MAdCAM-1 costimulation in the presence of retinoic acid and TGF-ß promotes HIV infection and differentiation of CD4+ T cells into CCR5+ TRM-like cells.

CD4+ tissue resident memory T cells (TRMs) are implicated in the formation of persistent HIV reservoirs that are established during the very early stages of infection. The tissue-specific factors that direct T cells to establish tissue residency are not well defined, nor are the factors that establish viral latency. We report that costimulation via MAdCAM-1 and retinoic acid (RA), two constituents of gut tissues, together with TGF-ß, promote the differentiation of CD4+ T cells into a distinct subset α4ß7+CD69+CD103+ TRM-like cells. Among the costimulatory ligands we evaluated, MAdCAM-1 was unique in its capacity to upregulate both CCR5 and CCR9. MAdCAM-1 costimulation rendered cells susceptible to HIV infection. Differentiation of TRM-like cells was reduced by MAdCAM-1 antagonists developed to treat inflammatory bowel diseases. These finding provide a framework to better understand the contribution of CD4+ TRMs to persistent viral reservoirs and HIV pathogenesis.

A 44-y perspective on the influence of cash on Ju/'hoansi Bushman networks of sharing and gifting.

Money has been portrayed by major theorists as an agent of individualism, an instrument of freedom, a currency that removes personal values attached to things, and a generator of avarice. Regardless, the impact of money varies greatly with the cultural turf of the recipient societies. For traditional subsistence economies based on gifting and sharing, surplus perishable resources foraged from the environment carry low costs to the giver compared with the benefits to the receiver. With cash, costs to the giver are usually the same as benefits to the receiver, making sharing expensive and introducing new choices. Using quantitative data on possessions and expenditures collected over a 44-y period from 1974 to 2018 among the Ju/'hoansi (!Kung) in southern Africa, former hunter-gatherers, we look at how individuals spend monetary income, how a partial monetary economy alters traditional norms and institutions (egalitarianism, gifting, and sharing), and how institutions from the past steer change. Results show that gifting declines as cash is spent to increase the well-being of individual families and that gifting and sharing decrease and networks narrow. The sharing of meals and casual gifting hold fast. Substantial material inequalities develop, even between neighbors, but social, gender, and political equalities persist. A strong tradition for individual autonomy combined with monetary income allows individuals to spend their money as they choose, adapt to modern conditions, and pursue new options. However, new challenges are emerging to develop greater community cooperation and build substantial and sustainable economies in the face of such centrifugal forces.

Chagas Disease Diagnostic Practices at Four Major Hospital Systems in California and Texas.

BACKGROUND: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy. METHODS: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis. RESULTS: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all testing, and the most frequently cited cardiac condition was heart failure. Fewer than 1% of tests were ordered by obstetric and gynecologic services. Fewer than half (47%) of patients had confirmatory testing performed at the Centers for Disease Control and Prevention. DISCUSSION: Four major hospitals systems in California and Texas demonstrated low overall rates of CD diagnostic testing, testing primarily among older patients with end-organ damage, and incomplete confirmatory testing. This suggests missed opportunities to diagnose CD in at-risk individuals early in the course of infection when antiparasitic treatment can reduce the risk of disease progression and prevent vertical transmission.

C. elegans vab-6 encodes a KIF3A kinesin and functions cell non-autonomously to regulate epidermal morphogenesis.

Cells undergo strict regulation to develop their shape in a process called morphogenesis. Caenorhabditis elegans with mutations in the variable abnormal (vab) class of genes have been shown to display epidermal and neuronal morphological defects. While several vab genes have been well-characterized, the function of the vab-6 gene remains unknown. Here, we show that vab-6 is synonymous with a subunit of the kinesin-II heterotrimeric motor complex called klp-20/Kif3a, a motor well-understood to be involved in developing sensory cilia in the nervous system. We show that certain klp-20 alleles cause animals to develop a bumpy body phenotype that is variable but most severe in mutants containing single amino-acid substitutions in the catalytic head-domain sites of the protein. Surprisingly, animals carrying a klp-20 null allele do not show the bumpy epidermal phenotype suggesting genetic redundancy and only when mutant versions of the KLP-20 protein are present, the epidermal phenotype is observed. The bumpy epidermal phenotype was not observed in other kinesin-2 mutants, suggesting that KLP-20 is functioning independently from its role in intraflagellar transport (IFT) during ciliogenesis. Interestingly, despite having such a prominent epidermal phenotype, KLP-20 is not expressed in the epidermis, strongly suggesting a cell non-autonomous role in which it regulates epidermal morphogenesis.

Promoting mental and physical health of Vietnamese immigrants through a cultural movement intervention.

OBJECTIVES: Older Vietnamese adults are among the most underserved groups in the United States, despite being at high risk for stress and other negative experiences (e.g., access to same-language practitioners, transportation barriers, lack of health care). Minimal progress has been made in decreasing treatment barriers for this underserved population. One promising approach involves using indigenous, culturally based interventions to enhance psychological and physical well-being. Such interventions may reduce utilization and quality of care disparities because they emphasize a more holistic approach to health, thereby limiting the shame and face loss often experienced due to the stigma associated with mental illness. The present study examined the efficacy of lishi, a traditional East Asian movement form of exercise, in promoting mental and physical health outcomes for older Vietnamese immigrant adults. METHOD: Seventy-one older Vietnamese adults participated in this randomized waitlist control study. Participants were between 60 and 75 years old. Multivariate analysis of covariance was used to determine posttest outcomes differences between the intervention and control groups. RESULTS: Intervention group participants experienced significantly higher levels of self-efficacy and physical energy, less bodily pains, and better body balance at posttest compared to the control group. CONCLUSIONS: Lishi may be an effective culturally valid intervention for older Vietnamese adults and demonstrated promise at engaging this hard-to-reach population in treatment and services. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Caseworker assessment of child risk and functioning and their relation to service use in the child welfare system.

Children within the child welfare system are more likely to experience emotional and behavioral problems than children not involved with the system. Many states have adopted standardized risk and assessment measures to inform decision-making on appropriate levels of care related to placement or service intensity for children within the system. This study examined the relationship of caseworker ratings of risk across multiple domains to youth functioning and service use for a sample of children open to the child welfare system. The study identified a stratified random sample of youth who were between the ages of five and 21 and open to the child welfare system (n = 184). Stratification was based on current placement (i.e., in-home, foster home, congregate care, and juvenile justice placements). Administrative data was used to access caseworker ratings of risk across child, parent, and family domains using a standardized risk assessment tool. Children's caseworkers (n = 103) completed a standardized measure of child functioning and reported on youth utilization of services across multiple sectors including specialty mental health, school-based, juvenile justice, and medical settings. Regression analyses using variance-corrected estimation for clustered data (by caseworker) revealed higher levels of child risk were associated with poorer child functioning, which, in turn, were associated with higher rates of multi-sector service use. Recommendations and future directions are discussed.

Bio-inspired melanin nanoparticles induce cancer cell death by iron adsorption.

Dysregulation of iron metabolism is a common characteristic of cancer cells. The rapid proliferation of the tumour cells means that there is an increased dependence upon iron compared to healthy cells. Chelation of iron can be undertaken with a number of different compounds, however, simply lowering systemic iron levels to control tumour growth is not possible since iron is essential for cellular metabolism in the rest of the body. Nanoparticulate iron chelators could overcome this difficulty by targeting to the tumour either by the passive enhanced permeation and retention effect, or by targeting ligands on the surface. Nanoparticles were prepared from melanin, which is a naturally occurring pigment that is widely distributed within the body, but that can chelate iron. The prepared nanoparticles were shown to be ~220 nm, and could adsorb 16.45 mmoles iron/g melanin. The nanoparticles showed no affect on control fibroblast cells at a concentration of 200 µM, whereas the immortalised cancer cell lines showed at least 56% reduction in cell growth. At a concentration of 1 mM melanin nanoparticles the cell growth could be reduced by 99% compared to the control. The nanoparticles also show no significant haemotoxicity, even at concentration of 500 µM. Melanin nanoparticles are therefore a viable prospect for destroying cancer cells via iron starvation.

"Las Dos Cosas," or Why Mexican American Mothers Breast-Feed, But Not for Long.

OBJECTIVES: To determine why mothers in El Paso, Texas, choose to breast-feed but not exclusively and why breast-feeding duration is short. METHODS: This was a cross-sectional observational study of 300, mostly Mexican American, low-income mothers delivering at a county hospital who answered questions about breast-feeding and formula feeding, sociodemographics, and health habits. RESULTS: Most mothers (92.6%) in our study initiated breast-feeding, but only 20.3% breast-fed exclusively at the time of hospital discharge. Most mothers (73%) self-identified as Mexicans or Mexican Americans living on the border of the United States and Mexico. Mothers in our study chose to breast-feed if they decided to breast-feed during pregnancy, had breast-fed a previous child, had support from a female relative, and had attended college. Distinctively, most mothers in our study chose "las dos cosas" or to breast-feed and formula feed together early after birth. Acculturation failed to explain the breast-feeding decisions. CONCLUSIONS: Mexican American mothers who decided to breast-feed during pregnancy, breast-fed another child, attended college, and enlist a female relative's breast-feeding help were more likely to choose breast-feeding exclusively. Most Mexican American low-income mothers in our study chose "las dos cosas."

A simple and efficient system for regulating gene expression in human pluripotent stem cells and derivatives.

Regulatable transgene expression in human pluripotent stem cells (hPSCs) and their progenies is often necessary to dissect gene function in a temporal and spatial manner. However, hPSC lines with inducible transgene expression, especially in differentiated progenies, have not been established due to silencing of randomly inserted genes during stem cell expansion and/or differentiation. Here, we report the use of transcription activator-like effector nucleases-mediated targeting to AAVS1 site to generate versatile conditional hPSC lines. Transgene (both green fluorescent protein and a functional gene) expression in hPSCs and their derivatives was not only sustained but also tightly regulated in response to doxycycline both in vitro and in vivo. We modified the donor construct so that any gene of interest can be readily inserted to produce hPSC lines with conditional transgene expression. This technology will substantially improve the way we study human stem cells.

Health, emergency department use, and early identification of young children exposed to trauma.

BACKGROUND: Childhood trauma is an important public health problem with financial, physical health, and mental health repercussions. Emergency departments (EDs) are often the first point of contact for many young children affected by emotionally or psychologically traumatic events (e.g., neglect, separation from primary caregiver, maltreatment, witness to domestic violence within the family, natural disasters). STUDY OBJECTIVES: Describe the prevalence of physical health symptoms, ED use, and health-related problems in young children (birth through 5 years) affected by trauma, and to predict whether or not children experiencing trauma are more likely to be affected by health-related problems. METHODS: Community-based, cross-sectional survey of 208 young children. Traumatic events were assessed by the Traumatic Events Screening Inventory - Parent Report Revised. Child health symptoms and health-related problems were measured using the Caregiver Information Questionnaire, developed by ORC Macro (Atlanta, GA). RESULTS: Seventy-two percent of children had experienced at least one type of traumatic event. Children exposed to trauma were also experiencing recent health-related events, including visits to the ED (32.2%) and the doctor (76.9%) for physical health symptoms, and recurring physical health problems (40.4%). Children previously exposed to high levels of trauma (four or more types of events) were 2.9 times more likely to report having had recently visited the ED for health purposes. CONCLUSIONS: Preventing recurrent trauma or recognizing early trauma exposure is difficult, but essential if long-term negative consequences are to be mitigated or prevented. Within EDs, there are missed opportunities for identification and intervention for trauma-exposed children, as well as great potential for expanding primary and secondary prevention of maltreatment-associated illness, injury, and mortality.

Stakeholders' perspectives on community-based participatory research to enhance mental health services.

Historically, consumers of mental health services have not been given meaningful roles in research and change efforts related to the services they use. This is quickly changing as scholars and a growing number of funding bodies now call for greater consumer involvement in mental health services research and improvement. Amidst these calls, community-based participatory research (CBPR) has emerged as an approach which holds unique promise for capitalizing on consumer involvement in mental health services research and change. Yet, there have been few discussions of the value added by this approach above and beyond that of traditional means of inquiry and enhancement in adult mental health services. The purpose of this paper is to add to this discussion an understanding of potential multilevel and multifaceted benefits associated with consumer-involved CBPR. This is accomplished through presenting the first-person accounts of four stakeholder groups who were part of a consumer-involved CBPR project purposed to improve the services of a local community mental health center. We present these accounts with the hope that by illustrating the unique outcomes associated with CBPR, there will be invigorated interest in CBPR as a vehicle for consumer involvement in adult mental health services research and enhancement.

Relationship of risk assessment to placement characteristics in a statewide child welfare population.

Risk assessments allow child and youth services to identify children who are at risk for maltreatment (e.g., abuse, neglect) and help determine the restrictiveness of placements or need for services among youth entering a child welfare system. Despite the use of instruments by many agencies within the U.S. to determine the appropriate placements for youth, research has shown that placement decisions are often influenced by factors such as gender, age, and severity of social-emotional and behavior problems. This study examined ratings of risk across multiple domains using a structured assessment tool used by caseworkers in the Rhode Island child welfare system. The relationship between ratings of risk and placement restrictiveness was also examined. Risk levels varied across placement settings. Multivariate analyses revealed that lower caseworker ratings of parent risk and higher ratings of youth risk were associated with more restrictive placements for youth. Implications for the child welfare system are discussed.

The moderating role of emotion regulation strategies on Asian American parents' discrimination experiences and mental health during the COVID-19 pandemic.

Asian American parents have experienced significant stressors associated with racial discrimination and anticipatory COVID-19-related discrimination fear during the COVID-19 pandemic, which may adversely impact their mental health. Emotion regulation strategies may attenuate the negative effects of discrimination experiences on mental health, but existing findings have been inconsistent regarding the associations between these factors, particularly among the Asian American population. One hundred ninety-three Asian American parents (Mage = 40.58 years, SD = 6.42 years; 82.4% female) were assessed on their discrimination experiences (racial discrimination in the past year, COVID-19 discrimination fear), emotion regulation strategies (cognitive reappraisal, expressive suppression), and mental health (depression, anxiety). Significant interactions emerged between expressive suppression and racial discrimination in the past year on depression (b = .02, p = .006) and anxiety (b = .03, p < .001). Cognitive reappraisal did not significantly moderate the associations between discrimination experiences and mental health. Results indicated that greater use of expressive suppression exacerbated the adverse effects of racial discrimination on the mental health of Asian American parents. These findings inform research and practice regarding the deleterious effects of racial discrimination and the differential impact of using various emotion regulation strategies on the mental health of Asian American parents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.

The mammalian cortex is comprised of cells with different morphological, physiological, and molecular properties that can be classified according to shared properties into cell types. Defining the contribution of each cell type to the computational and cognitive processes that are guided by the cortex is essential for understanding its function in health and disease. We use transcriptomic and epigenomic cortical cell type taxonomies from mice and humans to define marker genes and enhancers, and to build genetic tools for cortical cell types. Here, we present a large toolkit for selective targeting of cortical populations, including mouse transgenic lines and recombinant adeno-associated virus (AAV) vectors containing genomic enhancers. We report evaluation of fifteen new transgenic driver lines and over 680 different enhancer AAVs covering all major subclasses of cortical cells, with many achieving a high degree of specificity, comparable with existing transgenic lines. We find that the transgenic lines based on marker genes can provide exceptional specificity and completeness of cell type labeling, but frequently require generation of a triple-transgenic cross for best usability/specificity. On the other hand, enhancer AAVs are easy to screen and use, and can be easily modified to express diverse cargo, such as recombinases. However, their use depends on many factors, such as viral titer and route of administration. The tools reported here as well as the scaled process of tool creation provide an unprecedented resource that should enable diverse experimental strategies towards understanding mammalian cortex and brain function.

Asian American parents' experiences of stress, discrimination, and mental health during COVID-19.

INTRODUCTION: COVID-19 has placed Asian Americans (AA) at higher risk for discrimination within the U.S. This exacerbates the mental health distress of AA parents, who are also experiencing COVID-19-related stress (e.g., health, financial, work, childcare). The risk factors associated with mental health outcomes for AA parents are not well understood. This brief report examined the relationships among COVID-19 stress, discrimination, and psychological distress of AA parents during the initial months of the pandemic. METHOD: Baseline data of an ongoing longitudinal examination into the COVID-19 experiences of AA parents and their families were utilized. Participants were 166 AA parents of children ages 2-19 years. They completed an online survey about their experiences of COVID-19-related stress (i.e., childcare, school, work), discrimination, and psychological distress. RESULTS: The majority of AA parents were highly stressed due to school closures and childcare changes; school-age parents reported significantly more stress resulting from school closures than parents of young children or adolescents. Over 21% of AA parents experienced some discrimination resulting from COVID-19; the majority reported discrimination fears for themselves and their family/friends. Experiencing discrimination was positively associated with psychological distress, as was COVID-19 stress related to work performance and relationship quality. Conversely, the majority of parents reported increased quality time with their family (i.e., children, partners). DISCUSSION: AA parents are experiencing high levels of COVID-19-related stress, and have the added psychological burden of experiencing and fearing racial/ethnic discrimination. However, the pandemic has led to families spending more quality time together. Implications for future studies are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Differential impact of the school context on ethnic and racial identity and depression for monoracial and multiracial early adolescents.

Introduction: This study examined the direct and indirect effects of school context (negative peer relationships, school environment) on ethnic and racial identity (ERI) development in middle school and later depression symptoms in high school. Differences by racial group were examined for non-Hispanic White (NHW) early adolescents, monoracial adolescents, and multiracial adolescents. Methods: This study used existing data from a large, multiwave, longitudinal study that included 593 racial/ethnically diverse adolescents from sixth grade through ninth grade across three public middle schools in the Pacific Northwest. Results: Using multigroup path analysis in structural equation modeling, the findings indicated differences by racial group-school environment was associated with positive ERI development in middle school for NHW and monoracial adolescents but not for multiracial adolescents. For multiracial adolescents, ERI predicted later depression symptoms. Discussion: These findings demonstrated the importance of examining school context and peer relationships in relation to ERI development and psychological wellbeing.

Differential encoding of temporal context and expectation under representational drift across hierarchically connected areas.

The classic view that neural populations in sensory cortices preferentially encode responses to incoming stimuli has been strongly challenged by recent experimental studies. Despite the fact that a large fraction of variance of visual responses in rodents can be attributed to behavioral state and movements, trial-history, and salience, the effects of contextual modulations and expectations on sensory-evoked responses in visual and association areas remain elusive. Here, we present a comprehensive experimental and theoretical study showing that hierarchically connected visual and association areas differentially encode the temporal context and expectation of naturalistic visual stimuli, consistent with the theory of hierarchical predictive coding. We measured neural responses to expected and unexpected sequences of natural scenes in the primary visual cortex (V1), the posterior medial higher order visual area (PM), and retrosplenial cortex (RSP) using 2-photon imaging in behaving mice collected through the Allen Institute Mindscope's OpenScope program. We found that information about image identity in neural population activity depended on the temporal context of transitions preceding each scene, and decreased along the hierarchy. Furthermore, our analyses revealed that the conjunctive encoding of temporal context and image identity was modulated by expectations of sequential events. In V1 and PM, we found enhanced and specific responses to unexpected oddball images, signaling stimulus-specific expectation violation. In contrast, in RSP the population response to oddball presentation recapitulated the missing expected image rather than the oddball image. These differential responses along the hierarchy are consistent with classic theories of hierarchical predictive coding whereby higher areas encode predictions and lower areas encode deviations from expectation. We further found evidence for drift in visual responses on the timescale of minutes. Although activity drift was present in all areas, population responses in V1 and PM, but not in RSP, maintained stable encoding of visual information and representational geometry. Instead we found that RSP drift was independent of stimulus information, suggesting a role in generating an internal model of the environment in the temporal domain. Overall, our results establish temporal context and expectation as substantial encoding dimensions in the visual cortex subject to fast representational drift and suggest that hierarchically connected areas instantiate a predictive coding mechanism.

Fibroblast growth factor regulates human neuroectoderm specification through ERK1/2-PARP-1 pathway.

Fibroblast growth factor (FGF) signaling and PAX6 transcription are required for neuroectoderm specification of human embryonic stem cells (hESCs). In this study, we asked how FGF signaling leads to PAX6 transcription and neuroectoderm specification from hESCs. Under a chemically defined medium, FGF inhibition blocked phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2) with a significant reduction of PAX6-expressing neuroepithelia, indicating that FGF regulates neural induction through ERK1/2 activation. Activation of FGF-ERK1/2 pathway was necessary for the activity of poly(ADP-ribose) polymerase-1 (PARP-1), a conserved nuclear protein catalyzing polymerization of ADP-ribose units. Pharmacological inhibition and genetic ablation of PARP-1 inhibited neural induction from hESCs, suggesting that FGF-ERK1/2 signal pathway regulates neuroectoderm specification through regulating PARP-1 activity. Furthermore, FGF-ERK1/2-PARP-1 cascade regulated the expression of PAX6, a transcription determinant of human neuroectoderm. Together, we propose that FGF regulates hESC neural specification through the ERK1/2-PARP-1 signaling pathway.

Examining risk and protective predictors of substance use among low-income Native Hawaiian and Pacific Islander adolescents.

Substance use (SU) among adolescents is a critical public health concern that increases the risk for negative outcomes. Although Asian American (AA) adolescents tend to report low rates of SU, Native Hawaiian and Pacific Islander (NH/PI) adolescents often report significantly higher rates of use. Yet, NH/PI youth are seldom studied as a separate group. Consequently, little is known about the factors involved in SU among NH/PI adolescents and how to prevent it. This prospective study investigated the effect of ecological risk and protective factors at the individual, family, and school levels on SU for NH/PI adolescents. This prospective study utilized longitudinal data from 120 NH/PI adolescents who were7 part of an SU prevention program. Information was collected at two time points-Time 1 and Time 2 (32 weeks later)-and included adolescents' SU behaviors and individual, family, and school factors. The parents of these adolescents also provided data; all information was self-report. Positive academic attitudes at Time 1 were negatively associated with alcohol and other drug (e.g., marijuana) use at Time 2. Specifically, NH/PI adolescents who had more positive attitudes toward their school, peers, and teachers reported less alcohol and other SU. Prevention efforts may be most effective for NH/PI adolescents if addressed within the school context. This may include programs implemented in schools, utilizing teachers as role models, and/or promoting prosocial peer relationships to support positive behaviors. Additional implications are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).