid",
"Asthma",
"Asthma, Exercise-Induced",
"Bronchoconstriction",
"Cross-Over Studies",
"Dietary Supplements",
"Double-Blind Method",
"Exercise Test",
"Female",
"Humans",
"Male",
"Respiratory Function Tests"
]
} | Ascorbic acid supplementation provides a protective effect against exercise-induced airway narrowing in asthmatic subjects. | yes | Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. |
22,554,774 | Is elevated immunoglobulin G4 level associated with reduced colectomy-free survival in patients with primary sclerosing cholangitis and ulcerative colitis? | {
"contexts": [
"Patients with primary sclerosing cholangitis (PSC) and elevated immunoglobulin (Ig) G4 have been shown to have more severe disease with a shorter time to orthotopic liver transplantation (OLT). The aim of the study was to investigate the clinical outcomes of PSC and UC in patients with elevated serum IgG4.",
"We analyzed data from 50 patients with PSC and known serum levels of IgG4. They were divided into groups called high IgG4 (>112 IU/L; n = 10) or normal IgG4 (n = 40). We compared the requirement of OLT and colectomy between groups.",
"High IgG4 was found in 10 PSC patients (20%). UC was associated in 9/10 patients with high IgG4 vs. 32/40 patients with normal IgG4 (p=0.67). Patients with high IgG4 were younger at PSC diagnosis (28.1 ± 13.9 vs. 37.6 ± 13.4 years, P=0.04), more likely to have backwash ileitis (7/9 vs. 12/32, P < 0.001) and UC flares (median of 5.5 vs. 1.5, P = 0.02). Kaplan-Meier curve analysis showed that patients with elevated IgG4 had reduced colectomy-free survival than patients with normal IgG4 (Log Rank p < 0.001). The median time to colectomy was 5 years from UC diagnosis in high IgG4 group vs. 12 years in the normal IgG4 group (p = 0.01)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Bile Duct Neoplasms",
"Bile Ducts, Intrahepatic",
"Chi-Square Distribution",
"Cholangiocarcinoma",
"Cholangitis, Sclerosing",
"Colectomy",
"Colitis, Ulcerative",
"Colon",
"Colonic Neoplasms",
"Female",
"Humans",
"Immunoglobulin G",
"Kaplan-Meier Estimate",
"Male",
"Middle Aged",
"Retrospective Studies",
"Severity of Illness Index",
"Statistics, Nonparametric",
"Time Factors"
]
} | Elevated IgG4 was seen in a small number of PSC patients. Most of these patients had associated UC, were younger at the time of PSC diagnosis, more likely to have backwash ileitis and had reduced colectomy-free survival than patients with normal IgG4. | yes | Elevated immunoglobulin G4 level is associated with reduced colectomy-free survival in patients with primary sclerosing cholangitis and ulcerative colitis. |
11,959,049 | Does addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure reduce levels of oxidative stress? | {
"contexts": [
"Angiotensin II exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure.",
"Twenty-eight heart failure patients, who were on stable ACE inhibitor therapy, were randomised to receive adjunctive therapy with candesartan or placebo. Plasma lipid-derived free radicals, TBARS and neutrophil O2-generation, markers of oxidative stress, were measured in venous blood. Arterial endothelial function was assessed as the response of the brachial artery to flow-related shear stress. Exercise capacity was determined by cardiopulmonary exercise testing. Compared with placebo, candesartan had no effect on changes in lipid derived free radicals (-0.1+/-1.2 vs. -0.1+/-1.0 units, respectively, P=NS), TBARS (-2.2+/-1.1 vs. -2.6+/-2.2 micromol/l, respectively, P=NS) or neutrophil O2-generating capacity (-7.3+/-5.1 vs. -8.4+/-7.9 mV/5x10(5) neutrophils, respectively, P=NS). There was no effect on changes in brachial artery flow-mediated dilatation (0.5+/-1.0 vs. 0.8+/-1.3%, respectively, P=NS) nor peak VO2 (1.6+/-0.7 ml/kg per min vs. 1.8+/-0.6 ml/kg per min; P=NS)."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Angiotensin-Converting Enzyme Inhibitors",
"Antihypertensive Agents",
"Benzimidazoles",
"Blood Pressure",
"Brachial Artery",
"Chronic Disease",
"Drug Therapy, Combination",
"Endothelium, Vascular",
"Exercise Tolerance",
"Female",
"Follow-Up Studies",
"Heart Failure",
"Heart Rate",
"Humans",
"Lipid Peroxidation",
"Male",
"Middle Aged",
"Natriuretic Peptide, Brain",
"Oxidative Stress",
"Stroke Volume",
"Tetrazoles",
"Time Factors",
"Treatment Outcome"
]
} | The addition of the candesartan to ACE inhibitor therapy had no effect on oxidative stress and did not improve endothelial function or exercise capacity in patients with CHF. | no | Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure reduces levels of oxidative stress. |
27,844,503 | Is attentional capture by physically salient stimuli in the gamma frequency associated with schizophrenia symptoms? | {
"contexts": [
"Aberrant salience mainly is attributed to excessive dopaminergic processing in the ventral striatum (Kapur 2003). Also, early sensory processing of physical salience has been shown to be associated with positive trait schizotypy (Kornmayer et al. 2015). In the present study, this is assessed in patients with schizophrenia.",
"The early evoked visual gamma-band response at 40Hz (GBR) was assessed for a schizophrenia patient group (N = 22) and a matched healthy control group (N = 22) applying EEG time-frequency analysis. The GBR was assessed for two conditions within a visual detection paradigm: a target with or without a physically-salient distracter and evaluated in relation to the PANSS (Van der Gaag, 2006).",
"A 2x2 ANOVA revealed a significant main effect of condition and a trend interaction of group and condition for the GBR, with highest power for schizophrenia patients in the physically-salient distracter condition. Moreover, evoked GBR power in this condition was correlated with positive (r =.664; p = .001**) and disorganized (r =.618; p = .002**) schizophrenia symptoms."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": []
} | Evoked GBR power during processing of physical salience in schizophrenia was associated with positive symptoms. We suggest that abnormal processing of physically salient stimuli might be involved in the pathophysiological genesis of positive symptoms. | yes | Attentional capture by physically salient stimuli in the gamma frequency is associated with schizophrenia symptoms. |
23,228,017 | Does dovitinib preferentially target endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis? | {
"contexts": [
"Dovitinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptors and platelet-derived growth factor receptor β. Dovitinib is currently in clinical trials for the treatment of hepatocellular carcinoma (HCC).",
"In this study, we used five HCC cell lines and five endothelial cell lines to validate molecular and cellular targets of dovitinib.",
"Tumor growth and pulmonary metastasis were significantly suppressed in an orthotopic HCC model. Immunoblotting revealed that among known dovitinib targets, only PDGFR-β was expressed in two HCC cell lines, while four of five endothelial lines expressed PDGFR-β, FGFR-1, and VEGFR-2. Dovitinib inhibited endothelial cell proliferation and motility at 0.04 μmol/L, a pharmacologically relevant concentration; it was unable to inhibit the proliferation or motility of HCC cells at the same concentration. Immunohistochemical analyses showed that dovitinib significantly decreased the microvessel density of xenograft tumors, inhibiting proliferation and inducing apoptosis in HCC cells."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Apoptosis",
"Benzimidazoles",
"Biomarkers, Tumor",
"Carcinoma, Hepatocellular",
"Cell Line, Tumor",
"Cell Movement",
"Cell Proliferation",
"Endothelial Cells",
"Humans",
"Liver Neoplasms",
"Male",
"Mice",
"Neoplasm Invasiveness",
"Neoplasm Metastasis",
"Neovascularization, Pathologic",
"Protein Kinase Inhibitors",
"Quinolones",
"Receptor Protein-Tyrosine Kinases",
"Signal Transduction",
"Xenograft Model Antitumor Assays"
]
} | Our findings indicate that dovitinib inhibits HCC growth and metastasis preferentially through an antiangiogenic mechanism, not through direct targeting of HCC cells. | yes | Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis. |
20,618,316 | Does access to computerised analysis of intrapartum cardiotocographs improve clinicians ' prediction of newborn umbilical artery blood pH? | {
"contexts": [
"To evaluate the impact of access to computerised cardiotocograph (CTG) analysis on reproducibility and accuracy of clinicians' predictions of umbilical artery blood pH (UAB pH) and 5-minute Apgar score.",
"Prospective evaluation of pre-recorded cases.",
"A tertiary-care university hospital.",
"From databases of intrapartum CTGs acquired in singleton term pregnancies, 204 tracings with low signal loss and short time interval to delivery were consecutively selected.",
"Tracings were randomly assigned to computer analysis by the Omniview-SisPorto 3.5 system (study group n = 104) or to no analysis (control group n = 100). Three experienced clinicians evaluated all tracing printouts independently and were asked to predict the newborns' UAB pH and 5-minute Apgar scores from them.",
"Interobserver agreement (measured by the intraclass correlation coefficient [ICC]) and accuracy in prediction of neonatal outcomes with 95% CI.",
"Agreement on prediction of UAB pH was significantly higher in the study group (ICC = 0.70; 95% CI 0.61-0.77) than in the control group (ICC = 0.43; 95% CI 0.21-0.60), and a trend towards better agreement was also seen in estimation of 5-minute Apgar scores (ICC = 0.55; 95% CI 0.38-0.68 versus ICC = 0.43; 95% CI 0.25-0.57). Observers predicted UAB pH values correctly within a 0.10 margin in 70% of cases in the study group (95% CI 0.61-0.79) versus 46% in the control group (95% CI 0.35-0.56). They predicted 5-minute Apgar scores within a margin of one in 81% of cases in the study group (95% CI 0.73-0.88) and in 70% of cases in the control group (95% CI 0.61-0.79)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Apgar Score",
"Cardiotocography",
"Clinical Competence",
"Diagnosis, Computer-Assisted",
"Female",
"Fetal Blood",
"Gestational Age",
"Humans",
"Hydrogen-Ion Concentration",
"Infant, Newborn",
"Male",
"Neonatology",
"Observer Variation",
"Prospective Studies",
"Umbilical Arteries"
]
} | Prediction of UAB pH is more reproducible and accurate when clinicians have access to computerised analysis of CTGs. | yes | Access to computerised analysis of intrapartum cardiotocographs improves clinicians ' prediction of newborn umbilical artery blood pH. |
24,561,282 | Does fK506 protect against articular cartilage collagenous extra-cellular matrix degradation? | {
"contexts": [
"Osteoarthritis (OA) is a non-rheumatologic joint disease characterized by progressive degeneration of the cartilage extra-cellular matrix (ECM), enhanced subchondral bone remodeling, activation of synovial macrophages and osteophyte growth. Inhibition of calcineurin (Cn) activity through tacrolimus (FK506) in in vitro monolayer chondrocytes exerts positive effects on ECM marker expression. This study therefore investigated the effects of FK506 on anabolic and catabolic markers of osteoarthritic chondrocytes in 2D and 3D in vitro cultures, and its therapeutic effects in an in vivo rat model of OA.",
"Effects of high and low doses of FK506 on anabolic (QPCR/histochemistry) and catabolic (QPCR) markers were evaluated in vitro on isolated (2D) and ECM-embedded chondrocytes (explants, 3D pellets). Severe cartilage damage was induced unilaterally in rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with FK506 orally and compared to twenty untreated controls. Subchondral cortical and trabecular bone changes (longitudinal microCT) and macrophage activation (SPECT/CT) were measured. Articular cartilage was analyzed ex vivo using contrast enhanced microCT and histology.",
"FK506 treatment of osteoarthritic chondrocytes in vitro induced anabolic (mainly collagens) and reduced catabolic ECM marker expression. In line with this, FK506 treatment clearly protected ECM integrity in vivo by markedly decreasing subchondral sclerosis, less development of subchondral pores, depletion of synovial macrophage activation and lower osteophyte growth."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Calcineurin Inhibitors",
"Cartilage, Articular",
"Case-Control Studies",
"Chondrocytes",
"Contrast Media",
"Disease Models, Animal",
"Humans",
"Macrophages",
"Male",
"Osteoarthritis, Knee",
"Rats",
"Rats, Wistar",
"Stifle",
"Tacrolimus",
"Tomography, Emission-Computed, Single-Photon",
"Treatment Outcome",
"X-Ray Microtomography"
]
} | FK506 protected cartilage matrix integrity in vitro and in vivo. Additionally, FK506 treatment in vivo reduced OA-like responses in different articular joint tissues and thereby makes Cn an interesting target for therapeutic intervention of OA. | yes | FK506 protects against articular cartilage collagenous extra-cellular matrix degradation. |
14,572,772 | Does hypothermia protect against gut ischemia/reperfusion-induced impaired intestinal transit by inducing heme oxygenase-1? | {
"contexts": [
"Gut ischemia/reperfusion (I/R) elicits an inflammatory response that impairs intestinal transit. We have previously shown that regional intraischemic hypothermia (IH) protects against moderate gut I/R-induced mucosal injury, is associated with decreased NF-kappaB activity and inducible nitric oxide synthase induction and preserves heme oxygenase-1 (HO-1) expression. HO-1 provides cytoprotection in various models of oxidant stress. We, therefore, tested the hypothesis that IH protects against gut I/R-induced impaired intestinal transit via HO-1 induction.",
"At laparotomy (lap), Sprague-Dawley rats had duodenal catheters placed followed by sham or gut I/R (superior mesenteric artery occlusion for 75 min) with or without regional IH (15 degrees C). Each animal was placed on a heating blanket maintaining systemic normothermia (37 degrees C). At 12 or 24 h of reperfusion, small intestinal transit was determined by quantitating the distribution of a tracer (FITC dextran) in the intestine 30 min after instillation (expressed as geometric center of distribution). Ileal samples were obtained for histology and HO-1 expression, assessed by Western immunoblot at 12 and 24 h of reperfusion. In separate experiments, rats were pretreated with an HO-1 inhibitor Sn protoporphyrin IX (25 mumol/kg, ip), 1 h before superior mesenteric artery occlusion and transit measured as above.",
"Rats treated with I/R had increased histological injury and impaired intestinal transit at both 12 and 24 h compared with sham. Rats treated with I/R+IH exhibited histological injury and transit comparable with sham controls. I/R induced HO-1 expression at 12 and 24 h of reperfusion and IH augmented this I/R-induced HO-1 expression. Sn protoporphyrin IX abrogated IH protection against histological injury and impaired transit."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Blotting, Western",
"Constriction",
"Enzyme Inhibitors",
"Gastrointestinal Transit",
"Heme Oxygenase (Decyclizing)",
"Heme Oxygenase-1",
"Hypothermia, Induced",
"Ileum",
"Intestine, Small",
"Intestines",
"Male",
"Mesenteric Artery, Superior",
"Metalloporphyrins",
"Protoporphyrins",
"Rats",
"Rats, Sprague-Dawley",
"Reperfusion Injury"
]
} | We conclude that intraischemic regional hypothermia protects against histological injury and impaired intestinal transit caused by severe gut I/R injury. Hypothermic protection under these conditions is in part due to HO-1 expression. | yes | Hypothermia protects against gut ischemia/reperfusion-induced impaired intestinal transit by inducing heme oxygenase-1. |
25,312,600 | Is electrical stimulation of the vagus nerve dermatome in the external ear protective in rat cerebral ischemia? | {
"contexts": [
"Although cervical vagus nerve stimulation is effective for reducing infarct volume in rats, it is not feasible for acute human stroke as it requires surgical incision of the neck. We hypothesized that stimulation of the dermatome in the external ear innervated by the vagus nerve (auricular vagus nerve stimulation; aVNS) reduces infarct volume after transient focal ischemia in rats.",
"Animals were randomized to active aVNS or sham stimulation. For aVNS, electrical stimulation of the left cavum concha (1 h duration) using percutaneous needles was initiated 30 min after induction of ischemia. Behavioral and tissue outcome were measured 24 h after induction of ischemia. In a separate experimental dataset, c-Fos immunohistochemistry was performed to identify the brain regions activated after the stimulation.",
"Stimulation of the left cavum concha resulted in bilateral c-Fos staining in the nuclei tractus solitarii and the loci coerulei in all animals. There was no c-Fos staining in any part of the brainstem in sham control animals. The mean infarct volume (SD) as calculated by indirect method was 44.20 ± 7.58% in controls and 31.65 ± 9.67% in treated animals (P < 0.0001). The effect of aVNS on tissue outcome was associated with better neurological scores at 24 h after ischemia (P < 0.0001)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Brain Ischemia",
"Cerebral Infarction",
"Ear, External",
"Locus Coeruleus",
"Male",
"Proto-Oncogene Proteins c-fos",
"Rats",
"Solitary Nucleus",
"Vagus Nerve Stimulation"
]
} | Electric stimulation of the vagus nerve dermatome in the external ear activates brainstem afferent vagal nuclei and reduces infarct volume in rats. This finding has potential to facilitate the development of treatments that leverage the brain's endogenous neuroprotective pathways at the setting of acute ischemic stroke. | yes | Electrical stimulation of the vagus nerve dermatome in the external ear is protective in rat cerebral ischemia. |
11,698,793 | Is antimeasles immunoglobulin G in sera of patients with otosclerosis lower than that in healthy people? | {
"contexts": [
"There is some evidence for an inflammatory process as a driving force in otosclerosis. Two popular hypotheses for the induction of this chronic inflammation have been proposed: an autoimmune phenomenon induced by an otic capsule specific antigen and measles virus infection.",
"Antibodies against measles virus hemagglutinin, polymerase, nucleocapsid, and matrix proteins were evaluated in sera from otosclerotic patients and in sera from healthy age-and sex-matched controls by use of the Western blot analyses.",
"Significant differences were not detected between healthy men and women or between otosclerotic men and women. There were significantly stronger reactions against all viral proteins in the group of healthy women as compared with otosclerotic women despite a high standard deviation. The group of healthy male blood donors demonstrated significantly stronger reactions against polymerase and nucleocapsid proteins. Healthy blood donors again demonstrated stronger reaction compared with respective otosclerotic patients in a separate reaction for viral matrix protein."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Antibodies, Viral",
"Blotting, Western",
"Female",
"Health Status",
"Hemagglutinins",
"Hemagglutinins, Viral",
"Humans",
"Immunoglobulin G",
"Male",
"Measles",
"Measles virus",
"Middle Aged",
"Otosclerosis",
"Polymerase Chain Reaction"
]
} | Our observation is consistent with viral participation in otosclerotic pathogenesis, but it is difficult to say if the diminished antimeasles humoral response is a consequence or the cause for a local measles infection. In light of the present data, we can discuss autoantibodies in otosclerosis as a sign of autoimmunity triggered by measles virus. | yes | Antimeasles immunoglobulin G in sera of patients with otosclerosis is lower than that in healthy people. |
24,112,605 | Do radiation testing of the AeroForm CO2-based breast tissue expander implant? | {
"contexts": [
"Tissue expanders are used in breast reconstruction after mastectomy to stretch the remaining tissue to create space for placement of permanent breast implants. The AeroForm™ Tissue Expander, developed by AirXpanders™ Inc., contains electronic components designed to activate the release of carbon dioxide from an internal reservoir to inflate the expander. Breast cancer patients who undergo mastectomy and tissue expander/implant-based breast reconstruction may require radiation therapy at doses up to 50-60 Gy while the expander is in place. The ionizing radiation used in postmastectomy radiation therapy interacts with electronic components in medical implants, which may cause degradation in performance above certain levels. Most commercial electronic components used in medical devices, such as complementary metal-oxide semiconductor or bipolar integrated circuits can withstand radiation levels in the 50 Gy range without any performance degradation. Beyond this level, the performance may still be sufficient to guarantee functionality, but this needs to be confirmed at the system and electronic circuit level. We assessed the impact of radiation levels up to 75 Gy on 32 AeroForm™ Tissue Expanders (AirXpanders, Inc., Palo Alto, CA USA) and on the associated internal printed circuit assemblies.",
"The electronics inside the AeroForm™ Tissue Expander implant continued to function properly after exposure to radiation levels up to 75 Gy, which is well above the maximum total dose level typically used in postmastectomy radiation therapy."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Breast Implants",
"Carbon Dioxide",
"Mammaplasty",
"Materials Testing",
"Tissue Expansion Devices"
]
} | Standard postmastectomy radiation therapy doses do not damage or affect the functionality of the AeroForm™ Tissue Expander. | yes | Radiation testing of the AeroForm CO2-based breast tissue expander implant is done. |
15,577,621 | Is t-cell function after interleukin-2 therapy in HIV-infected patients correlated with serum cortisol concentrations? | {
"contexts": [
"To examine the effects of interleukin (IL)-2 therapy on in-vitro lymphocyte responsiveness in HIV-infected patients and to correlate these data with serum cortisol concentrations.",
"German prospective study.",
"In adult patients (n = 32) treated with 9 x 10(6) IU/day interleukin-2, lymphocyte transformation tests (LTT), serum cortisol concentrations and CD4 T-cell counts were assessed before, during and after IL-2 therapy.",
"A significant decrease in responses towards mitogens and recall antigens (P < 0.05) was observed on day 7 after starting a 4- to 5-day IL-2 therapy as compared to baseline. Serum cortisol levels increased (P < 0.0001) reaching a maximum on day 4, and were still elevated on day 7 (P < 0.005). CD4 T-cell counts significantly decreased with a minimum on day 2 before increasing 2.4-fold above baseline on day 7 (P < 0.005 each). A positive correlation (P < 0.05 each) was observed for changes in cortisol levels and in LTT mitogen and antigen reactions (both day 7 - 0), changes in cortisol levels (day 3 - 0) and CD4 cell counts on day 2, and corticotrophin releasing hormone test results and LTT antigen reactions on day 7. LTT responses, cortisol levels and CD4 T-cell counts returned to baseline on day 30."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"CD4 Lymphocyte Count",
"Cohort Studies",
"Female",
"HIV Infections",
"Humans",
"Hydrocortisone",
"Interleukin-2",
"Lymphocyte Activation",
"Male",
"Middle Aged",
"Prospective Studies",
"T-Lymphocytes",
"Viral Load"
]
} | Serum cortisol concentrations are predictive of functional and numerical changes of T cells induced by IL-2 therapy. | yes | T-cell function after interleukin-2 therapy in HIV-infected patients is correlated with serum cortisol concentrations. |
16,956,895 | Does beta2 adrenergic antagonist inhibit cerebral cortical oxygen delivery after severe haemodilution in rats? | {
"contexts": [
"Haemodilution has been associated with neurological morbidity in surgical patients. This study tests the hypothesis that inhibition of cerebral vasodilatation by systemic beta2 adrenergic blockade would impair cerebral oxygen delivery leading to tissue hypoxia in severely haemodiluted rats.",
"Under general anaesthesia, cerebral tissue probes were placed to measure temperature, regional cerebral blood flow (rCBF) and tissue oxygen tension (P(Br)O2) in the parietal cerebral cortex or hippocampus. Baseline measurements were established before and after systemic administration of either a beta2 antagonist (10 mg kg(-1) i.v., ICI 118, 551) or saline vehicle. Acute haemodilution was then performed by simultaneously exchanging 50% of the estimated blood volume (30 ml kg(-1)) with pentastarch. Arterial blood gases (ABGs), haemoglobin concentration (co-oximetry), mean arterial blood pressure (MAP) and heart rate (HR) were also measured. Data were analysed using a two-way anova and post hoc Tukey's test [mean (sd)].",
"Haemodilution reduced the haemoglobin concentration comparably in all groups [71 (9) g litre(-1)]. There were no differences in ABGs, co-oximetry, HR and MAP measurements between control and beta2 blocked rats, either before or 60 min after drug or vehicle administration. In rats treated with the beta2 antagonist there was a significant reduction in parietal cerebral cortical temperature, regional blood flow and tissue oxygen tension, relative to control rats, 60 min after haemodilution (P<0.05 for each). These differences were not observed when probes were placed in the hippocampus."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adrenergic beta-2 Receptor Antagonists",
"Adrenergic beta-Antagonists",
"Animals",
"Blood Pressure",
"Brain",
"Cerebrovascular Circulation",
"Heart Rate",
"Hemodilution",
"Male",
"Oxygen",
"Oxygen Consumption",
"Partial Pressure",
"Rats",
"Rats, Sprague-Dawley",
"Temperature",
"Vasodilation"
]
} | Systemic beta2 adrenergic blockade inhibited the compensatory increase in parietal cerebral cortical oxygen delivery after haemodilution thereby reducing cerebral cortical tissue oxygen tension. | yes | Beta2 adrenergic antagonist inhibits cerebral cortical oxygen delivery after severe haemodilution in rats. |
15,345,036 | Does the phosphatidylserine receptor have essential functions during embryogenesis but not in apoptotic cell removal? | {
"contexts": [
"Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr) on phagocytes has been implicated in the recognition and engulfment of apoptotic cells and in anti-inflammatory signaling. To determine the biological function of the phosphatidylserine receptor in vivo, we inactivated the Ptdsr gene in the mouse.",
"Ablation of Ptdsr function in mice causes perinatal lethality, growth retardation and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. Ptdsr -/- mice with anophthalmia develop novel lesions, with induction of ectopic retinal-pigmented epithelium in nasal cavities. A comprehensive investigation of apoptotic cell clearance in vivo and in vitro demonstrated that engulfment of apoptotic cells was normal in Ptdsr knockout mice, but Ptdsr-deficient macrophages were impaired in pro- and anti-inflammatory cytokine signaling after stimulation with apoptotic cells or with lipopolysaccharide."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Anophthalmos",
"Apoptosis",
"Cytokines",
"Embryonic Development",
"Eye",
"Macrophages",
"Mice",
"Mice, Knockout",
"Organogenesis",
"Phagocytosis",
"Receptors, Cell Surface"
]
} | Ptdsr is essential for the development and differentiation of multiple organs during embryogenesis but not for apoptotic cell removal. Ptdsr may thus have a novel, unexpected developmental function as an important differentiation-promoting gene. Moreover, Ptdsr is not required for apoptotic cell clearance by macrophages but seems to be necessary for the regulation of macrophage cytokine responses. These results clearly contradict the current view that the phosphatidylserine receptor primarily functions in apoptotic cell clearance. | yes | The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal. |
20,152,032 | Do comparative analyses reveal distinct sets of lineage-specific genes within Arabidopsis thaliana? | {
"contexts": [
"The availability of genome and transcriptome sequences for a number of species permits the identification and characterization of conserved as well as divergent genes such as lineage-specific genes which have no detectable sequence similarity to genes from other lineages. While genes conserved among taxa provide insight into the core processes among species, lineage-specific genes provide insights into evolutionary processes and biological functions that are likely clade or species specific.",
"Comparative analyses using the Arabidopsis thaliana genome and sequences from 178 other species within the Plant Kingdom enabled the identification of 24,624 A. thaliana genes (91.7%) that were termed Evolutionary Conserved (EC) as defined by sequence similarity to a database entry as well as two sets of lineage-specific genes within A. thaliana. One of the A. thaliana lineage-specific gene sets share sequence similarity only to sequences from species within the Brassicaceae family and are termed Conserved Brassicaceae-Specific Genes (914, 3.4%, CBSG). The other set of A. thaliana lineage-specific genes, the Arabidopsis Lineage-Specific Genes (1,324, 4.9%, ALSG), lack sequence similarity to any sequence outside A. thaliana. While many CBSGs (76.7%) and ALSGs (52.9%) are transcribed, the majority of the CBSGs (76.1%) and ALSGs (94.4%) have no annotated function. Co-expression analysis indicated significant enrichment of the CBSGs and ALSGs in multiple functional categories suggesting their involvement in a wide range of biological functions. Subcellular localization prediction revealed that the CBSGs were significantly enriched in proteins targeted to the secretory pathway (412, 45.1%). Among the 107 putatively secreted CBSGs with known functions, 67 encode a putative pollen coat protein or cysteine-rich protein with sequence similarity to the S-locus cysteine-rich protein that is the pollen determinant controlling allele specific pollen rejection in self-incompatible Brassicaceae species. Overall, the ALSGs and CBSGs were more highly methylated in floral tissue compared to the ECs. Single Nucleotide Polymorphism (SNP) analysis showed an elevated ratio of non-synonymous to synonymous SNPs within the ALSGs (1.99) and CBSGs (1.65) relative to the EC set (0.92), mainly caused by an elevated number of non-synonymous SNPs, indicating that they are fast-evolving at the protein sequence level."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Arabidopsis",
"Arabidopsis Proteins",
"Brassicaceae",
"DNA Methylation",
"Polymorphism, Single Nucleotide"
]
} | Our analyses suggest that while a significant fraction of the A. thaliana proteome is conserved within the Plant Kingdom, evolutionarily distinct sets of genes that may function in defining biological processes unique to these lineages have arisen within the Brassicaceae and A. thaliana. | yes | Comparative analyses reveal distinct sets of lineage-specific genes within Arabidopsis thaliana. |
7,958,669 | Does glutamine dipeptide-supplemented parenteral nutrition maintain intestinal function in the critically ill? | {
"contexts": [
"Long-term total parenteral nutrition is accompanied with mucosal atrophy and subsequent malabsorption syndrome. Current information attests the important role of glutamine in maintaining intestinal structure and function. The aim of this study was to investigate the effect of glutamine dipeptide supplementation on small intestinal absorption capacity during critical illness.",
"Twelve intensive care unit patients were uniformly randomized to receive isonitrogenous (0.26 g nitrogen.kg-1.day-1) and isoenergetic (155 kJ.kg-1.day-1) parenteral nutrition over 9 days. The control group received a conventional amino acid solution (1.5 g amino acids.kg-1.day-1), and the test group received a complete amino acid solution containing the dipeptide L-alanyl-L-glutamine (20 g/L). On days 8 and 9, a modified D-xylose test was performed.",
"Excretion of D-xylose during the 5-hour test period was 7.4 +/- 1.1 g (test) vs. 3.8 +/- 0.9 g (control) (P < 0.05). The 2-hour serum D-xylose concentration was 38.7 +/- 3.0 (test) vs. 27.8 +/- 2.9 mg/100 mL (control) (P < 0.05). Kinetic evaluation showed higher maximum D-xylose blood concentration and higher values for the area under the curve with the peptide."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Atrophy",
"Critical Illness",
"Dipeptides",
"Female",
"Humans",
"Intestinal Absorption",
"Intestine, Small",
"Male",
"Middle Aged",
"Parenteral Nutrition",
"Xylose"
]
} | The results strongly suggest that glutamine dipeptide-containing total parenteral nutrition prevents intestinal atrophy and increased permeability associated with glutamine-free parenteral nutrition. | yes | Glutamine dipeptide-supplemented parenteral nutrition maintains intestinal function in the critically ill. |
15,458,975 | Is insulin resistance independently associated with postprandial alterations of triglyceride-rich lipoproteins in type 2 diabetes mellitus? | {
"contexts": [
"To evaluate the role of insulin resistance in development of postprandial dyslipidemia in type 2 diabetic patients in an experimental setting in which these patients were compared with nondiabetic subjects at similar glucose and insulin blood levels.",
"Eight type 2 diabetic patients in optimal blood glucose control and 7 control subjects (aged 50.0+/-2.6 and 48.1+/-1.3 years; body mass index 28.3+/-1.2 and 25.6+/-1.1 kg/m2; fasting plasma triglycerides 1.12+/-0.13 and 0.87+/-0.08 mmol/L, respectively; mean+/-SEM; NS) consumed a mixed meal during an 8-hour hyperinsulinemic glycemic clamp. Mean blood glucose during clamp was approximately 7.8 mmol/L, and plasma insulin during the preprandial steady state was approximately 480 pmol/L in both groups, that differed for insulin sensitivity (M/I value lower in diabetic subjects [1.65+/-0.30 and 3.42+/-0.60; P<0.05]). Subjects with diabetes had higher postprandial levels of lipids and apolipoprotein B (apoB) in large very low-density lipoprotein (incremental area for triglycerides 1814+/-421 versus 549+/-153 micromol/Lx6 hours; P<0.05; cholesterol 694+/-167 versus 226+/-41 micromol/Lx6 hours; P<0.05; apoB-48 6.3+/-1.0 versus 2.6+/-0.7 mg/Lx6 hours; P<0.05; apoB-100 56.5+/-14.9 versus 26.2+/-11.0 mg/Lx6 hours; NS). Basal lipoprotein lipase (LPL) activity before and after meal was higher in diabetic subjects, whereas postheparin LPL activity 6 hours after the meal was similar."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Apolipoproteins B",
"Blood Glucose",
"C-Peptide",
"Chylomicrons",
"Diabetes Mellitus, Type 2",
"Fatty Acids, Nonesterified",
"Female",
"Glucose",
"Humans",
"Infusions, Intravenous",
"Insulin",
"Insulin Resistance",
"Lipase",
"Lipids",
"Lipoprotein Lipase",
"Lipoproteins",
"Lipoproteins, HDL",
"Lipoproteins, IDL",
"Lipoproteins, LDL",
"Lipoproteins, VLDL",
"Male",
"Middle Aged",
"Postprandial Period",
"Triglycerides"
]
} | Insulin resistance is also associated with postprandial lipoprotein abnormalities in type 2 diabetes after acute correction for hyperglycemia and hyperinsulinemia. | yes | Insulin resistance is independently associated with postprandial alterations of triglyceride-rich lipoproteins in type 2 diabetes mellitus. |
22,622,332 | Does c5L2 receptor disruption enhance the development of diet-induced insulin resistance in mice? | {
"contexts": [
"Acylation stimulating protein (ASP) is a hormone secreted by the adipose tissue that has been shown to increase triglyceride storage and glucose transport in adipocytes. These effects are mediated by C5L2 receptor, which has also been associated with inflammatory effects. C5L2 deficient mice on a low-fat diet are hyperphagic yet lean due to increased energy expenditure. The present study assessed insulin sensitivity and metabolic and inflammatory changes in C5L2KO mice vs WT in diet-induced obesity.",
"We placed C5L2KO and WT mice on a diabetogenic diet for 12 weeks and examined in vivo and ex vivo metabolism.",
"C5L2KO mice on a diabetogenic diet exhibit decreased insulin sensitivity. Whole body substrate partitioning is evidenced through increased glucose uptake by the liver and decreased uptake by adipose tissue and skeletal muscle. Lipid content of both liver and skeletal muscle was higher in C5L2KO mice vs WT. Furthermore, elevated levels of macrophage markers were found in adipose tissue, liver and skeletal muscle of C5L2KO mice vs WT. Several inflammatory cytokines such as IL-6, MIP-1α and KC were also elevated in plasma of C5L2KO mice vs WT."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adipose Tissue",
"Animals",
"Body Fat Distribution",
"Cells, Cultured",
"Complement C3",
"Cytokines",
"Diet",
"Inflammation Mediators",
"Insulin Resistance",
"Intercellular Signaling Peptides and Proteins",
"Liver",
"Mice",
"Mice, Inbred C57BL",
"Mice, Knockout",
"Muscle, Skeletal",
"Obesity",
"Receptors, Chemokine",
"Triglycerides"
]
} | Overall, we demonstrated that C5L2KO mice fed a diabetogenic diet develop more severe insulin resistance than WT mice through altered substrate partitioning, ectopic fat deposition and a pro-inflammatory phenotype. | yes | C5L2 receptor disruption enhances the development of diet-induced insulin resistance in mice. |
22,098,918 | Do dietary treatments enriched in olive and safflower oils regulate seric and placental matrix metalloproteinases in maternal diabetes? | {
"contexts": [
"Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in placental development and function, although related to the pro-inflammatory environment when produced in excess. Previous studies have identified MMP-2 and MMP-9 overactivities in the placenta from diabetic rats. In this study, we aimed to determine whether diets supplemented with olive and safflower oil, enriched in natural PPAR ligands, are able to regulate MMP-2 and MMP-9 activities in the placenta and serum from diabetic rats.",
"Diabetes was induced in rat neonates by streptozotocin administration (90mg/kg s.c.). Control and diabetic rats were fed with 6% olive oil- or 6% safflower oil-supplemented diets from days 0.5-13.5 of gestation.",
"On day 13.5 of gestation, placentas and sera were isolated for further determination of matrix metalloproteinases (MMPs) 2 and 9 activities by zymography. Placental MMP-2 and MMP-9 protein concentration and immunolocalization were also determined.",
"Sera from diabetic pregnant animals showed MMP-2 and MMP-9 overactivities when compared to controls. Serum MMP-9 activity was significantly decreased when the diabetic animals received the olive and safflower oil dietary treatments. Placentas from diabetic rats showed increased MMP-2 and MMP-9 activities and protein concentrations, and both were decreased when diabetic rats received the olive and safflower dietary treatments."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Anti-Inflammatory Agents, Non-Steroidal",
"Biomarkers",
"Enzyme Precursors",
"Female",
"Ligands",
"Matrix Metalloproteinase 2",
"Matrix Metalloproteinase 9",
"Olive Oil",
"Peroxisome Proliferator-Activated Receptors",
"Placenta",
"Plant Oils",
"Pregnancy",
"Pregnancy Proteins",
"Pregnancy in Diabetics",
"Protein Transport",
"Random Allocation",
"Rats",
"Rats, Wistar",
"Safflower Oil",
"Streptozocin"
]
} | This study demonstrates that both olive and safflower oil-supplemented diets were able to prevent MMPs overactivities in the placenta from diabetic rats, and that these beneficial effects are reflected in rat sera. | yes | Dietary treatments enriched in olive and safflower oils regulate seric and placental matrix metalloproteinases in maternal diabetes. |
20,371,761 | Is socioeconomic position , not race , linked to death after cardiac surgery? | {
"contexts": [
"Health disparities have been associated with the prevalence of cardiovascular disease. In cardiac surgery, association has been found between race, sex, and poorer prognosis after surgery. However, there is a complex interplay between race, sex, and socioeconomic position (SEP). In our investigation we sought to identify which of these was the driver of risk-adjusted survival.",
"From January 1, 1995, and December 30, 2005, 23 330 patients (15 156 white men, 6932 white women, 678 black men, and 564 black women) underwent isolated coronary artery bypass grafting, valve, or combined coronary artery bypass grafting and valve procedures. Median follow-up was 5.8 years (25th and 75th percentiles: 3 and 8.6 years). Effect of race, sex, and SEP on all-cause mortality was examined with 2-phase Cox model and generalized propensity score technique. As expected, blacks and women had lower SEP as compared with whites and men for all 6 SEP indicators. Patients with lower SEP had more atherosclerotic disease burden, more comorbidity, and were more symptomatic. Lower SEP was associated with a risk-adjusted dose-dependent reduction in survival after surgery (men, P<0.0001; women, P=0.0079), but black race, once adjusted for SEP, was not."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Aged",
"Cardiovascular Diseases",
"Comorbidity",
"Continental Population Groups",
"Coronary Artery Bypass",
"Female",
"Follow-Up Studies",
"Heart Valve Prosthesis",
"Humans",
"Hypertension",
"Male",
"Middle Aged",
"Prosthesis Implantation",
"Risk Factors",
"Sex Factors",
"Social Class",
"Stroke",
"Survival Analysis"
]
} | Our large investigation demonstrates that disparities in SEP are present and significantly affect health outcomes. Although race per se was not the driver for reduced survival, patients of low SEP were predominantly represented by blacks and women. Socioeconomically disadvantaged patients had significantly higher risk-adjusted mortality after surgery. Further investigation and targeted intervention should focus specifically on patients of low SEP, their health behaviors, and secondary prevention efforts. | yes | Socioeconomic position, not race, is linked to death after cardiac surgery. |
24,815,169 | Does cBRH-7919 cell supernate promote fibroblasts to express cyclooxygenase-2 and hepatocyte growth factor? | {
"contexts": [
"Transplanted cells need a microenvironment for proliferation and neovascularization. As an important component of the microenvironment, fibroblasts play a role in the process of tumor growth. With that in mind, we planned to activate fibroblasts in vitro and investigate the expression of cyclooxygenase-2 (COX-2) and hepatocyte growth factor (HGF) which can promote the proliferation and neovascularization of the transplanted liver cells.",
"Fibroblasts were isolated from 20-day-old fetal Sprague-Dawley rats and incubated in the absence or presence of rat hepatoma CBRH-7919 cell supernate. On days 1, 2, 3, 5, and 7 the incubated fibroblasts were taken for detection of the levels of HGF and COX-2 by immunocytochemistry and the levels of HGF mRNA and COX-2 mRNA by reverse-transcription polymerase chain reaction.",
"When incubated in the presence of CBRH-7919 cell supernate, the fibroblasts could be activated to myofibroblasts that expressed alpha-smooth muscle actin at a high level, and the fibroblasts expressed COX-2, COX-2 mRNA, HGF, and HGF mRNA at higher levels, reaching a peak on day 3 and maintained at high levels until on day 7."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Actins",
"Animals",
"Carcinoma, Hepatocellular",
"Cell Fractionation",
"Cell Line, Tumor",
"Cyclooxygenase 2",
"Fibroblasts",
"Genetic Markers",
"Hepatocyte Growth Factor",
"Liver Neoplasms",
"Myofibroblasts",
"RNA, Messenger",
"Rats, Sprague-Dawley",
"Subcellular Fractions",
"Time Factors"
]
} | Fibroblasts can be activated by CBRH-7919 cell supernate. Activated fibroblasts can express COX-2 and HGF at higher levels. Maybe we can take advantage of the activated fibroblasts to promote the neovascularization and proliferation of transplanted liver cells. | yes | cBRH-7919 cell supernate promotes fibroblasts to express cyclooxygenase-2 and hepatocyte growth factor. |
23,742,776 | Does propofol inhibit the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression? | {
"contexts": [
"Propofol is one of the extensively and commonly used intravenous anesthetics and has the ability to influence the proliferation, motility, and invasiveness of many cancer cells. In this study, the effects of propofol on hepatocellular carcinoma cells invasion ability were examined.",
"We assessed the invasion ability of HepG2 cells in vitro by determining enzyme activity and protein expression of MMP-9 using gelatin zymography assay and Western blot. The real-time PCR was used to evaluate the effect of propofol on microRNA-199a (miR-199a) expression, and miR-199a-2 precursor to evaluate whether over-expression of miR-199a can affect MMP-9 expression. Finally, the effect of miR-199a on propofol-induced anti-tumor activity using anti-miR-199a was assessed.",
"Propofol significantly elevated the expression of miR-199a and inhibited the invasiveness of HepG2 cells. Propofol also efficiently decreased enzyme activity and protein expression of MMP-9. Moreover, the over-expression of miR-199a decreased MMP-9 protein level. Interestingly, the neutralization of miR-199a by anti-miR-199a antibody reversed the effect of propofol on alleviation of tumor invasiveness and inhibition of MMP-9 activity in HepG2 cells."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Anesthetics, Intravenous",
"Carcinoma, Hepatocellular",
"Cell Adhesion",
"Cell Movement",
"Dose-Response Relationship, Drug",
"Down-Regulation",
"Gene Expression Regulation, Enzymologic",
"Gene Expression Regulation, Neoplastic",
"Hep G2 Cells",
"Humans",
"Liver Neoplasms",
"Matrix Metalloproteinase 9",
"MicroRNAs",
"Neoplasm Invasiveness",
"Propofol",
"Transfection",
"Up-Regulation"
]
} | Propofol decreases hepatocellular carcinoma cell invasiveness, which is partly due to the down-regulation of MMP-9 expression by miR-199a. | yes | Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression. |
23,456,384 | Does body surface area predict plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy? | {
"contexts": [
"Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia.",
"We collected blood and peritoneal perfusate samples from ten patients undergoing HIPEC with a BSA-based dose of 250 mg/m(2) oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. We monitored blood glucose for 24 h postoperatively. Areas under concentration-time curves (AUC) were calculated by trapezoidal rule. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/AUC[plasma]). We used linear regression to test for statistical significance.",
"Higher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Antineoplastic Agents",
"Area Under Curve",
"Ascitic Fluid",
"Body Surface Area",
"Chemotherapy, Cancer, Regional Perfusion",
"Cohort Studies",
"Colonic Neoplasms",
"Combined Modality Therapy",
"Female",
"Follow-Up Studies",
"Humans",
"Hyperthermia, Induced",
"Male",
"Mesothelioma",
"Middle Aged",
"Neoplasm Staging",
"Organoplatinum Compounds",
"Oxaliplatin",
"Peritoneal Neoplasms",
"Prognosis",
"Pseudomyxoma Peritonei",
"Serum Albumin, Bovine",
"Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization",
"Survival Rate",
"Tissue Distribution"
]
} | Higher BSA is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration. Plasma glucose levels after oxaliplatin HIPEC were not clearly related to BSA. | yes | Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy. |
24,350,714 | Is high protein intake associated with low prevalence of frailty among old Japanese women : a multicenter cross-sectional study? | {
"contexts": [
"Protein intake has been inversely associated with frailty. However, no study has examined the effect of the difference of protein sources (animal or plant) or the amino acid composing the protein on frailty. Therefore, we examined the association of protein and amino acid intakes with frailty among elderly Japanese women.",
"A total of 2108 grandmothers or acquaintances of dietetic students aged 65 years and older participated in this cross-sectional multicenter study, which was conducted in 85 dietetic schools in 35 prefectures of Japan. Intakes of total, animal, and plant protein and eight selected amino acids were estimated from a validated brief-type self-administered diet history questionnaire and amino acid composition database. Frailty was defined as the presence of three or more of the following four components: slowness and weakness (two points), exhaustion, low physical activity, and unintentional weight loss.",
"The number of subjects with frailty was 481 (23%). Adjusted ORs (95% CI) for frailty in the first, second, third, fourth, and fifth quintiles of total protein intake were 1.00 (reference), 1.02 (0.72, 1.45), 0.64 (0.45, 0.93), 0.62 (0.43, 0.90), and 0.66 (0.46, 0.96), respectively (P for trend = 0.001). Subjects categorized to the third, fourth, and fifth quintiles of total protein intake (>69.8 g/d) showed significantly lower ORs than those to the first quintile (all P <0.03). The intakes of animal and plant protein and all selected amino acids were also inversely associated with frailty (P for trend <0.04), with the multivariate adjusted OR in the highest compared to the lowest quintile of 0.73 for animal protein and 0.66 for plant protein, and 0.67-0.74 for amino acids, albeit that the ORs for these dietary variables were less marked than those for total protein."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Aging",
"Amino Acids",
"Cohort Studies",
"Cross-Sectional Studies",
"Databases, Protein",
"Diet, Protein-Restricted",
"Dietary Proteins",
"Female",
"Frail Elderly",
"Health Surveys",
"Humans",
"Japan",
"Lethargy",
"Muscle Weakness",
"Plant Proteins",
"Prevalence",
"Sarcopenia",
"Sedentary Behavior",
"Weight Loss"
]
} | Total protein intake was significantly inversely associated with frailty in elderly Japanese women. The association of total protein with frailty may be observed regardless of the source of protein and the amino acid composing the protein. | yes | High protein intake is associated with low prevalence of frailty among old Japanese women: a multicenter cross-sectional study. |
19,088,637 | Do medical students learn over distance using virtual reality simulation? | {
"contexts": [
"This article presents the results of a demonstration project that was designed with the goal to determine the feasibility and acceptability of medical students in using distance technology and virtual reality (VR) simulation within a problem-based learning (PBL).",
"This pilot project involved students from the Universities of New Mexico and Hawaii and compared (1) control groups consisting of medical students in a tutor-guided PBL session using a text-based case, (2) distance groups using the same text-based case but interacting over distance from multiple sites, (3) groups using a VR simulation scenario integrated into the case without interaction over distance, and (4) combination groups interacting over distance from multiple sites with integration of a VR simulation scenario.",
"The study results suggest that it is possible to successfully conduct a PBL tutorial with medical students from two institutions with the integration VR and distributed distance interaction in combination or independently. The addition of these modalities did not interfere with learning dynamics when compared with traditional tutorial sessions."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Computer Simulation",
"Computer-Assisted Instruction",
"Education, Distance",
"Education, Medical",
"Feasibility Studies",
"Humans",
"Pilot Projects",
"Problem-Based Learning",
"Program Evaluation",
"User-Computer Interface"
]
} | These findings suggest the feasibility and acceptability by students in the use of VR simulation integrated into a PBL learning session, as well as multipoint distance technologies that allowed interaction between students and tutors in different locations. The authors believe that these modalities can be applied where students and tutors from different institutions are in separate locations and can be used to support interactive experiential learning in a distributed network or on site and suggest areas for additional research. | yes | Medical students learn over distance using virtual reality simulation. |
23,694,840 | Does vitamin D supplementation reduce the risk of acute otitis media in otitis-prone children? | {
"contexts": [
"The aim of this study was to evaluate whether a deficit in vitamin D (VD) is associated with an increased risk of recurrent acute otitis media (AOM) and whether VD supplementation is effective in reducing the number of AOM episodes in otitis-prone children.",
"A total of 116 children with a history of recurrent AOM (≥3 episodes in preceding 6 months or ≥4 episodes in preceding 12 months) were prospectively and blindly randomized to receive oral VD 1000 IU/d or placebo for 4 months. Episodes of AOM were monitored for 6 months.",
"Fifty-eight children received placebo and 58 with similar characteristics were treated with VD. The number of children experiencing ≥1 AOM episode during the study period was significantly lower in the treatment group (26 versus 38; P = 0.03). There was a marked difference in the number of children who developed uncomplicated AOM (P < 0.001), but no difference in the number of children with ≥1 episode of spontaneous otorrhea. The likelihood of AOM was significantly reduced in the patients whose serum VD concentrations were ≥30 ng/mL."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Acute Disease",
"Chi-Square Distribution",
"Child, Preschool",
"Double-Blind Method",
"Female",
"Humans",
"Infant",
"Kaplan-Meier Estimate",
"Male",
"Otitis Media",
"Placebos",
"Prospective Studies",
"Treatment Outcome",
"Vitamin D"
]
} | VD hypovitaminosis is common in children with recurrent AOM and associated with an increase in the occurrence of AOM when serum 25(OH)D levels are <30 ng/mL. The administration of VD in a dosage of 1000 IU/d restores serum values of ≥30 ng/mL in most cases and is associated with a significant reduction in the risk of uncomplicated AOM. | yes | Vitamin D supplementation reduces the risk of acute otitis media in otitis-prone children. |
27,729,282 | Does clausenidin from Clausena excavata induce apoptosis in hepG2 cells via the mitochondrial pathway? | {
"contexts": [
"Clausena excavata Burm.f. is used locally in folk medicine for the treatment of cancer in South East Asia.",
"To determine the mechanism of action of pure clausenidin crystals in the induction of hepatocellular carcinoma (hepG2) cells apoptosis.",
"Pure clausenidin was isolated from Clausena excavata Burm.f. and characterized using ",
"Clausenidin induced significant (p<0.05) and dose-dependent apoptosis of hepG2 cells. Cell cycle assay showed that clausenidin induced a G2/M phase arrest, caused mitochondrial membrane depolarization and significantly (p<0.05) increased expression of caspases 3 and 9, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, clausenidin caused decreased expression of the anti-apoptotic protein, Bcl 2 and increased expression of the pro-apoptotic protein, Bax. This finding was confirmed by the downregulation of Bcl-2 gene and upregulation of the Bax gene in the treated hepG2 cells."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Apoptosis",
"Caspase 3",
"Caspase 9",
"Clausena",
"Gene Expression",
"Hep G2 Cells",
"Humans",
"Membrane Potential, Mitochondrial",
"Microscopy, Electron, Scanning",
"Mitochondria",
"Plant Extracts"
]
} | Clausenidin extracted from Clausena excavata Burm.f. is an anti-hepG2 cell compound as shown by its ability to induce apoptosis through the mitochondrial pathway of apoptosis. Clausenidin can potentially be developed into an anticancer compound. | yes | Clausenidin from Clausena excavata induces apoptosis in HepG2 cells via the mitochondrial pathway. |
21,596,869 | Does application of pulsed radiofrequency currents to rat dorsal root ganglia modulate nerve injury-induced tactile allodynia? | {
"contexts": [
"Application of pulsed radiofrequency (PRF) currents to the dorsal root ganglia (DRG) has been reported to produce relief from certain pain states without causing thermal ablation. In this study, we examined the direct correlation between PRF application to DRG associated with spinal nerve injury and reversal of injury-induced behavioral hypersensitivity in a rat neuropathic pain model.",
"Neuropathic lesioning was performed via left L5 spinal nerve ligation on male adult Sprague-Dawley rats. Once the injured rats had developed tactile allodynia, one group was then assigned to PRF treatment of the L5 DRG and another group was assigned to the sham treatment to the DRG. Behavioral testing was performed on both the control and treated paws using the von Frey filament test before the surgery and at indicated days. The resulting data were analyzed using a linear mixed model to assess the overall difference between the treatment groups and the overall difference among the study days. Cohen's d statistic was computed from paired difference-from-baseline scores for each of the 14 study days after treatment and these measures of effect size were then used to descriptively compare the recovery patterns over time for each study group.",
"Spinal nerve injury resulted in the development of behavioral hypersensitivity to von Frey filament stimulation (allodynia) in the hindpaw of the left (injury) side. Mixed linear modeling showed a significant difference between the treatment groups (P = 0.0079) and a significant change of paw withdrawal threshold means over time (P = 0.0006) for all 12 animals. Evaluation of Cohen's d (effect size) revealed that the PRF-treated animals exhibited better recovery and recorded larger effect sizes than the sham-treated animals on 10 of the 14 post-PRF treatment days and exhibited moderate-to-strong effects posttreatment at days 8 to 10 and at and beyond day 32."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Analysis of Variance",
"Animals",
"Behavior, Animal",
"Disease Models, Animal",
"Electric Stimulation Therapy",
"Ganglia, Spinal",
"Hyperalgesia",
"Ligation",
"Linear Models",
"Male",
"Neuralgia",
"Pain Measurement",
"Pain Threshold",
"Rats",
"Rats, Sprague-Dawley",
"Spinal Nerves",
"Time Factors"
]
} | Findings from this study support that PRF of the DRG causes reversal of nerve injury (spinal nerve ligation)-induced tactile allodynia in rats. This allodynia reversal indicates that nonablative PRF acting via modulation of the DRG can speed recovery in nerve injury-induced pain. | yes | Application of pulsed radiofrequency currents to rat dorsal root ganglia modulates nerve injury-induced tactile allodynia. |
11,813,829 | Does recombinant plasma gelsolin diminish the acute inflammatory response to hyperoxia in mice? | {
"contexts": [
"The acute respiratory distress syndrome remains a common and poorly understood complication of a variety of insults. Ventilation with high concentrations of inspired oxygen may further damage already compromised lungs. By scavenging extracellular actin and modulating the effects of lysophosphatidic acid, plasma gelsolin could serve a critical protective role against oxidant injury.",
"Mice exposed to >95% O2 for a total of 72 hours were treated with gelsolin or albumin after 24 and 48 hours.",
"Neutrophil counts in bronchoalveolar fluid rose (P=0.0002) and gelsolin levels dropped (P<0.00001) in mice with acute hyperoxic lung injury. The acute inflammatory response to hyperoxia was significantly reduced in the gelsolin- compared with the bovine serum albumin-treated mice (P=0.03)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Gelsolin",
"Humans",
"Hyperoxia",
"Inflammation",
"Lung",
"Lung Injury",
"Mice",
"Mice, Inbred BALB C",
"Recombinant Proteins",
"Respiratory Distress Syndrome, Adult"
]
} | These data imply that i) gelsolin depletion contributes to the pathogenesis of oxygen toxicity and ii) repletion of gelsolin can partially abrogate the resultant exudative response. | yes | Recombinant plasma gelsolin diminishes the acute inflammatory response to hyperoxia in mice. |
18,635,401 | Does sex chromosome complement affect nociception and analgesia in newborn mice? | {
"contexts": [
"In animal studies of nociception, females are often more sensitive to painful stimuli, whereas males are often more sensitive to analgesia induced by mu-agonists. Sex differences are found even at birth, and in adulthood are likely caused, at least in part, by differences in levels of gonadal hormones. In this report, we investigate nociception and analgesia in neonatal mice and assess the contribution of the direct action of sex chromosome genes in hotplate and tail withdrawal tests. We used the 4 core genotypes mouse model, in which gonadal sex is independent of the complement of sex chromosomes (XX vs XY). Mice were tested at baseline and then injected with mu-opioid agonist morphine (10 mg/kg) or with the kappa-opioid agonist U50,488H (U50, 12.5 mg/kg) with or without the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (0.1 mg/kg). On the day of birth, XX mice showed faster baseline latencies than XY in tail withdrawal, irrespective of their gonadal type. Gonadal males showed greater effects of morphine than gonadal females in the hotplate test, irrespective of their sex chromosome complement. U50 and morphine were effective analgesics in both tests, but MK-801 did not block the U50 effect. The results suggest that sex chromosome complement and gonadal secretions both contribute to sex differences in nociception and analgesia by the day of birth."
],
"labels": [
"UNLABELLED"
],
"meshes": [
"3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer",
"Analgesia",
"Analgesics",
"Analgesics, Non-Narcotic",
"Analgesics, Opioid",
"Analysis of Variance",
"Animals",
"Animals, Newborn",
"Behavior, Animal",
"Dizocilpine Maleate",
"Excitatory Amino Acid Antagonists",
"Female",
"Injections, Subcutaneous",
"Male",
"Mice",
"Mice, Knockout",
"Morphine",
"Pain",
"Pain Measurement",
"Pain Threshold",
"Sex Characteristics",
"Sex Chromosomes",
"Sex Determination Processes",
"Sex Factors"
]
} | Sex differences in pain may stem not only from the action of gonadal hormones on pain circuits but from the sex-specific action of X and Y genes. Identification of sex chromosome genes causing sex differences could contribute to better pain therapy in females and males. | yes | Sex chromosome complement affects nociception and analgesia in newborn mice. |
22,329,816 | Do hydroxylated estrogens ( 2-OH-E2 AND 4-OH-E2 ) activate cAMP/PKA and ERK1/2 pathways activation in a breast cancer MCF-7 cell line? | {
"contexts": [
"The current study was undertaken to determine the involvement of cAMP/PKA and MAPK-mediated signalling pathways in the regulation of cell proliferation by hydroxylated metabolites of 17β-estradiol (E2).",
"MCF-7, human breast cancer cells, were cultured in phenol red-free DMEM and treated with 1 nM 2-OH-E2 or 4-OH-E2. E2 was used as a positive control. Cell proliferation was measured using the BrdU incorporation assay. Cellular levels of cAMP and PKA were determined using ELISA kits. ERK1/2 protein expression was evaluated by Western Blot analysis. To determine the involvement of different intracellular pathways in the regulation of cell proliferation appropriate activators or inhibitors were used.",
"Hydroxylated estrogens, as E2, exhibited no influence on cAMP accumulation and PKA activation. In concomitant treatments with forskolin, cell proliferation decreased to the amount noted under the influence of forskolin alone. A PKA inhibitor (PKI) had no statistically significant effect on proliferation stimulated by E2 and its hydroxylated metabolites. Phospho-ERK1/2 protein expression in cells stimulated with E2, 2-OH-E2 and 4-OH-E2 was not significantly different from the control. However, co-treatment with both PD98059 and E2 or its hydroxylated metabolites reversed the effect of tested compounds on cell proliferation."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Breast Neoplasms",
"Carcinoma",
"Cell Line, Tumor",
"Cyclic AMP",
"Cyclic AMP-Dependent Protein Kinases",
"Drug Evaluation, Preclinical",
"Enzyme Activation",
"Estradiol",
"Estrogens",
"Estrogens, Catechol",
"Female",
"Humans",
"Hydroxylation",
"MAP Kinase Signaling System",
"Signal Transduction"
]
} | We have shown that E2 hydroxylated metabolites do not activate cAMP/PKA in breast cancer cells and confirm previously published data, which showed a lack of ERK1/2 activation in a breast cancer cell line. The observed reversible action of PD98059 on cell proliferation can be explained by the fact that hydroxylated estrogens, as E2, stimulate secretion of a number of growth factors, which affect MAPK activity, suggested by Lobenhofer et al. (2000). | no | Hydroxylated estrogens (2-OH-E2 and 4-OH-E2) activate cAMP/PKA and ERK1/2 pathways activation in a breast cancer MCF-7 cell line. |
12,172,358 | Does the clinical significance of thickened gastric fold found on upper gastrointestinal series? | {
"contexts": [
"To assess the impact of upper endoscopy and biopsy on the outcome of patients with isolated thickened gastric folds found on barium upper gastrointestinal series (UGIS).",
"A total of 8,325 consecutive UGIS reports were reviewed to identify 182 patients who were found to have isolated thickened gastric folds. Patients with other serious radiographic abnormalities were excluded. The 182 patients were studied by a systematic review of the esophagogastroduodenoscopy (EGD) findings, gastric biopsy results, and clinical outcome.",
"The study included 96 men (52.7%) and 86 women (47.3%) who had isolated thickened gastric folds on the UGIS. Seventy-four patients underwent EGD; 108 patients did not. The two groups were similar in demographic and clinical features. The EGD results were normal, 18 (24.3%); thick gastric folds, 12 (16.2%); hiatal hernia, 12 (16.2%); erythema/inflammation, 11 (14.9%); erosions, 8 (10.8%); portal gastropathy, 3 (4.1%); and gastric ulcer, 1 (1.4%). Forty-eight of the 74 EGD patients had a gastric biopsy. The findings were chronic active gastritis, 39 (81.3%); and chronic gastritis, 5 (10.4%). Evidence for H. pylori infection was present in 91.7% of the gastric biopsies. Outcome (mean follow-up, 28.5 months) was assessed in 49 patients in the EGD group and in 55 patients in the non-EGD group. There were no cases of serious or new UGI problems in either group."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Aged",
"Barium",
"Biopsy",
"Contrast Media",
"Endoscopy, Gastrointestinal",
"Female",
"Helicobacter Infections",
"Helicobacter pylori",
"Humans",
"Male",
"Middle Aged",
"Radiography",
"Retrospective Studies",
"Stomach",
"Stomach Diseases"
]
} | Isolated thickened gastric folds found on UGIS are frequently associated with H. pylori infection. Performing endoscopy and biopsy did not appear to alter the outcome in these patients. | yes | The clinical significance of thickened gastric fold is found on upper gastrointestinal series. |
26,882,436 | Does fNA smear as a potential source of DNA for targeted next-generation sequencing of lung adenocarcinomas? | {
"contexts": [
"Diff-Quik-stained fine-needle aspiration (FNA) smears and touch preparations from biopsies represent alternative specimens for molecular testing when cell block or biopsy material is insufficient. This study describes the use of these samples for targeted next-generation sequencing (NGS) of primary and metastatic lung adenocarcinoma and reports the DNA quality and success rates of FNA smears versus other specimens from 1 year of clinical use.",
"A validation set of 10 slides from 9 patients with prior clinical epidermal growth factor receptor (EGFR) Sanger sequencing and KRAS pyrosequencing (5 KRAS-positive/EGFR-negative and 4 KRAS-negative/EGFR-negative) underwent DNA extraction, quality assessment, and targeted NGS. Subsequently, lung adenocarcinoma specimens submitted for NGS solid tumor mutation panel testing in 1 calendar year (60 biopsies, 57 resections, 33 FNA cell blocks, 12 FNA smears, and 10 body fluid cell blocks) were reviewed for specimen adequacy, sequencing success, and DNA quality.",
"All 10 validation samples met the DNA quality threshold (delta Ct threshold < 8; range, -2.2 to 4.9) and yielded 0.5 to 22 μg of DNA. The KRAS and EGFR mutation status from FNA smears according to NGS was concordant with previous clinical testing for all 10 samples. In the 1-year review, FNA smears were 100% successful, and this suggested a performance equivalent to or better than the performance of established specimen types, including FNA cell blocks. DNA quality according to ΔCt was significantly better with FNA smears versus biopsies, resections, and FNA cell blocks."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenocarcinoma",
"Biomarkers, Tumor",
"Biopsy, Fine-Needle",
"Carcinoma, Non-Small-Cell Lung",
"DNA Mutational Analysis",
"ErbB Receptors",
"High-Throughput Nucleotide Sequencing",
"Humans",
"Lung Neoplasms",
"Lymphatic Metastasis",
"Mutation",
"Neoplasm Grading",
"Prognosis",
"Proto-Oncogene Proteins p21(ras)"
]
} | FNA smears of lung adenocarcinomas are high-quality alternative specimens for a targeted NGS panel with a high success rate in clinical practice. Cancer Cytopathol 2016;124:406-14. © 2016 American Cancer Society. | yes | fNA smear is a potential source of DNA for targeted next-generation sequencing of lung adenocarcinomas. |
27,833,819 | Are salivary microbiomes of indigenous Tsimane mothers and infants distinct despite frequent premastication? | {
"contexts": [
"Premastication, the transfer of pre-chewed food, is a common infant and young child feeding practice among the Tsimane, forager-horticulturalists living in the Bolivian Amazon. Research conducted primarily with Western populations has shown that infants harbor distinct oral microbiota from their mothers. Premastication, which is less common in these populations, may influence the colonization and maturation of infant oral microbiota, including via transmission of oral pathogens. We collected premasticated food and saliva samples from Tsimane mothers and infants (9-24 months of age) to test for evidence of bacterial transmission in premasticated foods and overlap in maternal and infant salivary microbiota. We extracted bacterial DNA from two premasticated food samples and 12 matched salivary samples from maternal-infant pairs. DNA sequencing was performed with MiSeq (Illumina). We evaluated maternal and infant microbial composition in terms of relative abundance of specific taxa, alpha and beta diversity, and dissimilarity distances.",
"The bacteria in saliva and premasticated food were mapped to 19 phyla and 400 genera and were dominated by Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. The oral microbial communities of Tsimane mothers and infants who frequently share premasticated food were well-separated in a non-metric multi-dimensional scaling ordination (NMDS) plot. Infant microbiotas clustered together, with weighted Unifrac distances significantly differing between mothers and infants. Infant saliva contained more Firmicutes ("
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": []
} | Salivary microbiota of Tsimane infants and young children up to two years of age do not appear closely related to those of their mothers, despite frequent premastication and preliminary evidence that maternal bacteria is transmitted to premasticated foods. Infant physiology and diet may constrain colonization by maternal bacteria, including several oral pathogens. | yes | Salivary microbiomes of indigenous Tsimane mothers and infants are distinct despite frequent premastication. |
10,639,191 | Is prostatic involution in men taking finasteride associated with elevated levels of insulin-like growth factor-binding proteins ( IGFBPs ) -2 , -4 , and -5? | {
"contexts": [
"Insulin-like growth factor-binding proteins (IGFBPs)-2, -4, and -5 are associated with upregulation of apoptosis in the ovary. The purpose of this study was to assess the roles of IGF-I and IGFBPs during involution of the prostate. Frozen and fixed tissue was collected by transurethral prostatectomy from Caucasian men, aged 52-82 years, scheduled for prostatectomy for benign prostatic hyperplasia, who took either placebo (n = 7) or the 5alpha-reductase inhibitor finasteride for 6 days to 6 years (n = 15) prior to surgery.",
"Intraprostatic androgen levels were measured by radioimmunoassay. Tissues were immunostained for IGF-I and IGFBP-2, -3, -4, and -5, and staining was quantitated by computerized image analysis. Serial sections were stained for markers of apoptosis (TUNEL and tissue transglutaminase) and IGFBP-2, -4, or -5.",
"IGF-I staining was significantly decreased in the medium-term (18-43 days) treatment group and remained so for the duration of the study (P = 0.026). IGFBP-3 staining was unchanged in the early and medium-term treatment groups; however, a transient earlier rise in the level of this proapoptotic protein cannot be ruled out. The percentage of epithelial cell area staining positively for IGFBP-2 increased significantly, from 1.6 +/- 0.5 in the placebo group to 12.0 +/- 2.0 (P < 0.0001), and 7.6 +/- 1.9 (P = 0.003) in the short (6-13 days) and medium-term treatment groups, respectively. IGFBP-4 staining increased from 2.2 +/- 0.6 to 9.8 +/- 1.9 (P < 0.0001) and 7.4 +/- 1.2 (P = 0.004) in the short and medium-term groups, respectively, and IGFBP-5 staining increased from 0.2 +/- 0.1 to 3.8 +/- 2.0 (P = 0.004) in the medium-term group. The results from serial sections showed that IGFBP-2 and -4 costained with markers of apoptosis, while IGFBP-5 did not."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Double-Blind Method",
"Enzyme Inhibitors",
"Finasteride",
"Humans",
"Immunohistochemistry",
"Insulin-Like Growth Factor Binding Protein 2",
"Insulin-Like Growth Factor Binding Protein 4",
"Insulin-Like Growth Factor Binding Protein 5",
"Insulin-Like Growth Factor Binding Proteins",
"Insulin-Like Growth Factor I",
"Male",
"Middle Aged",
"Prostate",
"Prostatic Hyperplasia"
]
} | These results indicate that IGFBP-2, -4, and -5 are associated with prostatic involution. Because of the timing and distribution of expression, we hypothesize that IGFBP-2 and -4 have a role as signals for apoptosis, but that IGFBP-5 likely does not. | yes | Prostatic involution in men taking finasteride is associated with elevated levels of insulin-like growth factor-binding proteins ( IGFBPs ) -2 , -4 , and -5. |
21,190,639 | Is suicidality associated with medication access problems in publicly insured psychiatric patients? | {
"contexts": [
"Beginning January 1, 2006, the Medicare Part D prescription drug benefit shifted drug coverage from Medicaid to the new Medicare Part D program for patients who were eligible for both Medicare and Medicaid benefits (\"dual-eligibles\"). These patients were randomly assigned to a private Part D plan and came under specific formulary and utilization management procedures of the plan in which they were enrolled.",
"To examine the relationship between physician-reported medication switches, discontinuations, and other access problems and suicidal ideation or behavior among \"dual-eligible\" psychiatric patients.",
"Data were collected in 3 cross-sectional cycles in 2006 (January-April, May-August, and September-December) as part of the National Study of Medicaid and Medicare Psychopharmacologic Treatment Access and Continuity using through-the-mail, practice-based survey research methods. Data from the third cycle, representing all events since January 1, 2006, were used for these analyses. A national sample of psychiatrists randomly selected from the AMA Masterfile provided clinically detailed data on 1 systematically selected, dual-eligible psychiatric patient (N = 908). Propensity score analyses adjusted for patient sociodemographics, treatment setting, diagnoses, and psychiatric symptom severity.",
"Patients who experienced medication switches, discontinuations, and other access problems had 3 times the rate of suicidal ideation or behavior compared with patients with no access problems (22.0% vs 7.4%, P < .0001). Mean odds ratios and excess probabilities were highest for patients who were clinically stable but were required to switch medications (31.8%; mean OR = 4.87, mean P = 8.92(-5), excess probability = 0.21). Patients who experienced discontinuations (26.4%; mean OR = 2.13, mean P = 2.12(-2), excess probability = 0.12), other access problems (18.7%; mean OR = 3.01, mean P = 1.03(-5), excess probability = 0.15), and multiple access problems (22.3%; mean OR = 2.88, mean P = 4.10(-5), excess probability = 0.14) also had significantly increased suicidal ideation or behavior."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Cross-Sectional Studies",
"Eligibility Determination",
"Female",
"Health Services Accessibility",
"Humans",
"Insurance, Psychiatric",
"Male",
"Medicaid",
"Medicare",
"Medicare Part D",
"Medication Adherence",
"Mental Disorders",
"Middle Aged",
"Prescription Drugs",
"Risk Factors",
"Self Administration",
"Suicidal Ideation",
"United States"
]
} | Increased occurrences of suicidal ideation or behavior appear to be associated with disruptions in patient medication access and continuity. Clinicians need to be aware of the possibility of increased suicidality when, for administrative reasons, a clinically stable patient's medication regimen is altered. Dual-eligible psychiatric patients represent a highly vulnerable group with a substantial burden of illness; these findings underscore the need to provide special protections for this population. | yes | Suicidality is associated with medication access problems in publicly insured psychiatric patients. |
21,659,358 | Does the Wiskott-Aldrich syndrome protein permit assembly of a focused immunological synapse enabling sustained T-cell receptor signaling? | {
"contexts": [
"T-cell activation relies on the assembly of the immunological synapse, a structure tightly regulated by the actin cytoskeleton. The precise role of the Wiskott-Aldrich syndrome protein, an actin cytoskeleton regulator, in linking immunological synapse structure to downstream signaling remains to be clarified.",
"To address this point, CD4(+) T cells from patients with Wiskott-Aldrich syndrome were stimulated with antigen-presenting cells. The structure and dynamics of the immunological synapse were studied by confocal and video-microscopy.",
"Upon stimulation by antigen-presenting cells, Wiskott-Aldrich syndrome protein-deficient T cells displayed reduced cytokine production and proliferation. Although Wiskott-Aldrich syndrome T cells formed conjugates with antigen-presenting cells at normal frequency and exhibited normal T-cell receptor down-regulation, they emitted actin-rich protrusions away from the immunological synapse area and their microtubule organizing center failed to polarize fully towards the center of the immunological synapse. In parallel, abnormally dispersed phosphotyrosine staining revealed unfocused synaptic signaling in Wiskott-Aldrich syndrome T cells. Time-lapse microscopy confirmed the anomalous morphology of Wiskott-Aldrich syndrome T-cell immunological synapses and showed erratic calcium mobilization at the single-cell level."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Antigen-Presenting Cells",
"CD4-Positive T-Lymphocytes",
"Calcium",
"Cell Communication",
"Cell Line",
"Humans",
"Immunological Synapses",
"Lymphocyte Activation",
"Receptors, Antigen, T-Cell",
"Signal Transduction",
"Superantigens",
"Wiskott-Aldrich Syndrome",
"Wiskott-Aldrich Syndrome Protein"
]
} | Taken together, our data show that the Wiskott-Aldrich syndrome protein is required for the assembly of focused immunological synapse structures allowing optimal signal integration and sustained calcium signaling. | yes | The Wiskott-Aldrich syndrome protein permits assembly of a focused immunological synapse enabling sustained T-cell receptor signaling. |
26,311,066 | Does rhizoma Paridis Saponins induce Cell Cycle Arrest and Apoptosis in Non-Small Cell Lung Carcinoma A549 Cells? | {
"contexts": [
"As a traditional Chinese medicine herb, Chonglou (Paris polyphylla var. chensiins) has been used as anticancer medicine in China in recent decades, as it can induce cell cycle arrest and apoptosis in numerous cancer cells. The saponins extract from the rhizoma of Chonglou [Rhizoma Paridis saponins (RPS)] is known as the main active component for anticancer treatment. However, the molecular mechanism of the anticancer effect of RPS is unknown.",
"The present study evaluated the effect of RPS in non-small-cell lung cancer (NSCLC) A549 cells using the 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. Subsequently, the expression of several genes associated with cell cycle and apoptosis were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and Western blotting.",
"RPS was revealed to inhibit cell growth, causing a number of cells to accumulate in the G 1 phase of the cell cycle, leading to apoptosis. In addition, the effect was dose-dependent. Moreover, the results of qRT-PCR and Western blotting showed that p53 and cyclin-dependent kinase 2 (CDK2) were significantly downregulated, and that BCL2, BAX, and p21 were upregulated, by RPS treatment."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Antineoplastic Agents, Phytogenic",
"Apoptosis",
"Carcinoma, Non-Small-Cell Lung",
"Cell Line, Tumor",
"Cyclin-Dependent Kinase 2",
"Cyclin-Dependent Kinase Inhibitor p21",
"G1 Phase Cell Cycle Checkpoints",
"Gene Expression",
"Genes, bcl-2",
"Genes, p53",
"Humans",
"Lung Neoplasms",
"Magnoliopsida",
"Medicine, Chinese Traditional",
"Plants, Medicinal",
"Saponins",
"bcl-2-Associated X Protein"
]
} | We speculated that the RPS could act on a pathway, including p53, p21, BCL2, BAX, and CDK2, and results in G1 cell cycle arrest and apoptosis in NSCLC cells. | yes | Rhizoma Paridis Saponins induces cell cycle arrest and apoptosis in non-small cell lung carcinoma A549 cells. |
26,337,653 | Does sarcopenia Evaluated Using the Skeletal Muscle Index be a Significant Prognostic Factor for Metastatic Urothelial Carcinoma? | {
"contexts": [
"The purpose of the study was to evaluate the prognostic value of sarcopenia (muscle loss) in patients with metastatic urothelial carcinoma (UC), in a comparison of several methods of computed tomography (CT)-based evaluation of sarcopenia.",
"We retrospectively reviewed 100 patients with metastatic UC who underwent first-line systemic chemotherapy between 2003 and 2014. Sarcopenia was assessed by the following CT-based methods: skeletal muscle index (SMI), total psoas area (TPA), axial and/or transversal psoas thickness at the level of the third lumbar vertebrae, and axial and/or transversal psoas thickness at the umbilicus level (U-TPT). All parameters were standardized by either height or height squared. Cutoff points were SMI: < 55 cm(2)/m(2) (men), < 39 cm(2)/m(2) (women); others: lowest sex-specific quartiles. Predictive values for cancer-specific survival (CSS) were assessed using the Cox proportional hazards regression model.",
"Sixty-four patients met the eligibility criterion for analysis: those who underwent CT scans within 30 days before chemotherapy. Of them, 52 (81%) died of UC during the follow-up, with a median survival time of 13 months. Univariate analysis associated decreased SMI, TPA, and U-TPT with poor CSS. Multivariate analysis together with other pretreatment clinicopathologic parameters showed decreased SMI to be an independent predictor of poor CSS."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Carcinoma, Transitional Cell",
"Female",
"Humans",
"Kaplan-Meier Estimate",
"Lymphatic Metastasis",
"Male",
"Middle Aged",
"Multivariate Analysis",
"Muscle, Skeletal",
"Prognosis",
"Retrospective Studies",
"Sarcopenia",
"Urinary Bladder Neoplasms"
]
} | Evaluation using SMI showed sarcopenia was an independent predictor of poor prognosis for patients with metastatic UC who underwent first-line systemic chemotherapy. Our results might improve stratification of patients and help optimize evaluation of sarcopenia. | yes | Sarcopenia evaluated using the skeletal muscle index is a significant prognostic factor for metastatic urothelial carcinoma. |
17,371,524 | Are we mothers too : childbearing experiences of lesbian families? | {
"contexts": [
"To describe lesbians' personal and health care experiences of becoming pregnant, giving birth, and being mothers and comothers within the context of potentially oppressive family, social, and political structures.",
"Critical ethnography.",
"Participants' homes, lesbian mother support group, and prenatal clinics and hospitals in the Pacific Northwest.",
"English-speaking self-identified lesbian women, including 21 interview and six focus-group participants and approximately 43 observed in a support group.",
"In-depth open-ended interviews, focus group, and participant observation.",
"Content/categorical analysis followed by discussion of the mother's stories and a critical conversation about lesbian mothering.",
"The seven organizing themes are as follows: preparing the way: becoming ready; conception: you can't just fall into it; you can hear a heartbeat: pregnancy; birthing our babies; the work of mothers and mothers who work; families who sustain and families who oppose; and sources of support in everyday life. The first four are described in this article."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Female",
"Health Knowledge, Attitudes, Practice",
"Health Services Needs and Demand",
"Homosexuality, Female",
"Humans",
"Interpersonal Relations",
"Maternal Health Services",
"Middle Aged",
"Mothers",
"Northwestern United States",
"Parenting",
"Prejudice",
"Social Support",
"Stereotyping",
"Surveys and Questionnaires"
]
} | Health care providers, policy makers, and the public can be better informed about the specific needs of childbearing lesbians. | yes | We are mothers too: childbearing experiences of lesbian families. |
22,230,795 | Is androgen receptor signalling in Vascular Endothelial cells dispensable for spermatogenesis and male fertility? | {
"contexts": [
"Androgen signalling is essential both for male development and function of the male reproductive system in adulthood. Within the adult testis, Germ cells (GC) do not express androgen receptor (AR) suggesting androgen-mediated promotion of spermatogenesis must act via AR-expressing somatic cell-types. Several recent studies have exploited the Cre/lox system of conditional gene-targeting to ablate AR function from key somatic cell-types in order to establish the cell-specific role of AR in promotion of male fertility. In this study, we have used a similar approach to specifically ablate AR-signalling from Vascular Endothelial (VE) cells, with a view to defining the significance of androgen signalling within this cell-type on spermatogenesis.",
"AR expression in VE cells of the testicular vasculature was confirmed using an antibody against AR. A Cre-inducible fluorescent reporter line was used to empirically establish the utility of a mouse line expressing Cre Recombinase driven by the Tie2-Promoter, for targeting VE cells. Immunofluorescent detection revealed expression of YFP (and therefore Cre Recombinase function) limited to VE cells and an interstitial population of cells, believed to be macrophages, that did not express AR. Mating of Tie2-Cre males to females carrying a floxed AR gene produced Vascular Endothelial Androgen Receptor Knockout (VEARKO) mice and littermate controls. Ablation of AR from all VE cells was confirmed; however, no significant differences in bodyweight or reproductive tissue weights could be detected in VEARKO animals and spermatogenesis and fertility was unaffected."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": []
} | We demonstrate the successful generation and empirical validation of a cell-specific knockout of AR from VE cells, and conclude that AR expression in VE cells is not essential for spermatogenesis or male fertility. | yes | Androgen receptor signalling in vascular endothelial cells is dispensable for spermatogenesis and male fertility. |
19,700,954 | Is apathy associated with basal ganglia atrophy in frontotemporal dementia? | {
"contexts": [
"To determine whether basal ganglia atrophy, known to be associated with apathy in nondementia populations, was associated with presence of apathy in patients with frontotemporal dementia (FTD).",
"A cross-sectional case study was conducted at two tertiary dementia care clinics in Toronto, Ontario, Canada. Striatal and thalamic gray matter volumes and apathy measures were collected from 21 subjects with FTD, 6 of whom did not show apathy on the Neuropsychiatric Inventory.",
"No significant differences in gray matter volumes were found between apathetic and nonapathetic groups for the striatum or the thalamus."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Atrophy",
"Basal Ganglia",
"Cross-Sectional Studies",
"Dementia",
"Depression",
"Female",
"Humans",
"Magnetic Resonance Imaging",
"Male",
"Middle Aged",
"Neuropsychological Tests",
"Ontario",
"Quality of Life",
"Surveys and Questionnaires"
]
} | Our findings imply that the etiology of apathy seen in patients with FTD differs from that of patients with apathy after acquired injuries to the basal ganglia. Further study is needed to determine whether posterior thalamic atrophy correlates with apathy in FTD or functional imaging techniques might successfully find a relationship between basal ganglia dysfunction and apathy. | no | Apathy is associated with basal ganglia atrophy in frontotemporal dementia. |
23,103,189 | Does direct activation of sleep-promoting VLPO neurons by volatile anesthetics contribute to anesthetic hypnosis? | {
"contexts": [
"Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep.",
"Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, whereas neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Anesthetics",
"Animals",
"Halothane",
"Hypnosis, Anesthetic",
"Hypnotics and Sedatives",
"Isoflurane",
"Mice",
"Neurons",
"Potassium",
"Preoptic Area",
"Proto-Oncogene Proteins c-fos",
"Sleep",
"Unconsciousness"
]
} | Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties. | yes | Direct activation of sleep-promoting VLPO neurons by volatile anesthetics contributes to anesthetic hypnosis. |
19,091,200 | Does [ Early prediction of psychosocial intervention need in pneumology patients after nurses ' evaluation ]? | {
"contexts": [
"This study was aimed to verify whether it is possible to detect at hospital admission, by means of INTERMED, pneumonology patients at risk of \"complexity\" and of specialized psychosocial intervention.",
"With the Spanish version of INTERMED (for detection of risk for complexity of care) 144 patients were interviewed at admission by a standardized nurse. At discharge, patients were reassessed blindly with standardized Spanish versions of instruments including the Hospital Anxiety and Depression Scale (HADS). Somatic illness variables were independently documented, and severity was assessed by means of the Cumulative Illness Rating Scale. All variables were operationalized including complex (IM+; INTERMED>20) and non-complex patients (IM-), and probable need of psychosocial treatment/intervention. Statistical analysis included multivariate logistic regression.",
"A complex course was documented in 9.6% of patients, and 28.8% had complex discharge. Significantly higher proportions of severe anxiety and/or depression were documented in IM+ cases (12.1%) when compared to IM- cases (0.9%), and the need of psychosocial treatment/intervention was also significantly more frequent among the former (24.2% versus 6.3% respectively). Furthermore, in the multivariate analysis and controlling for medical and sociodemographic confounders INTERMED was significantly associated with the variable need of psychosocial intervention."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Anxiety Disorders",
"Female",
"Health Services Needs and Demand",
"Humans",
"Lung Diseases",
"Male",
"Mass Screening",
"Needs Assessment",
"Patient Selection",
"Prospective Studies",
"Psychotherapy",
"Pulmonary Medicine",
"Risk Factors"
]
} | In support of the clinical utility of the INTERMED method (Spanish version), this is the first report in the international literature documenting that standardized nurses are able to detect at admission those medical patients who will eventually need specialized psychosocial intervention. | yes | Early prediction of psychosocial intervention need in pneumology patients is needed after nurses' evaluation. |
24,331,679 | Do variant rs1421085 in the FTO gene contribute childhood obesity in Chinese children aged 3-6 years? | {
"contexts": [
"Childhood obesity has become a public health crisis worldwide due to an alarming increase in its prevalence. Numerous studies have demonstrated that the common variants (rs1421085 and rs17817449) of the fat mass and obesity associated (FTO) gene are associated with the obesity in adult and children in European. However, these two variants of FTO gene in childhood obesity have not been established in Chinese populations.",
"In this population-based case-control study, 158 obese preschooler and 397 normal population controls aged 3-6 years were recruited between June 2007 and April 2008 from 6 kindergartens of Huai-an city in Jiangsu Province, China. All the children were conducted the body examinations and provided blood sample to detect the serum lipid levels and FTO rs1421085 T>C and rs17817449 T>G genetic variances.",
"In the association analysis between the FTO gene variant and risk of childhood obesity, compared with the rs1421085TT wide-type genotype, rs1421085 CC and CT/CC genotypes were associated with 59% and 71% increased risks of childhood obesity (adjusted OR = 1.59, 95%CI = 1.00-2.53 for CC; adjusted OR = 1.71, 95%CI = 1.10-2.65 for CT/CC), while the rs17817449 T > G variant was not associated with the significantly increased risk of childhood obesity. In addition, the higher level of serum TG (>0.64 mmol/l) was associated with 93% increased risk of childhood obesity (adjusted OR = 1.93, 95%CI = 1.30-2.87), and the higher serum HDL-C level (>1.14 mmol/l) was associated with 45% decreased risk of childhood obesity (adjusted OR = 0.55, 95%CI = 0.37-0.81). But the quantitative phenotypes analysis regarding the levels of TC, TG, HDL-C, and LDL-C were not found to be significantly associated with the variants of rs1421085 and rs17817449 both in the cases and controls."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Alleles",
"Alpha-Ketoglutarate-Dependent Dioxygenase FTO",
"Asian Continental Ancestry Group",
"Case-Control Studies",
"Child",
"Child, Preschool",
"Dyslipidemias",
"Female",
"Genotype",
"Humans",
"Male",
"Odds Ratio",
"Pediatric Obesity",
"Phenotype",
"Polymorphism, Single Nucleotide",
"Proteins",
"Risk Factors",
"Triglycerides"
]
} | The FTO rs1421085 T>C polymorphism may modulate the magnitude of dyslipidemia in Chinese early-onset obesity. | yes | Variant rs1421085 in the FTO gene contributes to childhood obesity in Chinese children aged 3-6 years. |
21,873,660 | Is literacy an independent risk factor for vision impairment and poor visual functioning? | {
"contexts": [
"People with limited literacy are at increased risks of chronic systemic conditions. The authors therefore investigated the independent contribution of limited literacy on visual impairment and visual function in a large eye survey in Singapore.",
"The authors undertook a population-based, cross-sectional study of Asian Malays (≥ 40 years old). Visual impairment was defined as logMAR (logarithm of minimal angle of resolution) visual acuity > 0.30 in the better-seeing eye. Information regarding reading and writing literacy levels and other independent variables, including sociodemographic measures (e.g., education, income), were obtained from a standardized interview. Visual functioning was assessed using a modified and validated version of the Vision-Specific Functioning Scale using Rasch analysis.",
"Of the 3280 participants, 553 (16.9%) had inadequate reading literacy and 688 (21.0%) had inadequate writing literacy. In multivariate analysis, persons with inadequate reading literacy were more likely to have presenting visual impairment (odds ratio [OR] = 2.66; 95% confidence interval [CI] = 1.91 to 3.72; P < 0.001), best-corrected visual impairment (OR = 2.59; 95% CI = 1.70 to 3.96; P < 0.001), and poorer visual functioning (β coefficient = 0.58; 95% CI = 1.57 to 3.02; P < 0.001), even controlling for education, income, and other patients' characteristics. Similar associations were found for inadequate writing literacy."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Asian Continental Ancestry Group",
"Cross-Sectional Studies",
"Educational Status",
"Female",
"Health Surveys",
"Humans",
"Male",
"Middle Aged",
"Quality of Life",
"Reading",
"Risk Factors",
"Sickness Impact Profile",
"Singapore",
"Surveys and Questionnaires",
"Vision Disorders",
"Visual Acuity",
"Visually Impaired Persons",
"Writing"
]
} | Inadequate literacy is independently associated with visual impairment and poorer visual functioning. Interventions that address literacy may help to reduce socioeconomic disparities in visual impairment. | yes | Literacy is an independent risk factor for vision impairment and poor visual functioning. |
19,839,839 | Does atorvastatin prevent gentamicin-induced renal damage in rats through the inhibition of p38-MAPK and NF-kappaB pathways? | {
"contexts": [
"Gentamicin (GM) is still considered to be an important antibiotic against life-threatening, gram-negative bacterial infections despite its known nephrotoxic effects. We aimed to evaluate the potential protective effect of atorvastatin (ATO) against GM-induced nephrotoxicity in rats.",
"The rats were randomly divided into five groups of six animals each: control, GM (100 mg/kg/day), ATO (10 mg/kg/day), GM + ATO, and GM + Vehicle. Kidney function tests, tissue oxidative stress parameters, and histopathological and immunohistochemical studies clarified GM nephrotoxicity.",
"GM caused a marked reduction in renal functions and increased oxidative stress parameters. Histopathological examination revealed tubular necrosis especially in the renal cortex in GM rats. On immunohistochemical evaluation, GM rat showed more intense expressions of mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-kappaB), and inducible nitric oxide synthase (iNOS) compared with control. Kidney function tests and tissue oxidative stress parameters were normalized in the GM + ATO group. Histopathological and immunohistochemical pictures were also greatly ameliorated."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Analysis of Variance",
"Animals",
"Atorvastatin",
"Chi-Square Distribution",
"Disease Models, Animal",
"Free Radical Scavengers",
"Gentamicins",
"Heptanoic Acids",
"Immunohistochemistry",
"Kidney Function Tests",
"Kidney Tubular Necrosis, Acute",
"MAP Kinase Signaling System",
"Male",
"NF-kappa B",
"Nitric Oxide",
"Oxidative Stress",
"Probability",
"Pyrroles",
"Random Allocation",
"Rats",
"Rats, Wistar",
"p38 Mitogen-Activated Protein Kinases"
]
} | ATO acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM via the inhibition of MAPK and NF-kappaB signaling pathways and iNOS expression. | yes | Atorvastatin prevents gentamicin-induced renal damage in rats through the inhibition of p38-MAPK and NF-kappaB pathways. |
19,240,377 | Does antigen-induced expression of CD203c on basophils predict IgE-mediated wheat allergy? | {
"contexts": [
"For in vitro diagnosis of wheat allergy, specific IgE to wheat is known to be a poor predictive marker. Oral food challenge, the gold standard for the diagnosis, is accompanied by a risk of severe induced reactions. Reliable in vitro tests are needed to be developed for safe indication for oral challenge.",
"We examined the utility of a basophil activation marker, CD203c, for the diagnosis of IgE-mediated wheat allergy.",
"Fifty-eight children with suspected wheat allergy with positive CAP-FEIA to wheat were enrolled. On 70 occasions, the clinical distinction between patients with wheat allergy (WA) and patients tolerant to wheat (TW) was made by means of an oral food challenge test or recent history of immediate allergic reactions or tolerance after ingestion of wheat. Twelve replicate evaluations were performed in 9 patients over more than a 6-month interval. Thirty two patients on 43 occasions were diagnosed with WA and 27 were confirmed to be TW. One patient had both diagnoses 18 months apart. Peripheral blood was incubated with fractionated wheat extracts, purified native omega-5 gliadin (nOG5) and recombinant omega-5 gliadin (rOG5). Expression of CD203c on basophils was then analyzed by flow cytometry using a commercial kit.",
"All wheat proteins induced concentration-dependent enhancement of CD203c expression in WA, but did not in TW. The analysis of receiver operating characteristics (ROC) showed that nOG5-induced CD203c(high)% values provided the best power for discriminating between WA and TW, with a sensitivity of 85.0% and specificity of 77.0% at the cut-off level of 14.4%. AUC for CD203c with nOG5 were significantly higher than that for conventional CAP-FEIA, 0.89 and 0.73, respectively (p < 0.01)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Allergens",
"Antigens, Plant",
"Area Under Curve",
"Basophils",
"Child, Preschool",
"Female",
"Gliadin",
"Humans",
"Immunoglobulin E",
"Male",
"Phosphoric Diester Hydrolases",
"Plant Extracts",
"Plant Proteins",
"Predictive Value of Tests",
"Pyrophosphatases",
"ROC Curve",
"Recombinant Proteins",
"Sensitivity and Specificity",
"Wheat Hypersensitivity"
]
} | Measurement of nOG-induced enhancement of CD203c on basophils is useful for the diagnosis of immediate wheat allergy in children. | yes | Antigen-induced expression of CD203c on basophils predicts IgE-mediated wheat allergy. |
24,359,286 | Does neuropilin-2 gene expression correlate with malignant progression in cutaneous melanoma? | {
"contexts": [
"It is currently not possible to predict the metastatic potential of early-stage melanoma lesions by histological examination alone; however, a significant number of thin melanomas will progress over time to advanced disease. Molecular biomarkers that could identify patients with melanoma at high risk at the time of original diagnosis would contribute significantly to improved patient outcomes and increased survival. Neuropilin-2 (NRP2), a cell surface receptor involved in tumour-associated angiogenesis and lymphangiogenesis, has recently been shown to be expressed in melanoma.",
"To evaluate the potential value of NRP2 gene transcript levels as biomarkers for malignant melanoma progression.",
"We measured NRP2 gene expression in a panel of formalin-fixed paraffin-embedded tissue specimens consisting of naevi, primary melanomas and metastatic melanomas using quantitative reverse transcriptase-polymerase chain reaction technique.",
"NRP2 levels are clearly segregated among the groups of naevi, primary and metastatic melanoma samples with a statistical trend towards increasing NRP2 gene expression correlating with disease progression. Logistic regression analysis reveals that the probability of malignant progression increases with elevated levels of NRP2 (odds ratio of 2·60 with confidence interval 1·29-5·21). Within the group of primary melanomas, there is a positive correlation (r = 0·823) between NRP2 expression and Breslow depth. This correlation was validated in an independent sample set of patients with melanoma."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Analysis of Variance",
"Biomarkers, Tumor",
"Disease Progression",
"Female",
"Gene Expression",
"Genetic Markers",
"Humans",
"Male",
"Melanoma",
"Neuropilin-2",
"Skin Neoplasms"
]
} | This preliminary study strongly supports the significance of NRP2 as a useful biomarker for malignant progression of melanoma, which may be useful for early identification of patients with melanoma at high risk. | yes | Neuropilin-2 gene expression correlates with malignant progression in cutaneous melanoma. |
17,299,061 | Are serum anti-mullerian hormone concentrations altered by acute administration of follicle stimulating hormone in polycystic ovary syndrome and normal women? | {
"contexts": [
"In the human ovary, expression of anti-Mullerian hormone (AMH) is detected primarily in granulosa cells of preantral and small antral follicles. This finding is consistent with the tight correlation between circulating AMH levels and the number of small antral follicles (2-5 mm) in normal and polycystic ovary syndrome (PCOS) women. In addition, the greater follicle count in PCOS is mirrored by significantly higher serum AMH levels compared with those of normal women. Despite the utility of AMH measurements in evaluating ovarian physiology and function, the regulation of AMH remains poorly understood.",
"The objective was to determine whether gonadotropins acutely regulate serum AMH in women with PCOS and normal women.",
"We conducted a prospective study to compare ovarian responses to FSH in two groups of women.",
"The study was conducted in a General Clinical Research Center in a tertiary academic medical center.",
"Women with PCOS (age, 18-35 yr; n = 16) and normal ovulatory controls (age, 18-35 yr; n = 11) were recruited for study.",
"Serum samples were measured over a 24-h period after an iv injection of recombinant human FSH (150 IU).",
"Serum AMH responses after FSH administration were measured.",
"Basal serum AMH levels were markedly increased in women with PCOS compared with levels observed in normal women. After FSH injection, PCOS women failed to demonstrate changes in circulating AMH over 24 h. A similar lack of alteration in serum AMH was observed in normal women."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Anti-Mullerian Hormone",
"Estradiol",
"Female",
"Follicle Stimulating Hormone",
"Glycoproteins",
"Granulosa Cells",
"Humans",
"Luteinizing Hormone",
"Polycystic Ovary Syndrome",
"Prospective Studies",
"Recombinant Proteins",
"Testicular Hormones"
]
} | These findings suggest that in PCOS and normal women, acute exposure to FSH does not appear to exert an effect on AMH production. | no | Serum anti-mullerian hormone concentrations are altered by acute administration of follicle stimulating hormone in polycystic ovary syndrome and normal women. |
23,843,045 | Is overanticoagulation associated with renal function decline? | {
"contexts": [
"Recent studies suggest that overanticoagulation impairs renal function in patients on warfarin therapy, due to renal tubular obstruction from glomerular hemorrhage.",
"Data from the Rotterdam Study (The Netherlands), a prospective population-based cohort study of patients 55 years and older, were used for this study. Information on vitamin K antagonist (VKA) therapy was obtained from the regional anticoagulation clinic, where prothrombin times were monitored every 1-6 weeks depending on target level and stability of the international normalized ratio (INR). Linear regression was performed to study the association between the cumulative number of instances of overanticoagulation (defined as a measurement of an INR >6.0) and the change in renal function between baseline and third examination round based on estimated glomerular filtration rate (CKD-EPI equation). Age, sex, baseline renal function, baseline and incident heart failure, and indication for VKA therapy were included as potential confounders.",
"Information was available for analysis on 2,802 study participants in whom overanticoagulation was significantly associated with a decline in renal function, after adjustment for confounding by age, sex, heart failure, baseline glomerular filtration rate and indication for VKA therapy (-0.180 ml/min per 1.73 m(2) per year per event for INR >6.0, p = 0.030)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Anticoagulants",
"Cohort Studies",
"Drug Overdose",
"Female",
"Glomerular Filtration Rate",
"Humans",
"International Normalized Ratio",
"Kidney",
"Male",
"Middle Aged",
"Prospective Studies",
"Vitamin K",
"Warfarin"
]
} | Overanticoagulation (INR >6.0) is associated with a decline in renal function. Further studies are needed to evaluate the causal role of different degrees of overanticoagulation, including transient effects, in high-risk groups, and the association with the new oral anticoagulants. | yes | Overanticoagulation is associated with renal function decline. |
25,641,387 | Do neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction? | {
"contexts": [
"OPA1 mutations are responsible for more than half of autosomal dominant optic atrophy (ADOA), a blinding disease affecting the retinal ganglion neurons. In most patients the clinical presentation is restricted to the optic nerve degeneration, albeit in 20% of them, additional neuro-sensorial symptoms might be associated to the loss of vision, as frequently encountered in mitochondrial diseases. This study describes clinical and neuroradiological features of OPA1 patients.",
"Twenty two patients from 17 families with decreased visual acuity related to optic atrophy and carrying an OPA1 mutation were enrolled. Patients underwent neuro-ophthalmological examinations. Brain magnetic resonance imaging (T1, T2 and flair sequences) was performed on a 1.5-Tesla MR Unit. Twenty patients underwent 2-D proton spectroscopic imaging.",
"Brain imaging disclosed abnormalities in 12 patients. Cerebellar atrophy mainly involving the vermis was observed in almost a quarter of the patients; other abnormalities included unspecific white matter hypersignal, hemispheric cortical atrophy, and lactate peak. Neurological examination disclosed one patient with a transient right hand motor deficit and ENT examination revealed hearing impairment in 6 patients. Patients with abnormal MRI were characterized by: (i) an older age (ii) more severe visual impairment with chronic visual acuity deterioration, and (iii) more frequent associated deafness."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Atrophy",
"Brain",
"Child",
"Child, Preschool",
"Female",
"GTP Phosphohydrolases",
"Hearing Loss",
"Humans",
"Magnetic Resonance Imaging",
"Male",
"Mitochondrial Diseases",
"Motor Activity",
"Neurologic Examination",
"Optic Atrophy, Autosomal Dominant",
"Young Adult"
]
} | Our results demonstrate that brain imaging abnormalities are common in OPA1 patients, even in those with normal neurological examination. Lactate peak, cerebellar and cortical atrophies are consistent with the mitochondrial dysfunction related to OPA1 mutations and might result from widespread neuronal degeneration. | yes | Neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction. |
24,654,984 | Does vEGF-C induce lymphangiogenesis and angiogenesis in the rat mesentery culture model? | {
"contexts": [
"Lymphatic and blood microvascular systems are critical for tissue function. Insights into the coordination of both systems can be gained by investigating the relationships between lymphangiogenesis and angiogenesis. Recently, our laboratory established the rat mesentery culture model as a novel tool to investigate multicellular interactions during angiogenesis in an intact microvascular network scenario. The objective of this study was to determine whether the rat mesentery culture model can be used to study lymphangiogenesis.",
"Mesenteric tissue windows were harvested from adult male Wistar rats and cultured for three or five days in either serum-free MEM or MEM supplemented with VEGF-C. Tissues were immunolabeled for PECAM and LYVE-1 to identify blood and lymphatic endothelial cells, respectively. Tissues selected randomly from those containing vascular networks were quantified for angiogenesis and lymphangiogenesis.",
"VEGF-C treatment resulted in an increase in the density of blood vessel sprouting compared to controls by day 3. By day 5, lymphatic sprouting was increased compared to controls."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Endothelial Cells",
"Lymphangiogenesis",
"Male",
"Mesentery",
"Models, Biological",
"Neovascularization, Physiologic",
"Rats",
"Rats, Wistar",
"Receptors, Cell Surface",
"Splanchnic Circulation",
"Vascular Endothelial Growth Factor C"
]
} | These results are consistent with in vivo findings that lymphangiogenesis lags angiogenesis after chronic stimulation and establish a tool for investigating the interrelationships between lymphangiogenesis and angiogenesis in a multisystem microvascular environment. | yes | vEGF-C induces lymphangiogenesis and angiogenesis in the rat mesentery culture model. |
22,740,494 | Is frame shift mutation of LHX1 associated with Mayer-Rokitansky-Kuster-Hauser ( MRKH ) syndrome? | {
"contexts": [
"The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women who usually have normal ovaries and a 46, XX karyotype. MRKH can occur as an isolated form (type I) or in combination with various malformations as a syndromic or a type II MRKH. To date, in most of the cases the underlying etiology remains unclear. Recently, in approximately 6% of MRKH patients, deletions of chromosomal region 17q12 have been identified. The LHX1 gene, which is located in the deletion interval, has been suggested to be a strong candidate, because targeting inactivation of Lhx1 causes a complex phenotype including aplasia of the Müllerian ducts.",
"By sequence analysis of LHX1 in a large cohort of MRKH patients, we detected a heterozygous frame shift mutation resulting in a premature stop codon. Previously, we have reported a heterozygous missense mutation of LHX1 in another MRKH patient."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"46, XX Disorders of Sex Development",
"Abnormalities, Multiple",
"Codon, Terminator",
"Cohort Studies",
"Congenital Abnormalities",
"Female",
"Frameshift Mutation",
"Gene Deletion",
"Heterozygote",
"Humans",
"Karyotyping",
"Kidney",
"LIM-Homeodomain Proteins",
"Mullerian Ducts",
"Mutation, Missense",
"Phenotype",
"Somites",
"Spine",
"Transcription Factors",
"Uterus",
"Vagina"
]
} | We conclude that heterozygous mutations of LHX1 might be one cause of the MRKH syndrome in a subgroup of patients. | yes | Frame shift mutation of LHX1 is associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. |
17,403,744 | Does disaster medicine training survey result for dental health care providers in Illinois? | {
"contexts": [
"Ongoing vigilance by governments, public health agencies and health care professionals monitoring potential epidemic and pandemic outbreaks, terrorist threats and ever-present natural disasters requires the continuous evolution of comprehensive disaster response plans and teams, which include the integration of oral health care professionals.",
"The authors conducted a study in which oral health care professionals assessed their training in the American Medical Association's (AMA's) National Disaster Life Support (NDLS) courses. At the conclusion of each instructional session, the authors asked participants to complete an anonymous course evaluation form to report their impressions of the training activity. The authors included in the analysis those evaluations associated with sessions attended almost exclusively by dentists and hygienists.",
"The authors derived descriptive statistics from the selected course evaluations. Overall, oral health care professionals believed that the Core Disaster Life Support (CDLS) and Basic Disaster Life Support (BDLS) courses were of great educational value, rating course impact at 9.50 and 9.29, respectively, on a scale from 1 to 10."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"American Medical Association",
"Dentists",
"Disaster Planning",
"Humans",
"Illinois",
"Professional Role",
"Program Evaluation",
"United States"
]
} | Statistical evaluation instruments reveal satisfaction with the all-hazards awareness training received through the AMA's NDLS disaster medicine training curriculum. Licensed oral health care professionals in Illinois accepted the utility and merits of, and benefited from, the four-hour CDLS and eight-hour BDLS certification programs. Practice Implications. Dental professionals in Illinois require minimal additional training for dental emergency responder duties. The AMA's NDLS curriculum provides effective preparation for dental professionals. | yes | Disaster medicine training survey results for dental health care providers in Illinois. |
11,842,309 | Is cell-surface expression of CD25 , CD26 , and CD30 by allergen-specific T cells intrinsically different in cow 's milk allergy? | {
"contexts": [
"The release of T(H)2 cytokines by food-specific T cells is thought to be important in the etiology of food allergy. It has been suggested that the activation state of food-specific T cells also plays a significant role, but this has not yet been studied at the single-cell level.",
"Differences in the expression of cell-surface markers by cow's milk protein (CMP)-specific T cells between infants with and without cow's milk allergy (CMA) were evaluated at the clonal level. In addition, expression after the spontaneous development of tolerance of cow's milk in infants with CMA was analyzed.",
"We established CMP-specific T-cell clones (TCCs) from blood of infants with CMA and atopic dermatitis, from atopic controls with atopic dermatitis but without CMA, and from nonatopic controls. In addition, we established TCCs from infants with CMA after they had spontaneously developed tolerance to cow's milk. Expression levels of CD25, CD26, and CD30 by each TCC were analyzed by use of flow cytometry.",
"Cow's milk protein-specific T cells from infants with CMA expressed much higher levels of CD25 and CD30 than CMP-specific T cells from infants without CMA. Expression of CD26 was much lower than in normal controls. After development of tolerance for cow's milk, expression of CD25 and CD30 was decreased, whereas the expression of CD26 was increased to normal levels."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Allergens",
"Animals",
"Cattle",
"Cytokines",
"Dermatitis, Atopic",
"Dipeptidyl Peptidase 4",
"Humans",
"Infant",
"Ki-1 Antigen",
"Lymphocyte Activation",
"Milk Hypersensitivity",
"Milk Proteins",
"Receptors, Interleukin-2",
"T-Lymphocytes",
"Th1 Cells",
"Th2 Cells"
]
} | Antigen-specific T cells from patients with food allergy display an increased expression of cell-surface markers of activation compared with cells of patients without food allergy. This suggests an intrinsically stronger food-specific T-cell response in food-allergic patients, and points to the key role of food-specific T cells in the pathogenesis of food allergy. | yes | Cell-surface expression of CD25 , CD26 , and CD30 by allergen-specific T cells is intrinsically different in cow 's milk allergy. |
20,512,036 | Is acute renal failure an `` acute renal success '' -- a clinical study on the renal oxygen supply/demand relationship in acute kidney injury? | {
"contexts": [
"Acute kidney injury occurs frequently after cardiac or major vascular surgery and is believed to be predominantly a consequence of impaired renal oxygenation. However, in patients with acute kidney injury, data on renal oxygen consumption (RVO2), renal blood flow, glomerular filtration, and renal oxygenation, i.e., the renal oxygen supply/demand relationship, are lacking and current views on renal oxygenation in the clinical situation of acute kidney injury are presumptive and largely based on experimental studies.",
"Prospective, two-group comparative study.",
"Cardiothoracic intensive care unit of a tertiary center.",
"Postcardiac surgery patients with (n = 12) and without (n = 37) acute kidney injury were compared with respect to renal blood flow, glomerular filtration, RVO2, and renal oxygenation.",
"None",
"Data on systemic hemodynamics (pulmonary artery catheter) and renal variables were obtained during two 30-min periods. Renal blood flow was measured using two independent techniques: the renal vein thermodilution technique and the infusion clearance of paraaminohippuric acid, corrected for renal extraction of paraaminohippuric acid. The filtration fraction was measured by the renal extraction of Cr-EDTA and the renal sodium resorption was measured as the difference between filtered and excreted sodium. Renal oxygenation was estimated from the renal oxygen extraction. Cardiac index and mean arterial pressure did not differ between the two groups. In the acute kidney injury group, glomerular filtration (-57%), renal blood flow (-40%), filtration fraction (-26%), and sodium resorption (-59%) were lower, renal vascular resistance (52%) and renal oxygen extraction (68%) were higher, whereas there was no difference in renal oxygen consumption between groups. Renal oxygen consumption for one unit of reabsorbed sodium was 2.4 times higher in acute kidney injury."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Acute Kidney Injury",
"Aged",
"Cardiac Surgical Procedures",
"Cohort Studies",
"Female",
"Follow-Up Studies",
"Glomerular Filtration Rate",
"Hemodynamics",
"Humans",
"Intensive Care Units",
"Linear Models",
"Male",
"Middle Aged",
"Monitoring, Physiologic",
"Oxygen",
"Oxygen Consumption",
"Prospective Studies",
"Renal Circulation",
"Risk Assessment",
"Vascular Resistance"
]
} | Renal oxygenation is severely impaired in acute kidney injury after cardiac surgery, despite the decrease in glomerular filtration and tubular workload. This was caused by a combination of renal vasoconstriction and tubular sodium resorption at a high oxygen demand. | no | Acute renal failure is an `` acute renal success '' -- a clinical study on the renal oxygen supply/demand relationship in acute kidney injury. |
26,228,674 | Is medical nutrition therapy the essential cornerstone for effective treatment of `` refractory '' severe hypertriglyceridemia regardless of pharmaceutical treatment : Evidence from a Lipid Management Program? | {
"contexts": [
"Patients with refractory severe hypertriglyceridemia are at risk of pancreatitis and cardiovascular disease. The role of individualized nutrition therapy in these patients independent of pharmaceutical treatment has not been documented.",
"To document the effect of nutrition intervention on severe hypertriglyceridemia regardless of medication status or prior nutrition counseling.",
"Outcomes of new patients with triglycerides ≥ 500 mg/dL presenting to a Lipid Management Program over a 6-year period were tracked. Patients received comprehensive laboratory assessment, nutrition assessment, and initiation of an individualized diet intervention before seeing the lipidologist. Clinical and behavioral outcomes were recorded.",
"In all, 168 patients (117 men; mean age, 49.03 ± 11.22 years; body mass index, 32.61 ± 5.85 kg/m(2); 110 (65.5%) on lipid-lowering medications) returned for assessment of nutrition intervention. Triglycerides were reduced from median (interquartile range) 961.5 (611.5-1785.3) to 493.0 (337-736.3) mg/dL (P < .0001 for log transformation of triglycerides). There was no difference in median percentage reduction in triglycerides after nutrition intervention between those not on lipid-lowering medication, on a fibric acid derivative, on other lipid-lowering medication, or on a combination of lipid-lowering medications (P = .376) in a median (interquartile range) of 5 (3-7) weeks. Effect was independent of prior nutrition counseling (P = .260). Reported percentage fat in the diet at second visit correlated with log-transformed triglycerides achieved, independent of initial triglycerides level (r = 0.290; P = .001)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Body Mass Index",
"Cardiovascular Diseases",
"Cholesterol",
"Cholesterol, HDL",
"Female",
"Fibric Acids",
"Humans",
"Hypertriglyceridemia",
"Hypolipidemic Agents",
"Male",
"Middle Aged",
"Nutrition Therapy",
"Pancreatitis",
"Risk Factors",
"Treatment Outcome",
"Triglycerides"
]
} | Individualized nutrition therapy results in changes in eating behavior and reductions in triglyceride levels in patients with refractory severe hypertriglyceridemia independent of lipid-lowering medication(s) and prior nutrition counseling. | yes | Medical nutrition therapy is the essential cornerstone for effective treatment of `` refractory '' severe hypertriglyceridemia regardless of pharmaceutical treatment : Evidence from a Lipid Management Program. |
15,501,733 | Is [ A986S polymorphism of calcium-sensing receptor gene related to bone mineral density or bone size in premenopausal Chinese women ]? | {
"contexts": [
"To investigate the association of a calcium-sensing receptor (CaSR) gene missense polymorphism, 986Ala/Ser (A986S), with bone mineral density (BMD) and bone size in healthy Chinese premenopausal women.",
"A total of 285 healthy Chinese premenopausal women (20.0 to 41.9 years of age) of Han nationality in the urban area of Shanghai were recruited for this study. The BMD and bone size of the spine and hip were measured by dual-energy X-ray absorptiometry. All the subjects were genotyped at the CaSR A986S site in exon 7 with polymerase chain reaction followed by restriction enzyme BsaHI digestion. The presence of the restriction fragment site was represented by alanine (A), while its absence by serine (S), rendering the genotypes AA, AS, and SS.",
"The genotype AS was rare and SS absent in these Chinese women, and no significant differences in the BMD or bone size of either the spine or hip were found between the two genotypes."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Anthropometry",
"Asian Continental Ancestry Group",
"Bone Density",
"Female",
"Hip",
"Humans",
"Middle Aged",
"Osteoporosis, Postmenopausal",
"Polymorphism, Genetic",
"Premenopause",
"Receptors, Calcium-Sensing",
"Spine"
]
} | Given the important role of the CaSR in calcium metabolism, further studies with useful genetic markers may have better chances to define the association of the CaSR gene with bone phenotype variations. | no | The A986S polymorphism of calcium-sensing receptor gene is related to bone mineral density or bone size in premenopausal Chinese women. |
16,115,856 | Are abdominal obesity and smoking important determinants of C-reactive protein in renal transplant recipients? | {
"contexts": [
"C-reactive protein (CRP) is a predictor of coronary heart disease, total mortality and chronic allograft nephropathy in renal transplant recipients. The determinants of CRP have been investigated in the general population, but not in renal transplant recipients. CRP might reflect metabolic aberrations in association with central obesity and systemic atherosclerosis. However, it may also reflect a low-grade immune-mediated response to the graft. In this study we investigated the factors associated with CRP in a renal transplant population.",
"Between August 2001 and July 2003, renal transplant recipients with a functioning graft for more than 1 year (n = 847) were eligible for investigation at their next visit to the outpatient clinic. A total of 606 patients (55% male, aged 51+/-12 years) participated at a median (interquartile range) time of 6.0 (2.6-11.4) years post-transplant.",
"Median CRP concentration was 2.0 (0.80-4.8) mg/l and mean 24 h creatinine clearance was 62+/-22 ml/min. CRP was significantly associated with body mass index, waist circumference and waist-to-hip ratio (P-value < 0.0001). None of the transplant characteristics except creatinine clearance was associated with CRP. In multiple regression analysis, waist circumference, log sICAM-1 concentration, gender, creatinine clearance and current smoking were independently associated with CRP."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Biomarkers",
"Body Mass Index",
"C-Reactive Protein",
"Cardiovascular Diseases",
"Chronic Disease",
"Creatinine",
"Female",
"Follow-Up Studies",
"Graft Rejection",
"Humans",
"Immunosuppressive Agents",
"Kidney Transplantation",
"Male",
"Middle Aged",
"Obesity",
"Prognosis",
"Retrospective Studies",
"Risk Factors",
"Smoking"
]
} | In renal transplant recipients waist circumference and smoking are the two most important modifiable independent determinants of CRP. Furthermore, CRP is independently associated with the endothelial function parameter sICAM-1 and, in univariate analyses, associated with multiple cardiovascular risk factors. CRP is not associated with any of the transplant-related factors, except for renal transplant function. | yes | Abdominal obesity and smoking are important determinants of C-reactive protein in renal transplant recipients. |
15,950,849 | Does the number of injections influence absorption of bupivacaine after cervical plexus block for carotid endarterectomy? | {
"contexts": [
"To investigate the efficacy and kinetics of bupivacaine when used for deep cervical plexus block (CPB), using either a single-injection or multiple-injections technique.",
"Prospective, randomized, double-blind study.",
"Operating room of a university hospital.",
"Twenty-four adult patients (16 men, 8 women) scheduled for carotid endarterectomy.",
"Patients were randomly assigned to receive CPB either by a single injection or after 3 injections. Patients in the multiple-injections group received a total dose of 15 mL of 0.5% bupivacaine (5 mL each deposited at C2, C3, and C4 over 2 minutes). Patients in the single-injection group received a single 15-mL injection of 0.5% bupivacaine. After the deep CPB, a superficial CPB was performed with 20 mL of 0.5% bupivacaine in all patients.",
"An anesthesiologist and a surgeon graded the success of the block. Arterial plasma concentrations of bupivacaine were measured using liquid chromatography-mass spectroscopy.",
"No significant differences were seen between the 2 groups with respect to the mean peak concentration of bupivacaine (single injection 2314 +/- 1385 ng/mL vs multiple injections 2255 +/- 1105 ng/mL) or time to reach the maximal concentration (time to maximum concentration [single injection 12.1 +/- 7.2 minutes vs multiple injections 12.5 +/- 3.9 minutes]). Furthermore, there were no significant differences in mean block scores between the single-injection and the multiple-injections groups, evaluated either by the anesthesiologists or the surgeon."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Absorption",
"Aged",
"Bupivacaine",
"Cervical Plexus",
"Double-Blind Method",
"Endarterectomy, Carotid",
"Female",
"Humans",
"Injections",
"Male",
"Middle Aged",
"Nerve Block",
"Prospective Studies"
]
} | The results of this study showed that the absorption of bupivacaine is independent of the number of injections after CPB, and that anesthesia for carotid endarterectomy may be accomplished successfully using either technique. | no | The number of injections influences absorption of bupivacaine after cervical plexus block for carotid endarterectomy. |
26,886,562 | Is a functional variant in the coding region of CAMTA2 associated with left ventricular hypertrophy by affecting the activation of Nkx2.5-dependent transcription? | {
"contexts": [
"The calmodulin-binding transcription activator 2 (CAMTA2) promotes transcription of genes involved in cardiac hypertrophy through its interaction with Nkx2.5 and is an indispensable transcription coactivator for cardiac hypertrophy. We hypothesized that variants in the coding region of CAMTA2 would affect its function and confer a risk of cardiac hypertrophy.",
"The effects of the variant rs238234 on the activity of the atrial natriuretic factor promoter and on the cardiomyocytes hypertrophy were assessed in the H9C2 cell line and primary neonatal rat cardiomyocytes, respectively. Furthermore, the association of this variant with left ventricular hypertrophy (LVH) was tested in hypertensive patients with and without hypertrophy (N = 325 and 697), and this analysis was replicated in an independent population of 987 hypertensive patients without hypertrophy and 463 hypertensive patients with hypertrophy.",
"We found that the G allele of rs238234 activated the atrial natriuretic factor promoter more strongly than the C allele. The cell size of cardiomyocytes was larger in the presence of the Ad-CAMTA2 G allele, and the G allele was associated with significantly increased susceptibility to LVH in hypertensive [odds ratio (OR), 1.29; P = 0.009]. In the discovery cohort, after adjusting for age and sex, the GG genotype was significantly associated with increased LVH risk (OR, 1.75; P = 0.015). There was little attenuation of the ORs (1.62; P < 0.05) when adjusting for BMI, heart rate, blood pressure, smoking, and drinking and further adjusting all covariates including lipid levels and other major risk factors. However, the GC genotype did not show any association with LVH using three regressive models. Replication in the second study yielded similar results."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Alleles",
"Asian Continental Ancestry Group",
"Calcium-Binding Proteins",
"Calmodulin-Binding Proteins",
"China",
"Cross-Sectional Studies",
"Female",
"Gene Expression Regulation",
"Genetic Predisposition to Disease",
"Homeobox Protein Nkx-2.5",
"Humans",
"Hypertrophy, Left Ventricular",
"Male",
"Middle Aged",
"Promoter Regions, Genetic",
"Surveys and Questionnaires",
"Trans-Activators",
"Transcriptional Activation"
]
} | Our results provide evidence that the rs238234 GG genotype in the coding region of CAMTA2 may increase the risk of LVH by affecting the activation of Nkx2.5-dependent transcription. | yes | A functional variant in the coding region of CAMTA2 is associated with left ventricular hypertrophy by affecting the activation of Nkx2.5-dependent transcription. |
12,464,957 | Is tH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa a feature of asthma and eosinophilic bronchitis? | {
"contexts": [
"Asthma is characterized by variable airflow obstruction and airway hyperresponsiveness in association with airway inflammation under the influence of T(H)2 cytokines. Eosinophilic bronchitis has similar immunopathology to asthma but without disordered airway physiology. Whether eosinophilic bronchitis is associated with increased expression of T(H)2 cytokines is unknown.",
"We sought to assess the expression of T(H)2 cytokines in eosinophilic bronchitis.",
"Expression of activation markers and chemokine receptors from blood and bronchoalveolar lavage (BAL) fluid T cells and the T(H)2 cytokine expression from these T cells and bronchial mucosa biopsy specimens were assessed from subjects with eosinophilic bronchitis, subjects with asthma, and healthy control subjects.",
"The proportion of resting (stimulated) CD4 BAL fluid T cells expressing intracellular IL-4 was significantly higher in the subjects with eosinophilic bronchitis 7.2% (11.4%) and subjects with asthma 5.3% (5.5%) than in healthy control subjects 2.8% (3.9%) (P =.03). The number of IL-4(+) (P <.001) and IL-5(+) (P =.003) cells per square millimeter of bronchial submucosa was significantly higher in the disease groups than in the healthy control subjects. Expression of intracellular IFN-gamma was significantly higher in stimulated blood CD8 T cells from subjects with eosinophilic bronchitis (24%) and asthma (17%) than in the healthy control subjects (5%; P =.003). There were no between-group differences in expression of IFN-gamma in the BAL fluid T cells or in the bronchial submucosa and no differences in expression of activation markers or chemokine receptors."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Asthma",
"Bronchi",
"Bronchitis",
"Bronchoalveolar Lavage Fluid",
"Cytokines",
"Eosinophilia",
"Female",
"Humans",
"Interferon-gamma",
"Interleukin-4",
"Interleukin-5",
"Male",
"Middle Aged",
"T-Lymphocytes",
"Th2 Cells"
]
} | These findings support the concept of asthma as a disease associated with activation of T(H)2 lymphocytes in the airway and provide evidence that these cytokines play a role in the development of airway inflammation in eosinophilic bronchitis but suggest that the release of T(H)2 cytokines is not sufficient for the elaboration of disordered airway physiology in asthma. | yes | TH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis. |
25,299,859 | Does cigarette smoking among tuberculosis patients increase risk of transmission to child contacts? | {
"contexts": [
"Observational cohort study in Lima, Peru.",
"To determine the association between exposure to a smoking tuberculosis (TB) case and latent tuberculous infection (LTBI).",
"Between September 2009 and August 2012, we identified 2132 patients with drug-susceptible TB and their 2054 child household contacts. Data were collected on active and secondhand smoking status and other risk factors for infection specific to the index case, the household and the exposed contacts. Contacts underwent a tuberculin skin test (TST) to determine their tuberculous infection status at baseline, 6-month and 12-month follow-up. We estimated the association between exposure to a smoking index case and LTBI using a modified Poisson regression model.",
"The 21 children (age ⩿15 years) exposed to smoking index TB patients were more likely to be TST-positive at baseline (RR 2.64, 95%CI 1.78-3.91), by 6 months (RR 1.91, 95%CI 1.40-2.60) and by 12 months (RR 1.48, 95%CI 1.07-2.06), than those who were not exposed. TST positivity among children at these time points did not vary with secondhand smoke exposure."
],
"labels": [
"METHODS",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Child",
"Child, Preschool",
"Cohort Studies",
"Contact Tracing",
"Female",
"Follow-Up Studies",
"Humans",
"Infant",
"Latent Tuberculosis",
"Male",
"Middle Aged",
"Peru",
"Poisson Distribution",
"Risk Factors",
"Smoking",
"Time Factors",
"Tobacco Smoke Pollution",
"Tuberculin Test",
"Tuberculosis",
"Young Adult"
]
} | TB patients who smoke may be more likely to transmit infection to their contacts. Interventions designed to reduce smoking among TB patients may minimise further spread of the disease. | yes | Cigarette smoking among tuberculosis patients increases the risk of transmission to child contacts. |
25,311,704 | Does consumption of low-moderate level arsenic contaminated water increase spontaneous pregnancy loss : a case control study? | {
"contexts": [
"Previous work suggests an increased risk for spontaneous pregnancy loss linked to high levels of inorganic arsenic (iAs) in drinking water sources (>10 μg/L). However, there has been little focus to date on the impact of low-moderate levels of iAs in drinking water (<10 μg/L). To address this data gap we conducted a hospital-based case-control study in Timis County, Romania.",
"We recruited women with incident spontaneous pregnancy loss of 5-20 weeks completed gestation as cases (n = 150), and women with ongoing pregnancies matched by gestational age (±1 week) as controls (n = 150). Participants completed a physician-administered questionnaire and we collected water samples from residential drinking sources. We reconstructed residential drinking water exposure histories using questionnaire data weighted by iAs determined using hydride generation-atomic absorption spectrometry (HG-AAS). Logistic regression models were used to generate odds ratios (OR) and 95% confidence intervals (CI) for associations between iAs exposure and loss, conditioned on gestational age and adjusted for maternal age, cigarette smoking, education and prenatal vitamin use. We explored potential interactions in a second set of models.",
"Drinking water arsenic concentrations ranged from 0.0 to 175.1 μg/L, with median 0.4 μg/L and 90th%tile 9.4 μg/L. There were no statistically significant associations between loss and average or peak drinking water iAs concentrations (OR 0.98, 95% CI 0.96-1.01), or for daily iAs intake (OR 1.00, 95% CI 0.98-1.02). We detected modest evidence for an interaction between average iAs concentration and cigarette smoking during pregnancy (P = 0.057) and for daily iAs exposure and prenatal vitamin use (P = 0.085)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Abortion, Spontaneous",
"Adolescent",
"Adult",
"Arsenic",
"Case-Control Studies",
"Drinking Water",
"Female",
"Humans",
"Logistic Models",
"Maternal Exposure",
"Odds Ratio",
"Pilot Projects",
"Pregnancy",
"Romania",
"Spectrophotometry, Atomic",
"Water Pollutants, Chemical",
"Young Adult"
]
} | These results suggest no increased risk for spontaneous pregnancy loss in association with low to moderate level drinking water iAs exposure. Though imprecise, our data also raise the possibility for increased risk among cigarette smokers. Given the low exposures overall, these data should reassure pregnant women and policy makers with regard to the potential effect of drinking water iAs on early pregnancy, though a larger more definitive study to investigate the potential risk increase in conjunction with cigarette smoking is merited. | no | Consumption of low-moderate level arsenic contaminated water increases spontaneous pregnancy loss: a case control study. |
11,669,153 | Does removal of hyaline articular cartilage reduce lymphocyte infiltration and activation in rheumatoid synovial membrane? | {
"contexts": [
"To analyze the effect of removal of hyaline articular cartilage on synovial membrane pathology in chronic arthritis.",
"Synovial membrane samples were obtained from patients with rheumatoid arthritis or ankylosing spondylitis in association with total hip arthroplasty, either primary or revision surgery. Synovial membrane histopathology was assessed by immunochemical staining and morphometry.",
"CD68 positive macrophages were common in revision synovial membranes. In contrast, T lymphocytes were much more common in primary rheumatoid synovial membranes (p < 0.001). Many T lymphocytes in primary synovial membrane were HLA-D/DR positive (p < 0.001) and interleukin 2 receptor (IL-2R) positive (p < 0.001) and contained interferon-gamma(IFN-gamma; p < 0.001) and tumor necrosis factor-beta (TNF-beta; p < 0.001). In contrast, revision synovial membranes from patients with chronic arthritis contained only a few HLA-D/DR positive T cells and practically no IL-2R, IFN-gamma, or TNF-beta positive activated T lymphocytes."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Antigens, CD",
"Antigens, Differentiation, Myelomonocytic",
"Arthritis, Rheumatoid",
"Arthroplasty, Replacement, Hip",
"Cartilage, Articular",
"Cell Movement",
"Chronic Disease",
"Female",
"HLA-D Antigens",
"Humans",
"Hyalin",
"Macrophages",
"Male",
"Middle Aged",
"Synovial Membrane",
"T-Lymphocytes"
]
} | The components of hyaline articular cartilage may be the source of autoantigen responsible for perpetuation of chronic arthritides. | yes | Removal of hyaline articular cartilage reduces lymphocyte infiltration and activation in rheumatoid synovial membrane. |
23,870,730 | Does caffeine increase the expression of cystatin SN in human submandibular acinar-like HSG cells? | {
"contexts": [
"The study aimed at evaluating in vitro the effect of caffeine on expression of cystatin SN, a potential marker of sensitivity to bitterness in humans.",
"Differentiation of human submandibular gland (HSG) cells was induced by culturing cells on Matrigel. Caffeine cytotoxicity was assessed over 3 days by the Resazurin test. Finally, effects of 5, 50 and 100μM caffeine exposure on cystatin SN expression were explored over 3 days by ELISA.",
"At concentrations relevant to human adult plasma levels (5, 50 and 100μM), caffeine did not affect cell viability whether cells were differentiated or not. Cystatin SN levels were overall higher in differentiated cells and increased with time in both conditions. There was a significant (p<0.001) effect of caffeine on cystatin SN expression specifically in differentiated cells."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Caffeine",
"Cell Culture Techniques",
"Collagen",
"Drug Combinations",
"Enzyme-Linked Immunosorbent Assay",
"Humans",
"Laminin",
"Proteoglycans",
"Salivary Cystatins",
"Submandibular Gland"
]
} | The HSG cell line proved to be a relevant tool to study in vitro the effect of caffeine at concentrations consistent with dietary intake in human subjects. The results suggest that salivary cystatin SN abundance may depend on caffeine intake, with possible consequences on taste sensitivity. | yes | Caffeine increases the expression of cystatin SN in human submandibular acinar-like HSG cells. |
19,489,246 | Does [ Propofol provide ischemic postconditioning on myocardial ischemia-reperfusion injury in rats ]? | {
"contexts": [
"To investigate whether the infusion of propofol during early reperfusion provides ischemic postconditioning (I-postC) on myocardial ischemia-reperfusion injury in rats.",
"Sixty adult rats were randomly divided into 5 groups (n = 12 each): sham operation (group S); normal saline (group C); propofol 1 mg/kg (group P1); propofol 2 mg/kg (group P2); propofol 5 mg/kg (group P3). The left anterior descending coronary artery (LAD) was occluded for 60 min and reperfused for 120 min. Normal saline, propofol 1 mg/kg, 2 mg/kg or 5 mg/kg (propofol diluted to 2.5 ml with normal saline equally) were intravenously infused 3 min before reperfusion until 5 min after reperfusion. The heart were obtained for determination of (1) the size of area at risk and infarct size (Evans Blue and TTC staining); (2) expression of Caspase-3 (immunohistochemistry staining); (3) percentage of apoptotic cardiomyocytes (flow cytometry); (4) levels of phosphorylated Akt (Western blot).",
"Compared with group C [size of area at risk (41.5 +/- 1.0)%, infarct size (45.5 +/- 1.0)%, expression of caspase-3 (5.87 +/- 0.29), percentage of apoptotic cardiomyocytes (26.8 +/- 1.3)%, level of phosphorylated Akt (10.8 +/- 1.9)%], propofol 1 mg/kg and 2 mg/kg significantly reduced the size of area at risk and infarct size [size of area at risk (38.3 +/- 1.0)% and (37.3 +/- 1.2)%; infarct size (33.8 +/- 1.2)% and (30.2 +/- 1.7)%, P < 0.05], inhibited the expression of caspase-3 (1.50 +/- 0.36 and 1.48 +/- 0.30, P < 0.05), decreased the percentage of apoptotic cardiomyocytes [(16.3 +/- 1.2)% and (16.5 +/- 1.0)%, P < 0.05] and promoted the phosphorylation of Akt [(68.7 +/- 4.0)% and (58.3 +/- 2.8)%, P < 0.05]."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Apoptosis",
"Caspase 3",
"Disease Models, Animal",
"Female",
"Male",
"Myocardial Reperfusion Injury",
"Propofol",
"Proto-Oncogene Proteins c-akt",
"Rats",
"Rats, Wistar"
]
} | Propofol 1 mg/kg and 2 mg/kg can provide I-postC to myocardial ischemia-reperfusion injury in rats by activation of Akt pathway. | yes | Propofol provides ischemic postconditioning on myocardial ischemia-reperfusion injury in rats. |
25,962,901 | Is thymic stromal lymphopoietin activation of basophils in patients with allergic asthma IL-3 dependent? | {
"contexts": [
"Thymic stromal lymphopoietin (TSLP) released after antigenic stimulation of allergic asthmatic airways is a key initiator of type 2 inflammation. Basophils are important effectors of allergic inflammation in the airways. Murine basophils have been shown to respond to TSLP independently of IL-3 by increasing functional thymic stromal lymphopoietin receptor (TSLPR) expression.",
"The purpose of this study was to investigate the effect of TSLP stimulation on human basophil function.",
"Ten patients with mild allergic asthma underwent diluent and allergen inhalation challenges. Peripheral blood and sputum samples were collected at baseline and 7 and 24 hours after challenge, and bone marrow samples were collected at baseline and 24 hours after challenge to measure basophil TSLPR expression. In vitro experiments were conducted on purified human basophils to measure the effect of TSLP on degranulation, expression of activation markers and TH2 cytokines, and eotaxin-induced shape change.",
"Allergen inhalation increased basophil numbers in the airways and significantly upregulated the expression of activation markers, TH2 intracellular cytokines, and receptors for TSLP, IL-3, and eotaxin in blood, bone marrow, and sputum basophils. In vitro stimulation with TSLP primed basophil migration to eotaxin and induced rapid and sustained basophil activation mediated directly through TSLPR and indirectly through an IL-3-mediated basophil autocrine loop. Basophils responded to TSLP at a similar magnitude and potency as the well-described basophil-activating stimuli IL-3 and anti-IgE."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Administration, Inhalation",
"Adult",
"Allergens",
"Asthma",
"Basophils",
"Bone Marrow Cells",
"Bronchial Provocation Tests",
"Cell Count",
"Cells, Cultured",
"Cytokines",
"Female",
"Forced Expiratory Volume",
"Humans",
"Male",
"Middle Aged",
"Sputum",
"Young Adult"
]
} | Our findings indicate that basophil activation during early- and late-phase responses to inhaled allergen might be driven at least in part by TSLP. | yes | Thymic stromal lymphopoietin activation of basophils in patients with allergic asthma is IL-3 dependent. |
24,042,086 | Is leptin-induced endothelial dysfunction mediated by sympathetic nervous system activity? | {
"contexts": [
"The adipocyte-derived hormone leptin is elevated in obesity and may contribute to vascular risk associated with obesity. The mechanism(s) by which leptin affects vascular disease is unclear, although leptin has been shown to increase sympathetic activity. The aim of this study was to investigate the effect of leptin treatment on endothelial function and the role of the local sympathetic nervous system in mediating these effects.",
"Recombinant leptin was administered to C57BL6/J mice every other day for 1 week. Mesenteric arteriole myography revealed that leptin treatment caused significant impairment of endothelium-dependent vasorelaxation. Although leptin alone did not raise aortic blood pressure, leptin treatment augmented the blood pressure response to angiotensin II. The effects of leptin on mesenteric arteriolar function and aortic blood pressure response to angiotensin II were neutralized following sympathetic denervation to the mesenteric vasculature. The superoxide scavenger TEMPOL was also effective in preventing the effects of leptin on endothelial dysfunction."
],
"labels": [
"BACKGROUND",
"RESULTS"
],
"meshes": [
"Animals",
"Blood Pressure",
"Endothelium, Vascular",
"Leptin",
"Male",
"Mice",
"Mice, Inbred C57BL",
"Obesity",
"Sympathetic Nervous System"
]
} | Leptin causes endothelial dysfunction and enhances the effects of angiotensin II on blood pressure. These effects of leptin are mediated by sympathetic nervous system activation and superoxide and may contribute to vascular stiffness and hypertension in obesity. | yes | Leptin-induced endothelial dysfunction is mediated by sympathetic nervous system activity. |
24,565,485 | Does immediate allergic hypersensitivity to quinolones associate with neuromuscular blocking agent sensitization? | {
"contexts": [
"We identified a case of quinolone allergic hypersensitivity associated with quaternary ammonium (QA) sensitization, the allergic determinant of neuromuscular blocking agents (NMBAs). Concomitant sensitization to several chemically different drugs is rarely reported and raises the question of a nonfortuitous association.",
"We evaluated a potential association between quinolone immediate allergic hypersensitivity and NMBA sensitization.",
"QA-specific IgE detection was prospectively performed in 26 patients who presented an immediate hypersensitivity reaction to quinolones: 17 with a confirmed allergic hypersensitivity and 9 with allergic hypersensitivity not confirmed. We also included a control population of 88 outpatients without a history of quinolone or NMBA hypersensitivity. Patients with positive QA-specific IgE benefited from a NMBA allergologic workup.",
"The prevalence of positive QA-specific IgE was significantly higher in patients with quinolone allergic hypersensitivity (9/17, 53%) compared with patients with allergic hypersensitivity not confirmed (1/9, 11%) than in controls (3/88, 3.4%). In the quinolone allergic population, ofloxacin elicited inhibition of the 4 positive QA-specific IgE sera tested, in a dose-response manner. Among the 9 patients with positive QA-specific IgE, the QA sensitization (positivity of specific IgE) was confirmed by positive skin tests and/or basophil activation tests to at least 1 NMBA in 5 of the 7 tested patients."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Aged",
"Aged, 80 and over",
"Basophils",
"Female",
"Humans",
"Hypersensitivity, Immediate",
"Immunoglobulin E",
"Male",
"Middle Aged",
"Neuromuscular Blocking Agents",
"Prospective Studies",
"Quinolones"
]
} | We report here the first documentation of a high prevalence of QA sensitization in patients with quinolone allergic hypersensitivity. These results suggest a new way for NMBA sensitization. It thus seems appropriate to investigate NMBA sensitization when quinolone allergic hypersensitivity is diagnosed. | yes | Immediate allergic hypersensitivity to quinolones associates with neuromuscular blocking agent sensitization. |
22,878,592 | Does the high angiogenic activity in very early breast cancer enable reliable imaging with VEGFR2-targeted microbubbles ( BR55 )? | {
"contexts": [
"Tumour xenografts of well-discernible sizes can be examined well by molecular ultrasound. Here, we investigated whether very early breast carcinomas express sufficient levels of VEGFR2 for reliable molecular ultrasound imaging with targeted microbubbles.",
"MCF-7 breast cancer xenografts were orthotopically implanted in nude mice (n = 26). Tumours measuring from 4 mm(3) (2 mm diameter) up to 65 mm(3) (5 mm diameter) were examined with automated 3D molecular ultrasound using clinically translatable VEGFR2-targeted microbubbles (BR55). Additionally, the relative tumour blood volume was assessed with non-targeted microbubbles (BR38). In vivo ultrasound data were validated by quantitative immunohistochemistry.",
"Very small lesions 2 mm in diameter showed the highest binding of VEGFR2-specific microbubbles. In larger tumours significantly less BR55 accumulated (p = 0.023). Nonetheless, binding of VEGFR2-targeted microbubbles was still high enough for imaging. The relative blood volume was comparable at all tumour sizes. Both findings were confirmed by immunohistochemistry. Additionally, a significantly enhanced number of large and mature vessels were detected with increasing tumour size (p < 0.01), explaining the decrease in VEGFR2 expression during tumour growth."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Contrast Media",
"Disease Models, Animal",
"Early Detection of Cancer",
"Female",
"Mammary Glands, Animal",
"Mammary Neoplasms, Experimental",
"Mice",
"Microbubbles",
"Molecular Biology",
"Neovascularization, Pathologic",
"Predictive Value of Tests",
"Random Allocation",
"Sensitivity and Specificity",
"Transplantation, Heterologous",
"Ultrasonography, Doppler, Color",
"Vascular Endothelial Growth Factor Receptor-2"
]
} | 3D molecular ultrasound using BR55 is very well suited to depicting the angiogenic activity in very small breast lesions, suggesting its potential for detecting and characterising these lesions. | yes | The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles ( BR55 ). |
26,413,885 | Does a Single Dose of Intraoperative Antibiotics be Sufficient to Prevent Urinary Tract Infection During Ureteroscopy? | {
"contexts": [
"American Urology Association (AUA) Best Practice Guidelines for ureteroscopic stone treatment recommend antibiotic coverage for <24 hours following the procedure. The purpose of this study was to evaluate if the addition of postoperative antibiotics reduces urinary tract infections (UTIs) following ureteroscopic stone treatment beyond the recommended preoperative dose.",
"A retrospective review was performed of consecutive patients at two institutions, University of British Columbia and Massachusetts General Hospital, Harvard. All patients received a single dose of antibiotics before ureteroscopic stone treatment. A subset of patients was also given postoperative antibiotics. The rate of UTI was compared in patients receiving only preoperative antibiotics (group 1) vs those who received pre- and postoperative antibiotics (group 2).",
"Eighty-one patients underwent ureteroscopy for renal calculi. Mean time to follow up was 42 ± 88 days. Eight (9.9%) patients in total (two from group 1 and six from group 2, p = 0.1457) developed UTIs postoperatively. In group 1, both patients presented with pyelonephritis (n = 2); those patients with infections in group 2 presented with urosepsis (n = 2) and cystitis (n = 2) and two patients had asymptomatic bacteriuria. Risk factors such as preoperative stenting, nephrostomy tubes, and foley catheters neither differed between groups nor did they predispose patients to postoperative infections."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Anti-Bacterial Agents",
"Antibiotic Prophylaxis",
"Female",
"Humans",
"Intraoperative Care",
"Kidney Calculi",
"Logistic Models",
"Male",
"Middle Aged",
"Postoperative Care",
"Postoperative Complications",
"Retrospective Studies",
"Risk Factors",
"Sepsis",
"Stents",
"Ureteroscopy",
"Urinary Tract Infections",
"Young Adult"
]
} | The postoperative UTI rate in this study (9.9%) is consistent with previous reports. Our data suggest that a single preoperative dose of antibiotics is sufficient, and additional postoperative antibiotics do not decrease infection rates after ureteroscopic stone treatment. Risk for selection bias is a potential limitation. | yes | A single dose of intraoperative antibiotics is sufficient to prevent urinary tract infection during ureteroscopy. |
9,856,731 | Does halothane attenuate calcium sensitization in airway smooth muscle by inhibiting G-proteins? | {
"contexts": [
"Halothane directly relaxes airway smooth muscle partly by decreasing the Ca2+ sensitivity. In smooth muscle, receptor stimulation is thought to increase Ca2+ sensitivity via a cascade of heterotrimeric and small monomeric guanine nucleotide-binding proteins (G-proteins). Whether this model is applicable in the airway and where halothane acts in this pathway were investigated.",
"A beta-escin-permeabilized canine tracheal smooth muscle preparation was used. Exoenzyme C3 of Clostridium botulinum, which inactivates Rho monomeric G-proteins, was used to evaluate the involvement of this protein in the Ca2+ sensitization pathway. The effects of halothane on different stimulants acting at different levels of signal transduction were compared: acetylcholine on the muscarinic receptor, aluminum fluoride (AIF4-) on heterotrimeric G-proteins, and guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) on all G-proteins.",
"Exoenzyme C3 equally attenuated acetylcholine- and AIF4--induced Ca2+ sensitization, suggesting that these pathways are both mediated by Rho. Halothane applied before stimulation equally attenuated acetylcholine- and AIF4--induced Ca2+ sensitization. However, when added after Ca2+ sensitization was established, the effect of halothane was greater during Ca2+ sensitization induced by acetylcholine compared with AIF4-, which, along with the previous result, suggests that halothane may interfere with dissociation of heterotrimeric G-proteins. Halothane applied during GTPgammaS-induced Ca2+ sensitization had no significant effect on force, suggesting that halothane has no effect downstream from monomeric G-proteins."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"ADP Ribose Transferases",
"Acetylcholine",
"Aluminum Compounds",
"Anesthetics, Inhalation",
"Animals",
"Botulinum Toxins",
"Calcium",
"Dogs",
"Escin",
"Female",
"Fluorides",
"GTP-Binding Proteins",
"Guanosine 5'-O-(3-Thiotriphosphate)",
"Halothane",
"In Vitro Techniques",
"Isometric Contraction",
"Male",
"Muscle, Smooth",
"Trachea"
]
} | Halothane inhibits increases in Ca2+ sensitivity of canine tracheal smooth muscle primarily by interfering with the activation of heterotrimeric G-proteins, probably by inhibiting their dissociation. | yes | Halothane attenuates calcium sensitization in airway smooth muscle by inhibiting G-proteins. |
26,984,351 | Does reduced Proteolytic Shedding of Receptor Tyrosine Kinases be a Post-Translational Mechanism of Kinase Inhibitor Resistance? | {
"contexts": [
"Kinase inhibitor resistance often involves upregulation of poorly understood \"bypass\" signaling pathways. Here, we show that extracellular proteomic adaptation is one path to bypass signaling and drug resistance. Proteolytic shedding of surface receptors, which can provide negative feedback on signaling activity, is blocked by kinase inhibitor treatment and enhances bypass signaling. In particular, MEK inhibition broadly decreases shedding of multiple receptor tyrosine kinases (RTK), including HER4, MET, and most prominently AXL, an ADAM10 and ADAM17 substrate, thus increasing surface RTK levels and mitogenic signaling. Progression-free survival of patients with melanoma treated with clinical BRAF/MEK inhibitors inversely correlates with RTK shedding reduction following treatment, as measured noninvasively in blood plasma. Disrupting protease inhibition by neutralizing TIMP1 improves MAPK inhibitor efficacy, and combined MAPK/AXL inhibition synergistically reduces tumor growth and metastasis in xenograft models. Altogether, extracellular proteomic rewiring through reduced RTK shedding represents a surprising mechanism for bypass signaling in cancer drug resistance."
],
"labels": [
"UNLABELLED"
],
"meshes": [
"Animals",
"Antineoplastic Agents",
"Cell Line, Tumor",
"Cell Membrane",
"Disease Models, Animal",
"Drug Resistance, Neoplasm",
"Female",
"Humans",
"JNK Mitogen-Activated Protein Kinases",
"Melanoma",
"Mitogen-Activated Protein Kinases",
"Models, Biological",
"Phosphorylation",
"Protein Kinase Inhibitors",
"Protein Processing, Post-Translational",
"Proteolysis",
"Proto-Oncogene Proteins",
"Proto-Oncogene Proteins c-jun",
"Receptor Protein-Tyrosine Kinases",
"Xenograft Model Antitumor Assays"
]
} | Genetic, epigenetic, and gene expression alterations often fail to explain adaptive drug resistance in cancer. This work presents a novel post-translational mechanism of such resistance: Kinase inhibitors, particularly targeting MAPK signaling, increase tumor cell surface receptor levels due to widely reduced proteolysis, allowing tumor signaling to circumvent intended drug action. | yes | Reduced proteolytic shedding of receptor tyrosine kinases is a post-translational mechanism of kinase inhibitor resistance. |
7,478,835 | Does elevated serum lactate correlate with intracranial hemorrhage in neonates treated with extracorporeal life support? | {
"contexts": [
"To correlate the initial and maximal lactate levels with the occurrence of intracranial hemorrhage (ICH) and survival in patients treated with extracorporeal life support (ECLS).",
"Retrospective chart review.",
"Pediatric intensive care unit.",
"Eighty-two neonatal patients placed on ECLS for respiratory failure due to sepsis, meconium aspiration, or persistent pulmonary hypertension of the newborn.",
"The initial lactate level measured within 6 hours of initiating ECLS and the maximal lactate level measured throughout the ECLS course were collected. Lactate levels were described as mean lactate +/- SE (mM). Head ultrasound reports and survival were reviewed. Platelet counts and activated clotting times (ACTs) were examined.",
"The mean initial and maximal lactate levels were higher in ECLS patients who developed ICH (initial: 10 +/- 1.7 mM vs 6.4 +/- 0.8 mM, p = .05 and maximal: 12.4 +/- 2.5 mM vs 7.9 +/- 0.8 mM, p = .04). Initial and maximal lactate levels were also elevated in nonsurvivors (initial: 11.7 +/- 3 mM vs 6.4 +/- 0.7 mM, p = .01 and maximal: 14.8 +/- 3.3 mM vs 7.8 +/- 0.8 mM, P < .01). Platelet counts and ACT did not differ in patients with and without ICH."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Cerebral Hemorrhage",
"Extracorporeal Membrane Oxygenation",
"Humans",
"Infant, Newborn",
"Intensive Care Units, Neonatal",
"Lactates",
"Logistic Models",
"Predictive Value of Tests",
"Respiratory Insufficiency",
"Retrospective Studies",
"Survival Analysis"
]
} | Lactate is a useful marker for the development of ICH in ECLS patients. In addition, elevated lactates during ECLS identify a subgroup of patients with poor outcome. Prospective studies are needed to determine whether the incorporation of this information into pre-ECLS and ECLS management will decrease the occurrence of ICH and improve survival. | yes | Elevated serum lactate correlates with intracranial hemorrhage in neonates treated with extracorporeal life support. |
21,051,708 | Is the Streptococcus pneumoniae capsule required for full virulence in pneumococcal endophthalmitis? | {
"contexts": [
"To determine whether Streptococcus pneumoniae capsule was necessary for pathogenesis of pneumococcal endophthalmitis.",
"An isogenic capsule-deficient strain was created using homologous recombination. New Zealand White rabbits were injected intravitreously with 10(2) colony-forming units (CFU) of the parent strain or the capsule mutant. Slit lamp examination (SLE), electroretinography, and myeloperoxidase activity were performed 24 and 48 hours postinfection (PI). Serial dilutions of vitreous were plated to quantitate CFU, eyes were extracted for histology, and host cytokine mRNA expression was determined.",
"Eyes infected with the parent strain had significantly higher SLE scores than eyes infected with the capsule-deficient strain 24 and 48 hours PI (P < 0.001). CFU recovered from eyes infected with the capsule mutant were significantly fewer than CFU recovered from eyes infected with the parent strain 24 and 48 hours PI (P < 0.001). The parent strain caused a significantly greater decrease in retinal function and more retinal destruction than the mutant strain 48 hours PI (P = 0.026). Vitreal IL-1β, IL-6, and TNF-α were upregulated by both the parent and mutant strain 12 hours PI. By 48 hours PI, there was significantly more neutrophil infiltration in the vitreous infected with the parent strain."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Bacterial Capsules",
"Cell Movement",
"Colony Count, Microbial",
"Cytokines",
"Electroretinography",
"Endophthalmitis",
"Eye Infections, Bacterial",
"Intravitreal Injections",
"Neutrophils",
"Peroxidase",
"Pneumococcal Infections",
"RNA, Messenger",
"Rabbits",
"Reverse Transcriptase Polymerase Chain Reaction",
"Streptococcus pneumoniae",
"Virulence",
"Vitreous Body"
]
} | Endophthalmitis caused by the encapsulated strain is more damaging to retinal function and structural integrity. These findings indicate that capsule is an important virulence factor of S. pneumoniae endophthalmitis, in contrast to keratitis, suggesting that the anatomic host site in pneumococcal ocular infections is important. | yes | The Streptococcus pneumoniae capsule is required for full virulence in pneumococcal endophthalmitis. |
26,708,706 | 's `` It smoke . It 's not tar . It 's not 4000 chemicals . Case closed '' : Exploring attitudes , beliefs , and perceived social norms of e-cigarette use among adult users? | {
"contexts": [
"Electronic cigarette (e-cigarette) use is rapidly increasing among adults in the U.S. The purpose of this qualitative study was to explore consumer perceptions about e-cigarettes, including knowledge, attitudes, beliefs and perceived social norms.",
"A total of 14 focus groups (N=116) were conducted with current adult e-cigarette users in five U.S. cities from March through May, 2014. Focus groups were segmented by age (young adults aged 18-29 and older adults aged 30 and older) as well as by e-cigarette use status (exclusive e-cigarette users and non-exclusive e-cigarette users). Focus group discussions lasted approximately 60-min and were audio-recorded and transcribed; data were analyzed using a phenomenological approach.",
"Participants expressed many positive attitudes towards e-cigarettes and simultaneously reported a lack of information and knowledge about the products. Focus group participants overwhelmingly felt as though the ingredients of e-cigarettes were likely less harmful than conventional cigarettes. Additionally, many described positive reactions from family and friends, especially when e-cigarettes were used in place of conventional cigarettes."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Electronic Nicotine Delivery Systems",
"Female",
"Focus Groups",
"Health Knowledge, Attitudes, Practice",
"Humans",
"Male",
"Social Norms",
"United States",
"Young Adult"
]
} | Findings from this qualitative study provide insight into consumer knowledge, attitudes and beliefs about e-cigarettes increasing our understanding of why and how they are being used. Such information will help provide insight into the potential public health impact of these emerging products. | no | The statement "It's smoke, it's not tar, it's not 4000 chemicals, case closed" explores attitudes, beliefs, and perceived social norms of e-cigarette use among adult users. |
10,462,263 | Does alphav integrin regulate TNF-alpha-induced nitric oxide synthesis in rat mesangial cells -- possible role of osteopontin? | {
"contexts": [
"Tumour necrosis factor-alpha (TNF-alpha) induces nitric oxide (NO) synthesis in rat mesangial cells (MCs). We previously demonstrated that osteopontin (OP), a matrix protein that mainly interacts with the alphav integrin family, increased time-dependently by TNF-alpha stimulation at gene and protein levels. The regulation of NO synthesis by integrins or matrix proteins is unclear.",
"We examined whether integrin, especially alphav integrin, regulates NO synthesis in rat MCs and whether OP, an alphav integrin ligand, has an effect on TNF-alpha-induced NO synthesis. Furthermore, OP and inducible NO synthase (iNOS) gene expression was examined by Northern blotting.",
"TNF-alpha increased NO synthesis in MCs in a time-dependent manner. Synthetic GRGDSP peptide, which is known to inhibit various integrins that interact with RGD-containing extracellular matrices, increased TNF-alpha-induced NO levels in a dose-dependent manner. Cyclical RGD peptide, the specific inhibitor of alphav integrin, also exhibited a dose-dependent effect of increasing NO levels, while GRGESP peptide, which has very low affinity to integrins, had no effect. In addition, NO synthesis was found to be significantly reduced when MCs were plated on OP-coated dishes compared to type I or IV collagen-coated dishes. Furthermore, anti-OP antibody increased NO synthesis in MCs. iNOS mRNA levels were increased by TNF-alpha, and were abruptly diminished after OP mRNA was significantly induced."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Antigens, CD",
"Cells, Cultured",
"Gene Expression",
"Glomerular Mesangium",
"Integrin alphaV",
"Nitric Oxide",
"Nitric Oxide Synthase",
"Nitric Oxide Synthase Type II",
"Oligopeptides",
"Osteopontin",
"Rats",
"Rats, Sprague-Dawley",
"Sialoglycoproteins",
"Tumor Necrosis Factor-alpha"
]
} | The present study demonstrated the involvement of alphav integrin in TNF-alpha-induced NO synthesis in rat MCs, and the possible role of OP was suggested in the mechanism. TNF-alpha and extracellular matrices can co-operate to regulate the behaviour of MCs at least partly through NO synthesis, which may participate in the course of glomerular diseases. | yes | Alphav integrin regulates TNF-alpha-induced nitric oxide synthesis in rat mesangial cells -- possible role of osteopontin. |
9,484,941 | Does 9p21 deletion correlate with recurrence in head and neck cancer? | {
"contexts": [
"Deletion of 9p21 is a common event in many human tumors, including head and neck squamous cell carcinoma (HNSCC). The gene CDKN2, which encodes the protein p16, a cyclin-dependent kinase-4 inhibitor, maps to 9p21. The role of CDKN2 as the tumor suppressor gene in these neoplasms is unclear. The role of loss of heterozygosity (LOH) as a prognostic tool has not been described in HNSCC.",
"We performed deletion mapping using Southern and PCR-based LOH analysis and prospective survival analysis.",
"We demonstrate that LOH of 9p and, specifically, the interferon (IFN) gene cluster correlates with recurrence of HNSCC. We also demonstrate two separate areas of deletion on 9p, one centromeric to IFNbeta and telomeric to CDKN2 and the other centromeric to CDKN2 and telomeric to the polymorphic marker D9S19. All the deletions involve either the markers IFNalpha and/or D9S171 and D9S126 but not necessarily CDKN2."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Blotting, Southern",
"Carcinoma, Squamous Cell",
"Centromere",
"Chromosome Mapping",
"Chromosomes, Human, Pair 9",
"Cyclin-Dependent Kinase Inhibitor p16",
"Female",
"Follow-Up Studies",
"Gene Deletion",
"Genes, Tumor Suppressor",
"Genes, p16",
"Genetic Markers",
"Head and Neck Neoplasms",
"Humans",
"Interferon-beta",
"Interferons",
"Loss of Heterozygosity",
"Male",
"Middle Aged",
"Neoplasm Recurrence, Local",
"Polymerase Chain Reaction",
"Polymorphism, Genetic",
"Prognosis",
"Prospective Studies",
"Survival Analysis",
"Telomere"
]
} | These results suggest another tumor suppressor gene (TSG) may be involved in HNSCC carcinogenesis and may play a role in aggressive disease as manifest by local, regional, or distant recurrence. | yes | 9p21 deletion correlates with recurrence in head and neck cancer. |
21,112,201 | Are advanced glycation end products and its receptor ( RAGE ) increased in patients with COPD? | {
"contexts": [
"Advanced Glycation End products (AGEs) are the products of nonenzymatic glycation and oxidation of proteins and lipids. Formation of AGEs is increased in response to hyperglycaemia, reactive oxygen species and ageing. AGEs are proinflammatory and can modify the extracellular matrix. RAGE (Receptor for Advanced Glycation End Products) mediates some of the effects of AGEs.",
"Formalin-fixed lung tissue from patients who had lobectomy for bronchial carcinoma was used to investigate the presence of AGEs and RAGE. Subjects were divided into those with COPD and controls. Immunostaining for AGEs and RAGE was performed and the intensity of staining measured.",
"Subjects with COPD and controls were similar in age and smoking history but FEV(1)% predicted was lower for COPD than controls. Intensity of staining for AGEs was greater in the airways (p = 0.025) and alveolar walls (p = 0.004) in COPD. Intensity of staining for RAGE was also significantly increased in alveolar walls (p = 0.03) but not the airways. FEV(1)% predicted was correlated with the intensity of staining for AGEs in the airways and alveoli."
],
"labels": [
"UNLABELLED",
"METHODS",
"RESULTS"
],
"meshes": [
"Aging",
"Cells, Cultured",
"Female",
"Glycation End Products, Advanced",
"Humans",
"Hyperglycemia",
"Lung",
"Male",
"Middle Aged",
"Oxidative Stress",
"Pulmonary Disease, Chronic Obstructive",
"Reactive Oxygen Species",
"Receptor for Advanced Glycation End Products",
"Receptors, Immunologic",
"Smoking"
]
} | The increased staining for both AGEs and RAGE in COPD lung raises the possibility that the RAGE-AGEs interaction may have a role in the pathogenesis of COPD. | yes | Advanced glycation end products and its receptor ( RAGE ) are increased in patients with COPD. |
22,726,374 | Does pleural fluid C-reactive protein contribute to the diagnosis and assessment of severity of parapneumonic effusions? | {
"contexts": [
"Prompt identification of parapneumonic effusions has immediate therapeutic benefits. We aimed to assess whether C-reactive protein (CRP) and routine biochemistries in pleural fluid are accurate markers of parapneumonic effusions, and to evaluate their properties as indicators for drainage (complicated parapneumonic effusion).",
"A retrospective review of 340 non-purulent parapneumonic effusions and 1,659 non-parapneumonic exudates from a single center was performed and the discriminative properties of pleural fluid routine biochemistries and, when available, CRP were evaluated. CRP, along with classical fluid parameters, was also applied to classify patients as having complicated or uncomplicated parapneumonic effusions. ROC analysis established the threshold of CRP for discriminating between groups.",
"Pleural fluids with neutrophilic predominance and CRP levels >45 mg/dL were most likely to be parapneumonic in origin (likelihood ratio=7.7). When attempting to differentiate non-purulent complicated from uncomplicated effusions, a CRP >100mg/L had the same performance characteristics (area under the curve=0.81) as the widely accepted biochemistries pH and glucose. Combinations of CRP with pH or glucose resulted in incrementally discriminating values, pertaining to either sensitivity (75-80%) or specificity (97%), for complicated effusions."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"C-Reactive Protein",
"Exudates and Transudates",
"Humans",
"Middle Aged",
"Pleural Effusion",
"Retrospective Studies",
"Severity of Illness Index"
]
} | Pleural fluid CRP may be a useful adjunctive test in pleural effusions, both as a marker of parapneumonics and, particularly, as a differentiator between complicated and uncomplicated effusions. | yes | Pleural fluid C-reactive protein contributes to the diagnosis and assessment of severity of parapneumonic effusions. |
26,403,667 | Is subclinical synovitis detected by macrophage PET , but not MRI , related to short-term flare of clinical disease activity in early RA patients : an exploratory study? | {
"contexts": [
"Residual subclinical synovitis can still be present in joints of rheumatoid arthritis (RA) patients despite clinical remission and has been linked to ongoing radiological damage. The aim of the present study was to assess subclinical synovitis by positron emission tomography (PET; macrophage tracer (11)C-(R)-PK11195) in early RA patients with minimal disease activity without clinically apparent synovitis (MDA); and its relationship with clinical outcome and magnetic resonance imaging (MRI), respectively.",
"Baseline PET and MRI of hands/wrists were performed in 25 early MDA RA patients (DAS 44 < 1.6; no tender/swollen joints) on combined DMARD therapy. PET tracer uptake (semi-quantitative score: 0-3) and MRI synovitis and bone marrow edema (OMERACT RAMRIS) were assessed in MCP, PIP and wrist joints (22 joints/patient; cumulative score).",
"Eleven of 25 patients (44 %) showed enhanced tracer uptake in ≥ 1 joint. Fourteen of these 25 (56 %) patients developed a flare within 1 year: 8/11 (73 %) with a positive, and 6/14 (43 %) with a negative PET. In the latter, in 5/6 patients flare was located outside the scan region. Median cumulative PET scores of patients with a subsequent flare in the hands or wrists were significantly higher than those of patients without a flare (1.5 [IQR 0.8-5.3] vs 0.0 [IQR 0.0-1.0], p = 0.04); significance was lost when all flares were considered (1.0 [IQR 0.0-4.0] vs 0.0 [IQR 0.0-1.0], p = 0.10). No difference in cumulative MRI scores was observed between both groups."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Arthritis, Rheumatoid",
"Disease Progression",
"Female",
"Humans",
"Image Interpretation, Computer-Assisted",
"Isoquinolines",
"Macrophages",
"Magnetic Resonance Imaging",
"Male",
"Middle Aged",
"Positron-Emission Tomography",
"Radiopharmaceuticals",
"Synovitis"
]
} | Positive PET scans were found in almost half of early RA patients with MDA. Patients with a subsequent flare in hand or wrist had higher cumulative PET scores but not MRI scores, suggesting that subclinical arthritis on PET may predict clinical flare in follow-up. | yes | Subclinical synovitis detected by macrophage PET , but not MRI , is related to short-term flare of clinical disease activity in early RA patients : an exploratory study. |
17,893,116 | Is aRHGEF9 disruption in a female patient associated with X linked mental retardation and sensory hyperarousal? | {
"contexts": [
"We identified a female patient with mental retardation and sensory hyperarousal. She has a de novo paracentric inversion of one X chromosome with completely skewed inactivation of the normal X chromosome.",
"We aimed to identify whether a single gene or gene region caused her cognitive and behavioural impairment and that of others.",
"Fluorescent in situ hybridisation (FISH) showed that the centromeric breakpoint disrupts a single gene: ARHGEF9 (CDC42 guanine nucleotide exchange factor (GEF) 9). The telomeric break lies in a gene poor region. We also found that the levels of the ARHGEF9 transcript from the patient are 10-fold less than those found in control samples. Consequently, we sequenced the coding exons and intron/exon borders of the ARHGEF9 gene in 99 probands from families with X linked mental retardation (XLMR) and 477 mentally retarded males in whom a diagnosis of Fragile X syndrome had been excluded. We did not identify any pathogenic changes; however, we did identify intronic nucleotide changes that might alter splicing."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"RESULTS"
],
"meshes": []
} | ARHGEF9 encodes a RhoGEF family protein: collybistin (hPEM), which is highly expressed in the developing and adult brain. Collybistin can regulate actin cytoskeletal dynamics and may also modulate GABAergic and glycinergic neurotransmission through binding of a scaffolding protein, gephyrin, at the synapse. This potential dual role may explain both the mental retardation and hyperarousal observed in our patient. While ARHGEF9 appears to be an uncommon cause of mental retardation in males, it should be considered in patients with mental retardation and sensory hyperarousal. | yes | A disruption of aRHGEF9 in a female patient is associated with X-linked mental retardation and sensory hyperarousal. |
24,721,998 | Do patterns of transmitted HIV drug resistance in Europe vary by risk group? | {
"contexts": [
"In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported.",
"HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression.",
"From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Anti-HIV Agents",
"Drug Resistance, Viral",
"Europe",
"Female",
"HIV Infections",
"HIV-1",
"Heterosexuality",
"Homosexuality, Male",
"Humans",
"Logistic Models",
"Male",
"Middle Aged",
"Protease Inhibitors",
"Reverse Transcriptase Inhibitors",
"Risk",
"Risk-Taking",
"Sexual Behavior",
"Substance Abuse, Intravenous"
]
} | MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs. | yes | Patterns of transmitted HIV drug resistance in Europe vary by risk group. |
16,931,788 | Does dual PPARalpha/gamma agonist tesaglitazar reduce atherosclerosis in insulin-resistant and hypercholesterolemic ApoE*3Leiden mice? | {
"contexts": [
"We investigated whether the dual PPARalpha/gamma agonist tesaglitazar has anti-atherogenic effects in ApoE*3Leiden mice with reduced insulin sensitivity.",
"ApoE*3Leiden transgenic mice were fed a high-fat (HF) insulin-resistance-inducing diet. One group received a high-cholesterol (HC) supplement (1% wt/wt; HC group). A second group received the same HC supplement along with tesaglitazar (T) 0.5 micromol/kg diet (T group). A third (control) group received a low-cholesterol (LC) supplement (0.1% wt/wt; LC group). Tesaglitazar decreased plasma cholesterol by 20% compared with the HC group; cholesterol levels were similar in the T and LC groups. Compared with the HC group, tesaglitazar caused a 92% reduction in atherosclerosis, whereas a 56% reduction was seen in the cholesterol-matched LC group. Furthermore, tesaglitazar treatment significantly reduced lesion number beyond that expected from cholesterol lowering and induced a shift to less severe lesions. Concomitantly, tesaglitazar reduced macrophage-rich and collagen areas. In addition, tesaglitazar reduced inflammatory markers, including plasma SAA levels, the number of adhering monocytes, and nuclear factor kappaB-activity in the vessel wall."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Alkanesulfonates",
"Animals",
"Apolipoprotein E3",
"Apolipoproteins E",
"Atherosclerosis",
"Biomarkers",
"Blood Vessels",
"Cell Adhesion",
"Cholesterol",
"Cholesterol, Dietary",
"Collagen",
"Dietary Fats",
"Female",
"Hypercholesterolemia",
"Inflammation",
"Insulin Resistance",
"Lipids",
"Lipoproteins",
"Macrophages",
"Mice",
"Mice, Transgenic",
"Monocytes",
"NF-kappa B",
"PPAR alpha",
"PPAR gamma",
"Phenylpropionates"
]
} | Tesaglitazar has anti-atherosclerotic effects in the mouse model that go beyond plasma cholesterol lowering, possibly caused by a combination of altered lipoprotein profiles and anti-inflammatory vascular effects. | yes | Dual PPARalpha/gamma agonist tesaglitazar reduces atherosclerosis in insulin-resistant and hypercholesterolemic ApoE*3Leiden mice. |
21,442,053 | Is long-term interferon therapy after radiofrequency ablation effective in treating patients with HCV-associated hepatocellular carcinoma? | {
"contexts": [
"This study investigates the usefulness of long-term interferon (IFN) therapy following radiofrequency ablation (RFA) for HCV-associated hepatocellular carcinoma (HCC).",
"This is a retrospective observational study. Patients underwent pegylated IFN-α/ribavirin combination therapy for 48 weeks and then were maintained on IFN-α administration on average for 68 weeks (mean total duration 116 weeks). Patients who underwent IFN monotherapy were maintained on IFN administration on average for 78 weeks.",
"There were biases in the background factors between the IFN and non-IFN groups. Therefore, a covariate adjustment was performed using the propensity score. An analysis of 20-matched patients from each group showed the 5-year cumulative survival rate was higher in the IFN group than in the non-IFN group (100 and 76%, respectively), and the 3-year cumulative recurrence rate was significantly lower in the IFN group than in the non-IFN group (38.0 and 64.2%, respectively). In 14 patients (i.e., IFN responders), the serum alanine aminotransferase (ALT) level remained normalized at 30 IU/mL or lower, regardless of disappearance of serum HCV RNA. In these patients, the cumulative recurrence rate was low, the hazard ratio was 0.158 (95% confidence interval = 0.045-0.561, P = 0.004), and the serum albumin level was retained."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": []
} | These results show the importance of maintaining the liver function and suggest that long-term IFN administration after RFA inhibits recurrence and contributes to an improved outcome in patients (in particular, IFN responders) who initially develop HCC. | yes | Long-term interferon therapy after radiofrequency ablation is effective in treating patients with HCV-associated hepatocellular carcinoma. |
16,290,969 | Is oxygen pulse during exercise related to resting systolic and diastolic left ventricular function in older persons with mild hypertension? | {
"contexts": [
"The mechanisms responsible for impaired cardiovascular hemodynamics during exercise among persons with milder forms of hypertension are not well documented. We examined the relationship of oxygen pulse during exercise, a correlate of stroke volume, with echocardiographic indices of resting left ventricular function to determine whether abnormal contractility and relaxation are related to abnormal cardiovascular dynamics during exercise among such persons.",
"Subjects were 44 men and 55 women ages 55 to 75 years with mild hypertension but who were otherwise healthy. Resting left ventricular systolic and diastolic functions were assessed with 2-dimensional Doppler echocardiography and tissue Doppler imaging. Oxygen pulse (millimeters per beat) at rest and during multistage treadmill testing was derived from measurements of oxygen consumption and heart rate. The slope of oxygen pulse between successive exercise stages was calculated.",
"After a steep rise in oxygen pulse from rest to stage 1 of exercise, a markedly diminished oxygen pulse slope was seen between subsequent exercise stages. In stepwise regression analysis, the increase in the slope of oxygen pulse from rest to stage 1 was explained by a greater lean body mass (57%, P < .001) and a larger left atrial size (2%, P < .001). After exercise stage 1, the increase in the slope of oxygen pulse was explained by sex (24%, P < .001), higher mitral E/A ratio (6%, P < .001), and higher mitral annular systolic velocity (6%, P < .001)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Echocardiography, Doppler",
"Exercise",
"Female",
"Humans",
"Hypertension",
"Male",
"Middle Aged",
"Myocardial Contraction",
"Oxygen",
"Pulse",
"Rest",
"Severity of Illness Index",
"Ventricular Function, Left"
]
} | These results suggest that a blunted oxygen pulse response to exercise among older persons with milder forms of hypertension may reflect impaired left ventricular stroke volume changes during exercise secondary to subtle abnormalities in both systolic and diastolic left ventricular functions. | yes | Oxygen pulse during exercise is related to resting systolic and diastolic left ventricular function in older persons with mild hypertension. |
26,370,283 | Does phosphoproteomic analysis reveal Smarcb1 dependent EGFR signaling in Malignant Rhabdoid tumor cells? | {
"contexts": [
"The SWI/SNF ATP dependent chromatin remodeling complex is a multi-subunit complex, conserved in eukaryotic evolution that facilitates nucleosomal re-positioning relative to the DNA sequence. In recent years the SWI/SNF complex has emerged to play a role in cancer development as various sub-units of the complex are found to be mutated in a variety of tumors. One core-subunit of the complex, which has been well established as a tumor suppressor gene is SMARCB1 (SNF5/INI1/BAF47). Mutation and inactivation of SMARCB1 have been identified as the underlying mechanism leading to Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms.",
"We present a phosphoproteomic study of Smarcb1 dependent changes in signaling networks. The SILAC (Stable Isotopic Labeling of Amino Acids in Cell Culture) protocol was used to quantify in an unbiased manner any changes in the phosphoproteomic profile of Smarcb1 deficient murine rhabdoid tumor cell lines following Smarcb1 stable re-expression and under different serum conditions.",
"This study illustrates broad changes in the regulation of multiple biological networks including cell cycle progression, chromatin remodeling, cytoskeletal regulation and focal adhesion. Specifically, we identify Smarcb1 dependent changes in phosphorylation and expression of the EGF receptor, demonstrate downstream signaling and show that inhibition of EGFR signaling specifically hinders the proliferation of Smarcb1 deficient cells."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Brain Neoplasms",
"Cell Line, Tumor",
"Chromatin Assembly and Disassembly",
"Chromosomal Proteins, Non-Histone",
"ErbB Receptors",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Isotope Labeling",
"Kidney Neoplasms",
"Mice",
"Phosphoproteins",
"Proteomics",
"Rhabdoid Tumor",
"SMARCB1 Protein",
"Signal Transduction"
]
} | These results support recent findings regarding the effectivity of EGFR inhibitors in hindering the proliferation of human MRT cells and demonstrate that activation of EGFR signaling in Rhabdoid tumors is SMARCB1 dependent. | yes | Phosphoproteomic analysis reveals Smarcb1 dependent EGFR signaling in Malignant Rhabdoid tumor cells. |
17,666,472 | Does cinacalcet hydrochloride reduce the serum calcium concentration in inoperable parathyroid carcinoma? | {
"contexts": [
"Management of inoperable parathyroid carcinoma presents a challenge because until recently, effective medical therapy was not available. Morbidity and mortality result primarily from severe hypercalcemia. We assessed the ability of the calcimimetic cinacalcet HCl to reduce serum calcium in patients with parathyroid carcinoma as well as its effect on PTH concentrations, bone turnover markers, safety, and health-related quality of life variables.",
"Twenty-nine patients with parathyroid carcinoma were enrolled in this open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated (30 mg twice daily to 90 mg four times daily) for 16 wk or until serum calcium was no more than 10.0 mg/dl. The study endpoint was the proportion of patients with at least a 1 mg/dl reduction in serum calcium at the end of the titration phase (responders).",
"Mean (+/- se) serum calcium (14.1 +/- 0.4 mg/dl) and PTH (697 +/- 94 pg/ml) were markedly elevated at baseline. At the end of the titration period, serum calcium was reduced by at least 1 mg/dl in 62% of patients (mean decline to 12.4 +/- 0.5 mg/dl). In the 18 responders, serum calcium fell from 15.0 +/- 0.5 to 11.2 +/- 0.3 mg/dl (P < 0.001). The greatest reductions in serum calcium were observed in patients with highest baseline calcium levels. PTH levels decreased, but not significantly, to 635 +/- 73 pg/ml (-4.6%). Adverse events included nausea, vomiting, headache, and fracture."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Calcium",
"Cinacalcet",
"Female",
"Humans",
"Hypercalcemia",
"Hyperparathyroidism, Primary",
"Male",
"Middle Aged",
"Naphthalenes",
"Parathyroid Hormone",
"Parathyroid Neoplasms",
"Quality of Life",
"Treatment Outcome"
]
} | Cinacalcet effectively reduces hypercalcemia in approximately two thirds of patients with inoperable parathyroid carcinoma and may represent an important new treatment option for these patients. | yes | Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. |
19,561,377 | Does ganoderma lucidum induce the expression of CD40/CD86 on peripheral blood monocytes? | {
"contexts": [
"The major immuno-modulating effects of Ganoderma lucidum include mitogenicity and activation of immune effector cells such as T cells, macrophages and natural killer cells resulting in the production of cytokines.",
"The purpose of this study was to evaluate the expression of CD40 and CD80 by G. lucidum-treated human peripheral blood mononuclear cells.",
"Monocytes were isolated and incubated at 37 C and 5% CO2 for 24 h and 48 h in the presence or absence of different concentrations of G. lucidum. Cells were then incubated with labelled monoclonal antibodies against CD14, CD40 and B7-1(CD80) molecules utilizing standard protocols, and analyzed by flow cytometry.",
"The results showed that incubation of monocytes with G. lucidum led to marked enhancement of CD40 and B7-1 expression in a dose- and time- dependent manner (p<0.001). G. lucidum was more effective in enhancing the expression of CD80 and CD40 molecules of cells obtained from females than male donors (p<0.001)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Antigens, Differentiation",
"B7-2 Antigen",
"CD40 Antigens",
"Cell Differentiation",
"Cells, Cultured",
"Dose-Response Relationship, Drug",
"Female",
"Flow Cytometry",
"Humans",
"Immunophenotyping",
"Leukocytes, Mononuclear",
"Male",
"Middle Aged",
"Neoplasms",
"Phytotherapy",
"Plant Extracts",
"Reishi",
"Sex Factors"
]
} | G. lucidum enhanced the expression of CD40 and CD80 molecules on peripheral blood monocytic cells derived from both sexes in a dose-dependent manner, with a preferential higher effect on cells obtained from female donors. | yes | Ganoderma lucidum induces the expression of CD40/CD86 on peripheral blood monocytes. |
21,750,002 | Do glucocorticoids enhance Th17/Th1 imbalance and signal transducer and activator of transcription 3 expression in systemic lupus erythematosus patients? | {
"contexts": [
"To investigate the relative amounts of Th17 and Th1 cells present in SLE patients and the possible effects of treatments or disease features on these populations.",
"Peripheral blood mononuclear cells were collected from 75 SLE patients and 19 healthy controls and the proportion of Th17 and Th1 populations were assessed by flow cytometry measuring the amount of IL-17 and IFN-γ-producing cells. Gene expression of signal transducers and activators of transcription 3 (STAT3), STAT4, IL-6R and IL-12R were determined in 30 patients and 8 healthy individuals by real-time RT-PCR. Data were related to clinical and immunological parameters and to the treatment followed during the past 3 months.",
"Th17 cells and the Th17/Th1 ratio were significantly increased in SLE patients treated with glucocorticoids compared with healthy individuals, untreated patients or those under other treatments. No association was detected with clinical parameters, but patients with anti-ENA antibodies also displayed increased Th17 responses. Disease activity (SLEDAI) is associated with the Th17/Th1 index only in glucocorticoid-treated patients. In line with these results, gene expression of STAT3 and IL-6R was up-regulated in patients taking these drugs. Accordingly, we found a positive correlation between the Th17/Th1 ratio and STAT3 levels."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Drug Therapy, Combination",
"Female",
"Glucocorticoids",
"Humans",
"Immunosuppressive Agents",
"Interferon-gamma",
"Interleukin-17",
"Ionophores",
"Leukocyte Count",
"Leukocytes, Mononuclear",
"Lupus Erythematosus, Systemic",
"Male",
"STAT3 Transcription Factor",
"Tetradecanoylphorbol Acetate",
"Th1 Cells",
"Th17 Cells"
]
} | The present work provides the first evidence that aberrant Th17/Th1 balance in SLE is linked to the use of glucocorticoids and suggests that the up-regulatory effect of these drugs on the Th17 population could be associated with their ability to increase STAT3 and IL-6R expression. Additionally, anti-ENA positivity could represent a potential biomarker for Th17 bias. | yes | Glucocorticoids enhance Th17/Th1 imbalance and signal transducer and activator of transcription 3 expression in systemic lupus erythematosus patients. |
16,610,083 | Does [ COX-2 mediate U50488H-induced delayed cardioprotection in isolated rat heart ]? | {
"contexts": [
"To determine whether U50488H, a selective agonist of kappa-opioid receptor, could induce biphasic (early and late) cardioprotection against myocardial ischemia/reperfusion injury and to explore the underlying mechanisms.",
"Isolated perfused rat hearts were subjected to 30 min of ischemia followed by 120 min reperfusion and the cardiac function was evaluated.",
"Left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP) and maximal velocity of contraction and relaxation (+/-dP/dtmax) were improved when U50488H was administered 1 or 24 h before ischemia (P<0.05). Myocardial infarct size, activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary effluent were lower in the U50488H pretreatment group than those in the control group. Administration of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib abolished the late phase of cardioprotection produced by administration of U50488H 24 h before ischemia. Activities of CK and LDH in the coronary effluent were higher in U50488H and celecoxib co-pretreatment group than those in U50488H group. However, administration of celecoxib did not block the early phase of cardioprotection by 1 h treatment of U50488H before ischemia."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer",
"Animals",
"Cardiotonic Agents",
"Creatine Kinase",
"Cyclooxygenase 2",
"In Vitro Techniques",
"Ischemic Preconditioning, Myocardial",
"L-Lactate Dehydrogenase",
"Male",
"Myocardial Infarction",
"Myocardial Reperfusion Injury",
"Rats",
"Rats, Sprague-Dawley",
"Receptors, Opioid, kappa"
]
} | The late (but not the early) phase of cardioprotection induced by kappa-opioid receptor agonist might be mediated by COX-2. | yes | COX-2 mediates U50488H-induced delayed cardioprotection in isolated rat heart. |
24,300,974 | Does gambogic acid synergistically potentiate cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-κB and MAPK/HO-1 signalling? | {
"contexts": [
"Gambogic acid (GA) has been reported to have potent anticancer activity and is authorised to be tested in phase II clinical trials for treatment of non-small-cell lung cancer (NSCLC). The present study aims to investigate whether GA would be synergistic with cisplatin (CDDP) against the NSCLC.",
"1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), combination index (CI) isobologram, western blot, quantitative PCR, flow cytometry, electrophoretic mobility shift assay, xenograft tumour models and terminal deoxynucleotide transferase-mediated dUTP nick-end labelling analysis were used in this study.",
"The cell viability results showed that sequential CDDP-GA treatment resulted in a strong synergistic action in A549, NCI-H460, and NCI-H1299 cell lines, whereas the reverse sequence and simultaneous treatments led to a slight synergistic or additive action. Increased sub-G1 phase cells and enhanced PARP cleavage demonstrated that the sequence of CDDP-GA treatment markedly increased apoptosis in comparison with other treatments. Furthermore, the sequential combination could enhance the activation of caspase-3, -8, and 9, increase the expression of Fas and Bax, and decrease the expression of Bcl-2, survivin and X-inhibitor of apoptosis protein (X-IAP) in A549 and NCI-H460 cell lines. In addition, increased apoptosis was correlated with enhanced reactive oxygen species generation. Importantly, it was found that, followed by CDDP treatment, GA could inhibit NF-κB and mitogen-activated protein kinase (MAPK)/heme oxygenase-1 (HO-1) signalling pathways, which have been validated to reduce ROS release and confer CDDP resistance. The roles of NF-κB and MAPK pathways were further confirmed by using specific inhibitors, which significantly increased ROS release and apoptosis induced by the sequential combination of CDDP and GA. Moreover, our results indicated that the combination of CDDP and GA exerted increased antitumour effects on A549 xenograft models through inhibiting NF-κB, HO-1, and subsequently inducing apoptosis."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Antineoplastic Combined Chemotherapy Protocols",
"Apoptosis",
"Apoptosis Regulatory Proteins",
"Carcinoma, Non-Small-Cell Lung",
"Caspases",
"Cell Line, Tumor",
"Cell Survival",
"Cisplatin",
"Down-Regulation",
"Drug Synergism",
"Heme Oxygenase-1",
"Humans",
"Lung Neoplasms",
"MAP Kinase Signaling System",
"Mitogen-Activated Protein Kinases",
"NF-kappa B",
"Reactive Oxygen Species",
"Signal Transduction",
"Xanthones"
]
} | Gambogic acid sensitises lung cancer cells to CDDP in vitro and in vivo in NSCLC through inactivation of NF-κB and MAPK/HO-1 signalling pathways, providing a rationale for the combined use of CDDP and GA in lung cancer chemotherapy. | yes | Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-κB and MAPK/HO-1 signalling. |
Subsets and Splits