Broeblair3634

After identifying important predictors of nucleotide diversity with random forest regression, we conducted follow-up analyses to examine the roles of phylogenetic history, geography, and demographic processes on intraspecific diversity. Although life history traits were not important predictors for this data set, we found significant phylogenetic signal in genetic diversity within amphibians. We also found that salamander species at northern latitudes contained low genetic diversity. Data repurposing and machine learning provide valuable tools for detecting patterns with relevance for conservation, but concerted efforts are needed to compile meaningful data sets with greater utility for understanding global biodiversity.YKL-40, a mammalian chitinase 3- like protein that was associated with multiple inflammatory and immune diseases. Previous studies have suggested a role for YKL-40 in psoriasis based on its significantly higher levels in the serum of psoriatic patient compared with healthy controls. The aim of this study was to determine the correlation between serum YKL-40, psoriasis severity using PASI score and serum levels of IL-17 before and after narrow-band UVB therapy. 28 patients with moderate to severe plaque psoriasis, as defined by PASI scores, were enrolled in this prospective cohort study. All cases received NB-UVB phototherapy twice weekly for 3 months. Serum YKL-40 and IL-17 levels were evaluated before and after 3 months of treatment. Clinical photographs were taken both at baseline and after 3 months. There was a statistical positive correlation between serum levels of YKL-40 and serum IL-17 levels as well as PASI score in patients with moderate to severe psoriasis before and after treatment. YKL-40 represents a reliable marker for psoriasis severity estimated by PASI and positively correlated with IL 17 as an inflammatory marker in psoriasis.

This study describes Korean nurses' work schedule characteristics and identifies their components to investigate associations of work schedule components with missed nursing care and organizational commitment.

This cross-sectional secondary analysis used survey data of 1,057 nurses in 111 units at six hospitals in South Korea. Data were collected between April 2017 and March 2018.

A self-administered survey, including seven work schedule characteristic items, the Korean version of the MISSCARE Survey, and the Korean version of the Organizational Commitment Questionnaire, was employed. To construct independent components of work schedule characteristics, a principal component analysis was performed. The associations of work schedule components with missed nursing care and organizational commitment were analyzed using multiple linear regression models with generalized estimating equation methods.

The average number of daily work hours was 9.7. Nearly half of the study population worked while sick once ong issues to resolve them.Activating transcription factor 4 (ATF4) is critical for chondrocyte proliferation and bone formation. Exosomes are considered as promising gene-delivery vehicles for the treatment of osteoarthritis (OA). This study utilized the serum-derived exosomes from OA mice as the gene-delivery vehicles for ATF4 gene therapy and explored their therapeutic effects on OA. Meniscus injury-induced OA model was established by the excision of anterior part of medial meniscus in the right knee of C57BL/6J mice. Exosomes were isolated from serum samples of sham and OA mice, and were referred to as sham-Exo and OA-Exo, respectively. ATF4-overexpressing OA-Exo (ATF4-OA-Exo) was developed by introducing ATF4 mRNA into OA-Exo via electroporation. Four weeks after surgery, OA mice received intra-articular injections of sham-Exo, OA-Exo, and ATF4-OA-Exo, respectively. The results showed that intra-articular injection of ATF4-OA-Exo alleviated articular cartilage degeneration or damage and inflammatory response of OA mice. Autophagy was weakened in knee joint cartilage of OA mice, which was partially restored by intra-articular injection of ATF4-OA-Exo. Further in vitro assays revealed that ATF4-OA-Exo promoted chondrocyte autophagy and inhibited chondrocyte apoptosis in the TNF-α- or tunicamycin-treated chondrocytes. Together, ATF4-modified serum exosomes derived from OA mice protect cartilage and alleviate OA progression by inducing autophagy.Human serine racemase (hSR) catalyzes the biosynthesis of D-serine, an obligatory co-agonist of the NMDA receptors. It was previously found that the reversible S-nitrosylation of Cys113 reduces hSR activity. Here, we show by site-directed mutagenesis, fluorescence spectroscopy, mass spectrometry, and molecular dynamics that S-nitrosylation stabilizes an open, less-active conformation of the enzyme. The reaction of hSR with either NO or nitroso donors is conformation-dependent and occurs only in the conformation stabilized by the allosteric effector ATP, in which the ε-amino group of Lys114 acts as a base toward the thiol group of Cys113. In the closed conformation stabilized by glycine-an active-site ligand of hSR-the side chain of Lys114 moves away from that of Cys113, while the carboxyl side-chain group of Asp318 moves significantly closer, increasing the thiol pKa and preventing the reaction. We conclude that ATP binding, glycine binding, and S-nitrosylation constitute a three-way regulation mechanism for the tight control of hSR activity. We also show that Cys113 undergoes H2 O2 -mediated oxidation, with loss of enzyme activity, a reaction also dependent on hSR conformation.Before a new method is used for clinical testing, it is essential that it is evaluated for suitability for its intended purpose. This document gives guidance for the performance of verification, validation and implementation processes required by regulatory and accreditation bodies. It covers the planning and execution of an evaluation of the commonly performed screening tests (prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen assay), and instrument-specific issues. Advice on selecting an appropriate haemostasis analyser, planning the evaluation, and assessing the reference, interval, precision, accuracy, and comparability of a haemostasis test system are also given. A second companion document will cover specialist haemostasis testing.

LGR5 enhances Wnt-β-catenin signalling; however, involvement of LGR5 or Wnt-β-catenin signalling in ICC progression has not been reported.

Functions and regulations of LGR5-mediated β-catenin activation in ICC progression were evaluated using surgical specimens collected from 61 ICC patients or 2 ICC cell lines.

LGR5 expression was increased in some cases of ICC. It was positively correlated with β-catenin activation, OLFM4 expression and STAT3 activation, and negatively correlated with GRIM19 expression in ICC, thereby enhancing cancer stem cell (CSC)-like property and EMT. High LGR5 expression was an independent factor for poor prognosis in ICC after operation. In vitro, Wnt inhibition by IWP-2 suppressed β-catenin activation, OLFM4 expression and STAT3 activation. IWP-2 treatment decreased expression of EpCAM, CD133, vimentin and increased E-cadherin expression. The rate of mesenchymal cells was decreased and cell invasiveness was suppressed after IWP-2 treatment, suggesting that Wnt-β-catenin signalostic predictor and a promising therapeutic target for ICC.

Intraabdominal surgery is a known risk factor for splanchnic vein thrombosis (SVT). SVT incidence, management, and prognosis after hepatopancreatobiliary surgery are unknown.

To determine the incidence and prognosis of SVT following hepatopancreatobiliary surgery and describe current practices in anticoagulation for postoperative SVT.

Multicenter retrospective cohort study of adults undergoing hepatopancreatobiliary surgery. Multivariable analyses for predictors of SVT, major bleeding, and 90-day mortality were performed.

Of 1815 patients included, 89 (4.9%) had cirrhosis and 1532 (84.4%) had active cancer. The most frequent surgeries were pancreaticoduodenectomy (40.6%), open (30.7%), and laparoscopic (11.0%) liver resection. Sixty (3.3%) patients experienced SVT within 90days of surgery. Among patients with SVT, 23.3% were symptomatic and 75.0% were treated with therapeutic anticoagulation. Planned duration of anticoagulation averaged 3 to 6months. By multivariable analysis, SVT predictors were operative time (adjusted odds ratio [aOR] per hour increase 1.32, 95% confidence interval [CI] 1.20-1.46), cirrhosis (aOR 3.22, 95% CI 1.28-8.10), and postoperative intraabdominal infection (aOR 2.99, 95% CI 1.72-5.19). Postoperative major bleeding occurred in 22.1% of patients and 4.0% died within 90days. Predictors of postoperative mortality were age (aOR per 10-year increase 1.79, 95% CI 1.38-2.30), operative time (aOR 1.31 (1.17-1.45), cirrhosis (aOR 4.42, 95% CI 1.96-9.96), postoperative intraabdominal infection (aOR 2.66, 95% CI 1.55-4.57), postoperative major bleeding (aOR 4.12, 95% CI 2.36-7.30), and postoperative SVT (aOR 3.15, 95% CI 1.42-6.97).

SVT occurred in 1 in 30 patients after hepatopancreatobiliary surgery and was associated with a 3-fold independent increase in 90-day mortality.

SVT occurred in 1 in 30 patients after hepatopancreatobiliary surgery and was associated with a 3-fold independent increase in 90-day mortality.

Most high-risk thrombotic antiphospholipid syndrome (APS) patients test positive for anti-β2-glycoprotein I (aβ2GPI) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies. Information on the influence of these antibodies on thrombin generation and activated protein C resistance (aPCr) is still sparse and contradictory.

Plasma of 16 patients poured into a β2GPI affinity column allowed the perfect separation of aβ2GPI and aPS/PT antibodies. aPS/PT antibodies were further purified through a prothrombin affinity column. Obtained material was spiked into normal pooled plasma (NPP) and tested in the thrombin generation assay in the absence or presence of aPC.

aPS/PT antibodies showed a marked anticoagulant effect. Affinity purified aPS/PT and aβ2GPI antibodies from five patients were compared. aPS/PT antibodies showed significantly prolonged lag time and time to peak (5.0minutes [interquartile range (IQR)3.5-6.1] versus 2.7minutes [IQR2.2-3.5], P = .03 and 8.7minutes [IQR6.7-10.3] versus 5.7minutes [IQR4.5-6.2], P=.05, respectively) and significantly lower peak and velocity index (143nmol/L [IQR131-163] versus 171nmol/L [IQR157-182], P=.03 and 35nmol/L/min [IQR32-59] versus 72nmol/L/min [IQR54-77], P=.03, respectively). When aPC was added to the system, aPCr was significantly increased compared to controls for both aβ2GPI and aPS/PT antibodies. However, it was significantly stronger using aPS/PT antibodies. Median inhibition of endogenous thrombin potential was 22% (IQR16-33) with aPS/PT compared to 52% (IQR46-56) with aβ2GPI antibodies (P=.002).

Aβ2GPI antibodies show a mild anticoagulant and moderate procoagulant effect in thrombin generation and moderate aPC resistance. Conversely, aPS/PT antibodies show a strong anticoagulant effect and a strong aPCr.

Aβ2GPI antibodies show a mild anticoagulant and moderate procoagulant effect in thrombin generation and moderate aPC resistance. Conversely, aPS/PT antibodies show a strong anticoagulant effect and a strong aPCr.