Scalable Design of Ru-Embedded Carbon Fabric Using Conventional Carbon Fiber Processing for Robust Electrocatalysts.

Metal-carbon composites are extensively utilized as electrochemical catalysts but face critical challenges in mass production and stability. We report a scalable manufacturing process for ruthenium surface-embedded fabric electrocatalysts (Ru-SFECs) via conventional fiber/fabric manufacturing. Ru-SFECs have excellent catalytic activity and stability toward the hydrogen evolution reaction, exhibiting a low overpotential of 11.9 mV at a current density of 10 mA cm-2 in an alkaline solution (1.0 M aq KOH solution) with only a slight overpotential increment (6.5%) after 10,000 cycles, whereas under identical conditions, that of commercial Pt/C increases 6-fold (from 1.3 to 7.8 mV). Using semipilot-scale equipment, a protocol is optimized for fabricating continuous self-supported electrocatalytic electrodes. Tailoring the fiber processing parameters (tension and temperature) can optimize the structural development, thereby achieving good catalytic performance and mechanical integrity. These findings underscore the significance of self-supporting catalysts, offering a general framework for stable, binder-free electrocatalytic electrode design.

Life under the snow: A year-round transcriptome analysis of Antarctic mosses in natural habitats provides insight into the molecular adaptation of plants under extreme environment.

Mosses are vital components of ecosystems, exhibiting remarkable adaptability across diverse habitats from deserts to polar ice caps. Sanionia uncinata (Hedw.) Loeske, a dominant Antarctic moss survives extreme environmental condition through perennial lifecycles involving growth and dormancy alternation. This study explores genetic controls and molecular mechanisms enabling S. uncinata to cope with seasonality of the Antarctic environment. We analysed the seasonal transcriptome dynamics of S. uncinata collected monthly from February 2015 to January 2016 in King George Island, Antarctica. Findings indicate that genes involved in plant growth were predominantly upregulated in Antarctic summer, while those associated with protein synthesis and cell cycle showed marked expression during the winter-to-summer transition. Genes implicated in cellular stress and abscisic acid signalling were highly expressed in winter. Further, validation included a comparison of the Antarctic field transcriptome data with controlled environment simulation of Antarctic summer and winter temperatures, which revealed consistent gene expression patterns in both datasets. This proposes a seasonal gene regulatory model of S. uncinate to understand moss adaptation to extreme environments. Additionally, this data set is a valuable resource for predicting genetic responses to climatic fluctuations, enhancing our knowledge of Antarctic flora's resilience to global climate change.

COVID-19 and Mortality in the Global Surgical Population: A Systematic Review and Meta-Analysis.

INTRODUCTION: To date, no systematic review or meta-analysis has comprehensively estimated the risk of mortality by surgery type on an international scale. We aim to delineate the risk of mortality in patients with COVID-19 who undergo surgery. METHODS: PubMed (MEDLINE), Scopus, OVID, the World Health Organization Global Literature on Coronavirus Disease, and Corona-Central databases were searched from December 2019 through January 2022. Studies providing data on mortality in patients undergoing surgery were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for abstracting data were followed and performed independently by two reviewers. The main outcome was mortality in patients with COVID-19. RESULTS: Of a total of 4023 studies identified, 46 studies with 80,015 patients met our inclusion criteria. The mean age was 67 y; 57% were male. Surgery types included general (14.9%), orthopedic (23.4%), vascular (6.4%), thoracic (10.6%), and urologic (8.5%). Patients undergoing surgery with COVID-19 elicited a nine-fold increased risk of mortality (relative risk [RR] 8.99, 95% confidence interval [CI] 4.96-16.32) over those without COVID-19. In low-income and middle-income countries (RR: 16.04, 95% CI: 4.59-56.12), the mortality risk was twice as high compared to high-income countries (RR: 7.50, 95% CI: 4.30-13.09). CONCLUSIONS: Mortality risk in surgical patients with COVID-19 compared to those without is increased almost 10-fold. The risk was highest in low-income and middle-income countries compared to high-income countries, suggesting a disproportionate effect of the pandemic on resource-constrained regions.

Water Quality Monitoring with the Multiplexed Assay MitoOxTox for Mitochondrial Toxicity, Oxidative Stress Response, and Cytotoxicity in AREc32 Cells.

Mitochondria play a key role in the energy production of cells, but their function can be disturbed by environmental toxicants. We developed a cell-based mitochondrial toxicity assay for environmental chemicals and their mixtures extracted from water samples. The reporter gene cell line AREc32, which is frequently used to quantify the cytotoxicity and oxidative stress response of water samples, was multiplexed with an endpoint of mitochondrial toxicity. The disruption of the mitochondrial membrane potential (MMP) was quantified by high-content imaging and compared to measured cytotoxicity, predicted baseline toxicity, and activation of the oxidative stress response. Mitochondrial complex I inhibitors showed highly specific effects on the MMP, with minor effects on cell viability. Uncouplers showed a wide distribution of specificity on the MMP, often accompanied by specific cytotoxicity (enhanced over baseline toxicity). Mitochondrial toxicity and the oxidative stress response were not directly associated. The multiplexed assay was applied to water samples ranging from wastewater treatment plant (WWTP) influent and effluent and surface water to drinking and bottled water from various European countries. Specific effects on MMP were observed for the WWTP influent and effluent. This new MitoOxTox assay is an important complement for existing in vitro test batteries for water quality testing and has potential for applications in human biomonitoring.

Free Fatty Acid 4 Receptor Activation Attenuates Collagen-Induced Arthritis by Rebalancing Th1/Th17 and Treg Cells.

Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been found to be beneficial in rodent rheumatoid arthritis models and human trials. However, the molecular targets of n-3 PUFAs and their beneficial effects on rheumatoid arthritis are under-researched. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor for n-3 PUFA. We aim to investigate whether FFA4 activation reduces collagen-induced rheumatoid arthritis (CIA) by using an FFA4 agonist, compound A (CpdA), in combination with DBA-1J Ffa4 gene wild-type (WT) and Ffa4 gene knock-out (KO) mice. CIA induced an increase in the arthritis score, foot edema, synovial hyperplasia, pannus formation, proteoglycan loss, cartilage damage, and bone erosion, whereas the administration of CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA increased mRNA expression levels of pro-inflammatory Th1/Th17 cytokines, whereas CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA induced an imbalance between Th1/Th17 and Treg cells, whereas CpdA rebalanced them in spleens from Ffa4 WT mice but not Ffa4 gene KO mice. In SW982 synovial cells, CpdA reduced the LPS-induced increase in pro-inflammatory cytokine levels. In summary, the present results suggest that the activation of FFA4 in immune and synovial cells could suppress the characteristics of rheumatoid arthritis and be an adjuvant therapy.

Developmental inflection point for the effect of maternal childhood adversity on children's mental health from childhood to adolescence: Time-varying effect of gender differences.

Childhood adversities have a well-established dose-response relationship with later mental health. However, less attention has been given to intergenerational influences. Further, it is unknown how intergenerational influences intersect with children's developmental stages and gender. The current study examined whether a developmental inflection point exists when the intergenerational influences of childhood adversities gain salience and explored differences by children's gender. Data were from the Young Women and Child Development Study (n = 361). Time-varying effect models (TVEMs) and moderation TVEMs by child's gender were evaluated. Our findings reveal that ages 5-8, the period of transition into primary schools, may represent a developmental inflection point when the intergenerational influences of maternal childhood adversity start emerging substantially. The results from gender interaction TVEMs reveal that maternal childhood adversity was a statistically significant predictor of internalizing problems until age 11, regardless of child's gender, and remained statistically significant for girls' internalizing problems until age 16.7. For externalizing problems, maternal childhood adversity was a statistically significant predictor until age 13, regardless of gender.

Socioeconomic Disparities Associated With Healthcare Utilization Among Adults With Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic and debilitating disease associated with negative health outcomes and high healthcare utilization. Little is known about the role of demographic and socioeconomic factors associated with healthcare utilization in RA. OBJECTIVES: The purpose of this study was to explore the relationships between demographic and socioeconomic characteristics, insurance status, general health perception, and healthcare utilization among adults with RA. METHODS: In this cross-sectional analysis of data from 537 participants with a self-reported diagnosis of RA from the 2017-2020 National Health and Nutrition Examination Survey, multivariate logistic regression analyses were used to explore the relationships between demographic and socioeconomic factors, insurance status, general health perception, and healthcare utilization (i.e., whether an individual saw a provider, had a routine place to go for healthcare, and stayed overnight in the hospital). RESULTS: The mean age of participants was 57 years; 50% were female, 57.9% were non-Hispanic White, 17.9% were Black, and 15.2% were Mexican or other Hispanic. Individuals without health insurance were less likely than insured individuals with RA to have seen a provider, have a routine place to go for healthcare, and have stayed overnight in the hospital. Adults with RA who rated their health as very good or excellent were more likely to have a routine place for healthcare and less likely to stay overnight in the hospital than those who rated their health as fair or poor. DISCUSSION: Lack of health insurance significantly correlates with decreased healthcare utilization in adults with RA in the United States. Our findings underscore the need for more frequent assessment of insurance status in adults with RA to identify individuals at an increased risk for reduced healthcare utilization and who are more likely to experience poorly perceived general health.

Maternal childhood adversity and adolescent marijuana use at age 17 years: The role of parental mental health and parenting behaviors.

INTRODUCTION: Children's risk for marijuana use may be linked to their parents' history of childhood adversity, yet little is known about the mechanisms underlying this link. This study examined whether maternal parenting behavior and mental health serve as mechanisms linking maternal childhood adversity to their children's marijuana use at age 17 years, by gender. METHODS: Data were from the Young Women and Child Development Study (59% male), a longitudinal panel study, which began in 1988 and followed mother-child dyads for 17 years (n = 240). Participants were recruited from health and social services agencies located in a metropolitan region of Washington State. Hypotheses were tested using Structural Equation Modeling in Mplus. Multiple-group analysis was conducted to evaluate potential gender differences. RESULTS: Results showed that maternal childhood adversity was associated with their mental health outcomes (ß = .32, p < .001), which in turn was predictive of mothers' harsh parenting (ß = .27, p < .01). Maternal harsh parenting behavior was then associated with their children's marijuana use at age 17 years (ß = .34, p < .001). Multiple group analyses revealed that the path from harsh parenting to adolescent marijuana use differed across genders being only significant for boys (ß = .42, p < .001). CONCLUSIONS: The intergenerational impact of childhood adversity highlights the need for interventions that target both parents and children. This would support teen mothers with a history of childhood adversity to acquire skills and knowledge to help mitigate its impact on their parenting behaviors and offset risks for their children.

Genome-Wide Identification and Comprehensive Analysis of the GASA Gene Family in Peanuts (Arachis hypogaea L.) under Abiotic Stress.

Peanut (Arachis hypogaea L.) is a globally cultivated crop of significant economic and nutritional importance. The role of gibberellic-acid-stimulated Arabidopsis (GASA) family genes is well established in plant growth, development, and biotic and abiotic stress responses. However, there is a gap in understanding the function of GASA proteins in cultivated peanuts, particularly in response to abiotic stresses such as drought and salinity. Thus, we conducted comprehensive in silico analyses to identify and verify the existence of 40 GASA genes (termed AhGASA) in cultivated peanuts. Subsequently, we conducted biological experiments and performed expression analyses of selected AhGASA genes to elucidate their potential regulatory roles in response to drought and salinity. Phylogenetic analysis revealed that AhGASA genes could be categorized into four distinct subfamilies. Under normal growth conditions, selected AhGASA genes exhibited varying expressions in young peanut seedling leaves, stems, and roots tissues. Notably, our findings indicate that certain AhGASA genes were downregulated under drought stress but upregulated under salt stress. These results suggest that specific AhGASA genes are involved in the regulation of salt or drought stress. Further functional characterization of the upregulated genes under both drought and salt stress will be essential to confirm their regulatory roles in this context. Overall, our findings provide compelling evidence of the involvement of AhGASA genes in the mechanisms of stress tolerance in cultivated peanuts. This study enhances our understanding of the functions of AhGASA genes in response to abiotic stress and lays the groundwork for future investigations into the molecular characterization of AhGASA genes.

The development and evaluation of a self-efficacy enhancement program for older adults with mild cognitive impairment.

OBJECTIVE: The aims of this study were to develop a self-efficacy enhancement program and to evaluate its effect on cognitive function, dementia knowledge, self-efficacy, depression, and dementia preventive behaviors in older adults (age ≥ 65 years) with mild cognitive impairment (MCI). METHODS: This equivalent control group pretest-posttest study was conducted at a tertiary hospital in Seoul, South Korea. Older adults with MCI were randomly allocated to an experimental (EG, n = 16) or control group (CG, n = 16). The EG underwent an 8-week intervention (weekly 60-min session) utilizing self-efficacy enhancement strategies; the CG received usual care. The intervention was comprised of physical, cognitive, and emotional activities and was followed by 4-week maintenance during which both groups engaged in self-learning at home with a dementia preventive guidebook. Outcome data were evaluated at the pretest and 8, 10, and 12 weeks later. This study adhered to the CONSORT guidelines. RESULTS: There were significant differences in cognitive function, dementia knowledge, self-efficacy, and dementia preventive behaviors, but not in depression between the two groups over the time. Regarding cognitive function subdomains, significant differences were observed in visuospatial/executive, attention, language, and delayed recall. CONCLUSION: The integrated intervention consisting of physical, cognitive, and emotional activities was effective in improving cognitive function, dementia knowledge, self-efficacy, and dementia preventive behaviors. This suggests that this program can be utilized as an educational program to prevent dementia in older adults with MCI in dementia support centers, public health centers, clinics, and hospitals. TRIAL REGISTRATION: KCT0006094 in the Clinical Research Information Service. Retrospectively registered 23 April 2021, https://cris.nih.go.kr/cris/search/listDetail.do.

Alcohol use trajectories among U.S. adults during the first 42 weeks of the COVID-19 pandemic.

BACKGROUND: This study characterized the prevalence, drinking patterns, and sociodemographic characteristics of U.S. adult subpopulations with distinct drinking trajectories during the COVID-19 pandemic's first 42 weeks. METHODS: Adult respondents (n = 8130) in a nationally representative prospective longitudinal study completed 21 biweekly web surveys (March 2020 to January 2021). Past-week alcohol drinking frequency (drinking days [range: 0 to 7]) and intensity (binge drinking on usual past-week drinking day [yes/no]) were assessed at each timepoint. Growth mixture models identified multiple subpopulations with homogenous drinking trajectories based on mean drinking days or binge drinking proportional probabilities across time. RESULTS: Four drinking frequency trajectories were identified: Minimal/stable (72.8% [95% CI = 71.8 to 73.8]) with <1 mean past-week drinking days throughout; Moderate/late decreasing (6.7% [95% CI = 6.2 to 7.3) with 3.13 mean March drinking days and reductions during summer, reaching 2.12 days by January 2021; Moderate/early increasing (12.9% [95% CI = 12.2 to 13.6) with 2.13 mean March drinking days that increased in April and then plateaued, ending with 3.20 mean days in January 2021; and Near daily/early increasing (7.6% [95% CI = 7.0 to 8.2]) with 5.58 mean March drinking days that continued increasing without returning to baseline. Four drinking intensity trajectories were identified: Minimal/stable (85.8% [95% CI = 85.0% to 86.5%]) with <0.01 binge drinking probabilities throughout; Low-to-moderate/fluctuating (7.4% [95% CI = 6.8% to 8%]) with varying binge probabilities across timepoints (range:0.12 to 0.26); Moderate/mid increasing (4.2% [95% CI = 3.7% to 4.6%]) with 0.39 April binge drinking probability rising to 0.65 during August-September without returning to baseline; High/early increasing trajectory (2.7% [95% CI = 2.3% to 3%]) with 0.84 binge drinking probability rising to 0.96 by June without returning to baseline. Males, Whites, middle-aged/older adults, college degree recipients, those consistently working, and those above the poverty limit were overrepresented in various increasing (vs. minimal/stable) frequency trajectories. Males, Whites, nonmarried, those without college degree, 18 to 39-year-olds, and middle aged were overrepresented in increasing (vs. minimal/stable) intensity trajectories. CONCLUSIONS: Several distinct U.S. adult sociodemographic subpopulations appear to have acquired new drinking patterns during the pandemic's first 42 weeks. Frequent alcohol use assessment in the COVID-19 era could improve personalized medicine and population health efforts to reduce drinking.

Freezing-enhanced oxidation of iodide by hydrogen peroxide in the presence of antifreeze proteins from the Arctic yeast Leucosporidium sp.AY30.

Ice-binding proteins (IBPs), originating from Arctic or Antarctic microorganisms, have freeze-inhibiting characteristics, allowing these organisms to survive in polar regions. Despite their significance in polar environments, the mechanism through which IBPs affect the chemical reactions in ice by controlling ice crystal formation has not yet been reported. In this study, a new mechanism for iodide (I-) activation into triiodide (I3-), which is the abundant iodine species in seawater, by using hydrogen peroxide (H2O2) in a frozen solution with IBPs was developed. A significant enhancement of I- activation into I3- was observed in the presence of Arctic-yeast-originating extracellular ice-binding glycoprotein (LeIBP) isolated from Leucosporidium sp. AY30, and a further increase in the I3- concentration was observed with the introduction of H2O2 to the frozen solution (25 times higher than in the aqueous solution after 24 h of reaction). The reaction in the ice increased with an increase in LeIBP concentration. The in-situ pH measurement in ice using cresol red (CR) revealed protons accumulated in the ice grain boundaries by LeIBP. However, the presence of LeIBP did not influence the acidity of the ice. The enhanced freeze concentration effect of H2O2 by LeIBP indicated that larger ice granules were formed in the presence of LeIBP. The results suggest that LeIBP affects the formation and morphology of ice granules, which reduces the total volume of ice boundaries throughout the ice. This leads to an increased local concentration of I- and H2O2 within the ice grain boundaries. IBP-assisted production of gaseous iodine in a frozen environment provides a previously unrecognized formation mechanism of active iodine species in the polar regions.

Inhibition of neurite outgrowth and enhanced effects compared to baseline toxicity in SH-SY5Y cells.

Early life exposure to environmental chemicals can cause developmental neurotoxicity (DNT). The impairment of key neurodevelopmental processes such as neurite outgrowth inhibition can be used as endpoints for screening of DNT effects. We quantified neurite-specific effects using the ratio of effect concentrations for cytotoxicity and neurite outgrowth inhibition (SRcytotoxicity). Baseline cytotoxicity, the minimal toxicity of any chemical, was used to quantify enhanced cytotoxicity (toxic ratio, TR) and neuronal-specific toxicity (SRbaseline) by comparing baseline cytotoxicity with the effects on cell viability and neurite outgrowth, respectively. The effects on cell viability and neurite length were measured based on image analysis in human neuroblastoma SH-SY5Y cells. Baseline cytotoxicity was predicted from hydrophobicity descriptors using a previously published model for SH-SY5Y cells. Enhanced cytotoxicity and neuronal-specific toxicity were more often observed for hydrophilic chemicals, which indicates that they are more likely to act through specific modes of action (MOA) on cell viability and neurite outgrowth. Hydrophobic chemicals showed a tendency to act through baseline toxicity without showing specific or enhanced toxicity, but were highly potent considering their low effect concentrations for both cytotoxicity and neurite outgrowth inhibition. The endpoint-specific controls (narciclasine, colchicine, cycloheximide, and rotenone), two carbamates (3-hydroxycarbofuran and carbaryl), and two redox cyclers (diquat and paraquat) showed distinct neurite-specific effects (SRcytotoxicity > 4). By comparing neurite-specific effects with enhanced cytotoxicity, one can explain whether the observed effects involve specific inhibition of neurite outgrowth, other specific MOAs, or merely baseline toxicity arising from hydrophobicity.

Development of PD3 and PD3-B for PDEδ inhibition to modulate KRAS activity.

Despite extensive efforts over 40 years, few effective KRAS inhibitors have been developed to date, mainly due to the undruggable features of KRAS proteins. In addition to the direct approach to KRAS via covalent inhibition, modulation of the prenyl-binding protein PDEδ that binds with farnesylated KRAS has emerged as an alternative strategy to abrogate KRAS activity. For the verification of new therapeutic strategies, chemical probes with the dual functions of visualisation and pharmacological inhibition against oncogenic proteins are enormously valuable to understand cellular events related to cancer. Here, we report indolizino[3,2-c]quinoline (IQ)-based fluorescent probes (PD3 and PD3-B) for PDEδ inhibition. By using the unique fluorescent characteristics of the IQ scaffold, a fluorescence polarisation (FP)-based binding assay identified PD3 as the most effective PDEδ probe among the tested PD analogues, with a low Kd value of 0.491 µM and long retention time in the binding site of PDEδ. In particular, a FP-based competition assay using deltarasin verified that PD3 occupies the farnesylation binding site of PDEδ, excluding the possibility that the FP signals resulted from non-specific hydrophobic interactions between the ligand and protein in the assay. We also designed and synthesised PD3-B (5), an affinity-based probe (ABP) from the PD3 structure, which enabled us to pull down PDEδ from bacterial lysates containing a large number of intrinsic bacterial proteins. Finally, KRAS relocalization was verified in PANC-1 cells by treatment with PD3, suggesting its potential as an effective probe to target PDEδ.

Patient safety measurement tools used in nursing homes: a systematic literature review.

BACKGROUND: An increase in the number of older adults has highlighted the important issue of the safety of residents in nursing homes. This review aimed to review previous studies on patient safety of older adults living in nursing homes, analyze the tools used to measure it, and identify factors affecting patient safety of older adult residents in nursing homes. METHODS: A literature search was conducted using EMBASE, PubMed, CINHAL, and COCHRANE. The main search terms were "nursing home" or "skilled nursing facility" or "long-term care facility" and "patient safety." In total, 13,586 articles were identified. Two authors independently assessed the quality of each selected study using the Crowe Critical Appraisal Tool. RESULTS: Twenty-five studies were included in the analysis. There were a total of seven tools used to measure patient safety in nursing homes: the Nursing Home Survey on Patient Safety Culture (10 studies) and Hospital Survey on Patient Safety Culture (nine studies). Furthermore, the Nursing Home Survey on Patient Safety Culture-China, Safety Attitudes Questionnaire, Safety Attitudes Questionnaire in a Skilled Nursing Facility, Safety Attitudes Questionnaire-Ambulatory Version, and Modified Stanford Patient Safety Culture Survey Instrument were used in one study each. The most used tool among them was the Nursing Home Survey on Patient Safety Culture. Most tools used to measure patient safety in nursing homes were related to patient safety culture and employee attitudes. CONCLUSION: Organizational factors, such as the staff education system and the composition of appropriate personnel, should be strengthened to establish a patient safety culture in nursing homes, for which policy support is crucial.

Association of Tim-3/Gal-9 Axis with NLRC4 Inflammasome in Glioma Malignancy: Tim-3/Gal-9 Induce the NLRC4 Inflammasome.

Tim-3/Gal-9 and the NLRC4 inflammasome contribute to glioma progression. However, the underlying mechanisms involved are unclear. Here, we observed that Tim-3/Gal-9 expression increased with glioma malignancy and found that Tim-3/Gal-9 regulate NLRC4 inflammasome formation and activation. Tim-3/Gal-9 and NLRC4 inflammasome-related molecule expression levels increased with WHO glioma grade, and this association was correlated with low survival. We investigated NLRC4 inflammasome formation by genetically regulating Tim-3 and its ligand Gal-9. Tim-3/Gal-9 regulation was positively correlated with the NLRC4 inflammasome, NLRC4, and caspase-1 expression. Tim-3/Gal-9 did not trigger IL-1ß secretion but were strongly positively correlated with caspase-1 activity as they induced programmed cell death in glioma cells. A protein-protein interaction analysis revealed that the FYN-JAK1-ZNF384 pathways are bridges in NLRC4 inflammasome regulation by Tim-3/Gal-9. The present study showed that Tim-3/Gal-9 are associated with poor prognosis in glioma patients and induce NLRC4 inflammasome formation and activation. We proposed that a Tim-3/Gal-9 blockade could be beneficial in glioma therapy as it would reduce the inflammatory microenvironment by downregulating the NLRC4 inflammasome.

Cumulative Neighborhood Risk and Subsequent Internalizing Behavior among Asian American Adolescents.

Neighborhood disadvantage is a developmental context that may contribute to Asian American adolescent internalizing problems, yet there is a dearth of longitudinal studies as well as examination of cultural protective factors. Co-ethnic density, or the proportion of individuals of the same racial/ethnic background in the neighborhood that is often cited as a protective factor for racial/ethnic minority groups, has not been adequately examined in Asian American youth. This study examined the longitudinal association between cumulative neighborhood risk and internalizing behavior, and the moderating role of sex and co-ethnic density using an Asian American subsample (N = 177; 45.2% female; ages 10-12, 14-15; Cambodian, Chinese, Filipino, Hmong, Japanese, Korean, Laotian, Samoan, Vietnamese, and other ethnic backgrounds) of a longitudinal panel study over a span of 6 years. Cumulative neighborhood risk during early adolescence (ages 10-14) was significantly associated with internalizing behavior at mid-adolescence (age 15) controlling for prior levels of internalizing behavior. There was no evidence of moderation by co-ethnic density or sex, indicating that reducing neighborhood disadvantage may be a promising preventive measure to address mental health problems for both sexes of Asian American adolescents.

Critical Membrane Concentration and Mass-Balance Model to Identify Baseline Cytotoxicity of Hydrophobic and Ionizable Organic Chemicals in Mammalian Cell Lines.

All chemicals can interfere with cellular membranes and this leads to baseline toxicity, which is the minimal toxicity any chemical elicits. The critical membrane burden is constant for all chemicals; that is, the dosing concentrations to trigger baseline toxicity decrease with increasing hydrophobicity of the chemicals. Quantitative structure-activity relationships, based on hydrophobicity of chemicals, have been established to predict nominal concentrations causing baseline toxicity in human and mammalian cell lines. However, their applicability is limited to hydrophilic neutral compounds. To develop a prediction model that includes more hydrophobic and charged organic chemicals, a mass balance model was applied for mammalian cells (AREc32, AhR-CALUX, PPARγ-BLA, and SH-SY5Y) considering different bioassay conditions. The critical membrane burden for baseline toxicity was converted into nominal concentration causing 10% cytotoxicity by baseline toxicity (IC10,baseline) using a mass balance model whose main chemical input parameter was the liposome-water partition constants (Klip/w) for neutral chemicals or the speciation-corrected Dlip/w(pH 7.4) for ionizable chemicals plus the bioassay-specific protein, lipid, and water contents of cells and media. In these bioassay-specific models, log(1/IC10,baseline) increased with increasing hydrophobicity, and the relationship started to level off at log Dlip/w around 2. The bioassay-specific models were applied to 392 chemicals covering a broad range of hydrophobicity and speciation. Comparing the predicted IC10,baseline and experimental cytotoxicity IC10, known baseline toxicants and many additional chemicals were identified as baseline toxicants, while the others were classified based on specificity of their modes of action in the four cell lines, confirming excess toxicity of some fungicides, antibiotics, and uncouplers. Given the similarity of the bioassay-specific models, we propose a generalized baseline-model for adherent human cell lines: log[1/IC10,baseline (M)] = 1.23 + 4.97 × (1 - e-0.236 log Dlip/w). The derived models for baseline toxicity may serve for specificity analysis in reporter gene and neurotoxicity assays as well as for planning the dosing for cell-based assays.

Lipidomics reveals that acupuncture modulates the lipid metabolism and inflammatory interaction in a mouse model of depression.

Depression is a serious disease that has considerable impact on lipid metabolism and inflammatory responses. Recent studies have shown that leptin, which is well known as a mediator of energy homeostasis and is a cytokine in inflammatory response, plays an important role in depression. Acupuncture is widely used to treat depression; however, the underlying mechanisms and the effect of acupuncture on depression remain poorly understood. In this study, we utilized the chronic restraint stress (CRS) induced depression model and acupuncture treatment was performed at KI10, LR8, LU8, LR4 (AP) or non-acupoint (NP). Then, lipidomics was applied to investigate the effects of acupuncture on lipid metabolism and analyze leptin signals in the brain and changes of immune markers. Acupuncture treatment at AP improved depression-like behavior in an open-field test, forced swimming test, and marble burying test. Concurrently, CRS mice treated with AP acupuncture (CRS + AP) had significantly lower levels of aspartate aminotransaminase (AST, liver injury markers) and exhibited different lipid patterns in liver lipidomic profiles. In particular, triglycerides (TGs) contributed the change of lipid patterns. Compared to the CRS mice, TGs with relatively high degrees of unsaturated fatty acids increased in the CRS + AP mice, but did not change in CRS mice treated with NP acupuncture (CRS + NP). The levels of leptin in plasma and leptin receptor positive cells in the brain (hypothalamus and hippocampus) decreased and increased, respectively, in the CRS + AP mice, while opposite patterns were exhibited in the CRS and CRS + NP mice. These results indicated that acupuncture treatment at AP attenuated leptin insensitivity in CRS mice. Additionally, expression of pro-inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor-alpha were decreased in the spleen, plasma, and liver of CRS + AP mice, which was one of results of alleviation of leptin resistance. In conclusion, these results show that AP acupuncture treatment effectively alleviated the depression-like behavior, affected immune responses, and altered hepatic lipid metabolism through the attenuation of leptin insensitivity.

Violence, HIV Risks, and Polysubstance Use Among HIV-Positive People Who Inject Drugs in Ukraine.

Violence experience has been consistently associated with HIV risks and substance use behaviors. Although many studies have focused on intimate partner violence (IPV), the role of violence at a structural level (i.e., police abuse) remains relevant for people who inject drugs. This study evaluated the association of IPV and police-perpetrated violence experiences with HIV risk behaviors and substance use in a cohort of HIV-positive people who inject drugs in Ukraine. We also evaluated possible moderation effects of gender and socioeconomic status in the links between violence exposure and HIV risk and polysubstance use behaviors. Data came from the Providence/Boston-CFAR-Ukraine Study involving 191 HIV-positive people who inject drugs conducted at seven addiction treatment facilities in Ukraine. Results from logistic regressions suggest that people who inject drugs and experienced IPV had higher odds of polysubstance use than those who did not experience IPV. Verbal violence and sexual violence perpetrated by police were associated with increased odds of inconsistent condom use. The odds of engaging in polysubstance use were lower for women in relation to police physical abuse. We found no evidence supporting socioeconomic status moderations. Violence experiences were associated with substance use and sexual HIV risk behaviors in this cohort of HIV-positive people who inject drugs in Ukraine. Trauma-informed prevention approaches that consider both individual and structural violence could improve this population's HIV risks.

RESUMEN: La experiencia de violencia se ha asociado sistemáticamente con las conductas de riesgo para la adquisición o transmisión del VIH y con el uso de sustancias. Aunque muchos estudios se han centrado en la violencia infligida por la pareja íntima (VPI), el papel de la violencia estructural (es decir, el abuso policial) sigue siendo relevante para las personas que se inyectan drogas. Este estudio evaluó la asociación entre las experiencias de violencia perpetrada por la policía y la pareja íntima con los conductas de riesgo para la adquisición o transmisión del VIH y el uso de sustancias en una cohorte de personas VIH positivas que se inyectan drogas en Ucrania. También evaluamos los posibles efectos de moderación del género y el estatus socioeconómico entre la exposición a la violencia y los comportamientos de riesgo para la transmisión del VIH y uso de múltiples sustancias. Los datos provienen del estudio Providence / Boston-CFAR-Ucrania en el que participaron 191 personas infectadas por el VIH que se inyectan drogas, realizado en siete centros de tratamiento de adicciones en Ucrania. Los resultados de las regresiones logísticas sugieren que, en comparación con las personas que se inyectan drogas que no experimentaron IPV, las que experimentaron IPV tenían mayor probabilidad de uso de múltiples sustancias. La violencia sexual perpetrada por la policía se asoció con mayores probabilidades de un uso inconsistente del condón. No encontramos evidencia que apoye las moderaciones de género o estatus socioeconómico. Las experiencias de violencia se asociaron con el uso de sustancias y las conductas sexuales de riesgo para la transmisión del VIH en esta cohorte de personas VIH positivas que se inyectan drogas en Ucrania. Los enfoques de prevención basados en las experiencias traumáticas que tienen en cuenta tanto la violencia individual como la estructural podrían mejorar las conductas de riesgo para la transmission del VIH de esta población.