Identification of pediatric activated T-cell hepatitis using clinical immune studies.

BACKGROUND AND AIMS: The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TCHep group. METHODS: Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TCHep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia). RESULTS: 124 patients were identified: 83 with known diagnoses, 16 with TCHep, and 25 with IND-Hep. Patients with TCHep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8-8.9) vs 1.5 mg/dL (IQR 1.0-3.6), p < 0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073-5771) vs 2997 IU/mL (IQR 1957-3237), p = 0.02), and percent of CD8+ T-cells expressing perforin (14.5 % (IQR 8.0-20.0) vs 1.0 % (IQR 0.8-1.0), p = 0.004) and granzyme (37.5 % (IQR 15.8-54.8) vs 4.0 % (IQR 2.5-5.5), p = 0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TCHep patients had significantly increased percent CD8+ T cells (29.0 % (IQR 24.5-33.5) vs 23.6 % (IQR 19.8-25.8), p = 0.04) and HLA-DR+ (16.0 % (IQR 14.5-24.5) vs 2.7 (1.8-5.3), p < 0.001) compared to IND-Hep patients indicative of increase in CD8+ T cells that are activated. CONCLUSIONS: Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TCHep patients. These readily available immune function labs can be used to help distinguish patients with TCHep from those with other causes. This provides a non-invasive tool for early detection of potential TCHep before progression to liver failure.

MULTITARGETED POLYPHARMACOTHERAPY for CANCER TREATMENT. THEORETICAL CONCEPTS and PROPOSALS.

INTRODUCTION: . The pharmacological treatment of cancer has evolved from cytotoxic to molecular targeted therapy. The median survival gains of 124 drugs approved by the FDA from 2003 to 2021 is 2.8 months. Targeted therapy is based on the somatic mutation theory, which has some paradoxes and limitations. While efforts of targeted therapy must continue, we must study newer approaches that could advance therapy and affordability for patients. AREAS COVERED: This work briefly overviews how cancer therapy has evolved from cytotoxic chemotherapy to current molecular-targeted therapy. The limitations of the one-target, one-drug approach considering cancer as a robust system and the basis for multitargeting approach with polypharmacotherapy using repurposing drugs. EXPERT OPINION: Multitargeted polypharmacotherapy for cancer with repurposed drugs should be systematically investigated in preclinical and clinical studies. Remarkably, most of these proposed drugs already have a long history in the clinical setting, and their safety is known. In principle, the risk of their simultaneous administration should not be greater than that of a first-in-human phase I study as long as the protocol is developed with strict vigilance to detect early possible side effects from their potential interactions. Research on cancer therapy should go beyond the prevailing paradigm targeted therapy.

Use of Electronic Nicotine Delivery Systems and Age of Asthma Onset Among US Adults and Youths.

Importance: The association of use of electronic nicotine delivery systems (ENDS) with the age of asthma onset is unknown. Objective: To explore the association of past 30-day ENDS use with the age of asthma onset in adults and youths who did not have asthma or chronic obstructive pulmonary disease and never used cigarettes. Design, Setting, and Participants: This cohort study was a secondary analysis of waves 1 to 6 of the US nationally representative Population of Tobacco and Health Study (2013-2021). Eligible participants included adults (≥18 years) and youths (12-17 years) who did not have asthma or chronic obstructive pulmonary disease at the first wave of participation. Data analysis was conducted from September 2022 to April 2024. Exposure: Past 30-day ENDS use at the first wave of participation in the study preceding the onset of asthma. Main outcome and measures: Lower and upper age limits were estimated using the age reported at the first wave of participation and the number of weeks between follow-up waves until asthma was first reported or censored. The association of past 30-day ENDS use with the age of asthma onset was estimated using weighted interval-censoring Cox regression. The cumulative hazard function for the age of asthma onset was estimated using interval-censoring survival analysis. Results: A total of 24 789 participants were included, with 7766 adults (4461 female [weighted percentage, 59.11%] and 3305 male [weighted percentage, 40.89%]), representing 80.0 million adults, and 17 023 youths (8514 female [weighted percentage, 50.60%] and 8496 male [weighted percentage 49.32%]), representing 33.9 million youths. By age 27 years, 6.2 per 1000 adults reported asthma incidence (hazard ratio [HR], 0.62%; 95% CI, 0.46%-0.75%). While controlling for covariates, there was a 252% increased risk of the onset of asthma at earlier ages for adults who used ENDS in the past 30 days vs adults who did not (adjusted HR, 3.52; 95% CI, 1.24-10.02). For youths, there was no association of ENDS use in the past 30 days with age of asthma onset (adjusted HR, 1.79; 95% CI, 0.67-4.77), which could be due to a lack of statistical power. Conclusion and relevance: In this cohort study, past 30-day ENDS use among adults was associated with earlier ages of asthma onset. These findings suggest that prevention and cessation programs directed to adults who use ENDS are needed to educate the public, protect public health, prevent adverse health outcomes, and motivate users to stop. Furthermore, modifying symptom-screening asthma guidelines, resulting in earlier asthma detection and treatment, may reduce morbidity and mortality due to asthma.

Ketogenic diet therapies as a non-pharmacological adjuvant in resistant epilepsy: retrospective analysis of adult outpatients in Colombia.

Twelve patients between 18 and 53 years of age were included. MAD plus nutritional supplementation was administered to 75% (n = 10) of the participants, one (8.3%) received MAD alone, and 16.7 (n = 2) received Classic Ketogenic Diet (cKD) plus nutritional supplementation. Oral nutritional supplementation, administered in the outpatient setting, provided patients with between 31 and 55% of the total caloric value. In the first month of KDT treatment, 83.3% (n = 10) of patients reduced the number of weekly seizures by 40% (median). At six months of treatment, 75% of patients had at least halved the number of weekly seizures. At 12 months of treatment, the number of weekly seizures had been reduced by 85.7% (median). KDT was well tolerated, and there was no need to discontinue treatment. This study provides real-world information on the use of KDT, particularly MAD in adults, in developing countries. Future studies in larger cohorts will provide further information on different types of KDT, adherence, and patient-reported outcomes.

Chronic unpredictable mild stress increases serum aldosterone without affecting corticosterone levels and induces hepatic steatosis and renal injury in young adult male rats.

Stress is often associated with anxiety and depressive symptoms in adolescents. Stress is associated with components of metabolic syndrome and inflammation. The present study hypothesizes that aldosterone, more than corticosterone, promotes chronic stress-hepatic steatosis and fibrosis, as well as renal inflammation and fibrosis in young adult rats. Thirty-two young adult male Wistar rats of 51 days old were divided into four groups (n = 8 per group): Control (C), chronic unpredictable mild stress (CUMS), control plus vehicle (C plus veh), CUMS plus eplerenone, a selective aldosterone blocker (CUMS plus EP). On postnatal day 51, eplerenone was administered orally through a gastric tube two hours before the start of the stress test. The CUMS paradigm was administered once daily at different times, with no repetition of the stressor sequence for four weeks. Renal inflammation and fibrosis were measured, as well as liver glycogen, triacylglycerol, and fibrosis levels. The serum concentrations of corticosterone, aldosterone, sodium, and creatinine were measured in urine and serum. The CUMS group showed a high level of serum aldosterone without affecting the level of corticosterone, increased urinary sodium, tubular atrophy, glomerular sclerosis, the presence of inflammation, and fibrosis, without affecting creatinine, increased glycogen content, triacylglycerol, and moderate fibrosis in the liver, and treatment with eplerenone prevented the inflammation, fibrosis, glycogen, and triacylglycerol. Our results show that chronic stress-induced aldosterone promotes hepatic steatosis and renal injury more than corticosterone. The prevention by eplerenone supports our hypothesis.

Dementia friendly in the context of hospitalization: A concept analysis using the Walker & Avant Method.

AIM(S): To evaluate the literature to inform and propose a conceptual definition for dementia friendly in the context of hospitalization. METHODS: The Walker & Avant method for concept analysis was utilized for this review. DATA SOURCES (INCLUDE SEARCH DATES): Initial search conducted June 2022. Repeated search conducted in February 2023. Databases for the literature search include Scopus, PubMed, CINAHL, PsycINFO, and AGELINE. RESULTS: Five attributes of the concept of dementia friendly in the context of hospitalization were identified including: staff knowledge/education, environmental modification, person-centred care, nursing care delivery and inclusion of family caregivers. Based on these attributes a conceptual definition is proposed. CONCLUSION: A clarified definition for dementia friendly in the context of hospitalization will aid in understanding the concept, provide guidance for hospitals seeking to implement dementia-friendly interventions and benefit researchers aiming to study the impact of such programs. REPORTING METHOD: n/a. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Head circumference at birth and postnatal growth trajectory in vulnerable groups from Argentina.

OBJECTIVES: To investigate the association between the anthropometric status at birth and brain and bone growth during the first year of life. According to the brain-sparing hypothesis, we expect catch-up to be faster in head circumference (HC) than in body length. METHODS: This is a longitudinal design that included Argentinian infants under 12 months of age with at least three anthropometric records. We classified study participants into four growth status categories according to z-scores for HC (HCZ) and length (LAZ) at birth, with z-score = -2 as a threshold. We used the Count model to describe growth trajectories in HC and length in the first year of life according to the growth status at birth. Recovery indicator for HC and length was taken as the time until the predicted growth trajectory surpassed the threshold curve predicted by z-score = -2 for age. RESULTS: Growth models included 3399 infants. There were significant differences in the growth parameters between groups in all cases (p < 0.05). Within the group with a low HCZ and a low LAZ at birth, HC recovery was faster than length. In the case of a low z-score for only one of the variables, newborns with a low HCZ recovered faster than individuals born with a low LAZ. CONCLUSIONS: The postnatal growth pattern in HC and length is associated with the growth status of HC and length at birth. As we hypothesized, the fastest postnatal recovery occurs for HC in cases of intrauterine delayed growth.

Application of inverse weighting analysis to assess the association of youth perceptions with the age of initiation of tobacco products.

Introduction: To examine if perceptions of harmfulness and addictiveness of hookah and cigarettes impact the age of initiation of hookah and cigarettes, respectively, among US youth. Youth (12-17 years old) users and never users of hookah and cigarettes during their first wave of PATH participation were analyzed by each tobacco product (TP) independently. The effect of perceptions of (i) harmfulness and (ii) addictiveness at the first wave of PATH participation on the age of initiation of ever use of hookah was estimated using interval-censoring Cox proportional hazards models. Methods: Users and never users of hookah at their first wave of PATH participation were balanced by multiplying the sampling weight and the 100 balance repeated replicate weights with the inverse probability weight (IPW). The IPW was based on the probability of being a user in their first wave of PATH participation. A Fay's factor of 0.3 was included for variance estimation. Crude hazard ratios (HR) and 95% confidence intervals (CIs) are reported. A similar process was repeated for cigarettes. Results: Compared to youth who perceived each TP as "a lot of harm", youth who reported perceived "some harm" had younger ages of initiation of these tobacco products, HR: 2.53 (95% CI: 2.87-4.34) for hookah and HR: 2.35 (95% CI: 2.10-2.62) for cigarettes. Similarly, youth who perceived each TP as "no/little harm" had an earlier age of initiation of these TPs compared to those who perceived them as "a lot of harm", with an HR: 2.23 (95% CI: 1.82, 2.71) for hookah and an HR: 1.85 (95% CI: 1.72, 1.98) for cigarettes. Compared to youth who reported each TP as "somewhat/very likely" as their perception of addictiveness, youth who reported "neither likely nor unlikely" and "very/somewhat unlikely" as their perception of addictiveness of hookah had an older age of initiation, with an HR: 0.75 (95% CI: 0.67-0.83) and an HR: 0.55 (95% CI: 0.47, 0.63) respectively. Discussion: Perceptions of the harmfulness and addictiveness of these tobacco products (TPs) should be addressed in education campaigns for youth to prevent early ages of initiation of cigarettes and hookah.

Effects of Mind-Body Qigong Exercise on Overall Health, Fatigue/Sleep, and Cognition in Older Chinese Immigrants in the US: An Intervention Study with Control.

Background: Culturally relevant exercises may help improve health and address disparities faced by older immigrants due to language and cultural barriers. Few studies have focused on such exercise interventions among older Chinese immigrants at US daycare centers. Methods: We conducted a 10-week nonrandomized controlled trial in older Chinese immigrants in Philadelphia, US. The intervention group practiced Chinese Qigong (Baduanjin) 5 days a week guided by trained research assistants and video instructions. The control group maintained their usual daily activities. We collected self-report assessments on overall health, sleep, and fatigue and implemented two computerized cognitive tests measuring psychomotor vigilance task (PVT) and memory twice, preintervention and postintervention. Repeated measures general linear model (GLM) and paired samples t-tests were used for data analyses. Results: Eighty-eight older adults (Qigong, n = 53; control, n = 35) with an average age of 78.13 (SD = 5.05) were included. Groups showed no significant differences at baseline evaluation. After the 10-week exercise, the intervention group showed significant improvements in overall health (p=0.032), fatigue (p < 0.001), and cognitive functions including memory (p=0.01), response speed (p=0.002), and response time (p=0.012) on the PVT, as well as marginally significant benefits in sleep (p=0.058). Between-group comparisons identified significant group-by-time interactions in health (p=0.024), sleep (p=0.004), fatigue (p=0.004), and memory (p=0.004). Conclusion: We revealed significant positive effects of Qigong in older Chinese immigrants across multiple health domains. Findings highlight the potential of a culturally relevant exercise in addressing health disparities.

Timed Activity to Minimize Sleep Disturbance in People With Cognitive Impairment.

Background and Objectives: Sleep disturbances occur in >60% of persons living with cognitive impairment, affecting their quality of life (QOL). Regulating the sleep-wake cycle through engaging cognitive, physical, and sensory-based activities delivered at strategic times may reduce sleep disturbances and be a feasible nonpharmacological treatment for sleep problems. The objective of this trial was to test the efficacy of a timed-activity intervention in improving QOL and sleep disturbances in persons living with cognitive impairment. Research Design and Method: Randomized 2-group parallel design involving 209 dyads of community-residing persons living with cognitive impairment and care partners. Dyads were randomly assigned (1:1) to 1-hr home activity sessions administered weekly in the morning, afternoon, or evening over 4 weeks (the Healthy Patterns Sleep Program), or to an attention-control condition consisting of sleep hygiene training plus education on home safety and health promotion. QOL, objective and subjective sleep quality, and neuropsychiatric symptoms were assessed at baseline and 4 weeks later. Results: QOL was significantly improved in the intervention group compared to control (p = .0491). There were no significant effects on objective or subjective sleep or neuropsychiatric symptoms. In a subgroup analysis, subjective sleep as measured by the PROMIS (Patient Reported Outcomes Measurement Information System) Sleep-Related Impairment survey was significantly improved in the intervention group compared to the control group for individuals with symptoms of depression (p = .015) or poor observed sleep at baseline (p = .005). Discussion and Implications: The Healthy Patterns Intervention may benefit QOL for persons living with cognitive impairment and those with poor subjective sleep. A longer dose may be necessary to elicit improvement in actigraphically measured sleep-wake activity. Clinical Trial Registration Number: NCT0368218 5.

La equidad en la campaña de vacunación COVID de la Provincia de Buenos Aires (Argentina): un análisis del Municipio de Quilmes.

INTRODUCCIÓN: la pandemia de la COVID-19 ha acentuado las desigualdades sociales, económicas y relacionadas con la salud, afectando desproporcionadamente a las personas en situación de vulnerabilidad y perpetuando la inequidad en salud. En Argentina se implementó una campaña nacional gratuita de vacunación contra la COVID-19 con una perspectiva de equidad. OBJETIVO: identificar desigualdades territoriales en el acceso a la vacunación contra la COVID-19 en Quilmes. MÉTODOS: se analizó la información referida a la vacunación contra la COVID-19 de personas residentes en el Municipio. Se efectuó la georreferenciación de cada vacunatorio y de cada persona a partir del domicilio declarado en el momento de la vacunación. Para caracterizar el grado de vulnerabilidad de las personas vacunadas, a cada una se le asignó el índice de carencias múltiples (ICM) correspondiente al radio censal de residencia. RESULTADOS: al menos el 82 % de la población completó el esquema primario de vacunación (dosis 1 y dosis 2), porcentaje que alcanzó el 97 % en los mayores de 65 años. Analizando la media de dosis aplicadas se observa algo similar con un gradiente hacia los quintiles más altos pero con una mínima diferencia entre sí, situación que también se corrobora en todos los grupos etarios. DISCUSIÓN: no se observaron brechas significativas entre los diferentes niveles socioeconómicos. Si bien se observó un mínimo gradiente en el promedio de dosis recibidas, el tiempo de acceso a las diferentes vacunas y el porcentaje de esquemas primarios completos recibidos, las mismas tienen escasa relevancia clínica y sanitaria.

Using the Nutrition Facts Label to Make Food Choices Is Associated with Healthier Eating among 8th and 11th-Grade Students: An Analysis of Statewide Representative Data from the 2019-2020 Texas School Physical Activity and Nutrition Survey.

BACKGROUND: Nutrition labels are a tool to inform and encourage the public to make healthier food choices, but little information is available about use in multi-ethnic adolescent populations in the U.S. The purpose of this study was to examine associations between the level of nutrition label usage and healthy/unhealthy eating behaviors among a statewide representative sample of 8th and 11th-grade students in Texas. METHODS: We analyzed cross-sectional associations between the Nutrition Facts label use and eating behaviors from a statewide sample of 8th and 11th-grade students in Texas, (n = 4730, weighted n = 710,731, mean age = 14.7 ± 1.6 years; 49% female, 51% Hispanic), who completed the 2019-2020 Texas School Physical Activity and Nutrition (TX SPAN) survey. Students self-reported their level of nutrition label usage to make food choices (5-point Likert scale from "Never" to "Always") and previous day consumption of 26 food items (13 healthy, 13 unhealthy). The 26 food items were used to calculate a Healthy Eating Index (HEI) score (0-100), a Healthy Foods Index (HFI) score (0-100), and an Unhealthy Foods Index (UFI) score (0-100). Weighted linear regression models were employed to examine the associations between self-reported use of nutrition labels to make food choices and HEI, HFI, and UFI scores. Marginal predicted means of HEI, HFI, and UFI scores were calculated post hoc from linear regression models. The odds of consuming specific individual food items for nutrition label usage were also calculated from weighted logistic regression models. All linear and logistic regression models were adjusted for grade, sex, Body Mass Index (BMI), race/ethnicity, economic disadvantage, and percentage of English language learners by school. RESULTS: A total of 11.0% of students reported always/almost always using nutrition labels to make food choices, 27.9% reported sometimes using them, while 61.0% indicated they never/almost never used nutrition labels to make food choices. The average HEI score among students in the sample was 47.7 ± 5.9. Nutrition Facts label usage was significantly and positively associated with HEI (b = 5.79, 95%CI: 4.45, 7.12) and HFI (b = 7.28, 95%CI:4.48, 10.07), and significantly and negatively associated with UFI (b = -4.30, 95%CI: -6.25, -2.34). A dose-response relationship was observed between nutrition label usage and HEI, HFI, and UFI scores, such that the strength of these associations increased with each one-point increase in nutrition label usage. Students who reported using nutrition labels always/almost always to make food choices had significantly higher odds of consuming healthy foods including baked meat, nuts, brown bread, vegetables, whole fruit, and yogurt (ORrange = 1.31-3.07), and significantly lower odds of consuming unhealthy foods including chips, cake, candy, and soda (ORrange = 0.48-0.68) compared to students who reported never/almost never using the Nutrition Facts label. CONCLUSIONS: Using the Nutrition Facts labels to make food choices is beneficially associated with healthy and unhealthy eating among 8th and 11th-grade students, although the proportion of students using nutrition labels to make their food choices was low. Public health efforts should be made to improve nutrition literacy and encourage nutrition label use among secondary students in the United States.

Effects of the tetravanadate [V4O12]4- anion on the structural, magnetic, and biological properties of copper/phenanthroline complexes.

The aim to access linked tetravanadate [V4O12]4- anion with mixed copper(II) complexes, using α-amino acids and phenanthroline-derived ligands, resulted in the formation of four copper(II) complexes [Cu(dmb)(Gly)(OH2)]2[Cu(dmb)(Gly)]2[V4O12]·9H2O (1) [Cu(dmb)(Lys)]2[V4O12]·8H2O (2), [Cu(dmp)2][V4O12]·C2H5OH·11H2O (3), and [Cu(dmp)(Gly)Cl]·2H2O (4), where dmb = 4,4'-dimethioxy-2,2'-bipyridine; Gly = glycine; Lys = lysine; and dmp = 2,9-dimethyl-1,10-phenanthroline. The [V4O12]4- anion is functionalized with mixed copper(II) units in 1 and 2; while in 3, it acts as a counterion of two [Cu(dmp)]2+ units. Compound 4 crystallized as a unit that did not incorporate the vanadium cluster. All compounds present magnetic couplings arising from Cu⋯O/Cu⋯Cu bridges. Stability studies of water-soluble 3 and 4 by UV-Vis spectroscopy in cell culture medium confirmed the robustness of 3, while 4 appears to undergo ligand scrambling over time, resulting partially in the stable species [Cu(dmp)2]+ that was also identified by electrospray ionization mass spectrometry at m/z = 479. The in vitro cytotoxicity activity of 3 and 4 was determined in six cancer cell lines; the healthy cell line COS-7 was also included for comparative purposes. MCF-7 cells were more sensitive to compound 3 with an IC50 value of 12 ± 1.2 nmol. The tested compounds did not show lipid peroxidation in the TBARS assay, ruling out a mechanism of action via reactive oxygen species formation. Both compounds inhibited cell migration at 5 µM in wound-healing assays using MCF-7, PC-3, and SKLU-1 cell lines, opening a new window to study the anti-metastatic effect of mixed vanadium-copper(II) systems.

Selection of clinically relevant drug concentrations for in vitro studies of candidates drugs for cancer repurposing: a proposal.

Drug repurposing of widely prescribed patent-off and cheap drugs may provide affordable drugs for cancer treatment. Nevertheless, many preclinical studies of cancer drug repurposing candidates use in vitro drug concentrations too high to have clinical relevance. Hence, preclinical studies must use clinically achievable drug concentrations. In this work, several FDA-approved cancer drugs are analyzed regarding the correlation between the drug inhibitory concentrations 50% (IC50) tested in cancer cell lines and their corresponding peak serum concentration (Cmax) and area under the curve (AUC) reported in clinical studies of these drugs. We found that for most targeted cancer drugs, the AUC and not the Cmax is closest to the IC50; therefore, we suggest that the initial testing of candidate drugs for repurposing could select the AUC pharmacokinetic parameter and not the Cmax as the translated drug concentration for in vitro testing. Nevertheless, this is a suggestion only as experimental evidence does not exist to prove this concept. Studies on this issue are required to advance in cancer drug repurposing.

Endovascular closure of a congenital extrahepatic portosystemic shunt for the treatment of hepatopulmonary syndrome in an infant.

Congenital portosystemic shunts may result in the development of hepatopulmonary syndrome, typically presenting with progressive hypoxemia in later childhood. We describe a case of a 5-month-old male with heterotaxy with polysplenia presenting with new onset hypoxemia. Subsequent evaluation identified an extrahepatic portosystemic shunt arising from the confluence of the main portal and superior mesenteric veins draining into the left renal vein. To treat his hypoxemia and prevent future complications of shunting, the patient underwent a successful single-stage endovascular closure.

The Integration of Community Voice in the Implementation of a Mobile Health Program.

BACKGROUND: Health care access is vital to advancing health equity. The purpose of this paper was to use a community-based participatory research approach to engage underserved communities in the development of a new mobile health clinic (MHC) program and to discuss the lessons learned from the conversations. Community conversations helped identify barriers to access to health care, community strengths, and health concerns. They also helped the MHC leaders develop programming. METHODS: The community-based participatory research approach guided five community conversations conducted (N = 51 participants) from 2018 to 2019. Participants provided input on their personal experiences with a) existing facilitators and barriers to health, b) priority health issues and needs, and c) recommendations for MHC program development. RESULTS: Barriers to health care access were identified, as were many community strengths. Recommendations directly informed MHC program development and implementation, including availability of services at no cost, mammogram referrals, mental health screening, eye exams, and nutrition counseling. CONCLUSIONS: This project highlights the importance of collaboration between academic partners and communities to inform health care programs and the implementation of a MHC based on community voice and input.

The validity of self-rated alcohol susceptibility in predicting alcohol use in early adolescents in Latin America.

BACKGROUND: The measurement of substance use susceptibility was first conceived as part of the preparatory stage that precedes youth smoking initiation and is defined as the lack of a firm commitment not to smoke in the future. Despite being a consistent and validated predictor of smoking initiation, there has been little research on whether susceptibility can predict alcohol use. This study assessed the validity of an adapted alcohol susceptibility measure to predict alcohol consumption among early adolescent students in Argentina and Mexico who had not previously consumed alcohol. METHODS: A school-based longitudinal study was conducted among first-year students in 33 secondary schools in Argentina and 57 in Mexico. The baseline sample included 1504 never-drinker adolescents in Argentina and 5264 in Mexico, of whom 1055 and 3540, respectively, completed a follow-up survey one and a half years later. Logistic regression with school as a random effect was used to estimate the adjusted odds ratios for the transitions from never-drinker to ever-drinker, current drinker, and binge drinker. RESULTS: At baseline, 34% and 23.6% of adolescent never-users in Argentina and Mexico, respectively, were susceptible to alcohol. After controlling for other known predictors of alcohol use initiation, alcohol susceptibility was positively associated with ever-drinking (OR = 3.23, 95% CI 2.38-4.36 in Argentina, OR = 1.73, 95% CI 1.43-2.10 in Mexico), current drinking (OR = 2.41, 95% CI 1.71-3.4 in Argentina, OR = 1.77, 95% CI 1.37-2.28 in Mexico), and binge drinking (OR = 2.27, 95% CI 1.78-2.91 in Argentina, OR = 1.89, 95% CI 1.32-1.99 in Mexico). CONCLUSIONS: The susceptibility measure adapted for use with alcohol appears valid for identifying individuals or groups at risk of drinking initiation and problematic drinking among early adolescents in Argentina and Mexico.

DHA Supplementation during Pregnancy in Women with Obesity Normalizes IGF2R Levels in the Placenta of Male Newborns.

Introduction: Insulin-like growth factor receptor 2 (IGF2R) regulates placental nutrient transport, and its soluble form is related to obesity in adults. If the placental expression of IGF2R is altered in women with obesity is unknown. Whether maternal supplementation with docosahexaenoic acid (DHA), a polyunsaturated fatty acid with anti-inflammatory properties, has a modulatory role in IGF2R's function has not been elucidated. We hypothesized that maternal obesity (Ob) would be associated with alterations in placental IGF2R expression, which may be prevented with DHA supplementation during pregnancy. Methods: At delivery, we obtained placentas from women with Ob (BMI ≥ 30 kg/m2, n = 17), Ob supplemented with 800 mg/day of DHA during pregnancy (Ob + DHA, n = 13), and normal-weight women (Nw, BMI ≥ 18.5 ≤ 24.9 kg/m2, n = 14). The IGF2R mRNA and protein were determined by RT-PCR and western blotting, respectively. Moreover, we quantified the gene expression of molecules that modulate the IGF2R function in the extracellular domain, such as TACE/ADAM17, PLAU, and IGF2. Mann-Whitney and Kruskal-Wallis nonparametric tests were used to compare results between two or three groups accordingly. Results: The IGF2R levels in the Ob placentas of the male offspring were higher than in the Nw group. The DHA supplementation prevented this effect, suggesting an unknown relationship between IGF2R-Ob-DHA in placental tissues. Conclusion: We report, for the first time, that DHA supplementation during pregnancy in women with obesity normalizes the increased IGF2R levels in male placentas, reducing the risk of adverse outcomes related to the IGF2/IGF2R system in male newborns.