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["The neighborhood social environment has been identified as an important aspect of older people's well-being. Poor neighborhood conditions can pose difficulties in obtaining support, especially for older people who live alone. Although social environments have been found to be related to well-being among older people, the longitudinal relationship between the social environment and well-being remains poorly undestood. Research on the effects of changes in neighborhood characteristics, such as social cohesion and social belonging, on well-being is lacking. Therefore, the study aims are (i) describe social cohesion, social belonging, and instrumental goals to achieve well-being among community-dwelling older people, (ii) determine whether these factors varied according to neighborhood social deprivation and compare these findings to those from chronically ill/previously hospitalized older people, and (iii) identify longitudinal relationships between social cohesion and belonging and well-being.", 'Independently living Dutch older adults (aged\u2009≥\u200970\xa0years) were asked to complete questionnaires in 2011 (T0) and 2013 (T1). Response rates at T0 and T1 were 66% (945/1440) and 62% (588/945), respectively. Descriptive statistics, paired sample t-tests, analysis of variance, univariate analyses and multilevel regression analyses controlling for background characteristics and baseline well-being were performed.', 'Of 945 respondents [43% male; mean age, 77.5\u2009±\u20095.8 (range, 70-101) years], 34.7% were married and 83.3% were Dutch natives. Social cohesion remained constant over time, whereas social belonging improved (p\u2009≤\u20090.05). Older people living in socially deprived neighborhoods report poorer overall well-being and instrumental goals to achieve well-being. Baseline social cohesion, changes therein (both p\u2009≤\u2009.001), baseline social belonging, and changes therein (both p\u2009≤\u2009.05) predicted well-being at T1.']
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['Prenatal alcohol exposure via maternal liquid diet consumption by C57BL/6 (B6) mice causes conspicuous midline neural tube deficit (dysraphia) and disruption of genesis and development of serotonin (5-HT) neurons in the raphe nuclei, together with brain growth retardation. The current study tested the hypothesis that concurrent treatment with either an activity-dependent neurotrophic factor (ADNF) agonist peptide [SALLRSIPA, (SAL)] or an activity-dependent neurotrophic protein (ADNP) agonist peptide [NAPVSIPQ, (NAP)] would protect against these alcohol-induced deficits in brain development.', 'Timed-pregnant B6 dams consumed alcohol from embryonic day 7 (E7, before the onset of neurulation) until E15. Fetuses were obtained on E15 and brain sections processed for 5-HT immunocytochemistry, for evaluation of morphologic development of the brainstem raphe and its 5-HT neurons. Additional groups were treated either with SAL or NAP daily from E7 to E15 to assess the potential protective effects of these peptides. Measures of incomplete occlusion of the ventral canal and the frequency and extent of the openings in the rhombencephalon were obtained to assess fetal dysraphia. Counts of 5-HT-immunostained neurons were also obtained in the rostral and caudal raphe.', 'Prenatal alcohol exposure resulted in abnormal openings along the midline and delayed closure of ventral canal in the brainstem. This dysraphia was associated with reductions in the number of 5-HT neurons both in the rostral raphe nuclei (that gives rise to ascending 5-HT projections) and in the caudal raphe (that gives rise to the descending 5-HT projections). Concurrent treatment of the alcohol-consuming dams with SAL prevented dysraphia and protected against the alcohol-induced reductions in 5-HT neurons in both the rostral and caudal raphe. NAP was less effective in protecting against dysraphia and did not protect against 5-HT loss in the rostral raphe, but did protect against loss in the caudal raphe.']
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["Thiazolidinediones (TZDs) have been demonstrated to possess antitumor effects in breast cancer cells, although the mechanisms are not well established. We sought to better define TZDs' antitumor effects and molecular mechanisms to permit rational utilization of these agents.", 'We studied the effects of TZDs on DNA synthesis (BrdU enzyme-linked immunosorbent assay), gene expression (microarray, quantitative reverse transcription-polymerase chain reaction, and immunoblot), serine phosphorylation and localization of beta-catenin (nuclear/cytoplasmic fractionation and immunoblot), transactivation activity of beta-catenin/T cell factor 4 (TCF4) (luciferase assay with wild-type and mutant TCF4 responsive element), and beta-catenin/TCF4 complex (immunoprecipitation) in human breast cancer cells MDA-MB-231 and T47D.', 'Troglitazone (TG) down-regulated DNA synthesis in MDA-MB-231 and T47D and decreased mRNA expression of the Wnt co-receptors frizzled-1 and low-density lipoprotein-related protein 6 (LRP6) as well as protein level of LRP6. TG also targets downstream Wnt signaling molecules in T47D cells. TG down-regulates p-beta-catenin (S33/S37/T41) and promotes translocation of beta-catenin into the nucleus. However, TG inhibits beta-catenin-mediated transactivation by down-regulating TCF4 protein levels, thereby inhibiting beta-catenin/TCF4 complex formation. Finally, we found that inhibition of Akt augments TG-mediated down-regulation of DNA synthesis and this result was accompanied with the decreased protein levels of Wnt signaling molecules: LRP6, beta-catenin, and TCF4.']
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['City of Manaus, Amazonas, Brazil.', 'To explore the relationship between positivity to tuberculin and other environmental mycobacteria sensitins, according to a range of criteria and presence of BCG scar.', 'Dual skin testing with tuberculin and four mycobacterial sensitins, and BCG scar recording of 1070 schoolchildren aged 7-14. Four criteria for positivity were used: simple and dominant, with 5 and 10 mm cut-off points.', 'The standardised prevalence of reactions > or = 5 mm for BCG scar negative children was 58.3% for Mycobacterium avium, 54.2% for M. scrofulaceum, 26.8% for M. fortuitum, 17.9% for M. tuberculosis and 7.6% for M. kansasii. Correlations between tuberculin and each sensitin, for BCG scar negative children, were 0.47 for M. avium, 0.53 for M. scrofulaceum, 0.60 for M. kansasii and 0.22 for M. fortuitum (all with P < 0.01). BCG effect was particularly significant for tuberculin (odds ratio = 3.44 for reactions > or = 5 mm, P < 0.001) and influenced the balance between dominant/non-dominant reactions for all sensitins.']
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['Patient-specific glenoid guides (PSGs) claim an improvement in accuracy and reproducibility of the positioning of components in total shoulder arthroplasty (TSA). The results have not yet been confirmed in a prospective clinical trial. Our aim was to assess whether the use of PSGs in patients with osteoarthritis of the shoulder would allow accurate and reliable implantation of the glenoid component.', 'A total of 17 patients (three men and 14 women) with a mean age of 71 years (53 to 81) awaiting TSA were enrolled in the study. Pre- and post-operative version and inclination of the glenoid were measured on CT scans, using 3D planning automatic software. During surgery, a congruent 3D-printed PSG was applied onto the glenoid surface, thus determining the entry point and orientation of the central guide wire used for reaming the glenoid and the introduction of the component. Manual segmentation was performed on post-operative CT scans to compare the planned and the actual position of the entry point (mm) and orientation of the component (°).', 'The mean error in the accuracy of the entry point was -0.1 mm (standard deviation (sd) 1.4) in the horizontal plane, and 0.8 mm (sd 1.3) in the vertical plane. The mean error in the orientation of the glenoid component was 3.4° (sd 5.1°) for version and 1.8° (sd 5.3°) for inclination.']
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['Prostate cancer (PCa) is a leading cause of cancer-related death in men. Sodium phenylbutyrate (SPB) has shown its potential as an anticancer therapy in numerous cancer types. In the present study, we attempted to assess the effect of SPB against PCa and whether this treatment was associated with the regulation of survivin.', 'Two human PCa cancer cell lines, DU145 and PC3, were used in the present study. Cell Counting Kit-8 (CCK-8) assay was conducted to measure the proliferation of PCa cells incubated with SPB. The effect of SPB on the cell apoptosis, cell colony formation ability, and cell morphological change was also assessed. Transwell experiment and Western blotting assay were performed to determine the effect of SPB on the migration and invasion ability of both cell types. Moreover, the expression pattern of survivin and MAPK members in both cell types after the treatment of SPB was also detected. Additionally, an in vivo tumor formation assay was performed to evaluate the treatment potential of SPB against PCa.', 'We found that the viability of PCa cells was significantly inhibited by SPB treatment. As illustrated by flow cytometry, for DU145 cell line the average apoptotic rate of SPB-treated cells was significantly lower than that of the control group (P<0.05); similar results were also seen for PC3 (P<0.05). SPB administration also attenuated the colony formation and migration abilities in both cell lines. The expression level of survivin in SPB-treated cells was significantly downregulated, while the phosphorylation of p-38 and ERK was enhanced. Furthermore, in vivo tumor formation of both cell lines was suppressed by SPB as well.']
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['Cul-4, a member of the Caenorhabditis elegans "cullin" ubiquitin-ligase gene family, plays a critical role in regulation of DNA-replication in this nematode. It has been suggested that cul-4 might have an important role in the development and progression of human cancer, but no data on this subject exist. The aim of this study was to investigate the expression and prognostic relevance of CUL-4 protein in lymph node-negative breast cancer, one of the most common malignancies worldwide.', 'CUL-4 protein expression was determined with immunohistochemistry in 167 specimens of human node-negative invasive breast cancer with long-term follow-up. Results were correlated with overall and disease-free survival of patients.', 'Strong expression of CUL-4 protein was observed in 32 cases (19.2%), moderate expression in 59 (35.3%), weak expression in 64 (38.3%), and in 12 tumors (7.2%) no expression of CUL4 was observed. Patients with strong expression of CUL4 had a significantly shorter overall and disease-free survival (p = 0.04 and p = 0.029, respectively; Cox regression) compared to all other cases.']
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['Drug efflux pumps are one of the key machineries in bacterial drug resistance. Although quite a few of these transport systems have been functionally characterized in various organisms, due to large-scale genome sequencing efforts and improved prediction pipelines there are increasing numbers of putative drug efflux genes annotated. For phenotype identification of the proteins encoded by these genes, we developed a novel high-throughput phenotype screening strategy and demonstrated its utility in identifying phenotypes for putative efflux systems encoded by the human pathogen Acinetobacter baumannii.', 'Seventeen putative drug efflux systems from A. baumannii were heterologously expressed in Escherichia coli. For rapid and economical phenotype screening we employed a combination of multiplexed Biolog Phenotype Microarrays and quantitative PCR. Using this method we screened these putative drug efflux pumps against 240 antimicrobial conditions, equating to 4080 simultaneous phenotypic tests.', 'Of the 17 putative drug efflux systems, phenotypes were confirmed for two pumps and novel drug resistance phenotypes were identified for three new A. baumannii drug transporters, which exemplified the power of this method as a high-throughput screening technique. One of the phenotypically characterized putative drug efflux systems was classified within the ATP-binding cassette superfamily of transport proteins and represents the first drug resistance protein characterized from this superfamily in A. baumannii. The remaining two proteins were members of the major facilitator superfamily of efflux pumps.']
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['Cardiac surgery can be complicated by pulmonary abnormalities, but it is unclear how various manifestations interrelate.', 'A prospective study in the intensive care unit was performed on 26 mechanically ventilated patients without cardiac failure within 3 h after elective cardiac surgery involving cardiopulmonary bypass. Oedema (extravascular lung water, EVLW) was measured by the thermal-dye technique and permeability by a dual radionuclide technique, yielding a pulmonary leak index (PLI). Radiographic, mechanical and gas exchange features were used to calculate the lung injury score (LIS), ranging between 0 and 4. Evidence for left lower lobe atelectasis was obtained from plain radiographs. The plasma colloid osmotic pressure (COP) was measured by an oncometer.', 'The EVLW (normal, <7 ml/kg) was elevated in 36% of patients and the PLI (normal, <14.1 x 10(-3)/min) in 44%, but the variables did not interrelate directly. Patients with a supranormal EVLW had a lower COP than patients with normal EVLW. The duration of mechanical ventilation was prolonged in patients (20%) with EVLW > 10 ml/kg. There was no difference in EVLW and PLI in patients with LIS < 1 and LIS > 1 (31% of patients). In patients with radiographic evidence for atelectasis (46%), the positive end-expiratory pressure and inspiratory O2 fraction to maintain oxygenation were higher than in those without.']
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['The impact of timely empiric antimicrobial therapy on neonates is unclear. Our aim was to examine rates of effective timely empiric antimicrobial therapy on preterm neonates, together with the associated outcomes.', 'We performed a single-centre retrospective study of preterm infants (<32\xa0weeks of gestational age) with a late-onset (>72\xa0h of age) bloodstream infection (BSI). Empiric antimicrobial administration took place before the results of blood culture were available and its timing was determined by the electronic medical records.', 'Our cohort (n\xa0=\xa0105) was predominantly female (59%) and black (83%) with a mean (SD) gestational age of 27.4 (2.3) weeks and birthweight of 948 (335) g. Effective empiric antimicrobials were initiated in 114 (69%) of 165 BSI episodes, and a third of the BSIs without empiric antimicrobials were found to be fungal. Both antimicrobial timing (r\xa0=\xa00.27, p\xa0=\xa00.002) and fungal organism (r\xa0=\xa00.35, p\xa0=\xa00.0001) showed significant correlations and were independently associated with time to clearance. Neither variable was associated with survival or length of stay.']
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['To examine the effect of human conjunctival fibroblasts on the survival and functional activity of human peripheral blood eosinophils.', 'Eosinophils were purified by negative immunoselection [magnetic activated cell sorter (MACS), purity > 97%] from volunteers with mild atopia. Fibroblasts were cultured from conjunctival specimens of healthy donors. Eosinophils were cultured on confluent monolayers of conjunctival fibroblasts or in culture medium alone. Eosinophil survival was evaluated by the trypan blue exclusion test. Eosinophil adherence was assessed by counting the attached cells after washing the cultures. Eosinophil viability and adherence in coculture were also assessed in the presence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF), anti-interleukin (IL)-3, and anti-IL-5 neutralizing antibodies. Cocultured eosinophils were activated by lipopolysaccharide (LPS) after 4 days in culture, and eosinophil peroxidase (EPO) release was determined as a marker of their activation.', 'Eosinophils cocultured with conjunctival fibroblasts had a significantly increased viability of 35.9% (P = 0.004) and 12.8% (P = 0.003) on days 4 and 8, respectively. Fibroblast-conditioned medium did not enhance the survival of eosinophils. The increase in eosinophil survival in coculture was partially inhibited by anti-GM-CSF (P = 0.019), anti-IL-3 (P = 0.033), or anti-IL-5 (P = 0.011), whereas eosinophil adherence was reduced by anti-GM-CSF alone (P = 0.034). LPS activation of eosinophils cultured for 4 days with conjunctival fibroblasts induced higher EPO release than in freshly isolated eosinophils (P = 0.01).']
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['Clonal expansion of lymphocytes may account for asymptomatic lymphocytosis. Unlike monoclonal B lymphocytosis, the detection of T-cell clones is difficult using immunophenotype-based assays. This study aimed to evaluate PCR-based clonality assays for the identification of T-cell clones among patients with unexplained lymphocytosis.', 'We incorporated the BIOMED-2 multiplex PCR into the investigation of peripheral lymphocytosis. Clonality analysis was performed with three reactions for TCRβ and two reactions for TCRγ gene rearrangements. The analysis was performed with blood specimens from a total of 150 adult patients who presented with incidental lymphocytosis.', 'PCR assays were validated using confirmed T-cell malignancies and the detection sensitivity was determined at a level of 2%. Using the TCRβ and TCRγ combination, 25 (16.6%) of 150 patients were found to have clonal TCR arrangement. Patients who harboured clonal T cells presented with a mild to moderate absolute lymphocytosis, with a median lymphocyte count of 4.5 × 10(9)/l (range 3.7-9.8 × 10(9)) and the absence of other haematological abnormalities. Immunophenotyping confirmed T-cell lymphocytosis with an increase in CD8 T cells in the majority of patients.']
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['C4-2 prostate cancer (CaP) cells grown in mouse tibiae cause a mixed osteoblastic/osteolytic response with increases in osteoclast numbers and bone resorption. Administration of osteoprotegerin (OPG) blocks these increases, indicating the critical role of RANKL in osteolysis in this model. The objective of our study was to investigate whether RANKL expressed by tumor cells (human origin) directly stimulates osteolysis associated with the growth of these cells in bone or whether the increased osteolysis is caused by RANKL expressed by the host environment cells (murine origin). The relative contribution of tumor-vs. host-derived RANKL has been difficult to establish, even with human xenografts, because murine and human RANKL are both capable of stimulating osteolysis in mice, and the RANKL inhibitors used to date (OPG and RANK-Fc) inhibit human and murine RANKL.', 'To address this question we used a neutralizing, antibody (huRANKL MAb), which specifically neutralizes the biological activities of human RANKL and thereby the contribution of C4-2 derived RANKL in this tibial injection model of experimental bone metastases.', 'Administration of huRANKL MAb did not inhibit the osteolytic response of the bone to these cells, or affect the establishment and growth of the C4-2 tumors in this environment.']
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['Wolbachia are bacterial endosymbionts of many arthropod species in which they manipulate reproductive functions. The distribution of these bacteria in the Drosophila ovarian cells at different stages of oogenesis has been amply described. The pathways along which Wolbachia influences Drosophila oogenesis have been, so far, little studied. It is known that Wolbachia are abundant in the somatic stem cell niche of the Drosophila germarium. A checkpoint, where programmed cell death, or apoptosis, can occur, is located in region 2a/2b of the germarium, which comprises niche cells. Here we address the question whether or not the presence of Wolbachia in germarium cells can affect the frequency of cyst apoptosis in the checkpoint.', 'Our current fluorescent microscopic observations showed that the wMel and wMelPop strains had different effects on female germline cells of D. melanogaster. The Wolbachia strain wMel did not affect the frequency of apoptosis in cells of the germarium. The presence of the Wolbachia strain wMelPop in the D. melanogasterw1118 ovaries increased the number of germaria where cells underwent apoptosis in the checkpoint. Based on the appearance in the electron microscope, there was no difference in morphological features of apoptotic cystocytes between Wolbachia-infected and uninfected flies. Bacteria with normal ultrastructure and large numbers of degenerating bacteria were found in the dying cyst cells.']
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['Skin is the outermost tissue of the human body, and works as a mechanical, chemical, and biological barrier. The epidermis is the uppermost layer of the skin, and keratinocytes constitute the majority of epidermal cells. Wounds are disruptions of skin integrity, and cause tremendous disadvantages to humans; accordingly, rapid wound healing is very important. Interleukin (IL)-33 is expressed in barrier tissue cells, such as epithelial and endothelial cells. Upon injury, IL-33 is released to stimulate immune cells, functioning as an "alarmin." ST2 is a receptor for IL-33; its soluble form (s)ST2 acts as a decoy receptor and competes for IL-33 binding.', 'We aimed to clarify the role of IL-33 in wound healing.', 'Wild-type (WT), IL-33 knockout (IL33 KO) mice, and sST2 transgenic (Tg) mice were wounded with a 4-mm punch, and the wound healing process was compared. Immunohistochemical analyses were performed to detect macrophages, neutrophils, and mast cells. Total RNA was extracted from the skin samples and real-time PCR was performed. An in vitro scratch wound assay was performed.', 'Wound healing was delayed in IL33 KO mice compared to WT mice, while wound healing in sST2 Tg mice was comparable to that of WT mice. A histological examination showed delayed elongation of the epidermal tongue in IL-33 KO mice. An immunohistochemical study revealed prolonged neutrophilic infiltration at a later stage in IL-33 KO mice. IL-6, IL-1β, and CXCL1 transcripts were more abundant in the wounds of IL-33 KO mice than WT mice. Intraperitoneal administration of an NFκB inhibitor to IL-33 KO mice normalized the delayed wound healing and the enhanced expression of IL-6 in IL-33 KO mice. Epidermal keratinocytes from IL-33 KO mice showed delayed wound closure compared to those from WT mice.']
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['trans Palmitoleic acid (t-16:1n-7, or 16:1 t9 in the δ nomenclature usually applied to trans fatty acids and used herein) arouses great scientific interest because it has been suggested to serve as a biomarker for lower risks of type 2 diabetes and coronary artery disease.', 'Although 16:1 t9 has been assumed to derive from dietary sources, we examined the hypothesis that 16:1 t9 might also be endogenously produced from its metabolic precursor vaccenic acid (t-18:1n-7 or 18:1 t11).', 'We reevaluated fatty acid data obtained from one human intervention study and one cellular model in both of which 18:1 t11 was supplemented. Both studies have already been published, but to our knowledge, 16:1 t9 has not yet been considered. This reanalysis of the datasets was reasonable because a new methodology for identifying 16:1 cis and trans isomers allowed us to address the subject presented in this article.', 'Data showed that the systemic or intracellular increase in 16:1 t9 was strongly correlated with the increase in 18:1 t11 after the dietary intake or cellular uptake of 18:1 t11. The conversion rate in humans was, on average, 17%.']
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['Mortality prediction models can be used to adjust for presenting severity of illness in observational studies of treatment effectiveness. We aimed to determine the incremental benefit of adding information about critical care services to a sepsis mortality prediction model.', "In a retrospective cohort of 166\u2009931 eligible sepsis patients at 309 hospitals, we developed nested logistic regression models to predict mortality at the patient level. Our initial model included only demographic information. We then added progressively more detailed information such as comorbidities and initial treatments. We calculated each model's area under the receiver operating characteristic curve (AUROC) and also used a sheaf coefficient analysis to determine the relative effect of each additional group of variables.", 'Model discrimination increased as more detailed patient information was added. With demographics alone, the AUROC was 0.59; adding comorbidities increased the AUROC to 0.67. The final model, which took into account mixed (hierarchical) effects at the hospital level as well as initial treatments administered within the first two hospital days, resulted in an AUROC of 0.78. The standardized sheaf coefficient for the initial treatments was approximately 30% greater than that for demographics or infection source.']
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['To examine the functional role of membrane-bound SLF, we evaluated the growing skeletons of WT and SLF mutant (Sl/Sl(d)) mice that do not produce this protein using DXA, bone histomorphometry, cell culture, and flow cytometry. Deletion of membrane-bound SLF delays bone growth, decreases bone mass and BMD, impairs osteoblast function, and increases osteoclast surface in young mice.', 'Mutations at the murine steel locus lead to a defect in the development of hematopoietic stem cells, mast cells, and germ cells. Two isoforms of steel factor (SLF), soluble and membrane-associated, have been reported. Soluble SLF increases osteoclast formation and activity in cell culture. The effects of deletion of membrane-bound SLF on bone metabolism in mice have yet to be determined and are the subject of this study.', 'Five-, 7-, and 12-week-old male and 5-week-old female WCB6F1/J-Kitl(Sl)/Kitl(Sl-d) (Sl/Sl(d)) mice and wildtype (WT) littermates were used. BMD and bone mass, growth, architecture, and turnover were evaluated by DXA (males and females) and histomorphometry (males only). Primary osteoblasts isolated from humeri of 5-week-old male WT and Sl/Sl(d) mice were used to determine osteoblast function, and bone marrow cells from tibias and femurs of these mice were analyzed to determine cell surface expression of osteoclast precursors.']
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['Mortality in ST elevation myocardial infarction (STEMI) is strongly predicted by the time from first medical contact to reperfusion. The aim of this study was to examine the impact of pre-hospital diagnosis by paramedics in the field on the door-to-balloon (DTB) times of patients with ST elevation myocardial infarction undergoing primary percutaneous intervention.', 'Paramedics in the field identified patients with ST elevation myocardial infarction on a 12-lead electrocardiograph, activated the cardiac catheter laboratory team from the field and initiated therapy with anticoagulants and antiplatelet agents in the pre-hospital setting. This cohort of patients was compared to a similar group of patients without pre-hospital diagnosis and notification. The primary outcome measure was DTB times. A secondary end point was mortality at 30 days and mortality at six months.', 'A total of 281 patients, mean age of 61.1±12.9 years underwent primary percutaneous intervention with pre-hospital notification occurring in 63 cases. DTB times were lower in those with pre notification than in those without pre-hospital notification (40.4 vs. 75.6 minutes, p<0.001). This represented a 47.6% shorter DTB time. A non-statistically significant mortality reduction at one month and six months was observed in the pre-hospital notification group (1.6 versus 4.3%, p= 0.307 and 1.6 versus 6.4%, p= 0.203, respectively).']
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['To compare the results of foldable acrylic intraocular lens (IOL) implantation through a clear corneal incision with those of rigid IOL implantation in eyes having pars plana vitrectomy (PPV).', 'Tertiary referral-based university institute.', 'A consecutive retrospective comparative chart review was performed in all eyes that had PPV and foldable IOL implantation between May 15, 1999, and November 1, 2000 (n = 30), and all eyes that had PPV and rigid IOL implantation between April 1, 1996, and May 14, 1999 (n = 30). Preoperative baseline data and postoperative outcome data were recorded. Pars plana vitrectomy and associated vitreoretinal procedures were performed as indicated according to individual circumstances. A minimum of 1 week of follow-up information was available for all eyes.', 'Baseline characteristics in both groups of patients, including age, sex, eye involved, and phakic state, were similar. The preoperative visual acuities were also similar, ranging from 20/30 to hand motions; the mean visual acuity was 20/200. The IOL was implanted in all eyes uneventfully and did not restrict fundoscopy. The mean follow-up was significantly longer in the rigid IOL group (20 months) than in the foldable IOL group (7 months) (P<.001), probably because of the earlier case acquisition. The mean postoperative best corrected visual acuity was 20/200 in the foldable IOL group and 20/100 in the rigid IOL group. There was no difference between the 2 groups in the rate of postoperative retinal detachment, recurrent macular hole, or repeat PPV. Elevated intraocular pressure (IOP) on the first postoperative day was more common in the rigid IOL group than in the foldable IOL group (P =.078) because more patients in the rigid IOL group had surgery for diabetic ocular complications and these patients had a greater IOP rise.']
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['Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea.', 'Women (n=59, mean age 42.6 years [(range 23.3-52.5]) with eBC were recruited before any treatment. Pretreatment ovarian reserve markers (anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], inhibin B) were analysed in relation to ovarian status at 2 years.', 'Pretreatment AMH was significantly lower in women with amenorrhoea at 2 years (4.0 ± 0.9 pmol/L versus 17.2 ± 2.5, P<0.0001), but FSH and inhibin B did not differ between groups. By logistic regression, pretreatment AMH, but not age, FSH or inhibin B, was an independent predictor of ovarian status at 2 years (P=0.005; odds ratio 0.013). We combined these data with a similar cohort (combined n=75); receiver-operator characteristic analysis for AMH gave area under curve (AUC) of 0.90 (95% confidence interval (CI) 0.82-0.97)). A cross-validated classification tree analysis resulted in a binary classification schema with sensitivity 98.2% and specificity 80.0% for correct classification of amenorrhoea.']
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['To identify the effects of indium on the lung and to assess exposure-effect and exposure-response relations between indium exposure and effects on the lungs.', 'Ninety three male indium exposed and 93 male non-exposed workers from four ITO manufacturing or ITO recycling plants were analysed in a cross-sectional study. Indium in serum (In-S) was determined as a biological exposure index. Geometric means (GSD) of In-S were 8.25 ng/ml (4.55) in the exposed workers and 0.25 (2.64) in the non-exposed workers. The maximum concentration of In-S was 116.9 ng/ml. A questionnaire for respiratory symptoms and job histories, spirometry, high-resolution computerised tomography (HRCT) of the chest, serum KL-6, serum SP-A, serum SP-D and serum CRP were measured as the effect indices.', 'Spirometry, subjective symptoms and the prevalence of interstitial or emphysematous changes on lung HRCT showed no differences between exposed and non-exposed workers. Geometric means (GSD) of KL-6, SP-D and SP-A in the exposed workers were 495.4 U/ml (2.26), 85.2 ng/ml (2.02) and 39.6 ng/ml (1.57), and were significantly higher than those in the non-exposed workers. The prevalence (%) of the exposed and non-exposed workers exceeding the reference values were also significantly higher in KL-6 (41.9 vs 2.2), SP-D (39.8 vs 7.5), and SP-A (43.0 vs 24.7). Very sharp exposure-effect and exposure-response relations were discovered between In-S and KL-6 and between In-S and SP-D when the exposed workers were classified into seven groups by In-S.']
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['Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the first successful global dispersal. This initial migration may have passed through Yemen, a region that has experienced multiple migrations events with Africa and Eurasia throughout human history. We use Bayesian phylogenetics to determine how ancient and recent migrations have shaped Yemeni mitogenomic variation.', 'We sequenced 113 mitogenomes from multiple Yemeni regions with a focus on haplogroups M, N, and L3(xM,N) as these groups have the oldest evolutionary history outside of Africa. We performed Bayesian evolutionary analyses to generate time-measured phylogenies calibrated by Neanderthal and Denisovan mitogenomes in order to determine the age of Yemeni-specific clades.', 'As defined by Yemeni monophyly, Yemeni in situ evolution is limited to the Holocene or latest Pleistocene (ages of clades in subhaplogroups L3b1a1a, L3h2, L3x1, M1a1f, M1a5, N1a1a3, and N1a3 range from 2 to 14 kya) and is often situated within broader Horn of Africa/southern Arabia in situ evolution (L3h2, L3x1, M1a1f, M1a5, and N1a1a3 ages range from 7 to 29 kya). Five subhaplogroups show no monophyly and are candidates for Holocene migration into Yemen (L0a2a2a, L3d1a1a, L3i2, M1a1b, and N1b1a).']
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['Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro.', 'Plexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKTSer473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining.', 'Expression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell proliferation was not affected.']
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['In the International Ski Federation (FIS), World Cup (WC) snowboard cross (SBX) and ski cross (SX), the injury incidence in individual qualification runs versus final runs in heats of four athletes is unknown. Objective To investigate the injury incidence in individual qualification runs versus final runs of SBX and SX.', 'Injuries were recorded by the FIS injury surveillance system (FIS ISS) through retrospective athlete interviews at the end of each season during four WC seasons (2006-2010). A total of 713 athletes (345 SBX and 368 SX) were interviewed. Time-loss injuries occurring during SBX and SX competitions were included. Injury incidence was expressed as the relative injury rate (per 1000 runs).', 'For SBX, the injury incidence per 1000 runs in finals was 12.1 vs. 6.1 in qualifications (RR 1.9, 95% CI 1.1-3.5). The injury incidence was 12.9 in finals and 4.4 in qualifications (RR 2.9, 95% CI 1.4-6.2) for SBX males and 10.5 vs. 9.3 (RR 1.1, 95% CI 0.5-2.8) for females. For SX, the injury incidence in finals was 12.4 and 9.2 in qualifications (RR 1.4, 95% CI 0.8-2.3). The injury incidence for SX males was 13.6 in finals vs. 8.8 in qualifications (RR 1.5, 95% CI 0.8-3.1) and10.8 vs. 9.8 (RR 1.1, 95% CI 0.5-2.6) for females.']
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["Sugar intake may be causally associated with chronic disease risk, either directly or by contributing to obesity. However, evidence from observational studies is mixed, in part due to the error and bias inherent in self-reported measures of sugar intake. Objective biomarkers may clarify the relationship between sugar intake and chronic disease risk. We have recently validated a biomarker of sugar intake in an Alaska Native (Yup'ik) study population that incorporates red blood cell carbon and nitrogen isotope ratios in a predictive model. This study tested associations of isotopic estimates of sugar intake with body mass index (BMI), waist circumference (WC) and a broad array of other physiological and biochemical measures of chronic disease risk in Yup'ik people.", "In a cross-sectional sample of 1076 Yup'ik people, multiple linear regression was used to examine associations of sugar intake with BMI, WC and other chronic disease risk factors.", 'Isotopic estimates of sugar intake were not associated with BMI (P=0.50) or WC (P=0.85). They were positively associated with blood pressure, triglycerides (TG) and leptin, and are inversely associated with total-, high-density lipoprotein- and low-density lipoprotein-cholesterol and adiponectin.']
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['Type 2 diabetes (T2D) is an independent risk factor for atrial fibrillation (AF) and stroke. The serine protease cathepsin A (CatA) is up-regulated in diabetes and plays an important role in the degradation of extracellular peptides. This study sought to delineate the role of CatA for the development of atrial remodelling under diabetic conditions.', 'Zucker Diabetic Fatty rats (ZDF) were treated with vehicle (n = 20) or CatA-inhibitor (SAR; 50 mg/kg; n = 20), and compared with age-matched non-diabetic littermates (Ctr, n = 20). Left-atrial (LA) emptying function [magnetic resonance imaging (MRI)] and atrial electrophysiological parameters were measured before sacrifice for histological and biochemical analysis. The impact of enhanced cardiac CatA expression on atrial remodelling was determined using CatA-transgenic mice. At the age of 9.5 months, atrial tissues of ZDF rats showed increased CatA gene expression and CatA-activity, along with increased AF-susceptibility and impaired LA-emptying function. CatA-inhibition reduced CatA-activity in ZDF comparable to Ctr values and decreased LA-fibrosis formation and connexin 43 lateralization. This was associated with shorter median duration of LA-tachyarrhythmia (12.0 ± 1.7 vs. 1.2 ± 0.47 s, P < 0.01) induced by burst pacing and diminished regions of slow conduction. Cardiac MRI revealed better LA-emptying function parameters (active per cent emptying: 29 ± 1 vs. 23 ± 2%, P < 0.01) after CatA-inhibition. CatA-inhibition reduced LA bradykinin-degrading activity in ZDF. Transgenic mice overexpressing CatA demonstrated enhanced atrial fibrosis formation and increased AF-susceptibility.']
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['Our previous results demonstrated that aggregated low density lipoprotein (agLDL) induces tissue factor (TF) expression and activation through Rho A translocation in human vascular smooth muscle cells (VSMC). We also previously demonstrated that membrane sphingomyelin (SM) content is higher in agLDL-exposed VSMC than in control cells. The main enzymes regulating cellular SM content are the family of sphingomyelinases (Smases) that hydrolize SM to phosphorylcholine and ceramide (CER).', 'We wished to investigate whether agLDL has the ability to modulate acidic- (A-) and neutral (N-) Smase activity and whether or not this effect is related to the upregulatory effect of agLDL on Rho A translocation and TF activation in human VSMC.', 'By measuring generated [(14)C]-phosphorylcholine, we found that agLDL significantly decreased A-Smase and specially N-Smase activity. Pharmacological Smase inhibitors increased Rho A and TF. Specific loss-of-function of A-Smase or N-Smase 1 (N1-Smase) by siRNA treatment (500 nmol L(-1), 12 hours) dramatically increased membrane Rho A protein levels (5- and 3-fold, respectively). Concomitantly, TF protein expression and TF procoagulant activity were also increased. Inhibition of A-Smase or N-Smase activity by agLDL, siRNA-anti A- or N1-Smase or pharmacological treatment significantly increased the SM content of vascular cells. The inhibition of SM synthesis by fumonisin B(1) (FB(1)) prevented the upregulatory effect of agLDL on TF.']
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["Australian sexually deceptive Chiloglottis orchids attract their specific male wasp pollinators by means of 2,5-dialkylcyclohexane-1,3-diones or 'chiloglottones', representing a newly discovered class of volatiles with unique structures. This study investigated the hypothesis that UV-B light at low intensities is directly required for chiloglottone biosynthesis in Chiloglottis trapeziformis.", 'Chiloglottone production occurs only in specific tissue (the callus) of the labellum. Cut buds and flowers, and whole plants with buds and flowers, sourced from the field, were kept in a growth chamber and interactions between growth stage of the flowers and duration and intensity of UV-B exposure on chiloglottone production were studied. The effects of the protein synthesis inhibitor cycloheximide were also examined.', 'Chiloglottone was not present in buds, but was detected in buds that were manually opened and then exposed to sunlight, or artificial UV-B light for ≥5\u2009min. Spectrophotometry revealed that the sepals and petals blocked UV-B light from reaching the labellum inside the bud. Rates of chiloglottone production increased with developmental stage, increasing exposure time and increasing UV-B irradiance intensity. Cycloheximide did not inhibit the initial production of chiloglottone within 5\u2009min of UV-B exposure. However, inhibition of chiloglottone production by cycloheximide occurred over 2\u2009h of UV-B exposure, indicating a requirement for de novo protein synthesis to sustain chiloglottone production under UV-B.']
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['The use of enteral nutrition in patients with nonocclusive splanchnic hypoperfusion is controversial. This study aims to quantitate enterocyte nutrient transport and correlate function with morphology during intestinal ischemia.', 'New Zealand White rabbits were randomized to control (celiotomy only) 60-minute infrarenal aortic clamp (IRC) or 60-minute supraceliac aortic clamp (SCC). Small intestinal brush border membrane vesicles (BBMVs) were prepared by magnesium precipitation and serial differential centrifugation. Sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into BBMVs was quantitated by rapid mixing and filtration. Histologic examination of the intestine was performed by a pathologist blinded to groups. Data are reported as mean values+/-SEM, with significance determined by analysis of variance at p < .05.', 'Villus heights in the IRC and SCC groups were 20% and 48% less than control, respectively. SCC histology was characterized by extensive epithelial denudation and necrosis, whereas IRC had mild focal villus edema only. Sodium-dependent glucose and leucine transport each exhibited nonsignificant increases of 20% to 25% in the IRC group and 30% to 55% in the SCC group. No changes were noted in sodium-dependent glutamine, alanine, and arginine uptake or sodium-independent transport.']
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['The beneficial effect of propionyl-L-carnitine (PLC) on cardiac function in diabetes mellitus is well documented. This study was designed to determine whether the improvement in cardiac function mediated by PLC in the diabetic rat heart is associated with an increase in ATP production and tricarboxylic acid (TCA) cycle activity.', 'Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg). Following diagnosis of diabetes, treatment was initiated by supplementing the drinking water with PLC at a concentration of 1 g/L for a period of 6 weeks. ATP production and TCA cycle activity were determined from oxidative rates of glucose and palmitate measured in isolated working hearts from control and diabetic animals.', 'The effect of diabetes was associated with a decrease in heart function, expressed as rate-pressure product (RPP), and in rates of myocardial glucose oxidation. Rates of palmitate oxidation in diabetic hearts were similar to those of control hearts. In PLC-treated diabetic hearts, rates of both glucose and palmitate oxidation were increased and a significant improvement in RPP was observed. As a result, overall ATP production and TCA cycle activity from glucose and palmitate oxidation were increased in diabetic hearts.']
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['The functional impact of gout is poorly understood. The aim of this study was to determine predictors of hand function in gout.', 'Twenty unselected patients with gout were recruited from rheumatology clinics. No patient had an acute gout flare at assessment. Participants were assessed for clinical characteristics of gout, including the site and number of tophi. Hand function was assessed by the Sollerman hand function test. Fingertip to palm (FTP) distance measurement, grip strength and the Disability Assessment of Shoulder and Hand (DASH) questionnaire scores were also recorded. Data were analysed by simple and multiple linear regression models.', 'The median Sollerman score was 75.5 (range 31-80). The median hand FTP distance was 2.91 (0.88-6.69) cm, grip strength was 31 (4-71) kg, and DASH score was 28.77 (0-76.47). Of the clinical characteristics measured, the number of joints of the hand with overlying tophi (hand tophus joint count) was the strongest single predictor of the Sollerman score (r2 = 0.59), and also predicted the other measures of hand mobility and function. A multiple regression model including hand tophus joint count, sex, number of gout flares in the preceding 6 months, gout disease duration and hand tender joint count was a better predictor of the Sollerman score than hand tophus joint count alone (r2 = 0.81, F(4,14) = 3.94, P = 0.024).']
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['Plasmin role in transforming growth factor-beta (TGF-beta)-responsive gene regulation remains to be elucidated. Also, plasmin action on co-repressor Ski-related novel protein N (SnoN) and differential activation of matrix metalloproteinases (MMPs) are unknown. Thus, the role of plasmin on profibrogenic molecule expression, SnoN transcriptional kinetics and gelatinase activation was investigated.', 'Hepatic stellate cells (HSC) were transduced with adenovirus-mediated human urokinase plasminogen activator (Ad-huPA) (4 x 10(9) viral particles/ml). Overexpression of urokinase plasminogen activator and therefore of plasmin, was blocked by tranexamic acid (TA) in transduced HSC. Gene expression was monitored by reverse transcriptase polymerase chain reaction. HSC-free supernatants were used to evaluate MMP-2 and MMP-9 by zymography. SnoN, TGF-beta and tissue inhibitor of metalloproteinase (TIMP)-1 were analysed by Western blot. Plasmin and SnoN expression kinetics were evaluated in bile duct-ligated (BDL) rats.', 'Plasmin overexpression in Ad-huPA-transduced HSC significantly decreased gene expression of profibrogenic molecules [alpha1(I)collagen 66%, TIMP-1 59%, alpha-smooth muscle actin 90% and TGF-beta 55%]. Interestingly, both SnoN gene and protein expression increased prominently. Plasmin inhibition by TA upregulated the profibrogenic genes, which respond to TGF-beta-intracellular signalling. In contrast, SnoN mRNA and protein dropped importantly. Plasmin-activated MMP-9 and MMP-2 in HSC supernatants. Taken together, these findings indicate that MMP-9 activation is totally plasmin dependent. SnoN levels significantly decreased in cholestatic-BDL rats (82%) as compared with control animals. Interestingly, hepatic plasmin levels dropped 46% in BDL rats as compared with control.']
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['The Malone antegrade continence enema procedure revolutionized the surgical management of fecal incontinence. Open and laparoscopic antegrade continence enemas are often performed with cecoplication and mesenteric manipulation. Since our initial laparoscopic antegrade continence enema description, we have simplified our technique. We present our series of laparoscopic antegrade continence enema procedures, discuss technique and outcomes, and review the literature.', 'We retrospectively reviewed children who underwent laparoscopic antegrade continence enema between 2001 and 2007. Outcome measures included operative time, length of stay, stomal complications and resolution of incontinence or constipation. Using an umbilical port and 1 to 2 additional ports, the appendix was mobilized to allow transposition to the umbilicus. No cecoplication was performed. The appendix was not straightened unless catheterization was difficult.', 'A total of 22 patients (mean age 7.8 years) underwent laparoscopic antegrade continence enema. Of the patients 21 were discharged home on postoperative day 1. Mean operative time was 65 minutes (range 30 to 116). In the last 10 patients only 1 working port was used. No perioperative complications were encountered. Mean followup was 24 months (range 1 to 68). Constipation and fecal incontinence resolved in all cases. No patient experienced stomal complications. One obese patient with kyphosis could not pass the catheter beyond the mid appendix at 1 month postoperatively. She had the same problem 1 month following open antegrade continence enema with cecoplication.']
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["Parkinson's disease (PD) is a movement neurodegenerative disorder characterized by death of dopaminergic neurons in the substantia nigra pars compacta of the brain that leads to movement impairments including bradykinesia, resting tremor, postural instability and rigidity. Mutations in several genes have been associated with familial PD, such as parkin, pink, DJ-1, LRKK2 and α-synuclein. Lately, mutations in the GBA gene were recognized as a major cause for the development of PD.Mutations in the GBA gene, which encodes for lysosomal β-glucocerebrosidase (GCase), lead to Gaucher disease (GD), an autosomal recessive sphingolipidosis characterized by accumulation of glucosylceramide, mainly in monocyte-derived cells. It is a heterogeneous disease, with Type 1 patients that do not present any primary neurological signs, and Type 2 or Type 3 patients who suffer from a neurological disease. The propensity of type 1 GD patients and carriers of GD mutations to develop PD is significantly higher than that of the non-GD population.We have shown in the past that parkin and mutant GCase, expressed in heterologous systems, interact with each other, and that normal but not mutant parkin mediates K48-dependent proteasomal degradation of mutant GCase variants.", 'We tested possible competition between mutant GCase and PARIS or ARTS on the E3 ubiquitin ligase parkin, using coimmunoprecipitation assays and quantitative real-time PCR.', 'We show that endogenous mutant GCase variants associate with parkin and undergo parkin-dependent degradation. Mutant GCase competes with the known parkin substrates PARIS and ARTS, whose accumulation leads to apoptosis. Dopaminergic cells expressing mutant GCase are more susceptible to apoptotic stimuli than dopaminergic cells expressing normal GCase, present increased cleavage of caspase 3 and caspase 9 levels and undergo cell death.']
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['It has been reported that hemodialysis (HD) stimulates hepatocyte growth factor (HGF) release, but it is not clear if this stimulation is due to HD itself or to heparin used during HD. To clarify this issue, we undertook the present study.', 'We studied 18 HD patients using high-flux dialyzers, during a single 4-hr hemodialysis session (session A). The dialyzers were pre-rinse with normal saline without heparin, and HD was started with zero ultrafiltration and without anticoagulation. Anticoagulation was administered as IV injection (80 IU/kg of LMWH enoxaparin sodium) 10 min after the beginning of HD. HD was continued for 10 more minutes and then as prescribed. HGF serum levels were measured before the beginning of the HD session (sample t0) as well as 10 and 20 minutes after the beginning of the session (samples t10 and t20). In six more patients (controls), the same study was repeated but without the administration of LMWH during the first 20 min of HD initiation (session B).', 'In comparison with t0, t10 HGF serum levels changed significantly in neither session A nor in session B. However, at t20, HGF levels increased significantly in session A compared with t0 (increment 666.3 +/- 211.0%, p < 0.0001) and t10 (increment 894.2 +/- 506.0%, p < 0.0001), but not in session B. No differences were found between sessions A and B at samples t0 and t10 (p = NS). HGF serum levels at t20 in session A were found to be higher compared with corresponding levels in session B (p < 0.0001).']
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['The possibility that smoking prevalence among junior and senior high school students may decrease with increasing mobile phone bill was reported by the mass media in Japan. We conducted a nationwide survey on adolescent smoking and mobile phone use in Japan in order to assess the hypothesis that mobile phone use has replaced smoking.', 'A total of 70 junior high schools (response rate; 71%), and 69 high schools (90%) from all over Japan responded to 2005 survey. Students in the responding schools were asked to fill out an anonymous questionnaire about smoking behavior, mobile phone bill, and pocket money. Questionnaires were collected from 32,615 junior high school students and 48,707 senior high school students.', 'The smoking prevalence of students with high mobile phone bill was more likely to be high, and that of students who used mobile phones costing 10,000 yen and over per month was especially high. When "quitters" were defined as students who had tried smoking but were not smoking at the time of survey, the proportion of quitters decreased as the mobile phone bill increased. The proportion of students who had smoking friends increased with the increase in the mobile phone bill per month.']
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['Thiazolidinedione ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), are used to treat diabetes. PPARgamma is highly expressed in the colon, and exposure to thiazolidinediones has been proposed to affect the risk for colorectal neoplasia. In vitro models suggest that thiazolidinediones have antineoplastic effects, whereas in vivo studies have produced mixed results: Some indicate an increased risk for intestinal tumors. This study examined the association between PPARgamma-targeted therapies and the risk of colonic neoplasia in patients with diabetes.', 'We conducted 3 retrospective case-control studies nested within the cohort of diabetic patients who were cared for within the Kaiser Permanente of Northern California system from 1994 to 2005. Case subjects were those with colonic neoplasia identified at the time of colonoscopy (study 1), sigmoidoscopy (study 2), or at follow-up lower endoscopy (study 3). Controls had no neoplasia identified at the endoscopic examination. A minimum of 1 year of therapy was used to define medication exposure.', 'Fourteen thousand eighty-six patients were included. Among patients undergoing colonoscopy, there was an inverse association between thiazolidinedione exposure and prevalence of neoplasia (adjusted odd ratio [OR], 0.73; 95% confidence interval [CI], 0.57-0.92); however, this was not evident among patients without anemia (adjusted OR, 0.97; 95% CI, 0.64-1.49). Significant associations between any or long-term thiazolidinedione use and colonic neoplasia were not observed among patients undergoing sigmoidoscopy or serial lower endoscopies.']
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['The VACTERL association is the nonrandom co-occurrence of Vertebral anomalies, Anal atresia, Cardiovascular malformations, Tracheo-esophageal fistula (TEF) and/or Esophageal atresia (EA), Renal anomalies, and/or Limb-anomalies. The full phenotype of patients with EA/TEF and other anomalies of the VACTERL spectrum of defects association is not well described in the literature.', 'Data on patients with EA/TEF seen in two pediatric surgical centers in the Netherlands between January 1988 and August 2006 were evaluated for defects of the VACTERL spectrum as well as non-VACTERL-type defects. The presence of two or more defects of the VACTERL spectrum in addition to EA/TEF was the criterion for inclusion in this study. A detailed description was made of all defects.', 'Of 463 patients with EA and/or TEF, 107 (23.1%) fulfilled the inclusion criterion, of which seventeen cases had a recognized etiology and were excluded, leaving 90 cases (19.4%) for analysis. Other than the esophagus and the trachea, the vertebrae/ribs and the cardiovascular system were most commonly affected (68.9 and 65.6%, respectively). Interestingly, 70% of cases had additional non-VACTERL-type defects, with high occurrences for single umbilical artery (20%), genital defects (23.3%), and respiratory tract anomalies (13.3%).']
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['International comparisons of social inequalities in alcohol use have not been extensively investigated. The purpose of this study was to examine the relationship of country-level characteristics and individual socio-economic status (SES) on individual alcohol consumption in 33 countries.', "Data on 101,525 men and women collected by cross-sectional surveys in 33 countries of the GENACIS study were used. Individual SES was measured by highest attained educational level. Alcohol use measures included drinking status and monthly risky single occasion drinking (RSOD). The relationship between individuals' education and drinking indicators was examined by meta-analysis. In a second step the individual level data and country data were combined and tested in multilevel models. As country level indicators we used the Purchasing Power Parity of the gross national income, the Gini coefficient and the Gender Gap Index.", 'For both genders and all countries higher individual SES was positively associated with drinking status. Also higher country level SES was associated with higher proportions of drinkers. Lower SES was associated with RSOD among men. Women of higher SES in low income countries were more often RSO drinkers than women of lower SES. The opposite was true in higher income countries.']
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['Online weight loss programmes allow members to use social media tools to give and receive social support for weight loss. However, little is known about the relationship between the use of social media tools and the perception of specific types of support.', 'To test the hypothesis that the frequency of using social media tools (structural support) is directly related to perceptions of Encouragement, Information and Shared Experiences support (functional support).', 'Online survey.', 'Members of an online weight loss programme.', 'The outcome was the perception of Encouragement (motivation, congratulations), Information (advice, tips) and Shared Experiences (belonging to a group) social support. The predictor was a social media scale based on the frequency of using forums and blogs within the online weight loss programme (alpha = 0.91). The relationship between predictor and outcomes was evaluated with structural equation modelling (SEM) and logistic regression, adjusted for sociodemographic characteristics, BMI and duration of website membership.', 'The 187 participants were mostly female (95%) and white (91%), with mean (SD) age 37 (12) years and mean (SD) BMI 31 (8). SEM produced a model in which social media use predicted Encouragement support, but not Information or Shared Experiences support. Participants who used the social media tools at least weekly were almost five times as likely to experience Encouragement support compared to those who used the features less frequently [adjusted OR 4.8 (95% CI 1.8-12.8)].']
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['Sarcopenia impairs the outcome of patients with liver cirrhosis independently of liver function reserves. The aim of this study was to investigate whether the rate of skeletal muscle wasting predicts mortality in cirrhotic patients.', 'This retrospective study evaluated 149 cirrhotic patients who visited our hospital between March 2004 and September 2012. The skeletal muscle cross-sectional area at the level of the third lumbar vertebra was measured by computed tomography, from which the skeletal muscle index was obtained for diagnosis of sarcopenia. The relative change in skeletal muscle area per year (ΔSMA/y) was calculated in each patient. Cox proportional hazards regression analysis was performed to evaluate risk factors for mortality.', 'Of the 149 cirrhotic patients, 94 (63%) were diagnosed with sarcopenia. The median of ΔSMA/y in all patients was -2.2%. For patients in Child-Pugh class A, B and C, ΔSMA/y was -1.3%, -3.5% and -6.1%, respectively. During a median follow-up period of 39\xa0months (range, 1-110), 45 patients (30%) died. The optimal cut-off value of ΔSMA/y for predicting mortality was -3.1%; the survival rate in patients with ΔSMA/y of -3.1% or less was significantly lower than in patients with ΔSMA/y of more than -3.1% (P\u2009<\xa00.0001). The multivariate Cox proportional hazards model found ΔSMA/y of -3.1% or less to be significantly associated with mortality in cirrhotic patients (hazard ratio\u2009=\u20092.73, 95% confidence interval\u2009=\u20091.43-5.44, P\u2009<\xa00.01).']
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['the red cell distribution width (RDW), an automated measure of variability in the red blood cell size on full blood count (FBC) is an independent predictor of mortality in several disease states and in healthy older people.', 'we wanted to determine the prognostic value of RDW in patients following a hip fracture-a condition associated with high mortality.', 'we examined the relationship between admission RDW and mortality in 698 consecutive patients admitted with hip fracture.', 'regression analysis was used to examine admission RDW and subsequent mortality, adjusting for admission haemoglobin, mean corpuscular volume, age, gender, pre-morbid residence and independence level, Charlson co-morbidity index and post-operative complications.', 'the mean age was 78 ± 13 years. Unadjusted 1-year mortality was 12, 15, 29 and 36% across quartiles of increasing RDW. Along with age and post-operative complications, RDW remained significantly associated with in-hospital, 120-day and 1-year mortality [adjusted hazard ratios: HR: 1.119, 95% CI: (1.000-1.253), P = 0.05, 1.134 (1.047-1.227), P = 0.004 and 1.131 (1.067-1.199), P < 0.001, respectively]. These relationships remained significant at all three time points on repeat analysis in non-anaemic patients (n = 548).']
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["Inflammatory bowel diseases (IBDs), consisting of ulcerative colitis (UC) and Crohn's disease (CD), are complex disorders with multiple genes contributing to disease pathogenesis. A recent genome-wide association scan identified three novel susceptibility loci for UC: HNF4α, CDH1, and LAMB1. We performed an analysis of these three loci in an independent cohort.", 'In all, 821 UC patients and 1260 healthy controls of central European Caucasian descent were genotyped for single nucleotide polymorphisms (SNPs): rs6017342 (HNF4α), rs1728785 (CDH1), and rs6949033 (LAMB1). Differences in allele and genotype distribution in cases and controls were tested for significance with the χ² test.', 'Allelic association analysis showed that SNP rs6017342 in the HNF4α locus was strongly associated with UC (P = 1,04 × 10(-11) , odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.37-1.77) and SNP rs1728785 (CDH1) was associated with P = 0.01 (OR = 1.23, 95% CI = 1.05-1.44). SNP rs6949033 in LAMB1 was not associated in our cohort (P = 0.12, OR = 1.11, 95% CI = 0.97-1.26). We found an association for SNP rs6949033 (LAMB1) for disease limited to the rectum (P = 0.02). However, this association was lost after correcting for multiple testing. No further specific subphenotype associations were identified.']
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['To evaluate the ability of the papillomacular bundle (PMB) retinal nerve fiber layer and macular inner retinal layer thickness measurements with Spectralis optical coherence tomography (OCT) to differentiate eyes with nonarteritic anterior ischemic optic neuropathy (NAION) from uninvolved eyes and to evaluate whether their thicknesses correlate with visual acuity.', 'An observational, cross-sectional study was performed, including 29 eyes with NAION and 29 uninvolved eyes from 29 patients. Eyes underwent scanning with Cirrus OCT (peripapillary and macular scanning) and Spectralis OCT (N-site axonal peripapillary scan and a new automated segmentation macular scan to measure individual retinal layers) in both eyes.', 'The NAION eyes showed significant thinning versus uninvolved eyes in the macular retinal nerve fiber (P < 0.05), ganglion cell layer (GCL; P < 0.001), and inner plexiform layer (IPL; P < 0.01) by Spectralis and in the GCL-IPL by Cirrus (P < 0.02). Average and sectors of peripapillary retinal nerve fiber layer (pRNFL) and total macular thickness (TMT) were significantly reduced in NAION eyes, with both Spectralis and Cirrus OCT (P < 0.05). Spectralis temporal (ρSpearman = -0.768; P < 0.001) and PMB pRNFL thicknesses (ρSpearman = -0.675; P < 0.001), as well as central macular IPL thickness (ρSpearman = -0.735; P < 0.001), correlated strongly with best corrected visual acuity (BCVA). Quadratic regression using outer nasal TMT by Cirrus OCT and temporal pRNFL thickness by Spectralis were the best models to predict BCVA.']
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['the mainstay of treatment of polymyalgia rheumatica (PMR) is oral glucocorticoids, but randomized controlled trials of treatment are lacking. As a result, there is no evidence from controlled studies on the efficacy of different initial doses or glucocorticoid tapering. The aim of this study is to test if 12.5 mg prednisone/day is an adequate starting dose in PMR and to evaluate clinical predictors of drug response.', '60 consecutive PMR patients were treated with a starting dose of 12,5 mg/day prednisone. Clinical, laboratory, and, in a subset of 25 patients, ultrasonographic features were recorded as possible predictors of response to prednisone. Remission was defined as disappearance of at least 75% of the signs and symptoms of PMR and normalization of ESR and CRP within the first month, a scenario allowing steroid tapering.', '47/60 (78.3%) patients responded to 12.5 mg of prednisone after a mean interval of 6.6±5.2 days. In univariate analysis, body weight and gender discriminated the two groups. In multivariate analysis, the only factor predicting a good response was low weight (p=0.004); the higher response rate observed in women was explained by their lower weight. The mean prednisone dose per kg in the responders was 0.19±0.03 mg in comparison with 0.16±0.03 mg for non responders (p=0.007).']
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['Operative hysteroscopy procedure is extensively used for the treatment of intrauterine abnormalities that can potentially cause infertility. To date, there are little data addressing the effect of operative hysteroscopy that applies electrical current for excision and its subsequent effect on endometrial thickness. This study was aimed to assess the effect of thermal resection used in operative hysteroscopy on endometrial thickness and on fertility outcome in women undergoing in vitro fertilization (IVF).', 'A retrospective study conducted at Hadassah-Hebrew University Medical Center, a tertiary referral center. Included were IVF women who underwent an operative hysteroscopy throughout the years 2000-2010 for intrauterine pathologies.', 'Throughout the years 2000-2010, 41 IVF women who underwent an operative hysteroscopy using electric current between their 82 IVF cycles were studied. The mean age of women at the time of the intervention was 37.1 years (36.7 and 37.5 at the IVF cycles before and after intervention, respectively). The maximal endometrial thickness before operative hysteroscopy was 10.7 mm compared to 9.5 mm after all procedures (P < 0.001). Excluding polypectomy cases (n = 24) the endometrial thickness was 9.9 mm before vs. 9.1 mm after operative hysteroscopy (P < 0.001). The clinical pregnancy rate was 19.5 % before as compared to 24.4 % after operative hysteroscopy (NS). The take home baby rate (THBR), however, was significantly increased following operative hysteroscopy for all indications from 2.4 to 12.2 % (P < 0.05).']
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['Single Nucleotide Polymorphisms (SNPs) are widely used molecular markers, and their use has increased massively since the inception of Next Generation Sequencing (NGS) technologies, which allow detection of large numbers of SNPs at low cost. However, both NGS data and their analysis are error-prone, which can lead to the generation of false positive (FP) SNPs. We explored the relationship between FP SNPs and seven factors involved in mapping-based variant calling - quality of the reference sequence, read length, choice of mapper and variant caller, mapping stringency and filtering of SNPs by read mapping quality and read depth. This resulted in 576 possible factor level combinations. We used error- and variant-free simulated reads to ensure that every SNP found was indeed a false positive.', 'The variation in the number of FP SNPs generated ranged from 0 to 36,621 for the 120 million base pairs (Mbp) genome. All of the experimental factors tested had statistically significant effects on the number of FP SNPs generated and there was a considerable amount of interaction between the different factors. Using a fragmented reference sequence led to a dramatic increase in the number of FP SNPs generated, as did relaxed read mapping and a lack of SNP filtering. The choice of reference assembler, mapper and variant caller also significantly affected the outcome. The effect of read length was more complex and suggests a possible interaction between mapping specificity and the potential for contributing more false positives as read length increases.']
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['To explain the impact of the 10% annual increase in mortality rate in the life tables from about age 45 to 90 years on mean expected mortality rate in any follow-up (FU) group with a wide age range. Use of the mean age to enter a life table invariably underestimates the true mean expected mortality rate in small age groups with an age range of 5 to 10 years. As a result, when mean age and standard deviation (SD) are the only age characteristic given for the cohort reported in a FU study, the mean age must be adjusted upward to enter the life table to obtain a valid mean expected mortality rate of the entire cohort.', "The 1989-91 Decennial US Life Table is used to illustrate the variation of expected annual rate, q', with age, x. The magnitude of the error in mean q' introduced by failure to adjust mean age to obtain mean q' is illustrated in examples of both cardiovascular and cancer FU studies. Other tabular analytical data are also presented.", "From the 1989-91 US Life Tables for the white population, it is shown that the mean increase in annual mortality rate between ages 45 and 90 years has been found to be 9.36 +/- 0.79% per year for males and 9.94 +/- 1.13 for females. For age groups with a narrow range (10 years or less), a mean age can be used to estimate an accurate mean q'. But if the range exceeds about 15 years, as it does in most groups of patients in a FU study, a tabular q; obtained by entering the life table with the mean age is underestimated and is lower than the actual mean q'. The magnitude of the error increases with the magnitude of the range or SD. Examples are given of the magnitude of the error in one group as patients with coronary heart disease and in another group with cancer. Summary data on the magnitude of the error are also given for multiple groups in each category."]
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['An urban primary health care facility in Khayelitsha, South Africa.', 'To determine the difference in total tuberculosis (TB) treatment delay in patients who initially seek care at National TB Control Programme (NTP) facilities after the onset of TB-related symptoms, compared to patients who initially seek care from non-NTP health care practitioners (HCP); and to describe the relative contributions of diagnostic, treatment initiation, patient and health system (HS) delay.', 'A cross-sectional study of adult TB patients treated by the NTP.', 'A total of 210 patients (median age 31 years) were enrolled from May to December 2009: 46% were male, and 58% were human immunodeficiency virus (HIV) infected. The median duration of total delay was 31 days, diagnostic delay 26, treatment initiation delay 0, patient delay 8 and HS delay 17 days. Initial visit to a non-NTP HCP was independently associated with total (P = 0.007), HS (P = 0.014) and diagnostic delays (P = 0.012). HIV infection was an independent risk factor for total (P = 0.047) and HS delay (P = 0.021); 27% of patients reported first going to a non-NTP HCP.']
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['To examine human papillomavirus (HPV) status, the expression of podoplanin and epithelial-mesenchymal transition (EMT) markers and lymphatic vessel counts (LVC) in oropharyngeal squamous cell carcinoma (OPSCC) tissues, and to evaluate whether these factors were associated with survival and nodal status.', 'A total of 53 OPSCC specimens were evaluated for HPV status and expression of proteins such as podoplanin and EMT markers by immunohistochemistry. E-cadherin-negative and vimentin-positive specimens were defined as EMT-positive. Twenty-two OPSCCs were HPV-positive. There was significant progression of nodal status in patients with HPV-positive tumours (P = 0.0475). HPV-positive cases had significantly lower expression of podoplanin (P = 0.0016) and were more frequently EMT-positive (P = 0.0172). Podoplanin-negative cases and EMT-positive cases showed significantly more advanced nodal status than their respective counterparts (P = 0.0082 and P = 0.0186, respectively). LVC correlated with neither HPV nor nodal status. Multivariate analyses revealed that HPV infection was an independent marker of longer disease-specific survival (P = 0.014).']
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['Endoscopic biopsy after chemoradiation therapy (CRT) for esophageal cancer has been used to determine response to treatment. We wanted to determine if endoscopic biopsy can accurately establish evidence of local pathologic complete response (pCR) in patients undergoing CRT.', 'We queried a prospectively maintained database for patients seen at Memorial Sloan-Kettering Cancer Center from 1996 to the present who underwent, (1) CRT for local-regionally advanced esophageal cancer, (2) post-CRT endoscopic biopsy, and (3) esophagectomy. Data points included pathology of post-CRT endoscopy and surgical specimens, tumor histology, and survival. Correlations were analyzed by the chi2 test and one-way analysis of variance. Survival comparisons were assessed using the Kaplan-Meier method and log-rank analysis.', 'One hundred fifty-six patients were identified. Over 80% of patients received cisplatin-based chemotherapy and 5040 cGy of radiation. One hundred eighteen patients had no tumor identified on endoscopic biopsy. A negative biopsy at endoscopy was a poor predictor of pCR (negative predictive value: 31%), with 69% having local disease at esophagectomy. A positive biopsy was predictive of residual disease (positive predictive value: 95%). Negative endoscopic biopsy better predicted a pCR for squamous cell carcinomas versus adenocarcinomas (P[r] < 0.001). Nodal status of surgical specimens was not correlated with post-treatment endoscopic findings. Survival was equivalent after surgery in patients with a negative endoscopic biopsy versus patients with positive pathology.']
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['To explore the antitumor effects of 2-deoxyglucose (2-DG) plus docetaxel (Doc) on PC3 and DU145 cells and its mechanism.', 'The proliferation of cells was detected by methyl thiazolyl tetrazolium (MTT) assay. Then propidium iodide (PI) staining measured apoptotic cells on flow cytometry. ATP assay kit was used to detect ATP content. The expressions of proteins ubiquitinated protein (Ub) and Hsp70 were measured by Western blot.', '2-DG could inhibit proliferation of PC3 and DU145 cells in a dose- and time-dependent manner. However, it could not induce apoptosis in PC3 or DU145. The inhibition rates for PC3 proliferation at 48 h by Doc with concentrations of 0.1, 0.5, 2.5 nmol/L were 10.71%, 25.32% and 56.46% respectively. The inhibition rates for DU145 cell proliferation at 48h by Doc with concentrations of 0.1, 0.5, 2.5 nmol/L were 12.28%, 23.94% and 63.43% respectively. The inhibition rates for PC3 cell proliferation by Doc plus 2-DG with a concentration of 1.0 g/L were 27.15%, 58.74% and 87.95% respectively and 29.53%, 59.41%, and 90.48% for DU145 respectively. 2-DG could enhance the effectiveness of inhibition to PC3 and DU145 proliferation by Doc with a synergistic manner (all q>1.15). The apoptotic rates for PC3 and DU145 induced by Doc 0.5 nmol/L plus 2-DG 1.0 g/L at 48 h were 46.49% and 53.64% respectively. The apoptotic rates were significantly higher than Doc 0.5 nmol/L alone (21.30% for PC3 and 18.92% for DU145 respectively) (P < 0.05). The ATP relative concentration for PC3 in 2-DG 1.0 g/L at 0, 12, 24, 48, and 72 h were 13.75, 11.23, 10.19, 9.81 and 9.02 and for DU145 15.00, 12.59, 11.38, 10.54 and 10.37 respectively. Simultaneously, Western blot showed that Ub and Hsp70 protein were expressed intensively.']
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['Irritable bowel syndrome (IBS) is regarded as a functional bowel disorder. Few studies have looked for histopathologic changes in the gut and only then in biopsy specimens from intestinal mucosa. Because bowel function is governed mainly by nerve plexuses in the bowel wall, we have investigated full-thickness bowel biopsy specimens in patients with severe IBS.', 'We used a laparoscopy-assisted technique to obtain full-thickness biopsy specimens from the proximal jejunum. Tissue specimens were investigated with light microscopy using routine stainings and immunohistochemical techniques. Horizontal sectioning was done to visualize large areas of the myenteric plexus. Fifteen autopsy specimens were used as controls regarding the myenteric plexus. Colorectal adenoma controls with terminal ileum biopsy specimens and full-thickness jejunal biopsy specimens from patients with degenerative enteric neuropathy were used as control groups for intraepithelial lymphocyte counts.', 'Ten patients (2 males, 8 females) were studied. In 9 patients, we found low-grade infiltration of lymphocytes in the myenteric plexus. Lymphocytes had peri- and intraganglionic location. The mean number of lymphocytes per ganglion ranged from 1.9 to 7.1 per patient, with an overall mean of 3.4. No intraganglionic lymphocytes were found in the control group and only a few periganglionic lymphocytes (mean, 0.2). Four patients had concomitant intraepithelial lymphocytosis. Neuron degeneration was evident in 6 of 9 patients with and 1 patient without ganglionic lymphocyte infiltration.']
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['The rate of ocular growth can be modified by the imposition of either plus or minus lenses before the eyes, which creates changes in retinal defocus. Several hypotheses with relatively complicated mechanisms have been proposed to explain these changes, but the underlying mechanism has remained elusive.', 'Our new analysis using schematic models, however, provides a relatively simple and logically-consistent explanation of how retinal defocus magnitude alone during ocular growth gives the requisite sign for an appropriate change in ocular growth rate.', 'During a normal genetically-determined incremental increase in axial length, the presence of either an imposed plus or minus lens results in an increase or decrease, respectively, of the blur circle magnitude. Neuromodulators in the retina are proposed to regulate the sensitivity to retinal-image contrast by means of a local feedback mechanism, and the alteration in retinal-image contrast associated with the change in blur circle causes an increase or decrease, respectively, in the rate of release of neuromodulators as well as the rate of proteoglycan synthesis, the latter being associated with the structural integrity of the sclera.']
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['Recent studies have revealed an association between coronary risk factors and both the number and function of bone marrow-derived endothelial progenitor cells (EPCs). Although hypertension is an important coronary risk factor, the influence to the EPCs is not fully understood. We investigated the effect of hypertension on EPC senescence.', 'Experimental study We investigated the number and senescence of EPCs in spontaneously hypertensive rats (SHR/Izm) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. EPCs were isolated from peripheral blood of rats and were characterized. EPC senescence was detected by acidic beta-galactosidase staining. In addition, we measured the telomerase activity using polymerase chain reaction-enzyme-linked immunosorbent assay.', 'EPCs were isolated from peripheral blood samples in 37 patients with essential hypertension. After ex-vivo cultivation, we detected senescence and measured the telomerase activity. The total severity index of hypertension-induced organ damage was calculated by the summation of each severity index in the classification of hypertension severity by Tokyo University (1984).', 'Experimental study The EPC senescence in SHR/Izm and DOCA-salt hypertensive rats was significantly increased compared with that of control rats. The telomerase activities in SHR/Izm and DOCA-salt hypertensive sensitive rats were also significantly lowered compared with those of control rats. Clinical study Compared with the control group, EPCs from hypertensive patients showed accelerated senescence and also showed reduced telomerase activity. In hypertensive patients, the degree of hypertension-induced organ damage was negatively correlated with telomerase activity, and was positively correlated with EPC senescence.']
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['The neuropeptide calcitonin gene-related peptide (CGRP) is a migraine trigger that plays a crucial role in migraine pathophysiology, and CGRP antagonism is efficient in the treatment of migraine attacks. Familial hemiplegic migraine (FHM) is a dominantly inherited subtype of migraine with aura associated with several gene mutations. FHM shares many phenotypical similarities with common types of migraine, indicating common neurobiological pathways. We tested the hypothesis that the FHM genotype confers a CGRP hypersensitive phenotype.', 'We included 9 FHM patients with known mutations in the CACNA1A and ATP1A2 genes and 10 healthy controls. All subjects received i.v. infusion of CGRP (1.5 microg/min). We recorded headache intensity on a verbal rating scale and vascular changes in the middle cerebral artery and the superficial temporal artery.', 'CGRP infusion did not induce an aura in any of the participants. The incidences of reported migraine and migraine-like headache were not different in the two groups, with 22% (2 of 9) reporting migraine in the patient group and 10% (1 of 10) reporting migraine-like headache in the control group (95% CI -0.31 to 0.55; p = 0.58). Headache severity and intensity were not different between the groups.']
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['Hyperglycemia aggravates ischemic brain damage. Since catecholamines increase hepatic gluconeogenesis, resulting in hyperglycemia, we investigated whether norepinephrine and dopamine elevate arterial blood glucose, thereby increasing pericontusional cortical glucose and lactate concentrations and brain edema in brain-injured rats.', 'Prospective, randomized, controlled animal study.', 'Male Sprague Dawley rats.', 'Physiological saline solution, norepinephrine, or dopamine were infused intravenously for 90 min beginning 4.5 h after inducing a focal cortical contusion. Blood glucose, lactate, and pericontusional cortical extracellular glucose and lactate were determined before, during and up to 60 min after the infusion period. Thereafter brains were removed to assess hemispheric water content.', 'Continuous norepinephrine and dopamine infusion significantly increased pericontusional glucose concentrations, being mostly sustained by norepinephrine (NaCl: 1.3+/-0.2, dopamine: 2.7+/-0.2, norepinephrine: 4.8+/-1.1 mM). While arterial blood glucose was only significantly elevated in norepinephrine-treated rats from 8.6+/-0.6 to 12.6+/-1.6 mM, the extracellular to blood glucose ratio was significantly increased in dopamine- and norepinephrine-treated rats (0.28+/-0.01 and 0.38+/-0.05 vs. 0.17+/-0.01). Plasma and pericontusional lactate remained unchanged, and brain edema was similar in all groups.']
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['DUF642 proteins constitute a highly conserved family of proteins that are associated with the cell wall and are specific to spermatophytes. Transcriptome studies have suggested that members of this family are involved in seed development and germination processes. Previous in vitro studies have revealed that At4g32460- and At5g11420-encoded proteins interact with the catalytic domain of pectin methyl esterase 3 (AtPME3, which is encoded by At3g14310). PMEs play an important role in plant development, including seed germination. The aim of this study was to evaluate the function of the DUF642 gene At4g32460 during seed germination and plant development and to determine its relation to PME activity regulation.', 'Our results indicated that the DUF642 proteins encoded by At4g32460 and At5g11420 could be positive regulators of PME activity during several developmental processes. Transgenic lines overexpressing these proteins showed increased PME activity during seed germination, and improved seed germination performance. In plants expressing At4g32460 antisense RNA, PME activity was decreased in the leaves, and the siliques were very short and contained no seeds. This phenotype was also present in the SALK_142260 and SALK_054867 lines for At4g32460.']
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['It has been demonstrated that the interplay of adhesion molecule CD44 and its ligands can regulate cancer cell proliferation, migration and invasion, as well as tumor-associated angiogenesis and is related to breast cancer patient survival. In this two-stage, case control study, we determined whether common functional tagSNPs (single nucleotide polymorphisms) are associated with breast cancer risk and prognosis.', 'Five tagSNPs of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were selected and genotyped in 1,853 breast cancer patients and 1,992 healthy control subjects in Eastern and Southern populations. Potential function of rs13347C>T and association between this variation and breast cancer were further studied.', "Compared with the most common rs13347CC genotype, variant genotypes (CT and TT) increased an individual's susceptibility to breast cancer, especially in estrogen receptor (ER) negative patients (odds ratio (OR) = 1.37, 95%CI = 1.17 to 1.59 for ER positive patients; OR = 2.37, 95% CI = 2.00 to 2.80 for ER negative patients). We also found that rs13347CT+ TT genotypes predicts lower five-year survival rate (hazard ratio (HR) = 1.85, 95% CI = 1.09 to 3.15, P = 0.023), with the lowest survival probability in ER negative T allele carriers. Furthermore, our reporter assay findings, although preliminary and rather modest, showed that miR-509-3p may suppress CD44 expression more strongly in C allele carriers than T allele carriers (P < 0.01). Similarly, rs13347 variant genotypes (CT and TT) carriers were shown to have more CD44 expression than CC carriers in both immunohistochemistry (P < 0.001) and western blotting (P = 0.001) results."]
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['Platelet-derived growth factor (PDGF) is the strongest stimulator of the proliferation of hepatic stellate cells (HSCs). PDGF receptor beta subunit (PDGFR-beta) is acquired on HSCs proliferation induced by PDGF. In this study, we aim to investigate the effect of PDGFR-beta small interference RNA (siRNA) on experimental hepatic fibrosis.', 'We constructed a PDGFR-beta siRNA expression plasmid and investigated its effect on the activation of HSCs. Bromodeoxyuridine incorporation was performed to investigate the effect of PDGFR-beta siRNA on HSCs proliferation. A hydrodynamics-based transfection method was used to deliver PDGFR-beta siRNA to rats with hepatic fibrosis. The distribution of transgenes in the liver was observed by immunofluorescence. The antifibrogenic effect of PDGFR-beta siRNA was investigated pathologically.', 'Platelet-derived growth factor receptor-beta subunit siRNA could significantly downregulate PDGFR-beta expression, suppress HSCs activation, block the mitogen-activated protein kinase signalling pathway and inhibit HSCs proliferation in vitro. PDGFR-beta siRNA expression plasmid could be delivered into activated HSCs by the hydrodynamics-based transfection method, and remarkably improve the liver function of the rat model induced by dimethylnitrosamine and bile duct ligation. Furthermore, the progression of fibrosis in the liver was significantly suppressed by PDGFR-beta siRNA in both animal models.']
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['Natural killer (NK) cells have emerged as major players in anti-viral and anti-tumour immune responses. Like cytotoxic T lymphocytes (CTL), they express perforin and are potent secretors of gamma-interferon (IFN-gamma). However, there is conflicting evidence about their role in mediating rejection of xenogeneic tissue.', 'A pig-to-mouse peritoneal cell model of xenotransplantation was used to investigate the effect of NK deficiency on xenograft recovery and the possible mechanisms behind this NK-mediated graft rejection. gamma c(-/-)RAG(-/-) mice were used as a model of NK deficiency. Additionally, NK cells were depleted in RAG(-/-) mice using anti-asialo GM1. The contributions of IFN-gamma, perforin and NKT cells were studied using knock-out mice that were depleted in vivo of T cells. Mice were injected with 10(7) pig cells intraperitoneally and peritoneal fluid was assessed 5 days later for xenograft recovery and phenotypic analysis. The requirement for NK cells for xenograft rejection was also assessed using luciferase-transfected porcine cells in a renal subcapsular model of transplantation.', 'Pig cell recovery was enhanced in both gamma c(-/-)RAG(-/-) and NK-depleted RAG(-/-) mice when compared with RAG(-/-) control mice. IFN-gamma(-/-) mice depleted of T cells also demonstrated superior graft survival compared with their B6 counterparts. However, there were minimal graft survival differences between Pfp(-/-) and B6 control mice. Similarly, a deficiency in NKT cells did not improve pig xenograft recovery from the peritoneum of these mice.']
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['This study aimed to investigate the influence of hypoxia on angiogenesis in a 3D gel, with co-culturing adipose-derived stromal cells (ASCs) and endothelial cells (ECs).', 'ASCs from green fluorescent protein-labeled mice and ECs from red fluorescent protein-labeled mice were co-cultured in 3D collagen gels at 1:1 ratio, in normal and hypoxic oxygen conditions, and morphology of angiogenesis was observed using confocal laser scanning microscopy. To discover changes in growth factors between monoculture ASCs and ECs, transwell co-cultures of ASCs and ECs were applied. Semi-quantitative PCR was performed to explore mRNA expression of growth factors.', 'Enhanced angiogenesis was observed in 3D gels implanted with 1:1 mixture of ASCs and ECs after 7 days hypoxia. Genes including VEGFA/B, EGF-1, HIF-1a, IGF-1, PDGF, TGF-β1 and BMP-2/4 in ECs, both monoculture and co-culture, were significantly enhanced after being cultured under hypoxia. In comparison, genes VEGFA/B, EGF-1, HIF-1a, TGF-β1 and BMP-2 in ASCs increased. In all, factors VEGFA/B, EGF-1, HIF-1a, TGF-β1 and BMP-2 increased in both ASCs and ECs after being cultured in hypoxia no matter whether as monoculture or co-culture.']
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['This study was designed to identify the inhibitory effect of curcumin on ox-LDL-induced monocyte chemoattractant protein-1 (MCP-1) production and investigated whether the effects are mediated by mitogen-activated protein kinase (MAPK) and NF-κB pathways in rat vascular smooth muscle cells (VSMCs).', 'The VSMCs cells were pretreated with curcumin, before stimulation with ox-LDL. The ox-LDL-induced MCP-1 expression was determined by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Intracellular signaling was investigated by Western blot.', 'The concentrations of MCP-1 in cell supernatant and were upregulated by ox-LDL in a dose- and time-dependent manner. Additionally, curcumin decreased the expression of MCP-1 in a dose-dependent manner under treatment with ox-LDL (100\xa0μg/ml). Signal transduction studies indicated that the ox-LDL-induced MCP-1 expression in VSMCs could be partly reversed by the inhibitor of p38 MAPK (SB203580) and NF-κB (BAY11-7082), whereas the ERK inhibitor (PD98059) and the JNK inhibitor (SP600125) had no effect. Western blot revealed that curcumin reduced ox-LDL- induced p38 MAPK phosphorylation and nuclear NF-κB p65 protein at the indicated concentration.']
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['The aim of this study was to consider whether adenomas in the resection margins could represent a risk factor for pouch polyps in familial adenomatous polyposis (FAP) patients.', 'We reviewed 46 patients treated by restorative proctocolectomy (RPC) for FAP: 9 hand-sewn and 37 stapled ileal pouch-anal anastomosis (IPAA). We analyzed the presence of polyps in the doughnuts from stapled anastomosis and in the resection margins from hand-sewn anastomosis. The presence of polyps in the IPAA was then assessed in 30 patients (6 hand-sewn and 24 stapled IPAA): 4 from the histology of the excised pouch and 26 by endoscopy (range 4 months to 12 years after operation, mean 6 years).', 'Surprisingly, pouch adenomas were found in only 2 of 30 (7%) of patients, 1 of 6 hand-sewn and 1 of 24 stapled anastomosis (P > 0.1), 9 and 11 years, respectively, after operation. However, there were 6 patients with inflammatory (3), fibroepithelial (2), or lymphoid (1) polyps. The risk of pouch adenomas after 8 years was 20% (P < 0.05). Pouch adenomas were found in 1 of 11 patients having adenomas in the margins or in the doughnuts (9%) and in 1 of 19 with no adenomas at the margins (5%; P > 0.1).']
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['Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma.', 'All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation.', 'A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0\u2009g/dL (P\u2009<\u20090.01), cancer antigen 19-9 ≤200\u2009U/mL (P\u2009=\u20090.03), carcinoembryonic antigen ≤10 ìg/L (P\u2009<\u20090.01) or patients without a history of cirrhosis (P\u2009<\u20090.01) or diabetes (P\u2009=\u20090.02) were associated with a greater length of overall survival. A serum albumin level >3.0\u2009g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14-0.70) with a survival benefit of 44 weeks.']
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['Stem cell factor (SCF) and its receptor, c-kit, are modulators of angiogenesis. Neonatal hyperoxia-induced lung injury (HILI) is characterized by disordered angiogenesis. The objective of this study was to determine whether exogenous SCF improves recovery from neonatal HILI by improving angiogenesis.', 'Newborn rats assigned to normoxia (RA: 20.9% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to 15, received daily injections of SCF 100 μg/kg or placebo (PL) from P15 to P21. Lung morphometry was performed at P28. Capillary tube formation in SCF-treated hyperoxia-exposed pulmonary microvascular endothelial cells (HPMECs) was determined by Matrigel assay.', 'As compared with RA, hyperoxic-PL pups had decrease in alveolarization and in lung vascular density, and this was associated with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and vascular remodeling. In contrast, SCF-treated hyperoxic pups had increased angiogenesis, improved alveolarization, and attenuation of pulmonary hypertension as evidenced by decreased RVSP, right ventricular hypertrophy, and vascular remodeling. Moreover, in an in vitro model, SCF increased capillary tube formation in hyperoxia-exposed HPMECs.']
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['Bacillus subtilis glucokinase (GlcK) (GenBank NP_390365) is an ATP-dependent kinase that phosphorylates glucose to glucose 6-phosphate. The GlcK protein has very low sequence identity (13.7%) to the Escherichia coli glucokinase (Glk) (GenBank P46880) and some other glucokinases (EC 2.7.1.2), yet glucose is merely its substrate. Our lab has previously isolated and characterized the glcK gene.', "Microbial glucokinases can be grouped into two different lineages. One of the lineages contains three conserved cysteine (C) residues in a CXCGX(2)GCXE motif. This motif is also present in the B. subtilis GlcK. The GlcK protein occurs in both monomer and homodimer. Each GlcK monomer has six cysteines. All cysteine residues have been mutated, one-by-one, into alanine (A). The in vivo GlcK enzymatic activity was assayed by functional complementation in E. coli UE26 (ptsG ptsM glk). Mutation of the three motif-specific residues led to an inactive enzyme. The other mutated forms retained, or in one case (GlcKC321A) even gained, activity. The fluorescence spectra of the GlcKC321A showed a red shift and enhanced fluorescence intensity compare to the wild type's."]
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['To investigate differences in viral and proviral load between the peripheral blood and the intestinal mucosal immune system in HIV-infected patients.', 'HIV-1 p24 and HIV DNA content were compared in blood samples and intestinal biopsies from HIV-infected patients.', 'Intestinal biopsies and peripheral blood were simultaneously obtained from 27 HIV-infected patients undergoing diagnostic endoscopy. The p24 concentrations were measured in serum and homogenized intestinal biopsies by enzyme-linked immunosorbent assay after acid-dissociation of immune complexes. Proviral load was determined in blood and intestinal biopsies by a quantitative competitive polymerase chain reaction amplifying the HIV-1 nef gene from genomic DNA.', 'No significant differences were found in proviral load comparing HIV copies per 1.5 x 10(5) cell equivalents in blood [2650 (600-44000)] and intestinal biopsies [4200 (1325-19 625)]. Paired analysis revealed a strong positive correlation between serum and mucosal proviral load. In contrast, HIV core protein p24 was detected in intestinal biopsies from 18 patients in much higher concentrations than in serum [858 (262-4111) pg/g versus 34 (9-242) pg/g; P < 0.005]. The p24 concentrations in serum and intestinal biopsies did not correlate and no significant correlation was observed in serum or intestinal biopsies between proviral load and p24 concentrations. No clear correlations were observed between clinical parameters and HIV DNA or HIV p24 levels in blood or biopsies.']
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['Helicobacter pylori infection is less prevalent and atrophic gastritis is less extensive in patients with reflux oesophagitis than those without it, but few studies have examined this relationship directly.', 'We investigated the relationship between H pylori infection, acid secretion, and reflux oesophagitis in Japanese subjects.', 'A total of 105 patients with erosive reflux oesophagitis were compared with 105 sex and age matched patients without reflux oesophagitis.', 'The diagnosis of H pylori infection was made by histological examination of gastric mucosal biopsy specimens, rapid urease test, and detection of serum IgG antibodies. Acid secretion was assessed by the endoscopic gastrin test.', 'H pylori infection was present in 36 patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects (76.2%) (odds ratio 0.163, 95% confidence interval 0.09-0.29). Overall acid secretion was significantly greater in patients with reflux oesophagitis. Among H pylori positive patients, acid secretion was greater in patients with reflux oesophagitis than those without oesophagitis.']
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['We previously demonstrated the HMG-CoA reductase inhibitor, pravastatin, is actively taken up into isolated rat hepatocytes through multispecific organic anion transporters. The present study examined whether a newly cloned organic anion transporting polypeptide (oatp2) transports pravastatin.', 'We investigated functional expression of oatp2 in Xenopus laevis oocytes, to examine [14C] pravastatin uptake.', '[14C] Pravastatin (30 microM) uptake into oatp2 cRNA-injected oocytes was 40 times higher than that of water-injected control oocytes. The oatp2-mediated pravastatin uptake was Na+-independent and saturable. The Michaelis-Menten constant was 37.5+/-9.9 microM, a level comparable to that obtained in isolated rat hepatocytes in our previous study. As is the case with rat hepatocytes, the uptake of pravastatin (30 microM) was inhibited by 300 microM concentrations of taurocholate, cholate, bromosulfophthalein, estradiol-17beta-glucuronide, and simvastatin acid, but not by para-aminohippurate. On the other hand, [14C] simvastatin acid (30 microM) uptake of oatp2 cRNA-injected oocytes was not significantly different from that of water-injected oocytes.']
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['HER2/neu-positive breast cancer cells have recently been shown to use a unique Warburg-like metabolism for survival and aggressive behavior. These cells exhibit increased fatty acid synthesis and storage compared to normal breast cells or other tumor cells. Disruption of this synthetic process results in apoptosis. Since the addition of physiological doses of exogenous palmitate induces cell death in HER2/neu-positive breast cancer cells, the pathway is likely operating at its limits in these cells. We have studied the response of HER2/neu-positive breast cancer cells to physiological concentrations of exogenous palmitate to identify lipotoxicity-associated consequences of this physiology. Since epidemiological data show that a diet rich in saturated fatty acids is negatively associated with the development of HER2/neu-positive cancer, this cellular physiology may be relevant to the etiology and treatment of the disease. We sought to identify signaling pathways that are regulated by physiological concentrations of exogenous palmitate specifically in HER2/neu-positive breast cancer cells and gain insights into the molecular mechanism and its relevance to disease prevention and treatment.', 'Transcriptional profiling was performed to assess programs that are regulated in HER2-normal MCF7 and HER2/neu-positive SKBR3 breast cancer cells in response to exogenous palmitate. Computational analyses were used to define and predict functional relationships and identify networks that are differentially regulated in the two cell lines. These predictions were tested using reporter assays, fluorescence-based high content microscopy, flow cytometry and immunoblotting. Physiological effects were confirmed in HER2/neu-positive BT474 and HCC1569 breast cancer cell lines.', 'Exogenous palmitate induces functionally distinct transcriptional programs in HER2/neu-positive breast cancer cells. In the lipogenic HER2/neu-positive SKBR3 cell line, palmitate induces a G2 phase cell cycle delay and CHOP-dependent apoptosis as well as a partial activation of the ER stress response network via XBP1 and ATF6. This response appears to be a general feature of HER2/neu-positive breast cancer cells but not cells that overexpress only HER2/neu. Exogenous palmitate reduces HER2 and HER3 protein levels without changes in phosphorylation and sensitizes HER2/neu-positive breast cancer cells to treatment with the HER2-targeted therapy trastuzumab.']
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['Endothelial progenitor cells (EPCs) can differentiate into endothelial cells (ECs) and participate in postnatal vasculogenesis, but the mechanism of EPC differentiation remains largely unknown. We investigated the role of AMP-activated protein kinase (AMPK) in EPC differentiation and functions.', 'Vascular endothelial growth factor caused the phosphorylation of AMPK, acetyl-coenzymeA (CoA) carboxylase (ACC), and eNOS in human cord blood-derived EPCs. The expression of EC markers, including VE-cadherin and intercellular adhesion molecule1 (ICAM-1), was also increased but blocked by Compound C, an AMPK inhibitor. AICAR, an AMPK agonist, increased the phosphorylation of ACC and eNOS and the expression of EC markers in a time- and dose-dependent manner, which reinforces the positive effect of AMPK on EPC differentiation. The effects of AICAR could be blocked by treatment with L-NAME, an eNOS inhibitor. Functionally, AICAR increased but Compound C decreased the angiogenesis of EPCs in vitro and in vivo. Furthermore, lovastatin promoted the activation of AMPK and eNOS, the expression of EC markers, tube formation, adhesion, and in vivo vasculogenesis of EPCs, which could be blocked by treatment with Compound C.']
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['To study the role of long non-coding RNA (lncRNA) MALAT1 in transforming growth factor beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells.', 'ARPE-19 cells were cultured and exposed to TGF-β1. The EMT of APRE-19 cells is confirmed by morphological change, as well as the increased expression of alpha-smooth muscle actin (αSMA) and fibronectin, and the down-regulation of E-cadherin and Zona occludin-1(ZO-1) at both mRNA and protein levels. The expression of lncRNA MALAT1 in RPE cells were detected by quantitative real-time PCR. Knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). The effect of inhibition of MALAT1 on EMT, migration, proliferation, and TGFβ signalings were observed. MALAT1 expression was also detected in primary RPE cells incubated with proliferative vitreoretinopathy (PVR) vitreous samples.', 'The expression of MALAT1 is significantly increased in RPE cells incubated with TGFβ1. MALAT1 silencing attenuates TGFβ1-induced EMT, migration, and proliferation of RPE cells, at least partially through activating Smad2/3 signaling. MALAT1 is also significantly increased in primary RPE cells incubated with PVR vitreous samples.']
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['There is evidence that depression impairs natural killer cell activity (NKA); this could have implications for anti-tumour immunity. Our aim was to examine the role of the hypothalamic-pituitary-adrenal (HPA) axis in suppressing NKA in a population of patients with early breast cancer, screened for depression. Secondary aims were to study the relationship between psychological, endocrine and immune variables and baseline tumour characteristics.', 'A cross-sectional population of female patients (n=55) with early breast cancer was sampled prior to primary surgery. Structured interview and psychometric instruments measured psychological distress. Flow cytometry was used to enumerate NK cells and lymphocytes were cryopreserved for use in a 51Cr-release assay, to estimate NKA. Midnight and three early morning saliva samples were collected to measure free cortisol levels. Tumour characteristics were obtained from hospital laboratory data.', 'A high rate of psychological morbidity (40%) was observed in the population. NKA was reduced in those with past or current psychiatric illness compared to those without (344 v. 553 LU20 and 455 v. 569 LU20 respectively, p < 0.05 for both). Cortisol was not related to psychological status but was modestly positively correlated to NKA. A positive correlation was observed between the Fighting Spirit subscale of the Mental Adjustment to Cancer Scale and tumour size (r=0.383, p=0.012).']
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['Blood oxygenation level-dependent (BOLD)-weighted and vessel-encoded arterial spin labeling (VE-ASL) MRI provide complementary information and can be used in sequence to gauge hemodynamic contributions to cerebrovascular reactivity. Here, cerebrovascular reactivity is assessed using dual echo VE-ASL MRI to understand how VE labeling preparations influence BOLD and ASL contrast in flow-limited and healthy perfusion territories.', 'Patients (n\u2009=\u200912; age\u2009=\u200955 +/- 14 years; 6F/6M) presenting with ischemic steno-occlusive cerebrovascular disease underwent 3.0T angiographic imaging, T1 -weighted structural, and planning-free dual echo hypercarbic hyperoxic (i.e., carbogen) VE-ASL MRI. Vasculopathy extent, timecourses, and cerebrovascular reactivity (signal change and Z-statistic) for different VE-ASL images were contrasted across flow territories and Bonferroni-corrected P-values reported.', 'BOLD cerebrovascular reactivity (i.e., long-TE VE-ASL) Z-statistics were similarly sensitive to asymmetric disease (P\u2009≤\u20090.002) regardless of labeling scenario. Cerebral blood flow reactivity correlated significantly with BOLD reactivity (Z-statistic). However, BOLD signal changes did not differ significantly between labeling scenarios (P\u2009>\u20090.003) or across territories (P\u2009>\u20090.002), indicating BOLD signal changes in response to carbogen offer low sensitivity to lateralizing disease.']
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['Heart failure (HF) is a major cause of death and morbidity. Connexin 43 (Cx43) content is reduced in the failing myocardium, but regulating factors have not been identified. In HF, inducible nitric oxide synthase (iNOS)-induced high levels of nitric oxide (NO) cause apoptosis and cardiac dysfunction. However, a direct iNOS-Cx43 link has not been demonstrated. We investigated this relationship in mice after myocardial infarction.', 'Effects of myocardial infarction were evaluated 2 weeks after coronary artery ligation in wild-type C57BL/6 (WT) and iNOS(-/-) knockout mice. Myocardial Cx43 and Cx45 content were assessed by immunofluorescence confocal imaging and western blotting. Cardiac function was evaluated in anaesthetized mice using a micro pressure-tipped catheter inserted into the left ventricle.', 'Despite similar infarct size, deficiency in iNOS resulted in significantly lower plasma nitrate/nitrite levels, better haemodynamic performance and lower mortality 2 weeks after coronary ligation. Myocardial Cx43, but not Cx45, content was lower in WT mice following ligation. The reduction in Cx43 was less in iNOS(-/-) compared with WT mice. To assess the direct effect of NO on Cx43 expression, cultured neonatal mouse cardiomyocytes were employed. Incubation with the NO donor, S-nitroso-N-acetylpenicillamine, elicited a dose-dependent decrease in Cx43 content in cultured neonatal cardiomyocytes.']
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['The clinical benefit of gemcitabine, the standard systemic therapy of pancreatic cancer (PaCa), remains modest as a result of high chemoresistance. The proteasome inhibitor bortezomib has antitumour activity against PaCa in vitro and in vivo. We examined the antitumour activity of combination PaCa therapy with bortezomib and gemcitabine.', 'Cell proliferation assays were performed using WST-1 reagent. Protein expression was determined by Western blotting. Efficacy of bortezomib and/or gemcitabine was tested in vivo in a survival study.', 'Bortezomib at 10 microM caused 29% and 72% inhibition in AsPC-1 PaCa cell proliferation at 48 and 96 h incubation, respectively. Bortezomib was even more active against PaCa cell lines Panc-1 and MiaPaCa, with 80% inhibition of proliferation at 48 h. The combination of bortezomib and gemcitabine inhibited AsPC-1 proliferation more effectively compared with each single agent alone. Poly(ADP-ribose) polymerase (PARP) cleavage, an apoptotic indicator, reached 6.6-, 2- and 8.5-fold over controls for bortezomib, gemcitabine and the combination. The median survival was 31 (controls and bortezomib), 40 (gemcitabine) and 48 days (combination), respectively (P < 0.002).']
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['beta-catenin has recently been reported to act as a cell growth promoter through cyclin D1 transcription. However, the correlation between beta-catenin and cyclin D1 expressions is not fully understood in endometrial tissues.', 'Immunohistochemical expression of beta-catenin was examined in normal endometria (32 cases) and endometrial carcinomas (82 cases), and its expression was compared with that of cyclins (D1, E, A, B1).', "Sporadic nuclear staining of beta-catenin and cyclins was observed from proliferative phase of early secretory phase endometria, however, spacial correlations between beta-catenin and cyclins were not evident. In endometrial carcinomas, positivity for nuclear beta-catenin and cyclins increased compared to the normal endometria. Topologically, the cyclin D1-positive cells were frequently found in nuclear beta-catenin-positive cells. In addition, Spearman's rank correlation analysis revealed that the nuclear expression of beta-catenin correlated positively with that of cyclin D1 (p < 0.0001)."]
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['Congenital cytomegalovirus (CMV) brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV) and the pattern of injury to the developing brain.', 'We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs) and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi) cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection.']
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['Despite therapeutic innovations, metastatic colorectal cancer (mCRC) is still characterized by poor prognosis and few molecular markers predict the risk of progression. Polycomb group genes (PcGs) are epigenetic modifiers involved in tumor suppressor gene silencing. PcG member EZH2 mediates gene silencing through histone-H3 lysine-27 methylation. In colorectal cancer (CRC), EZH2 overexpression predicts shorter survival. Recently, four EZH2 single-nucleotide polymorphisms (SNPs) have been described. The present study was aimed at evaluating the correlation between EZH2 SNPs and outcome parameters in mCRC patients.', 'DNA was extracted from blood samples of 110 mCRC patients treated with first-line 5-fluorouracil, folinic acid, irinotecan (FOLFIRI) and bevacizumab. Genotyping was carried out by real-time PCR. Genotype was used to predict objective response, progression-free survival (PFS) and overall survival (OS). EZH2 messenger RNA levels were evaluated on lymphocytes of a parallel cohort of 50 CRC patients.', 'One allelic variant (rs3757441 C/C versus C/T or T/T) was significantly associated with shorter PFS and OS (P < 0.01 and P < 0.05, respectively). At multivariate analysis, the same variant resulted an independent predictor of PFS and OS (P < 0.05). The C/C variant was associated with significantly higher EZH2 expression (P < 0.05).']
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['In kidney transplanted children, it is difficult to obtain blood levels of mycophenolic acid between 2 and 4 microg/mL, when mycophenolate mofetil doses up to 30 mg/kg/d are given two or three times a day. We proposed that using mycophenolic acid, instead of the salt mycophenolate mofetil, may help us to reach target levels.', 'We sought to describe the pharmacokinetics of mycophenolic acid in eight kidney transplanted children over a period of 1.2 +/- 0.8 years.', 'Eight patients (5 boys and 3 girls) aged 7.0 +/- 1.8 years received cadaveric kidney transplantations. Induction with basiliximab was followed by cyclosporine (n = 4) or tacrolimus (n = 4), tapered steroids (withdrawal at 12 months in six cases and maintained at 0.15 mg/kg/d in two cases), and mycophenolate mofetil (25 to 30 mg/kg/d two or three times a day). For 1.0 +/- 0.3 years mycophenolic acid levels were between 0.8 +/- 0.3 microg/mL. When mycophenolic acid sodium tablets were available, all patients were switched to this drug.', 'After the conversion, blood levels obtained at 8 +/- 3 days were 1.5 to 5.0 microg/mL (median, 3.2), which were far closer to the target 2 to 4 microg/mL. No gastrointestinal disorders were observed with the follow-up of 72 +/- 18 days.']
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['Ebolavirus species Zaire (ZEBOV) causes highly lethal hemorrhagic fever, resulting in the death of 90% of patients within days. Most information on immune responses to ZEBOV comes from in vitro studies and animal models. The paucity of data on human immune responses to this virus is mainly due to the fact that most outbreaks occur in remote areas. Published studies in this setting, based on small numbers of samples and limited panels of immunological markers, have given somewhat different results.', 'Here, we studied a unique collection of 56 blood samples from 42 nonsurvivors and 14 survivors, obtained during the five outbreaks that occurred between 1996 and 2003 in Gabon and Republic of Congo. Using Luminex technology, we assayed 50 cytokines in all 56 samples and performed phenotypic analyses by flow cytometry. We found that fatal outcome was associated with hypersecretion of numerous proinflammatory cytokines (IL-1β, IL-1RA, IL-6, IL-8, IL-15 and IL-16), chemokines and growth factors (MIP-1α, MIP-1β, MCP-1, M-CSF, MIF, IP-10, GRO-α and eotaxin). Interestingly, no increase of IFNα2 was detected in patients. Furthermore, nonsurvivors were also characterized by very low levels of circulating cytokines produced by T lymphocytes (IL-2, IL-3, IL-4, IL-5, IL-9, IL-13) and by a significant drop of CD3+CD4+ and CD3+CD8+ peripheral cells as well as a high increase in CD95 expression on T lymphocytes.']
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['Aggressive screening, early angiographic diagnosis, and prompt anticoagulation for blunt carotid artery injuries (CAIs) improves neurologic outcome.', 'From January 1, 1996, through December 31, 2002, there were 13 280 blunt trauma admissions to our level I center, of which 643 underwent screening angiography for blunt CAI on the basis of a protocol including injury patterns and symptoms. Patients without contraindications underwent anticoagulation immediately for documented lesions.', 'A state-designated, level I urban trauma center.', 'Of the 643 patients undergoing screening angiography, 114 (18%) had confirmed CAI.', 'Early angiographic diagnosis and prompt anticoagulation.', 'Diagnosis, stroke rate, and complications stratified by method of intervention.', 'A CAI was identified in 114 patients during the 7-year study period; the majority were men (71%), with a mean +/- SD age of 34 +/- 1.3 years and a mean +/- SD Injury Severity Score of 29 +/- 1.5. Seventy-three patients underwent anticoagulation after diagnosis (heparin in 54, low-molecular-weight heparin in 2, antiplatelet agents in 17); none had a stroke. Of the 41 patients who did not receive anticoagulation (because of a contraindication in 27, symptoms before diagnosis in 9, and carotid coil or stent in 5), 19 patients (46%) developed neurologic ischemia. Ischemic neurologic events occurred in 100% of patients who presented with symptoms before angiographic diagnosis and those receiving a carotid coil or stent without anticoagulation.']
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['The majority of gastrointestinal stromal tumors (GIST) are driven by KIT, PDGFRA, or, less commonly, BRAF mutations, and SDH gene inactivation is involved in a limited fraction of gastric lesions. However, about 10% of GISTs are devoid of any of such alterations and are poorly responsive to standard treatments. This study aims to shed light on the molecular drivers of quadruple-negative GISTs.', 'Twenty-two sporadic quadruple-negative GISTs with no prior association with Neurofibromatosis Type 1 syndrome were molecularly profiled for a panel of genes belonging to tyrosine kinase pathways or previously implicated in GISTs. For comparison purposes, 24 GISTs carrying KIT, PDGFRA, or SDH gene mutations were also analyzed. Molecular findings were correlated to clinicopathologic features.', 'Most quadruple-negative GISTs featured intestinal localization, with a female predilection. About 60% (13/22) of quadruple-negative tumors carried NF1 pathogenic mutations, often associated with biallelic inactivation. The analysis of normal tissues, available in 11 cases, indicated the constitutional nature of the NF1 mutation in 7 of 11 cases, unveiling an unrecognized Neurofibromatosis Type 1 syndromic condition. Multifocality and a multinodular pattern of growth were common findings in NF1-mutated quadruple-negative GISTs.']
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['Lymphopenia results in the proliferation and differentiation of naïve T cells into memory-like cells in the apparent absence of antigenic stimulation. This response, at least in part due to a greater availability of cytokines, is thought to promote anti-self responses. Although potentially autoreactive memory-like CD8(+) T cells generated in a lymphopenic environment are subject to the mechanisms of peripheral tolerance, they can induce autoimmunity in the presence of antigen-specific memory-like CD4(+) T helper cells.', 'Here, we studied the mechanisms underlying CD4 help under lymphopenic conditions in transgenic mice expressing a model antigen in the beta cells of the pancreas. Surprisingly, we found that the self-reactivity mediated by the cooperation of memory-like CD8(+) and CD4(+) T cells was not abrogated by CD40L blockade. In contrast, treatment with anti-IL-2 antibodies inhibited the onset of autoimmunity. IL-2 neutralization prevented the CD4-mediated differentiation of memory-like CD8(+) T cells into pathogenic effectors in response to self-antigen cross-presentation. Furthermore, in the absence of helper cells, induction of IL-2 signaling by an IL-2 immune complex was sufficient to promote memory-like CD8(+) T cell self-reactivity.']
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['Temporary vascular in- and outflow occlusion is an effective technique for bleeding control during liver resection. However, occlusion can result in ischemia/reperfusion (I/R) injury to the liver. The aim of this study in a porcine model was to investigate the effect of in- and outflow occlusion of part of the liver on the metabolism of the normally perfused parenchyma of the same liver measured by microdialysis.', 'Eight pigs underwent laparotomy. A microdialysis catheter was inserted into in the left and right part of the liver, respectively. Microdialysis samples were collected every 30 min. Occlusion of the left part of the liver was achieved for 60 min, followed by 5 h of reperfusion. Samples were analyzed for glucose, lactate, pyruvate and glycerol. Blood samples were drawn to determine standard liver and biochemical parameters.', 'Comparing the ischemic part of the liver with the normally perfused part, significant differences in the levels of lactate, pyruvate and glycerol were found. During reperfusion, similar and continuous decreases below baseline levels were observed for lactate and pyruvate in both the ischemic and normally perfused part of the liver. No significant changes in liver parameters or blood glucose levels were seen.']
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['Monitoring critically ill, brain-injured patients with a decreased level of consciousness is challenging. Our goal is to determine in this population the correlation between the Bispectral Index (BIS) and three commonly used sedation agitation scales: the Richmond Agitation-Sedation Scale (RASS), the Sedation-Agitation Scale (SAS) and the Glasgow Coma Scale (GCS) scores.', 'Prospective, single-blinded observational study.', 'Eight-bed neurology-neurosurgery intensive care unit at the Cleveland Clinic Foundation.', 'Thirty critically ill patients admitted to the neurointensive care unit with primary brain injury and a decreased level of consciousness.', "Patients were prospectively evaluated for level of consciousness using the RASS, SAS, and GCS every hour and simultaneously were monitored continuously with a BIS monitor for 6 hrs. A Spearman's correlation coefficient was used to correlate the BIS scores with clinical scales. In 15 patients monitored with the newer BIS XP version, the BIS values correlated significantly with the RASS (R2 = .810; p < .0001), SAS (R2 = .725; p < .0001), and GCS (R2 = .655; p < .0001). In 15 patients monitored with the older BIS 2.1.1 software, the correlation was as follows: for RASS, R2 = .30 (p < .008), for SAS: R2 = .376 (p < .001), and for GCS: R2 = .274 (p < .015). This correlation was maintained in patients who received sedative medications."]
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['Traditional Chinese Medicine compound HuangQi decoction is widely used in clinical treatment of chronic kidney disease, but its role on renal interstitial fibrosis and the underlying mechanism remains unclear. The aim of this study is to investigate the effect of HuangQi decoction on renal interstitial fibrosis and its association with the TGF-β/Smad signaling pathway Methods: A total of 120 C57/BL mice were randomly divided into six groups: sham group, sham plus high-dose HuangQi decoction (1.08g/kg) group, unilateral ureteral obstruction (UUO) model group, and UUO model plus low to high doses of HuangQi decoction (0.12g/kg, 0.36g/kg and 1.08g/kg respectively) groups. Animals were sacrificed 14 days after the administration and ipsilateral kidney tissue was sampled for pathologic examinations. Immunohistochemistry, PCR and western blot were used to detect the expressions of related molecules in the TGF-β/Smad signaling pathway. TGF-β1 was used in in vitro experiments to induce human kidney proximal tubule epithelial cells (HK2).', 'HuangQi decoction improved ipsilateral kidney fibrosis in UUO mice and downregulated the expressions of TGF-β1, TβRI, TβRII, Smad4, Smad2/3, P-Smad2/3, α-SMA, collagen type I, III and IV in a dose-dependent manner while upregulated the expression of Smad7 in the same fashion. Similar results were found in in vitro studies.']
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['High expression of IL-5 by T cells in the airways of asthmatic individuals is believed to play a fundamental role in the eosinophilia associated with this disease. Recently, the transcription factor GATA-3 was shown to be critical for IL-5 gene expression in TH2 cells in vitro.', 'Our aim was to examine the expression of GATA-3 mRNA and its colocalization within the airways of asthmatic and nonasthmatic individuals.', 'We investigated the association between GATA-3 gene expression, airway inflammatory cells, and IL-5 gene expression in bronchoalveolar lavage fluid and bronchial biopsy specimens from atopic asthmatic subjects (n = 10) and normal control subjects (n = 10).', 'We report that GATA-3 mRNA expression is significantly increased in the airways of asthmatic subjects compared with those of normal control subjects (P <.001). Numbers of cells expressing GATA-3 transcripts correlated significantly with reduced airway caliber (P <.05) and airways hyperresponsiveness (P <.05) in asthmatic subjects. Colocalization studies showed that the majority (approximately 60% to 90%) of GATA-3 mRNA+ cells in asthmatic airways were CD3(+) T cells, with smaller contributions from major basic protein+ eosinophils and tryptase+ mast cells. The density of GATA-3 mRNA+ cells correlated significantly with the numbers of cells expressing IL-5 mRNA (P <.001, r = 0.879 for bronchoalveolar lavage fluid; P <. 05, r = 0.721 for biopsy specimens). Furthermore, double in situ hybridization demonstrated that approximately 76% of GATA-3 mRNA+ cells coexpressed IL-5 mRNA and that 91% of IL-5 mRNA+ cells coexpressed GATA-3 mRNA.']
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['VEGF is one of the key drivers of physiological or pathological angiogenesis hence several VEGF inhibitors are in different stages of clinical development. To further dissect the role of VEGF in different stages of tumor progression in lung tumors, we utilized KrasG12D-LSL GEMMs (genetically engineered mouse models).', 'Intranasal delivery of adenoviruses expressing cre recombinase in KrasG12D-LSL mice results in the expression of mutant Kras that leads to development of tumor lesions ranging from adenomatous hyperplasia to large adenoma and adenocarcinoma over time in lung. In the current study, we treated KrasG12D-LSL mice at 14\xa0weeks post inhalation with three different angiogenic inhibitors including axitinib and PF-00337210 both of which are selective inhibitors of VEGFR and sunitinib which targets VEGFR, C-SF1-R, PDGFR and KIT.', 'Pathology findings showed no significant difference in percentage of adenomatous hyperplastic lesions between the vehicle vs. any of the treatments suggesting that angiogenesis may not play a major role at early stages of tumorigenesis. However, each inhibitor suppressed percentage of benign adenoma lesions and almost fully inhibited growth of adenocarcinoma lesions in the recipients which was consistent with a reduction in tumor vasculature. Treatment with sunitinib which is a multi-targeted RTKI did not provide any advantage compared to selective VEGFR inhibitor further emphasizing role of VEGF in tumor angiogenesis in this model.']
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['The aim of this study was to determine whether abdominal drainage is beneficial after elective hepatic resection in patients with underlying chronic liver diseases.', 'Traditionally, in patients with chronic liver diseases, an abdominal drainage catheter is routinely inserted after hepatic resection to drain ascitic fluid and to detect postoperative hemorrhage and bile leakage. However, the benefits of this surgical practice have not been evaluated prospectively.', 'Between January 1999 and March 2002, 104 patients who had underlying chronic liver diseases were prospectively randomized to have either closed suction abdominal drainage (drainage group, n = 52) or no drainage (nondrainage group, n = 52) after elective hepatic resection. The operative outcomes of the 2 groups of patients were compared.', "Fifty-seven (55%) patients had major hepatic resection with resection of 3 Coiunaud's segments or more. Sixty-nine (66%) patients had liver cirrhosis and 35 (34%) had chronic hepatitis. Demographic, surgical, and pathologic details were similar between both groups. The primary indication for hepatic resection was hepatocellular carcinoma (n = 100, 96%). There was no difference in hospital mortality between the 2 groups of patients (drainage group, 6% vs. nondrainage group, 2%; P = 0.618). However, there was a significantly higher overall operative morbidity in the drainage group (73% vs. 38%, P < 0.001). This was related to a significantly higher incidence of wound complications in the drainage group compared with the nondrainage group (62% vs. 21%, P < 0.001). In addition, a trend toward a higher incidence of septic complications in the drainage group was observed (33% vs. 17%, P = 0.07). The mean (+/- standard error of mean) postoperative hospital stay of the drainage group was 19.0 +/- 2.2 days, which was significantly longer than that of the nondrainage group (12.5 +/- 1.1 days, P = 0.005). With a median follow-up of 15 months, none of the 51 patients with hepatocellular carcinoma in the drainage group developed metastasis at the drain sites. On multivariate analysis, abdominal drainage, underlying liver cirrhosis, major hepatic resection, and intraoperative blood loss of >1.5L were independent and significant factors associated with postoperative morbidity."]
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['Recent studies have identified a major locus for risk for coronary artery disease and myocardial infarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk.', 'In an initial screen, 15 single nucleotide polymorphisms (SNPs) covering the critical genetic interval on 9p21 were genotyped in samples from Southern Germany (1,090 cases, 1,244 control subjects) and the United Kingdom (758 cases, 872 control subjects, 3 SNPs). SNPs significantly associated with ischemic stroke or individual stroke subtypes in either of the screening samples were subsequently genotyped in 2,528 additional cases and 2,189 additional control subjects from Europe and North America.', 'Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p < 0.05). Analysis of the full sample confirmed associations between six SNPs and atherosclerotic stroke in multivariate analyses controlling for demographic variables, coronary artery disease, myocardial infarction, and vascular risk factors (all p < 0.05). The odds ratios for the lead SNP (rs1537378-C) were similar in the various subsamples with a pooled odds ratio of 1.21 (95% confidence interval, 1.07-1.37) under both fixed- and random-effects models (p = 0.002). The point estimate for the population attributable risk is 20.1% for atherosclerotic stroke.']
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['Acute normovolaemic haemodilution with subsequent autologous blood transfusion after surgery is widely used to reduce homologous blood requirements during cardiac surgery. The hypothesis tested was whether a low intraoperative haematocrit (Hct) resulting from haemodilution decreases gastric mucosal pH (pHi).', 'Prospective clinical investigation.', 'University Hospital of Vienna, Austria.', '16 consecutive patients scheduled for elective cardiac surgery.', 'The patients were randomly assigned to one of two groups: In 10 patients (group 1), 500 ml of blood was withdrawn and stored after anaesthesia induction. An equal amount of 6% hydroxyethyl starch was simultaneously infused. After discontinuation of cardiopulmonary bypass (CPB), the autologous blood unit was transfused. Six patients (group 2), who were not subjected to haemodilution and autologous blood transfusion served as controls. In all patients, a gastric tonometry probe was inserted.', 'Measurements of pHi and Hct were performed before and after acute normovolaemic haemodilution, during pulsatile hypothermic (30-32 degrees C) CPB, after rewarming, and 30 min after autologous blood transfusion in group 1, and at corresponding time intervals in group 2. Repeated measures analysis of variance and the Mann-Whitney U test were used for statistical analysis. Data are presented as means +/- standard error of the mean. Haemodilution in group 1 caused a significant and persistent decrease in Hct (after haemodilution in group 1 34 +/- 1 vs 40 +/- 1% in group 2). In both groups, pHi decreased during rewarming and after termination of CPB. However, in group 1, pHi was better preserved than in group 2 (rewarming: 7.44 +/- 0.02 vs 7.34 +/- 0.04; after CPB: 7.38 +/- 0.03 vs 7.28 +/- 0.02; p < 0.05).']
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["Australia's Early Parenting Services support families and intervene early in mental health problems in parents. The Victorian Early Parenting Strategy, a platform for government policy recommended a stronger evidence base for early parenting services. Tweddle Child and Family Health Service (TCFHS) is a not-for-profit public sector early parenting centre, which provides residential, day stay, home visiting and outreach programs. This study aimed i) to examine the health, social circumstances and presenting needs of clients attending the Tweddle Day Stay Program (DSP) with infants under 12\u2009months old and ii) to assess the parent mental health and infant behaviour outcomes and the factors associated with program success.", "A cohort of clients was recruited prior to admission and followed-up 8\u2009weeks after discharge. Data were collected using standardised measures in a study specific questionnaire at baseline, participant's Tweddle records and a follow-up telephone interview. Health, social circumstances and presenting needs of clients were described. Changes in parents' symptoms of depression and infants' sleep and settling between admission and follow-up were calculated. Multiple regression analyses were conducted to examine factors associated with changes in primary outcomes.", "Of the total 162 clients who were eligible and invited to participate, 115 (72%) were recruited. Parents admitted to the DSP had worse general self-reported physical and mental health than community samples. Infants of DSP participants were no more likely to be premature or have low birth weight, but significantly more unsettled than other community samples. Participants' mental health and their infants' behaviours were significantly improved after DSP admission. In multivariate analysis, higher depression score at baseline and greater educational attainment were significantly associated with improvements in parents' mental health. Worse unsettled infant behaviours and longer time between discharge and follow up were significantly associated with improvements in infant sleep and settling."]
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['Genipin is a component of Japanese traditional herbal medicine (Kampo), inchinkoto, and is used for the treatment of various liver injuries. However, there are few scientific evidence for its anti-inflammatory effects and mechanisms. In inflamed liver, proinflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-1β stimulate liver cells, followed by the expression of inducible nitric oxide synthase (iNOS). Excessive levels of NO produced by iNOS have been implicated as one of the factors in liver injury. We examined the protective effects of genipin on the liver by studying its influence on the induction of iNOS and NO production as a liver injury marker in cultured hepatocytes "in vitro liver injury model".', 'Primary cultured rat hepatocytes were treated with IL-1β in the presence or absence of genipin. The induction of NO production and iNOS, and its signaling pathway were analyzed.', 'In IL-1β-stimulated hepatocytes, genipin inhibited the production of NO dose- and time-dependently, and reduced the levels of iNOS protein and its mRNA expression. Genipin also reduced mRNA expressions of TNF-α and IL-6. Genipin inhibited two essential signaling pathways for iNOS induction, IκB degradation/NF-κB activation and type I IL-1 receptor upregulation. Transfection experiments revealed that genipin decreased the expression of iNOS mRNA through both inhibitions of the promoter activation and mRNA stabilization. Delayed administration of genipin after IL-1β addition also inhibited iNOS induction.']
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['Remote Ischemic postconditioning (RIPoC) is a cardioprotective strategy for alleviating the reperfusion injury. We hypothesized that RIPoC or ischemic postconditioning (IPoC) could protect the engrafted mesenchymal stem cells (MSCs) in reperfusion myocardium.', 'Female Sprague-Dawley rats were subject to 30 minutes of occlusion of left anterior descending (LAD). Ischemia reperfusion (IR) received reperfusion without interruption after ischemia. RIPoC received 3 cycles of 30 seconds reperfusion and re-occlusion on the limb at the onset of reperfusion. IPoC received 3 cycles of 30 seconds reperfusion and re-occlusion on the LAD at the same time. Male MSCs were intramyocardially administered after ischemia.', 'Compared with that in IR group, ischemic myocardium in RIPoC+IPoC group, RIPoC group and IPoC group were found to have higher anti-oxidative stress and mitochondrial function level, lower lipid peroxidation and inflammational injury level, higher level of stromal cell derived factor-1 alpha and vascular endothelium growth factor gene expression at 3 days later. By immunohistochemical examination and quantitative polymerase chain reaction, more engrafted MSCs, better cardiac function and less cardiac fibrosis in RIPoC+IPoC group, RIPoC group and IPoC group were detected at 3 weeks after delivery. There were no significant differences between RIPoC and RIPoC+IPoC group.']
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['A case control study was conducted to test the hypothesis that plasminogen activator inhibitor type-1 (PAI-1) 4G/5G gene polymorphism confers an increased risk for myocardial infarction (MI) in patients with known coronary atherosclerosis.', 'One hundred fifty-six consecutive patients who presented with acute MI and 111 stable coronary artery disease (SCAD) patients with documented critical coronary artery stenoses were prospectively enrolled. PAI-1 4G/5G gene polymorphism and conventional atherosclerotic risk factors were studied in all patients. PAI-1 4G/5G gene polymorphism was studied in another 281 healthy blood bank donors.', 'The frequency 4G4G genotype was significantly higher in the MI group as compared to SCAD group (32.7% vs. 15.3%, P = 0.001) while it was not statistically significant between MI and healthy control groups (32.7% vs. 26.0%, P = 0.136). Comparing with healthy controls SCAD group had significantly lower frequency of 4G4G genotype (P = 0.024). In comparison with SCAD group PAI-1 4G/4G genotype, male sex and smoking habits favored to MI in univariate analysis with a P value of less than 0.2. These variables were included in multivariate regression model to estimate the associated risk for MI. PAI-1 4G/4G genotype was the only independent variable (OR 2.67, 95%CI 1.43-4.96, P = 0.002) associated with MI in this regression model. Comparing with healthy control group 4G4G genotype was not associated with MI (OR 1.38, 95%CI 0.90-2.12). However, presence of 4G4G genotype had a protective effect against development of SCAD (OR 0.52, 96%CI 0.29-0.92).']
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["The mechanisms that regulate mitogenic and antiapoptotic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we assessed the effect of apigenin (4',5,7-trihydroxyflavone), a flavonoid on a panel of PEL cell lines.", 'We studied the effect of apigenin on four PEL cell lines. Apoptosis was measured by annexin V/PI dual staining and DNA laddering. Protein expression was measured by immunoblotting.', "Apigenin induced apoptosis in PEL cell lines in a dose dependent manner. Such effects of apigenin appeared to result from suppression of constitutively active kinase AKT resulting in down-regulation of SKP2, hypo-phosphorylation of Rb and accumulation of p27Kip1. Apigenin treatment of PEL cells caused dephosphorylation of p-Bad protein leading to down regulation of the anti-apoptotic protein, Bcl-2 and an increase in Bax/Bcl2 ratio. Apigenin treatment also triggered Bax conformational change and subsequently translocation from cytosole to mitochondria causing loss of mitochondrial membrane potential with subsequent release of cytochrome c. Released cytochrome c onto the cytosole activated caspase-9 and caspase-3, followed by polyadenosin-5'-diphosphate-ribose polymerase (PARP) cleavage. Finally, treatment of PEL cells with apigenin down-regulated the expression of inhibitor of apoptosis protein (IAPs)."]
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['When patients return to the emergency department (ED) shortly after being seen, it is generally assumed that their initial evaluation or treatment was inadequate.', 'The purpose of this study was to determine the rates and causes of revisits to the ED of a 710-bed secondary teaching referral hospital (Kuang Tien General Hospital), to identify areas for improvement, and to define the initial ED presentations that are associated with such revisits.', 'The study period was from January 1, 2006 to December 31, 2006. There were 34,714 patients seen and discharged in the ED; 1899 patients returned within 72 h. Monthly revisit rates were calculated. The patients who revisited the ED within 72 h were retrospectively identified by the authors, and their charts were examined to determine the causes of the revisits.', 'There were 1899 patients (5.47% of total) found to have revisited the ED within 72 h after their initial visit. The monthly revisit rates ranged from 2.85% to 6.25% (average, 5.47%). The rates of revisits that were related to factors of illness, patients, and doctors were 80.9%, 10.9%, and 8.2%, respectively. Among the factors related to doctors, 3.7% (70 cases) were misdiagnosis, and abdominal pain was the most common presentation (55.7%, 39/70). The most common initial ED presentations were for abdominal pain (12.9%), fever (12.6%), vertigo (4.5%), headache (2.1), and upper respiratory infection (2.1%).']
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