Developmental Factors Research Articles

The Role of Family, Microsocial and Medical History in The Shaping of Trajectories of Complex Opioid and Cannabis Addiction: Results of Machine Learning Modeling

Introduction: The widespread misuse of opioids and cannabis is a notable global public health concern. The substantial public health concern due to the misuse of opioids and cannabis, individually and concurrently, is associated with vast societal implications. Identification of risk factors for developing misuse of these substances is of utmost importance. This study aims at developing a machine learning-based model to classify groups of opioid or cannabis dependents using family, microsocial, and medical history variables, and to identify the most significant variables associated with each group.Methods: This naturalistic observational non-interventional study enrolled adult patients diagnosed with opioid use disorder, cannabis use disorder, or a combination of both. Machine learning models, including Stacking, Logistic Regression, Gradient Boosting, k-Nearest Neighbors (kNN), Naive Bayes, Support Vector Machines (SVM), Random Forest, and Decision Tree, were used to classify patients and predict their risk factors based on various personal history variables.Results: The patient groups showed significant differences in their working fields, marital status before and after the formation of drug addiction, substance misuse in relatives, family type, parent-child relationships, and birth order. They also differed significantly in fleeing from home and personality types. Machine learning models provided high classification accuracy across all substance dependence groups, particularly for the cannabis group (>90% accuracy). Significant differences were found among the complex misuse group, where individuals faced severe psychosocial issues originating from the familial environment, such as a history of fleeing home, coming from a single-parent family, and dominant parent-child relationships.Discussion: The methods used in this study provided robust and reliable assessments of the models' predictive performances. The results pointed to significant differences in familial and developmental factors between the three dependence groups. The complex dependence group showed more severe psychosocial issues originating from the family environment. This group also revealed a specific sequence of life events and conditions predictive of complex dependence. These findings highlight the importance of interventions that address risk factors across various life stages and domains. Conclusion: Early identification of high-risk individuals and understanding the risk factors can inform the development of effective interventions at both individual and societal levels, ultimately aiming at mitigating dependence risks and improving overall well-being. Further research with longitudinal designs and diverse populations are needed to increase our understanding of trajectory of addiction formation in order to deliver effective interventions for individuals at risk.

CSIG-24. LINEAR GRADING COEFFICIENT REVEALS EMBRYONIC DEVELOPMENT GENE SIGNATURE AS TREATMENT-INDEPENDENT PROGNOSTIC FACTOR IN IDH-MUTANT ASTROCYTOMA

Abstract BACKGROUND Since there is variation in prognosis within grade II/III and grade IV IDH-mutant astrocytomas, we sought to identify features that may aid further tumor grading. METHODS RNAseq was performed on IDH-mutant astrocytomas from the CATNON trial and overlaid with matching genome-wide methylation data. This dataset was extended by multi-omics data of IDH-mutant astrocytomas from the TCGA and GLASS-NL studies. We defined a linear grading coefficient (LGC) based on calibrated DNA methylation-based probability scores and performed differential gene expression (DGE) regression analysis on the LGC. Statistical analyses were intersected across the CATNON and TCGA cohorts ("discovery set") and validated on GLASS-NL. Single-nucleus RNA-sequencing (snRNAseq) data of high-grade IDH-mutant astrocytomas were utilized to explore the source of expression signals. Immunofluorescence was used to confirm findings on protein level. RESULTS DGE regression analysis revealed that higher-grade IDH-mutant tumors (high LGC) exhibited mRNA upregulation of key embryonic developmental transcription factors (HOX[A/C/D], NKX, PAX, and TBX). Although the vast majority of CpG sites in LGC high tumors were hypomethylated, homeobox genes were strongly hypermethylated in our discovery set. HOX gene clusters showed gene-ordered (differential) expression where e.g. HOXD10 >D9 >D8 >D4 >D1 and HOXA3 >A7 >A9 >A13 suggesting derepression of enhancer sequences up/downstream of the gene cluster. Our expression-based embryonic development signature was positively correlated with, but not restricted to, the G-CIMP-low subtype and homozygous CDKN2AB deletion. The signature was prognostic (log-rank test) on both the discovery (CATNON: p< 0.0005, TCGA: p< 0.0005) and validation set (GLASS-NL: p< 0.005). As our signature was developed on molecular data from primary resections, its prognostic value is treatment-independent. SnRNAseq on high-grade IDH-mutant astrocytomas indicated expression of embryonic development genes from tumor cells, not restricted to the stemness program. CONCLUSION Our study highlights upregulation of embryonic development genes as potential molecular mechanism associated with malignancy of IDH-mutant astrocytomas.

EPCO-33. H3K4 METHYLATION IS A PREREQUISITE OF CELL FATE CHANGE DURING IDH-MUTANT GLIOMAGENESIS

Abstract RATIONALE: Low grade gliomas (LGGs) are defined by isocitrate dehydrogenase (IDH)-mutations that mediate broad epigenetic changes. However, additional determinants of low-grade gliomagenesis remain unknown, including factors necessary for the activation of LGG gene programs. Here, we aim at identifying epigenetic prerequisites of IDH-dependent gliomagenesis by modulating key chromatin modifiers in a conditionally IDHR132H-expressing immortalized human astrocyte (IHA) model system. METHODS: Using chemical compounds, we targeted key histone modifications and DNA methylation in an inducibly IDHR132H expressing IHA cell line. Flow cytometry for the LGG-associated marker L1CAM served as a primary read-out. Compound candidates were further assessed with RNA-Seq and mass spectrometry. Phenotypic evaluation included sphere formation, clonogenicity, cell viability and invasion assays. Relevant findings were additionally assessed in established LGG cell lines TS603, NCH612 and NCH1681. RESULTS: L1CAM was significantly altered by DOT1L inhibitor EPZ00477, MLL1 inhibitor MM-102, and EZH2 inhibitor GSK-126. MM-102 treatment was associated with broad transcriptional downregulation. Intersecting data from MM-102 and GSK126 treated cells, we identified potential bivalent genes directly affected by inhibitor treatment that were enriched for Wnt signaling and developmental transcription factors implicated in gliomagenesis. Overlapping transcriptional and proteomics data, MM-102-treated cells exhibited a signature of predominantly downregulated genes associated with invasion/migration, extracellular matrix (ECM) and cholesterol metabolism. Fittingly, cells showed impaired invasion, clonal proliferation and sphere forming capacity. The negative effect on sphere formation tracked inversely with aggressiveness of established LGG cell lines. CONCLUSION: Interfering with histone H3K4 methylation through MLL1 inhibition is associated with broad downregulation of gene sets related to cell identity and ECM/migration, reflected by disruption of clonal proliferation in IDHR132H astrocytes and LGG cell lines. This points to deposition of H3K4 methylation as a prerequisite of cell fate change in LGG development. Persisting effects on established LGG cell lines warrant its investigation as a potential therapeutic target.

Influence of birth weight on later life cardiovascular structure, function and disease: unpacking influences from direct genetic effects versus intrauterine programming

Abstract Aims The cardinal risk factors for cardiovascular disease in adulthood are well-recognised. In addition to these, observational studies have suggested that intrauterine and early developmental factors might play a role. However, observational associations are liable to influence by residual confounding and bias. Additionally, observational and genetic studies to date have not been able to isolate the fetal versus maternal influences. Purpose We aim to explore the causal relevance of birth weight on cardiovascular disease and cardiac structure and function using Mendelian randomization (MR), and specifically investigate the role of fetal genetic effects (reflecting the direct causal influence of birth weight) versus maternal genetic effects (reflecting the influence of the intrauterine environment). Methods Uncorrelated (r2<0.001), genome-wide significant (p<5x10-8) SNPs were extracted from genome-wide association study summary statistics for gestational age-adjusted birth weight overall, and after isolating the indirect maternal versus direct fetal genetic effects. Inverse-variance weighted Mendelian randomisation (MR) was utilised for primary analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 15 measures of cardiac structure and function indexed to body surface area. Multivariable MR was utilised to explore potential mediation of effects observed on cardiovascular outcomes by cardiometabolic risk factors. P-values were FDR-adjusted to account for multiple testing. Results Higher genetically-predicted birth weight was associated with higher risk of atrial fibrillation (OR 1.26 [1.15-1.39], p<0.001), but lower risk of coronary artery disease (OR 0/78 [0.71-0.86] p<0.001). These associations were driven predominantly by direct fetal genetic effects. For the association with atrial fibrillation, there was no evidence of mediation through body mass index or height. For the association with coronary artery disease, there was at least partial mediation through systolic blood pressure (Figure 1). Higher genetically-predicted birth weight was associated with a greater chamber volumes, but lower ejection fraction (Figure 2), driven by direct fetal genetic effects. Conclusion The results of this study suggest that lower birthweight is associated with higher risk of coronary artery disease, partly mediated by a higher systolic blood pressure. Conversely, a greater birth weight was associated with higher risk of atrial fibrillation, and this was not mediated by body mass index or height. Higher birth weight was also associated with greater chamber volumes and lower ejection fraction. The associations were in all cases predominantly driven by direct fetal effects, suggesting a causal relevance of birth weight itself, and not of the intrauterine environment, on later life cardiovascular disease.Figure 1Figure 2

Maternal determination of soldier proportion and paternal determination of soldier sex ratio in hybrid Reticulitermes (Isoptera: Rhinotermitidae) termite colonies.

Altruistic caste, including worker and soldier (derived from worker), plays a critical role in the ecological success of social insects. The proportion of soldiers, soldier sex ratios, and the number of workers vary significantly between species, and also within species, depending on colony developmental stage and environmental factors. However, it is unknown whether there are sex-linked effects from parents on controlling the caste fate or not. Here, we compared soldier sex ratios, soldier proportions, and population size among a four mating types of Reticulitermes amamianus (Ra) and R. speratus (Rs) (male × female, mRa × fRa, mRa × fRs, mRs × fRa, mRs × fRs) and demonstrate that the soldier sex ratio and worker population size of hybrid colonies skew to colonies of king's species, while the soldier proportion skew to queen's species. The survival rate of offspring resulting from interspecies hybridization was significantly higher for mRa × fRs than for mRs × fRa. The results of this study demonstrate the asymmetric influence of kings and queens on caste determination and colony growth, which can contribute to our better understanding of parental influence on the colony dynamics of social insects.

Assessing the Imperative for Underpass Safety Technologies in Climate Change Challenges

Amidst the heightening urgency of climate change impacts, underpass roadways are particularly susceptible to the intensifying and unpredictable weather events, with flooding being a primary concern. This paper highlights the dire need for sophisticated safety assessment technologies specifically catered to these critical infrastructures. Herein, we present a pioneering risk assessment model that holistically incorporates environmental variables along with urban developmental factors to yield an exhaustive evaluation of flood vulnerability. Our proposed methodological framework offers a robust scientific foundation for the identification of high-risk areas, which is crucial for effective emergency response planning, optimized resource allocation, and enhancing the adaptive capacity of urban environments to weather extremes. The adoption of such advanced assessment tools is not just beneficial but becomes essential for informed urban planning and safeguarding the populace against the dire consequences of flood events.

Factors Associated with the Prevalence and Treatment of Depression in Adolescent Males in the US during the Period of the COVID-19 Pandemic

Background: Much of the research on the effect of the COVID-19 pandemic on mental health has overlooked the experiences of adolescent boys. Objective: To examine the prevalence of depression, treatment trends, and associated risk factors among adolescent boys, controlling for the pandemic year. Methods: Data for boys aged 12 to 17 years (n = 4518) in the 2021 National Survey on Drug Use and Health were analyzed. Time trends and factors associated with depression were examined using a multiple regression analysis. Results: The prevalence of 12-month major depressive episodes (TMDEs) was 11.6% during the first year of the COVID-19 pandemic. Among the boys with TMDEs, 37.8% received treatment overall, and 19.0% received prescription medication. Higher rates of TMDEs were estimated in boys who were older (adjusted odds ratio (AOR): 1.66, p < 0.001), lived in single-mother households (AOR: 1.47, p < 0.001), did not have authoritative parents (AOR: 1.78, p < 0.001), and had negative school experiences (AOR: 2.45, p < 0.001). Although Black boys were less likely to report depression than white boys (AOR: 0.70, p < 0.05), nonwhite boys who had depression were significantly less likely to receive treatment. Boys living in a household without a mother were also less likely to receive treatment (AOR: 0.49, p < 0.05). Conclusions: This study reveals the unique developmental, social, and psychological factors that influence depression among adolescent boys. During the pandemic, more than one out of ten adolescent boys had a major depressive episode, and four of ten of them received treatment; half of these treatments were prescription medication. Recognizing these factors may allow for more targeted and effective interventions to improve mental health outcomes for this demographic.

Progress and Perspectives in Colon Cancer Pathology, Diagnosis, and Treatments.

Worldwide, colon cancer is the third most frequent malignancy and the second most common cause of death. Although it can strike anybody at any age, colon cancer mostly affects the elderly. Small, non-cancerous cell clusters inside the colon, commonly known as polyps, are typically where colon cancer growth starts. But over time, if left untreated, these benign polyps may develop into malignant tissues and develop into colon cancer. For the diagnosis of colon cancer, with routine inspection of the colon region for polyps, several techniques, including colonoscopy and cancer scanning, are used. In the case identifying the polyps in the colon area, efforts are being taken to surgically remove the polyps as quickly as possible before they become malignant. If the polyps become malignant, then colon cancer treatment strategies, such as surgery, chemotherapy, targeted therapy, and immunotherapy, are applied to the patients. Despite the recent improvements in diagnosis and prognosis, the treatment of colorectal cancer (CRC) remains a challenging task. The objective of this review was to discuss how CRC is initiated, and its various developmental stages, pathophysiology, and risk factors, and also to explore the current state of colorectal cancer diagnosis and treatment, as well as recent advancements in the field, such as new screening methods and targeted therapies. We examined the limitations of current methods and discussed the ongoing need for research and development in this area. While this topic may be serious and complex, we hope to engage and inform our audience on this important issue.

Developmental factors associated with inappropriate coping strategies among sexual aggressors of children

BackgroundMany studies in the field of sexual offending focus on the presence of inadequate coping strategies prior to sexual offending, and the role these strategies play in the sequence of the offense. However, little is known about the development of strategies—such as substance abuse and, especially, deviant sexual fantasies—to manage daily difficulties. ObjectiveTo better understand the antecedents of the development of inadequate coping strategies, we conducted a series of structural equation modeling (SEM) analyses. Participants and settingsBased on 274 sexual aggressors of children, these analyses were based on components of Maniglio (2011a) theoretical model, in which victimization before the age of 18 leads to the development of psychological problems and, ultimately, the reliance on deviant sexual fantasies as a coping strategy. MethodsTwo models were created through exploratory factorial analysis: the first model comprised 19 manifest variables, while the second model consisted of 15 manifest variables. All the retained variables were related to Maniglio's (2011a) hypothesis. ResultsThe analyses not only confirm Maniglio's hypothesis but also produced two statistically significant models (RMSEA = 0.069, CFI = 0.93 and TLI = 0.92 for Model 1 & RMSEA = 0.074, CFI = 0.93 and TLI = 0.91 for Model 2) composed of three indirect trajectories and one direct trajectory on the one hand, and four indirect trajectories and one direct trajectory on the other hand. ConclusionsThese results are consistent with those of studies that have highlighted the heterogeneity of sexual aggressors of children.

Social influences on alcohol outcome expectancy development from childhood to young adulthood: A narrative review.

Alcohol outcome expectancies emerge in early childhood, develop throughout adolescence, and predict alcohol outcomes well into adulthood. Social factors shape how expectancies are learned in myriad ways, yet such social learning influences seldom are examined in the context of developmental factors. This review summarized literature on the social origins of alcohol expectancies through vicarious (observational) and experiential (direct) alcohol-related learning from childhood to young adulthood within a social learning framework. Young children primarily endorse negative expectancies, which decline rapidly with age amidst escalations in positive expectancies across adolescence. Parents and peers can contribute to vicarious learning about alcohol and facilitate experiential learning in different ways and to varying degrees across development. Media and social media, which children are increasingly exposed to as they mature, often depict alcohol-outcome relations that may further contribute to expectancy development in later adolescence and young adulthood. Social influences on alcohol expectancy learning are complex and change over time, although this dynamic complexity typically is not depicted in extant literature. Developmentally-informed research capturing co-occurring shifts in social influences and alcohol expectancies is needed.

Effect of leaf development on the composition of Coleus amboinicus Lour. hydroethanolic extracts

Coleus amboinicus Lour. is an aromatic shrub widely used for therapeutic and culinary purposes. Although its phytochemistry has been broadly reported in the literature, mainly essential oil composition, little is known about the effect of developmental factors on the composition of C. amboinicus extracts. Thus, we evaluated the chemical composition of C. amboinicus extracts from leaves in different stages of development via liquid chromatography coupled to mass spectrometry. After data processing and filtering, 143 and 101 mass features were detected in the negative and positive ion modes, respectively, most of which varied between at least two leaf stages. Among the compounds represented by these mass features, phenolic acids and flavonoids were annotated for this species. In general, leaves from the first and second nodes showed different composition in comparison to older leaves, indicating that a change in the chemical profile occurs towards the end of leaf expansion. This chemical variation may ultimately result in changes in the biological activities; therefore further research about the effects of developmental factors on C. amboinicus bioactivities is required.

Sexual Health in Adolescents and Young Adults With Cancer.

Sexual health (SH), an integral aspect of overall health and quality of life, can be negatively affected by cancer and cancer treatment. SH is influenced by biological, psychological, social, and cultural factors, and, for adolescents and young adults (AYAs), developmental factors. The AYA population (age 15-39 years) is diverse in terms of psychosexual development, interpersonal relationships, and varying levels of independence, resulting in unique SH needs for this population. AYAs with cancer are particularly vulnerable to unmet SH needs related to contraception and infection prevention, sexual function, body image, and romantic/sexual relationships. Sexual dysfunction during and after cancer treatment is reported by 30%-100% of AYA cancer survivors. Clinical guidelines recommend discussing SH and screening for dysfunction but currently lack specifics regarding psychosexual interventions and strategies for incorporating screening into clinical care. Research and clinical priorities include improved provider-AYA communication regarding SH, standardization of SH measures and screening tools, infrastructure to support the SH needs of AYAs across pediatric and adult clinical environments, and engagement of sexual and gender minority AYAs in research. As the field of SH in cancer evolves, interventions need to be tailored to the developmental needs that are unique to AYAs and address the multidimensional aspects of SH.

Icelandic Whimbrel first migration: Non‐stop until West Africa, yet later departure and slower travel than adults

Migratory behaviour in young individuals is probably developed by using a complex suite of resources, from molecular information to social learning. Comparing the migration of adults and juveniles provides insights into the possible contribution of those developmental factors to the ontogeny of migration. We show that, like adults, juvenile Icelandic Whimbrel Numenius phaeopus islandicus fly non‐stop to West Africa, but on average depart later, follow less straight paths and stop more after reaching land, resulting in slower travel speeds. We argue how the variation in departure dates, the geographical location of Iceland and the annual migration routine of this population make it a good model to study the ontogeny of migration.

What childhood and related developmental factors are relevant to the risk of onset and course of depression and other mood disorders?

One of the most strongly held beliefs in developmental psychiatry is that various emotional, cognitive, behavioural and temperamental factors observed in childhood set the individual trajectory for the risk of onset, course and likely response to treatments in youth and adults with depressive and other mood disorders (Hickie et al., 2019).

SAT394 Over-representation Of Adoptees Among Transgender Subjects Seeking Gender-Affirming-Hormonal-Therapy (GAHT) In A Large Tertiary Medical Center

Abstract Disclosure: I. Yaish: None. G. Keltch: None. Y. Greenman: None. T. Kolitz: None. K.M. Tordjman: None. Background: The etiology of transgenderism is still unclear. Possible mechanisms range from inborn brain-specific anatomical characteristics, to endocrine-related genetic polymorphisms. In addition, psychosocial developmental factors, particularly trauma from early childhood, are believed to contribute. In line with a handful of previous reports, we were struck by what seemed to be an over-representation of adoptees among adult subjects seeking GAHT at our Transgender Health Center. Aims of Study: To confirm that adopted individuals are more likely to seek a gender transition process than nonadopted subjects, and to determine whether there are major differences between the 2 subgroups. Design and Methods: A retrospective study of treatment-naïve adult subjects seeking GAHT at our center between 01.05.2014 and 31.12.2022. The prevalence of adopted subjects in the cohort was compared with the national rate by one sample binomial test. Adoptees were compared to nonadopted subjects in the cohort by nonparametric tests. Results: During the study period, 671 new adult transgender subjects initiated GAHT at our clinic. Among them, 14 adoptees or 2.09%, which is an order of magnitude greater than the corresponding national rate of 0.22% (P<0.0001). This rate is lower than that reported from clinics for transgender youth in Canada (7.6%), in the US (8.2%), and in Britain (3.8%). Age of adoption was at, or below, one year in 13 cases, and at age 2.7 yr in one. The distribution of assigned-at-birth sexes was different between the 2 groups. Among the 657 nonadopted subjects, the breakdown was quite balanced, 323 had been assigned male sex (49.2%), and 334 female (50.8%). Among adoptees, only 3/14 (21.4%) were born males, and 11 (78.6%) females, P=0.056, by Fisher’s exact test. There was also a trend for adopted subjects to be somewhat older than non-adopted subjects. Their median age was 25.5 yr [IQR 23-30.75], as opposed to 23 yr [IQR 19-30] in non-adopted subjects, P=0.08. Characterization, and comparisons of parameters such as socioeconomic status, co-morbidities, and others, are still ongoing. Conclusions: There is an over-representation of adopted adults requesting GAHT at our center. However, the rate is lower than what has been reported from pediatric clinics, suggesting some of these subjects may seek help at a younger age. The findings support a contributory role of adoption in early infancy and the trauma around it in the development of transgenderism. Further research should attempt to decipher the mechanisms through which this early life event interacts with inborn properties. Presentation: Saturday, June 17, 2023

Various delayed tooth eruption in children, management and outcome: A case series

It is estimated that 4.3% of patients experience delayed eruption of permanent teeth due to local causes. Mandibular second premolars were the most frequent permanent teeth associated with delayed eruption, followed by maxillary canines, and maxillary central incisors. While rare, unerupted permanent teeth should be treated promptly to avoid potential impacts on future function, esthetics, confidence, mental health, and pronunciation. For this reason, parents often seek dental examinations and treatment for their children. Delayed tooth eruption (DTE) can also affect treatment planning and orthodontic timing. This report presents three cases of unerupted teeth. All cases were treated with a simple excision of overlying tissue to expose the crown using either a scalpel or electrocautery. Two of three lesion diagnosis was confirmed by Histopathology anatomy (HPA). In all cases, the involved teeth spontaneously erupted immediately following treatment, providing good aesthetics. However, one case experienced complications due to allergies during the wound healing process. In conclusion, proper diagnosis and treatment of DTE, including consideration of developmental disturbance factors, can help ensure normal eruption patterns and satisfactory aesthetic results.

The development of Early Childhood intellectual Capacities in the Child Development Centers of the Local Administrative Organizations, Chaiyaphum

Background and Aim: The early stage of childhood is a crucial period that significantly impacts a child's learning and growth trajectory. Research has shown a strong connection between cognitive ability, developmental milestones during this phase, and future outcomes in adolescence and adulthood. Therefore, it is imperative for preschool learning programs to prioritize age-appropriate and holistic development. To enhance the intellectual capabilities of preschoolers, an integrated learning activity program was implemented and analyzed for its effectiveness in improving young learners' intellectual and other developmental factors. Material and Methods: This study used pre- and post-test experimental designs. Through a multi-stage random sampling procedure, 113 preschoolers were chosen from five sub-district centers in Nai Faai, Nai Sineun, Ban Lao, Tha Hinong, and Huen. Developmental Assessment Scales, developed by the researcher, were used to compare cognitive abilities and development levels of children aged 24, 36, and 48 months before and after the 8-week Integrated learning program. The reliability of the scales was 0.85, 0.80, and 0.83, respectively. The t-test was employed for comparison analysis. Results: The results indicated that the motor skills, language, problem-solving, and personal-social awareness of preschoolers aged 24, 36, and 48 months significantly improved at the .01 level after participating in the integrated learning activities. Conclusions: Integrated learning activities could effectively support and enhance intellectual capacities and age-appropriate development.

Screening of Early Developmental Delay and Its Risk Factors Among Children Seeking Health Care in India-exploring Missed Opportunities

Background and Objectives: Early years are considered to be critical for a child’s development. Lower middle-income countries report developmental delays late, resulting in limited access to early intervention and rehabilitation services. The opportunity to screen children during immunization and regular outpatient department (OPD) clinics is missed. To estimate the proportion of developmental delay and its risk factors among children under two years of age. Methods: A cross-sectional study was conducted among 169 children attending outpatient department (OPD) and immunization clinics of five health centers in Bengaluru City, India. A standardized developmental delay screening tool was used to screen for developmental delay among children under 2 years of age. After receiving informed written consent, a pretested questionnaire was administered, including the child’s socio-demographic details and risk factors responsible for the developmental delay. Proportions were calculated. The relationship between risk factors and developmental delay was assessed using a chi-square test. The odds ratio and adjusted odds ratio were calculated. Results: A total of 59 children (34.9%) were from rural primary health care (PHC), 79(46.7%) from urban primary health care (PHC), and 31(18.3%) from the hospital. A total of 111(65.7%) of them were females, mean age was 10.6±5.5 months. Developmental delay was reported among 30 children (17.8%). Developmental delay was significantly higher among children younger than 12 months of age and those screened in immunization clinics than compared to the other counterparts. Conclusion: The proportion of developmental delay and risk factors for developmental delay is high among children seeking health care. It is required to implement mandatory monitoring and opportunistic screening during immunization sessions to effectively identify developmental delays early in children.

Prevalence of developmental delay and associated risk factors among At Risk Surveillance System (ARSS) children at United Bulawayo Hospitals, Zimbabwe

Globally, 8.4% of children under five years of age have developmental disorders, with sub-Saharan Africa having the highest prevalence. In Zimbabwe, the At Risk Surveillance System (ARSS) follows up on babies with known developmental risk factors for early detection of developmental delay. This study aimed to determine the prevalence and severity of developmental delay in children under the ARSS at United Bulawayo Hospitals (UBH). A descriptive cross-sectional study systematically sampled 160 babies enrolled in the ARSS between 2019 and 2020. The Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) tool was used to assess cognitive, motor, and language domains. Developmental delay risk factors were also noted from caregivers and patient files. A prevalence of 83.7% developmental delay was established in our sample, the majority of whom had mild developmental delay. The most important risk factors for developmental delay in all three domains were neonatal convulsions (Adjusted Odds Ratio, aOR, 5.6, p=0.03), Apgar scores of <5 (aOR 2.6, p=0.02), and being a boy (aOR 7.1, p<0.001). Developmental delay of 83.7% is higher than in previous findings because children included in this study had known risk factors for developmental delay. The risk factors were similar to those identified by other studies. Children with the most important risk factors need close monitoring as they have a high chance of developmental delay. Children with known risk factors should be closely monitored using the BSID-III, while the rest can be screened using cheaper and faster tools such as the Ages and Stages Questionnaire (ASQ).

Epigenomic signature of accelerated ageing in progeroid Cockayne syndrome.

Cockayne syndrome (CS) and UV-sensitive syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and multifunctional CSA or CSB protein, but only CS patients display a progeroid and neurodegenerative phenotype, providing a unique conceptual and experimental paradigm. As DNA methylation (DNAm) remodelling is a major ageing marker, we performed genome-wide analysis of DNAm of fibroblasts from healthy, UVSS and CS individuals. Differential analysis highlighted a CS-specific epigenomic signature (progeroid-related; not present in UVSS) enriched in three categories: developmental transcription factors, ion/neurotransmitter membrane transporters and synaptic neuro-developmental genes. A large fraction of CS-specific DNAm changes were associated with expression changes in CS samples, including in previously reported post-mortem cerebella. The progeroid phenotype of CS was further supported by epigenomic hallmarks of ageing: the prediction of DNAm of repetitive elements suggested an hypomethylation of Alu sequences in CS, and the epigenetic clock returned a marked increase in CS biological age respect to healthy and UVSS cells. The epigenomic remodelling of accelerated ageing in CS displayed both commonalities and differences with other progeroid diseases and regular ageing. CS shared DNAm changes with normal ageing more than other progeroid diseases do, and included genes functionally validated for regular ageing. Collectively, our results support the existence of an epigenomic basis of accelerated ageing in CS and unveil new genes and pathways that are potentially associated with the progeroid/degenerative phenotype.