Polygenic risk and hostile environments: Links to stable and dynamic antisocial behaviors across adolescence.

Adverse environments are linked to elevated youth antisocial behavior. However, this relation is thought to depend, in part, on genetic susceptibility. The present study investigated whether polygenic risk for antisociality moderates relations between hostile environments and stable as well as dynamic antisocial behaviors across adolescence. We derived two antisocial-linked polygenic risk scores (PRS) (N = 721) based on previous genome-wide association studies. Forms of antisocial behavior (nonaggressive conduct problems, physical aggression, social aggression) and environmental hostility (harsh parenting and school violence) were assessed at age 13, 15, and 17 years. Relations to individual differences stable across adolescence (latent stability) vs. time-specific states (timepoint residual variance) of antisocial behavior were assessed via structural equation models. Higher antisocial PRS, harsh parenting, and school violence were linked to stable elevations in antisocial behaviors across adolescence. We identified a consistent polygenic-environment interaction suggestive of differential susceptibility in late adolescence. At age 17, harsher parenting was linked to higher social aggression in those with higher antisocial PRS, and lower social aggression in those with lower antisocial PRS. This suggests that genetics and environmental hostility relate to stable youth antisocial behaviors, and that genetic susceptibility moderates home environment-antisocial associations specifically in late adolescence.

Associations between epigenetic aging and childhood peer victimization, depression, and suicidal ideation in adolescence and adulthood: A study of two population-based samples.

Background: Prior studies indicate that peer victimization (including bullying) is associated with higher risk for depression and suicidal ideation across the life course. However, molecular mechanisms underlying these associations remain unclear. This two-cohort study proposes to test whether epigenetic aging and pace of aging, as well as a DNA methylation marker of responsive to glucocorticoids, are associated to childhood peer victimization and later depressive symptoms, or suicidal ideation. Methods: Cohort 1: Epigenome-wide DNA methylation (EPIC array) was measured in saliva collected when participants were 10.47 years (standard deviation = 0.35) in a subsample of the Quebec Longitudinal Study of Child Development (QLSCD, n = 149 participants), with self-reported peer victimization at 6-8 years, depressive symptoms (mean symptoms, and dichotomized top 30% symptoms) and suicidal ideation at 15-17 years. Cohort 2: Epigenome-wide DNA methylation (EPIC array) was measured in blood collected from participants aged 45.13 years (standard deviation = 0.37) in a subsample of the 1958 British Birth cohort (1958BBC, n = 238 participants) with information on mother-reported peer victimization at 7-11 years, self-reported depressive symptoms at 50 years, and suicidal ideation at 45 years. Five epigenetic indices were derived: three indicators of epigenetic aging [Horvath's pan-tissue (Horvath1), Horvath's Skin-and-Blood (Horvath2), Pediatric-Buccal-Epigenetic age (PedBE)], pace of aging (DunedinPACE), and stress response reactivity (Epistress). Results: Peer victimization was not associated with the epigenetic indices in either cohort. In the QLSCD, higher PedBE epigenetic aging and a slower pace of aging as measured by DunedinPACE predicted higher depressive symptoms scores. In contrast, neither the Horvath1, or Horvath2 epigenetic age estimates, nor the Epistress score were associated with depressive symptoms in either cohort, and none of the epigenetic indices predicted suicidal ideation. Conclusion: The findings are consistent with epigenome-wide and candidate gene studies suggesting that these epigenetic indices did not relate to peer victimization, challenging the hypothesis that cumulative epigenetic aging indices could translate vulnerability to depressive symptoms and suicidal ideation following peer victimization. Since some indices of epigenetic aging and pace of aging signaled higher risk for depressive symptoms, future studies should pursue this investigation to further evaluate the robustness and generalization of these preliminary findings.

In utero and peripartum antiretroviral exposure as predictor of cognition in 6- to 10-year-old HIV-exposed Ugandan children - a prospective cohort study.

OBJECTIVES: To quantify association between in utero/peripartum antiretroviral (IPA) exposure and cognition, i.e. executive function (EF) and socioemotional adjustment (SEA), in school-aged Ugandan children who were perinatally HIV-infected (CPHIV, n = 100) and children who were HIV-exposed but uninfected (CHEU, n = 101). METHODS: Children were enrolled at age 6-10 years and followed for 12 months from March 2017 to December 2018. Caregiver-reported child EF and SEA competencies were assessed using validated questionnaires at baseline, 6 and 12 months. IPA type - combination antiretroviral therapy (cART), intrapartum single-dose nevirapine ± zidovudine (sdNVP ± ZDV), nevirapine + zidovudine + lamivudine (sdNVP + ZDV + 3TC) - or no IPA (reference) was verified via medical records. IPA-related standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) in cognitive competencies were estimated from regression models with adjustment for caregiver sociodemographic and contextual factors. Models were fitted separately for CPHIV and CHEU. RESULTS: Among CPHIV children, cART (SMD = -0.82, 95% CI: -1.37 to -0.28) and sdNVP ± ZDV (SMD = -0.41, 95% CI: -0.81 to -0.00) vs. no IPA predicted lower executive dysfunction over 12 months. Intrapartum sdNVP + ZDV + 3TC vs. no IPA predicted executive dysfunction (SMD = 0.80, 95% CI: 0.30-1.31), SEA problems (SMD = 0.63-0.76, 95% CI: 0.00-1.24) and lower adaptive skills (SMD = -0.36, 95% CI: -0.75-0.02) over 12 months among CHEU. Further adjustment for contextual factors attenuated associations, although most remained of moderate clinical importance (|SMD| > 0.33). CONCLUSIONS: Among CPHIV children, cART and sdNVP ± ZDV IPA exposure predicted, on average, lower executive dysfunction 6-10 years later. However, peripartum sdNVP + ZDV + 3TC predicted executive and SEA dysfunction among CHEU 6-10 years later. These data underscore the need for more research into long-term effects of in utero ART to inform development of appropriate interventions so as to mitigate cognitive sequelae.

Motor control and cognition deficits associated with protein carbamoylation in food (cassava) cyanogenic poisoning: Neurodegeneration and genomic perspectives.

A case-control design determined whether konzo, an upper motoneuron disease linked to food (cassava) toxicity was associated with protein carbamoylation and genetic variations. Exon sequences of thiosulfate sulfurtransferase (TST) or mercaptopyruvate sulfurtransferase (MPST), plasma cyanide detoxification rates, and 2D-LC-MS/MS albumin carbamoylation were assessed in 40 children [21 konzo-affected and 19 putatively healthy controls, mean (SD) age: 9.2 (3.0) years] subjected to cognition and motor testing using the Kaufman Assessment Battery and the Bruininks/Oseretsky Test, respectively. Konzo was significantly associated with higher levels of carbamoylated peptides 206-219 (LDELRDEGKASSAK, pep1) after adjusting for age, gender, albumin concentrations and BUN [regression coefficient: 0.03 (95%CI:0.02-0.05), p = 0.01]. Levels of pep1 negatively correlated with performance scores at all modalities of motor proficiency (r = 0.38 to 0.61; all p < 0.01) or sequential processing (memory)(r = - 0.59, p = 0.00) and overall cognitive performance (r = - 0.48, p = 0.00) but positively with time needed for cyanide detoxification in plasma (r = 0.33, p = 0.04). Rare potentially damaging TST p.Arg206Cys (rs61742280) and MPST p.His317Tyr (rs1038542246) heterozygous variants were identified but with no impact on subject phenotypes. Protein carbamoylation appears to be a reliable marker for cassava related neurodegeneration.

The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Associations among oxytocin receptor gene (OXTR) DNA methylation in adulthood, exposure to early life adversity, and childhood trajectories of anxiousness.

Recent models propose deoxyribonucleic acid methylation of key neuro-regulatory genes as a molecular mechanism underlying the increased risk of mental disorder associated with early life adversity (ELA). The goal of this study was to examine the association of ELA with oxytocin receptor gene (OXTR) methylation among young adults. Drawing from a 21-year longitudinal cohort, we compared adulthood OXTR methylation frequency of 46 adults (23 males and 23 females) selected for high or low ELA exposure based on childhood socioeconomic status and exposure to physical and sexual abuse during childhood and adolescence. Associations between OXTR methylation and teacher-rated childhood trajectories of anxiousness were also assessed. ELA exposure was associated with one significant CpG site in the first intron among females, but not among males. Similarly, childhood trajectories of anxiousness were related to one significant CpG site within the promoter region among females, but not among males. This study suggests that females might be more sensitive to the impact of ELA on OXTR methylation than males.

Parenting begets parenting: A neurobiological perspective on early adversity and the transmission of parenting styles across generations.

The developing brains of young children are highly sensitive to input from their social environment. Nurturing social experience during this time promotes the acquisition of social and cognitive skills and emotional competencies. However, many young children are confronted with obstacles to healthy development, including poverty, inappropriate care, and violence, and their enhanced sensitivity to the social environment means that they are highly susceptible to these adverse childhood experiences. One source of social adversity in early life can stem from parenting that is harsh, inconsistent, non-sensitive or hostile. Parenting is considered to be the cornerstone of early socio-emotional development and an adverse parenting style is associated with adjustment problems and a higher risk of developing mood and behavioral disorders. Importantly, there is a growing literature showing that an important predictor of parenting behavior is how parents, especially mothers, were parented themselves. In this review, we examine how adversity in early-life affects mothering behavior in later-life and how these effects may be perpetuated inter-generationally. Relying on studies in humans and animal models, we consider evidence for the intergenerational transmission of mothering styles. We then describe the psychological underpinnings of mothering, including responsiveness to young, executive function and affect, as well as the physiological mediators of mothering behavior, including hormones, brain regions and neurotransmitters, and we consider how development in these relevant domains may be affected by adversity experienced in early life. Finally, we explore how genes and early experience interact to predict mothering behavior, including the involvement of epigenetic mechanisms. Understanding how adverse parenting begets adverse parenting in the next generation is critical for designing interventions aimed at preventing this intergenerational cycle of early adversity.

Lower sulfurtransferase detoxification rates of cyanide in konzo-A tropical spastic paralysis linked to cassava cyanogenic poisoning.

Using a matched case-control design, we sought to determine whether the odds of konzo, a distinct spastic paraparesis associated with food (cassava) cyanogenic exposure in the tropics, were associated with lower cyanide detoxification rates (CDR) and malnutrition. Children with konzo (N=122, 5-17 years of age) were age- and sex-matched with presumably healthy controls (N=87) and assessed for motor and cognition performances, cyanogenic exposure, nutritional status, and cyanide detoxification rates (CDR). Cyanogenic exposure was ascertained by thiocyanate (SCN) concentrations in plasma (P-SCN) and urine (U-SCN). Children with a height-for-age z-score (HAZNCHS)<-2 were classified as nutritionally stunted. CDR was measured as time required to convert cyanide to SCN, and expressed as ms/µmol SCN/mg protein or as mmolSCN/ml plasma/min. Mean (SD) U-SCN in children with konzo was 521.9 (353.6) µmol/l and was, significantly higher than 384.6 (223.7) µmol/l in those without konzo. Conditional regression analysis of data for age- and sex- matched case-control pairs showed that konzo was associated with stunting (OR: 5.8; 95% CI: 2.7-12.8; p<0.01; N=83 paired groups) and higher U-SCN (OR: 1.1; 95% CI: 1.02-1.20 per 50-µmol increase in U-SCN; p=0.02; N=47 paired groups). After adjusting for stunting and U-SCN, the odds of developing konzo was reduced by 63% (95% CI: 11-85%, p=0.03; N=41 paired groups) for each 5mmol SCN/(ml plasma/min)-increase in CDR. Linear regression analysis indicated a significant association between BOT-2 or KABC-II scores and both the HAZNCHS z-score and the U-SCN concentration, but not the CDR. Our findings provide evidence in support of interventions to remove cyanogenic compounds from cassava prior to human consumption or, peharps, enhance the detoxification of cyanide in those relying on the cassava as the main source of food.

Environmental influence of problematic social relationships on adolescents' daily cortisol secretion: a monozygotic twin-difference study.

BACKGROUND: This study investigated the potential environmental effects of peer victimization and the quality of relationships with parents and friends on diurnal cortisol secretion in mid-adolescence. METHOD: This study used the monozygotic (MZ) twin-difference design to control for genetic effects and thus estimate the unique environmental influences on diurnal cortisol. Participants were 136 MZ twin pairs (74 female pairs) for whom cortisol was assessed four times per day over four collection days grouped in a 2-week period in grade 8 (mean age = 14.07 years). Participants also provided self-reports of peer victimization from grade 4 to grade 8 and of the relationship quality with the mother, father and best friend in grade 8. RESULTS: The expected pattern of diurnal cortisol secretion was observed, with high levels at awakening followed by an increase 30 min later and a progressive decrease subsequently. Controlling for a host of confounders, only within-twin pair differences in peer victimization and a problematic relationship with the mother were significantly linked to twin differences in diurnal cortisol secretion. Specifically, whereas a more problematic mother-child relationship was associated with morning cortisol secretion, peer victimization was linked to cortisol secretion later in the day (diurnal slope). CONCLUSIONS: Controlling for genetic influences and other confounders, stressful relationships with peers and the mother exert unique and time-specific environmental influences on the pattern of diurnal cortisol secretion in mid-adolescence.

Caregiver mental health and HIV-infected child wellness: perspectives from Ugandan caregivers.

Prior studies indicate a substantial link between maternal depression and early child health but give limited consideration to the direction of this relationship or the context in which it occurs. We sought to create a contextually informed conceptual framework of this relationship through semi-structured interviews with women that had lived experience of caring for an HIV-infected child while coping with depression and anxiety symptoms. Caregivers explained their role in raising healthy children as complex and complicated by poverty, stigma, and isolation. Caregivers discussed the effects of their own mental health on child well-being as primarily emotional and behavioral, and explained how looking after a child could bring distress, particularly when unable to provide desired care for sick children. Our findings suggest the need for investigation of the reciprocal effects of child sickness on caregiver wellness and for integrated programs that holistically address the needs of HIV-affected families.

Fitness, obesity and risk of asthma among Army trainees.

BACKGROUND: Epidemiological data suggest an association between overweight/obesity and asthma. However, less is known about the relationship between physical fitness and asthma. AIMS: To enumerate new-onset asthma diagnoses in Army recruits during the first 2 years of service and determine associations with fitness and excess body fat (EBF) at military entrance. METHODS: New asthma diagnoses over 2 years in Army recruits at six entrance stations were obtained from military health and personnel records. Poisson regression models were used to determine associations of asthma diagnosis with pre-accession fitness testing, EBF and other potential factors. RESULTS: In 9979 weight-qualified and 1117 EBF entrants with no prior history of asthma, 256 new cases of asthma were diagnosed within 2 years of military entry. Low level of fitness, defined by a step test and EBF, was significantly associated with new asthma diagnosis [adjusted incidence rate ratio (IRR), 1.47; 95% confidence interval (CI) 1.11-1.96 and adjusted IRR, 1.53; 95% CI 1.06-2.20, respectively]. CONCLUSIONS: Individuals with low fitness levels, EBF or both are at higher risk of asthma diagnosis in the first 2 years of military service.

Genetic and environmental aetiology of the dimensions of Callous-Unemotional traits.

BACKGROUND: A Callous-Unemotional trait specifier (termed 'Limited Prosocial Emotions') was added to the diagnosis of conduct disorder in DSM-5. The Inventory of Callous-Unemotional Traits (ICU) is a comprehensive measure of these traits assessing three distinct, yet correlated dimensions--Callousness, Uncaring, and Unemotional--all thought to reflect the general Callous-Unemotional construct. The present study was the first to examine the degree to which the aetiology of these dimensions is shared v. independent. METHOD: Parent-reported ICU data from 5092 16-year-old twin pairs from the Twins Early Development Study were subjected to confirmatory factor analysis. Multivariate genetic modelling was applied to the best-fitting structure. RESULTS: A general-specific structure, retaining a general factor and two uncorrelated specific factors (Callousness-Uncaring, Unemotional), provided the best fit to the data. The general factor was substantially heritable (h2 = 0.58, 95% CI 0.51-0.65). Unusually, shared environmental influences were also important in accounting for this general factor (c2 = 0.26, 95% CI 0.22-0.31), in addition to non-shared environmental influences. The Unemotional dimension appeared phenotypically and genetically distinct as shown by the substantial loadings of unemotional items on a separate dimension and a low genetic correlation between Unemotional and Callousness-Uncaring. CONCLUSIONS: A general factor, indicative of a shared phenotypic structure across the dimensions of the ICU was under substantial common genetic and more modest shared environment influences. Our findings also suggest that the relevance of the Unemotional dimension as part of a comprehensive assessment of CU traits should be investigated further.

Severe congenital malformations, family functioning and parents' separation/divorce: a longitudinal study.

BACKGROUND: We aim to explore the association of a severe congenital malformation (SCM) with postnatal family functioning and parents' separation/divorce and to examine if this association might be moderated by birth order of the child and parental level of education. SCM refers to malformations that, without medical intervention, cause handicap or death. METHODS: Using the Quebec Longitudinal Study of Child Development, an ongoing population-based birth cohort study initiated in 1998, we compared 1675 families of children with and without a SCM to identify if having a child with a SCM was associated with maternal perception of family functioning. We examined if an SCM was associated with parents' separation and examined parents' education level and birth order of the children to evaluate whether these factors had any moderating effect on the results. RESULTS: There were no significant differences in family functioning between families with and without a SCM child at 5 and 17 months. At 5 months, family functioning was significantly better (P = 0.03) for families with a SCM firstborn child than for families with a SCM child that is not firstborn. For parental separation, no significant differences were observed at 5 and 29 months and 4 years. No significant moderating effects were observed for birth order and parental education on parental separation. CONCLUSIONS: Families of children with a SCM do not appear to be at higher risk of family dysfunction within the first 17 months after birth nor of parental separation within the first 4 years after birth. Family functioning tends to be worst in families where the child with SCM is the second or subsequent child born.

Lower serum levels of selenium, copper, and zinc are related to neuromotor impairments in children with konzo.

We assessed the relationship between key trace elements and neurocognitive and motor impairments observed in konzo, a motor neuron disease associated with cassava cyanogenic exposure in nutritionally challenged African children. Serum concentrations of iron, copper, zinc, selenium, and neurotoxic lead, mercury, manganese, cadmium, and cobalt were measured in 123 konzo children (mean age 8.53 years) and 87 non-konzo children (mean age 9.07 years) using inductively coupled plasma mass spectrometry (ICPMS). Concentrations of trace elements were compared and related to performance scores on the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) for cognition and Bruininks-Oseretsky Test, 2nd edition (BOT-2) for motor proficiency. Children with konzo had low levels of selenium, copper, and zinc relative to controls. Selenium concentration significantly correlated with serum 8,12-iso-iPF2α-VI isoprostane (Spearman r=0.75, p<0.01) and BOT-2 scores (r=0.31, p=0.00) in children with konzo. Elemental deficiency was not associated with poor cognition. Mean (SD) urinary level of thiocyanate was 388.03 (221.75) µmol/l in non-konzo compared to 518.59 (354.19) µmol/l in konzo children (p<0.01). Motor deficits associated with konzo may possibly be driven by the combined effects of cyanide toxicity and Se deficiency on prooxidant mechanisms. Strategies to prevent konzo may include dietary supplementation with trace elements, preferentially, those with antioxidant and cyanide-scavenging properties.

Executive function and attention-deficit/hyperactivity disorder in Ugandan children with perinatal HIV exposure.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is among the most commonly diagnosed mental disorders in childhood and is associated with substantial deficits in executive functioning and lost academic and occupational attainment. This study evaluates symptoms of ADHD and their association with neurocognitive deficits in a cohort of rural Ugandan children who were born to HIV-infected mothers. METHODS: We assessed ADHD symptoms and executive function (including memory and attention) in a non-clinical sample of children born to HIV-infected mothers in rural eastern Uganda. Analyses included assessments of the psychometric properties, factor structure, and convergent and discriminant validity of the ADHD measure (ADHD-Rating Scale-IV); and executive function deficits in children meeting symptom criteria for ADHD. RESULTS: 232 children [54% female; mean age 7.8 years (s.d. 2.0)] were assessed for ADHD and executive function deficits. The ADHD measure showed good internal consistency (α = 0.85.) Confirmatory factor analysis showed an acceptable fit for the diagnostic and statistical manual of mental disorders (DSM-5) two-factor model. Subjects meeting DSM-5 symptom criteria for ADHD had worse parent-rated executive function on six out of seven subscales. CONCLUSIONS: Our results demonstrate structural validity of the ADHD measure with this population, strong associations between ADHD symptom severity and poorer executive function, and higher levels of executive function problems in perinatally HIV-exposed Ugandan children with ADHD. These findings suggest that ADHD may be an important neurocognitive disorder associated with executive function problems among children in sub-Saharan African settings where perinatal HIV exposure is common.

Designing and evaluating Brain Powered Games for cognitive training and rehabilitation in at-risk African children.

BACKGROUND: Valid, reliable, accessible, and cost-effective computer-training approaches can be important components in scaling up educational support across resource-poor settings, such as sub-Saharan Africa. The goal of the current study was to develop a computer-based training platform, the Michigan State University Games for Entertainment and Learning laboratory's Brain Powered Games (BPG) package that would be suitable for use with at-risk children within a rural Ugandan context and then complete an initial field trial of that package. METHODS: After game development was completed with the use of local stimuli and sounds to match the context of the games as closely as possible to the rural Ugandan setting, an initial field study was completed with 33 children (mean age = 8.55 ± 2.29 years, range 6-12 years of age) with HIV in rural Uganda. The Test of Variables of Attention (TOVA), CogState computer battery, and the Non-Verbal Index from the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) were chosen as the outcome measures for pre- and post-intervention testing. The children received approximately 45 min of BPG training several days per week for 2 months (24 sessions). RESULTS: Although some improvements in test scores were evident prior to BPG training, following training, children demonstrated clinically significant changes (significant repeated-measures outcomes with moderate to large effect sizes) on specific TOVA and CogState measures reflecting processing speed, attention, visual-motor coordination, maze learning, and problem solving. CONCLUSIONS: Results provide preliminary support for the acceptability, feasibility, and neurocognitive benefit of BPG and its utility as a model platform for computerized cognitive training in cross-cultural low-resource settings.

Immunological correlates of behavioral problems in school-aged children living with HIV in Kayunga, Uganda.

BACKGROUND: HIV can affect the neuropsychological function of children, including their behavior. We aim to identify immunological correlates of behavioral problems among children living with HIV in Uganda. METHODS: Children participating in a parent randomized control trial in Kayunga, Uganda were assessed with the Behavior Rating Inventory of Executive Function (BRIEF) and the Child Behavior Checklist (CBCL). We constructed simple and multiple linear regression models to identify immunological correlates of behavioral problems. RESULTS: A total of 144 children living with HIV (50% male) with a mean age of 8.9 years [Standard Deviation (s.d.) = 1.9] were included in the analysis. Eighty-two children were on antiretroviral therapy. Mean CD4 cell count % was 35.1 cells/µl (s.d. = 15.0), mean CD4 cell activation 5.7% (s.d. = 5.1), mean CD8 cell activation was 17.5% (s.d. = 11.2) and 60 children (41.7%) had a viral load of <4000 copies/ml. In the adjusted models for the BRIEF, higher scores were associated with higher viral loads (aß = 16.7 × 10-6, 95% CI -5.00 × 10-6 to 28.4 × 10-6), specifically on the behavioral regulation index. Higher mean CD8 activation % was associated with higher scores on the Externalizing Problems  and Total Problems  scales of the CBCL (aß = 0.17, 95% CI 0.04-0.31 and aß = 0.15, 95% CI 0.00-0.28, respectively). CONCLUSIONS: Poorer behavioral outcomes were associated with higher viral loads while higher CD8 activation was associated with poorer emotional and behavioral outcomes. Complete immunological assessments for children living with HIV could include commonly used viral and immunological parameters to identify those at higher risk of having negative behavior outcomes and who would benefit the most from behavioral interventions.

Fitness, obesity and risk of heat illness among army trainees.

BACKGROUND: Exertional heat illness (EHI) affects military personnel, athletes and occupational groups such as agricultural workers, despite knowledge of preventive measures. AIMS: To evaluate EHI diagnoses during US Army basic training and its associations with fitness and body fat on entering military service. METHODS: From February 2005 to September 2006, US Army recruits at six different military entrance stations took a pre-accession fitness test, including a 5-min step test scored as pass or fail. Subsequent EHI incidence and incidence rate ratios were analysed with reference to subjects' fitness (step test performance) and whether they met (weight qualified [WQ]) or exceeded body fat (EBF) standards. RESULTS: Among the 8621 WQ and 834 EBF male subjects, there were 67 incidents of EHI within 180 days of entering military service. Among WQ subjects, step test failure was significantly associated with EHI (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.13, 3.53). For those passing the step test, the risk of EHI was significantly higher in EBF than in WQ subjects (OR 3.98, 95% CI 2.17, 7.29). Expected ORs for the joint effects of step test failure and EBF classification under additive and multiplicative models were 4.98 and 7.96, respectively. There were too few women to evaluate their data in detail. CONCLUSIONS: This study demonstrated that fitness and body fat are independently associated with incident EHI, and the effect of both was substantially higher. Those with low fitness levels and/or obesity should be evaluated further before engaging in intense physical activity, especially in warmer months.

Determinants of cognitive performance in children relying on cyanogenic cassava as staple food.

While risk factors for konzo are known, determinants of cognitive impairment in konzo-affected children remain unknown. We anchored cognitive performance (KABC-II scores) to serum levels of free-thyroxine (free-T4), thyroid-stimulating hormone (TSH), albumin, and motor proficiency (BOT-2 scores) in 40 children including 21 with konzo (median age: 9 years) and 19 without konzo (median age: 8 years). A multiple regression model was used to determine variables associated with changes in KABC-II scores. Age (ß: -0.818, 95% CI: -1.48, -0.152) (p = 0.018), gender (ß: -5.72; 95% CI: -9.87, -1.57 for females) (p = 0.009), BOT-2 score (ß: 0.390; 95% CI: 0.113, 0.667) (p = 0.008), and free-T4 (ß: 1.88; 95% CI: 0.009, 3.74) (p = 0.049) explained 61.1 % of variation in KABC-II scores. Subclinical hypothyroidism was not associated with poor cognition. A crude association was found between serum albumin and KABC-II scores (ß: 1.26; 95 % CI: 0.136, 2.39) (p = 0.029). On spot urinary thiocyanate reached 688 µmol/l in children without konzo and 1,032 µmol/L in those with konzo. Female gender and low serum albumin are risk factors common to cognitive and proportionally associated motor deficits in children exposed to cassava cyanogens. The two types of deficits may share common mechanisms.

A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome.

BACKGROUND: Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period. METHOD: Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model. RESULTS: The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA. CONCLUSIONS: Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic-environment correlation (r GE) and interaction (G×E) analyses.