Hair cortisol measurement: A systematic review of current practices and a proposed checklist for reporting standards.

Summarising hair cortisol concentration (HCC) methodology may provide much-needed data toward protocol standardisation to maximise future comparability of findings across studies. We searched five electronic databases, reviewing 11,716 publications focused on protocols previously used to measure hair cortisol. Our aim was to determine the frequency with which each procedure was reported in the literature. We then conducted a meta-analysis of the HCC results and proposed a checklist for reporting methodological procedures related to HCC. Using pre-selected key terms, we searched for population-based, non-experimental studies reporting HCC outcomes published up to November 2023. Eighty-seven analytical samples were included in the qualitative analysis and 28 in the quantitative analysis. The analyzed studies predominantly included children (≤10 years; 45.4 %) and mainly involved participants from European populations (72.6 %). There was significant variation in hair sample collection procedures across the studies. Most used hair samples up to 3 cm in length (92 %), with around one-third employing either milled (33.3 %) or minced (29.9 %) as grinding methods. For quantification, LC-MS was the most common method (47.1 %), followed by ELISA (24.1 %). Meta-analysis showed significant variability in the mean HCC observed. Meta-regression showed no association between differences in methodology and HCC. In conclusion, the absence of a standardized protocol in HCC research may result in procedural variability, making it difficult to compare findings across studies. Many published studies lacked sufficient detail in describing their methods. To address this, we propose a checklist of reporting guidelines for measurement procedures related to HCC.

Perinatal Factors and Their Association with Early-Adulthood Suicidal Behavior in a Brazilian Birth Cohort.

BACKGROUND: The objectives of this study were to investigate the relationship between perinatal risk factors and suicidal ideation and attempts in young adults in Pelotas, Brazil. METHODS: The data were collected from the 1993 Pelotas Birth Cohort study. Every pregnant woman who gave birth in one of the hospitals in Pelotas Brazil in 1993 was invited to participate in the study. The current study uses perinatal data collected in 1993, and follow-ups at ages 18 and 22. The primary outcome was lifetime suicide attempts with past month suicide ideation a secondary outcome. The association between perinatal predictors and suicidal ideation or lifetime suicide attempts was investigated using hierarchical logistic regression. FINDINGS: There was an analytic sample size of 3493. The perinatal factors association with lifetime suicide attempts were sex (OR = 2.25 CI: 1.76-2.89), paternal education at birth (OR = 0.60, 95%CI: 0.36-0.99), maternal education (9-11 years OR = 2.81, 95%CI: 1.41-5.59, & 0-8 years OR = 2.21, 95%CI: 1.07-4.58), support from friends or neighbors at birth (OR = 0.36 95%CI: 0.17-0.77), and maternal smoking during pregnancy (OR = 1.41, 95%CI: 1.10-1.79). Patterns of associations were broadly similar with suicidal ideation. Interactions between sex and the perinatal factors paternal education, maternal education, smoking and support from friends were assessed and found to be not significant. CONCLUSION: Several factors during the perinatal period are associated with risk of lifetime suicide attempts and ideation in young adults in Brazil. Early-life factors associated with suicide-related concerns in early adulthood were similar to those observed in studies from high-income settings.

Perinatal factors associated with suicidal behaviour were determined using data from upper-middle income setting.Maternal education, and maternal smoking are associated with risk of lifetime suicide attempts.Perinatal factors associated with suicidal ideation were similar to those of suicide attempts, including sex, maternal education, and maternal smoking.

CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors.

For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) with CTLA4 inhibitors and PD-1 or PD-L1 inhibitors (hereafter, PD-(L)1 inhibitors) is associated with higher rates of anti-tumour activity and immune-related toxicities, when compared with treatment with PD-(L)1 inhibitors alone. However, there are currently no validated biomarkers to identify which patients will benefit from dual ICB1,2. Here we show that patients with NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical benefit from dual ICB with the PD-L1 inhibitor durvalumab and the CTLA4 inhibitor tremelimumab, but not from durvalumab alone, when added to chemotherapy in the randomized phase III POSEIDON trial3. Unbiased genetic screens identified loss of both of these tumour suppressor genes as independent drivers of resistance to PD-(L)1 inhibition, and showed that loss of Keap1 was the strongest genomic predictor of dual ICB efficacy-a finding that was confirmed in several mouse models of Kras-driven NSCLC. In both mouse models and patients, KEAP1 and STK11 alterations were associated with an adverse tumour microenvironment, which was characterized by a preponderance of suppressive myeloid cells and the depletion of CD8+ cytotoxic T cells, but relative sparing of CD4+ effector subsets. Dual ICB potently engaged CD4+ effector cells and reprogrammed the tumour myeloid cell compartment towards inducible nitric oxide synthase (iNOS)-expressing tumoricidal phenotypes that-together with CD4+ and CD8+ T cells-contributed to anti-tumour efficacy. These data support the use of chemo-immunotherapy with dual ICB to mitigate resistance to PD-(L)1 inhibition in patients with NSCLC who have STK11 and/or KEAP1 alterations.

Prevalence and Risk Factors of Gang Membership in a Brazilian Birth Cohort.

Importance: There is no longitudinal evidence on risk factors for gang membership in low- and middle-income countries, despite organized crime groups posing major challenges, including high homicide rates in Latin America. Furthermore, adverse childhood experiences (ACEs) have been largely overlooked in gang-related research worldwide. Objectives: To examine the associations of ACEs up to 15 years of age with past-year gang membership at 18 years of age and to compare crime and criminal justice involvement between gang members and non-gang members. Design, Setting, and Participants: This cohort study assessed children from the 1993 Pelotas (Brazil) Birth Cohort-an ongoing population-based, prospective study. Assessments were undertaken perinatally (1993) and when the children were ages 11 (2004), 15 (2008), 18 (2011), and 22 (2015) years. All children born in 1993 were eligible (N = 5265), and 5249 (99.7%) were enrolled at birth. The study sample (N = 3794 [72.1%]) included those with complete data on ACEs. Data analyses were conducted from February to August 2024. Exposures: Twelve ACEs were assessed up to 15 years of age via child self-report and/or maternal report, including physical neglect, physical abuse, emotional abuse, sexual abuse, domestic violence, maternal mental illness, parental divorce, ever being separated from parents, parental death, poverty, discrimination, and neighborhood fear. These experiences were examined using a single adversity approach, cumulative risk, and latent classes. Main Outcomes and Measures: The main outcome was past-year gang membership at 18 years of age, assessed via self-report and analyzed using multivariate imputation. Results: Of 3794 participants, 1964 (51.8%) were female and 1830 (48.2%) were male, and 703 (18.5%) were Black, 2922 (77.0%) were White, and 169 (4.5%) were coded as "other" race or ethnicity (no additional details are available to further disaggregate the other category). On the basis of the imputed data, 1.6% (SE, 0.2 percentage points) of participants reported gang membership at 18 years of age. Physical abuse (odds ratio [OR], 2.76; 95% CI, 1.27-5.98), emotional abuse (OR, 2.76; 95% CI, 1.51-5.02), domestic violence (OR, 3.39; 95% CI, 1.77-6.48), parental divorce (OR, 2.04; 95% CI, 1.17-3.54), and separation from parents (OR, 3.13; 95% CI, 1.54-6.37) were associated with an increased risk of gang membership. A dose-response association was observed, with 4 or more ACEs increasing the risk (OR, 8.86; 95% CI, 2.24-35.08). In latent class analysis, the class with child maltreatment and household challenges was associated with a higher risk of gang membership than the low-adversities class (OR, 7.10; 95% CI, 2.37-21.28). There was no robust evidence that children exposed to household challenges and social risks were at increased risk of gang membership (OR, 2.28; 95% CI, 0.46-11.25). Conclusions and Relevance: In this prospective cohort study, ACEs, particularly child maltreatment and family conflict, were associated with gang involvement when examined individually, cumulatively, and as clusters in a high-crime environment in Brazil. These findings underscore the value of integrating the ACE framework into gang-related research and the potential to reduce gang-related crime by reducing ACEs.

Impact of polarization pulling on optimal spectrometer design for stimulated Brillouin scattering microscopy.

Brillouin spectroscopy has become an important tool for mapping the mechanical properties of biological samples. Recently, stimulated Brillouin scattering (SBS) measurements have emerged in this field as a promising technology for lower noise and higher speed measurements. However, further improvements are fundamentally limited by constraints on the optical power level that can be used in biological samples, which effectively caps the gain and signal-to-noise ratio (SNR) of SBS biological measurements. This limitation is compounded by practical limits on the optical probe power due to detector saturation thresholds. As a result, SBS-based measurements in biological samples have provided minimal improvements (in noise and imaging speed) compared with spontaneous Brillouin microscopy, despite the potential advantages of the nonlinear scattering process. Here, we consider how a SBS spectrometer can circumvent this fundamental trade-off in the low-gain regime by leveraging the polarization dependence of the SBS interaction to effectively filter the signal from the background light via the polarization pulling effect. We present an analytic model of the polarization pulling detection scheme and describe the trade-space unique to Brillouin microscopy applications. We show that an optimized receiver design could provide >25× improvement in SNR compared to a standard SBS receiver in most typical experimental conditions. We then experimentally validate this model using optical fiber as a simplified test bed. With our experimental parameters, we find that the polarization pulling scheme provides 100× higher SNR than a standard SBS receiver, enabling 100× faster measurements in the low-gain regime. Finally, we discuss the potential for this proposed spectrometer design to benefit low-gain spectroscopy applications such as Brillouin microscopy by enabling pixel dwell times as short as 10 µs.

The Parenting and Family Adjustment Scales (PAFAS) questionnaire: psychometric qualities of the parenting scale in two large Brazilian birth cohorts.

Objective: Analyse the psychometric properties of the Portuguese version of the PAFAS (Parenting and Family Adjustment Scales) parenting scale, using data from two large Brazilian birth cohorts. Methods: The original PAFAS parenting scale, which consists of 18 items (parental inconsistency 5 items, coercive parenting 5 items, positive encouragement 3 items, and parent-child relationship 5 items) was applied in two Brazilian birth cohorts in Pelotas (ages 4 [n = 4010] and 6-7 [n = 3867]) and Rio Grande (age 3 [n = 992]). Confirmatory factor analysis was conducted, and internal consistency assessed, as well as construct validity in relation to maternal depression measured on the Edinburgh Postnatal Depression Scale. Results: The model with a structure of 4 subscales showed that the global scale of parenting on the PAFAS had a good fit, but certain items did not fit well on sub-scales and were removed (2 items from parental inconsistency, 1 from coercive parenting, and 1 from positive encouragement). The original form of the parent-child relationship sub-scale was maintained. Considering the total PAFAS parenting score, we found that mothers with maternal depression had a higher likelihood of more problematic parental practices than mothers without depression. Conclusions: A revised 14-item PAFAS parenting scale has good psychometric properties and we encourage its use in Brazilian populations.

Underreporting of violence against women: an analysis of two data sources. / Subnotificação de violência contra as mulheres: uma análise de duas fontes de dados.

This article aims to estimate the underreporting of violence against women (VAW) in the Notifiable Diseases Information System (SINAN), based on data from the National Survey of Health (NSH), in Brazil and subnational units (SU). This work was an ecological study using SINAN and NSH, both from 2019. In SINAN, reports of sexual, physical, and psychological VAW, aged 18 years or older, were selected. In the NSH, women of the same age group who reported psychological, physical, or sexual violence, and who had sought health care due to consequences of the violence were selected. SINAN underreporting was calculated in reference to the NSH's estimated population, for Brazil and each SU. Underreporting of VAW in Brazil was 98.5%, 75.9%, and 89.4% for psychological, physical, and sexual violence, respectively. The North and Northeast states presented the lowest reporting rates among the states. VAW in Brazil is highly underreported by the health sector, showing the need for adequate training of health professionals to recognize situations of violence and raise awareness of the importance of reporting.

O objetivo do artigo é estimar a subnotificação da violência contra as mulheres (VCM) no Sistema de Informação de Agravos de Notificação (SINAN) a partir de dados da Pesquisa Nacional de Saúde (PNS), para o Brasil e as unidades federadas (UF). Estudo ecológico utilizando o SINAN e a PNS, ambos do ano de 2019. No SINAN, foram selecionadas as notificações de casos de violências sexual, física e psicológica contra mulheres com idade igual ou superior a 18 anos. Na PNS, foram selecionadas as mulheres da mesma faixa etária com relato de violência psicológica, física ou sexual que tenham procurado atendimento em saúde em razão de consequência relacionada à violência vivida. Calculou-se a subnotificação do SINAN a partir da estimativa da população da PNS para o Brasil e cada UF. A subnotificação de VCM no Brasil foi de 98,5%, 75,9% e 89,4% para as violências psicológica, física e sexual, respectivamente. Os estados do Norte e Nordeste apresentaram os menores índices de notificação entre as UF. A VCM no Brasil apresenta grande subnotificação no setor saúde, demonstrando a necessidade de capacitação dos profissionais de saúde para o reconhecimento de situações de violência e conscientização da importância da notificação.

Gluten-Dependent Activation of CD4+ T Cells by MHC Class II-Expressing Epithelium.

BACKGROUND & AIMS: Intestinal epithelial cell (IEC) damage is a hallmark of celiac disease (CeD); however, its role in gluten-dependent T-cell activation is unknown. We investigated IEC-gluten-T-cell interactions in organoid monolayers expressing human major histocompatibility complex class II (HLA-DQ2.5), which facilitates gluten antigen recognition by CD4+ T cells in CeD. METHODS: Epithelial major histocompatibility complex class II (MHCII) was determined in active and treated CeD, and in nonimmunized and gluten-immunized DR3-DQ2.5 transgenic mice, lacking mouse MHCII molecules. Organoid monolayers from DR3-DQ2.5 mice were treated with or without interferon (IFN)-γ, and MHCII expression was evaluated by flow cytometry. Organoid monolayers and CD4+ T-cell co-cultures were incubated with gluten, predigested, or not by elastase-producing Pseudomonas aeruginosa or its lasB mutant. T-cell function was assessed based on proliferation, expression of activation markers, and cytokine release in the co-culture supernatants. RESULTS: Patients with active CeD and gluten-immunized DR3-DQ2.5 mice demonstrated epithelial MHCII expression. Organoid monolayers derived from gluten-immunized DR3-DQ2.5 mice expressed MHCII, which was upregulated by IFN-γ. In organoid monolayer T-cell co-cultures, gluten increased the proliferation of CD4+ T cells, expression of T-cell activation markers, and the release of interleukin-2, IFN-γ, and interleukin-15 in co-culture supernatants. Gluten metabolized by P aeruginosa, but not the lasB mutant, enhanced CD4+ T-cell proliferation and activation. CONCLUSIONS: Gluten antigens are efficiently presented by MHCII-expressing IECs, resulting in the activation of gluten-specific CD4+ T cells, which is enhanced by gluten predigestion with microbial elastase. Therapeutics directed at IECs may offer a novel approach for modulating both adaptive and innate immunity in patients with CeD.

Harsh parenting trajectories from childhood through adolescence and socioemotional competences at age 18: 2004 Pelotas Birth Cohort Study.

BACKGROUND: Limited research has explored the course of harsh parenting practices throughout childhood and adolescence and its impact on socioemotional competences from a longitudinal perspective. This study examined the association between harsh parenting trajectories and socioemotional competences at age 18. METHODS: Data from the 2004 Pelotas (Brazil) Birth Cohort study, originally comprising 4231 live births, were used. Harsh parenting was measured using the parent-report version of the Parent-Child Conflict Tactics Scale at ages 6, 11, 15 and 17 years, and trajectories were identified using a group-based modelling approach. Socioemotional competences were emotion regulation, assessed by the Emotional Regulation Index for Children and Adolescents; self-esteem, measured by the self-report Rosenberg Self-esteem Scale; prosocial behaviour and peer relationship problems, both assessed by the Strengths and Difficulties Questionnaire. Multivariate linear and Poisson regression models were applied to examine the effects of harsh parenting trajectories on socioemotional competences, adjusting for confounding variables. RESULTS: We identified three trajectories: a "low harsh parenting" trajectory (49.7 %), a "moderate harsh parenting" (44.7 %), and a "high harsh parenting" trajectory (5.6 %). Compared to those belonging to the low harsh parenting trajectory group, adolescents who experienced either a moderate or high harsh parenting trajectory exhibited lower scores in emotion regulation, self-esteem, and prosocial behaviour scales, along with higher scores of peer relationships problems. LIMITATIONS: Data on harsh parenting at 15 and 17 years were available only for a sub-sample. CONCLUSIONS: Our study extends the evidence of the adverse effects of persistent harsh parenting on socioemotional competences during adolescence.

Laboratory Testing for Celiac Disease: Clinical and Methodological Considerations.

BACKGROUND: Celiac disease (CeD) has an estimated prevalence of 1%-3%. The classical clinical presentation is malabsorption, but now patients may present with more subtle symptoms such as constipation, osteoporosis, or iron deficiency anemia. Children may also present with poor growth.CeD has a strong genetic component, and high-risk groups include first-degree relatives with CeD, patients with co-existing autoimmune diseases, and patients with chromosomal aberrations. CONTENT: Diagnostic tests for CeD include duodenal histology, serology, and genetic testing. Duodenal histology has traditionally been the gold standard of diagnosis. However, serological tests, especially IgA tissue transglutaminase antibodies (TTG-IgA), are widely used and diagnostic algorithms are based primarily on TTG-IgA as a starting point. Human leukocyte antigen typing may also be incorporated to determine genetic risk for CeD. Guidelines for children endorse biopsy avoidance provided high levels of TTG-IgA, with diagnostic accuracy being comparable to duodenal biopsy. Confirmation may be achieved by identifying IgA endomysial antibodies in a separate blood sample. Subjects with low positive TTG-IgA levels and subjects with IgA deficiency need a biopsy to establish a diagnosis of CeD. The clinical follow-up of CeD usually includes a repeat TTG-IgA examination. In adults, healing may be delayed or incomplete, and a rare consequence of refractory celiac disease is transformation to enteric T-cell lymphoma. SUMMARY: Laboratory testing, in particular TTG-IgA, plays a central role in the diagnosis and has an accuracy comparable to histology. Diagnostic algorithms utilizing laboratory testing are critical for the development of novel strategies to improve diagnosis.

Predictors of early child development for screening pregnant women most in need of support in Brazil.

Background: Home visiting programmes can support child development and reduce inequalities, but failure to identify the most vulnerable families can undermine such efforts. We examined whether there are strong predictors of poor child development that could be used to screen pregnant women in primary health care settings to target early interventions in a Brazilian population. Considering selected predictors, we assessed coverage and focus of a large-scale home visiting programme named Primeira Infância Melhor (PIM). Methods: We undertook a prospective cohort study on 3603 children whom we followed from gestation to age four years. We then used 27 potential socioeconomic, psychosocial, and clinical risk factors measurable during pregnancy to predict child development, which was assessed by the Battelle Developmental Inventory (BDI) at the age of four years. We compared the results from a Bonferroni-adjusted conditional inference tree with exploratory linear regression and principal component analysis (PCA), and we conducted external validation using data from a second cohort from the same population. Lastly, we assessed PIM coverage and focus by linking 2015 cohort data with PIM databases. Results: The decision tree analyses identified maternal schooling as the most important variable for predicting BDI, followed by paternal schooling. Based on these variables, a group of 214 children who had the lowest mean BDI (BDI = -0.48; 95% confidence interval (CI) = -0.63, -0.33) was defined by mothers with ≤5 years and fathers with ≤4 years of schooling. Maternal and paternal schooling were also the strongest predictors in the exploratory analysis using regression and PCA, showing linear associations with the outcome. However, their capacity to explain outcome variance was low, with an adjusted R2 of 5.3% and an area under the receiver operating characteristic curve of 0.62 (95% CI = 0.60, 0.64). External validation showed consistent results. We also provided an online screening tool using parental schooling data to support programme's targeting. PIM coverage during pregnancy was low, but the focus was adequate, especially among families with longer enrolment, indicating families most in need received higher dosage. Conclusions: Information on maternal and paternal schooling can improve the focus of home visiting programmes if used for initial population-level screening of pregnant women in Brazil. However, enrolment decisions require complementary information on parental resources and direct interactions with families to jointly decide on inclusion.

Life-course influences of poverty on violence and homicide: 30-year Brazilian birth cohort study.

BACKGROUND: Homicide is the leading cause of death among young people in Latin America, one of the world's most violent regions. Poverty is widely considered a key cause of violence, but theories suggest different effects of poverty, depending on when it is experienced in the life-course. Longitudinal studies of violence are scarce in Latin America, and very few prospective data are available worldwide to test different life-course influences on homicide. METHODS: In a prospective birth cohort study following 5914 children born in southern Brazil, we examined the role of poverty at birth, in early childhood, and in early adulthood on violence and homicide perpetration, in criminal records up to age 30 years. A novel Structured Life Course Modelling Approach was used to test competing life-course hypotheses about 'sensitive periods', 'accumulation of risk', and 'downward mobility' regarding the influence of poverty on violence and homicide. RESULTS: Cumulative poverty and poverty in early adulthood were the most important influences on violence and homicide perpetration. This supports the hypothesis that early adulthood is a sensitive period for the influence of poverty on lethal and non-lethal violence. Results were replicable using different definitions of poverty and an alternative outcome of self-reported fights. CONCLUSION: Cumulative poverty from childhood to adulthood was an important driver of violence and homicide in this population. However, poverty experienced in early adulthood was especially influential, suggesting the importance of proximal mechanisms for violence in this context, such as unemployment, organized crime, drug trafficking, and ineffective policing and justice systems.

Photonic next-generation reservoir computer based on distributed feedback in optical fiber.

Reservoir computing (RC) is a machine learning paradigm that excels at dynamical systems analysis. Photonic RCs, which perform implicit computation through optical interactions, have attracted increasing attention due to their potential for low latency predictions. However, most existing photonic RCs rely on a nonlinear physical cavity to implement system memory, limiting control over the memory structure and requiring long warm-up times to eliminate transients. In this work, we resolve these issues by demonstrating a photonic next-generation reservoir computer (NG-RC) using a fiber optic platform. Our photonic NG-RC eliminates the need for a cavity by generating feature vectors directly from nonlinear combinations of the input data with varying delays. Our approach uses Rayleigh backscattering to produce output feature vectors by an unconventional nonlinearity resulting from coherent, interferometric mixing followed by a quadratic readout. Performing linear optimization on these feature vectors, our photonic NG-RC demonstrates state-of-the-art performance for the observer (cross-prediction) task applied to the Rössler, Lorenz, and Kuramoto-Sivashinsky systems. In contrast to digital NG-RC implementations, we show that it is possible to scale to high-dimensional systems while maintaining low latency and low power consumption.

First-line Osimertinib for Lung Cancer With Uncommon EGFR Exon 19 Mutations and EGFR Compound Mutations.

Introduction: Up to 20% of EGFR-mutated NSCLC cases harbor uncommon EGFR mutations, including atypical exon 19 and compound mutations. Relatively little is known about the efficacy of osimertinib in these cases. Methods: Patients treated with first-line osimertinib for NSCLC with rare EGFR exon 19 (non E746_A750del) or compound mutations were included. Response assessment and time to progression were determined using Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Kaplan-Meier analyses were used to estimate progression-free survival (PFS), time to treatment discontinuation (TTD), and overall survival (OS). Results: Thirty-seven patients with NSCLC harboring an atypical EGFR exon 19 mutation or compound mutation were treated with first-line osimertinib at Johns Hopkins from 2016 to 2021. Overall response rate (ORR) was 76% and median PFS, TTD, and OS were 13 months (95% confidence interval [CI]: 10-15), 22 months (95% CI: 17-32) and 36 months (95% CI, 29-48), respectively. Among atypical exon 19 mutations (n = 25), ORR was 80%, median PFS was 12 months (95% CI: 10-15), median TTD was 19 months (95% CI: 17-38), and median OS was 48 months (95% CI: 25-not reached). Compound mutations (n = 12) had an ORR of 67%, median PFS of 14 months (95% CI: 5-22), median TTD of 26 months (95% CI: 5-36), and median OS of 36 months (95% CI: 20-46). Twelve patients (32%) continued first-line osimertinib after local therapy for oligoprogression. Conclusions: Osimertinib exhibited favorable outcomes for rare EGFR exon 19 and compound mutations. The heterogeneity in outcomes among these groups of tumors with similar mutations underscores the need for continued reporting and further study of outcomes among rare variants to optimize management for each patient.

Effects of Two Early Parenting Programmes on Child Aggression and Risk for Violence in Brazil: a Randomised Controlled Trial.

Violence is a major public health problem globally, with the highest rates in low- and middle-income countries (LMICs) in the Americas and southern Africa. Parenting programmes in high-income countries can diminish risk for violence, by reducing risk factors such as child aggression and harsh parenting, and increasing protective factors such as child cognitive development and school readiness. However, there is critical need to identify low-cost programmes with replicable benefits that work in real-world LMICs contexts. A three-arm, randomised, single-blind trial evaluated effects of two low-cost, group-based parenting programmes recommended for LMICs (ACT: Raising Safe Kids; DBS: dialogic book-sharing) on child aggression (primary outcome), child development, parenting, maltreatment, and stress. Participants were 369 children with medium-high levels of aggression (mean age 3.1 years at baseline) in poor households. Interventions were implemented in city health and education services in southern Brazil. Maternal reports, filmed observations, child tasks, and hair cortisol were assessed at baseline, 1-month post-intervention, and 8-month follow-up. Intention-to-treat analyses compared each of ACT and DBS with a control group. Three hundred sixty-eight (99.7%) participants completed follow-up assessments 8 months after the interventions. There was no effect of ACT (standardised mean difference, SMD 0.11, 95% CI - 0.05, 0.27) or DBS (SMD 0.05, 95% CI - 0.11, 0.21) on the primary outcome of child aggression. ACT reduced harsh parenting behaviour post-intervention (SMD - 0.23; 95% CI - 0.46, - 0.01), but not at follow-up. DBS improved book-sharing practices at both time points (e.g., maternal sensitivity at follow-up SMD 0.33; 95% CI 0.08, 0.57). There were no benefits of either programme for other parenting, child development, or stress outcomes. Two parenting programmes in Brazil had small effects on parenting practices but did not reduce child aggression or several other important risk/protective factors for violence. Effective early interventions that reduce violence in real-world LMIC settings are highly desirable but may be challenging to achieve.

Gender Division of Housework and Intimate Partner Violence Among Mothers of Toddlers During the COVID-19 Pandemic: Findings from the 2019 Rio Grande (Brazil) Birth Cohort.

During the COVID-19 pandemic, we evaluated the association between gender division of housework and intimate partner violence (IPV) victimization in a population-based cohort of mothers. We collected data on psychological, physical, and sexual IPV using an adapted version of the World Health Organization Violence Against Women instrument and division of housework using a validated questionnaire. We used logistic regression to calculate adjusted odds ratios. We found that in mothers who reported an unequal gender division of housework (higher load), the odds of suffering psychological, physical, or sexual IPV were higher during the first and second years of the pandemic.

Gene - maltreatment interplay in adult ADHD symptoms: main role of a gene-environment correlation effect in a Brazilian population longitudinal study.

Childhood maltreatment correlates with attention-deficit/hyperactivity disorder (ADHD) in previous research. The interaction between ADHD genetic predisposition and maltreatment's impact on ADHD symptom risk remains unclear. We aimed to elucidate this relationship by examining the interplay between a polygenic score for ADHD (ADHD-PGS) and childhood maltreatment in predicting ADHD symptoms during young adulthood. Using data from the 2004 Pelotas (Brazil) birth cohort comprising 4231 participants, we analyzed gene-environment interaction (GxE) and correlation (rGE). We further explored rGE mechanisms through mediation models. ADHD symptoms were assessed at age 18 via self-report (Adult Self Report Scale - ASRS) and mother-reports (Strength and Difficulties Questionnaire - SDQ). The ADHD-PGS was derived from published ADHD GWAS meta-analysis. Physical and psychological child maltreatment was gauged using the Parent-Child Conflict Tactics Scale (CTSPC) at ages 6 and 11, with a mean score utilized as a variable. The ADHD-PGS exhibited associations with ADHD symptoms on both ASRS (ß = 0.53; 95% CI: 0.03; 1.03, p = 0.036), and SDQ (ß = 0.20; 95% CI: 0.08; 0.32, p = 0.001) scales. The total mean maltreatment score was associated with ADHD symptoms using both scales [(ßASRS = 0.51; 95% CI: 0.26;0.77) and (ßSDQ = 0.24; 95% CI: 0.18;0.29)]. The ADHD-PGS was associated with total mean maltreatment scores (ß = 0.09; 95% CI: 0.01; 0.17; p = 0.030). Approximately 47% of the total effect of ADHD-PGS on maltreatment was mediated by ADHD symptoms at age 6. No evidence supported gene-environment interaction in predicting ADHD symptoms. Our findings underscore the significant roles of genetics and childhood maltreatment as predictors for ADHD symptoms in adulthood, while also indicating a potential evocative mechanism through gene-environment correlation.

The Economic Iceberg of Celiac Disease: More Than the Cost of Gluten-Free Food.

Celiac disease (CeD) is a chronic autoimmune disorder of global relevance, with the potential for acute and long-term complications. However, the economic burden of CeD is rarely considered and largely thought of as limited to the cost of gluten-free food. Fortunately, recent research has shed light on the various societal costs of CeD across the health care continuum. This article summarizes the current evidence on the economic impacts of CeD, which suggest that the societal economic burden of CeD stretches beyond the cost of gluten-free food. This review provides ample evidence of larger but hidden costs related to excess health care use for complications and comorbidities, as well as reduced productivity. Although significant advances are expected in the management of CeD, their effect on the economic burden of CeD remain uncertain. The aim of this review was to inform stakeholders across society and contribute to improved policies to support patients with CeD.

The effects of a large-scale home visiting programme for child development on use of health services in Brazil.

Partnership between early childhood development interventions and primary health care services can help catalyse health care uptake by socially vulnerable families. This study aimed to assess the real-life effects of a large-scale home visiting programme [Primeira Infância Melhor (PIM)] in Brazil on the use of preventive (prenatal visits, well child visits, dentist visits and vaccination) and recovery (emergency room visits and hospitalization) health services. A quasi-experiment nested in a population-based birth cohort study was conducted. The intervention group was firstly defined as all children enrolled in PIM up to age 6 months, and afterwards stratified between those enrolled during pregnancy or after birth up to 6 months. Children receiving PIM were matched with controls on propensity scores based on 27 confounders to estimate effects on health service use from prenatal to age 2 years. Double adjustment was applied in outcome Quasi-Poisson regressions. No evidence was found for effects of PIM starting anytime up to 6 months (262 pairs), or for the children enrolled only after birth (133 pairs), on outcomes occurring after age 6 months. When the programme started during pregnancy (129 pairs), there was a 13% higher prevalence of adequate prenatal visits (prevalence ratio = 1.13; 95% confidence interval 1.01-1.27), but no effect on use of any other health service. Sensitivity analyses suggested longer participation in the programme with reduced visitor turnover might improve its impact on prenatal visits. Integration between PIM and primary health care was not adequate to affect overall patterns of contacts with health services. Nevertheless, prenatal home visits showed potential to increase health service contact during a sensitive period of development, indicating the need to start such programmes before birth, when there is more time for maternal care, and family engagement in a network of services is facilitated.