Riissander5370

OBJECTIVE Different adipokines have been reported to play a role in the development, progression, and severity of knee osteoarthritis, but this association may be mediated by obesity. The aim of this study was to evaluate separately the associations of leptin and adiponectin with clinical severity and inflammatory markers in nonobese and obese women with knee osteoarthritis. DESIGN Cross-sectional study with systematic inclusion of 115 women with symptomatic primary knee osteoarthritis. Age, physical exercise, symptoms duration, and body mass index were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-total, -pain, -function subscales. Two adipokines (leptin and adiponectin) and 3 inflammatory markers (TNF-α, hsCRP, and IL-6) were measured by ELISA in synovial fluid and serum. RESULTS Synovial fluid adiponectin was associated with WOMAC pain, function, and total and with synovial fluid IL-6 in nonobese female knee osteoarthritis after controlling by confounders (partial correlation coefficient [PCC] = 0.395, 0.387, 0.427, and 0.649, respectively). Synovial fluid and serum leptin were significantly associated with IL-6 (PCC = 0.354) after controlling by confounders but associations with clinical severity and the rest of inflammatory markers were mitigated after control. CONCLUSIONS Adiponectin in synovial fluid was associated with clinical severity and local inflammatory markers in knee osteoarthritis women, while leptin relation was attenuated when controlled by confounders.Objectives To discuss (1) recent and emerging data for pharmacological management of untreated and relapsed/refractory (R/R) mantle cell lymphoma (MCL) with agents approved in the United States, (2) important considerations for toxicity monitoring and management, and (3) preliminary data and ongoing studies for agents in MCL-specific clinical trials. selleckchem Data Sources PubMed/MEDLINE, EMBASE, Google Scholar, product labeling, National Comprehensive Cancer Network, American Cancer Society, and ClinicalTrials.gov were searched for studies published between January 1, 2017, and January 31, 2020, and key historical trials. Study Selection and Data Extraction Relevant studies conducted in humans and selected supporting preclinical data were reviewed. Data Synthesis MCL is a rare but usually aggressive non-Hodgkin lymphoma that most commonly affects the older population. Traditionally, the treatment of MCL has been determined based on transplant eligibility. Newer data suggest that more tolerable frontline therapy may produce outcomes similar to intensive historical induction regimens, possibly precluding fewer patients from autologous stem cell transplant and producing better long-term outcomes in transplant-ineligible patients. link2 In the R/R setting, novel regimens are improving outcomes and changing the landscape of treatment. Relevance to Patient Care and Clinical Practice This review summarizes and discusses recent and emerging data for management of newly diagnosed and R/R MCL; key supportive care considerations for agents are also discussed. Conclusions Recent study results are changing management of MCL. Although these data have complicated the picture of regimen selection, increasingly effective and tolerable therapy and additional anticipated data point to a brighter future for patients with MCL.RATIONALE Exposure to biomass smoke is believed to increase the risk of developing chronic obstructive pulmonary disease (COPD). However, little is known about the mechanisms underlying responses to biomass smoke in human lung. OBJECTIVES This study had 2 objectives firstly to quantify 'real-life' exposures to particulate matter (PM2.5) and carbon monoxide (CO) measured during cooking on stoves in rural areas of Nepal in different geographical settings, and secondly to assess the effect of biomass smoke extracts on inflammatory responses in human lung tissue. METHODS Personal exposures to PM2.5 and indoor near stove CO concentrations were measured during cooking on a range of stoves in 103 households in 4 different Nepalese villages situated at altitudes between ~100m to 4000m above sea level. Inflammatory profiles to smoke extracts collected in the field were assessed by incubating extracts with human lung tissue fragments and subsequent Luminex analysis. RESULTS In households using traditional cooking stoves the overall mean personal exposure to PM2.5 was 276.1 µg/m3 (SD 265 µg/m3) and indoor CO concentration was 16.3 ppm (SD 19.65 ppm) The overall mean PM2.5 exposure was reduced by 51% (p=0.04) in households using biomass fuel in improved cook stoves (ICS) and 80% (p less then 0.0001) in households using LPG. Similarly, the indoor CO concentration was reduced by 72% (p less then 0.001) and 86% (p less then 0.0001) in households using ICS and LPG respectively. Significant responses occurred to biomass smoke extract stimulation in human lung tissue for IL8, IL6, TNFα, IL1β, CCL2, CCL3, and CCL13. CONCLUSIONS High levels of real life exposures to PM2.5 and CO occur during cooking events in rural Nepal. These exposures induce lung inflammation which may in part explain the increased risk of COPD in these communities.Research suggests that disruption of brain networks might explain cognitive deficits in multiple sclerosis (MS). The reliability and effectiveness of graph-theoretic network metrics as measures of cognitive performance were tested in 37 people with MS and 23 controls. Specifically, relationships to cognitive performance (linear regression against the Paced Auditory Serial Addition Test [PASAT-3], Symbol Digit Modalities Test [SDMT] and Attention Network Test [ANT]) and one-month reliability (using the intra-class correlation coefficient [ICC]) of network metrics were measured using both resting-state functional and diffusion MRI data. Cognitive impairment was directly related to measures of brain network segregation and inversely related to network integration (prediction of PASAT-3 by small-worldness, modularity, characteristic path length, R2=0.55; prediction of SDMT by small-worldness, global efficiency and characteristic path length, R2=0.60). Reliability of the measures over one month in a subset of 9 participants was mostly rated as good (ICC>0.6) for both controls and MS patients in both functional and diffusion data but was highly dependent on the chosen parcellation and graph density, with the 0.2-0.5 density range being the most reliable. This suggests that disrupted network organisation predicts cognitive impairment in MS and its measurement is reliable over a 1-month period. These new findings support the hypothesis of network disruption as a major determinant of cognitive deficits in MS and the future possibility of the application of derived metrics as surrogate outcomes in trials of therapies for cognitive impairment.SIGNIFICANCE Mitochondria represent a major source of intracellular reactive oxygen species (ROS) generation. This is often a consequence of oxidative phosphorylation (OXPHOS), which can produce ROS as a result of leakage from the electron transport chain (ETC). In addition, quality control mechanisms exist to protect cells at from cytotoxic ROS production. One such mechanism is selective autophagic degradation of ROS-producing mitochondria, termed mitophagy, that ultimately results in elimination of mitochondria in the lysosome. Recent Advances. However, while the relationship between mitophagy and ROS production are clearly interwoven, they have yet to be fully untangled. In some circumstances, mitochondrial ROS (mtROS) are elevated as as a consequence of mitophagy induction. CRITICAL ISSUES In this review, we discuss mtROS generation and their detrimental effects on cellular viability. Additionally, we consider the cellular defense mechanisms that the eukaryotic cell employs to abrogate superfluous oxidative stress. In particular, we delve into the prominent mechanisms governing mitophagy induction that bear on oxidative stress. FUTURE DIRECTIONS Finally, we examine the pathological conditions associated with defective mitophagy where additional research may help to facilitate understanding.Recombinant forms contribute substantially to the genetic diversity of HIV-1. Recent studies have also revealed that three major viral strains (CRF07_BC, CRF01_AE, and subtype B) have been cocirculating among MSM in Anhui, suggesting a high probability of generating new recombinants. Here, we reported a novel CRF01_AE and CRF07_BC HIV-1 recombinant form in men who have sex with men (MSM) in Fuyang city of China. Two near full-length sequences (NFLG) named FY184, FY208 were successfully obtained. The genomic composition analysis of the NFLG reveals that it was divided into four segments by three breakpoints, with two regions of CRF07_BC inserted into a CRF01_AE backbone's gag, pol regions. The CRF01_AE regions were originated from a sub-cluster lineage of CRF01_AE, which mainly circulating among MSM in China. The emergence of a novel recombinant of CRF01_AE/CRF07_BC is indicative of the increasing genetic diversity of the HIV epidemic in MSM in Anhui.Carrier multiplication (CM) is an effective mechanism that makes it possible to use hot carriers (HCs) to bypass the Shockley-Queisser limit for solar-cell efficiency. In this paper, we present a detailed study of both CM and HC cooling dynamics in quantum-confined CsPbI3 perovskite nanocrystals (NCs), using femtosecond transient absorption spectroscopy. Our results show that barrierless CM, with an efficiency exceeding 90%, can be achieved in strongly confined NCs on a time scale of ≪200 fs. A low CM efficiency (∼40%), however, is observed in weakly confined NCs. HC cooling dynamics suggests the absence of an intrinsic phonon bottleneck in strongly confined NCs. Furthermore, the biexciton Auger rate increased 4-fold in strongly confined NCs compared to that in weakly confined NCs. These results suggest that the enhanced CM in strongly confined NCs likely originates from enhanced Coulomb coupling and relaxed momentum conservation.We determined that consuming chungkookjang fermented by Bacillus subtilis(BS) or Bacillus amyloliquefaciens(BA) alleviated hyperglycemia in partially pancreatectomized(Px) rats, an Asian type 2 diabetic(T2D) animal model. Px rats had deteriorated glucose metabolism with decreased glucose-stimulated insulin secretion and insulin sensitivity. Insulin secretion capacity was improved in the ascending order of the Px-control, positive-control(3 mg metformin/kg bw), BS(4.5% BS diet), BA(4.5% BA diet), and normal-control(sham-operated rats). BA and BS increased β-cell mass and decreased malondialdehyde contents and TNF-α expression in the islets. BA increased hepatic PPAR-α and PPAR-β similar to the positive-control. link3 Bacillales, Lactobacillales, and Verrucomicrobiales(Akkermentia muciniphila) increased and Enterobacteriales decreased in the BA and BS compared to the Px-control. BA prevented the decrease in villi area and number of goblet cells in intestinal tissues. In conclusion, BA improved glucose regulation by potentiating insulin secretion and reducing insulin resistance while maintaining gut mucin contents by improving gut microbiota in lean T2D rats.