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.

Genetic risk for attention-deficit/hyperactivity disorder predicts cognitive decline and development of Alzheimer's disease pathophysiology in cognitively unimpaired older adults.

Attention-deficit/hyperactivity disorder (ADHD) persists in older age and is postulated as a risk factor for cognitive impairment and Alzheimer's Disease (AD). However, these findings rely primarily on electronic health records and can present biased estimates of disease prevalence. An obstacle to investigating age-related cognitive decline in ADHD is the absence of large-scale studies following patients with ADHD into older age. Alternatively, this study aimed to determine whether genetic liability for ADHD, as measured by a well-validated ADHD polygenic risk score (ADHD-PRS), is associated with cognitive decline and the development of AD pathophysiology in cognitively unimpaired (CU) older adults. We calculated a weighted ADHD-PRS in 212 CU individuals without a clinical diagnosis of ADHD (55-90 years). These individuals had baseline amyloid-ß (Aß) positron emission tomography, longitudinal cerebrospinal fluid (CSF) phosphorylated tau at threonine 181 (p-tau181), magnetic resonance imaging, and cognitive assessments for up to 6 years. Linear mixed-effects models were used to test the association of ADHD-PRS with cognition and AD biomarkers. Higher ADHD-PRS was associated with greater cognitive decline over 6 years. The combined effect between high ADHD-PRS and brain Aß deposition on cognitive deterioration was more significant than each individually. Additionally, higher ADHD-PRS was associated with increased CSF p-tau181 levels and frontoparietal atrophy in CU Aß-positive individuals. Our results suggest that genetic liability for ADHD is associated with cognitive deterioration and the development of AD pathophysiology. Findings were mostly observed in Aß-positive individuals, suggesting that the genetic liability for ADHD increases susceptibility to the harmful effects of Aß pathology.

Trajectory of maternal depression and parasomnias.

Maternal depressive symptoms are associated with poorer sleep quality in their children. Although parasomnias can occur at any age, this group of sleep disorders is more common in children. The aim of this study was to assess whether maternal depression trajectories predict parasomnias at the age of 11 years. Data were from a Birth Cohort of 4231 individuals followed in the city of Pelotas, Brazil. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) at 12, 24, and 48 months, and 6 and 11 years postpartum. Maternal depression trajectories were calculated using a group-based modelling approach. Information on any parasomnias (confused arousals, sleepwalking, night terrors, and nightmares) was provided by the mother. Five trajectories of maternal depressive symptoms were identified: chronic-low (34.9%), chronic-moderate (41.4%), increasing (10.3%), decreasing (8.9%), and chronic-high (4.4%). The prevalence of any parasomnia at the age of 11 years was 16.8% (95% confidence interval [CI] 15.6%-18.1%). Confusional arousal was the most prevalent type of parasomnia (14.5%) and varied from 8.7% to 14.7%, 22.9%, 20.3%, and 27.5% among children of mothers at chronic-low, moderate-low, increasing, decreasing, and chronic-high trajectories, respectively (p < 0.001). Compared to children from mothers in the chronic-low trajectory, the adjusted prevalence ratio for any parasomnia was 1.58 (95% CI 1.29-1.94), 2.34 (95% CI 1.83-2.98), 2.15 (95% CI 1.65-2.81), and 3.07 (95% CI 2.31-4.07) among those from mothers in the moderate-low, increasing, decreasing, and chronic-high trajectory groups, respectively (p < 0.001). In conclusion, parasomnias were more prevalent among children of mothers with chronic symptoms of depression.

Changes in splenic tissue and immune response profile of Schistosoma mansoni infected mice submitted to chronic ethanol intake.

In Schistosoma mansoni infection, the spleen is one of the organs affected, causing its enlargement (splenomegaly). Intake of ethanol through alcoholic beverages can cause spleen atrophy and interfere with immune activity. To gain knowledge of this association on the spleen and on the immune response profile, male mice were used as an experimental model. These animals were divided into four groups: C. control; EC. uninfected/ethanol gavage; I. infected; and IE. infected/ethanol gavage. Groups I and IE were infected with about 100 cercariae (BH strain) of S. mansoni and in the fifth week of infection, gavage 200 µL/day/animal of 18 % ethanol was started for 28 consecutive days. At the end of the gavage (9th week of infection) all animals were euthanized. The spleen was removed and longitudinally divided in two parts. After histological processing, the sections were stained with H&E and Gomori's Reticulin for histopathological and stereological analyses, white pulp morphometry and quantification of megakaryocytes. The other fragment was macerated (in laminar flow) and the cell suspension, after adjusting the concentration (2 × 106), was plated to obtain cytokines produced by spleen cells that were measured by flow cytometry (Citometric Bead Array). Histopathological and quantitative analyzes in the spleen of the IE group showed an increase in the number of trabeculae and megakaryocytes, a decrease in reticular fibers, as well as important organizational changes in the white pulp and red pulp. Due to the decrease in the levels of cytokines measured and the result of the calculation of the ratio between the IFN-y and IL-10 cytokines (p = 0.0079) of the infected groups, we suggest that ethanol decreased the inflammatory and anti-inflammatory response generated by the infection (group IE, the production of cytokines was significantly decreased (p < 0.01). These changes demonstrate that ethanol ingestion interferes with some parameters of experimental S. mansoni infection, such as changes in splenic tissue and in the pattern of cytokine production.

Bilateral Peters' anomaly, aniridia and Wilms tumour (WAGR syndrome) in monozygotic twins.

AIM: This study reports the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins subsequently diagnosed with Wilms tumour (WAGR syndrome). METHODS: Two monozygotic female twins were referred at age 2 months with bilateral corneal opacity. A diagnosis of Peters' anomaly associated to aniridia was made in both eyes of both twins. Physical examination and ultrasonography were carried out at 12 months of age to explore the possibility of WAGR-related anomalies, specifically Wilms tumour. DNA were isolated and subjected to whole exome sequencing. RESULTS: Peters' anomaly associated to aniridia in both eyes as well as bilateral Wilms tumour in both children were diagnosed. Exome analyses showed a large heterozygous deletion encompassing 6 648 473 bp in chromosome 11p13, using Integrative Genomics Viewer and AnnotSV software. CONCLUSION: WAGR syndrome is a rare contiguous gene deletion syndrome with a greater risk of developing Wilms tumour associated with Peters' anomaly and congenital aniridia. However, co-occurrence of both anomalies was rarely reported in twins, and never in both eyes of monozygotic twins. Here, we report the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins with WAGR syndrome.

Early risk factors for conduct problem trajectories from childhood to adolescence: the 2004 Pelotas (BRAZIL) Birth Cohort.

Conduct problems are associated with an increased risk of a wide range of physical, mental, and social problems. However, there is still uncertainty about how early risk factors differentiate different developmental patterns of conduct problems and whether findings replicate across diverse social contexts. We aimed to identify developmental trajectories of conduct problems, and test early risk factors, in the 2004 Pelotas Birth Cohort in Brazil. Conduct problems were measured at ages 4, 6, 11, and 15 years from caregiver reports on the Child Behaviour Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ). Conduct problem trajectories were estimated using group-based semi-parametric modeling (n = 3938). Multinomial logistic regression was used to examine associations between early risk factors and conduct problem trajectories. We identified four trajectories: three with elevated conduct problems, including early-onset persistent (n = 150; 3.8%), adolescence-onset (n = 286; 17.3%), and childhood-limited (n = 697; 17.7%), and one with low conduct problems (n = 2805; 71.2%). The three elevated conduct problem trajectories were associated with a wide range of sociodemographic risk factors, prenatal smoking, maternal mental health, harsh parenting, childhood trauma, and child neurodevelopmental risk factors. Early-onset persistent conduct problems were particularly associated with trauma, living without a father figure, and attention difficulties. The four trajectories of conduct problems from ages 4 to 15 years in this Brazilian cohort have similar longitudinal patterns to those identified in high-income countries. The results confirm previous longitudinal research and developmental taxonomic theories on the etiology of conduct problems in a Brazilian sample.

IFITM3 rs12252 polymorphism association with COVID-19 severity and mortality in a Brazilian sample: an update and a meta-analysis.

This study investigated the association between the IFITM3 rs12252 polymorphism and the severity and mortality of COVID-19 in hospitalized Brazilian patients. A total of 102 COVID-19 patients were included, and the outcomes of interest were defined as death and the need for mechanical ventilation. Genotypes were assessed using Taqman probes. No significant associations were found between the rs12252 polymorphism and COVID-19 outcomes in the original sample, both for death and the need for mechanical ventilation. A meta-analysis, incorporating previous studies that used death as a severity indicator, revealed no association in the allelic and C-recessive models. However, due to the rarity of the T allele and its absence in the sample, further replication studies in larger and more diverse populations are needed to clarify the role of rs12252 in COVID-19 prognosis.

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.

Women's multi-partner behavior, multi-partner fertility, and pregnancy outcomes: findings from the 2004 Pelotas Birth Cohort.

STUDY QUESTION: Do women with multi-partner fertility or multi-partner behavior conceive more often than women with a single partner? SUMMARY ANSWER: Women with multi-partner behavior conceived more frequently and had more children than non-multi-partner women and multi-partner fertility women. WHAT IS KNOWN ALREADY: Some women experience having biological children with more than one partner: those women are considered as multi-partner fertility. Women with multi-partner fertility have more children and are substantially less likely to have planned their first birth. Individuals with multi-partner fertility become parents at a younger age, largely with unintended first births, and often do so outside of marriage, compared to parents with two or more children from only one partner. Unmarried women, particularly, are at greater risk of having unintended births. Studies are still scarce and there is a need to assess the contribution of women's multi-partners fertility and multi-partner behavior to family composition, particularly in low- and middle-income countries. STUDY DESIGN, SIZE, DURATION: This longitudinal birth cohort study evaluated 1215 mothers whose children belonging to the 2004 Pelotas Birth Cohort were their first pregnancy, and who attended the perinatal, 48-month, 6-year, and 11-year follow-ups. Information was obtained from responses to a questionnaire. The number of years at risk of having children was treated as the exposure, and woman's multi-partner behavior and multi-partner fertility, dichotomized as 'Yes' or 'No', were considered endogenous treatment variables. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from mothers with a first pregnancy, and with information available from the perinatal, 48-month, 6-year, and 11-year follow-ups, were evaluated. The exposures studied were women's multi-partner behavior and multi-partner fertility (i.e. conceiving/giving birth), and the outcomes evaluated were the number of pregnancies, the number of children currently alive, and experience of unintended pregnancies from the birth of the child belonging to the 2004 birth cohort until 11 years later. Crude and adjusted risk ratios (RRs) were estimated through Poisson regression with endogenous treatment effects, robust standard errors, and their respective 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: Multi-partner behavior women had 16% (RR 1.16; 95% CI: 1.08-1.25) and 11% (RR 1.11; 95% CI 1.03-1.19) greater risk of having a new pregnancy and having more children alive, respectively, than those with non-multi-partner behavior. Women with multi-partner fertility had a 23% (RR 1.23; 95% CI: 1.11-1.37) and 20% (RR 1.20; 95% CI: 1.08-1.33) higher risk of having a new pregnancy and having more children alive, respectively, than single-partner fertility mothers. Women who had multiple partners (i.e. behavior), as well as those with multi-partner fertility, showed a lesser proportion of unintended pregnancies when compared to the non-multi-partner ones (34.08%; 95% CI: 28.12-40.60 vs 36.17%; 95% CI: 31.93-40.63), compared to their counterparts' single partners fertility (33.16%; 95% CI: 26.83-40.17 vs 36.26%; 95% CI: 31.85-40.92), although these findings were not statistically significant. LIMITATIONS, REASONS FOR CAUTION: The mothers who were not included in the study owing to missing data for some of the follow-up had 5-11 years of education, a low socio-economic level, and were younger, thus the number of pregnancies may be underestimated because these groups presented a high number of pregnancies and children alive. We did not have information about the complete woman's conjugal history. Therefore, misclassification error of the exposure may be present and, consequently, the measures of association may be underestimated. Furthermore, this study was not truly representative of the Pelotas study female population. WIDER IMPLICATIONS OF THE FINDINGS: In this study of multi-partner behavior and fertility, women who have multiple partners may be less likely to get married and have a stable partner. Compared to single-partner women, multi-partner fertility and multi-partner behavior women may predominantly become pregnant for the purpose of having children, rather than accidentally. STUDY FUNDING/COMPETING INTEREST(S): This article is based on data from the study 'Pelotas Birth Cohort, 2004' conducted by the Postgraduate Program in Epidemiology at the Universidade Federal de Pelotas, with the collaboration of the Brazilian Public Health Association (ABRASCO). From 2009 to 2013, the Wellcome Trust supported the 2004 birth cohort study. The World Health Organization, National Support Program for Centers of Excellence (PRONEX), Brazilian National Research Council (CNPq), Brazilian Ministry of Health, and Children's Pastorate supported previous phases of the study, and also was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance Code 001. The authors declare that the supported agencies have no role in any step of performing this study. No conflicts of interest exist. TRIAL REGISTRATION NUMBER: N/A.

BDNF Levels According to Variations in the CACNA1C Gene: Sex-Based Disparity.

The CACNA1C gene encodes the pore-forming alpha-1c subunit of L-type voltage-gated calcium channels. The calcium influx through these channels regulates the transcription of the brain-derived neurotrophic factor (BDNF). Polymorphisms in this gene have been consistently associated with psychiatric disorders, and alterations in BDNF levels are a possible biological mechanism to explain such associations. Here, we sought to investigate the effect of the CACNA1C rs1006737 and rs4765913 polymorphisms and their haplotypes on serum BDNF concentration. We further aim to investigate the regulatory function of these SNPs and the ones linked to them. The study enrolled 641 young adults (362 women and 279 men) in a cross-sectional population-based survey. Linear regression was used to test the effects of polymorphisms and haplotypes on BDNF levels adjusted for potential confounders. Moreover, regulatory putative functional roles were assessed using in silico approach. BDNF levels were not associated with CACNA1C polymorphisms/haplotype in the total sample. When the sample was stratified by sex, checking the effect of polymorphisms on men and women separately, the A-allele of rs4765913 was associated with lower BDNF levels in women compared with the TT genotype (p = 0.010). The AA (rs1006737-rs4765913) haplotype was associated with BDNF levels in opposite directions regarding sex, with lower levels of BDNF in women (p = 0.040) compared to those without this haplotype, while with higher levels in men (p = 0.027). These findings were supported by the presence of regulatory marks only on the male fetal brain. Our results suggest that the BDNF levels regulation may be a potential mechanism underpinning the association between CACNA1C and psychiatric disorders, with a differential role in women and men.

Chronic rhinosinusitis with nasal polyps does not harbor KRAS, BRAF, and EGFR mutations.

BACKGROUND: Chronic rhinosinusitis is a chronic inflammation of the nasal mucosa and nasal polyps are present in ~25%-30% of cases (chronic rhinosinusitis with nasal polyps [CRSwNP]). CRSwNP is associated with significant morbidity and decreased quality of life, making it clinically important. Inflammation leads to DNA damage and DNA mutations occur in some inflammatory diseases. Notably, mutations in KRAS, BRAF, and EGFR have been reported in different human benign and malignant neoplastic lesions. In addition, KRAS mutations have also been reported in non-neoplastic tissues under chronic inflammatory conditions. Importantly, KRAS mutations have been reported in oncocytic sinonasal papillomas and sinonasal squamous cell carcinoma associated with oncocytic sinonasal papilloma and EGFR mutations have been reported in sinonasal adenocarcinoma, inverted sinonasal papilloma, and sinonasal squamous cell carcinoma associated with inverted sinonasal papilloma. The molecular pathogenesis of nasal polyps remains unclear. Therefore, the present study aimed to investigate the presence of KRAS, BRAF, and EGFR pathogenic mutations in CRSwNP. METHODS: Fourteen chronic rhinosinusitis-associated nasal polyp samples were direct sequenced, targeting KRAS exons 2, 3, and 4 (encompassing important hotspot mutations, including codons 12, 13, 61 and 146), BRAF exons 11 and 15, and EGFR exons 19 and 20. RESULTS: No pathogenic mutations were detected in the sequenced regions of KRAS, BRAF, and EGFR genes. CONCLUSION: This finding suggests that mutations in these genes are not a frequent event in CRSwNP, and, if they occur, they might represent marginal events at best.

Temperament traits mediate the relationship between CACNA1C polymorphisms and bipolar disorder in cisgender women.

The influence of temperament traits on bipolar disorder (BD) has been investigated. Both temperament traits and BD are partially genetically determined and seem to be influenced by variations in the CACNA1C gene. These variations presented a significant interactive effect with biological sex, although studies that evaluate this relationship are scarce. Here, we assessed the mediation effect of temperament traits on the relationship between two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) and BD according to sex. This is a cross-sectional study consisting of 878 Caucasian individuals (508 women and 370 men), aged 18-35, enrolled in a population-based study in the city of Pelotas, Southern Brazil. BD diagnosis was evaluated using the clinical interview MINI 5.0, and temperament traits were assessed via the application of the Affective and Emotional Composite Temperament Scale (AFECTS). Mediation models were tested using the modeling tool PROCESS (version 3.3) for SPSS. Bootstrapping-enhanced mediation analyses in women indicated that traits anger (39%) and caution (27%) mediated the association between the rs4765913 SNP and BD, while traits volition (29%), anger (35%), and caution (29%) mediated the association between the AA haplotype (rs1006737-rs4765913) and the BD. No effect was encountered for cisgender men. Our model revealed that paths from CACNA1C SNPs to BD are mediated by specific temperament traits in women, reinforcing the definition of temperament traits as endophenotypes.

Impact of covid-19 pandemic over depressive symptoms among mothers from a population-based birth cohort in southern brazil.

PURPOSE: Our aim was to assess the impact of COVID-19 on depressive symptoms among mothers from a population-based birth cohort in Pelotas, Southern Brazil. METHODS: A subgroup of mothers from the Pelotas 2004 Birth Cohort was assessed pre-pandemic (November,2019 to March,2020) and mid-pandemic (August-December,2021). In both follow-ups, depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Pre-pandemic (T1) and pandemic-related predictors (T2) were analyzed. Prevalence of depression (EPDS score ≥ 13) at T1 and T2 were compared with chi-square test. Changes in EPDS from T1 to T2 were estimated by multivariate latent change score modelling. RESULTS: 1,550 women were assessed. Prevalence of depression increased 38.1% (from 18.9% at T1 to 26.1% at T2) (p < 0.001). At T1, higher schooling, higher family income and being employed or working were related to lower EPDS, whereas being beneficiary of a cash transfer program and a larger number of people living in the household predicted higher EPDS. The deterioration of ones' own perception of quality of overall health (ß = 0.191; SE = 0.028; p < 0.001) and worst family financial situation due to the pandemic (ß = 0.083; SE = 0.024; p = 0.001) predicted the increase in EPDS from T1 to T2. CONCLUSION: Almost two years after the beginning of the pandemic, the prevalence of depressive symptoms among the women was higher than before the pandemic. The deterioration of ones' own perception of quality of overall health and worst family financial situation due to the pandemic are proxies for the effect of COVID-19 pandemic (the true exposure of interest) in the women mental health.

Association of 3p21.31 Locus (CXCR6 and LZTFL1) with COVID-19 Outcomes in Brazilian Hospitalyzed Subjects.

The 3p21.31 locus has been associated with severe COVID-19 prognosis in GWAS studies. Here, we evaluated whether three polymorphisms (LZTFL1 rs10490770, CXCR6 rs2234355 and rs2234358) in the reported locus were associated with the need for mechanical ventilation, hospitalization length and death in 102 COVID-19 hospitalized Brazilian subjects. No genetic association was found with the need for mechanical ventilation and hospitalization length. CXCR6 rs2234355 was associated with mortality under the codominance model, with carriers of the A/A genotype having a greater chance of death than A/G (OR: 10.5; 95% CI: 1.55-70.76). Our results further suggest that the CXCR6 genetic variant contributes to COVID-19 outcomes.

Associations of hospitalisation - admission, readmission and length to stay - with multimorbidity patterns by age and sex in adults and older adults: the ELSI-Brazil study.

BACKGROUND: Although the association between multimorbidity (MM) and hospitalisation is known, the different effects of MM patterns by age and sex in this outcome needs to be elucidated. Our study aimed to analyse the association of hospitalisations' variables (occurrence, readmission, length of stay) and patterns of multimorbidity (MM) according to sex and age. METHODS: Data from 8.807 participants aged ≥ 50 years sourced from the baseline of the Brazilian Longitudinal Study of Ageing (ELSI-Brazil) were analysed. Multimorbidity was defined as ≥ 2 (MM2) and ≥ 3 (MM3) chronic conditions. Poisson regression was used to verify the association between the independent variables and hospitalisation according to sex and age group. Multiple linear regression models were constructed for the outcomes of readmission and length of stay. Ising models were used to estimate the networks of diseases and MM patterns. RESULTS: Regarding the risk of hospitalisation among those with MM2, we observed a positive association with male sex, age ≥ 75 years and women aged ≥ 75 years. For MM3, there was a positive association with hospitalisation among males. For the outcomes hospital readmission and length of stay, we observed a positive association with male sex and women aged ≥ 75 years. Network analysis identified two groups that are more strongly associated with occurrence of hospitalisation: the cardiovascular-cancer-glaucoma-cataract group stratified by sex and the neurodegenerative diseases-renal failure-haemorrhagic stroke group stratified by age group. CONCLUSION: We conclude that the association between hospitalisation, readmission, length of stay, and MM changes when sex and age group are considered. Differences were identified in the MM patterns associated with hospitalisation according to sex and age group.

Maternal depression trajectories in childhood, subsequent maltreatment, and adolescent emotion regulation and self-esteem: the 2004 Pelotas birth cohort.

This study aimed to examine the impact of maternal depressive symptoms trajectories on 15-year-old adolescents' self-esteem and emotion regulation and test the mediating role of child maltreatment in this association. The 2004 Pelotas Birth Cohort is an ongoing cohort study originally comprised of 4231 live births in a southern Brazilian city. We examined a subsample of 1949 adolescents at age 15 years. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. Trajectories of maternal depression from 3 months until the 11-year follow-up were calculated using a group-based modeling approach. Child maltreatment at age 11 years was measured using the parent-report version of the Parent-Child Conflict Tactics Scale. Adolescent outcomes at age 15 years were assessed by the self-report version of the Rosenberg Self-esteem Scale and the Emotion Regulation Index for Children and Adolescents. Path model analysis was conducted using a structural equation modeling framework in Mplus software. All maternal depression trajectories were negatively associated with offspring self-esteem and emotion regulation compared to the reference group (low depression trajectory). There was a significant indirect effect of maternal depression trajectories on emotion regulation mediated via child maltreatment. No evidence of moderation by sex was found for any pathway. The effects of maternal depression on adolescents' emotion regulation are partly mediated by child maltreatment at age 11.

Association between preterm infant size at 1 year and ADHD later in life: data from 1993 and 2004 Pelotas Birth Cohorts.

The objective of this study is to examine the association between preterm infants' size at 1 year and attention-deficit/hyperactivity disorder (ADHD) assessed categorically and dimensionally in childhood and adolescence. We studied infants born < 37 weeks' gestation from two Brazilian birth cohorts (n = 653). ADHD was evaluated using the Development and Well-Being Assessment (DAWBA) interview at the age of 6 years in one cohort and by a structured interview according to DSM-5 criteria at 18 years in the other one. The presence of child attention difficulties was measured by the Strengths and Difficulties Questionnaire (SDQ) at 6 and 11 years in the 2004 and 1993 cohorts, respectively. We estimated associations of weight, length, head circumference, and BMI z-scores at 1-year chronological age with ADHD using Poisson Regression Model; and with attention difficulties using Linear Regression, adjusting for covariates. Mean birth weight was 2500 g and gestational age was 34.5 weeks. The aggregated ADHD prevalence in the two cohorts was 2.7%, and the median score for attention difficulties was 3.0. We found that increased head circumference at 1 year was associated with a lower risk of ADHD diagnosis (RR = 0.7, 95% CI 0.4, 0.9; p = 0.04 per standard deviation difference) and with fewer dimensional attention symptoms. In sensitivity analysis with other mental disorders, head circumference was associated with depression, but not with anxiety. Our findings emphasize poor head growth in the first year of life as a potential determinant of attentional difficulties in the preterm infant population.

ADHD in childhood predicts BMI and body composition measurements over time in a population-based birth cohort.

BACKGROUND/OBJECTIVES: Obesity has been reported as an attention-deficit hyperactivity disorder (ADHD) comorbidity. So far, few studies have aimed to explore the potential causal relationship between ADHD and obesity, as well as used other measures of body composition like fat-free mass (FFM) and fat mass (FM) as measures of obesity. This study aimed to test the association between ADHD and body composition (body mass index [BMI] and others) and to evaluate the potential causal relationship with obesity. SUBJECTS/METHODS: Data from the 1993 Pelotas (Brazil) birth cohort at age 11-, 15-, 18-, and 22-year follow-up was used. We performed a cross-lagged panel model (CLPM) analysis between ADHD symptoms and BMI to explore the causal relationship between both traits. Finally, we tested whether ADHD, inattention, and hyperactivity symptom scales were associated with BMI, FM, and FFM at 22 years. RESULTS: In the CLPM, higher ADHD scores at age 11 predicted higher BMI at age 15 (ß = 0.055, 95% CI [0.037; 0.073]). ADHD symptoms at age 11 was also associated with a decrease in the FFM (ß = -0.16, 95% CI [-0.28; -0.05]), and an increase in the BMI (ß = 0.17, 95% CI [0.10; 0.23]) and FM (ß = 0.17, 95% CI [0.06; 0.29]) at 22 years. At 22 years of age, ADHD was associated with FFM and FM. Moreover, an increase in BMI was observed with an increase in several symptoms of ADHD in general (ß = 0.06, 95% CI [0.004; 0.12]), and hyperactivity symptoms (ß = 0.15, 95% CI [0.05; 0.25]). CONCLUSION: ADHD at 11 years predicted a higher BMI at 15 years, and body fat composition in adulthood, suggesting higher scores on ADHD symptoms in early life may be a critical point for body composition in early adulthood. The hyperactivity symptoms may play an important role in the BMI increase.

Adenoid ameloblastoma harbors beta-catenin mutations.

Adenoid ameloblastoma is a very rare benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. We assessed CTNNB1 (beta-catenin) exon 3 mutations in a cohort of 11 samples of adenoid ameloblastomas from 9 patients. Two of the 9 patients were female and 7 male and in 7/9 patients the tumors occurred in the maxilla. Tumors of 4 of these 9 patients harbored CTNNB1 mutations, specifically p.Ser33Cys, p.Gly34Arg, and p.Ser37Phe. Notably, for one patient 3 samples were analyzed including the primary tumour and two consecutive recurrences, and results were positive for the mutation in all three tumors. Therefore, 6/11 samples tested positive for the mutation. In the 6 mutation-positive samples, ghost cells were present in only 2/6, indicating beta-catenin mutations are not always revealed by ghost cell formation. Dentinoid matrix deposition was observed in 5/6 mutation-positive samples and clear cells in all 6 cases. None of the cases harbored either BRAF or KRAS mutations. Beta-catenin immunoexpression was assessed in the samples of 8 patients. Except for one wild-type case, all cases showed focal nuclear expression irrespective of the mutational status. Together with the absence of BRAF mutation, the detection of beta-catenin mutation in adenoid ameloblastomas supports its classification as a separate entity, and not as a subtype of ameloblastoma. The presence of this mutation may help in the diagnosis of challenging cases.

Association between multimorbidity and hospitalization in older adults: systematic review and meta-analysis.

BACKGROUND: Multimorbidity is defined as the presence of multiple chronic conditions in the same individual. Multimorbidity is more prevalent in older adults and can lead to several adverse health outcomes. METHODS: We systematically reviewed evidence from observational studies to verify the association between multimorbidity and hospitalization in older adults. Furthermore, we also aimed to identify whether it changes according to gender, advanced age, institutionalization, and wealth of the country of residence. We searched the PubMed, Embase and Scopus databases from December 2020 to April 2021. The analysed outcomes were as follows: hospitalization, length of stay and hospital readmission. RESULTS: Of the 6,948 studies identified in the databases, 33 were included in this review. From the meta-analysis results, it was found that multimorbidity, regardless of the country's wealth, was linked to hospitalization in older adults (OR = 2.52, CI 95% = 1.87-3.38). Both definitions of multimorbidity, ≥2 (OR = 2.35, 95% CI = 1.34-4.12) and ≥3 morbidities (OR = 2.52, 95% CI = 1.87-3.38), were associated with hospitalization. Regardless of gender, multimorbidity was associated with hospitalization (OR = 1.98, 95% CI = 1.67-2.34) and with readmission (OR = 1.07, 95% CI = 1.04-1.09). However, it was not possible to verify the association between multimorbidity and length of stay. CONCLUSIONS: Multimorbidity was linked to a higher hospitalization risk, and this risk was not affected by the country's wealth and patient's gender. Multimorbidity was also linked to a higher hospital readmission rate in older adults. PROSPERO Registration (Registration number: CRD42021229328).