Microbial Metabolite 3-Indolepropionic Acid Mediates Immunosuppression.

The microbial-derived metabolite, 3-indolepropionic acid (3-IPA), has been intensely studied since its origins were discovered in 2009; however, 3-IPA's role in immunosuppression has had limited attention. Untargeted metabolomic analyses of T-cell exhaustion and immunosuppression, represented by dysfunctional under-responsive CD8+ T cells, reveal a potential role of 3-IPA in these responses. T-cell exhaustion was examined via infection of two genetically related mouse strains, DBA/1J and DBA/2J, with lymphocytic choriomeningitis virus (LCMV) Clone 13 (Cl13). The different mouse strains produced disparate outcomes driven by their T-cell responses. Infected DBA/2J presented with exhausted T cells and persistent infection, and DBA/1J mice died one week after infection from cytotoxic T lymphocytes (CTLs)-mediated pulmonary failure. Metabolomics revealed over 70 metabolites were altered between the DBA/1J and DBA/2J models over the course of the infection, most of them in mice with a fatal outcome. Cognitive-driven prioritization combined with statistical significance and fold change were used to prioritize the metabolites. 3-IPA, a tryptophan-derived metabolite, was identified as a high-priority candidate for testing. To test its activity 3-IPA was added to the drinking water of the mouse models during LCMV Cl13 infection, with the results showing that 3-IPA allowed the mice to survive longer. This negative immune-modulation effect might be of interest for the modulation of CTL responses in events such as autoimmune diseases, type I diabetes or even COVID-19. Moreover, 3-IPA's bacterial origin raises the possibility of targeting the microbiome to enhance CTL responses in diseases such as cancer and chronic infection.

The Development and Implementation of Preventive Medicine Resident Rotations in a Shelter Serving Asylum-Seekers at the US-Mexico Border.

Asylum-seekers present to the US-Mexico border with a variety of acute health needs. In December 2018, the County of San Diego Health and Human Services Agency partnered with the University of California, San Diego to provide health screenings to asylum-seekers at a humanitarian shelter administered by Jewish Family Services. The assessments screened for communicable diseases and acute conditions. Preventive medicine residents in the HRSA-funded UCSD-SDSU (University of California, San Diego-San Diego State University) Residency were trained to become an integral part of the program. Training included cultural competency, public health interface, protocol development and implementation, interdisciplinary teamwork, and quality improvement. Over 18 months, nearly 20000 asylum-seekers were screened, which allowed for the detection of an imported influenza outbreak and prevented any major public health incidents or medical errors. This health screening program for asylum-seekers provided an important experience for preventive medicine trainees. In turn, preventive medicine and other trainees were valuable contributors to the program.

Process Evaluation of an Early Care and Education Intervention: The California Childhood Obesity Research Demonstration Study (CA-CORD).

Given the widespread use of out-of-home child care in the United States, early care and education (ECE) providers offer ideal settings to promote health behaviors among Hispanic/Latino children whose obesity prevalence remains high. This study details the process evaluation of ECE intervention strategies of a childhood obesity research demonstration study (California Childhood Obesity Research Demonstration [CA-CORD]) to prevent and control obesity among Hispanic/Latino children aged 2 to 12 years. Participating ECE providers received the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) materials and action planning sessions with a trained interventionist; Sports, Play, and Active Recreation for Kids (SPARK) physical activity (PA), health behavior, and body mass index assessment trainings; and health behavior toolkit, cooking kit, water dispensers, and posters to promote healthy eating, PA, water consumption, and quality sleep. Intervention logs and director/lead teacher interviews evaluated how well 14 center-based and 9 private ECE providers implemented policy, system, and environmental changes. NAP SACC was implemented with higher fidelity than other strategies, and participation in SPARK trainings was lower than health behavior trainings. ECE directors/lead teachers reported that the intervention activities and materials helped them promote the targeted behaviors, especially PA. Results demonstrated that the use of NAP SACC, trainings, and toolkit had high fidelity and were potentially replicable for implementation in ECE settings among Hispanic/Latino communities.

Universal HIV and Birth Cohort HCV Screening in San Diego Emergency Departments.

Universal HIV and HCV screening in emergency departments (ED) can reach populations who are less likely to get tested otherwise. The objective of this analysis was to evaluate universal opt-out HIV and HCV screening in two EDs in San Diego. HIV screening for persons aged 13-64 years (excluding persons known to be HIV+ or reporting HIV testing within last 12 months) was implemented using a 4th generation HIV antigen/antibody assay; HCV screening was offered to persons born between 1945 and 1965. Over a period of 16 months, 12,575 individuals were tested for HIV, resulting in 33 (0.26%) new HIV diagnoses, of whom 30 (90%) were successfully linked to care. Universal screening also identified 74 out-of-care for >12-months HIV+ individuals of whom 50 (68%) were successfully relinked to care. Over a one-month period, HCV antibody tests were conducted in 905 individuals with a seropositivity rate of 9.9% (90/905); 61 seropositives who were newly identified or never treated for HCV had HCV RNA testing, of which 31 (51%) resulted positive (3.4% of all participants, including 18 newly identified RNA positives representing 2% of all participants), and 13/31 individuals (42%) were linked to care. The rate of newly diagnosed HCV infections exceeded the rate of newly diagnosed HIV infections by >7-fold, underlining the importance of HCV screening in EDs.

Lymphocytic choriomeningitis virus Clone 13 infection causes either persistence or acute death dependent on IFN-1, cytotoxic T lymphocytes (CTLs), and host genetics.

Understanding of T cell exhaustion and successful therapy to restore T cell function was first described using Clone (Cl) 13 variant selected from the lymphocytic choriomeningitis virus (LCMV) Armstrong (ARM) 53b parental strain. T cell exhaustion plays a pivotal role in both persistent infections and cancers of mice and humans. C57BL/6, BALB, SWR/J, A/J, 129, C3H, and all but one collaborative cross (CC) mouse strain following Cl 13 infection have immunosuppressed T cell responses, high PD-1, and viral titers leading to persistent infection and normal life spans. In contrast, the profile of FVB/N, NZB, PL/J, SL/J, and CC NZO mice challenged with Cl 13 is a robust T cell response, high titers of virus, PD-1, and Lag3 markers on T cells. These mice all die 7 to 9 d after Cl 13 infection. Death is due to enhanced pulmonary endothelial vascular permeability, pulmonary edema, collapse of alveolar air spaces, and respiratory failure. Pathogenesis involves abundant levels of Cl 13 receptor alpha-dystroglycan on endothelial cells, with high viral replication in such cells leading to immunopathologic injury. Death is aborted by blockade of interferon-1 (IFN-1) signaling or deletion of CD8 T cells.

Rethinking Antimicrobial Prophylaxis in the Transplant Patient in the World of Emerging Resistant Organisms-Where Are We Today?

PURPOSE OF REVIEW: The use of prophylactic antibiotics during the neutropenic period in hematopoietic stem cell transplantation has been the standard of care at most institutions for the past 20 years. We sought to review the benefits and risks of this practice. RECENT FINDINGS: Emerging data has highlighted the potential costs of antibacterial prophylaxis, from selecting for antibiotic resistance to perturbing the microbiome and contributing to increase risk for Clostridium difficile and perhaps graft-versus-host-disease, conditions which may lead to poorer outcomes. Though in many studies prophylactic antibiotics improved morbidity and mortality outcomes, the potential harms including antibiotic resistance, Clostridium difficile infection, and alterations of the gut microbiome should be considered. Future studies aimed to better risk-stratify patients and limit the use of broad-spectrum antibiotics are warranted.

Validation of the modified Parenting Strategies for Eating and Physical Activity Scale-Diet (PEAS-Diet) in Latino children.

Research shows that Latino parenting practices influence children's dietary and weight outcomes. Most studies use parent-reported data, however data from children may provide additional insight into how parents influence their children's diet and weight outcomes. The Parenting Strategies for Eating and Activity Scale (PEAS) has been validated in Latino adults, but not in children. This study evaluated the factor structure and concurrent and predictive validity of a modified version of the PEAS (PEAS-Diet) among Latino children. Data were collected from 361 children ages 7-13 from Imperial County, California, enrolled in a randomized controlled trial to promote healthy eating. The PEAS-Diet included 25 candidate items targeting six parenting practices pertaining to children's eating behaviors: (a) monitoring; (b) disciplining; (c) control; (d) permissiveness; (e) reinforcing; and (f) limit-setting. Children were on average ten years old (±2), 50% boys, 93% self-identified as Latino, 81% were US-born, and 55% completed English versus Spanish-language interviews. Using varimax rotation on baseline data with the total sample, six items were removed due to factor loadings <.40 and/or cross-loading (>.32 on more than one component). Parallel analysis and interpretability suggested a 5-factor solution explaining 59.46% of the variance. The subscale "limit-setting" was removed from the scale. The final scale consisted of 19 items and 5 subscales. Internal consistency of the subscales ranged from α = .63-.82. Confirmatory factor analyses provided additional evidence for the 5-factor scale using data collected 4 and 6 months post-baseline among the control group (n = 164, n = 161, respectively). Concurrent validity with dietary intake was established for monitoring, control, permissiveness, and reinforcing subscales in the expected directions. Predictive validity was not established. Results indicated that with the reported changes, the interview-administered PEAS-Diet is valid among Latino children aged 7-13 years.

A Process Evaluation of an Efficacious Family-Based Intervention to Promote Healthy Eating: The Entre Familia: Reflejos de Salud Study.

Entre Familia: Reflejos de Salud was a successful family-based randomized controlled trial designed to improve dietary behaviors and intake among U.S. Latino families, specifically fruit and vegetable intake. The novel intervention design merged a community health worker (promotora) model with an entertainment-education component. This process evaluation examined intervention implementation and assessed relationships between implementation factors and dietary change. Participants included 180 mothers randomized to an intervention condition. Process evaluation measures were obtained from participant interviews and promotora notes and included fidelity, dose delivered (i.e., minutes of promotora in-person contact with families, number of promotora home visits), and dose received (i.e., participant use of and satisfaction with intervention materials). Outcome variables included changes in vegetable intake and the use of behavioral strategies to increase dietary fiber and decrease dietary fat intake. Participant satisfaction was high, and fidelity was achieved; 87.5% of families received the planned number of promotora home visits. In the multivariable model, satisfaction with intervention materials predicted more frequent use of strategies to increase dietary fiber (p ≤ .01). Trends suggested that keeping families in the prescribed intervention timeline and obtaining support from other social network members through sharing of program materials may improve changes. Study findings elucidate the relationship between specific intervention processes and dietary changes.

Evidence supporting a promotora-delivered entertainment education intervention for improving mothers' dietary intake: the Entre Familia: Reflejos de Salud Study.

Entertainment education and the promotora model are 2 evidence-based health communication strategies. This study examined their combined effect on promoting healthy eating among mothers in a family-based intervention. Participants were 361 Mexican-origin families living in Imperial County, California, who were randomly assigned to an intervention or delayed treatment condition. The intervention involved promotoras (community health workers) who delivered 11 home visits and 4 telephone calls. Home visits included a 12-minute episode of a 9-part situation comedy depicting a family struggling with making healthy eating choices; an accompanying family workbook was reviewed to build skills and left with the family. Baseline and immediate postintervention data were collected from the mothers, including the primary outcome of daily servings of fruits and vegetables. Other dietary and psychosocial factors related to healthy eating were examined. At postintervention, mothers in the intervention reported increases in daily vegetable servings (p ≤ .05); however, no changes were observed in fruit consumption. Improvements were observed in behavioral strategies to increase fiber (p ≤ .001) and to decrease fat intake (p ≤ .001), unhealthy eating behaviors (p ≤ .001), and individual (p ≤ .05) and family-related (p ≤ .01) perceived barriers to healthy eating. Entertainment education and promotoras engaged families and improved mothers' diets. Further research should examine the dose needed for greater changes.

Family support is associated with behavioral strategies for healthy eating among Latinas.

BACKGROUND: Healthy eating is important for obesity control. Dietary interventions target the adoption of behavioral strategies to increase fiber and decrease fat consumption. However, little is known about the contributions of psychosocial factors to the use of these strategies. PURPOSE: This study examined psychosocial correlates of behavioral strategies for healthy eating among Latinas. METHOD: Participants included 361 Latino mothers living along the U.S.-Mexico border in California. Data included measures of sociodemographics, acculturation, and psychosocial determinants of healthy eating. A 30-item dietary behavioral strategies scale assessed strategies to increase fiber and decrease fat consumption. RESULTS: Family interactions regarding dietary habits (ß = .224, p < .001) and financial status (ß = .148, p = .029) were associated with the use of strategies to decrease fat consumption. Positive family interactions regarding dietary habits (ß = .226, p < .001), fewer barriers to obtaining fruits and vegetables (ß = -.207, p < .001), and more family support for vegetable purchasing (ß = .070, p = .047) were associated with use of strategies to increase fiber consumption. CONCLUSIONS: Future interventions would benefit from improving family systems associated with healthy eating.

Targeting children's dietary behaviors in a family intervention: 'Entre familia: reflejos de salud' / Enfoque en hábitos alimenticios de los hijos en una intervención familiar: 'Entre familia: reflejos de salud'

Objective. This intervention sought to promote healthy eating with the ultimate goal of reducing childhood obesity risk. Materials and methods. Three hundred and sixty-one Latino families living on the US-Mexico border with at least one child between 7-13 years of age were eligible to participate. Families randomly assigned to the four-month intervention received 14 contacts with a promotora (community health worker), consisting of 11 home visits and three telephone calls; the control condition was a delayed treatment intervention. Children reported on their dietary intake at baseline, immediately post-intervention and at the six month follow-up visit. Results. The intervention reduced weekly consumption of fast food (p<0.05). A dose-response relationship was observed such that for every seven hours of promotora contact, monthly variety of fruits (p<0.01) and vegetables (p<0.01) increased by one. No other intervention effects were observed. Conclusions. Family-based interventions can improve children's eating habits, with the amount of contact with the promotora being key to success.

Objetivo. Promover una alimentación saludable con el objetivo final de reducir el riesgo de obesidad infantil. Material y métodos. Trescientas sesenta y una familias latinas que viven en la frontera de EU y México, y que cuentan con por lo menos un hijo entre 7 y 13 años, fueron elegibles para participar. Las familias asignadas al azar a la intervención de cuatro meses tuvieron contacto 14 veces (11 visitas familiares y tres llamadas telefónicas) con una promotora; el grupo de control recibió el tratamiento de intervención al final del programa. Los niños reportaron su ingesta alimenticia al inicio, inmediatamente después de la intervención y en la visita de seguimiento a los seis meses. Resultados. La intervención redujo el consumo semanal de comida rápida (p<0.05). Se observó una relación dosis-respuesta tal que por cada siete horas de contacto con la promotora, la variedad mensual de frutas (p<0.01) y verduras (p<0.01) tuvo un incremento de uno. No se observaron otros efectos de intervención. Conclusiones. Las intervenciones basadas en la familia pueden mejorar los hábitos alimenticios de los niños, siendo la cantidad de contacto con la promotora clave para el éxito.