UNASSIGNED: Childhood family environment is associated with adulthood health behaviours and cardiovascular health, but limited data are available concerning the relationship between childhood family environment and adulthood haemodynamic determinants of blood pressure. We evaluated how childhood family environment predicts adulthood systemic haemodynamics.
UNASSIGNED: The sample came from the Cardiovascular Risk in Young Finns Study (n=1554-1620). Childhood family environment (1980) was assessed with four cumulative risk scores: socioeconomic family risk, risky emotional family atmosphere, stressful life events, and parents\' risky health behaviours. Haemodynamic outcomes in 2007 (participants being 30-45 year-olds) included stroke volume index, systemic vascular resistance index, cardiac output index and heart rate. Analyses were adjusted for childhood (1980) cardiovascular risk factors (high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, insulin, body mass index and systolic blood pressure); and adulthood (2007) health behaviours (alcohol consumption, smoking, physical activity); and finally for adulthood cardiovascular risk factors.
UNASSIGNED: When adjusted for age and sex, high socioeconomic family risk predicted lower stroke volume index (P=0.001), higher heart rate (P=0.001) and higher systemic vascular resistance index (P=0.030). These associations remained after controlling for childhood cardiovascular covariates or adulthood health behaviours (P⩽0.02 for all) but diluted after controlling for adulthood cardiovascular risk factors. The other childhood cumulative risk scores (stressful life events, risky emotional atmosphere, or parents\' risky health behaviour) did not predict adulthood haemodynamic outcomes.
UNASSIGNED: High childhood socioeconomic family risk predicted adulthood haemodynamic outcomes independently of childhood cardiovascular risk factors and adulthood health behaviours, while other childhood psychosocial adversities were not associated with cardiovascular function in adulthood.

BACKGROUND: Bilirubin has antioxidant properties, and elevated levels within the normal range have been associated with improved lung function and decreased risk of asthma in adults, but studies of young children are scarce. Here, we investigate associations between bilirubin in early life and respiratory health endpoints during preschool age in two independent birth cohorts.
METHODS: Bilirubin metabolites were assessed at ages 0.5, 1.5, and 6 years in COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) and ages 1, 3, and 6 years in the VDAART (The Vitamin D Antenatal Asthma Reduction Trial) cohort. Meta-analyses were done to summarize the relationship between levels of bilirubin metabolites and asthma, infections, lung function, and allergic sensitization until age 6 across the cohorts. Interaction with the glucuronosyltransferase family 1 member A1 (UGT1A) genotype encoding for an enzyme in the bilirubin metabolism was explored, and metabolomics data were integrated to study underlying mechanisms.
RESULTS: Increasing bilirubin (Z,Z) at ages 1.5-3 years was associated with an increased risk of allergic sensitization (adjusted relative risk [aRR] = 1.85 [1.20-2.85], p = 0.005), and age 6 bilirubin (Z,Z) also showed a trend of association with allergic sensitization at age 6 (aRR = 1.31 [0.97-1.77], p = 0.08), which showed significant interaction for the age 6 bilirubin (Z,Z)xUGT1A genotype. Further, increasing bilirubin (E,E), bilirubin (Z,Z), and biliverdin at ages 1.5-3 years was associated with a lower forced expiratory volume at age 6 (aRR range = 0.81-0.91, p < 0.049) but without a significant interaction with the UGT1A genotype (p interactions > 0.05). Network analysis showed a significant correlation between bilirubin metabolism and acyl carnitines. There were no associations between bilirubin metabolites and the risk of asthma and infections.
CONCLUSIONS: Bilirubin metabolism in early life may play a role in childhood respiratory health, particularly in children with specific UGT1A genotypes.
BACKGROUND: The Lundbeck Foundation (Grant no R16-A1694), The Ministry of Health (Grant no 903516), Danish Council for Strategic Research (Grant no 0603-00280B), and The Capital Region Research Foundation have provided core support to the COPSAC research center. This project has received funding from the European Research Council (ERC) under the European Union\'s Horizon 2020 research and innovation programme (grant agreement No. 946228). The Vitamin D Antenatal Asthma Reduction Trial (VDDART, ClinicalTrials.gov identifier: NCT00920621) was supported by grant U01HL091528 from NHLBI, U54TR001012 from the National Centers for Advancing Translational Sciences (NCATS). Metabolomics work by VDAART was supported by the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL123915 and R01HL141826. S.T.W. was supported by R01HL091528 from the NHLBI, UG3OD023268 from Office of The Director, National Institute of Health, and P01HL132825 from the NHLBI.

UNASSIGNED: Solid pseudopapillary neoplasm (SPN) of the pancreas in children is a rare tumor with low malignant potential. Some tumors, however, behave aggressively. There is very little literature on managing these variants, especially in children. We share our experience of managing large and recurrent SPN and explore the clinicopathological findings correlating to the risk of recurrence.
UNASSIGNED: This is a retrospective study of children treated for SPN between 2012 and 2022 at a tertiary care center in India. The clinicopathological features and management strategies in these children were evaluated.
UNASSIGNED: Sixteen children with SPN were treated during this period (88% of girls). The median age of presentation was 12 years (interquartile range [IQR]: 9-14). All children presented with abdominal pain. Computed tomography gave a definitive diagnosis in 81% of cases. The tumor predominantly involved the head of the pancreas (n = 9, 56%). Eight of nine children classified as high-grade (HG) malignant had a benign course. One child had a recurrence of the tumor 4 years after the initial resection and further recurrence on chemotherapy. She required radiation therapy in addition to reoperation following which she was disease free for 77 months. The overall median follow-up was 46 months (IQR: 18-72 months).
UNASSIGNED: Complete resection of the tumor provides a cure in most patients with SPN. Recurrent tumors require a multi-modality approach. Long-term survival is good. There is a need for clear definitions of the components within the WHO criteria for HG malignancy.

UNASSIGNED: Diarrhea is a significant health problem in the Third World. Identification of the pathogen that causes diarrhea is vital for measures to prevent and control this disease. There are also very few reports of diarrhea in Sudan. Our study aimed to determine the Prevalence of specific protozoan pathogens ( Entamoeba histolytica, Cryptosporidium parvum., and Giardia spp) in children in Khartoum, Sudan.
UNASSIGNED: We conducted a cross-sectional survey among children under five years of age who were hospitalized with acute diarrhea between April and December 2014. Diarrheal stool samples were collected and E. histolytica, C. parvum, and Giardia spp were examined using multiplex real-time PCR.
UNASSIGNED: Four hundred and thirty-seven children with acute diarrheawere included in this study; the higher Prevalence of diarrhea was in the age less than ≤ 2 years old (403,92.2%). The male-to-female ratio in this study was 1:1.7. infection with intestinal parasite was found in 155 (35.5%) cases, and co-infection was detected in 16 (10.3%) cases. Giardia spp(18.8%) and C. parvum (15.8 %) were the most frequently identified parasites, followed by E. histolytica (0.9). The parasite infection rate was highest and lowest in the under 2-year-old group (92.3%) and the 2-4-year-old group (7.3%). The infection rate was higher in boys (67.1%) than in girls (32.9%). The incidence of protozoan infection was higher in the rainy season (August to December) (92.2%), corresponding with that in the dry Season (April to June). (7.8%).
UNASSIGNED: Our present study demonstrated the high prevalence of Giardia spp and C. parvum in children with diarrhea in the Khartoum region and the usefulness of the multiplex real-time method in disclosing pathogenic protozoal agents. Our result highlighted the necessity of developing intervention measurement and control strategies to deal with childhood parasitic diarrhea in this region.

OBJECTIVE: Cannabis legalization has triggered an increase in prenatal cannabis use. Given that tobacco is commonly co-used with cannabis, determining outcomes associated with prenatal cannabis and tobacco co-exposure is crucial. While literature exists regarding the individual effects of prenatal cannabis and tobacco exposure on childhood behaviour, there is a gap regarding their combined use, which may have interactive effects. Therefore, we investigated whether prenatal cannabis and tobacco co-exposure was associated with greater externalizing and internalizing problems in middle childhood compared to prenatal exposure to either substance alone or no exposure.
METHODS: Baseline data from the Adolescent Brain Cognitive Development (ABCD) Study (collected in children ages 9-11) were used to explore differences in externalizing and internalizing scores derived from the Childhood Behavior Checklist across four groups: children with prenatal cannabis and tobacco co-exposure (CT, n = 290), children with prenatal cannabis-only exposure (CAN, n = 225), children with prenatal tobacco-only exposure (TOB, n = 966), and unexposed children (CTL, n = 8,311). We also examined if the daily quantity of tobacco exposure modulated the effect of cannabis exposure on outcomes.
RESULTS: Adjusting for covariates, a 2 × 2 ANCOVA revealed significant main effects for prenatal cannabis (p = 0.03) and tobacco exposure (p < 0.001), and a significant interaction effect on externalizing scores (p = 0.032); no significant main effects or interactions were found for internalizing scores. However, interactions between daily quantity of cannabis and tobacco exposure significantly predicted both externalizing and internalizing scores (p < 0.01).
CONCLUSIONS: These findings indicate that co-exposure is associated with greater externalizing problems than exposure to either substance alone, which did not differ from each other. Further, greater tobacco exposure may amplify the negative effect of cannabis exposure on both externalizing and internalizing behaviours in children. These findings underscore the need for interventions that target cannabis and tobacco co-use in pregnant women to circumvent their adverse impact on middle childhood behaviour.
Prenatal Cannabis and Tobacco Co-exposure and its Association with Middle Childhood BehavioursPlain Language SummaryGiven the high rates of both cannabis and tobacco use during pregnancy, we explored if their combined use was associated with greater problematic behaviour in 10-year-old children compared to either substance alone or no substance use. We found that children with prenatal co-exposure had greater externalizing behaviours, such as attention problems and aggression, compared to children with prenatal exposure to one of the substances or no exposure. Prenatal co-exposure, cannabis-only exposure and tobacco-only exposure had no effect on childhood internalizing behaviours (e.g., depression, anxiety). However, the amount of tobacco consumed by the mother amplified the negative effect of cannabis on both childhood externalizing and internalizing behaviours. These findings emphasize the need for specialized treatment for cannabis and tobacco co-use in pregnant women to circumvent the adverse impact of these substances on externalizing behaviours in middle childhood.

Purpose: Childhood cancer survivors (CCS) represent a growing population worldwide, and lifelong follow-up care is recommended for most. Once CCS become adults, the transition to adult care is emerging. Today, there is no transition or long-term follow-up care model in the adult setting that clearly outweighs others. We therefore aimed to evaluate the transition to physicians outside the hospital. Methods: In this single-center, cross-sectional, questionnaire-based study, we assessed in 2022 the current follow-up care situation of CCS who already transitioned to physicians outside the hospital (family physicians, pediatricians). We asked CCS about cancer knowledge, worries, self-management skills, and expectations and physicians about their experience with CCS and their needs when caring for CCS. We included physicians where a CCS was transitioned to. We compared the results with CCS transitioned in a hospital setting and used descriptive statistics. Results: Twenty-three CCS responded to the questionnaire (median age at questionnaire of 22 years, median 14 years since diagnosis). Nearly two-thirds reported not being in follow-up care anymore. The cancer knowledge was good, and cancer worries were low. Twenty-eight physicians responded with 21 reporting that they care for CCS. Half of them see CCS for acute problems only. Physicians are open to care for CCS but request the necessary recommendations and would also be available for respective training. Conclusion: Transition to physicians might be an option for selected CCS. However, education and empowerment of CCS early on and education of physicians is urgently needed to prevent loss to follow-up, which may lead to lifelong nonengagement and incorrect perceptions about future health.

Environmental exposures and gene-exposure interactions are the major causes of some diseases. Early-life exposome studies are needed to elucidate the role of environmental exposures and their complex interactions with biological mechanisms involved in childhood health. This study aimed to determine the contribution of early-life exposome to DNA damage and the modifying effect of genetic polymorphisms involved in air pollutants metabolism, antioxidant defense, and DNA repair. We conducted a cohort study in 416 Colombian children under five years. Blood samples at baseline were collected to measure DNA damage by the Comet assay and to determine GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2 genetic polymorphisms. The exposome was estimated using geographic information systems, remote sensing, LUR models, and questionnaires. The association exposome-DNA damage was estimated using the Elastic Net linear regression with log link. Our results suggest that exposure to PM2.5 one year before the blood draw (BBD) (0.83, 95 %CI: 0.76; 0.91), soft drinks consumption (0.94, 0.89; 0.98), and GSTM1 null genotype (0.05, 0.01; 0.36) diminished the DNA damage, whereas exposure to PM2.5 one-week BBD (1.18, 1.06; 1.32), NO2 lag-5 days BBD (1.27, 1.18; 1.36), in-house cockroaches (1.10, 1.00; 1.21) at the recruitment, crowding at home (1.34, 1.08; 1.67) at the recruitment, cereal consumption (1.11, 1.04; 1.19) and H2AX (AG/GG vs. AA) (1.44, 1.11; 1.88) increased the DNA damage. The interactions between H2AX (AG/GG vs. AA) genotypes with crowding and PM2.5 one week BBD, GSTM1 (null vs. present) with humidity at the first year of life, and OGG1 (SC/CC vs. SS) with walkability at the first year of life were significant. The early-life exposome contributes to elucidating the effect of environmental exposures on DNA damage in Colombian children under five years old. The exposome-DNA damage effect appears to be modulated by genetic variants in DNA repair and antioxidant defense enzymes.

BACKGROUND: Prepubertal transgender, nonbinary, and gender-diverse (TGD) children (ie, those asserting gender identity, expressing gender-role behavior outside of culturally defined norms for their sex registered at birth, or both) are presenting in greater numbers to pediatric gender clinics across the United States and abroad. A large subset of TGD children experiences gender dysphoria, that is, distress that arises from the incongruence between gender identity and sex registered at birth. A lack of consensus exists regarding care for prepubertal TGD children due, in part, to a dearth of empirical research on longitudinal developmental trajectories of gender identity, role behavior, and gender dysphoria (when present).
OBJECTIVE: The objective of this National Institutes of Health-funded study is to provide evidence to inform clinical care for prepubertal TGD children by establishing a US longitudinal cohort (N=248) of prepubertal TGD children and their caregivers that is followed prospectively at 6-month intervals across 18 months.
METHODS: At each timepoint, clinical and behavioral data are collected via web-based visit from child and caregiver reporters. Latent class analysis, among other methods, is used to identify subgroups and longitudinally characterize the gender identity and gender-role behavior of TGD children. These models will define longitudinal patterns of gender identity stability and characterize the relationship between TGD classes and mental and behavioral health outcomes, including the moderating role of social gender transition (when present), on these associations.
RESULTS: Baseline data collection (N=248) is complete, and the identification of TGD subgroups based on gender identity and expression using latent class analysis is anticipated in 2024. The completion of all 4 waves of data collection is anticipated in July 2024, coinciding with the start of a no-cost study extension period. We anticipate longitudinal analyses to be completed by winter 2024.
CONCLUSIONS: Through a longitudinal observational design, this research involving prepubertal TGD children and their caregivers aims to provide empirical knowledge on gender development in a US sample of TGD children, their mental health symptomology and functioning over time, and how family initiated social gender transition may predict or alleviate mental health symptoms or diagnoses. The research findings have promise for clinicians and families aiming to ensure the best developmental outcome for these children as they develop into adolescents.
UNASSIGNED: DERR1-10.2196/55558.

BACKGROUND: The Hispanic/Latino population experiences socioeconomic disadvantages across the lifespan. Yet, little is known about the role of these disadvantages in cardiovascular health (CVH). We assessed the association of lifecourse socioeconomic position (SEP) with ideal CVH and change in Hispanic/Latino adults.
RESULTS: We used longitudinal data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Childhood SEP was determined using parental educational attainment. Adult SEP was determined through an index combining participants\' education, occupation, income, and assets at baseline. We classified participants into 4 socioeconomic mobility categories (eg, stable low or high SEP, upward or downward mobility). Using the 4 health factors of the American Heart Association \"Life\'s Essential 8,\" we built a score of ideal CVH at baseline and the 6-year follow-up. Linear mixed-effects models using inverse probability weighting were fitted to assess the main associations. Higher childhood SEP was associated with higher ideal CVH at baseline (β for high school versus high school versus CONCLUSIONS: Although high childhood and adult SEP and socioeconomic mobility were associated with higher levels of ideal CVH, they were not associated with change in ideal-CVH.

UNASSIGNED: Early-life adversities are known to alter drug reward processing in rodents. Despite the well-known link between early adversity and the risk of substance use disorder, few studies have measured how childhood adversity affects human drug reward. Here, we assessed the relationship between historical childhood adversities and responses to single doses of methamphetamine, d-amphetamine or buprenorphine in healthy participants.
UNASSIGNED: Using a secondary analysis approach, we assessed the impact of childhood adversity on drug effects from three randomised, placebo-controlled studies in which healthy volunteers received methamphetamine (20 mg oral; n = 35), d-amphetamine (20 mg oral; n = 54) or buprenorphine (0.2 mg sublingual; n = 35). Ratings of feeling effect, liking, disliking, feeling high and wanting more of the drug were collected 15-210 min post-administration, and heart rate changes were analysed using random-intercept mixed-effect models. The area under the curve from these and previous studies was calculated to visualise the relationship between childhood adversity severity and drug effects.
UNASSIGNED: Greater childhood adversity was associated with reduced feel effects (significant three-way interactions b = -0.07, 95% CI [-0.12, -0.02], p = 0.009), like effects (b = -0.07, 95% CI [-0.13, -0.00], p = 0.038) and feel high (b = -0.06, 95% CI [-0.10, -0.01], p = 0.020) towards the stimulant drugs 90-180 min post-administration.
UNASSIGNED: Childhood adversity was not significantly associated with other subjective or heart rate responses to the drugs. Overall, participants with more childhood adversities reported dampened subjective responses to stimulant drugs, but not to buprenorphine. Future studies should examine the generalisability of these relationships, to identify the mechanisms underlying the link between childhood adversity and drug responsiveness.