492 research outputs found

    The role of trauma team activation by emergency physicians on outcomes in severe trauma patients

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    AbstractBackgroundIn our region, trauma team activation (TTA) is initiated by emergency physicians once an injured patient meets any of the criteria of TTA after the injured patient arrives at the emergency department (ED).PurposeTo evaluate the role of TTA on outcomes in patients with severe trauma.MethodsAll trauma patients who had injury severity score (ISS) >15 and were admitted from ED between January 2010 to December 2010 were included in the study. Mann–Whitney U test (non-normal distribution) or Student's t test (normal distribution) for continuous variables and Fisher exact test or Chi-square test for categorical variables were used to compare the statistically significant differences between TTA and non-TTA groups. Logistic regression was applied to determine any significant differences found in the statistical analysis for 30-day mortality.ResultsA total of 231 patients were signed up in the study. The TTA group had shorter time from ED to operation room (170 minutes vs. 534 minutes, p = 0.02) and tended to have more emergent operations (42.7% vs. 23.2%, p = 0.002). Emergent operation [odds ratio (OR), 0.34; 95% confidence interval (CI), 0.12–0.92, p = 0.035) was associated with lower mortality while ISS > 25 (OR, 7.48; 95% CI, 2.48–22.57, p < 0.0001), Glasgow coma scale score <13 (OR, 32.1; 95% CI, 4.30–94.6, p < 0.0001), hypotension (OR, 3.0; 95% CI, 1.1–7.9, p = 0.03), and coagulopathy (OR, 9.3; 95% CI, 1.2–71.4, p = 0.033) were associated with higher mortality.ConclusionThis study shows that TTA may shorten the time from ED to operation room in trauma patients with an ISS > 15

    Comparison of outcomes in emergency department patients with suspected cardiac chest pain: two-centre prospective observational study in Southern China

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    Background Hong Kong (HK) and Guangzhou (GZ) are cities in China with different healthcare systems. This study aimed to compare 30-day and 6-month mortality and characteristics of patients with suspected cardiac chest pain admitted to two emergency departments (ED) in HK and GZ. Methods A prospective observational study enrolled patients with suspected cardiac chest pain presenting to EDs in the Prince of Wales Hospital (PWH), HK and the Second Affiliated Hospital of Guangzhou Medical University (AHGZMU),GZ. The primary outcome was 30-day and 6-month mortality. Results In total, 996 patients were recruited, 407 cases from GZ and 589 cases from HK.The 30-day and 6-month mortality of chest patients were 3.7% and 4.7% in GZand 0.3% and 1.9% in HK, respectively. Serum creatinine level (Cr) was an independent factor for 30-day mortality whilst Cr and systolic blood pressure (SBP) were independent factors for 6-month mortality. In Cox regression analysis, unadjusted and adjusted hazard ratios for 30-day and 6-month mortality in GZ were significantly increased. Conclusion The 30-day and 6-month mortality of patients with suspected cardiac chest pain in Guangzhou were higher than in Hong Kong due to due to different baseline clinical characteristics of patients and different distributions of diagnoses, which were associated with different healthcare systems. Serum creatinine and SBP were independent factors for 30-day and 6-month mortality

    GIS Approaches for the Estimation of Residential-Level Ambient PM Concentrations

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    Spatial estimations are increasingly used to estimate geocoded ambient particulate matter (PM) concentrations in epidemiologic studies because measures of daily PM concentrations are unavailable in most U.S. locations. This study was conducted to a) assess the feasibility of large-scale kriging estimations of daily residential-level ambient PM concentrations, b) perform and compare cross-validations of different kriging models, c) contrast three popular kriging approaches, and d ) calculate SE of the kriging estimations. We used PM data for PM with aerodynamic diameter ≤10 μm (PM10) and aerodynamic diameter ≤ 2.5 μm (PM2.5) from the U.S. Environmental Protection Agency for the year 2000. Kriging estimations were performed at 94,135 geocoded addresses of Women’s Health Initiative study participants using the ArcView geographic information system. We developed a semiautomated program to enable large-scale daily kriging estimation and assessed validity of semivariogram models using prediction error (PE), standardized prediction error (SPE), root mean square standardized (RMSS), and SE of the estimated PM. National- and regional-scale kriging performed satisfactorily, with the former slightly better. The average PE, SPE, and RMSS of daily PM10 semivariograms using regular ordinary kriging with a spherical model were 0.0629, −0.0011, and 1.255 μg/m3, respectively; the average SE of the estimated residential-level PM10 was 27.36 μg/m3. The values for PM2.5 were 0.049, 0.0085, 1.389, and 4.13 μg/m3, respectively. Lognormal ordinary kriging yielded a smaller average SE and effectively eliminated out-of-range predicted values compared to regular ordinary kriging. Semiautomated daily kriging estimations and semivariogram cross-validations are feasible on a national scale. Lognormal ordinary kriging with a spherical model is valid for estimating daily ambient PM at geocoded residential addresses

    Patient-derived iPSCs link elevated mitochondrial respiratory complex I function to osteosarcoma in Rothmund-Thomson syndrome

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    Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarcoma. Here, we generated RTS patient-derived induced pluripotent stem cells (iPSCs) to dissect the pathological signaling leading to RTS patient-associated osteosarcoma. RTS iPSC-derived osteoblasts showed defective osteogenic differentiation and gain of in vitro tumorigenic ability. Transcriptome analysis of RTS osteoblasts validated decreased bone morphogenesis while revealing aberrantly upregulated mitochondrial respiratory complex I gene expression. RTS osteoblast metabolic assays demonstrated elevated mitochondrial respiratory complex I function, increased oxidative phosphorylation (OXPHOS), and increased ATP production. Inhibition of mitochondrial respiratory complex I activity by IACS-010759 selectively suppressed cellular respiration and cell proliferation of RTS osteoblasts. Furthermore, systems analysis of IACS-010759-induced changes in RTS osteoblasts revealed that chemical inhibition of mitochondrial respiratory complex I impaired cell proliferation, induced senescence, and decreased MAPK signaling and cell cycle associated genes, but increased H19 and ribosomal protein genes. In summary, our study suggests that mitochondrial respiratory complex I is a potential therapeutic target for RTS-associated osteosarcoma and provides future insights for clinical treatment strategies

    Functional characterization of cellulases identified from the cow rumen fungus Neocallimastix patriciarum W5 by transcriptomic and secretomic analyses

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    <p>Abstract</p> <p>Background</p> <p><it>Neocallimastix patriciarum</it> is one of the common anaerobic fungi in the digestive tracts of ruminants that can actively digest cellulosic materials, and its cellulases have great potential for hydrolyzing cellulosic feedstocks. Due to the difficulty in culture and lack of a genome database, it is not easy to gain a global understanding of the glycosyl hydrolases (<it>GHs</it>) produced by this anaerobic fungus.</p> <p>Results</p> <p>We have developed an efficient platform that uses a combination of transcriptomic and proteomic approaches to <it>N. patriciarum </it>to accelerate gene identification, enzyme classification and application in rice straw degradation. By conducting complementary studies of transcriptome (Roche 454 GS and Illumina GA IIx) and secretome (ESI-Trap LC-MS/MS), we identified 219 putative <it>GH </it>contigs and classified them into 25 <it>GH</it> families. The secretome analysis identified four major enzymes involved in rice straw degradation: β-glucosidase, endo-1,4-β-xylanase, xylanase B and Cel48A exoglucanase. From the sequences of assembled contigs, we cloned 19 putative cellulase genes, including the <it>GH1</it>, <it>GH3</it>, <it>GH5</it>, <it>GH6</it>, <it>GH9</it>, <it>GH18</it>, <it>GH43 </it>and <it>GH48 </it>gene families, which were highly expressed in <it>N. patriciarum </it>cultures grown on different feedstocks.</p> <p>Conclusions</p> <p>These <it>GH </it>genes were expressed in Pichia pastoris and/or Saccharomyces cerevisiae for functional characterization. At least five novel cellulases displayed cellulytic activity for glucose production. One β-glucosidase (W5-16143) and one exocellulase (W5-CAT26) showed strong activities and could potentially be developed into commercial enzymes.</p

    Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial

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    Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment

    Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer

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    Targeting the mitogen-activated protein kinase (MAPK) cascade in pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful. We aim to develop a MAPK inhibitor-based therapeutic combination with strong preclinical efficacy. Utilizing a reverse-phase protein array, we observe rapid phospho-activation of human epidermal growth factor receptor 2 (HER2) in PDAC cells upon pharmacological MAPK inhibition. Mechanistically, MAPK inhibitors lead to swift proteasomal degradation of dual-specificity phosphatase 6 (DUSP6). The carboxy terminus of HER2, containing a TEY motif also present in extracellular signal-regulated kinase 1/2 (ERK1/2), facilitates binding with DUSP6, enhancing its phosphatase activity to dephosphorylate HER2. In the presence of MAPK inhibitors, DUSP6 dissociates from the protective effect of the RING E3 ligase tripartite motif containing 21, resulting in its degradation. In PDAC patient-derived xenograft (PDX) models, combining ERK and HER inhibitors slows tumour growth and requires cytotoxic chemotherapy to achieve tumour regression. Alternatively, MAPK inhibitors with trastuzumab deruxtecan, an anti-HER2 antibody conjugated with cytotoxic chemotherapy, lead to sustained tumour regression in most tested PDXs without causing noticeable toxicity. Additionally, KRAS inhibitors also activate HER2, supporting testing the combination of KRAS inhibitors and trastuzumab deruxtecan in PDAC. This study identifies a rational and promising therapeutic combination for clinical testing in PDAC patients

    Perceptual Advantage of Animal Facial Attractiveness: Evidence From b-CFS and Binocular Rivalry

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    © Copyright © 2020 Shang, Liu, Yang, Wang, Zheng, Chen and Liu. Research has shown that attractive human faces enjoy an advantage in both conscious and preconscious processing. Here we examined whether this preference for attractiveness is exclusive to human faces by measuring participants’ sensitivity to the attractiveness of cat and tiger faces. Experiment 1 measured the time taken to break continuous flash suppression (b-CFS), whereas Experiment 2 measured the dominant time in binocular rivalry (BR). The results showed that attractive cat faces were detected more quickly (Experiment 1) and dominated for longer time in visual awareness (Experiment 2). However, no effect of attractiveness was found for tiger faces in Experiment 1, while attractive tiger faces also dominated for longer time in visual awareness in Experiment 2. The results provide first evidence that the preference for attractive animal faces can be shown involuntarily or without apparent conscious control. The findings suggest that human preference for facial attractiveness may contain an aesthetic element rather than being a purely adaptive means for mate choice
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