A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

La communication médecin/pharmacien/patient, enquête sur les attentes des différents acteurs, quelles solutions pour améliorer la concertation médecin/pharmacien au bénéfice du patient ?

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Forced swimming-induced oxytocin release into blood and brain: Effects of adrenalectomy and corticosterone treatment

The oxytocin (OXT) system is functionally linked to the HPA axis in a reciprocal and complex manner. Certain stressors are known to cause the simultaneous release of OXT and adrenocorticotrophic hormone (ACTH) followed by corticosterone (CORT). Furthermore, brain OXT attenuates ACTH and CORT responses. Although there are some indications of CORT influencing OXT neurotransmission, specific effects of CORT on neurohypophyseal or intra-hypothalamic release of OXT have not been studied in detail. In the present set of experiments, adult male rats were adrenalectomized (ADX) or sham-operated and fitted with a jugular vein catheter and/or microdialysis probe targeting the hypothalamic paraventricular nucleus (PVN). Blood samples and dialysates were collected before and after forced swimming (FS) and analyzed for CORT, ACTH and AVP concentrations (in plasma) and OXT concentrations (in plasma and dialysates). Experimental treatments included acute infusion of CORT (70 or 175 mu g/kg i.v.) 5 min prior to FS, or subcutaneous placement of 40% CORT pellets resulting in stable CORT levels in the normal basal range. Although ADX did not alter basal OXT concentrations either in plasma or in microdialysates from the PVN, it did cause an exaggerated peripheral secretion of OXT and a blunted intra-PVN release of OXT in response to FS. CORT pellets did not influence either of these ADX-induced effects, while acute infusion of 175 mu g/kg CORT rescued the stress-induced rise in OXT release within the PVN and modestly increased peripheral OXT secretion. In conclusion, these results indicate that CORT regulates both peripheral and intracerebral OXT release, but in an independent manner. Whereas the peripheral secretion of OXT occurs simultaneously to HPA axis activation in response to FS and is modestly influenced by CORT, HPA axis activation and circulating CORT strongly contribute to the stress-induced stimulation of OXT release within the PVN. (C) 2016 Elsevier Ltd. All rights reserved

Assessing the association of epigenetic age acceleration with osteoarthritis in the Multicenter Osteoarthritis Study (MOST).

PURPOSE: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA. METHODS: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race. RESULTS: Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99-1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration. CONCLUSIONS: Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age

Generation of quadratically spatially trapped beams with short pulsed light

Article InvitéInternational audienc

Common data elements collected among universities for sport-related concussion studies

Abstract Background Universities are increasingly implementing programs to effectively respond to and manage sport-related concussions (SRCs). One such effort is to develop common data elements (CDEs) and standardize data collection methods. The objectives of this study were to describe CDEs currently collected by Big Ten and Ivy League universities for SRC studies, and to compare the data collected with the core CDEs recommended by the National Institute of Neurological Disorders and Stroke (NINDS). Methods We conducted an anonymous cross-sectional online survey among medical staff at the 14 Big Ten and 8 Ivy League universities (one per university) between September and October 2015. The survey instrument, including 9 questions corresponding to the concussion data collected before, during, and after a concussion, was developed and pilot-tested before field use. We analyzed patterns of the concussion CDEs being collected, including when, what, and how the data were collected and stored, and compared them with the NINDS' recommended core CDEs. Results A total of 19 out of 22 universities were included, with 13 from Big Ten and 6 from Ivy-League universities. All 19 participating universities currently collected concussion data with athletes before, during, and after a concussion. Great similarities in data collection were observed at baseline and acutely post-concussion across participating universities. All 19 universities collected at least one of the ten recommended acute symptoms checklists, and 18 universities collected one of the four recommended core neuropsychological function cognitive measures. However, CDEs in the sub-acute and chronic timeframes were limited, with only 9 (47%) universities collecting post-concussion short to long term outcome data. While over 60% of universities collected and stored concussion data electronically, only 17% to 42% of data collected were readily available for research. Conclusions Significant inter-institutional similarities in acute concussion CDEs were found. Further efforts should focus on collecting sub-acute and chronic timeframe core CDEs and creating data access protocols to facilitate evidence-based concussion prevention and treatment for all collegiate athletes