• Paaske Randall opublikował 5 miesięcy, 1 tydzień temu

    Acetylcarnitine emerged as highly viable for the prediction of an L-carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with pretreatment acetylcarnitine greater than or equal to 35 µM were less likely to die at 90 days if treated with L-carnitine (18 g) versus placebo (p = 0.01 by log rank test). Metabolomics also identified independent predictors of 90-day sepsis mortality. Our proof-of-concept approach shows how pharmacometabolomics could be useful for tackling the heterogeneity of sepsis and informing clinical trial design. In addition, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, because sepsis induces alterations in numerous metabolite concentrations.Platforms with liquid cores are extensively explored as cell delivery vehicles for cell-based therapies and tissue engineering. However, the recurrence of synthetic materials can impair its translation into the clinic. Inspired by the adhesive proteins secreted by mussels, liquefied capsule is developed using gelatin modified with hydroxypyridinones (Gel-HOPO), a catechol analogue with oxidant-resistant properties. The protein-based liquefied macrocapsule permitted the compartmentalization of living cells by an approachable and non-time-consuming methodology resorting to i) superhydrophobic surfaces as a processing platform of hydrogel beads, ii) gelation of gelatin at temperatures less then 25 °C, iii) iron coordination of the hydroxypyridinone (HOPO) moieties at physiological pH, and iv) core liquefaction at 37 °C. With the design of a proteolytically degradable shell, the possibility of encapsulating human adipose-derived mesenchymal stem cells (hASC) with and without the presence of polycaprolactone microparticles (μPCL) is evaluated. Showing prevalence toward adhesion to the inner shell wall, hASC formed a monolayer evidencing the biocompatibility and adequate mechanical properties of these platforms for proliferation, diminishing the need for μPCL as a supporting substrate. This new protein-based liquefied platform can provide biofactories devices of both fundamental and practical importance for tissue engineering and regenerative medicine or in other biotechnology fields.

    Cachexia is common in patients with chronic heart failure and is associated with poor prognosis. How best to measure body composition is not clear.

    We characterized body composition in 120 patients with chronic heart failure mean (SD) age 70 (10) years, left ventricular ejection fraction 44 (10) %, and median (Q1-Q3) N-terminal pro B-type natriuretic peptide 845 (355-1368) ng/L. We measured body composition using dual-energy X-ray absorptiometry (DEXA) and a multi-frequency bioelectrical impedance analysis (BIA) device (Tanita BIA MC-180MA). Mean (SD) fat mass (FM) was 27.2 (11.7) kg by BIA and 32.3 (12.2) kg by DEXA (mean difference -5.1kg, 95% limits of agreement -11.7, 1.5; 4% of values outside limit of agreement); mean (SD) lean mass (LM) was 56.6 (10.9) kg by BIA and 51.1 (9.9) kg by DEXA (mean difference 5.5kg, 95% limits of agreement -1.3, 12.3; 6% of values outside limit of agreement); and mean (SD) bone mass (BM) was 3.0 (0.5) kg by BIA and 2.8 (0.6) kg by DEXA (mean difference 0.2kg, 95% limits of agreement -0.5, 0.8; 5% of values outside limit of agreement). There was a close correlation between DEXA and BIA for both LM and FM (LM r=0.95, P<0.001; FM r=0.96, P<0.001) but less so for BM (r=0.84, P<0.001). Both DEXA and BIA body composition measurements correlated well with other measures of body size (body mass index, hip circumference, and waist circumference).

    There are differences in the measurements of FM, LM, and BM between the two techniques, which should not be used interchangeably.

    There are differences in the measurements of FM, LM, and BM between the two techniques, which should not be used interchangeably.Invited for this month’s cover is the group of Sheng Dai at the Oak Ridge National Laboratory. The image shows the CO2 chemisorption behavior of coordination-derived phenolate sorbents. The Communication itself is available at 10.1002/cssc.202100666.Color polymorphisms have become a major topic in evolutionary biology and substantial efforts have been devoted to the understanding of the mechanisms responsible for originating such colorful systems. Within-morph continuous variation, on the other hand, has been neglected in most of the studies. Here, we combine spectrophotometric/visual modeling and genetic data to study the mechanisms promoting continuous variation within categorical color morphs of Podarcis muralis. Our results suggest that intra-morph variability in the pterin-based orange morph is greater compared to white and yellow morphs. We also show that continuous variation within the orange morph is partially discriminable by conspecifics. Genotyping results indicate that allelic variants at the BCO2 locus (responsible for deposition of yellow carotenoids) contribute to generate continuous variation in orange individuals. However, other intrinsic and/or extrinsic mechanisms, such as body size, might be involved, opening a new avenue for future research on the drivers of continuous variation within-morphs.

    The objective of this prospective, multicenter study is to characterize responses to percutaneous medial branch peripheral nerve stimulation (PNS) to determine if results from earlier, smaller single-center studies and reports were generalizable when performed at a larger number and wider variety of centers in patients recalcitrant to nonsurgical treatments.

    Participants with chronic axial low back pain (LBP) were implanted with percutaneous PNS leads targeting the lumbar medial branch nerves for up to 60days, after which the leads were removed. Participants were followed long-term for 12months after the 2-month PNS treatment. Data collection is complete for visits through end of treatment with PNS (primary end point) and 6months after lead removal (8months after start of treatment), with some participant follow-up visits thereafter in progress.

    Clinically and statistically significant reductions in pain intensity, disability, and pain interference were reported by a majority of participants. Seventy-thlation treatment option for patients with chronic axial back pain.The COVID-19 pandemic has highlighted the vulnerability of people with diabetes mellitus (DM) to respiratory viral infections. Despite the short history of COVID-19, various studies have shown that patients with DM are more likely to have increased hospitalisation and mortality rates as compared to patients without. At present, the mechanisms underlying this susceptibility are unclear. However, prior studies show that the course of COVID-19 disease is linked to the efficacy of the host’s T-cell responses. Healthy individuals who can elicit a robust T-cell response are more likely to limit the severity of COVID-19. Here, we investigate the hypothesis that an impaired T-cell response in patients with type 2 diabetes mellitus (T2DM) drives the severity of COVID-19 in this patient population. While there is currently a limited amount of information that specifically addresses T-cell responses in COVID-19 patients with T2DM, there is a wealth of evidence from other infectious diseases that T-cell immunity is impaired in patients with T2DM. The reasons for this are likely multifactorial, including the presence of hyperglycaemia, glycaemic variability and metformin use. This review emphasises the need for further research into T-cell responses of COVID-19 patients with T2DM in order to better inform our response to COVID-19 and future disease outbreaks.

    The study aimed to elucidate the effects of rare genetic variants on the risk of type 2 diabetes (T2D).

    Weighted burden analysis of rare variants was applied to a sample of 200,000 exome-sequenced participants in the UK Biobank project, of whom over 13,000 were identified as having T2D. Variant weights were allocated based on allele frequency and predicted effect, as informed by a previous analysis of hyperlipidaemia.

    There was an exome-wide significant increased burden of rare, functional variants in three genes, GCK, HNF4A and GIGYF1. GIGYF1 has not previously been identified as a diabetes risk gene and its product appears to be involved in the modification of insulin signalling. A number of other genes did not attain exome-wide significance but were highly ranked and potentially of interest, including ALAD, PPARG, GYG1 and GHRL. Loss of function (LOF) variants were associated with T2D in GCK and GIGYF1 whereas nonsynonymous variants annotated as probably damaging were associated in GCK and HNF4A. Overall, fewer than 1% of T2D cases carried one of these variants. In HNF1A and HNF1B there was an excess of LOF variants among cases but the small numbers of these fell short of statistical significance.

    Rare genetic variants make an identifiable contribution to T2D in a small number of cases but these may provide valuable insights into disease mechanisms. As larger samples become available it is likely that additional genetic factors will be identified.

    Rare genetic variants make an identifiable contribution to T2D in a small number of cases but these may provide valuable insights into disease mechanisms. As larger samples become available it is likely that additional genetic factors will be identified.There are still many problems that hinder the development of sodium-ion batteries (SIBs), including poor rate performance, short-term cycle lifespan, and inferior low-temperature property. Herein, excellent Na-storage performance in fluorophosphate (Na3 V2 (PO4 )2 F3 ) cathode is achieved by lattice regulation based on charge balance theory. Lattice regulation of aliovalent Mn2+ for V3+ increases both electronic conductivity and Na+ -migration kinetics. Because of the maintaining of electrical neutrality in the material, aliovalent Mn2+ -introduced leads to the coexistence of V3+ and V4+ from charge balance theory. It decreases the particle size and improves the structural stability, suppressing the large lattice distortion during cathode reaction processes. These multiple effects enhance the specific capacity (123.8 mAh g-1 ), outstanding high-rate (68% capacity retention at 20 C), ultralong cycle (only 0.018% capacity attenuation per cycle over 1000 cycles at 1 C) and low-temperature (96.5% capacity retention after 400 cycles at -25 °C) performances of Mn2+ -induced Na3 V1.98 Mn0.02 (PO4 )2 F3 when used as cathode in SIBs. Importantly, a feasible sodium-ion full battery is assembled, achieving outstanding rate capability and cycle stability. The strategy of aliovalent ion-induced lattice regulation constructs cathode materials with superior performances, which is available to improve other electrode materials for energy storage systems.

    A validated, standardized, and feasible test to assess muscle power in older adults has recently been reported the sit-to-stand (STS) muscle power test. This investigation aimed to assess the relationship between relative STS power and age and to provide normative data, cut-off points, and minimal clinically important differences (MCID) for STS power measures in older women and men.

    A total of 9320 older adults (6161 women and 3159 men) aged 60-103years and 586 young and middle-aged adults (318 women and 268 men) aged 20-60years were included in this cross-sectional study. Relative (normalized to body mass), allometric (normalized to height squared), and specific (normalized to legs muscle mass) muscle power values were assessed by the 30s STS power test. Body composition was evaluated by dual energy X-ray absorptiometry and bioelectrical impedance analysis, and legs skeletal muscle index (SMI; normalized to height squared) was calculated. Habitual and maximal gait speed, timed up-and-go test, and 6min walking distance were collected as physical performance measures, and participants were classified into two groups well-functioning and mobility-limited older adults.

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