Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats.

Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues; both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats in a Pavlovian conditioned approach task, in which we characterized the individual responses to food-associated stimuli ("cues"). Rats exhibited either cue-directed "sign-tracking" behavior or food-cup directed "goal-tracking" behavior. We then used the conditioned reinforcement procedure to determine whether rats would perform a novel operant response for unrewarded presentations of the cue. We found that these measures were moderately heritable (SNP heritability, h2 = .189-.215). GWAS identified 14 quantitative trait loci (QTLs) for 11 of the 12 traits we examined. Interval sizes of these QTLs varied widely. 7 traits shared a QTL on chromosome 1 that contained a few genes (e.g. Tenm4, Mir708) that have been associated with substance use disorders and other mental health traits in humans. Other candidate genes (e.g. Wnt11, Pak1) in this region had coding variants and expression-QTLs in mesocorticolimbic regions of the brain. We also conducted a Phenome-Wide Association Study (PheWAS) on other behavioral measures in HS rats and found that regions containing QTLs on chromosome 1 were also associated with nicotine self-administration in a separate cohort of HS rats. These results provide a starting point for the molecular genetic dissection of incentive salience and provide further support for a relationship between attribution of incentive salience and drug abuse-related traits.

Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non-genetic risk factors for Alzheimer's disease among Asian Americans and Canadians.

INTRODUCTION: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population. METHODS: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese. RESULTS: ACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception. DISCUSSION: ACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness. HIGHLIGHTS: The Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

Multifocal fatty liver nodules mimicking a metastatic disease: A case report.

Multifocal fatty liver nodules can present a diagnostic challenge due to their resemblance to metastatic liver disease. This case report illustrates the complexity of such scenarios through the presentation of a middle-aged male patient. Despite the common nature of fatty liver disease, characterized by hepatocyte fat accumulation leading to diffuse and uniform liver lesions, rare instances exhibit heterogeneous appearances. The case underlines the potential confusion arising from imaging modalities when multiple small nodules disperse throughout the liver, mimicking multifocal tumors or metastases. The report emphasizes the critical role of comprehensive diagnostic procedures in preventing misdiagnosis and unwarranted interventions. Effective management hinges on multidisciplinary collaboration among specialists, ensuring accurate differentiation and appropriate treatment. This study serves as a reminder of the intricacies involved in interpreting multifocal fatty liver nodules that may masquerade as metastatic disease, highlighting the need for precision in clinical practice.

The relationship between population growth and precipitation change in some regions across Vietnam: implications for urbanization effect.

According to a review of numerous publications and scientific reports, the effects of urbanization on urban climate are of greatest concern. This study aims to evaluate the impact of urbanization focusing on population growth on precipitation trends in 11 provinces across Vietnam during the period 2008-2018 by identifying the relationship between population growth and precipitation change. Regression analysis is used to determine the trends of precipitation and population growth. Precipitation maps and graphs show the overall precipitation trends, changes, and patterns in past decades. Overall, population growth tends to correlate with precipitation change trends. Furthermore, the type of region groups (countryside region, small city, or medium city) also plays a crucial role in determining the magnitude of the change in precipitation trends for each region. This further lends credibility to the notion that urbanization contributes to changes in precipitation trends.

A distinct human cell type expressing MHCII and RORγt with dual characteristics of dendritic cells and type 3 innate lymphoid cells.

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt+ MHCII+ type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota-specific Tregs. While RORγt+ APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. Herein, we identify a rare subset of RORγt+ cells with dendritic cell (DC) features through integrated single-cell RNA sequencing and single-cell ATAC sequencing. These cells, which we term RORγt+ DC-like cells (R-DC-like), exhibit DC morphology, express the MHC class II machinery, and are distinct from all previously reported DC and ILC3 subsets, but share transcriptional and epigenetic similarities with DC2 and ILC3. We have developed procedures to isolate and expand them in vitro, enabling their functional characterization. R-DC-like cells proliferate in vitro, continue to express RORγt, and differentiate into CD1c+ DC2-like cells. They stimulate the proliferation of allogeneic T cells. The identification of human R-DC-like cells with proliferative potential and plasticity toward CD1c+ DC2-like cells will prompt further investigation into their impact on immune homeostasis, inflammation, and autoimmunity.

The practice of sustainable fashion of luxury boutique fashion brands in Vietnam: What go right, and what go wrong.

This study investigated the current practices and challenges for the sustainable fashion of luxury boutique fashion brands (LBFBs) in Vietnam. A series of in-depth interviews with 20 founders and managers of LBFBs in Vietnam was conducted. Findings show that sustainable practices improve ethnic cultures, strengthen the usage of local resources, promote sustainable lifestyle, and thereby contributing to sustainable development of the boutique fashion brands. However, the brands face some challenges while dealing with their stakeholders such as shortage of available internal resources, bias in consumer perception and purchase behaviors, and legal barriers to achieve accredited environment certification that, in turn, weaken the sustainable practices in the local context. Results also provide some insightful information for small & medium sized enterprises (SMEs) to adjust their sustainability practices in order to improve their competitive advantages in the marketplace.

Causal Genetic Loci for a Motivated Behavior Spectrum Harbor Psychiatric Risk Genes.

Behavioral diversity is critical for population fitness. Individual differences in risk-taking are observed across species, but underlying genetic mechanisms and conservation are largely unknown. We examined dark avoidance in larval zebrafish, a motivated behavior reflecting an approach-avoidance conflict. Brain-wide calcium imaging revealed significant neural activity differences between approach-inclined versus avoidance-inclined individuals. We used a population of ∼6,000 to perform the first genome-wide association study (GWAS) in zebrafish, which identified 34 genomic regions harboring many genes that are involved in synaptic transmission and human psychiatric diseases. We used CRISPR to study several causal genes: serotonin receptor-1b ( htr1b ), nitric oxide synthase-1 ( nos1 ), and stress-induced phosphoprotein-1 ( stip1 ). We further identified 52 conserved elements containing 66 GWAS significant variants. One encoded an exonic regulatory element that influenced tissue-specific nos1 expression. Together, these findings reveal new genetic loci and establish a powerful, scalable animal system to probe mechanisms underlying motivation, a critical dimension of psychiatric diseases.

Intersectional Disparities in Emergency Medicine Residents' Performance Assessments by Race, Ethnicity, and Sex.

Importance: Previous studies have demonstrated sex-specific disparities in performance assessments among emergency medicine (EM) residents. However, less work has focused on intersectional disparities by ethnoracial identity and sex in resident performance assessments. Objective: To estimate intersectional sex-specific ethnoracial disparities in standardized EM resident assessments. Design, Setting, and Participants: This retrospective cohort study used data from the Association of American Medical Colleges and the Accreditation Council for Graduate Medical Education Milestones (Milestones) assessments to evaluate ratings for EM residents at 128 EM training programs in the US. Statistical analyses were conducted in June 2020 to January 2023. Exposure: Training and assessment environments in EM residency programs across comparison groups defined by ethnoracial identity (Asian, White, or groups underrepresented in medicine [URM], ie, African American/Black, American Indian/Alaska Native, Hispanic/Latine, and Native Hawaiian/Other Pacific Islander) and sex (female/male). Main Outcomes and Measures: Mean Milestone scores (scale, 0-9) across 6 core competency domains: interpersonal and communications skills, medical knowledge, patient care, practice-based learning and improvement, professionalism, and system-based practice. Overall assessment scores were calculated as the mean of the 6 competency scores. Results: The study sample comprised 128 ACGME-accredited programs and 16 634 assessments for 2708 EM residents of which 1913 (70.6%) were in 3-year and 795 (29.4%) in 4-year programs. Most of the residents were White (n = 2012; 74.3%), followed by Asian (n = 477; 17.6%), Hispanic or Latine (n = 213; 7.9%), African American or Black (n = 160; 5.9%), American Indian or Alaska Native (n = 24; 0.9%), and Native Hawaiian or Other Pacific Islander (n = 4; 0.1%). Approximately 14.3% (n = 386) and 34.6% (n = 936) were of URM groups and female, respectively. Compared with White male residents, URM female residents in 3-year programs were rated increasingly lower in the medical knowledge (URM female score, -0.47; 95% CI, -0.77 to -0.17), patient care (-0.18; 95% CI, -0.35 to -0.01), and practice-based learning and improvement (-0.37; 95% CI, -0.65 to -0.09) domains by postgraduate year 3 year-end assessment; URM female residents in 4-year programs were also rated lower in all 6 competencies over the assessment period. Conclusions and Relevance: This retrospective cohort study found that URM female residents were consistently rated lower than White male residents on Milestone assessments, findings that may reflect intersectional discrimination in physician competency evaluation. Eliminating sex-specific ethnoracial disparities in resident assessments may contribute to equitable health care by removing barriers to retention and promotion of underrepresented and minoritized trainees and facilitating diversity and representation among the emergency physician workforce.

Before Omicron's Arrival: Effects of Negative Emotions and Comparative Optimism on COVID-19 Protection and Detection Behaviors.

This study examined the associations of emotions, cognitions, and behavioral intentions in response to exposure to news stories reporting on the arrival of Omicron variant in Vietnam. Outcomes included fear, anxiety, anger, comparative optimism, intentions to conduct prevention behavior (wash hands with soap), detection behavior (test for Omicron infection), and share health information. Two experiments were conducted with participants being randomized to either low-risk or high-risk condition that contained information promoting hand-washing with soap (Experiment 1, N = 303), or information promoting COVID-19 testing (Experiment 2, N = 303). Results indicated that viewing high-risk news stories led to higher fear, anxiety, and anger than low-risk news stories. Fear fully mediated the effect of news exposure on intentions to test for Omicron infection and share health information. Comparative optimism moderated the indirect effect of news exposure on intentions to wash hands with soap and share information about COVID-19 testing. Theoretical and practical implications were discussed.

Effect of biowaste and construction waste additives on mechanical dewaterability of lake sediment for brick production.

Nowadays, when the zero-waste strategy is an inevitable component of the circular economy, the reuse of waste, including dredged sludges, has drawn the attention of many researchers. This study evaluated four kinds of bio-wastes (corn core powder, rice husk powder, sugarcane bagasse powder, and peanut shell powders) and two kinds of construction wastes (autoclaved aerated concrete-AAC and pavement stone) in enhancing the dewaterability of dredged sludge from the lake, in which the sludges would then be reused for brick production. The results showed that the moisture contents decreased from 62 ± 0.14% to 57 ± 1.89% after mixing and then to 35 ± 8.31% after compressing for the construction waste-blended sludge. Among the bio-wastes, the sugarcane bagasse additive performed the best at a mixing ratio of 1:3 by weight and rice husk powder worked best at a mixing ratio of 1:5 by weight. The organic matter was increased up to 80% when the bio-wastes were added, while it was decreased to 5% for the case of construction wastes. The optimum percentage of sludge in the mixture to meet all the oxide contents in the brick and energy saving shall be about 30%. The results have revealed a potentially green route for brick production with lake sediment and bio-waste/construction wastes.Implications: It is the first time the reuse of agro-wastes/construction waste was evaluated to mix with lake sediment to partly replace clay for brick production; Among the bio-wastes, the sugarcane bagasse additive performed the best at a mixing ratio of 1:3 by weight; Moisture contents decreased from 62 ± 0.14% to 57 ± 1.89% after mixing and then to 35 ± 8.31% after compressing for the blended sludge; The optimum percentage of mixed sludge, possibly replaced the clay in brick production, considering oxide contents and energy saving shall be up to 30%.

Effects of Three-Hour Wearing Personal Protective Equipment on Heart Rate Variability in Healthcare Workers for the Treatment of COVID-19 Patients.

Background: Personal protective equipment (PPE), an essential shield to protect healthcare workers (HCWs) during the COVID-19 pandemic, has been reported to affect their heart rate variability (HRV). Objective: To investigate the changes of very short-term heart rate variability in HCWs after three hours of wearing PPE to treat COVID-19 patients at different working times and intensities, and related factors. Methods: Sixty-five healthy HCWs were enrolled at the Number 2 Infectious Field Hospital (formed by Military Hospital 103), Vietnam. Two-minute 12-lead electrocardiograms were recorded before wearing and after removing PPE. Results: After three hours of wearing PPE, the mean heart rate of HCWs increased (p = 0.048) meanwhile, the oxygen saturation decreased significantly (p = 0.035). Standard deviation of all normal to normal intervals (SDNN), mean intervals RR (mean NN), and root mean square successive difference (rMSSD) after wearing PPE was also reduced significantly. SDNN, Mean NN, and rMSSD decreased as the working intensity increased (as in mild, moderate, and severe patient departments). In univariate regression analysis, logSDNN, logmean NN and logrMSSD were positively correlated with SpO2 and QT interval (r = 0.14, r = 0.31, r = 0.25; r = 0.39, r = 0.77, r = 0.73, respectively) and were negatively correlated with ambient temperature inside PPE (r = -0.41, r = -0.405, r = -0.25, respectively) while logmean NN and log rMSSD were negatively correlated with diastolic blood pressure (r = -0.43, r = -0.39, respectively). In multivariable regression analysis, logSDNN and logmean NN were negatively correlated to ambient temperature inside PPE (r = -0.34, r = -0.18, respectively). Conclusion: Time-domain heart rate variability decreased after wearing PPE. Time-domain HRV parameters were related to ambient temperature inside PPE, diastolic blood pressure, QT interval, and SpO2.

Mechanical Evaluation of Hydrogel-Elastomer Interfaces Generated through Thiol-Ene Coupling.

The formation of hybrid hydrogel-elastomer scaffolds is an attractive strategy for the formation of tissue engineering constructs and microfabricated platforms for advanced in vitro models. The emergence of thiol-ene coupling, in particular radical-based, for the engineering of cell-instructive hydrogels and the design of elastomers raises the possibility of mechanically integrating these structures without relying on the introduction of additional chemical moieties. However, the bonding of hydrogels (thiol-ene radical or more classic acrylate/methacrylate radical-based) to thiol-ene elastomers and alkene-functional elastomers has not been characterized in detail. In this study, we quantify the tensile mechanical properties of hybrid hydrogel samples formed of two elastomers bonded to a hydrogel material. We examine the impact of radical thiol-ene coupling on the crosslinking of both elastomers (silicone or polyesters) and hydrogels (based on thiol-ene crosslinking or diacrylate chemistry) and on the mechanics and failure behavior of the resulting hybrids. This study demonstrates the strong bonding of thiol-ene hydrogels to alkene-presenting elastomers with a range of chemistries, including silicones and polyesters. Overall, thiol-ene coupling appears as an attractive tool for the generation of strong, mechanically integrated, hybrid structures for a broad range of applications.

Multi-Objective Topology Optimization of a Broadband Piezoelectric Energy Harvester.

In recent years, topology optimization has proved itself to be state of the art in the design of mechanical structures. At the same time, energy harvesting has gained a lot of attention in research and industry. In this work, we present a novel topology optimization of a multi-resonant piezoelectric energy-harvester device. The goal is to develop a broadband design that can generate constant power output over a range of frequencies, thus enabling reliable operation under changing environmental conditions. To achieve this goal, topology optimization is implemented with a combined-objective function, which tackles both the frequency requirement and the power-output characteristic. The optimization suggests a promising design, with satisfactory frequency characteristics.

A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages.

Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex. Deletion of the transcription factor SMAD4 in microglia and embryonic-derived BAMs using Crybb1-Cre caused a developmental arrest of microglia, which instead acquired a BAM specification signature. By contrast, the development of genuine BAMs remained unaffected. Our results reveal that SMAD4 drives a transcriptional and epigenetic program that is indispensable for the commitment of brain macrophages to the microglia fate and highlight Crybb1-Cre as a tool for targeting embryonic brain macrophages.

Cannabis use for Sleep Disturbance Among Older Patients in a Geriatrics Clinic.

Cannabis use is growing among older adults to manage medical concerns including poor sleep. In this study, we characterized how patients seen at a geriatrics clinic use cannabis to address sleep disturbance. Specifically, we conducted an anonymous survey of 568 adults, including 83 who reported cannabis use within the past 3 years, to inquire about such use. We compared cannabis use characteristics between those using it for sleep disturbance versus all other conditions. We considered a p-value <.10 to be statistically significant. Among the cannabis users in our sample, 29% reported using cannabis for sleep disturbance (N = 24). They were more likely than other users to be female (p = .07), consume cannabis more frequently (p = .01), use products containing tetrahydrocannabinol (THC) (vs. cannabidiol [CBD]-only; p < .01), and use cannabis to target more symptoms (p < .01). As cannabis use continues to grow in older populations, it is essential to delineate better how cannabis may be used safely and effectively to improve older adults' sleep health.

Preventing the COVID-19 Outbreak in Vietnam: Social Media Campaign Exposure and the Role of Interpersonal Communication.

The present study focused on the success story of Vietnam's ability to control the COVID-19 outbreak in the early stages to examine the associations between exposure to the Vietnam Ministry of Health's COVID-19 prevention social media campaign messages, interpersonal communication, attitudes, perceived norms, self-efficacy, and intentions to stay at home. A cross-sectional survey was conducted with residents in Ho Chi Minh City (N = 360). Results from mediation analyses indicated that interpersonal communication mediated the effect of social media campaign exposure on intentions to stay at home. Moreover, interpersonal communication shaped injunctive norms and self-efficacy that were conducive to behavioral intentions. These results underscored the need to leverage the power of social media and interpersonal communication in public health campaigns to prevent infectious outbreaks.

Genome-wide association study of delay discounting in Heterogenous Stock rats.

Delay discounting refers to the behavioral tendency to devalue rewards as a function of their delay in receipt. Heightened delay discounting has been associated with substance use disorders, as well as multiple co-occurring psychopathologies. Genetic studies in humans and animal models have established that delay discounting is a heritable trait, but only a few specific genes have been associated with delay discounting. Here, we aimed to identify novel genetic loci associated with delay discounting through a genome-wide association study (GWAS) using Heterogenous Stock rats, a genetically diverse outbred population derived from eight inbred founder strains. We assessed delay discounting in 650 male and female rats using an adjusting amount procedure in which rats chose between smaller immediate sucrose rewards or a larger reward at variable delays. Preference switch points were calculated for each rat and both exponential and hyperbolic functions were fitted to these indifference points. Area under the curve (AUC) and the discounting parameter k of both functions were used as delay discounting measures. GWAS for AUC, exponential k, and indifference points for a short delay identified significant loci on chromosomes 20 and 14. The gene Slc35f1, which encodes a member of the solute carrier family of nucleoside sugar transporters, was the only gene within the chromosome 20 locus. That locus also contained an eQTL for Slc35f1, suggesting that heritable differences in the expression of that gene might be responsible for the association with behavior. The gene Adgrl3, which encodes a member of the latrophilin family of G-protein coupled receptors, was the only gene within the chromosome 14 locus. These findings implicate novel genes in delay discounting and highlight the need for further exploration.

Polypharmacy in the Emergency Department.

Polypharmacy in the emergency department (ED) presents additional challenges for older adults with acute illnesses but is also an opportunity for healthcare providers to prevent adverse drug events as well as the use of potentially inappropriate medications. Older patients have complex health-related needs and are at risk for medication-related complications during an ED visit. Implementing mitigating strategies of performing medication reconciliation and review, using existing implicit or explicit tools to evaluate medications, and deprescribing or de-escalating high-risk medications are critical to positive health outcomes. These practices can help to optimize pharmacologic interventions for older patients in the ED.

TREM2 drives microglia response to amyloid-ß via SYK-dependent and -independent pathways.

Genetic studies have highlighted microglia as pivotal in orchestrating Alzheimer's disease (AD). Microglia that adhere to Aß plaques acquire a transcriptional signature, "disease-associated microglia" (DAM), which largely emanates from the TREM2-DAP12 receptor complex that transmits intracellular signals through the protein tyrosine kinase SYK. The human TREM2R47H variant associated with high AD risk fails to activate microglia via SYK. We found that SYK-deficient microglia cannot encase Aß plaques, accelerating brain pathology and behavioral deficits. SYK deficiency impaired the PI3K-AKT-GSK-3ß-mTOR pathway, incapacitating anabolic support required for attaining the DAM profile. However, SYK-deficient microglia proliferated and advanced to an Apoe-expressing prodromal stage of DAM; this pathway relied on the adapter DAP10, which also binds TREM2. Thus, microglial responses to Aß involve non-redundant SYK- and DAP10-pathways. Systemic administration of an antibody against CLEC7A, a receptor that directly activates SYK, rescued microglia activation in mice expressing the TREM2R47H allele, unveiling new options for AD immunotherapy.