Identifying therapeutic chemical agents for osteoarthritis by high throughput screening

Poster no. 1138INTRODUCTION: An articular cartilage lesion, notably generated by osteoarthritis (OA), is initiated partly by the loss of proteoglycan content from the extracellular matrix and manifests as pain or disturbed joint function [1]. Strategies that restore the proteoglycan content would be of therapeutic benefit to prevent, delay, or even reverse the progression of the lesion. Numerous clinical and experimental approaches have been widely applied [2-4] to relieve the pain or induce healing of the lesion; however these require surgical intervention. Orally administrated …postprin

Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study

Background/Aims Understanding of non-alcoholic fatty liver disease (NAFLD) continues to expand, but the relationship between race and ethnicity and NAFLD outside the use of cross-sectional data is lacking. Using longitudinal data, we investigated the role of race and ethnicity in adverse outcomes in NAFLD patients. Methods Patients with NAFLD confirmed by imaging via manual chart review from any clinics at Stanford University Medical Center (1995–2021) were included. Primary study outcomes were incidence of liver events and mortality (overall and non-liver related). Results The study included 9,340 NAFLD patients: White (44.1%), Black (2.29%), Hispanic (27.9%), and Asian (25.7%) patients. For liver events, the cumulative 5-year incidence was highest among White (19.1%) patients, lowest among Black (7.9%) patients, and similar among Asian and Hispanic patients (~15%). The 5-year and 10-year cumulative overall mortality was highest for Black patients (9.2% and 15.0%, respectively, vs. 2.5–3.5% and 4.3–7.3% in other groups) as well as for non-liver mortality. On multivariable regression analysis, compared to White patients, only Asian group was associated with lower liver-related outcomes (aHR: 0.83, P=0.027), while Black patients were at more than two times higher risk of both non-liver related (aHR: 2.35, P=0.010) and overall mortality (aHR: 2.13, P=0.022) as well as Hispanic patients (overall mortality: aHR: 1.44, P=0.022). Conclusions Compared to White patients, Black patients with NAFLD were at the highest risk for overall and non-liver-related mortality, followed by Hispanic patients with Asian patients at the lowest risk for all adverse outcomes. Culturally sensitive and appropriate programs may be needed for more successful interventions

Aberrant Water Homeostasis Detected by Stable Isotope Analysis

While isotopes are frequently used as tracers in investigations of disease physiology (i.e., 14C labeled glucose), few studies have examined the impact that disease, and disease-related alterations in metabolism, may have on stable isotope ratios at natural abundance levels. The isotopic composition of body water is heavily influenced by water metabolism and dietary patterns and may provide a platform for disease detection. By utilizing a model of streptozotocin (STZ)-induced diabetes as an index case of aberrant water homeostasis, we demonstrate that untreated diabetes mellitus results in distinct combinations, or signatures, of the hydrogen (δ2H) and oxygen (δ18O) isotope ratios in body water. Additionally, we show that the δ2H and δ18O values of body water are correlated with increased water flux, suggesting altered blood osmolality, due to hyperglycemia, as the mechanism behind this correlation. Further, we present a mathematical model describing the impact of water flux on the isotopic composition of body water and compare model predicted values with actual values. These data highlight the importance of factors such as water flux and energy expenditure on predictive models of body water and additionally provide a framework for using naturally occurring stable isotope ratios to monitor diseases that impact water homeostasis

Search for heavy charged long-lived particles in the ATLAS detector in 36.1 fb−1 of proton-proton collision data at √s=13 TeV

A search for heavy charged long-lived particles is performed using a data sample of 36.1     fb − 1 of proton-proton collisions at √ s = 13     TeV collected by the ATLAS experiment at the Large Hadron Collider. The search is based on observables related to ionization energy loss and time of flight, which are sensitive to the velocity of heavy charged particles traveling significantly slower than the speed of light. Multiple search strategies for a wide range of lifetimes, corresponding to path lengths of a few meters, are defined as model independently as possible, by referencing several representative physics cases that yield long-lived particles within supersymmetric models, such as gluinos/squarks ( R -hadrons), charginos and staus. No significant deviations from the expected Standard Model background are observed. Upper limits at 95% confidence level are provided on the production cross sections of long-lived R -hadrons as well as directly pair-produced staus and charginos. These results translate into lower limits on the masses of long-lived gluino, sbottom and stop R -hadrons, as well as staus and charginos of 2000, 1250, 1340, 430, and 1090 GeV, respectively

Measurement of W^±Z production cross sections and gauge boson polarisation in pp collisions at √s=13 TeV with the ATLAS detector

This work is licensed under a Creative Commons Attribution 4.0 International License.This paper presents measurements of ± production cross sections in pp collisions at a centre-of-mass energy of 13 TeV. The data were collected in 2015 and 2016 by the ATLAS experiment at the Large Hadron Collider, and correspond to an integrated luminosity of 36.1 fb−1. The ± candidate events are reconstructed using leptonic decay modes of the gauge bosons into electrons and muons. The measured inclusive cross section in the detector fiducial region for a single leptonic decay mode is fid.±→ℓ′ℓℓ=63.7± 1.0 (stat.)± 2.3 (syst.)± 1.4 (lumi.) fb, reproduced by the next-to-next-to-leading-order Standard Model prediction of 61.5+1.4−1.3 fb. Cross sections for + and − production and their ratio are presented as well as differential cross sections for several kinematic observables. An analysis of angular distributions of leptons from decays of W and Z bosons is performed for the first time in pair-produced events in hadronic collisions, and integrated helicity fractions in the detector fiducial region are measured for the W and Z bosons separately. Of particular interest, the longitudinal helicity fraction of pair-produced vector bosons is also measured

Sonographic measurement of the lower uterine segment thickness: is it truly predictive of uterine rupture?

BACKGROUND: Sonographic examination of the lower uterine segment (LUS) has been used to diagnose a uterine defect and to determine the degree of LUS thinning in women with previous Caesarean section. Previous studies have demonstrated that the LUS thickness measured sonographically has a high negative predictive value for uterine rupture, suggesting that a normal LUS thickness predicts a safe trial of vaginal birth after previous Caesarean section (VBAC). However, the clinical application of LUS measurement in the management of VBAC remains controversial. Because uterine rupture is rare and the number of women willing to attempt VBAC is declining, it would be difficult to recruit sufficient patients for an adequate sample size when designing studies to evaluate LUS measurement in predicting uterine rupture. CASE: A healthy 34-year-old, gravida 7, para 5, had a lower segment transverse Caesarean section for her fifth delivery. She underwent a trial of VBAC for her subsequent pregnancy. Despite a normal sonographic LUS evaluation at 37 weeks' gestation, she had uterine rupture during labour. CONCLUSION: Clinical experience with the use of LUS measurement in predicting uterine rupture and managing VBAC is limited. Having a national registry to record data and review all cases of uterine rupture would accelerate the accumulation of experience on this subject.link_to_subscribed_fulltex

The GyneFix intrauterine device.

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Accessory ovary

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