The contribution of inflammation to the chronic joint disease osteoarthritis (OA) is unclear, and this lack of clarity is detrimental to efforts to identify therapeutic targets. Here we show that ...chondrocytes under inflammatory conditions undergo a metabolic shift that is regulated by NF-κB activation, leading to reprogramming of cell metabolism towards glycolysis and lactate dehydrogenase A (LDHA). Inflammation and metabolism can reciprocally modulate each other to regulate cartilage degradation. LDHA binds to NADH and promotes reactive oxygen species (ROS) to induce catabolic changes through stabilization of IκB-ζ, a critical pro-inflammatory mediator in chondrocytes. IκB-ζ is regulated bi-modally at the stages of transcription and protein degradation. Overall, this work highlights the function of NF-κB activity in the OA joint as well as a ROS promoting function for LDHA and identifies LDHA as a potential therapeutic target for OA treatment.
Objective
Childhood maltreatment has been linked to impairments in social functioning and social cognition in adults with affective disorders. However, conclusions have been limited by inconsistent ...findings across different maltreatment subtypes and social domains. We conducted a systematic review and meta‐analysis to quantify associations between childhood maltreatment (overall and subtypes ‐ physical, emotional and/or sexual abuse, and/or physical and/or emotional neglect) and different domains of social functioning and social cognition in adults with affective disorders (bipolar disorder or major depressive disorder). We also examined effect moderators and mediators of these associations.
Methods
A systematic search was performed on 12.12.2022 which identified 29 studies included in qualitative synthesis (n = 3022 individuals with affective disorders), of which 27 (n = 2957) were pooled in meta‐analyses. Across studies, five social functioning and five social cognition domains were examined, of which four domains of social functioning and two domains of social cognition had sufficient data for meta‐analysis (PROSPERO CRD42022288976).
Results
Social functioning: childhood maltreatment was associated with lower global social functioning (r = −0.11 to −0.20), poorer interpersonal relations (r = −0.18 to −0.33), and with aggressive behaviour (r = 0.20–0.29) but was unrelated to vocational functioning. Emotional abuse and emotional neglect showed the largest magnitudes of effect. Social cognition: there was no meta‐analytic evidence of associations between maltreatment and social cognition domains. Exploratory moderation analyses did not identify any consistent moderators. Narrative synthesis identified attachment style as possible moderator, and sensory patterns, anxiety, and depressive symptoms as possible mediators between childhood maltreatment and social outcomes. Overall, the available evidence was limited, particularly in relation to social cognition.
Conclusions
Adults with affective disorders are at risk of social functioning difficulties after childhood maltreatment exposure, an effect observed across multiple maltreatment subtypes, social functioning domains, and diagnoses. Addressing social functioning problems may benefit maltreated adults with both bipolar disorder and major depressive disorder.
Childhood maltreatment (CM) has been related to social functioning and social cognition impairment in people with psychotic disorders (PD); however, evidence across different CM subtypes and social ...domains remains less clear. We conducted a systematic review and meta-analysis to quantify associations between CM, overall and its different subtypes (physical/emotional/sexual abuse, physical/emotional neglect), and domains of social functioning and social cognition in adults with PD. We also examined moderators and mediators of these associations. A PRISMA-compliant systematic search was performed on 24 November 2022 (PROSPERO CRD42020175244). Fifty-three studies (N = 13 635 individuals with PD) were included in qualitative synthesis, of which 51 studies (N = 13 260) with 125 effects sizes were pooled in meta-analyses. We found that CM was negatively associated with global social functioning and interpersonal relations, and positively associated with aggressive behaviour, but unrelated to independent living or occupational functioning. There was no meta-analytic evidence of associations between CM and social cognition. Meta-regression analyses did not identify any consistent moderation pattern. Narrative synthesis identified sex and timing of CM as potential moderators, and depressive symptoms and maladaptive personality traits as possible mediators between CM and social outcomes. Associations were of small magnitude and limited number of studies assessing CM subtypes and social cognition are available. Nevertheless, adults with PD are at risk of social functioning problems after CM exposure, an effect observed across multiple CM subtypes, social domains, diagnoses and illness stages. Maltreated adults with PD may thus benefit from trauma-related and psychosocial interventions targeting social relationships and functioning.
Rotavirus (RV) vaccine efficacy is significantly reduced in lower- and middle-income countries (LMICs) compared to high-income countries. This review summarizes current research into the mechanisms ...behind this phenomenon, with a particular focus on the evidence that maternal antibody (matAb) interference is a contributing factor to this disparity. All RV vaccines currently in use are orally administered, live-attenuated virus vaccines that replicate in the infant gut, which leaves their efficacy potentially impacted by both placentally transferred immunoglobulin G (IgG) and mucosal IgA Abs conferred via breast milk. Observational studies of cohorts in LMICs demonstrated an inverse correlation between matAb titers, both in serum and breast milk, and infant responses to RV vaccination. However, a causal link between maternal humoral immunity and reduced RV vaccine efficacy in infants has yet to be definitively established, partially due to limitations in current animal models of RV disease. The characteristics of Abs mediating interference and the mechanism(s) involved have yet to be determined, and these may differ from mechanisms of matAb interference for parenterally administered vaccines due to the contribution of mucosal immunity conferred via breast milk. Increased vaccine doses and later age of vaccine administration have been strategies applied to overcome matAb interference, but these approaches are difficult to safely implement in the setting of RV vaccination in LMICs. Ultimately, the development of relevant animal models of matAb interference is needed to determine what alternative approaches or vaccine designs can safely and effectively overcome matAb interference of infant RV vaccination.
The purpose of this study was to compare cardiovascular and respiratory effects of two volumes of bupivacaine 0.25% (0.2 mL kg-1-treatment BUP02-and 0.4 mL kg-1 -treatment BUP04) administered ...epidurally at the lumbosacral intervertebral space in dogs anesthetized with isoflurane. This experimental prospective randomized crossover design trial used six mixed breed adult dogs, four neutered males and two spayed females. Each dog was anesthetized on three different occasions: the first for isoflurane minimum alveolar concentration (MAC) measurement, and the following two assigned treatments (BUP02 or BUP04). On the two treatment days, anesthesia was induced and maintained with isoflurane at 1.3 MAC during the experiments. Cardiovascular and respiratory measurements were recorded before (T0) and 5, 15, 30, 60 and 90 minutes after the epidural administration of bupivacaine. Comparisons between and within groups were performed by a mixed-model ANOVA and Friedman's test when appropriate followed by Bonferroni post-hoc test or Dunnet's test to compare time points within each treatment with T0 (p < 0.05). Mean arterial pressure decreased significantly from 15 to 90 minutes after the administration of BUP02 and from 5 to 60 minutes in BUP04, with lower values in BUP04 than in BUP02 lasting up to 30 minutes after bupivacaine administration. No significant changes in cardiac output and systemic vascular resistance were observed in either treatment. Hypoventilation was only detected in BUP04. Hemoglobin concentration and arterial oxygen content decreased after both treatment of bupivacaine with no significant decrease in oxygen delivery. Two dogs in BUP04 developed Horner's syndrome. The epidural administration of 0.4 mL.kg-1 of bupivacaine to dogs in sternal recumbency anesthetized with isoflurane 1.3 MAC caused more cardiovascular and respiratory depression than 0.2 mL.kg-1.
Dry sliding wear behavior of rheocast AZ91 magnesium alloy and AZ91/SiCp composites reinforced with 5 and 10vol% SiC particles were investigated under normal loads of 10–250N and sliding speeds of ...0.1, 0.3, 0.5 and 1m/s using pin-on-disc configuration against a 1045 steel disc counterbody. In this work, rheocast alloys and composites have been tested to determine the role played by the globular microstructure, and to evaluate if the increase observed in other mechanical properties is also translated to wear behavior. Wear rates and friction coefficients were registered during wear tests. Worn tracks and wear debris were studied by Scanning Electron Microscope (SEM) and Energy Dispersive X-Ray Spectrometry (EDS) in order to obtain the predominant wear mechanisms maps of the studied materials. The following wear mechanisms were found in the worn surface of the three materials: abrasion, oxidation delamination and melt wear. The composites with globular microstructure exhibit slightly superior wear resistance at low testing sliding speeds (0.1 and 0.3m/s) and medium loads (40–80N) than the AZ91 Mg alloy. But, for other conditions, the presence of SiC particles seems to be detrimental to the wear behavior of AZ91 magnesium alloy. A wear mechanisms map that allows identifying the main wear mechanisms for each wear condition and material composition has been developed. Rheocast microstructure improves the wear resistance of alloys in most conditions but the addition of SiCp reinforcement is only favorable in few of them.
•Wear behavior of rheocast AZ91, AZ91/5%SiCp and AZ91/5%SiCp was studied.•Abrasion, oxidation, delamination and melt wear mechanisms were found.•Al low testing sliding speeds and medium loads, composites have better wear behavior than the alloy.•At the most severe condition, the SiC particles seem to be detrimental to the wear behavior.•A mechanism wear map was developed.
Antibodies that can bind to viruses but are unable to block infection in cell culture are known as "nonneutralizing antibodies." Such antibodies are nearly universally elicited following viral ...infection and have been characterized in viral infections such as influenza, rotavirus, cytomegalovirus, HIV, and SARS-CoV-2. It has been widely assumed that these nonneutralizing antibodies do not function in a protective way in vivo and therefore are not desirable targets of antiviral interventions; however, increasing evidence now shows this not to be true. Several virus-specific nonneutralizing antibody responses have been correlated with protection in human studies and also shown to significantly reduce virus replication in animal models. The mechanisms by which many of these antibodies function is only now coming to light. While nonneutralizing antibodies cannot prevent viruses entering their host cell, nonneutralizing antibodies work in the extracellular space to recruit effector proteins or cells that can destroy the antibody-virus complex. Other nonneutralizing antibodies exert their effects inside cells, either by blocking the virus life cycle directly or by recruiting the intracellular Fc receptor TRIM21. In this review, we will discuss the multitude of ways in which nonneutralizing antibodies function against a range of viral infections.
Modeling signal power path loss (SPPL) for deployment of wireless communication systems (WCSs) is one of the most time consuming and expensive processes that require data collections during link ...budget analysis. Radio frequency (RF) engineers mainly employ either deterministic or stochastic approaches for the estimation of SPPL. In the case of stochastic approach, empirical propagation models use predefined estimation parameters for different environments such as reference distance path loss PL<inline-formula> <tex-math notation="LaTeX">(d_{0}) </tex-math></inline-formula>(dB), path loss exponent <inline-formula> <tex-math notation="LaTeX">(n) </tex-math></inline-formula>, and log-normal shadowing <inline-formula> <tex-math notation="LaTeX">(X_{\sigma } </tex-math></inline-formula> with <inline-formula> <tex-math notation="LaTeX">N(\sigma ,\mu =0)) </tex-math></inline-formula>. Since empirical models broadly classify the environment under urban, suburban, and rural area, they do not take into account every micro-variation on the terrain. Therefore, empirical models deviate significantly from actual measurements. This paper proposes a smart deployment method of WCS to minimize the need for predefined estimation parameters by creating a 3-D deployment environment which takes into account the micro-variations in the environment. Tree canopies are highly complex structures which create micro-variations and related unidentified path loss due to scattering and absorption. Thus, our proposed model will mainly focus on the effect of tree canopies and can be applied to any environment. The proposed model uses a 2-D image color classification to extract features from a 3-D point cloud and a machine learning (ML) algorithm to predict SPPL. Empirical path loss models have received signal level (RSL) errors in the range of 6.29%-16.9% from the actual RSL measurements while the proposed model has an RSL error of 4.26%.
A fundamental step towards atomic- or molecular-scale spintronic devices has recently been made by demonstrating that the spin of an individual atom deposited on a surface, or of a small paramagnetic ...molecule embedded in a nanojunction, can be externally controlled. An appealing next step is the extension of such a capability to the field of information storage, by taking advantage of the magnetic bistability and rich quantum behaviour of single-molecule magnets (SMMs). Recently, a proof of concept that the magnetic memory effect is retained when SMMs are chemically anchored to a metallic surface was provided. However, control of the nanoscale organization of these complex systems is required for SMMs to be integrated into molecular spintronic devices. Here we show that a preferential orientation of Fe4 complexes on a gold surface can be achieved by chemical tailoring. As a result, the most striking quantum feature of SMMs-their stepped hysteresis loop, which results from resonant quantum tunnelling of the magnetization-can be clearly detected using synchrotron-based spectroscopic techniques. With the aid of multiple theoretical approaches, we relate the angular dependence of the quantum tunnelling resonances to the adsorption geometry, and demonstrate that molecules predominantly lie with their easy axes close to the surface normal. Our findings prove that the quantum spin dynamics can be observed in SMMs chemically grafted to surfaces, and offer a tool to reveal the organization of matter at the nanoscale.
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