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An estimated 41,000 lives are lost to suicide each year in World Health Organization Eastern Mediterranean Region Office (WHO EMRO) countries. The objective of this study was to conduct a situation analysis for suicide and self-harm in the WHO EMRO region. Data on suicide were obtained from the WHO Global Health Estimates for the years 2000–2019. Information on risk groups efforts to prevent self-harm and suicide in the EMRO region were retrieved through scientific studies, grey literature, and public websites. During 2000–2019, the age-standardized suicide rate was 6.7 per 100,000 inhabitants, albeit there are concerns regarding data quality. Self-harm and suicide remain criminal acts in more than half of the countries. Few countries have a national plan for prevention of suicide. Toxic agents, such as pesticides and black henna, are easily available and frequently used for suicide in some areas, as are firearms and self-immolation. Successful prevention measures include means restriction and psychosocial interventions after self-harm. Many WHO EMRO countries remain underserved in terms of mental health care. Decriminalization of suicide and means restriction might be further promoted. Online-based tools for mental health literacy and psychosocial therapy are other options to explore. Suicidal behavior remains a criminal act in more than half of the WHO EMRO countries. Easily available toxic agents, such as pesticides and black henna, and firearms are common methods used for suicidal behavior in the WHO EMRO countries. Access to mental health care is limited in many of the WHO EMRO countries. Online-based psychoeducation and psychosocial intervention programs might be further explored as preventive efforts. [ABSTRACT FROM AUTHOR]

Summary: Aims: The purpose of this systematic review and meta‐analysis was to investigate the effects of family‐based health promotion interventions on child‐level risk factors for type 2 diabetes in vulnerable families. Methods: The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) checklist for systematic reviews formed the methodological framework. CINAHL, Embase, MEDLINE, PsycINFO, and Web of Science were searched on January 12, 2024. The NTP‐OHAT Risk of Bias Assessment Tool was used to assess the risk of bias in the individual studies, and meta‐analyses were performed. Results: The 4723 studies were identified, and 55 studies met the inclusion criteria. Results showed significant effects on children's body mass index (mean difference [MD], −0.18, 95% CI [−0.33 to −0.03], p = 0.02), body fat percentage (MD, −2.00, 95% CI [−3.31 to −0.69], p = 0.003), daily activity (standardized mean difference [SMD], 0.23, 95% CI [0.01; 0.44], p = 0.04), physical activity self‐efficacy (SMD, 0.73, 95% CI [0.36 to 1.10], p < 0.01), intake of snacks (MD, −0.10, 95% CI [−0.17 to −0.04], p = 0.002), and sugar‐sweetened beverages (SMD, −0.21, 95% CI [−0.42 to −0.01], p = 0.04). Subgroup analyses suggested that interventions aiming to change child and parent behavior simultaneously have larger effect on fasting glucose and nutrition consumption, and that interventions longer than 26 weeks have larger effects on body composition and physical activity behavior than shorter interventions. [ABSTRACT FROM AUTHOR]

Background: Although plausible links between language development and personality have been suggested, longitudinal studies of these associations into adulthood have not been conducted. Aim: To investigate whether children's age at attaining language milestones is associated with later adult personality. Methods: Mothers' of 8,400 children from the Copenhagen Perinatal Cohort recorded six language milestones during the child's first 3 years of life. Information on at least one language milestone was available for two subsamples with adult follow-up information on personality: The Eysenck Personality Questionnaire was available for 691 individuals with a mean age of 27.5 years and The NEO Five-Factor Inventory was available for 902 individuals with a mean age of 50.0 years. Results: Faster attainment of language milestones was associated with lower neuroticism in young adulthood and with higher extraversion and openness to experience in midlife. A total of 1.9% of the variance in neuroticism, 2.5% of the variance in extraversion, and 1.6% of the variance in openness to experience was explained by language milestones. Conclusion: Only a modest part of variance in personality traits was explained by language milestones. However, the study adds to the literature on potential consequences of the timing of language development and suggests a link between language milestones and personality in adulthood.

Human induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CMs) offer potential as an in vitro model for studying drug cardiotoxicity and patient‐specific cardiovascular disease. The inherent electrophysiological heterogeneity of these cells limits the depth of insights that can be drawn from well‐designed experiments. In this review, we provide our perspective on some sources and the consequences of iPSC‐CM heterogeneity. We demonstrate the extent of heterogeneity in the literature and explain how such heterogeneity is exacerbated by patch‐clamp experimental artifacts in the manual and automated set‐up. Finally, we discuss how this heterogeneity, caused by both intrinsic and extrinsic factors, limits our ability to build digital twins of patient‐derived cardiomyocytes. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising tool to study arrhythmia-related factors, but the variability of action potential (AP) recordings from these cells limits their use as an in vitro model. In this study, we use recently published brief (10 s), dynamic voltage-clamp (VC) data to provide mechanistic insights into the ionic currents contributing to AP heterogeneity; we call this approach rapid ionic current phenotyping (RICP). Features of this VC data were correlated to AP recordings from the same cells, and we used computational models to generate mechanistic insights into cellular heterogeneity. This analysis uncovered several interesting links between AP morphology and ionic current density: both L-type calcium and sodium currents contribute to upstroke velocity, rapid delayed rectifier K+ current is the main determinant of the maximal diastolic potential, and an outward current in the activation range of slow delayed rectifier K+ is the main determinant of AP duration. Our analysis also identified an outward current in several cells at 6 mV that is not reproduced by iPSC-CM mathematical models but contributes to determining AP duration. RICP can be used to explain how cell-to-cell variability in ionic currents gives rise to AP heterogeneity. Because of its brief duration (10 s) and ease of data interpretation, we recommend the use of RICP for single-cell patch-clamp experiments that include the acquisition of APs. NEW & NOTEWORTHY We present rapid ionic current phenotyping (RICP), a current quantification approach based on an optimized voltage-clamp protocol. The method captures a rich snapshot of the ionic current dynamics, providing quantitative information about multiple currents (e.g., ICa, L, IKr) in the same cell. The protocol helped to identify key ionic determinants of cellular action potential heterogeneity in iPSC-CMs. This included unexpected results, such as the critical role of IKr in establishing the maximum diastolic potential. [ABSTRACT FROM AUTHOR]

Background and purpose: Pulmonary arteriovenous malformations (PAVMs) may cause recurrent brain abscess. The primary aim was to determine the prevalence of PAVM amongst survivors of brain abscess. The proportion with cardiac right‐to‐left shunts was also assessed post hoc. Methods: This was a cross‐sectional population‐based study of adult (≥18 years) survivors of cryptogenic bacterial brain abscess in Denmark from 2007 through 2016. Patients were invited for bubble‐echocardiography to detect vascular right‐to‐left shunting and, if abnormal, subsequent computed tomography thorax for diagnosis of PAVM. Data are presented as n/N (%) or median with interquartile range (IQR). Results: Study participation was accepted by 47/157 (30%) eligible patients amongst whom two did not appear for scheduled bubble‐echocardiography. The median age of participants was 54 years (IQR 45–62) and 19/57 (33%) were females compared with 59 years (IQR 48–68, p = 0.05) and 41/85 females (48%, p = 0.22) in non‐participants. Bubble‐echocardiography was suggestive of shunt in 10/45 (22%) participants and PAVM was subsequently confirmed by computed tomography in one patient with grade 1 shunting. The corresponding prevalence of PAVM was 2% (95% confidence interval 0.06–11.8) amongst all examined participants. Another 9/45 (20%) were diagnosed with patent in persistent foramen ovale (n = 8) or atrial septum defect (n = 1), which is comparable with the overall prevalence of 25% amongst adults in the Danish background population. Conclusions: Undiagnosed PAVM amongst adult survivors of cryptogenic bacterial brain abscess is rare but may be considered in select patients. The prevalence of cardiac right‐to‐left shunts amongst brain abscess patients corresponds to the prevalence in the general population. [ABSTRACT FROM AUTHOR]

This document is a collection of editorials from the Journal of the American Medical Association (JAMA) Psychiatry, covering various topics related to psychiatry and mental health. The editorials provide insights and perspectives from experts in the field. [Extracted from the article]

Few studies have investigated associations of milestone development in early childhood with intelligence in adulthood in typically developing children. The current study is an extension of 2 previous studies on smaller samples and investigated associations of age at attainment of 32 developmental milestones attained between 0 and 3 years of age with adult intelligence and explored whether the effects of early infant milestones are mediated through later development during subsequent years. Mothers of 8,400 children from the Copenhagen Perinatal Cohort recorded 32 developmental milestones during the child's first 3 years of life. Information on at least 1 developmental milestone was available for 2 subsamples with adult follow-up information on intelligence: Børge Priens Prøve (BPP) was available for 2,567 men while Wechsler Adult Intelligence Scale (WAIS) was available for 1,000 men and women. The study found that early attainment of milestones, primarily those related to standing/walking and language development, was associated with higher intelligence in adulthood. The adjusted BPP means were 103.7, 101.7, and 99.5, respectively, for being able to name objects/animals in pictures at less than 18 months, 18-24 months, and later than 24 months. Mediation analyses showed direct associations of the 1-year milestones related to standing/walking with intelligence with the direct association accounting for 74.6% and 64.4% of the total association in each subsample. Thus, milestones related to standing and walking primarily show a direct association with adult intelligence and are to a smaller extent mediated by milestones reflecting development during the subsequent years, in particular language development.

The study investigated whether age at attainment of 20 developmental milestones within the areas of language, walking, eating, dressing, social interaction, and toilet training was associated with adult intelligence. Mothers of 821 children of the Copenhagen Perinatal Cohort recorded 20 developmental milestones at a 3-year examination, and all children were administered the Wechsler Adult Intelligence Scale when they were 20-34 years old. Later attainment of a number of milestones was associated with lower adult IQ with the strongest associations found for those related to language and social interaction. The adjusted full-scale IQ means were 107.0, 101.8, and 100.6 for being able to form a sentence at less than 24 months, at 24 months, and later than 24 months.

Cardiac ion currents may compensate for each other when one is compromised by a congenital or drug-induced defect. Such redundancy contributes to a robust repolarization reserve that can prevent the development of lethal arrhythmias. Most efforts made to describe this phenomenon have quantified contributions by individual ion currents. However, it is important to understand the interplay between all major ion-channel conductances, as repolarization reserve is dependent on the balance between all ion currents in a cardiomyocyte. Here, a genetic algorithm was designed to derive profiles of nine ion-channel conductances that optimize repolarization reserve in a mathematical cardiomyocyte model. Repolarization reserve was quantified using a previously defined metric, repolarization reserve current, i.e., the minimum constant current to prevent normal action potential repolarization in a cell. The optimization improved repolarization reserve current up to 84% compared to baseline in a human adult ventricular myocyte model and increased resistance to arrhythmogenic insult. The optimized conductance profiles were not only characterized by increased repolarizing current conductances but also uncovered a previously unreported behavior by the late sodium current. Simulations demonstrated that upregulated late sodium increased action potential duration, without compromising repolarization reserve current. The finding was generalized to multiple models. Ultimately, this computational approach, in which multiple currents were studied simultaneously, illuminated mechanistic insights into how the metric's magnitude could be increased and allowed for the unexpected role of late sodium to be elucidated. [ABSTRACT FROM AUTHOR]