Long-term Behavioral Problems Research Articles

How does family functioning contribute to child externalizing and internalizing behavior problems after childhood TBI? Evidence from a prospective cohort study.

Despite a well-documented association between childhood traumatic brain injury and elevated risk for internalizing and externalizing behavior problems, the mechanisms through which family functioning contributes to individual variation in these behavioral outcomes remains poorly understood. This prospective cohort study aimed to assess the respective contribution of family functioning and child emotion regulation (ER) to post-injury behavior problems at 1-year follow-up, with a specific focus on evaluating the role of emotional dysregulation in mediating the effects of familial affective responsiveness and communication on child behavioral outcomes. The study included 129 participants, comprising 86 children with medically confirmed mild-to-severe TBI, identified from consecutive hospital admissions, and 43 typically developing (TD) control children, of similar age and sex. Participants ranged in age from 6 to 15 years (mean age = 11.2 years). Parents completed validated assessments of post-acute family functioning and child emotion regulation difficulties at 6 months post-injury, as well as measures of child behavior problems at 1-year post-injury. Although group differences in internalizing behaviors did not reach statistical significance, the TBI group exhibited significantly higher overall externalizing symptoms and was significantly more likely to display clinically elevated symptoms than TD controls at 1-year post-injury. Compared to TD controls, the TBI group displayed significantly greater ER problems, which mediated the effects of lower familial affective responsiveness and communication on child behavior problems 1-year-post-injury. Evidence for these robust, prospective associations suggests that child emotional dysregulation plays a key role in mediating the effect of post-acute family functioning on long-term behavior problems in children with TBI. Early assessment and screening for relevant risk factors may help identify those children and families who could benefit from therapeutic interventions designed to address emotional dysregulation and mitigate risk for post-injury behavioral problems. Importantly, these findings underscore the value of adopting family-centred care approaches in rehabilitation, where involving families in therapeutic processes and addressing family dynamics may enhance child emotion regulation and improve long-term behavioral outcomes.

B-291 Validation of a Simple Qualitative Immunoassay for 21 Drugs of Abuse in Meconium on a Single Biochip Array

Abstract Background Drugs use during pregnancy is a major social and medical issue, which may lead to significant pre- and post-natal complications, such as preterm birth and newborn mortality. Exposed newborns may have long-term behavioral, cognitive, and developmental problems. Accurate detection of in utero drug exposure is crucial for timely medical intervention for the newborn and the mother. Meconium is the ‘gold standard' matrix for detection of drugs in newborn which reflects drug exposure during pregnancy. This study aims to develop and optimize a clinical assay for simultaneous screening of 21 drugs in meconium using a custom biochip array. Methods Custom biochip array (Randox Laboratories Ltd.) included 21 discrete test regions (DTRs) for amphetamine, methamphetamine, opioids/opiates (targeting morphine, oxymorphone, oxycodone, hydrocodone, 6-monoacetyl morphine, tramadol, buprenorphine, fentanyl, and methadone), phencyclidine (PCP), cocaine (targeting benzoylecgonine), benzodiazepines (targeting oxazepam, lorazepam, and clonazepam), zolpidem, barbiturates (targeting phenobarbital), ethyl glucuronide, methylphenidate, and marijuana metabolite (targeting Delta-9-Carboxy-Tetrahydrocannabinol [THC-COOH]). Patient samples were obtained from the residual meconium samples that had been previously used for other tests. Blank meconium samples were spiked at in-house cutoff, negative and positive assay control levels. All samples were extracted in specimen diluent using Biotage® Lysera and centrifuged. The supernatant was analyzed on a fully automated Randox Evidence+® Analyzer. A robotic arm pipetted 60 µL sample on to a biochip and then the analyzer performed a competitive chemiluminescent immunoassay. The results were generated as relative light units (RLUs). Results The sample results were determined to be “positive” or “negative” based on average RLU of cutoff controls for each analyte on an assay. The intra-assay (CV ≤ 15%) and inter-assay (CV ≤ 18%) precision was 100% agreement for positive and negative controls and there was no observed carryover for any of the analytes. The sample recovery was excellent with minimal to no matrix suppression for all analytes. Accuracy was performed by comparing spiked analyte results from Randox Evidence+® Analyzer with the expected results and all the spiked samples matched (positive or negative). When authentic patient or spiked results were compared with external laboratory test results, some discordant results were obtained. However, the discrepancies could be explained based on the different cutoffs (e.g., the Randox assay had lower cutoffs) or the known assay cross reactivities within the analytes of same class. These deviations did not affect clinical utility of the assay. Conclusions We validated a novel and simple qualitative chemiluminescent immunoassay in meconium using a custom biochip array. Unlike other routine screening/ELISA methods, which require separate assays for detection of similar drug targets, the custom biochip array offers a convenient, rapid and efficient method that utilizes only a single sample preparation for the screening of all 21 drug targets. Therefore, this technology has potential to be utilized as high-throughput screening assay. Like all qualitative assays, the limitation of this test is that all positive results will need to be assessed quantitatively for a definitive interpretation.

Effectiveness of educational interventions for the prevention of lead poisoning in children: a systematic review.

Childhood exposure to lead has severe health consequences including long-term physical, behavioral, and learning problems. Lead poisoning often occurs in the home and persists as a form of environmental injustice, disparately impacting certain children based on factors such as socioeconomic status, immigration status, and race. Because abatement is costly, many prevention programs rely on educational interventions. We conducted a systematic review to assess the effectiveness of educational interventions on reducing blood lead levels (BLL) in children. Following PRISMA-P guidelines, a librarian-guided search strategy incorporated database-specific subject headings and keywords related to lead poisoning and education, and encompassed four databases: Ovid MEDLINE, Scopus, Web of Science Core Collection and CINAHL. Two reviewers screened the results for those that met inclusion criteria (original research, study population of children under 18 years, inclusion of an educational intervention, outcome of BLL). We screened the titles of 2,062 non-duplicate studies, the abstracts of 78 studies, and full texts of 23 articles, resulting in 17 articles that met eligibility criteria. Thirteen studies used multi-pronged interventions, which precluded comprehensive assessment of the effectiveness of the educational component. Interventions that had success in lowering BLL included some notable elements: longevity of intervention, consideration of culture and ethnicity; use of a community or home-based approach; and provision of supplies or assistance with cleaning. Of the four of studies that used solely educational interventions, three were successful in reducing BLL. Among the 12 studies that used a control group, six found their interventions to be successful in reducing BLL. This review found that educational interventions, either alone or as part of a multi-pronged approach, do not consistently reduce BLL in children. However, educational interventions may decrease severity of lead poisoning in children when more robust interventions are not feasible.

The Effectiveness of Teaching Self-regulatory Strategies on Attention Deficit, Social Adjustment, and Self-efficacy in Children With Attention -Deficit/Hyperactivity Disorder

Background and Aims One of the common childhood disorders is attention-deficit hyperactivity disorder, which can be caused by a lack of self-regulation. This study aimed to evaluate the effectiveness of teaching self-regulatory strategies on elementary students’ attention deficit, social adjustment, and self-efficacy in Tehran City, Iran. Methods This quasi-experimental study employed a pre-test-post-test design with a control group. In this research, 100 students with attention-deficit/hyperactivity disorder were selected by cluster sampling from 9-11 years old male elementary schools of District 16, Tehran City, Iran, in the 2018-2019 academic year. They were studied using the Conners questionnaire, attention-deficit questionnaire, general self-efficacy questionnaire, social adjustment questionnaire, and Russell Barkley’s 8-session educational protocol. Results he study’s results demonstrated the effect of self-regulatory strategic teaching on the reduction of attention deficit, increase in social adjustment, and self-efficacy of students in the experimental group compared to the control group (P<0.05). Conclusion Cognitive skills and instructional programs in early life play an essential role in children’s learning and self-regulation improvement. Furthermore, they can reduce the occurrence rate of long-term behavioral problems.

Schools as critical settings for mental and behavioral health efforts in the United States: Key initiatives for substantive impact

In this article we propose that nation-wide investment in mental and behavioral health (MBH) prevention efforts in public schools has the potential for powerful impact on developmental MBH in the United States (U.S.). We first provide an overview of the structure of public school systems in the U.S. Next, we apply the multi-tiered support system (MTSS) public health model to propose three key initiatives for optimal promotion of youth MBH through public schools in the U.S.: (a) universal access to high quality pre-kindergarten, (b) universal evidence-based social and emotional learning across all grades, and (c) universal MBH screening accompanied by tiered targeted and intensive support services. Within each proposed initiative, we summarize the evidence base and consider barriers and facilitators to implementation. We conclude that public schools in the U.S. represent an optimal place to promote children's and adolescents’ MBH in ways that prevent long-term mental and behavioral health problems.

Synaptic and mitochondrial mechanisms behind alcohol-induced imbalance of excitatory/inhibitory synaptic activity and associated cognitive and behavioral abnormalities.

Alcohol consumption during pregnancy can significantly impact the brain development of the fetus, leading to long-term cognitive and behavioral problems. However, the underlying mechanisms are not well understood. In this study, we investigated the acute and chronic effects of binge-like alcohol exposure during the third trimester equivalent in postnatal day 7 (P7) mice on brain cell viability, synapse activity, cognitive and behavioral performance, and gene expression profiles at P60. Our results showed that alcohol exposure caused neuroapoptosis in P7 mouse brains immediately after a 6-hour exposure. In addition, P60 mice exposed to alcohol during P7 displayed impaired learning and memory abilities and anxiety-like behaviors. Electrophysiological analysis of hippocampal neurons revealed an excitatory/inhibitory imbalance in alcohol-treated P60 mice compared to controls, with decreased excitation and increased inhibition. Furthermore, our bioinformatic analysis of 376 dysregulated genes in P60 mouse brains following alcohol exposure identified 50 synapse-related and 23 mitochondria-related genes. These genes encoded proteins located in various parts of the synapse, synaptic cleft, extra-synaptic space, synaptic membranes, or mitochondria, and were associated with different biological processes and functions, including the regulation of synaptic transmission, transport, synaptic vesicle cycle, metabolism, synaptogenesis, mitochondrial activity, cognition, and behavior. The dysregulated synapse and mitochondrial genes were predicted to interact in overlapping networks. Our findings suggest that altered synaptic activities and signaling networks may contribute to alcohol-induced long-term cognitive and behavioral impairments in mice, providing new insights into the underlying synaptic and mitochondrial molecular mechanisms and potential neuroprotective strategies.

Psychological aftereffects experienced by sexually abused children: Psychopathological characteristics revealed by the K-CBCL.

Children who have been sexually abused may experience various short- and long-term psychological sequelae and behavioral problems. This study assessed the mental health of sexually abused children using the Korean-Child Behavior Checklist (K-CBCL) and examined differences from a control group. The participants were 97 children who had been sexually abused and who visited a local Sunflower Center, and 178 control participants. Data were collected via the K-CBCL and analyzed using SPSS version 25.0. T-tests, cross-tabulation, and logistic regression analyses were performed. Scores from the K-CBCL Problem Behavior Syndrome scale were compared between sexually abused children and the control participants. Significant differences were observed between the 2 groups in all the subscales. Compared to the control group, children who were sexually abused showed statistically significant differences in the total problem behavior, internalization, anxiety/depression, withdrawal/depression (withdrawn), somatic symptoms, externalization, rule-breaking behavior (delinquency), aggressive behavior, social immaturity, thought problems, attention problems, and other subscale scores. Sexual violence hurts the overall mental health of children who are abused, including their emotional, behavioral, and social factors. Our findings suggest that multidisciplinary assessment and treatment are required for children who have experienced sexual abuse.

The Association Between Prenatal Infection and Adolescent Behavior: Investigating Multiple Prenatal, Perinatal, and Childhood Second Hits

Exposure to infections during pregnancy may be a potential risk factor for later psychopathology, but large-scale epidemiological studies investigating associations between prenatal infection and long-term offspring behavioral problems in the general population are scarce. In our study, we aimed to investigate the following: (1) the association between prenatal infection and adolescent behavior, (2) putative underlying pathways (mediation), and (3) "second hits" interacting with prenatal infection to increase the risk of adolescent behavior problems (moderation). Our study was embedded in a prospective Dutch pregnancy cohort (Generation R; n= 2,213 mother-child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. At age 13 to 16 years, we assessed total, internalizing, and externalizing problems, and autistic traits using the Child Behavioral Checklist and the Social Responsiveness Scale, respectively. We investigated maternal lifestyle and nutrition, perinatal factors (placental health and delivery outcomes), and child health (lifestyle, traumatic events, infections) as mediators and moderators. We observed associations of prenatal infection with adolescent total behavioral, internalizing, and externalizing problems. The association between prenatal infection and internalizing problems was moderated by higher levels of maternal psychopathology, alcohol and tobacco use, and a higher number of traumatic childhood events. We found no association between prenatal infection and autistic traits. Yet, children exposed to prenatal infections and maternal substance use, and/or traumatic childhood events, had a higher risk of autistic traits in adolescence. Prenatal infection may be a risk factor for later psychiatric problems as well as a disease primer making individuals susceptible to other hits later in life. Prenatal maternal infection and adverse neurodevelopment: a structural equation modelling approach to downstream environmental hits; https://osf.io/cp85a; cp85a. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants.

COVID-19 Pandemisinin Türkiye’de Tipik Gelişen Çocukların Uzun Dönem Davranış Sorunları Üzerindeki Etkisi

Objective: Pandemics such as COVID 19, cause severe stress for both parents and children due to social constraints, changes in daily routines, and economic challenges, and can lead to long-term developmental and behavioral problems in children. We evaluated the behavioral problems of typically developing healthy children at the end of the second year of the pandemic, as well as the effect of family sociodemographic characteristics. Materials and Methods: This case-control study included 28 children between the ages of 18 to 60 months who admitted to Hacettepe University İhsan Doğramacı Children’s Hospital between January and February 2022 and 23 children from the pre-pandemic period. All of the children scored normally on the Ages and Stages Questionnaire (ASQ) in all developmental domains. The Child Behavior Check List (CBCL) was completed by parents. Results: In terms of family sociodemographic characteristics, no significant difference existed between the two groups. Anxiety-depression scores were significantly higher in the post-pandemic group once CBCL scores were assessed (p=0.047). In the final stepwise multiple regression model, maternal education level was significantly associated with lower anxiety-depression scores (p=0.030). It was revealed that a maternal education level above high school reduced the anxiety-depression scores by 2.53 points in the post-pandemic group. Conclusions: Families, pediatricians, and all other healthcare providers need to closely monitor preschoolers, who are among the groups most vulnerable to the negative effects of the pandemic. Additionally, new policies are required to eliminate health and social inequalities that deepen during the pandemic, especially in middle income and developing countries.

Hidden impacts of conservation management on fertility of the critically endangered kākāpō.

Animal conservation often requires intensive management actions to improve reproductive output, yet any adverse effects of these may not be immediately apparent, particularly in threatened species with small populations and long lifespans. Hand-rearing is an example of a conservation management strategy which, while boosting populations, can cause long-term demographic and behavioural problems. It is used in the recovery of the critically endangered kākāpō (Strigops habroptilus), a flightless parrot endemic to New Zealand, to improve the slow population growth that is due to infrequent breeding, low fertility and low hatching success. We applied Bayesian mixed models to examine whether hand-rearing and other factors were associated with clutch fertility in kākāpō. We used projection predictive variable selection to compare the relative contributions to fertility from the parents' rearing environment, their age and previous copulation experience, the parental kinship, and the number of mates and copulations for each clutch. We also explored how the incidence of repeated copulations and multiple mates varied with kākāpō density. The rearing status of the clutch father and the number of mates and copulations of the clutch mother were the dominant factors in predicting fertility. Clutches were less likely to be fertile if the father was hand-reared compared to wild-reared, but there was no similar effect for mothers. Clutches produced by females copulating with different males were more likely to be fertile than those from repeated copulations with one male, which in turn had a higher probability of fertility than those from a single copulation. The likelihood of multiple copulations and mates increased with female:male adult sex ratio, perhaps as a result of mate guarding by females. Parental kinship, copulation experience and age all had negligible associations with clutch fertility. These results provide a rare assessment of factors affecting fertility in a wild threatened bird species, with implications for conservation management. The increased fertility due to multiple mates and copulations, combined with the evidence for mate guarding and previous results of kākāpō sperm morphology, suggests that an evolutionary mechanism exists to optimise fertility through sperm competition in kākāpō. The high frequency of clutches produced from single copulations in the contemporary population may therefore represent an unnatural state, perhaps due to too few females. This suggests that opportunity for sperm competition should be maximised by increasing population densities, optimising sex ratios, and using artificial insemination. The lower fertility of hand-reared males may result from behavioural defects due to lack of exposure to conspecifics at critical development stages, as seen in other taxa. This potential negative impact of hand-rearing must be balanced against the short-term benefits it provides.

Behavioral outcome of very preterm children at 5 years of age: Prognostic utility of brain tissue volumes at term‐equivalent‐age, perinatal, and environmental factors

Prematurity is associated with a high risk of long-term behavioral problems. This study aimed to assess the prognostic utility of volumetric brain data at term-equivalent-age (TEA), clinical perinatal factors, and parental social economic risk in the prediction of the behavioral outcome at 5 years in a cohort of very preterm infants (VPT, <32 gestational weeks). T2-weighted magnetic resonance brain images of 80 VPT children were acquired at TEA and automatically segmented into cortical gray matter, deep subcortical gray matter, white matter (WM), cerebellum (CB), and cerebrospinal fluid. The gray matter structure of the amygdala was manually segmented. Children were examined at 5 years of age with a behavioral assessment, using the strengths and difficulties questionnaire (SDQ). The utility of brain volumes at TEA, perinatal factors, and social economic risk for the prediction of behavioral outcome was investigated using support vector machine classifiers and permutation feature importance. The predictive modeling of the volumetric data showed that WM, amygdala, and CB volumes were the best predictors of the SDQ emotional symptoms score. Among the perinatal factors, sex, sepsis, and bronchopulmonary dysplasia were the best predictors of the hyperactivity/inattention score. When combining the social economic risk with volumetric and perinatal factors, we were able to accurately predict the emotional symptoms score. Finally, social economic risk was positively correlated with the scores of conduct problems and peer problems. This study provides information on the relation between brain structure at TEA and clinical perinatal factors with behavioral outcome at age 5 years in VPT children. Nevertheless, the overall predictive power of our models is relatively modest, and further research is needed to identify factors associated with subsequent behavioral problems in this population.

The Role of Oxytocin in Abnormal Brain Development: Effect on Glial Cells and Neuroinflammation

The neonatal period is critical for brain development and determinant for long-term brain trajectory. Yet, this time concurs with a sensitivity and risk for numerous brain injuries following perinatal complications such as preterm birth. Brain injury in premature infants leads to a complex amalgam of primary destructive diseases and secondary maturational and trophic disturbances and, as a consequence, to long-term neurocognitive and behavioral problems. Neuroinflammation is an important common factor in these complications, which contributes to the adverse effects on brain development. Mediating this inflammatory response forms a key therapeutic target in protecting the vulnerable developing brain when complications arise. The neuropeptide oxytocin (OT) plays an important role in the perinatal period, and its importance for lactation and social bonding in early life are well-recognized. Yet, novel functions of OT for the developing brain are increasingly emerging. In particular, OT seems able to modulate glial activity in neuroinflammatory states, but the exact mechanisms underlying this connection are largely unknown. The current review provides an overview of the oxytocinergic system and its early life development across rodent and human. Moreover, we cover the most up-to-date understanding of the role of OT in neonatal brain development and the potential neuroprotective effects it holds when adverse neural events arise in association with neuroinflammation. A detailed assessment of the underlying mechanisms between OT treatment and astrocyte and microglia reactivity is given, as well as a focus on the amygdala, a brain region of crucial importance for socio-emotional behavior, particularly in infants born preterm.

Longitudinal assessment of behaviour in young children undergoing general anaesthesia

BackgroundExposure to general anaesthesia in children might increase the risk of long-term behavioural problems. It is unclear if any behavioural changes in the short term after anaesthesia could be associated with long-term problems. The goal of the current study was to evaluate the short-term trajectory of parent-reported behaviour measured by the Behaviour Assessment System for Children, third edition (BASC-3) amongst children aged 2.5–6 yr who underwent general anaesthesia for elective surgery. MethodsChildren who were undergoing general anaesthesia for surgery were recruited for assessment of behaviour on two occasions: preoperatively (from 1 week to 1 day before anaesthesia), and 3 months postoperatively. To assess longitudinal changes in the parent-reported behaviour measured by BASC-3, linear mixed models were built with visit number included as a categorical variable and subject-specific random intercepts. ResultsSixty-eight children (37 girls [54%]) were enrolled in the study and completed both assessments. At 3 months after anaesthesia, statistically significant improvements (decrease in T scores) in internalising problems (−2.7 [95% confidence interval −4.2 to −1.1]), anxiety (−2.5 [−4.4 to −0.5]), and somatisation (−3.0 [−5.2 to −0.9]) were found. There were no significant differences in scores between visits for other composites or scales. The pattern of results did not depend upon prior anaesthesia exposure. ConclusionsAnaesthesia for elective surgery in young children was associated with a small decrease in internalising problems but no changes in other areas of behavioural problems when assessed at 3 months postoperatively, including in children with prior exposure to anaesthesia.

Integrated Excitatory/Inhibitory Imbalance and Transcriptomic Analysis Reveals the Association between Dysregulated Synaptic Genes and Anesthetic-Induced Cognitive Dysfunction.

Emerging evidence from human epidemiologic and animal studies has demonstrated that developmental anesthesia neurotoxicity could cause long-term cognitive deficits and behavioral problems. However, the underlying mechanisms remain largely unknown. We conducted an electrophysiological analysis of synapse activity and a transcriptomic assay of 24,881 mRNA expression on hippocampal tissues from postnatal day 60 (P60) mice receiving propofol exposure at postnatal day 7 (P7). We found that developmentally propofol-exposed P60 mouse hippocampal neurons displayed an E/I imbalance, compared with control mice as evidenced by the decreased excitation and increased inhibition. We found that propofol exposure at P7 led to the abnormal expression of 317 mRNAs in the hippocampus of P60 mice, including 23 synapse-related genes. Various bioinformatic analyses revealed that these abnormally expressed synaptic genes were associated with the function and development of synapse activity and plasticity, E/I balance, behavior, and cognitive impairment. Our findings suggest that the altered E/I balance may constitute a mechanism for propofol-induced long-term impaired learning and memory in mice. The transcriptomic and bioinformatic analysis of these dysregulated genes related to synaptic function paves the way for development of therapeutic strategies against anesthetic neurodegeneration through the restoration of E/I balance and the modification of synaptic gene expression.

Rehabilitation for children with chronic acquired brain injury in the Child in Context Intervention (CICI) study: study protocol for a randomized controlled trial

BackgroundPediatric acquired brain injury (pABI) is associated with long-term cognitive, behavioral, social, and emotional problems, which may affect the quality of life, school, and family functioning. Yet, there is a lack of evidence-based community-centered rehabilitation programs for chronic pABI and these children do not systematically receive comprehensive rehabilitation. The Child In Context Intervention (CICI) study is a pragmatic randomized controlled trial (RCT) for children with chronic pABI, which aims to evaluate the effectiveness of an individualized and goal-oriented intervention targeting everyday functioning of the child and family.MethodsChildren aged 6–16 years with MRI/CT-verified intracranial abnormalities will be included in the CICI study if they have persistent self- or parent-reported cognitive, emotional, and/or behavioral challenges 1 year or more after insult and attend school regularly. A total of 70 families will be randomized 1:1 to an intervention or a control group. The intervention consists of seven family sessions, one parent seminar, and four school sessions delivered over approximately 6 months. The parent seminar will be held in person, and the other sessions will mainly be video based. The children’s and families’ self-reported major challenges in everyday life will be targeted using SMART goals. Evidence-based strategies, when available, will be applied to achieve the goals, combined with psychoeducation. Goal attainment scaling (GAS) will be used to evaluate goal attainment. Data is collected at baseline and after approximately 6 and 9 months. External assessors are blinded to group allocation. Primary outcomes are parent-reported brain injury symptoms in children and parenting self-efficacy at 9 months of follow-up. Secondary outcomes include child-reported brain injury symptoms, quality of life, executive functioning in daily life, parent emotional symptoms, family functioning, and unmet family health care needs. A process evaluation will be conducted.DiscussionThe current study provides an innovative approach to rehabilitation for children in the chronic phase of ABI and their families. This complex intervention may contribute to the development of evidence-based, high-quality rehabilitation for a large patient group, which is underrepresented in clinical research. It may also improve collaboration between specialized rehabilitation facilities, schools, and local health care services. Inclusion for the trial started in April 2021.Trial registrationClinicalTrials.govNCT04798859. Registered on March 15, 2021

POS-173 ACUTE KIDNEY INJURY AND RENAL RECOVERY IN UGANDAN CHILDREN WITH SEVERE MALARIA

Acute kidney injury (AKI) is increasingly recognized as an important clinical complication in children with severe malaria associated with increased morbidity and mortality, including long-term neurocognitive and behavioral problems in surviving children. The objective of this study was to evaluate AKI and renal recovery in a prospective cohort study of children with severe malaria admitted to two hospitals in Uganda: Mulago National Referral Hospital in Kampala in Central Uganda and Jinja Regional Referral Hospital in Eastern Uganda.

Prenatal smoke exposure is associated with increased anogenital distance in female infants: a prospective case-control study.

To investigate the effects of maternal smoking during pregnancy on newborn infants' anogenital distance (AGD). Fifty-six female and sixty-four male newborn infants from mothers who smoked during pregnancy were included in this study. A control group for each sex was selected from infants whose mothers had no active or passive (in either the household or the workplace) smoke exposure before or during pregnancy. Questionnaire data on maternal demographic characteristics and information about cigarette use were collected. We assessed genital anthropometry which included AGD for both male and female neonates, and stretched penile length (SPL), penile girth for males within the first 48h after birth. AGD measurements were also normalized according to birth weight (AGD/weight in grams), length (AGD/height in millimeters), and ponderal index [AGD/(weight in grams/height in cubic centimeters)]. Anogenital index (AGI) was calculated by dividing the AGD by cube root of birth weight. In female infants, prenatal smoke exposure was associated with significantly increased weight-adjusted AGD (p=0.03). There was also a significant correlation between mothers' daily smoking rates and weight-adjusted AGD (r=0.27/p=0.03). In male infants, fetal smoke exposure was not associated with any AGD measurements, SPL and penile girth. A significant increase in weight-adjusted AGD in female infants exposed to maternal smoking may be an indicator of antenatal androgen exposure and may pose a risk for short and long-term endocrine, metabolic and behavioral problems.

Brains, bacteria and behaviors: the role of interferon-gamma in the pathogenesis of pneumococcal meningitis.

Pneumococcal meningitis is a highly lethal form of bacterial meningitis that occurs following brain infection by the Gram-positive cocci Streptococcus pneumoniae. Not only does it cause acute mortality, but pneumococcal meningitis also accounts for the highest proportion of survivors living with neurological sequelae, including behavioral disorders, cognitive deficits, hearing loss, motor impairment and epilepsy. More than 90 distinct pneumococcal serotypes have been identified worldwide based on their capsular compositions and serological responses. Serotype replacement continually poses great challenge to costly vaccination programs in developed countries (Koelman et al., 2020), this has therefore emphasized the need to develop new treatment strategies in addition to improving vaccine coverage. Various immunomodulatory agents, such as complement system inhibitors and matrix metalloproteinase inhibitors, have been shown to improve disease severity and mortality when tested in animal models (Bewersdorf et al., 2018). Nevertheless, given the evidence of long-term cognitive deficits and behavioral problems in patients who were clinically well recovered from pneumococcal meningitis, it remains unclear how the protection at the early inflammatory stage may translate into long-term functional recovery. With this in mind, we have established an integrated approach to investigate the interplay between acute host inflammatory response and ensuing neurological deficits in a mouse model of pneumococcal meningitis in animals that survive the lethal disease due to antibiotic ceftriaxone treatment. This has enabled the identification of a nexus between the toll-like receptors (TLRs) 2 and 4, interferon-gamma (IFN-γ) and the enzyme indoleamine 2,3-dioxygenase-1 (IDO-1) that contributes to enduring neurological impairments. Here, we will highlight the findings of our systematic studies in the hope of opening avenues for future research relevant to both meningitis as well as other neurological diseases.

Domestic Violence and Safe Storage of Firearms in the COVID-19 Era.

Domestic Violence and Safe Storage of Firearms in the COVID-19 Era.

The Role of Adverse Childhood Experience on Depression Symptom, Prevalence, and Severity among School Going Adolescents.

Methods A cross-sectional school-based study was employed. Five hundred forty-six secondary school students were selected using multistage sampling technique from 5 selected secondary schools. We obtained retrospective information on adverse childhood experiences of adolescents by ACEs, self-reported 10-item questionnaire, and current depression prevalence and severity by PHQ-9. Multivariate linear regression models were used to estimate child depression severity by retrospective ACE count. Results Among the 546 adolescents who participated in this study, 285 (50.7%) of the participants answered yes to at least one or more questions among the total 10 questions of ACEs. Experiences of ACEs increased the risk for depressive symptoms, with unstandardized β = 1.123 (β = 1.123, 95% CI (0.872, 1.373). We found a strong, dose–response relationship between the ACE score and the probability of lifetime and recent depressive disorders (p < 0.0001). Conclusions The number of ACEs has a graded relationship to both the prevalence and severity of depressive symptoms. These results suggest that exposure to ACEs is associated with an increased risk of depressive symptoms up to decades after their occurrence. Early recognition of childhood abuse and appropriate intervention may thus play an important role in the prevention of depressive disorders throughout the life span.