Search

Therapeutic agents targeting the tumor necrosis factor (TNF) superfamily cytokines B‐cell activating factor (BAFF, BLyS) and/or A PRoliferation Inducing Ligand (APRIL) have demonstrated clinical effectiveness in multiple autoimmune diseases, such as systemic lupus erythematosus, lupus nephritis, and immunoglobulin A nephropathy (IgAN). However, their clinical utility can often be limited by incomplete and/or prolonged times to clinical response and inconvenient dosing regimens, which may be improved by more potent dual inhibition of both cytokines. Povetacicept (ALPN‐303; TACI vTD‐Fc) is a crystallizable fragment (Fc) fusion protein of an engineered transmembrane activator and CAML interactor (TACI) domain which mediates more potent inhibitory activity than wild‐type TACI‐Fc or BAFF‐ or APRIL‐specific antibodies and demonstrates superior pharmacokinetic and pharmacodynamic activity in multiple preclinical disease models. In this first‐in‐human study in healthy adults, povetacicept was well‐tolerated as single ascending doses of up to 960 mg administered intravenously or subcutaneously. Dose‐dependent pharmacokinetics were observed. Coverage of BAFF and APRIL was observed for 2–3 weeks and ≥4 weeks after doses of 80 mg and ≥240 mg, respectively. Maximal pharmacodynamic effects were observed at dose levels ≥80 mg for a single dose, associated with on‐target reductions in antibody‐secreting cells as well as in all circulating immunoglobulin isotypes, including the IgAN disease‐related biomarker galactose‐deficient‐immunoglobulin A1 (Gd‐IgA1), and were superior to results reported for wild‐type TACI‐Fc. These data strongly support further development of povetacicept for the treatment of B‐cell‐mediated automimmune diseases. [ABSTRACT FROM AUTHOR]

Millions of people around the world are affected by mental illness, yet a substantive portion of individuals with mental illness do not regularly seek help from medical professionals or utilize mental health services. Help-seeking involves an individual's communicative intention and behaviors to solicit advice and/or treatment and thus is essentially a communicative process. This manuscript reports a longitudinal study that examined predictors and outcomes of help-seeking in mental illness contexts. Three-wave data from 223 participants clinically diagnosed with one or more mental illness conditions were collected and analyzed. Results indicated that expected outcomes of help-seeking from counselors were significantly associated with participants' communication efficacy and target efficacy at Wave 1, which subsequently influenced motivation to seek help and actual help-seeking behaviors at Wave 2. Actual help-seeking behaviors predicted post-traumatic growth and cognitive reappraisal at Wave 3. Importantly, communication efficacy and target efficacy interacted in their effects on help-seeking motivation and behaviors. Theoretical implications for help-seeking communication processes and practical implications for mental health help-seeking are discussed. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that individuals with internet gaming disorder (IGD) display abnormal autonomic activities at rest and during gameplay. Here, we examined whether and how in-game autonomic activity is modulated by human characteristics and behavioral performance of the player. We measured heart rate variability (HRV) in 42 male university student habitual gamers (HGs) when they played a round of League of Legends game online. Short-term HRV indices measured in early, middle and late phases of the game were compared between the players at high risk of developing IGD and those at low risk, as assessed by the revised Chen Internet addiction scale (CIAS-R). Multiple linear regression (MLR) was used to identify significant predictors of HRV measured over the whole gameplay period (WG), among CIAS-R, ranking score, hours of weekly playing and selected in-game performance parameters. The high-risk players showed a significantly higher low-frequency power/high-frequency power ratio (LF/HF) relative to the low-risk players, regardless of game phase. MLR analysis revealed that LF/HF measured in WG was predicted by, and only by, CIAS-R. The HRV indicators of sympathetic activity were found to be predicted only by the number of slain in WG (NSlain), and the indicators of parasympathetic activity were predicted by both CIAS-R and NSlain. Collectively, the results demonstrated that risk of developing IGD is associated with dysregulated autonomic balance during gameplay, and in-game autonomic activities are modulated by complex interactions among personal attributes and in-game behavioral performance of the player, as well as situational factors embedded in game mechanics. [ABSTRACT FROM AUTHOR]

Objective: Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high‐affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors. Methods: A variant of TACI‐Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN‐303). Povetacicept was compared to wild‐type (WT) TACI‐Fc and related molecules in vitro and in vivo. Results: Povetacicept inhibited APRIL and BAFF more effectively than all evaluated forms of WT TACI‐Fc and selective APRIL and BAFF inhibitors in cell‐based reporter assays and primary human B cell assays, mediating potent suppression of B cell proliferation, differentiation, and immunoglobulin (Ig) secretion. In mouse immunization models, povetacicept significantly reduced serum immunoglobulin titers and antibody‐secreting cells more effectively than anti‐CD20 monoclonal antibodies, WT TACI‐Fc, or APRIL and BAFF inhibitors. In the NZB × NZW mouse lupus nephritis model, povetacicept significantly enhanced survival and suppressed proteinuria, anti–double‐stranded DNA antibody titers, blood urea nitrogen, glomerulonephritis, and renal immunoglobulin deposition. In the bm12 mouse lupus model, povetacicept significantly reduced splenic plasmablasts, follicular helper T cells, and germinal center B cells. In non‐human primates, povetacicept was well tolerated, exhibited high serum exposure, and significantly decreased serum IgM, IgA, and IgG levels after a single dose. Conclusion: Enhanced APRIL and BAFF inhibition by povetacicept led to greater inhibition of B cell populations critical for autoantibody production compared to WT TACI‐Fc and CD20‐, APRIL‐, or BAFF‐selective inhibitors. Potent, dual inhibition by povetacicept has the potential to significantly improve clinical outcomes in autoantibody‐related autoimmune diseases. [ABSTRACT FROM AUTHOR]

In response to scholars who recommend additional research concerning the role of communication technologies in relational conflict, we employ the communicative interdependence perspective (Caughlin & Sharabi, 2013) to explore mode integration and segmentation during serial arguments. More specifically, we found that technologically-mediated communication (TMC) and face-to-face (FtF) communication are commonly integrated during serial arguments. Mode integration was especially likely when serial arguments were seen as serious, relationally threatening, and less resolvable. Yet, integration of TMC and FtF communication and integration of multiple TMC channels during serial arguments were negatively associated with relational closeness and satisfaction for dating partners. Segmentation to one mode was rare and was not associated with relational satisfaction or closeness. We discuss the implications of these findings for the communicative interdependence perspective and our understanding of serial arguments in relationships. Key Words: communicative interdependence, serial arguments, conflict, technology, THE ROLE OF COMMUNICATION TECHNOLOGIES IN SERIAL ARGUMENTS: A COMMUNICATIVE INTERDEPENDENCE PERSPECTIVE The study of technologically-mediated communication (TMC) within personal relationships has become a significant topic of study (Baym, 2010). [...]

Individuals with mental illness commonly experience uncertainty related to not only the condition itself but also personal and social implications surrounding mental illness. Support from family has the potential to alleviate uncertain feelings and reduce perceived stress. Drawing on the sensitive interaction systems theory, this longitudinal study investigated the support seeking processes and outcomes in mental illness. Results suggested that perceived uncertainty about mental illness was negatively associated with desired emotional and informational support from close family. Desired support predicted received support and reduced perceived stress 2 weeks later. The effect of desired support on received support was mediated by direct support seeking behaviors. Communication efficacy, relational trust, and motivation to seek support moderated the associations between desired support and support seeking behaviors. Findings offer theoretical and practical implications for support seeking from family members in mental illness. [ABSTRACT FROM AUTHOR]

Owing to the toxicity and adverse effects of arsenic on human health, its levels in aquatic environments are among the most serious threats to humans globally. To improve our understanding of its occurrence and cycling in aquatic environments, herein we review the concentration, speciation, and distribution of arsenic in freshwater, seawater, and sediments. Many natural processes, such as rock weathering and geothermal activities, contribute to the background arsenic concentrations in the natural environment, whereas metal mining and smelting are anthropogenic sources of arsenic in the water. The high solubility and mobility of arsenic in aquatic environments affects its global cycling. Furthermore, the biological processes in the aquatic environment are discussed, especially the possible microbe-mediated reactions of arsenic in sediments. In addition, various environmental factors, such as redox conditions, pH, and salinity, which influence the transformation of arsenic species, are summarized. Finally, the differences between freshwater and seawater with reference to the concentration as well as speciation and distribution patterns of arsenic are addressed. This review provides deep insights into arsenic occurrence and cycling between freshwater and seawater aquatic environments, which can more accurately distinguish the risks of arsenic in different water environments, and provides theoretical guidance for the prevention and control of arsenic risks. [ABSTRACT FROM AUTHOR]