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['To analyse the causes of malpractice claims related specifically to cataract surgery in the National Health Service in England from 1995 to 2008.', 'All the malpractice claims related to cataract surgery from 1995 to 2008 from the National Health Service Litigation Authority were analysed. Claims were classified according to causative problem. Total numbers of claims, total value of damages, mean level damages and paid:closed ratio (a measure of the likelihood of a claim resulting in payment of damages) were determined for each cause.', 'Over the 14-year period, there were 324 cataract surgery claims with total damages of £ 1.97 million and mean damages for a paid claim of £ 19,900. Negligent surgery (including posterior capsule tear and dropped nucleus) was the most frequent cause for claims, while reduced vision accounted for the highest total and mean damages. Claims relating to biometry errors/wrong intraocular lens power were the second most frequent cause of claims and result in payment of damages in 62% of closed cases. The claims with the highest paid:closed ratio were inadequate anaesthetic (75%) and complications of anaesthetic injections including globe perforation (67%).'] Does causes of cataract surgery malpractice claim in England 1995-2008?
qiaojin/PubMedQA
2
[ -0.8131825923919678, -0.8001624345779419, 0.720579206943512 ]
['There was a report that microRNA (miRNA) controls multiple genes. In addition, there are some reports that the presence of neoplastic cells that are hypoxic because of rapid tumor development is related to prognosis. As a step toward identifying the role of miRNA in hypoxic tumor cells, the present study was designed to determine which miRNAs have increased expression and which have decreased expression in hypoxic neuroblastoma cells.', 'For this study, we used seven neuroblastoma cell lines. In four with MYCN was amplified; in the other three MYCN was non-amplified. Neuroblastoma cells were cultured under hypoxic conditions. The expression levels of 662 kinds of miRNA in the hypoxic cells were quantified by gene array.', 'We found that the expression of 85 kinds of miRNA was increased. Expression of six of these mRNAs was increased in two or more cell lines. Hsa-miR-143, -145, and -210 were each expressed in four of the seven cell lines. In addition, expression of 48 kinds of miRNA was decreased. Expression of five was decreased in two cell lines. There was no relation between the expression of miRNA and the amplification of MYCN.'] Are expression patterns of microRNAs altered in hypoxic human neuroblastoma cells?
qiaojin/PubMedQA
2
[ -2.2441046237945557, -0.016397738829255104, 1.2546989917755127 ]
["Diffuse large B-cell lymphoma (DLCL) accounts for 30-40% of adult non-Hodgkin's Lymphoma (NHL). Current anti-NHL therapies often target cellular growth suppression pathways and include R-CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone plus monoclonal anti-CD20 antibody rituximab). However, since many patients relapse, resistant cells to these therapies remain a significant problem and necessitate development of new intervention strategies. Cell cycle and apoptosis regulatory protein (CARP)-1 functions in a biphasic manner to regulate growth factor as well as chemotherapy (adriamycin, etoposide, or iressa)-dependent signaling.", 'To determine whether CARP-1 is a novel suppressor of lymphoma growth.', 'Flow cytometric analyses coupled with Western immunoblotting, cell growth, apoptosis, and immunocytochemistry methodologies were utilized to determine CARP-1-dependent lymphoma growth inhibition in vitro and in vivo.', 'CARP-1 expression correlated with activated caspase-3 and inversely correlated with activated Akt in DLCL. Exposure to adriamycin stimulated CARP-1 expression and inhibited growth of Raji cells, but not CHOP-resistant WSU-DLCL2 cells. Expression of wild-type CARP-1 or its apoptosis-inducing mutants inhibited growth of Raji as well as CHOP-resistant WSU-DLCL2 cells, in part by activating caspase-9 and apoptosis. Since CARP-1 harbors multiple, apoptosis-promoting subdomains, we investigated whether epigenetic compensation of CARP-1 function by intracellular delivery of trans-activator of transcription (TAT) domain-tagged CARP-1 peptide(s) will inhibit lymphoma growth. Treatments with TAT-tagged CARP-1 peptides suppressed growth of the Raji and WSU-DLCL2 cells by stimulating apoptosis. TAT-CARP-1 (1-198) as well as (896-1150) peptides also suppressed growth of WSU-DLCL2 cell-derived tumor xenografts in SCID mice, while administration of TAT-CARP-1 (1-198) also inhibited growth of WSU-FSCCL cell-derived ascites and prolonged host survival.'] Is cell cycle and apoptosis regulatory protein ( CARP ) -1 a novel , adriamycin-inducible , diffuse large B-cell lymphoma ( DLBL ) growth suppressor?
qiaojin/PubMedQA
2
[ -2.435779094696045, -1.3675625324249268, 2.8543169498443604 ]
['To determine which aspects of ED management are adversely affected by patient obesity, to determine the level of obesity above which management is made more difficult and to make recommendations on how these effects might be mitigated.', "This was a cross-sectional survey of patients and the staff caring for them in a single ED. Doctors, nurses and radiographers managing consecutive patients, during a range of enrolment periods, completed a self-administered questionnaire. Each was asked to record how the level of their patient's obesity increased the difficulty of specific management items, using a Likert scale. Staff also provided recommendations to mitigate the effects of obesity for each patient, if applicable. For each management item, body mass index (BMI) and management difficulty were correlated (Spearman's rank correlation).", 'Seven hundred and fifty patients and their ED carers were enrolled. Patient BMI was positively correlated with all aspects of ED clinical management examined (correlation coefficient range 0.28-0.57, P < 0.001). BMI most strongly correlated with difficulty in finding anatomical landmarks, venous pressure measurement, physical examination, patient positioning and procedures generally, especially cannulation and venipuncture (coefficient > 0.5, P < 0.001). Doctors reported more difficulties than nurses and radiographers. Generally, management difficulty did not increase until the BMI was in the obese or morbidly obese range. Most staff recommendations related to issues of patient mobility including equipment, staffing and bariatric devices.'] Does obesity significantly increase the difficulty of patient management in the emergency department?
qiaojin/PubMedQA
2
[ -1.8584051132202148, -0.4467417895793915, 1.480234980583191 ]
['To evaluate the activity of neck extensor muscles during different extension exercises with muscle functional magnetic resonance imaging (mfMRI).', 'Cross-sectional.', 'University laboratory.', 'Healthy subjects (N=11; 7 men, mean age +/- SD, 34+/-5.6y; 4 women, mean age +/- SD, 23.3+/-5.2y; group mean age +/- SD, 30.1+/-7.5y).', 'Not applicable.', 'mfMRI measures of T2 relaxation were made for the multifidus (Mul), the semispinalis cervicis (SCe), the semispinalis capitis (SCa), and the splenius capitis (SpC) at C2-3, C5-6, and C7-T1 in response to 2 head/neck orientations: craniocervical neutral (CCN) and craniocervical extension (CCE). Subjects performed three 1-minute repetitions of each condition at 20% maximum voluntary contraction.', 'Significant shifts were observed in all muscle groups at the C5-6 and C7-T1 levels after both conditions (P=.04) except the SpC muscle at C5-6 with CCN (P=.17). T2 shifts in the SCa were significantly greater in response to CCE than CCN at C2-3 (P=.03) and C5-6 (P=.02). Similarly, CCE resulted in larger shifts than CCN in the Mul/SCe at C7-T1 (P=.003). No segmental differences were observed between exercises for SpC (P=.25).'] Does craniocervical orientation affect muscle activation when exercising the cervical extensors in healthy subjects?
qiaojin/PubMedQA
2
[ -1.6915758848190308, -1.3521013259887695, 2.078859806060791 ]
['High mobility group box 1 (HMGB1) is released by necrotic cells or secreted in response to inflammatory stimuli. Extracellular HMGB1 may act as a pro-inflammatory cytokine in rheumatoid arthritis. We have recently reported that HMGB1 is released by osteoarthritic synoviocytes after activation with interleukin-1beta (IL-1β) The present study investigated the role of HMGB1 in synovial inflammation in osteoarthritis (OA).', 'HMGB1 was determined in human synovium using immunohistochemistry, comparing normal to OA. OA synoviocytes were incubated with HMGB1 at 15 or 25 ng/ml in the absence or presence of IL-1β (10 ng/ml). Gene expression was analyzed by quantitative PCR and protein expression by Western Blot and ELISA. Matrix metalloproteinase (MMP) activity was studied by fluorometric procedures and nuclear factor (NF)-κB activation by transient transfection with a NF-κB-luciferase plasmid.', 'In the normal synovium, HMGB1 was found in the synovial lining cells, sublining cells, and in the vascular wall cells. The distribution of HMGB1 in OA synovium was similar but the number of HMGB1 positive cells was higher and HMGB1 was also present in infiltrated cells. In normal synovial membrane cells, HMGB1 was found mostly in the nuclei, whereas in OA, HMGB1 was generally found mostly in the cytoplasm. In OA synoviocytes, HMGB1 alone at concentrations of 15 or 25 ng/ml did not affect the production of IL-6, IL-8, CCL2, CCL20, MMP-1 or MMP-3, but in the presence of IL-1β, a significant potentiation of protein and mRNA expression, as well as MMP activity was observed. HMGB1 also enhanced the phosphorylated ERK1/2 and p38 levels, with a lower effect on phosphorylated Akt. In contrast, JNK1/2 phosphorylation was not affected. In addition, HMGB1 at 25 ng/ml significantly potentiated NF-κB activation in the presence of IL-1β.'] Does high mobility group box 1 potentiate the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes?
qiaojin/PubMedQA
2
[ -2.1932373046875, -1.454402208328247, 2.6834793090820312 ]
["Entomopathogenic fungi, Metarhizium anisopliae and Beauveria bassiana, are promising bio-pesticides for application against adult malaria mosquito vectors. An understanding of the behavioural responses of mosquitoes towards these fungi is necessary to guide development of fungi beyond the 'proof of concept' stage and to design suitable intervention tools.", 'Here we tested whether oil-formulations of the two fungi could be detected and avoided by adult Anopheles gambiae s.s., Anopheles arabiensis and Culex quinquefasciatus. The bioassays used a glass chamber divided into three compartments (each 250 × 250 × 250 mm): release, middle and stimulus compartments. Netting with or without fungus was fitted in front of the stimulus compartment. Mosquitoes were released and the proportion that entered the stimulus compartment was determined and compared between treatments. Treatments were untreated netting (control 1), netting with mineral oil (control 2) and fungal conidia formulated in mineral oil evaluated at three different dosages (2 × 1010, 4 × 1010 and 8 × 1010 conidia m-2).', 'Neither fungal strain was repellent as the mean proportion of mosquitoes collected in the stimulus compartment did not differ between experiments with surfaces treated with and without fungus regardless of the fungal isolate and mosquito species tested.'] Are anopheline and culicine mosquitoes repelled by surfaces treated with the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana?
qiaojin/PubMedQA
2
[ -2.2774906158447266, -0.6929728984832764, 1.9942164421081543 ]
['Interleukin-6 (IL-6) binds both the membrane and soluble forms of the IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of tumour cells. The aim of this study is to clarify the relationship between tumoral sIL-6R expression and disease progression in colorectal cancer patients.', 'We measured tissue concentrations of sIL-6R in tumour and normal mucosa from 161 colorectal cancer patients undergoing surgery, and in supernatants from colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by immunohistochemical analysis.', 'Loss of tumour expression of sIL-6R as defined by sIL-6R Ca/N ratio <1.0 was significantly associated with factors reflecting disease progression, and was an independent prognostic factor not only in all the patients in this study, but also in the patients with curative intent. Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation. Immunohistochemistry revealed that loss of tumour expression of sIL-6R was significantly inversely correlated with intense IL-6 expression in the cytoplasm of cancer cells. In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression.'] Is loss of tumoral expression of soluble IL-6 receptor associated with disease progression in colorectal cancer?
qiaojin/PubMedQA
2
[ -2.3896100521087646, -1.224400281906128, 2.6764419078826904 ]
['Only a fraction of molecular cancer markers identified in the scientific literature have found clinical use. Specifically, few predictors of invasiveness are established in diagnostics. Meta-analysis is a valuable tool for biomarker validation. Here, we evaluate Osteopontin as a marker for tumor aggressiveness (grade, stage, early progression) and patient survival.', "Publications through 2008 with the keywords 'osteopontin AND cancer' were retrieved. Titles and abstracts were screened for studies presenting original data on human subjects. This left 228 publications for data extraction. We applied categorical data analysis for testing the relationship between Osteopontin and a clinical variable.", 'Osteopontin ranks correlated with lower overall and disease-free/relapse-free survival in all tumors combined, as well as in lung cancer, breast cancer, prostate cancer, head and neck cancer, and liver cancer. Further, Osteopontin levels correlated with tumor grade and stage for all tumors combined and for several individual tumor types. Osteopontin levels were significantly associated with the early progression of eight cancers, independent in one, and inversely correlated in two.'] Is osteopontin a marker for cancer aggressiveness and patient survival?
qiaojin/PubMedQA
2
[ -2.390582323074341, -0.846470057964325, 2.3272595405578613 ]
['To determine whether the commencement and length of puberty influences dual x-ray absorptiometry (DXA) values of bone mineral content (BMC) and bone mineral density (BMD) in the axial and appendicular skeleton at skeletal maturity.', 'From the Bone Mineral Density in Childhood Study, we identified children who began puberty and completed sexual and skeletal development and examined whether the timing and length of puberty influence DXA values of BMC and BMD at skeletal maturity.', 'A total of 78 girls and 85 boys began puberty and completed skeletal maturity; 4.4 ± 0.8 and 4.5 ± 0.8 years later, respectively. Multiple linear regression analyses indicated that the age of onset of puberty was a strong negative predictor of DXA bone measurements at skeletal maturity, independent of bone values at the beginning of puberty, and the length of puberty. This negative relation was observed for all BMC and BMD measurements at all skeletal sites, in both boys and girls (all P < .0001). In contrast, length of puberty had no relation to any measures of bone.'] Does age at onset of puberty predict bone mass in young adulthood?
qiaojin/PubMedQA
2
[ -1.2582015991210938, -0.9807958006858826, 1.388725757598877 ]
['Postoperative cognitive dysfunction occurs frequently after cardiac, major vascular, and major orthopedic surgery. Aging and hypertensive cerebrovascular disease are leading risk factors for this disorder. Acute anemia, common to major surgery, has been identified as a possible contributor to postoperative cognitive dysfunction. The effect of hypoxia upon cognition and the cellular and molecular processes involved in learning and memory has been well described. Cerebrovascular changes related to chronic hypertension may expose cells to increased hypoxia with anemia.', 'Young to aged spontaneously hypertensive rats underwent testing for visuospatial memory and learning in the Morris water maze, measurement of cerebral tissue oxygenation via tissue oxygen probe, and measurement of hypoxia-sensitive genes and proteins, under conditions of sham and experimental isovolemic anemia.', 'Acute isovolemic anemia elicited evidence of aging-dependent visuospatial working memory and learning impairment. Isovolemic anemia did not result in cerebral tissue hypoxia, when measured via tissue oxygen probe. Evidence of cellular hypoxia was, however, identified in response to the anemic challenge, as hypoxia-sensitive genes and proteins were up-regulated. Importantly, cellular hypoxic gene responses were increased with anemia in an age-dependent manner in this model of aging with chronic hypertension.'] Does acute anemia elicit cognitive dysfunction and evidence of cerebral cellular hypoxia in older rats with systemic hypertension?
qiaojin/PubMedQA
2
[ -2.8169236183166504, -0.6081487536430359, 2.4884910583496094 ]
['To explore the role of group II metabotropic glutamate receptors in the modulation of basic respiratory rhythm.', "Neonatal (0-3 days) SD rats of either sex were used. The medulla oblongata brain slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared, and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O2 and 5% CO2) within 3 min. The brain slices were quickly transferred to a recording chamber and continuously perfused with oxygen-saturated MKS at a rate of 4-6 ml/min at 27-29 degrees celsius. Eighteen medulla oblongata slices were divided into 3 groups and treated for 10 min with group II metabotropic glutamate receptor-specific agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (APDC) (at concentrations of 10, 20, 50 micromol/L), group II metabotropic glutamate receptor antagonist (2S)-alpha-ethylglutamic acid (EGLU) (300 micromol/L), or APDC (50 micromol/L)+EGLU (300 micromol/L) after a 10 min APDC (50 micromol/L) application. Respiratory rhythmical discharge activity (RRDA) of the rootlets of the hypoglossal nerve was recorded by suction electrodes.", 'APDC produced a dose-dependent inhibitory effect on the RRDA, prolonging the respiratory cycle and expiratory time and decreasing the integral amplitude and inspiratory time. EGLU induced a significant decrease in the respiratory cycle and expiratory time. The effect of APDC on the respiratory rhythm was partially reversed by the application of APDC+EGLU.'] Is [ Group II metabotropic glutamate receptors involved in the modulation of respiratory rhythmical discharge activity in neonatal rat medullary brain slices ]?
qiaojin/PubMedQA
2
[ -2.3353312015533447, -1.4177310466766357, 2.8053483963012695 ]
['Cyclophosphamide is a cytotoxic chemotherapy drug that causes severe damages to hematopoietic and gastrointestinal systems. The aim of this study is to evaluate the protective effects of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) on chemotherapy-induced mucositis (CIM) in a murine model of cyclophosphamide chemotherapy.', 'In single chemotherapy models, equal numbers of gender-matched Balb/c mice were administered intraperitoneal injections of rhIL-1Ra at a dose of 1 mg/kg/day or vehicle for 5 continuous days, followed by single intraperitoneal injection of cyclophosphamide at doses of 100, 300, 400 or 550 mg/kg. In multiple cycles of chemotherapy models, mice were administered rhIL-1Ra or vehicle for 5 days, followed by cyclophosphamide injection at a dose of 300 mg/kg. The course has been repeated for 2 or 3 times with a 1-month break in between. In continuous chemotherapy models, mice were administered rhIL-1Ra or vehicle for 5 days, followed by cyclophosphamide injections at doses of 150 or 200 mg/kg/day for 3 days. Body weight and diarrhea were observed in each model. Intestinal morphology was observed in mice received 300 or 400 mg/kg cyclophosphamide chemotherapy.', 'CIM was induced by cyclophosphamide in a dose-dependent manner. RhIL-1Ra attenuated CIM with reduced body weight loss, diarrhea, intestinal injuries and mortality after CY chemotherapy.'] Does interleukin-1 receptor antagonist attenuate cyclophosphamide-induced mucositis in a murine model?
qiaojin/PubMedQA
2
[ -2.122408151626587, -1.4648737907409668, 2.6419312953948975 ]
['Cardiac tamponade is a life-threatening disease in which hypotension is believed to be a common finding. Prior inpatient studies have described normotensive or hypertensive cases of tamponade; however, because the data were not collected from the Emergency Department (ED), the hemodynamic spectrum may differ from those presenting to the ED.', 'We hypothesized that hypotension is uncommon in patients presenting to the ED with non-traumatic tamponade.', 'A retrospective chart review was conducted between January 2002 and December 2007 of patients presenting to our ED who were subsequently diagnosed with cardiac tamponade.', 'A total of 34 patients were identified with a diagnosis of tamponade. The mean blood pressure on ED arrival was 131/79mm Hg. Upon initial presentation to the ED, 35% (n=12) of patients were hypertensive, 50% (n=17) were normotensive, and 15% (n=5) were hypotensive. Of the 5 patients who were hypotensive on ED arrival, only 2 (6% of all patients) remained hypotensive upon admission to the hospital and before a pericardiocentesis. An average of 995mL of fluid was removed from the pericardium. The chief complaint for the majority of patients in tamponade was shortness of breath (70%); 59% were tachycardic in the ED, and 72% had cardiomegaly on chest X-ray study.'] Is hypotension uncommon in patients presenting to the emergency department with non-traumatic cardiac tamponade?
qiaojin/PubMedQA
2
[ -1.7461882829666138, -1.4320025444030762, 2.130953073501587 ]
['Few previous studies have focused on the involvement of the lymphatic system in Klippel-Trenaunay syndrome (KTS), although some evidence suggests that lymphatic abnormalities are associated with the disease. The aim of the present study was to investigate the involvement of the lymphatic system in KTS.', 'Magnetic resonance lymphangiography (MRL) with the use of gadobenate dimeglumine as the contrast was performed on 32 patients with KTS involving the extremities to evaluate lymphatic vessels, lymph nodes, and veins.', 'Thirty-one of 32 patients exhibited lymphatic vessel and/or lymph node anomalies, including hyperplasia (11/31), hypoplasia or aplasia (20/31) of lymphatic vessels, and lymphedema (31/31) of the affected limbs. Twenty-two patients showed asymmetry of the inguinal nodes exhibiting either the absence, or an increase or a decrease in number and size of the inguinal nodes. Venous dysplasia was found in 31 patients in superficial and/or deep veins. The results showed a high concomitance of malformations of the lymphatic system and veins in the affected limbs of patients with KTS.'] Is lymphatic malformation a common component of Klippel-Trenaunay syndrome?
qiaojin/PubMedQA
2
[ -2.4171297550201416, -1.286907434463501, 2.8352854251861572 ]
['Portal vein ligation (PVL) and portal vein embolization (PVE) are used to induce hypertrophy of the future remnant liver before major liver resection. The aim of our study was to compare the hypertrophy response of the liver after PVL versus PVE in a rabbit model.', 'Twenty rabbits were divided into an embolization group (n = 10) and a ligation group (n = 10). Both groups were divided in 2 subgroups of 5 rabbits that were humanely killed after days 7 and 14. The portal vein branches to the 3 cranial liver lobes (80% of the liver) were occluded. Regeneration of the caudal liver lobe was measured using volumetry based on computed tomography on days 3, 7, 10, and 14. Immunohistochemistry for Ki-67 and RAM11 was performed to quantify proliferating cells and macrophages. In addition, tissue tumor necrosis factor-α and interleukin-6 were assessed.', 'The caudal liver volume increased over time in both groups (P < .001), but this increase was greater after PVE than after PVL (P = .001) with a mean degree of hypertrophy of 15% ± 4% and 20% ± 2%, respectively. When comparing the groups on the separate time points, a difference was found on days 10 and 14 (P = .008 and P = .016, respectively). These data were confirmed by Ki-67 staining, which showed a greater number of proliferating hepatocytes on day 7 after embolization (P = .016). Cytokine analysis of liver tissue did not show significant differences between the ligation and embolization groups on days 7 and 14.'] Does portal vein embolization induce more liver regeneration than portal vein ligation in a standardized rabbit model?
qiaojin/PubMedQA
2
[ -1.6206564903259277, -1.5307602882385254, 2.184201240539551 ]
['Estradiol 17β-D-glucuronide (E(2)17G) is an endogenous, cholestatic metabolite that induces endocytic internalization of the canalicular transporters relevant to bile secretion: bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2). We assessed whether phosphoinositide 3-kinase (PI3K) is involved in E(2)17G-induced cholestasis. E(2)17G activated PI3K according to an assessment of the phosphorylation of the final PI3K effector, protein kinase B (Akt). When the PI3K inhibitor wortmannin (WM) was preadministered to isolated rat hepatocyte couplets (IRHCs), it partially prevented the reduction induced by E(2)17G in the proportion of IRHCs secreting fluorescent Bsep and Mrp2 substrates (cholyl lysyl fluorescein and glutathione methylfluorescein, respectively). 2-Morpholin-4-yl-8-phenylchromen-4-one, another PI3K inhibitor, and an Akt inhibitor (Calbiochem 124005) showed similar protective effects. IRHC immunostaining and confocal microscopy analysis revealed that endocytic internalization of Bsep and Mrp2 induced by E(2)17G was extensively prevented by WM; this effect was fully blocked by the microtubule-disrupting agent colchicine. The protection of WM was additive to that afforded by the classical protein kinase C (cPKC) inhibitor 5,6,7,13-tetrahydro-13-methyl-5-oxo-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-12-propanenitrile (Gö6976); this suggested differential and complementary involvement of the PI3K and cPKC signaling pathways in E(2)17G-induced cholestasis. In isolated perfused rat liver, an intraportal injection of E(2)17G triggered endocytosis of Bsep and Mrp2, and this was accompanied by a sustained decrease in the bile flow and the biliary excretion of the Bsep and Mrp2 substrates [(3)H]taurocholate and glutathione until the end of the perfusion period. Unlike Gö6976, WM did not prevent the initial decay, but it greatly accelerated the recovery to normality of these parameters and the reinsertion of Bsep and Mrp2 into the canalicular membrane in a microtubule-dependent manner.'] Is phosphoinositide 3-kinase/protein kinase B signaling pathway involved in estradiol 17β-D-glucuronide-induced cholestasis : complementarity with classical protein kinase C?
qiaojin/PubMedQA
2
[ -2.3615663051605225, -1.413346767425537, 2.8210701942443848 ]
["The aim of this qualitative study was to explore baby boomers' views and plans in the early days of the global financial crisis (GFC) in 2008.", 'Informants from National Seniors Australia were interviewed in 15 focus groups conducted nationally. Transcripts were analysed by themes from semi-structured questions.', 'The GFC was found to shake the confidence and plans of boomers. Many workers decided to delay retirement and save longer following losses in superannuation. Those retired on market-linked superannuation felt forced to reduce expenses and restrain lifestyles. Those on full pensions were relatively unaffected.'] Do australian baby boomers talk about the global financial crisis?
qiaojin/PubMedQA
1
[ -1.9555202722549438, 2.8614273071289062, -1.372912883758545 ]
['the effects of bisphenol A (BPA) on NCTC Clone 1469, non-parenchymal hepatocytes, were examined to clarify the molecular basis of BPA-induced liver injury.', "we analyzed the expression of C/EBP homologous protein (CHOP) mRNA, Bcl2 mRNA, caspase12, and glucose-regulated protein 78 kDa (GRP78)/Ig heavy chain-binding protein (BiP), to determine whether endoplasmic reticulum (ER) stress was involved in the 100 μM BPA-induced cell death. To examine the features of damaged hepatocytes, we analyzed the morphological changes in BPA-treated NCTC Clone 1469 by transmission electron microscopy. In addition, we analyzed the intracellular reactive oxygen species (ROS) level in BPA-treated NCTC Clone 1469 by the 2', 7'-dichlorofluorescein diacetate (DCFDA) method.", 'increases in the expression of CHOP mRNA, caspase-12, and GRP78/BiP in NCTC Clone 1469-treated with 100 μM BPA were detected (CHOP, 1.42 fold; caspase-12, 1.33 fold; GRP78/Bip, 1.36 fold). These observations suggested that BPA induced ER stress-associated apoptosis. A morphological analysis revealed remarkable elongation of the rough ER, supporting the finding of ER stress. Intracellular ROS production was increased in NCTC Clone 1469-treated with BPA, and N-acetyl-l-cysteine (NAC) prevented the cell damage induced by BPA. However, these effects of BPA were not inhibited by estrogen receptor inhibitors.'] Does bisphenol A induce endoplasmic reticulum stress-associated apoptosis in mouse non-parenchymal hepatocytes?
qiaojin/PubMedQA
2
[ -2.3177120685577393, -1.3928778171539307, 2.7388131618499756 ]
['A functional polymorphism leading to reduced levels of growth and differentiation factor 5 (GDF5) was recently identified as a susceptibility factor for osteoarthritis. The authors studied the potential mechanisms of GDF5 involvement in osteoarthritis using haploinsufficient Gdf5(Bp-J/+) mice.', 'Gdf5(Bp-J/+) mice were challenged in the collagenase-induced arthritis model, the medial meniscus destabilisation model, the papain-induced arthritis model and a treadmill running model. Bone density and subchondral bone parameters were determined using dual energy x-ray absorptiometry and peripheral quantitative CT. Additional in-vitro and ex-vivo analyses studied cartilage metabolism, gait and collagen characteristics.', 'Gdf5(Bp-J/+) mice appeared phenotypically normal. No difference in osteoarthritis severity was found in the different models, with the exception of increased synovial hyperplasia in the joints of Gdf5(Bp-J/+) mice in the treadmill model. However, in the collagenase-induced model severe joint damage was found in the contralateral joints of Gdf5(Bp-J/+) mice. Gait analysis demonstrated an aberrant walking pattern in Gdf5(Bp-J/+) mice. In addition, Gdf5(Bp-J/+) mice have a decreased subchondral bone density and a distorted arrangement of collagen fibres in bone.'] Is gDF5 deficiency in mice associated with instability-driven joint damage , gait and subchondral bone changes?
qiaojin/PubMedQA
2
[ -2.2863247394561768, -1.345543622970581, 2.6776928901672363 ]
['Previous studies have observed high prevalences of Trichomonas vaginalis infection among women entering US jails and state prisons (22%-47%). We sought to determine the prevalence among women incarcerated in 2 US female-only federal prisons.', 'Female inmates were recruited at 2 prisons (n = 624). Participants completed a self-administered questionnaire and provided self-collected first-catch urine and vaginal swab specimens. Specimens were tested for T. vaginalis DNA.', 'Approximately 8.5% of participants at the first prison, and 8.3% at the second prison had a positive urine result, vaginal swab result or both, for a combined prevalence of 8.5%. Using positivity in either specimen as the reference standard, urine polymerase chain reaction had a sensitivity of 66.7% and vaginal swab polymerase chain reaction had a sensitivity of 84.4%. The only significant positive correlate of T. vaginalis infection was lower household income before arrest. Other variables nonsignificantly positively correlated with T. vaginalis were being employed at the time of arrest, having experienced sexual, physical, or emotional abuse by a family member, having a parent who had not had a drug or alcohol addiction, never exchanging sex for money or drugs, ever being pregnant, having abnormal vaginal bleeding/spotting, and having concurrent chlamydia or gonorrhea.'] Does prevalence and correlate of Trichomonas vaginalis infection among female US federal prison inmates?
qiaojin/PubMedQA
2
[ -2.143608808517456, -0.596012532711029, 1.890366554260254 ]
['To identify associations between sleep-disordered breathing (SDB) and arterial stiffness.', 'Nested cross-sectional study.', 'One hundred fifty-three participants (ages 45-77 years, 43% women) in the population-based Wisconsin Sleep Cohort. Eighty-three had SDB and were not using continuous positive airway pressure therapy.', 'Measurement of aortic pulse wave velocity (PWV) by arterial tonometry. Nocturnal polysomnography.', 'SDB was defined as an apnea-hypopnea index (AHI) > or = 5 events/hour of sleep. By study design those with SDB had higher mean (SD) AHI (17.6 [16.2] vs 2.2 [1.3] events/h), as well as lower average nocturnal O2 saturation (91.5 [2.1] vs 93.0 [1.4] %, P < 0.001) and larger waist circumference (102.5 [13.2] vs 92.5 [12.5] cm, P < 0.001), but they had similar central aortic systolic (122.8 [15.1] vs 119.1 [11.8] mm Hg, P = 0.100) and diastolic blood pressures (77.1 [9.4] vs 77.4 [8.6] mm Hg, P = 0.834), and PWV (9.06 [2.15] vs 8.51 [1.88] m/s; all P > 0.10). Markers of SDB that were correlated with PWV were nocturnal O2 saturation (r = -0.24, P = 0.004) and AHI (r = 0.18, P = 0.032); however, these associations were not statistically significant after adjustment. In subjects not on antihypertensive medications, a significant interaction between nocturnal O2 saturation and age was identified (beta = -0.019, P = 0.039), such that the effect of nocturnal oxygen O2 on PWV increased with age (adjusted R2 = 0.468).'] Are the effects of sleep-disordered breathing on arterial stiffness modulated by age?
qiaojin/PubMedQA
2
[ -1.5370138883590698, -1.6002360582351685, 2.123952865600586 ]
['The APOE epsilon4 allele is an established risk factor for Alzheimer disease (AD), yet findings are mixed for how early its effects are manifest. One reason for the mixed results could be the presence of interaction effects with other AD risk factors. Increasing evidence indicates that testosterone may play a significant role in the development of AD. The aim of the present study was to examine the potential interaction of testosterone and APOE genotype with respect to hippocampal volume in middle age.', 'Participants were men from the Vietnam Era Twin Study of Aging (n = 375). The mean age was 55.9 years (range 51-59). Between-group comparisons were performed utilizing a hierarchical linear mixed model that adjusted for the nonindependence of twin data.', 'A significant interaction was observed between testosterone and APOE genotype (epsilon4-negative vs epsilon4-positive). Those with both low testosterone (> or =1 SD below the mean) and an epsilon4-positive status had the smallest hippocampal volumes, although comparisons with normal testosterone groups were not significant. However, individuals with low testosterone and epsilon4-negative status had significantly larger hippocampal volumes relative to all other groups. A main effect of APOE genotype on hippocampal volume was observed, but only when the APOE-by-testosterone interaction was present.'] Does testosterone modify the effect of APOE genotype on hippocampal volume in middle-aged men?
qiaojin/PubMedQA
2
[ -1.842818260192871, -0.8003389239311218, 1.656286358833313 ]
['The objective of this study was to assess the safety of general thoracic surgery in patients taking antiplatelet (clopidogrel) therapy.', 'A prospective study was conducted of consecutive patients who underwent general thoracic surgery and who were taking clopidogrel perioperatively. They were matched using a propensity score from our prospective database of 11,768 patients. Intraoperative and postoperative outcomes were compared.', 'Between January 2009 and April 2010 there were 33 patients on clopidogrel at the time of surgery and 132 controls. The most common procedures were thoracotomy with lobectomy in 11 patients (robotic in 1), video-assisted wedge resection in 6, mediastinoscopy in 4, and Ivor Lewis esophagogastrectomy in 2. Epidurals were not used. There was no intraoperative morbidity or bleeding in primary thoracotomy; however, 2 of the 4 patients who underwent redo thoracotomy had bleeding that required transfusions. None of the 8 patients receiving clopidogrel who had a coronary artery stent and underwent lobectomy had a perioperative myocardial infarction whereas 5 of the 14 control patients undergoing lobectomy who had a coronary artery stent did (P\xa0=\xa0.05). Otherwise, morbidity, mortality, and length of stay were no different.'] Is general thoracic surgery safe in patients taking clopidogrel ( Plavix )?
qiaojin/PubMedQA
2
[ -2.2916810512542725, -1.1611924171447754, 2.5119290351867676 ]
['l-Stepholidine (l-SPD), a tetrahydroprotoberberine alkaloid, possesses a pharmacological profile of a D₁/5-HT(1A) agonist and a D₂ antagonist. This unique pharmacological profile makes it a promising novel antipsychotic candidate. Preliminary clinical trials and animal experiments suggest that l-SPD improves both positive and negative symptoms of schizophrenia without producing significant extrapyramidal side effects. To further explore the antipsychotic mechanisms of the drug, we studied the effects of l-SPD on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) using in vivo single-unit recording technique in rats.', 'We found that l-SPD increased VTA DA neurons firing rate and induced slow oscillation in firing pattern. Moreover, l-SPD, not clozapine, reversed d-amphetamine-induced inhibition which induced an excitation of VTA DA neurons. Furthermore, our data indicated that the excitatory effect of l-SPD is associated with its partial agonistic action for the 5-HT(1A) receptor since the 5-HT(1A) receptor antagonist WAY100635 could block the l-SPD-induced excitatory effect. However, activation of 5-HT(1A) receptor alone by specific agonist (±)-8-Hydroxy-2-(dipropylamino) tetralin (8-OH-DPAT) was insufficient to elicit excitation of VTA DA neurons, but the excitation of 8-OH-DPAT on VTA DA neurons was elicited in the presence of D₂-like receptors antagonist raclopride. Collectively, these results indicate that l-SPD excited VTA DA neurons requiring its D₂-like receptors antagonistic activity and 5-HT(1A) receptor agonistic activity.'] Is l-Stepholidine-induced excitation of dopamine neurons in rat ventral tegmental area associated with its 5-HT ( 1A ) receptor partial agonistic activity?
qiaojin/PubMedQA
2
[ -2.281559467315674, -1.3129568099975586, 2.6154727935791016 ]
['To assess whether certain environmental factors temporally associated with the onset of juvenile idiopathic inflammatory myopathies (JIIMs) differ between phenotypes.', 'Physicians completed questionnaires regarding documented infections, medications, immunizations and an open-ended question about other noted exposures within 6 months before illness onset for 285 patients with probable or definite JIIM. Medical records were reviewed for 81% of the patients. Phenotypes were defined by standard clinical and laboratory measures.', 'Sixty per cent of JIIM patients had a reported exposure within 6 months before illness onset. Most patients (62%) had one recorded exposure, 26% had two and 12% had three to five exposures. Patients older than the median age at diagnosis, those with a longer delay to diagnosis and those with anti-signal recognition particle autoantibodies had a higher frequency of documented exposures [odds ratios (ORs) 95% CI 3.4, 31]. Infections were the most common exposure and represented 44% of the total number of reported exposures. Non-infectious exposures included medications (18%), immunizations (11%), stressful life events (11%) and unusual sun exposure (7%). Exposures varied by age at diagnosis, race, disease course and the presence of certain myositis autoantibodies.'] Do environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies?
qiaojin/PubMedQA
2
[ -2.165248394012451, -0.05094033107161522, 1.2828056812286377 ]
['The appearance of acetabular version differs between the supine and weight bearing positions in developmental dysplasia of the hip. Weight bearing radiographic evaluation has been recommended to ensure the best coherence between symptoms, functional appearance, and hip deformities. Previous prevalence estimates of acetabular retroversion in dysplastic hips have been established in radiographs recorded with the patient supine and with inclusion only if pelvic tilt met standardized criteria. We assessed the prevalence and the extent of acetabular retroversion in dysplastic hip joints in weight bearing pelvic radiographs.', 'We assessed 95 dysplastic hip joints (54 patients) in weight bearing anteroposterior pelvic radiographs, measuring the acetabular height and the distance from the acetabular roof to the point of crossing of the acetabular rims, if present.', 'Acetabular retroversion was found in 31 of 95 dysplastic hip joints. In 28 of 31 hip joints with retroversion, crossover of the acetabular rims was positioned within the cranial 30% sector. The degree of pelvic tilt differed between retroverted and non-retroverted dysplastic hip joints, though only reaching a statistically significant level in male dysplastic hip joints.'] Is cranial acetabular retroversion common in developmental dysplasia of the hip as assessed by the weight bearing position?
qiaojin/PubMedQA
2
[ -2.1548056602478027, -1.2761201858520508, 2.544518232345581 ]
['There is no standard for patient triage in total knee arthroplasty (TKA) based on joint functional characteristics. This is largely due to the lack of objective postoperative measurement of success in TKA in terms of function and longevity, and the lack of knowledge of preoperative metrics that influence outcome. We examined the association between the preoperative mechanical environment of the patients knee joint during gait and the post-TKA stability of the tibial component as measured with radiostereometric analysis (RSA).', '37 subjects were recruited out of a larger randomized RSA trial. 3-dimensional gait analysis was performed in the preoperative week. Longitudinal RSA data were gathered postoperatively at 6 months and 1 year.', 'We found a statistically significant association between the pattern of the knee adduction moment during gait preoperatively and the total migration of the implant at 6 months postoperatively. A substantial proportion of the variability in the total postoperative tibial component migration (R(2) = 0.45) was explained by a combination of implant type, preoperative knee joint loading patterns during gait, and body mass index at 6 months postoperatively. The relationships did not remain statistically significant at 1 year postoperatively.'] Are preoperative gait patterns and BMI associated with tibial component migration?
qiaojin/PubMedQA
2
[ -1.8170645236968994, -1.350570797920227, 2.2021846771240234 ]
['Let-7a, a molecule that is reduced in various cancers, has been associated with cell growth and proliferation. Upregulation of let-7a may inhibit tumor cell growth. To verify this hypothesis, let-7a gene overexpression was studied in gastric cancer cells in vitro and in vivo.', 'A lentiviral system harboring both enhanced green fluorescent protein reporter gene and the let-7a short hairpin RNA expression cassette was firstly constructed. Then the stable let-7a gene overexpression SGC-7901 cells were established and real-time RT-PCR analysis was used to evaluate the expression of the let-7a gene. Their growth-inhibiting, cell cycle arrest characteristics were identified.', 'In SGC-7901/let-7a cells, let-7a expression was significantly increased. Their proliferation was obviously retarded and the cell cycle changed with increased G0/G1 arrest and decreased S phase. In animal experiments, SGC-7901/let-7a cell xenografts demonstrated growth suppression compared to parental or control gastric cancer cell xenografts.'] Does lentiviral vector-mediated upregulation of let-7a inhibit gastric carcinoma cell growth in vitro and in vivo?
qiaojin/PubMedQA
2
[ -2.4280600547790527, -1.221186637878418, 2.6930136680603027 ]
['There is no standardized treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus. We previously reported the efficacy of interferon-alpha and 5-fluorouracil combination (IFN/5-FU) therapy for these patients and the potential mechanism via the regulation of vascular endothelial growth factor (VEGF). In this study, we showed the VEGF-related effects of IFN/5-FU therapy using VEGF-receptor (VEGFR) selective inhibitor, PTK787/ZK222584 (PTK/ZK), in HCC cells.', 'Using two VEGF secreting and VEGFR expressing human HCC cell lines, PLC/PRF/5 and HuH7, we performed growth inhibitory assays in vitro and in vivo, apoptosis assay, cell cycle analysis, and Western blot analysis for the mechanism, with or without PTK/ZK in IFN/5-FU therapy.', 'The combination of PTK/ZK and IFN/5-FU significantly inhibited cell growth in vitro and tended to reduce tumor growth in vivo in a HuH7 xenograft model in nude mice-in both cases without affecting VEGF secretion. PTK/ZK enhanced the IFN/5-FU induced apoptosis, based on increased proteins levels of Bax and reduced Bcl-xL and Bcl-2. Cell cycle analysis showed different results between the HCC cell lines following the combination therapy, possibly due to differences in p21 protein.'] Does tyrosine kinase inhibitor PTK/ZK enhance the antitumor effects of interferon-α/5-fluorouracil therapy for hepatocellular carcinoma cells?
qiaojin/PubMedQA
2
[ -2.3902196884155273, -1.3890399932861328, 2.800055980682373 ]
['Emergency department resuscitation plays a significant role in sepsis care, and it is unknown if patient outcomes vary by institution based on the level of sepsis experience of the emergency department. This study examines whether there is an association between the annual volume of patients admitted via the emergency department with sepsis and inpatient mortality.', 'Cross-sectional analysis of the 2007 Nationwide Inpatient Sample.', 'We included 87,166 adult emergency department sepsis admissions from 551 hospitals.', 'Hospitals were categorized into quartiles by 2007 emergency department sepsis volume. Univariate associations of patient characteristics, hospital characteristics, and inpatient mortality with sepsis volume level were evaluated by chi-square test. A population-averaged logistic regression model of inpatient mortality was used to estimate the effects of age, gender, comorbid conditions, payer status, median zip code income, hospital bed size, teaching status, and emergency department sepsis volume.', 'Overall inpatient sepsis mortality was 18.0% and early mortality (2 days after admission) was 6.9%. The risk-adjusted odds ratios of mortality were 0.73 (95% confidence interval, 0.64-0.83; p < .001) in quartile 4 (highest volume), 0.83 in quartile 3 (95% confidence interval, 0.74-0.93; p = .001), and 0.90 in quartile 2 (95% confidence interval, 0.82-0.99; p < .05) when compared to quartile 1 (lowest volume). Adjusted results were similar for early mortality: 0.69 (95% confidence interval, 0.61-0.76; p < .001) in quartile 4, 0.83 in quartile 3 (95% confidence interval, 0.74-0.93; p < .05), and 0.85 in quartile 2 (95% confidence interval, 0.77-0.94; p < .05) when compared to quartile 1.'] Is volume of emergency department admissions for sepsis related to inpatient mortality : results of a nationwide cross-sectional analysis?
qiaojin/PubMedQA
2
[ 0.2693061828613281, -1.47855544090271, 0.3617524206638336 ]
['Chicken Mx belongs to the Mx family of interferon-induced dynamin-like GTPases, which in some species possess potent antiviral properties. Conflicting data exist for the antiviral capability of chicken Mx. Reports of anti-influenza activity of alleles encoding an Asn631 polymorphism have not been supported by subsequent studies. The normal cytoplasmic localisation of chicken Mx may influence its antiviral capacity. Here we report further studies to determine the antiviral potential of chicken Mx against Newcastle disease virus (NDV), an economically important cytoplasmic RNA virus of chickens, and Thogoto virus, an orthomyxovirus known to be exquisitely sensitive to the cytoplasmic MxA protein from humans. We also report the consequences of re-locating chicken Mx to the nucleus.', 'Chicken Mx was tested in virus infection assays using NDV. Neither the Asn631 nor Ser631 Mx alleles (when transfected into 293T cells) showed inhibition of virus-directed gene expression when the cells were subsequently infected with NDV. Human MxA however did show significant inhibition of NDV-directed gene expression. Chicken Mx failed to inhibit a Thogoto virus (THOV) minireplicon system in which the cytoplasmic human MxA protein showed potent and specific inhibition. Relocalisation of chicken Mx to the nucleus was achieved by inserting the Simian Virus 40 large T antigen nuclear localisation sequence (SV40 NLS) at the N-terminus of chicken Mx. Nuclear re-localised chicken Mx did not inhibit influenza (A/PR/8/34) gene expression during virus infection in cell culture or influenza polymerase activity in A/PR/8/34 or A/Turkey/50-92/91 minireplicon systems.'] Is the cytoplasmic location of chicken mx the determining factor for its lack of antiviral activity?
qiaojin/PubMedQA
2
[ -2.262709379196167, -1.3778879642486572, 2.7032177448272705 ]
['Isotretinoin treatment causes hypertriglyceridaemia. Insulin resistance is also associated with hypertriglyceridaemia. It is not known if isotretinoin is related to insulin resistance.', 'To test this hypothesis, we measured insulin resistance in 48 patients with acne vulgaris (AV) before and after 3 months of isotretinoin treatment.', 'In total, 48 patients with AV who attended the dermatology outpatient clinic at Kecioren Research and Training Hospital were included. Screening for biochemical parameters was performed just before the start of treatment (pretreatment) and after 4 months of isotretinoin therapy (post-treatment). The parameters measured were insulin, C peptide, fasting blood glucose, aspartate and alanine aminotransferases (AST, ALT), total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and very low-density lipoprotein cholesterol. Insulin resistance was measured using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) method.', 'Compared with initial values, AST, ALT, TC, LDL-C and triglyceride levels were significantly increased (P < 0.01, < 0.05, < 0.01, < 0.05 and < 0.01, respectively), but there was no significant change in fasting blood glucose, insulin, C-peptide levels or HOMA-IR.'] Does isotretinoin induce insulin resistance in patients with acne?
qiaojin/PubMedQA
2
[ -2.093165636062622, -1.4070849418640137, 2.539635181427002 ]
['Dermal papilla cells (DPCs) are specialized fibroblasts found in the hair follicle papilla, which are associated with the development and cycle regulation of hair follicles (HFs). DPCs exhibit a multilayer aggregative growth character, which is closely related to induction of HF formation. Versican, a large chondroitin sulphate proteoglycan and one of the major components of the extracellular matrix, is involved in the formation of HF.', 'To confirm the relationship between versican and the aggregative growth of DPCs, we first induced and established an aggregative cell model in DPCs in vitro, with cells taken to passage 8. Simultaneously, aggregative passage 2 DPCs and nonaggregative passage 8 DPCs were selected as parallel controls. RNA interference (RNAi) targeted to versican was used in passage 2 DPCs using a lentiviral vector. Reverse transcriptase (RT)-PCR and western blotting were used to assay the expression of versican in DPCs.', 'RNAi targeted to versican efficiently suppressed the aggregative growth of passage 2 DPCs, and the inhibitory effect was significant 3 days after RNAi treatment. The mRNA and protein levels of versican were also downregulated in passage 2 DPCs, and were lower than levels in nonaggregative passage 8 DPCs. Notably, the aggregative growth of nonaggregative passage 8 DPCs was restored after induction in a 1 : 1 v/v mixture of fresh DMEM and medium recycled from a previous passage.'] Does versican targeting by RNA interference suppress aggregative growth of dermal papilla cells?
qiaojin/PubMedQA
2
[ -2.3866684436798096, -1.3258936405181885, 2.70904803276062 ]
['In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents.', 'Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment.', 'Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034).'] Do extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma?
qiaojin/PubMedQA
2
[ -1.6208773851394653, -1.5527675151824951, 2.191176414489746 ]
['The development of an HIV/AIDS vaccine has proven to be elusive. Because human vaccine trials have not yet demonstrated efficacy, new vaccine strategies are needed for the HIV vaccine pipeline. We have been developing a new HIV vaccine platform using a live enterovirus, coxsackievirus B4 (CVB4) vector. Enteroviruses are ideal candidates for development as a vaccine vector for oral delivery, because these viruses normally enter the body via the oral route and survive the acidic environment of the stomach.', 'We constructed a live coxsackievirus B4 recombinant, CVB4/p24(73(3)), that expresses seventy-three amino acids of the gag p24 sequence (HXB2) and assessed T cell responses after immunization of mice. The CVB4 recombinant was physically stable, replication-competent, and genetically stable. Oral or intraperitoneal immunization with the recombinant resulted in strong systemic gag p24-specific T cell responses as determined by the IFN-gamma ELISPOT assay and by multiparameter flow cytometry. Oral immunization with CVB4/p24(73(3)) resulted in a short-lived, localized infection of the gut without systemic spread. Because coxsackieviruses are ubiquitous in the human population, we also evaluated whether the recombinant was able to induce gag p24-specific T cell responses in mice pre-immunized with the CVB4 vector. We showed that oral immunization with CVB4/p24(73(3)) induced gag p24-specific immune responses in vector-immune mice.'] Does oral immunization with a live coxsackievirus/HIV recombinant induce gag p24-specific T cell responses?
qiaojin/PubMedQA
2
[ -2.259626865386963, -1.2118170261383057, 2.5848212242126465 ]
['This exploratory study examines the role of psychosocial-behavioral variables as predictors of elevated corticotropin-releasing hormone (CRH) at 14-20 weeks of gestation.', 'One hundred and twenty women were enrolled into the study. Blood samples were collected at 14-20 weeks of pregnancy and assayed for CRH. Participants completed questionnaires that included the Perceived Stress Scale, the Center for Epidemiologic Studies (CES) Depression Scale, the Pregnancy-Specific Anxiety (PAS) Scale, the Norbeck Social Support Questionnaire, the Life Orientation Test, the Brief COPE scale, and questions regarding violence/abuse, and work, sleep, and nutritional patterns.', "Pregnant women with high CRH levels (15 pcg/ml and above) perceived their income to be inadequate, slept more hours at night, stood more hours during the day, and used the coping styles of disengagement or religion but not humor. Logistic regression identified three predictors for high CRH (accounting for 42.2% of the variance): perceived inadequacy of income and the use of ''religion'' and ''disengagement'' to cope with stress."] Do maternal coping style and perceived adequacy of income predict CRH levels at 14-20 weeks of gestation?
qiaojin/PubMedQA
2
[ -2.2850229740142822, -0.6596612334251404, 1.985757827758789 ]
['Allergen sensitization and airway hyperresponsiveness (AHR) are the most important characteristics of bronchial asthma and their correlation has been speculated.', 'We attempted to investigate the relationship between sensitization to allergens and AHR to methacholine in Korean high school students.', 'A questionnaire survey, methacholine bronchial provocation tests, and skin-prick tests for 16 major allergens were performed on 724 students. The mean age of participants was 15.79 ± 0.40 years old. Serum total immunoglobulin E (IgE) and the fraction of blood eosinophils were measured.', 'AHR (PC(20) < 16 mg/ml) was present in 12.3%. Log total IgE was higher in AHR-positive group than negative group (4.22 ± 1.55, 3.70 ± 1.33, P = 0.001). Three hundred eighty-four students (53.0%) were sensitized to more than one allergen, and among them Dermatophagoides pteronyssinus (Der p, 295 students, 40.7%) and Dermatophagoides farinae (Der f, 301 students, 41.6%) were most common. The risk of AHR development was high in the group who had sensitization to one allergen (adjusted odds ratio [aOR] = 1.97, 95% confidence interval [CI]: 1.13-3.44, P = 0.018) and to more than two allergens (aOR = 2.94, 95% CI: 1.32-6.57, P = 0.009). Among the specific allergens, AHR was developed in those who were sensitized to Der f (aOR = 1.73, 95% CI: 1.04-2.86, P = 0.033), dog dander (aOR = 3.97, 95% CI: 1.67-9.51, P = 0.002), and Alternaria (aOR = 3.19, 95% CI: 1.24-6.41, P = 0.016). In the groups with high IgE (>300 IU/ml) and high eosinophil fraction (>4%), AHR was more developed than groups who were low in each (aOR = 2.73, 95% CI: 1.15-6.51, P = 0.023; aOR = 10.82, 95% CI: 3.33-35.08, P = 0.001).'] Is airway hyperresponsiveness associated with total serum immunoglobulin E and sensitization to aeroallergens in Korean adolescents?
qiaojin/PubMedQA
2
[ -0.9388568997383118, -1.698894739151001, 1.596381664276123 ]
['Plasma cells constitute the majority of tumor cells in multiple myeloma (MM) but lack the potential for sustained clonogenic growth. In contrast, clonotypic B cells can engraft and recapitulate disease in immunodeficient mice suggesting they serve as the MM cancer stem cell (CSC). These tumor initiating B cells also share functional features with normal stem cells such as drug resistance and self-renewal potential. Therefore, the cellular processes that regulate normal stem cells may serve as therapeutic targets in MM. Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC. Moreover, we carried out both long and short-term inhibition studies to examine telomere length-dependent and independent activities.', 'Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. In addition to these relatively long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth that was associated with MM CSC differentiation based on expression of the plasma cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term treatment of MM CSC also decreased the expression of genes typically expressed by stem cells (OCT3/4, SOX2, NANOG, and BMI1) as revealed by quantitative real-time PCR.'] Does telomerase inhibition target clonogenic multiple myeloma cells through telomere length-dependent and independent mechanisms?
qiaojin/PubMedQA
2
[ -2.439943552017212, -1.27186119556427, 2.7367684841156006 ]
['Recent evidence indicates that infant faces capture attention automatically, presumably to elicit caregiving behavior from adults and leading to greater probability of progeny survival. Elsewhere, evidence demonstrates that people show deficiencies in the processing of other-race relative to own-race faces. We ask whether this other-race effect impacts on attentional attraction to infant faces. Using a dot-probe task to reveal the spatial allocation of attention, we investigate whether other-race infants capture attention.', 'South Asian and White participants (young adults aged 18-23 years) responded to a probe shape appearing in a location previously occupied by either an infant face or an adult face; across trials, the race (South Asian/White) of the faces was manipulated. Results indicated that participants were faster to respond to probes that appeared in the same location as infant faces than adult faces, but only on own-race trials.'] Does attentional prioritization of infant face is limited to own-race infants?
qiaojin/PubMedQA
1
[ -2.457195520401001, 1.286543607711792, 0.30373287200927734 ]
['A femoral implant with a modular sleeve and stem has been designed to allow independent and complete metaphyseal-diaphyseal fit and fill as well as independent rotation to accommodate anteversion at the time of THA.', 'In a prospective study we asked whether such a modular femoral sleeve and stem implant used during THA could provide (1) high long-term survivorship; (2) radiographically stable implants without radiolucencies, stress shielding, or osteolysis; and (3) high clinical scores in patients 15 to 20 years after a primary THA.', 'We prospectively evaluated 31 hips that underwent a primary THA using a modular femoral component for clinical outcome (Harris hip score) and radiographic outcome (implant stability, femoral loosening, osteolysis and stress shielding) at a minimum followup of 15 years (mean, 17 years; range, 15-20.2 years).', 'There were no femoral revisions for aseptic loosening; all hips had radiographic evidence of bone ingrowth. Two well-ingrown components were revised for late hematogenous infection. Some degree of proximal femoral disuse atrophy from stress shielding occurred in 23 hips (74%) but was nonprogressive and did not result in any failures or complications. Femoral osteolysis occurred in 18 hips (58%), but we cannot definitively determine whether or not the modular junction contributed to this.'] Do modular femoral sleeve and stem implant provides long-term total hip survivorship?
qiaojin/PubMedQA
2
[ -2.405959367752075, -1.027288556098938, 2.567403793334961 ]
['Our objective was to report a single-center experience of the management of pituitary tumor apoplexy.', 'We retrospectively analyzed a series of 44 patients hospitalized for pituitary apoplexy between January 1996 and March 2008 at the Timone Hospital, Marseille, France.', "Most frequent presenting symptoms were headaches (93%), visual impairment (85%) and vomiting (59%). Hypopituitarism was present at diagnosis in 88% of patients, with a high incidence of corticotroph deficiency (70%). A risk factor was found in 52% of patients, mostly hypertension. Apoplexy occurred in a previously undiagnosed pituitary adenoma in 32/44 cases (73%). The apoplectic event concerned 12 secreting, 27 non-functioning, 4 uncharacterized adenomas and one Rathke's pouch cyst. Nineteen patients underwent surgery within the first month, and one patient had conventional radiotherapy. Twenty-four patients, who had no ophthalmic or neurological signs, were conservatively treated in first intention; among them, 6 received high dose corticosteroids. After a median follow-up of 21 months, there was no significant difference in terms of endocrine or visual recovery between the operated and the conservatively treated groups, nor between patients treated with corticosteroids or not. Panhypopituitarism was observed in 52% of patients, but partial or complete visual recovery was present in the majority of patients (91%), whatever the therapeutic approach."] Is a conservative management preferable in milder forms of pituitary tumor apoplexy?
qiaojin/PubMedQA
2
[ -2.3165152072906494, -1.1459039449691772, 2.4985971450805664 ]
['Recent studies suggest that stress can predispose an individual to the development of periodontal disease, but the exact biological mechanism is unknown. Considering that psychological stress can down-regulate the production of β-defensins (antimicrobial peptides produced in the oral cavity), the aim of the present study was to evaluate the association between stress and salivary levels of β-defensin 2 (HBD-2) and β-defensin 3 (HBD-3).', 'For this purpose, seventy five volunteers, classified as periodontally healthy, were submitted to a psychological evaluation using a validated questionnaire (Questionnaire of Lipp-ISS). Following analysis of the questionnaires, the subjects were divided in two groups (Group A: Absence of stress and Group B: Presence of stress). Unstimulated saliva samples were collected and the concentration of total protein was determined using the BCA method, and the concentrations of HBD-2 and HBD-3 were determined by ELISA.', 'The levels of total protein did not show a statistically significant difference between the groups. Analyses of HBD-2 and HBD-3 concentrations indicate that the stress condition was not associated with the levels of either peptide in saliva (P=0.3664 for HBD-2 and P=0.3608 for HBD-3).'] Does psychological stress have no association with salivary levels of β-defensin 2 and β-defensin 3?
qiaojin/PubMedQA
2
[ -2.0159013271331787, -1.3058098554611206, 2.3566370010375977 ]
['Mechanoreceptors to the internal anal sphincter (IAS) contribute to continence and normal defecation, yet relatively little is known about their function or morphology. We investigated the function and structure of mechanoreceptors to the guinea pig IAS.', 'Extracellular recordings from rectal nerve branches to the IAS in vitro, combined with anterograde labeling of recorded nerve trunks, were used to characterize extrinsic afferent nerve endings activated by circumferential distension.', 'Slowly adapting, stretch-sensitive afferents were recorded in rectal nerves to the IAS. Ten of 11 were silent under basal conditions and responded to circumferential stretch in a saturating linear manner. Rectal nerve afferents responded to compression with von Frey hairs with low thresholds (0.3-0.5 mN) and 3.4 ± 0.5 discrete, elongated mechanosensitive fields of innervation aligned parallel to circular muscle bundles (length = 62 ± 16 mm, n = 10). Anterogradely labeled rectal nerve axons typically passed through sparse irregular myenteric ganglia adjacent to the IAS, before ending in extensive varicose arrays within the circular muscle and, to a lesser extent, the longitudinal muscle overlying the IAS. Few (8%) IAS myenteric ganglia contained intraganglionic laminar endings. In eight preparations, mechanotransduction sites were mapped in combination with successful anterograde fills. Mechanotransduction sites were strongly associated with extensive fine varicose arrays within the circular muscle (P < 0.05), and not with any other neural structures.'] Does function and morphology correlate of rectal nerve mechanoreceptors innervating the guinea pig internal anal sphincter?
qiaojin/PubMedQA
2
[ -2.3643290996551514, -1.3830385208129883, 2.8162612915039062 ]
['Toll-like receptor (TLR) signaling has been found to be closely associated with tumor development. The aim of this study was to examine whether activation of TLRs promote migration and invasion of salivary gland adenocarcinoma.', 'TLR expression in SGT and HSG cells was examined by RT-PCR. Wound scratch and chemotaxis cell migration assay were performed. Invasiveness was determined by Matrigel invasion assay.', 'All the tested TLRs including TLR1, TLR2, TLR4, and TLR5 and myeloid differentiation factor-2 (MD-2) were expressed on SGT and HSG cells. Treatment of flagellin, but not Pam(3) CSK(4) and LPS, led to the production of IL-6 and IL-8, suggesting TLR5 is functional in both cells. Stimulation by flagellin also accelerated wound closure of SGT and HSG cells in a dose-dependent manner. In addition, flagellin promoted migration and invasion ability of SGT cells. Blocking of TLR5 using antibody restored the promoting effect of flagellin on migration and invasion of SGT cells.'] Does toll-like receptor 5 activation promote migration and invasion of salivary gland adenocarcinoma?
qiaojin/PubMedQA
2
[ -2.4027950763702393, -1.2544078826904297, 2.7346372604370117 ]
['Multipotent mesenchymal stromal cells suppress T-cell function in vitro, a property that has underpinned their use in treating clinical steroid-refractory graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. However the potential of mesenchymal stromal cells to resolve graft-versus-host disease is confounded by a paucity of pre-clinical data delineating their immunomodulatory effects in vivo.', 'We examined the influence of timing and dose of donor-derived mesenchymal stromal cells on the kinetics of graft-versus-host disease in two murine models of graft-versus-host disease (major histocompatibility complex-mismatched: UBI-GFP/BL6 [H-2(b)]→BALB/c [H-2(d)] and the sibling transplant mimic, UBI-GFP/BL6 [H-2(b)]→BALB.B [H-2(b)]) using clinically relevant conditioning regimens. We also examined the effect of mesenchymal stromal cell infusion on bone marrow and spleen cellular composition and cytokine secretion in transplant recipients.', 'Despite T-cell suppression in vitro, mesenchymal stromal cells delayed but did not prevent graft-versus-host disease in the major histocompatibility complex-mismatched model. In the sibling transplant model, however, 30% of mesenchymal stromal cell-treated mice did not develop graft-versus-host disease. The timing of administration and dose of the mesenchymal stromal cells influenced their effectiveness in attenuating graft-versus-host disease, such that a low dose of mesenchymal stromal cells administered early was more effective than a high dose of mesenchymal stromal cells given late. Compared to control-treated mice, mesenchymal stromal cell-treated mice had significant reductions in serum and splenic interferon-γ, an important mediator of graft-versus-host disease.'] Do mesenchymal stromal cells transiently alter the inflammatory milieu post-transplant to delay graft-versus-host disease?
qiaojin/PubMedQA
2
[ -2.33150315284729, -1.4085795879364014, 2.7655904293060303 ]
['With the advent of prostate-specific antigen (PSA) screening and the increase in the number of transrectal ultrasound-guided biopsy cores, there has been a dramatic rise in the incidence of low-risk prostate cancer (LRPC). Because > 97% of men with LRPC are likely to die of something other than prostate cancer, it is critical that patients give thought to whether early curative treatment is the only option at diagnosis.', 'To identify a group of men with LRPC who may not require initial treatment and monitor them on our active surveillance (AS) protocol, to determine the percentage treated and the outcome and to analyze the quality-of-life data.', 'We defined patients eligible for AS as Gleason ≤ 6, PSA ≤ 10, and two or fewer biopsy cores with ≤ 20% tumor in each core.', 'Kaplan Meier analysis was used to predict the 5-year treatment free survival. Logistic regression determined the predictors of treatment. Data on sexual function, continence, and outcome were obtained and analyzed.'] Does careful selection and close monitoring of low-risk prostate cancer patients on active surveillance minimize the need for treatment?
qiaojin/PubMedQA
2
[ -2.7587742805480957, -0.23425447940826416, 2.072032928466797 ]
['Early life stress is a risk factor for the development of psychopathology in later life. Consequences of adverse life events, however, may depend on the genetic makeup of an individual. Reduced serotonin(1A) receptor function may predispose to the development of anxiety disorders.', 'Determine susceptibility of serotonin(1A) receptor knockout (1AKO) mice on different background strains to the effects of maternal separation (MS) by assessing startle plasticity in adulthood.', '1AKO mice on a 129S6 and a Swiss Webster (SW) background were used. MS groups were separated daily from their mother for 180 min/day from postnatal days 2 to 14. Control groups underwent normal animal facility rearing. In adulthood, effects on acoustic startle response, habituation, prepulse inhibition (PPI), and foot shock sensitization were determined.', 'MS increased startle reactivity and reduced PPI in 129S6 mice. These effects of MS were independent of genotype. MS had no effect on the other readouts. In SW mice, MS had no consistent effect on startle reactivity and did not alter startle plasticity in wild type or in 1AKO mice. 1AKO mice did not differ from wild-type mice in startle plasticity.'] Does serotonin1A receptor deletion interact with maternal separation-induced increases in startle reactivity and prepulse inhibition deficits?
qiaojin/PubMedQA
2
[ -2.3508265018463135, -1.1667237281799316, 2.5362250804901123 ]
['To compare the effects of commercially sold menthol (3.5%) ointment and cold application on blood flow in the forearm.', ': Prospective counterbalanced design.', 'University research laboratory.', 'Twelve (6 men and 6 women) college-aged students.', 'Each participant had blood flow measured in the brachial artery for 5 minutes before and 10 minutes after menthol ointment or cold application to the forearm.', 'Blood velocity, arterial diameter size, and blood pressure were recorded during testing procedures. Vascular conductance was calculated based on these measures and used to describe limb blood flow.', 'We observed a significant reduction (35%; P = 0.004) in vascular conductance within 60 seconds of menthol and cold application to the forearm. Vascular conductance remained significantly reduced for 10 minutes by approximately 19% after both menthol and cold application [F(2.313, 43.594) = 10.328, P < 0.0001]. There was no significant difference between conditions [F(1, 19) = 0.000, P = 0.945].'] Is vascular conductance reduced after menthol or cold application?
qiaojin/PubMedQA
2
[ -0.582622766494751, -1.374799370765686, 1.095855951309204 ]
['Recent studies have suggested that Salmonella Typhimurium strains associated with mortality in UK garden birds are significantly different from strains that cause disease in humans and livestock and that wild bird strains may be host adapted. However, without further genomic characterization of these strains, it is not possible to determine whether they are host adapted. The aim of this study was to characterize a representative sample of Salm. Typhimurium strains detected in wild garden birds using multi-locus sequence typing (MLST)to investigate evolutionary relationships between them.', 'Multi-locus sequence typing was performed on nine Salm. Typhimurium strains isolated from wild garden birds. Two sequence types were identified, the most common of which was ST568. Examination of the public Salmonella enterica MLST database revealed that only three other ST568 isolates had been cultured from a human in Scotland. Two further isolates of Salm. Typhimurium were determined to be ST19.'] Does multi-locus sequence typing of Salmonella enterica serovar Typhimurium isolates from wild birds in northern England suggest host-adapted strain?
qiaojin/PubMedQA
2
[ -1.958116888999939, -0.3552718162536621, 1.4834504127502441 ]
['Endothelial gene silencing via small interfering RNA (siRNA) transfection represents a promising strategy for the control of vascular disease. Here, we demonstrate endothelial gene silencing in human saphenous vein using three rapid siRNA transfection techniques amenable for use in the operating room.', 'Control siRNA, Cy5 siRNA, or siRNA targeting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or endothelial specific nitric oxide synthase (eNOS) were applied to surplus human saphenous vein for 10 minutes by (i) soaking, (ii) applying 300 mm Hg hyperbaric pressure, or (iii) 120 mm Hg luminal distending pressure. Transfected vein segments were maintained in organ culture. siRNA delivery and gene silencing were assessed by tissue layer using confocal microscopy and immunohistochemistry.', 'Distending pressure transfection yielded the highest levels of endothelial siRNA delivery (22% pixels fluorescing) and gene silencing (60% GAPDH knockdown, 55% eNOS knockdown) as compared with hyperbaric (12% pixels fluorescing, 36% GAPDH knockdown, 30% eNOS knockdown) or non-pressurized transfections (10% pixels fluorescing, 30% GAPDH knockdown, 25% eNOS knockdown). Cumulative endothelial siRNA delivery (16% pixels fluorescing) and gene silencing (46% GAPDH knockdown) exceeded levels achieved in the media/adventitia (8% pixels fluorescing, 24% GAPDH knockdown) across all transfection methods.'] Are endothelial cells susceptible to rapid siRNA transfection and gene silencing ex vivo?
qiaojin/PubMedQA
2
[ -2.2208120822906494, -1.4732645750045776, 2.761669874191284 ]
['Chronic visceral pain is frequent, extremely debilitating, and generally resistant to pharmacological treatment. It has been shown that chronic visceral inflammation, through altered afferent visceral sensory input, leads to plastic changes in the central nervous system that ultimately sustain pain. Therefore approaches aiming at modulation of brain activity are attractive candidates to control visceral pain.', 'Here we report findings of a phase II, sham-controlled clinical trial assessing the clinical effects and brain metabolic correlates of a 10-day course of daily sessions of slow-frequency, repetitive transcranial magnetic stimulation (rTMS) targeting the right secondary somatosensory cortex (SII) in patients with chronic pancreatitis and severe visceral pain.', 'Our results show a significant reduction in pain after real rTMS that lasted for at least 3 weeks following treatment. These clinical changes were correlated with increases in glutamate and N-acetyl aspartate (NAA) levels--neurometabolites associated with cortical activity and brain damage--as measured by in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS). Adverse effects in the real rTMS group were mild and short-lasting.'] Does clinical effects and brain metabolic correlate in non-invasive cortical neuromodulation for visceral pain?
qiaojin/PubMedQA
2
[ -2.590125560760498, -1.1384742259979248, 2.8279201984405518 ]
['Aging is associated with progressive loss of muscle strength. Muscle tissue is vascularized by an elaborate vascular network. There is evidence that blood pressure (BP) is associated with muscle function in middle age. It is unknown how BP associates with muscle function in oldest old people. We studied the association between BP and handgrip strength in middle and old age.', 'BP was measured automatically in middle-aged subjects and with a mercury sphygmomanometer in the oldest old. Handgrip strength was measured with a handgrip strength dynamometer. Cross-sectional measurements of handgrip strength and BP were available for 670 middle-aged subjects (mean 63.2 ± 6.6 years) and 550 oldest old subjects (all 85 years). Prospective data were available for oldest old subjects only with a 4-year follow-up at 89 years. The association between BP and handgrip strength was analyzed by linear regression analysis.', 'In middle-aged subjects, BP and handgrip strength were not statistically significantly associated. In oldest old subjects, higher systolic BP (SBP), mean arterial pressure (MAP), and pulse pressure (PP) were associated with higher handgrip strength after adjusting for comorbidity and medication use (all P < 0.02). Furthermore, in oldest old subjects, changes in SBP, MAP, and PP after 4 years was associated with declining handgrip strength (all, P < 0.05).'] Is higher blood pressure associated with higher handgrip strength in the oldest old?
qiaojin/PubMedQA
2
[ -1.4590314626693726, -1.2898914813995361, 1.8577954769134521 ]
['Extracts of Andrographis paniculata Nees are used for various ethnomedical conditions including hyperglycemia and hypertension complications.', 'The purpose of this study is to evaluate the anti-diabetic nephropathy effect of diterpene lactones andrographolide (AP1) and 14-deoxy-11,12-didehydroandrographolide (AP2) from Andrographis paniculata.', 'MES-13, a SV40-transformed murine glomerular mesangial cell line, was cultured in high concentration of glucose to induce diabetic nephropathy phenotypes, which include secretion of extracellular matrix protein fibronectin, cytokine TGF-β, states of oxidative stress, and apoptosis marker caspase-3.', 'Our data suggest that addition of compounds AP1 or AP2 reduces the phenotypes indicating diabetic nephropathy in MES-13 cells. The compound AP2 showed potent activity than AP1 in the reduction of apoptosis marker caspase-3, fibrosis marker TGF-β, and PAI-1. Furthermore, AP1 and AP2 do not have antioxidant ability in acellular environment; however, addition of AP1 and AP2 reduced intracellular oxidative states in high glucose cultured MES-13 cells.'] Do andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines?
qiaojin/PubMedQA
2
[ -2.453562021255493, -1.296091079711914, 2.759404420852661 ]
['Hepatocytes in primary culture undergo apoptosis upon exposure to glycochenodeoxycholate (GCDC). The signaling mechanisms of GCDC-induced apoptosis remain unclear. To investigate the role of antiapoptotic genes, we compared apoptotic response in primary hepatocytes following GCDC treatment. The hepatocytes from adult Sprague-Dawley rats were cultured in collagen-coated dishes and treated with GCDC in varying concentrations, or the same concentration at different time intervals. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, DNA fragmentation assay, and caspase assays. Expression of apoptosis-related genes and proteins was evaluated by RT-PCR, quantitative real-time PCR (qRT-PCR), and Western blotting, respectively. The DNA-binding property of a nuclear protein was assessed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay. An interesting result was that GCDC caused hepatocyte apoptosis to display a biphasic phenomenon at a dosage of 50μM, whereas it was not found at higher dosages such as 200μM. GCDC stimulated the expression of antiapoptotic Survivin, which also presented a biphasic response. The activation of nuclear factor-kappaB (NF-κB) corresponded with the up-regulation of Survivin. The inhibitor of NF-κB, BAY 11-7082, suppressed the expression of Survivin and simultaneously eliminated the biphasic response. The expression of Survivin was transcriptionally mediated by the activation of NF-κB, as shown by EMSA and ChIP assay.'] Is survivin signaling regulated through nuclear factor-kappa B pathway during glycochenodeoxycholate-induced hepatocyte apoptosis?
qiaojin/PubMedQA
2
[ -2.360804319381714, -1.3933411836624146, 2.7688703536987305 ]
['To determine whether the GABA-containing neurons in rat central nucleus of amygdala (CeA) can be activated by acute sodium deprivation.', 'Acute sodium depletion was induced by subcutaneous injection of furosemide in rats followed by 24 h of dietary sodium deprivation. The rats underwent 0.3 mol/L NaCl/distilled water two bottle choice test, and the activated neurons were labeled and identified with GABA/Fos-double labeling immunohistochemistry.', 'The rats with acute sodium depletion exhibited significantly more numerous c-fos-positive neurons and GABA/Fos double-labeled neurons in the CeA than the control group (P<0.01, P<0.05). Consumption of 0.3 mol/L NaCl significantly increased the number of c-fos and GABA/Fos double labeled neurons compared to the distilled water group (P<0.001, P<0.01).'] Do [ GABAergic neurons in the central nucleus of amygdala modulate sodium appetite in rats ]?
qiaojin/PubMedQA
2
[ -2.1701548099517822, -1.1749491691589355, 2.3892717361450195 ]
['To investigate the role of PKD3 in prostate-specific antigen (PSA) expression regulation in androgen-dependent prostate cancer cells and explore the mechanism.', 'LNCaP cells containing low level of PKD3 were transfected with pEGFP-C2 or pEGFP-PKD3 plasmid followed by dihydrotestosterone (DHT) treatment, and PSA mRNA level was analyzed by RT-QPCR using 2(-delta delta Ct) method. Wild-type or kinase-dead PKD3 plasmids, human androgen receptor plasmid pSVAR0, pMMTV-luc of AR luciferase reporter and renilla luciferase reporter pRL-SV40 were cotransfected into HEK293 cells, and after treatment with DHT for 24 h, the cells were harvested and AR transcriptional activity were determined by dual-luciferase reporter assay. The subcellular localization of endogenous PKD3 and AR and their colocalization induced by DHT were observed by confocal microscopy.', 'PSA mRNA level triggered by DHT was significantly increased by overexpression of pEGFP-PKD3 in LNCaP cells compared with that in pEGFP-C2 control cells (P<0.001). AR transcription in response to DHT treatment was also significantly up-regulated by wild type PKD3 expression (P<0.001), but partially down-regulated by kinase-dead PKD3 mutant (P<0.01). Endogenous PKD3 and AR in LNCaP cells not only translocated from the cytoplasm to the nucleus, but also colocalized with each other after DHT stimulation.'] Does [ PKD3 contribute to up-regulation of prostate-specific antigen in prostate cancer cells ]?
qiaojin/PubMedQA
2
[ -2.255066156387329, -1.4116960763931274, 2.6671640872955322 ]
['To explore the role of protein kinase D3 (PKD3) in the regulation of matrix metalloproteinases 7 (MMP-7) expression in prostate cancer cells.', 'PC-3 cells were either stimulated with 100 nmol/L PMA to activate PKD3 kinase activity, or transiently transfected with PKD3 siRNA, and the relative expression level of MMP-7 mRNA were analyzed by real-time PCR using 2(-delta delta Ct) method. MMP-7 mRNA levels were also analyzed and quantified in HEK293 cells with over-expression of wild-type PKD3, PKD3 knockdown (using PKD3 siRNA), or over-expression of wild-type PKD3 followed by PKD3 knockdown.', 'MMP-7 mRNA expression in PC3 cells was significantly decreased after PMA-induced PKD3 kinase activation. In contrast, PKD3 knockdown by siRNA transfection markedly increased MMP-7 mRNA level (P<0.01). MMP-7 mRNA level in HEK293 cells was significantly decreased by PKD3 over-expression, whereas obviously increased by PKD3 knockdown. Down-regulation of MMP-7 mRNA level in HEK293 induced by PKD3 over-expression was rescued by PKD3 knockdown.'] Is [ Protein kinase D3 involved in negative regulation of MMP-7 in prostate cancer cells ]?
qiaojin/PubMedQA
2
[ -2.367443323135376, -0.7122483849525452, 2.1558690071105957 ]
['We have previously shown that non-psychotropic cannabidiol (CBD) protects retinal neurons in diabetic rats by inhibiting reactive oxygen species and blocking tyrosine nitration. Tyrosine nitration may inhibit glutamine synthetase (GS), causing glutamate accumulation and leading to further neuronal cell death. We propose to test the hypothesis that diabetes-induced glutamate accumulation in the retina is associated with tyrosine nitration of GS and that CBD treatment inhibits this process.', 'Sprague Dawley rats were made diabetic by streptozotocin injection and received either vehicle or CBD (10 mg/kg/2 days). After eight weeks, retinal cell death, Müller cell activation, GS tyrosine nitration, and GS activity were determined.', 'Diabetes causes significant increases in retinal oxidative and nitrative stress compared with controls. These effects were associated with Müller cell activation and dysfunction as well as with impaired GS activity and tyrosine nitration of GS. Cannabidiol treatment reversed these effects. Retinal neuronal death was indicated by numerous terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-labeled cells in diabetic rats compared with untreated controls or CBD-treated rats.'] Does cannabidiol protect retinal neurons by preserving glutamine synthetase activity in diabetes?
qiaojin/PubMedQA
2
[ -2.5611989498138428, -1.1403467655181885, 2.7491660118103027 ]
['Colonoscopy is the accepted gold standard for the detection of colorectal cancer. The aim of the current study was to prospectively compare high definition plus (HD+) colonoscopy with I-Scan functionality (electronic staining) vs. standard video colonoscopy. The primary endpoint was the detection of patients having colon cancer or at least one adenoma.', 'A total of 220 patients due to undergo screening colonoscopy, postpolypectomy surveillance or with a positive occult blood test were randomized in a 1\u200a:\u200a1 ratio to undergo HD+ colonoscopy in conjunction with I-Scan surface enhancement (90i series, Pentax, Tokyo, Japan) or standard video colonoscopy (EC-3870FZK, Pentax). Detected colorectal lesions were judged according to type, location, and size. Lesions were characterized in the HD+ group by using further I-Scan functionality (p- and v-modes) to analyze pattern and vessel architecture. Histology was predicted and biopsies or resections were performed on all identified lesions.', 'HD+ colonoscopy with I-Scan functionality detected significantly more patients with colorectal neoplasia (38\u200a%) compared with standard resolution endoscopy (13\u200a%) (200 patients finally analyzed; 100 per arm). Significantly more neoplastic (adenomatous and cancerous) lesions and more flat adenomas could be detected using high definition endoscopy with surface enhancement. Final histology could be predicted with high accuracy (98.6\u200a%) within the HD+ group.'] Is high definition colonoscopy combined with i-Scan superior in the detection of colorectal neoplasias compared with standard video colonoscopy : a prospective randomized controlled trial?
qiaojin/PubMedQA
2
[ -1.7220252752304077, -1.5729880332946777, 2.3703041076660156 ]
['This study clarified whether detrended fluctuation analysis (DFA) can evaluate how to advance the loss of complexity from impaired glucose tolerance (IGT) through mild diabetes mellitus (DM) to overt DM.', 'Continuous glucose monitoring (CGM) was done during a 48-h interval for 59 subjects from multiple centers. Subjects were divided according to CGM data into those with impaired glucose tolerance (IGT) (n = 20), mild DM (n = 13), and overt DM (n = 26). The short-term (α1) and long-term (α2) range exponentials by DFA were compared among the three groups.', 'The value of α1 within 1h was significantly lower in the IGT group than in either of the other two groups (IGT vs. mild DM vs. overt DM, 1.53 ± 0.22 vs. 1.71 ± 0.17 vs. 1.77 ± 0.13, P<0.0001), and α1 within 2h differed significantly among the three groups (1.49 ± 0.13 vs. 1.57 ± 0.10 vs. 1.72 ± 0.10, P<0.0001). The α1 within 3h was significantly higher in overt DM than in either of the other two groups but did not change between IGT and mild DM (1.44 ± 0.12 vs. 1.52 ± 0.11 vs. 1.67 ± 0.09, P<0.0001). All short-term exponents decreased gradually but significantly as the window widened in all groups (P<0.0001). The α2 over 1h was significantly higher in overt DM but was unchanged in IGT and mild DM (1.22 ± 0.11 vs. 1.27 ± 0.12 vs. 1.36 ± 0.13, P = 0.0010). The α2 over 3h did not differ among the three groups.'] Is detrended fluctuation analysis considered to be useful as a new indicator for short-term glucose complexity?
qiaojin/PubMedQA
2
[ 0.36415743827819824, -1.6166605949401855, 0.40664470195770264 ]
["To ascertain the frequency and geographical distribution of patients diagnosed with known genetic causes of Alzheimer's disease (AD) and inherited prion disease (IPD) in the UK 2001-2005. By comparison with frequencies predicted from published population studies, to estimate the proportion of patients with these conditions who are being accurately diagnosed.", 'All the positive diagnostic test results (from both genetic testing centres) were identified for mutations in presenilin-1 (PSEN1), presenilin-2 (PSEN2), amyloid precursor protein (APP) and prion protein genes (PRNP) for patients resident in the UK in a 5 year period. The variation in the incidence of mutation detection between UK regions was assessed with census population data. Published studies of the genetic epidemiology of familial early onset AD (EOAD) were reviewed to produce estimates of the number of patients in the UK that should be detected.', 'The rate of detection of EOAD and IPD varied very significantly and consistently between regions of the UK with low rates of detection in Northern and Western Britain (72% less detection in these regions compared with Central and Southeast Britain). The estimates from population studies further suggest a greater number of patients with EOAD than are diagnosed by genetic testing throughout the UK.'] Are familial Alzheimer 's disease and inherited prion disease in the UK poorly ascertained?
qiaojin/PubMedQA
2
[ -1.7763696908950806, -0.2815467417240143, 1.1045358180999756 ]
['Visual loss in age-related macular degeneration usually develops secondary to choroidal neovascularisation. Vascular endothelial growth factor (VEGF) is a critical regulator of retinal angiogenesis and vascular permeability, especially in hypoxic conditions. We hypothesise that hypothermia may reduce the retinal pigment epithelium (RPE) metabolism and, consequently, the levels of VEGF secretion by cultured RPE cells under hypoxic conditions. The effects of hypothermia were compared with the metabolic inhibiting effects of thiopental and nicotinamide.', 'ARPE-19 cells were grown in culture for up to 5 days under normoxic (20% O(2)) and hypoxic (1% O(2)) conditions at temperatures ranging from 27°C to 40°C. For experiments with pharmacological agents, thiopental and nicotinamide were added to the media. VEGF levels in the media were measured by ELISA and cell metabolic activity was measured by a fluorescent cell metabolic assay.', 'We found that hypothermia reduced ARPE-19 cell metabolism in a temperature-dependent fashion. Hypothermia also reduced ARPE-19 cell VEGF secretion in a temperature-dependent fashion. ARPE-19 cell VEGF secretion was reduced by 38% at 34°C compared with cells grown at 37°C. Conversely, ARPE-19 cell VEGF secretion was increased by 32% at 40°C compared with cells grown at 37°C. Hypoxia increased ARPE-19 cell VEGF secretion by 84% at 37°C. However, hypothermia decreased the hypoxia-induced increase of ARPE-19 cell VEGF secretion by 30%. The effect of hypothermia on ARPE-19 cell VEGF secretion was reversible after 4 days. In contrast to hypothermia, thiopental and nicotinamide were able to reduce RPE cell metabolism but not VEGF secretion.'] Does hypothermia reduce secretion of vascular endothelial growth factor by cultured retinal pigment epithelial cells?
qiaojin/PubMedQA
2
[ -2.1304714679718018, -1.3450082540512085, 2.4508893489837646 ]
['Minimization of blood loss during pancreatoduodenectomy requires careful surgical technique and specific preventative measures. Therefore, red blood cell (RBC) transfusions and operative time are potential surgical quality indicators. The aim of the present study was to compare peri-operative RBC transfusion and operative time with 30-day morbidity/mortality after pancreatoduodenectomy.', 'All pancreatoduodenectomies (2005 to 2008) were identified using the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP). RBC transfusions and operative time were correlated with 30-day morbidity/mortality.', 'Pancreatoduodenectomy was completed in 4817 patients. RBC transfusions were given to 1559 (32%) patients (1-35 units). Overall morbidity and mortality rates were 37% and 3.0%, respectively. Overall 30-day morbidity increased in a stepwise manner with the number of RBC transfusions (R = 0.69, P < 0.01). Although RBC transfusions and operative times were not statistically linked (P = 0.87), longer operative times were linearly associated with increased 30-day morbidity (R = 0.79, P < 0.001) and mortality (R = 0.65, P < 0.01). Patients who were not transfused also displayed less morbidity (33%) and mortality (1.9%) (P < 0.05).'] Are peri-operative blood transfusion and operative time quality indicators for pancreatoduodenectomy?
qiaojin/PubMedQA
2
[ -0.7924103736877441, -1.6358580589294434, 1.4501066207885742 ]
['Human lifespan is approximately 25% heritable, and genetic factors may be particularly important for achieving exceptional longevity. Accordingly, siblings of centenarians have a dramatically higher probability of reaching extreme old age than the general population.', 'To map the loci conferring a survival advantage, we performed the second genomewide linkage scan on human longevity and the first using a high-density marker panel of single nucleotide polymorphisms. By systematically testing a range of minimum age cutoffs in 279 families with multiple long-lived siblings, we identified a locus on chromosome 3p24-22 with a genomewide significant allele-sharing LOD score of 4.02 (empirical P = 0.037) and a locus on chromosome 9q31-34 with a highly suggestive LOD score of 3.89 (empirical P = 0.054). The empirical P value for the combined result was 0.002. A third novel locus with a LOD score of 4.05 on chromosome 12q24 was detected in a subset of the data, and we also obtained modest evidence for a previously reported interval on chromosome 4q22-25.'] Does high-density genomewide linkage analysis of exceptional human longevity identify multiple novel loci?
qiaojin/PubMedQA
2
[ -1.71043860912323, -0.45808592438697815, 1.2868434190750122 ]
['Chronic inhibition of nitric oxide (NO) synthesis is associated with hypertension, myocardial ischemia, oxidative stress and hypertrophy; expression of the vasodilator peptide, adrenomedullin (AM) and its receptors is augmented in cardiomyocytes, indicating that the myocardial AM system may be activated in response to pressure loading and ischemic insult to serve a counter-regulatory, cardio-protective role. The study examined the hypothesis that oxidative stress and hypertrophic remodeling in NO-deficient cardiomyocytes are attenuated by adenoviral vector-mediated delivery of the human adrenomedullin (hAM) gene in vivo.', 'The NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 15mg . kg(-1) . day(-1)) was given to rats for 4 weeks following systemic administration via the tail vein of a single injection of either adenovirus harbouring hAM cDNA under the control of the cytomegalovirus promoter-enhancer (Ad.CMV-hAM-4F2), or for comparison, adenovirus alone (Ad.Null) or saline. Cardiomyocytes were subsequently isolated for assessment of the influence of each intervention on parameters of oxidative stress and hypertrophic remodelling.', 'Cardiomyocyte expression of the transgene persisted for > or =4 weeks following systemic administration of adenoviral vector. In L-NAME treated rats, relative to Ad.Null or saline administration, Ad.CMV-hAM-4F2 (i) reduced augmented cardiomyocyte membrane protein oxidation and mRNA expression of pro-oxidant (p22phox) and anti-oxidant (SOD-3, GPx) genes; (ii) attenuated increased cardiomyocyte width and mRNA expression of hypertrophic (sk-alpha-actin) and cardio-endocrine (ANP) genes; (iii) did not attenuate hypertension.'] Is adrenomedullin gene delivery cardio-protective in a model of chronic nitric oxide deficiency combining pressure overload , oxidative stress and cardiomyocyte hypertrophy?
qiaojin/PubMedQA
2
[ -2.4449374675750732, -1.3938466310501099, 2.8942105770111084 ]
['The antioxidant action of diphenyl diselenide ((PhSe)(2)) is attributed to the mechanism by which (PhSe)(2) has pharmacological activity. Although (PhSe)(2) has glutathione peroxidase mimetic activity, the exact mechanism involved in its antioxidant effect has not yet been completely elucidated. In the present study, mechanisms involved in the antioxidant property of (PhSe)(2) (1-50 microM) were investigated.', "Dehydroascorbate (DHA) reductase- and glutathione S-transferase (GST)-like activity, 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical-scavenging activity and the protection against the oxidation of Fe(2+) were evaluated.", '(PhSe)(2) at concentrations equal to, or greater than, 5 microM showed DHA reductase- and GST-like activity. (PhSe)(2) was not a scavenger of DPPH or ABTS radicals and did not protect against the oxidation of Fe(2+).'] Does diphenyl diselenide in its selenol form have dehydroascorbate reductase and glutathione S-transferase-like activity dependent on the glutathione content?
qiaojin/PubMedQA
2
[ -2.2772607803344727, -1.0874638557434082, 2.4994149208068848 ]
['Low serum 25-hydroxyvitamin D (25(OH)D) concentrations are related to increased mortality. One possible explanation could be an association between serum 25(OH)D and serum lipids.', 'The study was performed at the University of Tromsø, Northern Norway. In total, 8018 nonsmoking and 2087 smoking subjects were included in a cross-sectional study performed in 2008, and 1762 nonsmoking and 397 smoking subjects in a longitudinal study from 1994/1995 to 2008. Nonfasting serum 25(OH)D, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio and triacylglycerol (TAG) were measured.', 'After adjustment for gender, age, sample month and body mass index in the cross-sectional study, there was a significant increase in serum TC, HDL-C and LDL-C, and a significant decrease in serum LDL-C/HDL-C ratio and TAG across increasing serum 25(OH)D quartiles. For serum HDL-C and TAG in nonsmokers the differences between the means for the highest and lowest serum 25(OH)D quartiles were 6.0 and 18.5%, respectively. In the longitudinal study, an increase in serum 25(OH)D was associated with a significant decrease in serum TAG.'] Are high serum 25-hydroxyvitamin D concentrations associated with a favorable serum lipid profile?
qiaojin/PubMedQA
2
[ -1.6830466985702515, -1.2702581882476807, 1.957934856414795 ]
['Repeated postprandial hyperglycemia and subsequent mild, late hypoglycemia as well as high postprandial insulin response lead to metabolic events that may eventually develop into type 2 diabetes. The aim of this study was to assess how sea buckthorn berries as well as two sea buckthorn extraction residues modulate the postprandial metabolism after a high-glucose meal.', 'Ten healthy normal-weight male volunteers consumed four study breakfasts, one control (A) and three sea buckthorn meals on four distinct study days. All the meals contained yoghurt and glucose (50\u2009g). The sea buckthorn ingredients used were dried and crushed whole berries (meal B1), supercritical fluid (SF)-carbon dioxide (CO(2))-extracted oil-free berries (meal B2) or ethanol-extracted SF-CO(2)-extraction residue (meal B3). Blood samples for glucose, insulin and tumor necrosis factor-α analyses were collected before and during the 6-h study period.', 'Meal B1 suppressed the postprandial peak insulin response when compared with meal A (Δconcentration of 30-min peak value--21.8\u2009mU/l, P=0.039), and stabilized postprandial hyperglycemia and subsequent hypoglycemia (Δconcentration of 30-min peak value--120-min value -30.4\u2009mU/l, P=0.036). Furthermore, meal B2 resulted in a more stable insulin response than the control meal (Δconcentration of 30-min peak value--120-min value -25.9\u2009mU/l, P=0.037).'] Are postprandial hyperglycemia and insulin response affected by sea buckthorn ( Hippophaë rhamnoides ssp . turkestanica ) berry and its ethanol-soluble metabolites?
qiaojin/PubMedQA
2
[ -1.7585716247558594, -1.4921236038208008, 2.2276110649108887 ]
['Studies suggest that honey has less influence on serum glucose concentrations than monosaccharides and disaccharides. Previous studies, however, have only analysed glucose metabolism.', 'This study investigated the influence of two types of honey (rapeseed and acacia) on the serum levels of glucose, fructose, insulin and C-peptide values in healthy subjects. The results were compared with honey-comparable glucose-fructose solutions. All solutions contained 75 g of glucose and/or fructose.', 'We found significantly higher fructose serum levels with rapeseed honey after 2 h but no such differences for acacia honey. C-peptide levels were significantly higher after administration of both honeys after 1 and 2 h.'] Does consumption of rapeseed honey lead to higher serum fructose levels compared with analogue glucose/fructose solutions?
qiaojin/PubMedQA
2
[ -1.3669462203979492, 0.059418968856334686, 0.3783208131790161 ]
['The structural arrangement of the γ-aminobutyric acid type A receptor (GABAAR) is known to be crucial for the maintenance of cerebral-dependent homeostatic mechanisms during the promotion of highly adaptive neurophysiological events of the permissive hibernating rodent, i.e the Syrian golden hamster. In this study, in vitro quantitative autoradiography and in situ hybridization were assessed in major hypothalamic nuclei. Reverse Transcription Reaction-Polymerase chain reaction (RT-PCR) tests were performed for specific GABAAR receptor subunit gene primers synthases of non-hibernating (NHIB) and hibernating (HIB) hamsters. Attempts were made to identify the type of αβγ subunit combinations operating during the switching ON/OFF of neuronal activities in some hypothalamic nuclei of hibernators.', 'Both autoradiography and molecular analysis supplied distinct expression patterns of all α subunits considered as shown by a strong (p < 0.01) prevalence of α1 ratio (over total α subunits considered in the present study) in the medial preoptic area (MPOA) and arcuate nucleus (Arc) of NHIBs with respect to HIBs. At the same time α2 subunit levels proved to be typical of periventricular nucleus (Pe) and Arc of HIB, while strong α4 expression levels were detected during awakening state in the key circadian hypothalamic station, i.e. the suprachiasmatic nucleus (Sch; 60%). Regarding the other two subunits (β and γ), elevated β3 and γ3 mRNAs levels mostly characterized MPOA of HIBs, while prevalently elevated expression concentrations of the same subunits were also typical of Sch, even though this time during the awakening state. In the case of Arc, notably elevated levels were obtained for β3 and γ2 during hibernating conditions.'] Are distinct α subunit variations of the hypothalamic GABAA receptor triplets ( αβγ ) linked to hibernating state in hamsters?
qiaojin/PubMedQA
2
[ -2.324554681777954, -1.4184682369232178, 2.775941848754883 ]
['Serum high molecular weight (HMW) adiponectin improves insulin sensitivity, and a decreased level of serum HMW adiponectin has been reported as a risk factor for the development of diabetes and coronary heart disease. This association may be further confounded by the alcohol drinking status, which is involved in the development of liver dysfunction. The aim of this study was to determine whether the alcohol drinking status is associated with serum HMW adiponectin levels in community-dwelling Japanese men.', 'A cross-sectional study was carried out in 2002. Study participants without a clinical history of diabetes (747 men aged 60 ± 14 (mean ± standard deviation) (range, 20-89) years) were randomly recruited from a single community at the time of their annual health examination. They were classified into never drinkers, light drinkers (< 1 unit/day), moderate drinkers (1-1.9 units/day), and heavy drinkers (≥ 2 units/day). We examined the effects of alcohol consumption on serum HMW adiponectin.', 'Overall, mean serum HMW adiponectin levels were significantly lower in the group with higher alcohol consumption, and there were inter-group differences in the alcohol drinking status. Moreover, age-adjusted mean serum HMW adiponectin levels were significantly lower in the group with higher alcohol consumption. Multiple linear regression analysis showed that the alcohol drinking status was significantly and independently associated with serum adiponectin as well as age, smoking status, TG, HDL-C, LDL-C, serum ALT, and HOMA-IR. Multivariate-adjusted mean serum HMW adiponectin levels were also significantly lower in the group with higher alcohol consumption.'] Is alcohol drinking status associated with serum high molecular weight adiponectin in community-dwelling Japanese men?
qiaojin/PubMedQA
2
[ -2.0811116695404053, -1.2919905185699463, 2.420860528945923 ]
['Inhibition of the UDP-glucuronosyltransferase (UGT) 1A1 by nilotinib was examined in vitro with SN-38 as a substrate, to estimate the possibility of drug-drug interaction of nilotinib with other medicines predominantly detoxified by UGT1A1.', 'Inhibition of UGT1A1-catalyzed SN-38 glucuronidation by nilotinib was examined with human liver microsomes (HLM) and recombinant human UGT1A1 as enzyme sources. Inhibition constants (K(i)) were estimated with kinetic analysis.', 'Nilotinib potently inhibited the SN-38 glucuronidation by human liver microsomal UGT1A1 and recombinant UGT1A1 in a noncompetitive manner, with K(i) values of 0.286 ± 0.0094 and 0.079 ± 0.0029 μM, respectively. If a drug that serves as a substrate of UGT1A1 is administered with nilotinib, the area under the plasma concentration-time curve of a drug estimated by using these K(i) values would be two times or higher than that without nilotinib, suggesting drug-drug interactions involving UGT1A1. These in vitro data and the prediction of drug-drug interaction are helpful for the clinical management of the nilotinib use.'] Is the small-molecule tyrosine kinase inhibitor nilotinib a potent noncompetitive inhibitor of the SN-38 glucuronidation by human UGT1A1?
qiaojin/PubMedQA
2
[ -2.262244462966919, -1.2694711685180664, 2.6063451766967773 ]
['Obstructive sleep apnea (OSA) is an independent risk factor for difficult and/or impossible mask ventilation during anesthesia induction. Postural change from supine to sitting improves nocturnal breathing in patients with OSA. The purpose of this study was to evaluate the effect of patient position on collapsibility of the pharyngeal airway in anesthetized and paralyzed patients with OSA. The authors tested the hypothesis that the passive pharynx is structurally less collapsible during sitting than during supine posture.', 'Total muscle paralysis was induced with general anesthesia in nine patients with OSA, eliminating neuromuscular factors contributing to pharyngeal patency. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. Comparison of static pressure-area plots between the supine and sitting (62° head-up) allowed assessment of the postural differences of the mechanical properties of the pharynx.', ': Maximum cross-sectional area was greater during sitting than during supine posture at both retropalatal (median (10th-90th percentile): 1.91 (1.52-3.40) versus 1.25 (0.65-1.97) cm) and retroglossal (2.42 (1.72-3.84) versus 1.75 (0.47-2.35) cm) airways. Closing pressure of the passive pharynx was significantly lower during sitting than supine posture. Differences of the closing pressures between the postures are 5.89 (3.73-11.6) and 6.74 (4.16-9.87) cm H2O, at retropalatal and retroglossal airways, respectively, and did not differ between the pharyngeal segments.'] Does sitting posture decrease collapsibility of the passive pharynx in anesthetized paralyzed patients with obstructive sleep apnea?
qiaojin/PubMedQA
2
[ -1.762471079826355, -1.4430220127105713, 2.1538643836975098 ]
['In vitro and in vivo studies in animal models have shown that parathyroid hormone (PTH) inhibits the expression of the SOST gene, which encodes sclerostin, an osteocyte-derived negative regulator of bone formation. We tested the hypothesis that chronic PTH excess decreases circulating sclerostin in humans.', 'We studied 25 patients with elevated serum PTH concentrations due to primary hyperparathyroidism (PHPT) and 49 patients cured from PHPT after successful parathyroidectomy (PTx; euparathyroid controls (EuPTH)).', 'We measured plasma PTH and serum sclerostin levels and the serum markers of bone turnover alkaline phosphatase, P1NP, and β-CTX.', 'As expected by the design of the study, mean plasma PTH was significantly higher (P<0.001) in PHPT patients (15.3 pmol/l; 95% confidence interval (CI): 11.1-19.5) compared with that of EuPTH controls (4.1 pmol/l; 95% CI: 3.6-4.5). PHPT patients had significantly lower serum sclerostin values compared with those in EuPTH subjects (30.5 pg/ml; 95% CI: 26.0-35.1 vs 45.4 pg/ml; 95% CI: 40.5-50.2; P<0.001) and healthy controls (40.0 pg/ml; 95% CI: 37.1-42.9; P=0.01). Plasma PTH concentrations were negatively correlated with serum sclerostin values (r=-0.44; P<0.001). Bone turnover markers were significantly correlated with PTH, but not with sclerostin.'] Do patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls?
qiaojin/PubMedQA
2
[ -1.5155149698257446, -1.5995219945907593, 2.0037102699279785 ]
['Exercise is a cornerstone of diabetes therapy in type 1 diabetes mellitus (DMT1) patients. The type of exercise is important in determining the propensity to hypoglycemia. We assessed, by continuous glucose monitoring (CGM), the glucose profiles during and in the following 20h after a session of two different types of exercise.', 'Eight male volunteers with well-controlled DMT1 were studied. They underwent 30min of both intermittent high-intensity exercise (IHE) and moderate-intensity exercise (MOD) in random order. Expired air was recorded during exercise, while metabolic and hormonal determinations were performed before and for 120 min after exercises. The CGM system and activity monitor were applied for the subsequent 20h.', 'Blood glucose level declined during both type of exercise. At 150 min following the start of exercise, plasma glucose content was slightly higher after IHE. No changes were observed in plasma insulin concentration. A significant increase of norepinephrine concentration was noticed during IHE. Between midnight and 6:00 a.m. the glucose levels were significantly lower after IHE than those observed after MOD (area under the curve, 23.3 ± 3 vs. 16 ± 3 mg/dL/420 min [P = 0.04]; mean glycemia at 3 a.m., 225 ± 31 vs. 147 ± 17 mg/dL [P<0.05]). The number of hypoglycemic episodes after IHE was higher than that observed after MOD (seven vs. two [P<0.05]).'] Does continuous glucose monitoring reveal delayed nocturnal hypoglycemia after intermittent high-intensity exercise in nontrained patients with type 1 diabetes?
qiaojin/PubMedQA
2
[ -0.9763377904891968, -1.6117126941680908, 1.590106725692749 ]
['This program was designed to evaluate the effect of morbidity and mortality peer review conferences (MMPRCs) for ventilator-associated pneumonia (VAP) on nurse accountability and compliance with evidence-based VAP prevention practices.', 'Ventilator-associated pneumonia is associated with longer average length of stay (ALOS), greater cost, and increased morbidity and mortality. Traditionally, passive or punitive methods have been used to reduce undesirable outcomes. The MMPRC is not a conventional nursing intervention.', 'Each MMPRC included case history, relevant hospital course, diagnostic comorbidities, and compliance with VAP prevention strategies. The preventability of each VAP was determined by RN peers. Ventilator days, VAP bundle compliance, VAP incidence, ICU ALOS, cost, and satisfaction data were collected.', 'Nurse accountability improved significantly (chi(2)= 24.041, P < .001), and VAP incidence was reduced. Data demonstrated satisfaction with the MMPRC. Number of ventilator days and ALOS did not change significantly, although VAP bundle compliance improved from 90.1% to 95.2%.'] Do effect of morbidity and mortality peer review on nurse accountability and ventilator-associated pneumonia rates?
qiaojin/PubMedQA
2
[ -1.84258234500885, -0.8930851817131042, 1.8326890468597412 ]
["\u2002 Problems of undernutrition are common in hospital in-patients. Multiple morbidity increases with age and may contribute to nutritional risks. This research aimed to determine whether increased burden of long-term conditions is associated with patients' difficulties gaining access to food in hospital.", "\u2002 A survey was implemented in 29 wards at four hospitals using a questionnaire measure of patients' experiences of food access and the Cumulative Illness Rating Scale (CIRS) to evaluate the burden of long-term illness in each patient. Experiences of food access were evaluated in relation to CIRS score category using random effects logistic regression to adjust for age group, sex and clustering by ward.", '\u2002 Data were analysed for 764/1154 (66%) eligible participants, including 384 women. The median age was 60\u2003years (range 18-96\u2003years). CIRS scores were analysed using the categories 0 (104 patients), 1-3 (197), 4-6 (285), 7-9 (144) and ≥10 (34). When the CIRS was zero, 10% of patients experienced physical problems with food access, whereas, when the CIRS was ≥10, 41% experienced physical barriers to food access, adjusted odds ratio 3.65 (1.14-11.7, P\u2003=\u20030.029). Problems with food quality were experienced by 13% with CIRS\u2003=\u20030 and 32% with CIRS\u2003≥\u200310 (adjusted odds ratio 3.97, 1.35-11.6, P\u2003=\u20030.012). Participants with greater morbidity were more likely to report that depression, breathing difficulties or chewing and swallowing difficulties affected the amount of food that they ate at mealtimes.'] Is multiple morbidity associated with increased problems of food access in hospital : a cross-sectional survey utilising the Cumulative Illness Rating Scale?
qiaojin/PubMedQA
0
[ 0.46314913034439087, -1.303037405014038, -0.004042001441121101 ]
['Modafinil may promote wakefulness by increasing cerebral dopaminergic neurotransmission, which importantly depends on activity of catechol-O-methyltransferase (COMT) in prefrontal cortex. The effects of modafinil on sleep homeostasis in humans are unknown. Employing a novel sleep-pharmacogenetic approach, we investigated the interaction of modafinil with sleep deprivation to study dopaminergic mechanisms of sleep homeostasis.', 'Placebo-controlled, double-blind, randomized crossover study.', 'Sleep laboratory in temporal isolation unit.', '22 healthy young men (23.4 +/- 0.5 years) prospectively enrolled based on genotype of the functional Val158Met polymorphism of COMT(10 Val/Val and 12 Met/Met homozygotes).', '2 x 100 mg modafinil and placebo administered at 11 and 23 hours during 40 hours prolonged wakefulness.', 'Subjective sleepiness and EEG markers of sleep homeostasis in wakefulness and sleep were equally affected by sleep deprivation in Val/Val and Met/Met allele carriers (placebo condition). Modafinil attenuated the evolution of sleepiness and EEG 5-8 Hz activity during sleep deprivation in both genotypes. In contrast to caffeine, modafinil did not reduce EEG slow wave activity (0.75-4.5 Hz) in recovery sleep, yet specifically increased 3.0-6.75 Hz and > 16.75 Hz activity in NREM sleep in the Val/Val genotype of COMT.'] Do effects of modafinil on the sleep EEG depend on Val158Met genotype of COMT?
qiaojin/PubMedQA
2
[ -2.1596176624298096, -1.3669099807739258, 2.5568642616271973 ]
['The association between depression and functional disability in late life remains unclear. This study aimed to explore the relationship between depressive symptoms and daily functioning through the mediation of cognitive abilities, measured by memory, reasoning, and speed of processing.', 'The authors recruited 2,832 older adults (mean age = 73.6 years, standard deviation = 5.9) participating in the Advanced Cognitive Training for Independent and Vital Elderly Study. Structural equation modeling was applied to illustrate the relationship between depressive symptoms and everyday problem-solving ability through the mediation of cognitive abilities.', 'Depressive symptoms were associated with impaired everyday problem-solving ability directly and indirectly mediated through learning and memory, and reasoning. Although depressive symptoms were associated with speed of processing, speed of processing was not significantly related to everyday problem-solving ability.'] Do depressive symptoms impair everyday problem-solving ability through cognitive abilities in late life?
qiaojin/PubMedQA
1
[ -2.321488618850708, 1.3572602272033691, 0.15336500108242035 ]
['Statin use has been reported to reduce risk for colorectal cancer (CRC) whereas atherosclerotic disease has been reported to increase risk, but findings have been inconsistent. We aimed to establish the association of statin use and coronary atherosclerosis with CRC.', 'We performed a population-based case control study of patients with a first diagnosis of CRC cancer between January 1, 1991, and December 31, 2008 (n = 9979), using the Danish National Registry of Patients. As many as 10 population controls were matched to each patient using risk set sampling (n = 99,790). Statin use before cancer diagnosis (or control index date) was determined via county prescription databases and evidence of coronary atherosclerosis using International Classification of Diseases codes. We calculated incidence rate ratios using conditional logistic regression, adjusted for multiple covariates.', 'Among patients with CRC, statin use was modest (7.7%), but 23.5% of use was long term (≥5 years). Ever use of statins (≥2 prescriptions) slightly reduced CRC risk, compared with relative to never/rare use (incidence rate ratio [IRR] = 0.87, 95% confidence interval = 0.80-0.96). However, long-term use did not affect risk compared with never/rare use (IRR = 0.95, 95% 0.80-1.12). No associations were observed between atherosclerosis, myocardial infarction, or stroke, and CRC incidence.'] Is neither long-term statin use nor atherosclerotic disease associated with risk of colorectal cancer?
qiaojin/PubMedQA
2
[ -1.2265840768814087, -1.6374670267105103, 1.8786450624465942 ]
['To identify appropriate strategies for pharmacotherapeutic agents in the management of pain in older adults with cancer.', 'PubMed literature searches, personal reference collection, and clinical experience.', 'To make good decisions about pain management when developing treatment plans for older adults, healthcare providers should focus on the pharmacokinetic and pharmacodynamic properties of drugs in the context of the physiologic changes that occur with aging.'] Does practical approach to pharmacologic management of pain in older adults with cancer?
qiaojin/PubMedQA
2
[ -3.1842410564422607, 0.9101412892341614, 1.4836809635162354 ]
['Collagen, a triple-helical, self-organizing protein, is the predominant structural protein in mammals. It is found in bone, ligament, tendon, cartilage, intervertebral disc, skin, blood vessel, and cornea. We have recently postulated that fibrillar collagens (and their complementary enzymes) comprise the basis of a smart structural system which appears to support the retention of molecules in fibrils which are under tensile mechanical strain. The theory suggests that the mechanisms which drive the preferential accumulation of collagen in loaded tissue operate at the molecular level and are not solely cell-driven. The concept reduces control of matrix morphology to an interaction between molecules and the most relevant, physical, and persistent signal: mechanical strain.', 'The investigation was carried out in an environmentally-controlled microbioreactor in which reconstituted type I collagen micronetworks were gently strained between micropipettes. The strained micronetworks were exposed to active matrix metalloproteinase 8 (MMP-8) and relative degradation rates for loaded and unloaded fibrils were tracked simultaneously using label-free differential interference contrast (DIC) imaging. It was found that applied tensile mechanical strain significantly increased degradation time of loaded fibrils compared to unloaded, paired controls. In many cases, strained fibrils were detectable long after unstrained fibrils were degraded.'] Does mechanical strain stabilize reconstituted collagen fibrils against enzymatic degradation by mammalian collagenase matrix metalloproteinase 8 ( MMP-8 )?
qiaojin/PubMedQA
2
[ -2.584019660949707, -1.1258397102355957, 2.8089234828948975 ]
['Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its association with host and viral factors and its link to both histological findings and sustained virological response (SVR). Two hundred thirty-six consecutive G1 CHC patients were evaluated by way of liver biopsy and anthropometric and metabolic measurements, including insulin resistance (IR), homeostasis model assessment (HOMA), and VAI using waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol. All biopsies were scored by one pathologist for staging and grading and graded for steatosis, which was considered moderate to severe if ≥ 30%. Multiple linear regression analysis revealed that VAI score was independently associated with higher HOMA score (P = 0.009), log10 hepatitis C virus RNA levels (P = 0.01), necroinflammatory activity (P = 0.04), and steatosis (P = 0.04). Multiple logistic regression analysis revealed that IR (OR 3.879, 95% CI 1.727-8.713, P = 0.001), higher VAI score (OR 1.472, 95% CI 1.051-2.062, P = 0.02), and fibrosis (OR 2.255, 95% CI 1.349-3.768, P = 0.002) were linked to steatosis ≥ 30%. Logistic regression analysis revealed that older age (OR 1.030, 95% CI 1.002-1.059, P = 0.03), higher VAI score (OR 1.618, 95% CI 1.001-2.617, P = 0.04), and fibrosis (OR 2.608, 95% CI 1.565-4.345, P < 0.001) were independently associated with moderate to severe necroinflammatory activity. No independent associations were found between VAI score and both fibrosis and SVR.'] Is visceral adiposity index associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1?
qiaojin/PubMedQA
2
[ -1.60442054271698, -1.642625093460083, 2.2057275772094727 ]
['Previous reports described the prognostic value of the serum CA125 level after primary treatment (CA125 nadir) in a selection of ovarian cancer patients. Our primary objective was to determine whether the CA125 nadir level is of prognostic value on the progression-free survival (PFS) and on overall survival (OS) in epithelial ovarian cancer (EOC) patients in all stages of disease who reached complete remission (CR).', 'Patients were selected from a population-based study on EOC patients diagnosed between 1996 and 2006 in 11 Dutch hospitals. All 331 patients who reached CR (i.e. no physical or radiological signs of residual disease and CA125 values ≤35 kU/L) after primary treatment were included. The Kaplan-Meier survival curves of PFS and OS in CA125 nadir ≤5 kU/L and >5 kU/L were compared using the log-rank test. Multivariate Cox regression analyses were performed to study the factors that independently influence survival.', 'A CA125 nadir ≤5 kU/L (n=69) was significantly associated with both a longer PFS and longer OS (log-rank test P<0.01 and P=0.03, respectively). The CA125 nadir was an independent prognostic variable (HR=1.51, 95% CI: 1.04-2.31) for PFS next to histological type, FIGO stage and residual tumor after surgery.'] Is cA125 nadir concentration an independent predictor of tumor recurrence in patients with ovarian cancer : a population-based study?
qiaojin/PubMedQA
2
[ -1.6955302953720093, -1.4426417350769043, 2.2044081687927246 ]
['Recent literature suggests that the inferior frontal gyrus, especially its posterior portion, has an important role in imitation and social reciprocity and in the pathophysiology of their disturbance in autism spectrum disorders (ASD). However, the structural abnormality of this region has not fully been clarified in subjects with ASD.', 'Here we obtained magnetic resonance images from 13 right-handed men with high-functioning ASD (Asperger disorder [n = 10] or autism [n = 3]) and from 11 age-, parental socioeconomic background-, and intelligence quotient-matched right-handed typical men. A reliable manual tracing methodology was employed to measure the gray matter volume of the pars opercularis, corresponding to Brodmann area 44, and the pars triangularis, corresponding to Brodmann area 45.', 'A significant gray matter volume reduction of both the pars opercularis and triangularis was found bilaterally in the subjects with ASD compared with the typical control subjects. The effect size seemed to be larger for pars opercularis (1.25) than for pars triangularis (.90). The reduced volume of right as well as total pars opercularis showed a significant association with the increased severity of social communication problems in the ASD group.'] Is reduced gray matter volume of pars opercularis associated with impaired social communication in high-functioning autism spectrum disorders?
qiaojin/PubMedQA
2
[ -2.2772376537323, -1.1935617923736572, 2.4967589378356934 ]
['Intensive mechanical stress and/or inflammation are known to induce alveolar bone resorption. This study investigated whether a distribution of mechanical stress would reduce residual ridge resorption or improve ischaemia.', "Thirty rats were divided into six experimental groups (n=5). The control group received no intentional stimulation, but rats in the experimental groups wore denture stimulators made of acrylic resin or a soft lining material. The stimulator transmitted masticatory pressure to the rats' palates for four weeks. The four types of soft lining materials investigated in this study dispersed the applied pressure, with compressive stress ranging from 20.8 to 90.8kPa. Volumes of blood flow and bone resorption of denture foundations were measured every week for 4 weeks. Statistical evaluation of these results was performed using two-way ANOVA and Holm-Sidak test within 5% error limits.", 'Non-viscoelastic material clearly induced bone resorption and ischaemia of denture foundations, while viscoelastic materials reduced these phenomena to different extents according to their viscoelastic properties. Ischaemia in the alveolar ridge preceded residual ridge resorption, because the amount of residual ridge resorption and blood flow rate showed a simple linear regression.'] Does stress distribution prevent ischaemia and bone resorption in residual ridge?
qiaojin/PubMedQA
2
[ -2.2348804473876953, -1.1842596530914307, 2.5225138664245605 ]
['Most of the literature on pathology of essential tremor (ET) has reported no consistent abnormalities. Some recent studies however indicate that cerebellar Purkinje cell (PC) loss is the pathological basis of ET in most patients.', "To compare cerebellar PC loss in ET, with normal and tremor dominant Parkinson's disease [PD] control brains.", 'Cerebellar PC counts were performed in seven ET, six PD and two normal control brains. Three different counting methods - sectioned through nucleolus, through nucleus and through any part of PC body, were used to count the PC.', 'There were individual differences in the PC counts both in the ET and the PD cases. In all three subgroups, there was a reduction in the number of PC with advancing age. When the individuals of comparable age in the three subgroups were considered, there was no clear distinction between ET, PD and normal control subjects. There was no association between the degree of PC loss and the severity or the duration of ET.'] Is cerebellar Purkinje cell loss pathognomonic of essential tremor?
qiaojin/PubMedQA
2
[ -2.3216943740844727, -1.0106428861618042, 2.361682653427124 ]
['The growing trend for women to postpone childbearing has resulted in a dramatic increase in the incidence of trisomic pregnancies. Maternal age-related miscarriage and birth defects are predominantly a consequence of chromosome segregation errors during the first meiotic division (MI), which involves the segregation of replicated recombined homologous chromosomes. Despite the importance to human reproductive health, the events precipitating female age-related meiotic errors are poorly understood.', 'Here we use a long-lived wild-type mouse strain to show that the ability to segregate chromosomes synchronously during anaphase of MI declines dramatically during female aging. This is preceded by depletion of chromosome-associated cohesin in association with destabilization of chiasmata, the physical linkages between homologous chromosomes, and loss of the tight association between sister centromeres. Loss of cohesin is not due to an age-related decline in the ability of the spindle checkpoint to delay separase-mediated cleavage of cohesin until entry into anaphase I. However, we find that reduced cohesin is accompanied by depletion of Sgo2, which protects centromeric cohesin during MI.'] Are age-related meiotic segregation errors in mammalian oocytes preceded by depletion of cohesin and Sgo2?
qiaojin/PubMedQA
2
[ -2.689880609512329, -0.6269109845161438, 2.393869638442993 ]
['During fertilization, pronuclear envelope breakdown (PNEB) is followed by the mingling of male and female genomes. Dynamic chromatin and protein rearrangements require posttranslational modification (PTM) for the postfertilization development.', 'Inhibition of poly(ADP-ribose) polymerase activity (PARylation) by either PJ-34 or 5-AIQ resulted in developmental arrest of fertilized embryos at the PNEB. PARylation inhibition affects spindle bundle formation and phosphorylation of Erk molecules of metaphase II (MII) unfertilized oocytes. We found a frequent appearance of multiple pronuclei (PN) in the PARylation-inhibited embryos, suggesting defective polymerization of tubulins. Attenuated phosphorylation of lamin A/C by PARylation was detected in the PARylation-inhibited embryos at PNEB. This was associated with sustained localization of heterodomain protein 1 (HP1) at the PN of the one-cell embryos arrested by PARylation inhibition.'] Is polyADP-ribosylation required for pronuclear fusion during postfertilization in mice?
qiaojin/PubMedQA
2
[ -2.477957010269165, -1.2551031112670898, 2.7938523292541504 ]
['Pathological angiogenesis contributes to various ocular, malignant, and inflammatory disorders, emphasizing the need to understand this process more precisely on a molecular level. Previously we found that CIB1, a 22 kDa regulatory protein, plays a critical role in endothelial cell function, angiogenic growth factor-mediated cellular functions, PAK1 activation, MMP-2 expression, and in vivo ischemia-induced angiogenesis. Since pathological angiogenesis is highly dependent on many of these same processes, we hypothesized that CIB1 may also regulate tumor-induced angiogenesis.', 'To test this hypothesis, we allografted either murine B16 melanoma or Lewis lung carcinoma cells into WT and CIB1-KO mice, and monitored tumor growth, morphology, histology, and intra-tumoral microvessel density.', 'Allografted melanoma tumors that developed in CIB1-KO mice were smaller in volume, had a distinct necrotic appearance, and had significantly less intra-tumoral microvessel density. Similarly, allografted Lewis lung carcinoma tumors in CIB1-KO mice were smaller in volume and mass, and appeared to have decreased perfusion. Intra-tumoral hemorrhage, necrosis, and perivascular fibrosis were also increased in tumors that developed in CIB1-KO mice.'] Is tumor growth and angiogenesis impaired in CIB1 knockout mice?
qiaojin/PubMedQA
2
[ -2.512091636657715, -1.0801122188568115, 2.6267669200897217 ]
['Studies have shown that Notch is essential for the maintenance of a T cell Th2 phenotype in vivo. It has also been shown that Notch ligands have diverse functions during T cell activation. We chose to investigate the role of Notch ligands during the Th2 response.', 'We studied the relationship of two Notch ligands, delta-like 4 and jagged-1, to T cell proliferation in C57 Bl/6 mice. Our findings indicate that jagged-1 does not affect the rate of T cell proliferation in any subset examined. However, delta-like 4 causes an increase in the expansion of Th2 memory cells and a decrease in effector cell proliferation. Our in vivo studies indicate that the Notch system is dynamically regulated, and that blocking one Notch ligand increases the effective concentration of other Notch ligands, thus altering the response. Examination of genes related to the Notch pathway revealed that the Notch receptors were increased in memory T cells. Expression of BMI1, a gene involved in T cell proliferation, was also higher in memory T cells. Further experiments demonstrated that Notch directly regulates the expression of the BMI1 gene in T cells and may govern T cell proliferation through this pathway.'] Does delta-like 4 differentially regulate murine CD4 T cell expansion via BMI1?
qiaojin/PubMedQA
2
[ -2.4073846340179443, -0.749286413192749, 2.2009711265563965 ]
["Human neuroblastoma (NB) cell lines may present with either one of the so-called S-and N-subtypes. We have previously reported a strong correlation between protein expression levels of vimentin, an S-subtype marker, and the p21Waf1 cyclin-dependent kinase inhibitor. We here investigated whether this correlation extend to the mRNA level in NB cell lines as well as in patients' tumors. We also further explored the relationship between expression of vimentin and p21, by asking whether vimentin could regulate p21 expression.", "Vimentin and p21 mRNA levels in NB cell lines as well as in patients' tumors (n = 77) were quantified using Q-PCR. Q-PCR data obtained from tumors of high risk NB patients (n = 40) were analyzed in relation with the overall survival using the Log-rank Kaplan-Meier estimation. siRNA-mediated depletion or overexpression of vimentin in highly or low expressing vimentin cell lines, respectively, followed by protein expression and promoter activation assays were used to assess the role of vimentin in modulating p21 expression.", "We extend the significant correlation between vimentin and p21 expression to the mRNA level in NB cell lines as well as in patients' tumors. Overall survival analysis from Q-PCR data obtained from tumors of high risk patients suggests that lower levels of p21 expression could be associated with a poorer outcome. Our data additionally indicate that the correlation observed between p21 and vimentin expression levels results from p21 transcriptional activity being regulated by vimentin. Indeed, downregulating vimentin resulted in a significant decrease in p21 mRNA and protein expression as well as in p21 promoter activity. Conversely, overexpressing vimentin triggered an increase in p21 promoter activity in cells with a nuclear expression of vimentin."] Is p21Waf1 expression regulated by nuclear intermediate filament vimentin in neuroblastoma?
qiaojin/PubMedQA
2
[ -2.241152048110962, -1.1194372177124023, 2.3860859870910645 ]
['Chronic periodontitis (CP) and aggressive periodontitis (AP) are inflammatory diseases and the main cause of dental loss in adults. We aimed to investigate the expression of adhesion molecules and the source of proinflammatory and anti-inflammatory cytokines in circulating mononuclear cells from patients with CP and AP.', 'Peripheral blood mononuclear cells from healthy controls and CP or AP patients were collected. The expression of the cell adhesion molecules CD11a and CD11b, and the cellular sources of interleukin (IL)-4, IL-10, IL-12, interferon-γ, and tumor necrosis factor-α by distinct subpopulations of circulating leukocytes were determined using flow cytometry.', 'The expression of CD11a, but not CD11b, was significantly higher within the CD4(+) and CD8(+) T cells in CP and AP than in healthy controls. The frequencies of tumor necrosis factor-α-expressing CD4(+) T cells and CD14(+) cells were higher in AP and CP, compared to healthy controls, respectively. Moreover, the frequency of IL-10 expressing CD14(+) cells was higher in CP, but not AP, compared to healthy controls CD4(+) T cells committed to IL-4 production was higher in CP than in healthy controls.'] Do aggressive and chronic periodontitis correlate with distinct cellular sources of key immunoregulatory cytokines?
qiaojin/PubMedQA
2
[ -2.458693027496338, -1.136500597000122, 2.600083827972412 ]
['Nonlinear small datasets, which are characterized by low numbers of samples and very high numbers of measures, occur frequently in computational biology, and pose problems in their investigation. Unsupervised hybrid-two-phase (H2P) procedures-specifically dimension reduction (DR), coupled with clustering-provide valuable assistance, not only for unsupervised data classification, but also for visualization of the patterns hidden in high-dimensional feature space.', "'Minimum Curvilinearity' (MC) is a principle that-for small datasets-suggests the approximation of curvilinear sample distances in the feature space by pair-wise distances over their minimum spanning tree (MST), and thus avoids the introduction of any tuning parameter. MC is used to design two novel forms of nonlinear machine learning (NML): Minimum Curvilinear embedding (MCE) for DR, and Minimum Curvilinear affinity propagation (MCAP) for clustering.", 'Compared with several other unsupervised and supervised algorithms, MCE and MCAP, whether individually or combined in H2P, overcome the limits of classical approaches. High performance was attained in the visualization and classification of: (i) pain patients (proteomic measurements) in peripheral neuropathy; (ii) human organ tissues (genomic transcription factor measurements) on the basis of their embryological origin.'] Do nonlinear dimension reduction and clustering by Minimum Curvilinearity unfold neuropathic pain and tissue embryological classes?
qiaojin/PubMedQA
2
[ -2.6834089756011963, -0.8130759596824646, 2.612657308578491 ]
['The immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients with acute myeloid leukemia, resulting in the inhibition of T-cell proliferation and the induction of regulatory T cells. Acute myeloid leukemia cells can be differentiated into dendritic cells, which have increased immunogenicity and have been proposed as vaccines against leukemia.', 'Leukemic dendritic cells were generated from acute myeloid leukemia cells and used as stimulators in functional assays, including the induction of regulatory T cells. Indoleamine 2,3-dioxygenase expression in leukemic dendritic cells was evaluated at molecular, protein and enzymatic levels.', "We demonstrate that, after differentiation into dendritic cells, both indoleamine 2,3-dioxygenase-negative and indoleamine 2,3-dioxygenase-positive acute myeloid leukemia samples show induction and up-regulation of indoleamine 2,3-dioxygenase gene and protein, respectively. Indoleamine 2,3-dioxygenase-positive acute myeloid leukemia dendritic cells catabolize tryptophan into kynurenine metabolite and inhibit T-cell proliferation through an indoleamine 2,3-dioxygenase-dependent mechanism. Moreover, indoleamine 2,3-dioxygenase-positive leukemic dendritic cells increase the number of allogeneic and autologous CD4(+)CD25(+) Foxp3(+) T cells and this effect is completely abrogated by the indoleamine 2,3-dioxygenase-inhibitor, 1-methyl tryptophan. Purified CD4(+)CD25(+) T cells obtained from co-culture with indoleamine 2,3-dioxygenase-positive leukemic dendritic cells act as regulatory T cells as they inhibit naive T-cell proliferation and impair the complete maturation of normal dendritic cells. Importantly, leukemic dendritic cell-induced regulatory T cells are capable of in vitro suppression of a leukemia-specific T cell-mediated immune response, directed against the leukemia-associated antigen, Wilms' tumor protein."] Do indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells?
qiaojin/PubMedQA
2
[ -2.459017753601074, -1.2683192491531372, 2.7628674507141113 ]
['This work aimed to verify the hypothesis that maternal intake of high-fat diet in critical periods of pregnancy and/or suckling period predisposes nonalcoholic fatty liver disease in adult C57BL/6 mice offspring.', 'Male pups were divided into 5 groups: (1) SC, from standard chow-fed dams; (2) G, from high-fat chow (HF)-fed dams during the gestation (G) period; (3) L, from HF-fed dams during the lactation (L) period; (4) GL, from HF-fed dams during the gestation and lactation (GL) periods; and (5) GL/HF, from HF-fed dams during GL, maintaining an HF diet from postweaning to adulthood. We analyzed body mass, plasma blood, and liver structure.', 'The G offspring showed insulin resistance and lower glucose transporter-2 expression. Hepatic steatosis was present in the G, L, GL, and mainly in GL/HF offspring. Sterol regulatory element-binding protein-1c expression was higher in G, GL, and GL/HF offspring.'] Does maternal high-fat intake predispose nonalcoholic fatty liver disease in C57BL/6 offspring?
qiaojin/PubMedQA
2
[ -2.2132041454315186, -0.5986793637275696, 1.9065666198730469 ]
['In surveys, almost 50% of women prefer a female endoscopist (FE) to perform their screening colonoscopies (SCOs).', 'To assess whether offering women an FE is associated with higher rates of SCOs.', 'Prospective cohort study.', 'University of Colorado Hospital primary care clinics.', 'Women of ages 50 to 69 years eligible for an SCO.', 'SCO offers through mail and telephone outreach, with and without an explicit FE option.', 'Outreach intervention differences in SCO completion rates and percentages of women requesting FE.', 'Of 396 women, 72 (18.2%) underwent SCO without difference by type of invitation. Women who received an FE invitation were more likely to request an FE than patients who received no invitation (44.2% and 4.8%, respectively, P < .001), but women who requested an FE were not more likely to undergo an SCO than those who did not.'] Are rates of screening colonoscopy increased when women are offered a female endoscopist in a health promotion outreach program?
qiaojin/PubMedQA
1
[ -1.1528841257095337, 0.4183068573474884, -0.17321829497814178 ]
['Laminin is the most abundant non-collagenous protein in the basement membrane. Recent studies have shown that laminin supports platelet adhesion, activation and aggregation under flow conditions, highlighting a possible role for laminin in hemostasis.', 'To investigate the ability of laminin to promote coagulation and support thrombus formation under shear.', 'Soluble laminin accelerated factor (F) XII activation in a purified system, and shortened the clotting time of recalcified plasma in a FXI- and FXII-dependent manner. Laminin promoted phosphatidylserine exposure on platelets and supported platelet adhesion and fibrin formation in recalcified blood under shear flow conditions. Fibrin formation in laminin-coated capillaries was abrogated by an antibody that interferes with FXI activation by activated FXII, or an antibody that blocks activated FXI activation of FIX.'] Does laminin promote coagulation and thrombus formation in a factor XII-dependent manner?
qiaojin/PubMedQA
2
[ -2.7125351428985596, -0.9501651525497437, 2.7461161613464355 ]
['To explore the inhibitory effect of norcantharidin (NCTD) on the expression of DNA replication initiation protein Cdc6 in cancer cells.', 'MTT assay was performed to detect the inhibitory effect on different cancer cell lines, including HeLa, HepG2, Jurkat and Ramos cells. The effect of NCTD on Cdc6 protein level was detected by Western blotting, and BrdU incorporation assay was used to evaluate the DNA replication of the cells.', 'NCTD significantly inhibited the proliferation of the cells and caused degradation of Cdc6 protein to result in the inhibition of the DNA replication of the cells shown by BrdU incorporation assay.'] Does [ Norcantharidin inhibit DNA replication initiation protein Cdc6 in cancer cells ]?
qiaojin/PubMedQA
2
[ -2.352768898010254, -0.9555739760398865, 2.3848276138305664 ]