Rare copy number variation in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Historical biogeography and local adaptation explain population genetic structure in a widespread terrestrial orchid.

BACKGROUND AND AIMS: Historical changes in environmental conditions and colonization-extinction dynamics have a direct impact on the genetic structure of plant populations. However, understanding how past environmental conditions influenced the evolution of species with high gene flow is challenging when signals for genetic isolation and adaptation are swamped by gene flow. We investigated the spatial distribution and genetic structure of the widespread terrestrial orchid Epipactis helleborine to identify glacial refugia, characterize postglacial population dynamics and assess its adaptive potential. METHODS: Ecological niche modelling was used to locate possible glacial refugia and postglacial recolonization opportunities of E. helleborine. A large single-nucleotide polymorphism (SNP) dataset obtained through genotyping by sequencing was used to define population genetic diversity and structure and to identify sources of postglacial gene flow. Outlier analyses were used to elucidate how adaptation to the local environment contributed to population divergence. KEY RESULTS: The distribution of climatically suitable areas was restricted during the Last Glacial Maximum to the Mediterranean, south-western Europe and small areas in the Alps and Carpathians. Within-population genetic diversity was high in E. helleborine (mean expected heterozygosity, 0.373 ± 0.006; observed heterozygosity, 0.571 ± 0.012; allelic richness, 1.387 ± 0.007). Italy and central Europe are likely to have acted as important genetic sources during postglacial recolonization. Adaptive SNPs were associated with temperature, elevation and precipitation. CONCLUSIONS: Forests in the Mediterranean and Carpathians are likely to have acted as glacial refugia for Epipactis helleborine. Postglacial migration northwards and to higher elevations resulted in the dispersal and diversification of E. helleborine in central Europe and Italy, and to geographical isolation and divergent adaptation in Greek and Italian populations. Distinguishing adaptive from neutral genetic diversity allowed us to conclude that E. helleborine has a high adaptive potential to climate change and demonstrates that signals of adaptation and historical isolation can be identified even in species with high gene flow.

Contribution of de novo and inherited rare CNVs to very preterm birth.

BACKGROUND: The genomic contribution to adverse health sequelae in babies born very preterm (<32 weeks' gestation) is unknown. We conducted an investigation of rare CNVs in infants born very preterm as part of a study to determine the feasibility and acceptability of a larger, well-powered genome-wide investigation in the UK, with follow-up using linked National Health Service records and DNA storage for additional research. METHODS: We studied 488 parent-offspring trios. We performed genotyping using Illumina Infinium OmniExpress Arrays. CNV calling and quality control (QC) were undertaken using published protocols. We examined de novo CNVs in infants and the rate of known pathogenic variants in infants, mothers and fathers and compared these with published comparator data. We defined rare pathogenic CNVs as those consistently reported to be associated with clinical phenotypes. RESULTS: We identified 14 de novo CNVs, representing a mutation rate of 2.9%, compared with 2.1% reported in control populations. The median size of these CNV was much higher than in comparator data (717 kb vs 255 kb). The rate of pathogenic CNVs was 4.3% in infants, 2.7% in mothers and 2% in fathers, compared with 2.3% in UK Biobank participants. CONCLUSION: Our findings suggest that the rate of de novo CNVs, especially rare pathogenic CNVs, could be elevated in those born very preterm. However, we will need to conduct a much larger study to corroborate this conclusion.

Impact of mating system on range size and niche breadth in Epipactis (Orchidaceae).

BACKGROUND AND AIMS: The geographical distribution of plant species is linked fundamentally not only to environmental variables, but also to key traits that affect the dispersal, establishment and evolutionary potential of a species. One of the key plant traits that can be expected to affect standing genetic variation, speed of adaptation and the capacity to colonize and establish in new habitats, and therefore niche breadth and range size, is the plant mating system. However, the precise role of the mating system in shaping range size and niche breadth of plant species remains unclear, and different studies have provided contrasting results. In this study, we tested the hypothesis that range size and niche breadth differed with mating system in the orchid genus Epipactis. METHODS: We modelled the ecological niches of 14 Epipactis species in Europe using occurrence records and environmental satellite data in Maxent. Niche breadth and niche overlap in both geographic and environmental space were calculated from the resulting habitat suitability maps using ENMTools, and geographic range was estimated using α-hull range definition. Habitat suitability, environmental variable contributions and niche metrics were compared among species with different mating systems. KEY RESULTS: We did not detect significant differences in niche breadth, occurrence probability or geographical range between autogamous and allogamous Epipactis species, although autogamous species demonstrated notably low variation in niche parameters. We also found no significant differences in niche overlap between species with the same mating system or different mating systems. For all Epipactis species, occurrence was strongly associated with land cover, particularly broad-leafed and coniferous forests, and with limestone bedrock. CONCLUSIONS: These results suggest that the mating system does not necessarily contribute to niche breadth and differentiation, and that other factors (e.g. mycorrhizal specificity) may be more important drivers of range size and niche breadth in Epipactis and orchids in general.

Acetyl-CoA carboxylase from Escherichia coli exhibits a pronounced hysteresis when inhibited by palmitoyl-acyl carrier protein.

Acetyl-CoA carboxylase (ACC) in bacteria is composed of three components: biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase. ACC catalyzes the first committed step in fatty acid synthesis: the carboxylation of acetyl-CoA to form malonyl-CoA via a two-step reaction. In the first half-reaction, biotin carboxylase catalyzes the ATP-dependent carboxylation of the vitamin biotin covalently linked to biotin carboxyl carrier protein. In the second half-reaction, the carboxyl group is transferred from biotin to acetyl-CoA by the enzyme carboxyltransferase, to form malonyl-CoA. In most Gram-negative and Gram-positive bacteria, the three components of ACC form a complex that requires communication for catalysis, and is subject to feedback inhibition by acylated-acyl carrier proteins. This study investigated the mechanism of inhibition of palmitoyl-acyl carrier protein (PACP) on ACC. Unexpectedly, ACC was found to exhibit a significant hysteresis, meaning ACC was subject to inhibition by PACP in a time dependent manner. Pull-down assays demonstrated PACP does not prevent formation of the multiprotein complex, while steady-state kinetic analyses showed PACP inhibited ACC activity allosterically. Structure-activity analyses revealed that the pantothenic acid moiety of PACP is responsible for the inhibition of ACC. This study provides the first evidence of the hysteretic nature of ACC.

Healthy eating patterns associated with acculturation, sex and BMI among Mexican Americans.

OBJECTIVE: Examine relationships of healthy and unhealthy dietary patterns with BMI, sex, age and acculturation among Mexican Americans. DESIGN: Cross-sectional. Participants completed culturally tailored Healthy and Unhealthy Eating Indices. Multivariable mixed-effect Poisson regression models compared food pattern index scores and dietary intake of specific foods by BMI, sex, age and acculturation defined by language preference and generational status. SETTING: Participants recruited from the Cameron County Hispanic Cohort study, Texas-Mexico border region, between 2008 and 2011. SUBJECTS: Mexican-American males and females aged 18-97 years (n 1250). RESULTS: Participants were primarily female (55·3 %), overweight or obese (85·7 %), preferred Spanish language (68·0 %) and first-generation status (60·3 %). Among first-generation participants, bilingual participants were less likely to have a healthy eating pattern than preferred Spanish-speaking participants (rate ratio (RR)=0·79, P=0·0218). This association was also found in males (RR=0·81, P=0·0098). Preferred English-speaking females were less likely to consume healthy foods than preferred Spanish-speaking females (RR=0·84, P=0·0293). Among second-generation participants, preferred English-speaking participants were more likely to report a higher unhealthy eating pattern than preferred Spanish-speaking participants (RR=1·23, P=0·0114). Higher unhealthy eating patterns were also found in females who preferred English v. females who preferred Spanish (RR=1·23, P=0·0107) or were bilingual (RR=1·26, P=0·0159). Younger, male participants were more likely to have a higher unhealthy eating pattern. BMI and diabetes status were not significantly associated with healthy or unhealthy eating patterns. CONCLUSIONS: Acculturation, age, sex and education are associated with healthy and unhealthy dietary patterns. Nutrition interventions for Mexican Americans should tailor approaches by these characteristics.

Exploring families' experiences of health: contributions to a model of family health.

Child health and developmental outcomes are influenced by the health of the family and the context created. Research suggests symptoms of poor family health (e.g. suboptimal family interactions, parenting stress) yet there is limited understanding of the factors which contribute to robust family health which may unveil opportunities for targeted intervention and family health promotion. The present study examined families' experiences of family health and factors contributing to family health. We performed a qualitative study using constructivist grounded theory methods to guide our understanding of family health for families with typically developing children aged 5-18. Interviews were conducted in family homes and all members were invited to participate. Data from interviews were transcribed, coded, thematically analyzed, and verified with select families. Ten families, including 10 mothers, 8 fathers, and 15 children participated in the study. Participants described family health as a process of balance, living purposefully, and sharing experiences together in alignment with family identity. Mediating family health were processes of awareness and reflection, and adapting, adjusting, and changing in response to family life including external stress factors. Results highlight the possibility for healthcare practitioners to facilitate families' self-reflection and awareness about their health in order to mediate family health development.

Carbon Fixation Driven by Molecular Hydrogen Results in Chemolithoautotrophically Enhanced Growth of Helicobacter pylori.

UNLABELLED: A molecular hydrogen (H2)-stimulated, chemolithoautotrophic growth mode for the gastric pathogen Helicobacter pylori is reported. In a culture medium containing peptides and amino acids, H2-supplied cells consistently achieved 40 to 60% greater growth yield in 16 h and accumulated 3-fold more carbon from [(14)C]bicarbonate (on a per cell basis) in a 10-h period than cells without H2 Global proteomic comparisons of cells supplied with different atmospheric conditions revealed that addition of H2 led to increased amounts of hydrogenase and the biotin carboxylase subunit of acetyl coenzyme A (acetyl-CoA) carboxylase (ACC), as well as other proteins involved in various cellular functions, including amino acid metabolism, heme synthesis, or protein degradation. In agreement with this result, H2-supplied cells contained 3-fold more ACC activity than cells without H2 Other possible carbon dioxide (CO2) fixation enzymes were not up-expressed under the H2-containing atmosphere. As the gastric mucus is limited in carbon and energy sources and the bacterium lacks mucinase, this new growth mode may contribute to the persistence of the pathogen in vivo This is the first time that chemolithoautotrophic growth is described for a pathogen. IMPORTANCE: Many pathogens must survive within host areas that are poorly supplied with carbon and energy sources, and the gastric pathogen Helicobacter pylori resides almost exclusively in the nutritionally stringent mucus barrier of its host. Although this bacterium is already known to be highly adaptable to gastric niches, a new aspect of its metabolic flexibility, whereby molecular hydrogen use (energy) is coupled to carbon dioxide fixation (carbon acquisition) via a described carbon fixation enzyme, is shown here. This growth mode, which supplements heterotrophy, is termed chemolithoautotrophy and has not been previously reported for a pathogen.

Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and µ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning.

Using a mixed-methods approach to measure impact of a school-based nutrition and media education intervention study on fruit and vegetable intake of Italian children.

OBJECTIVE: The purpose of the present study was to investigate the impact of a school-based nutrition and media education intervention on the promotion of fruit and vegetable consumption to help prevent childhood obesity. DESIGN: The 10-week-long intervention included sessions on nutrition education and media literacy. It also included a health communication media-based campaign workshop during which the children created posters, newsletters and video commercials related to fruits and vegetables targeted to their parents. For evaluation purposes, the study utilized a mixed-methods approach, including a quasi-experimental study (with one intervention group and one control group) and a focus group study. SETTING: Four different elementary schools in Treviso (Veneto Region of Italy) agreed to participate in the research. SUBJECTS: The target population for the study included 10-year-old Italian children and their parents. RESULTS: Data indicate that this intervention was effective for children but not for parents. Evaluation results show that the intervention was effective in significantly increasing children's fruit and vegetable intake (P<0·05) and all psychosocial determinants (P<0·05). CONCLUSIONS: The study results confirm the efficacy of a school-based health and media education intervention to address the children's obesity issue and, in particular, to increase children's fruit and vegetable intake. The study also opens a new perspective on the theoretical constructs investigated, because the development of 'ability of expression' could be considered one of the most important factors to determine the efficacy of the intervention.

Adolescents' awareness and use of menu labels in eating establishments: results from a focus group study.

OBJECTIVE: Menu labelling has been identified as a potential strategy to help individuals make healthier choices when eating out. Although adolescents eat out often, little research involving menu labelling has been conducted with this population. The objectives of the present study were to: (i) gather qualitative information from adolescents regarding use of menu labels when eating out; (ii) gather adolescents' suggestions for optimal ways to design menu labels; and (iii) examine differences between adolescents living in communities of different socio-economic status. DESIGN: Qualitative. Five focus groups of five to ten participants. SETTING: Austin, TX, USA, 2012. SUBJECTS: Forty-one adolescents living in diverse communities recruited using a snowballing technique at public and private recreation centres (twenty-four females; twenty-two African American). RESULTS: Participants reported that menu labelling, in general, does not influence food selections when eating out. Among participants living in low-income communities, food purchases were based on price, taste and familiarity. Among participants living in high-income areas, food purchases were based on quality and ability to satiate (among boys). According to participants, effective ways to present menu labels are by matching calorie levels with physical activity equivalents or through simple graphics. CONCLUSIONS: For adolescents, providing menu labels in their current format may not be an effective strategy to increase healthy food selection. Given that the current menu label format has been set by federal policy in the USA cannot be easily changed, research to determine how this format can be best presented or enhanced so that it can have an impact on all US sub-populations is warranted.

Association of parental social support with energy balance-related behaviors in low-income and ethnically diverse children: a cross-sectional study.

BACKGROUND: Parents play an important role in providing their children with social support for healthy eating and physical activity. However, different types of social support (e.g., instrumental, emotional, modeling, rules) might have different results on children's actual behavior. The purpose of this study was to assess the association of the different types of social support with children's physical activity and eating behaviors, as well as to examine whether these associations differ across racial/ethnic groups. METHODS: We surveyed 1169 low-income, ethnically diverse third graders and their caregivers to assess how children's physical activity and eating behaviors (fruit and vegetable and sugar-sweetened beverage intake) were associated with instrumental social support, emotional social support, modeling, rules and availability of certain foods in the home. We used sequential linear regression to test the association of parental social support with a child's physical activity and eating behaviors, adjusting for covariates, and then stratified to assess the differences in this association between racial/ethnic groups. RESULTS: Parental social support and covariates explained 9-13% of the variance in children's energy balance-related behaviors. Family food culture was significantly associated with fruit and vegetable and sugar-sweetened beverage intake, with availability of sugar-sweetened beverages in the home also associated with sugar-sweetened beverage intake. Instrumental and emotional support for physical activity were significantly associated with the child's physical activity. Results indicate that the association of various types of social support with children's physical activity and eating behaviors differ across racial/ethnic groups. CONCLUSIONS: These results provide considerations for future interventions that aim to enhance parental support to improve children's energy balance-related behaviors.

Socioeconomic inequalities in children's diet: the role of the home food environment.

BACKGROUND: It is well documented in the literature that low socioeconomic status (SES) is associated with lower consumption of healthy foods and that these differences in consumption patterns are influenced by neighborhood food environments. Less understood is the role that SES differences in physical and social aspects of the home food environment play in consumption patterns. METHODS: Using data on 4th grade children from the 2009-2011 Texas School Physical Activity and Nutrition (SPAN) study, we used mixed-effects regression models to test the magnitude of differences in the SPAN Health Eating Index (SHEI) by parental education as an indicator of SES, and the extent to which adjusting for measures of the home food environment, and measures of the neighborhood environment accounted for these SES differences. RESULTS: Small but significant differences in children's SHEI by SES strata exist (-1.33 between highest and lowest SES categories, p<0.01). However, incorporating home food environment and neighborhood environment measures in this model eliminates these differences (-0.7, p=0.145). Home food environment explains a greater portion of the difference. Both social (mealtime structure) and physical aspects (food availability) of the home food environment are strongly associated with consumption of healthy and unhealthy foods. CONCLUSIONS: Our findings suggest that modifiable parent behaviors at home can improve children's eating habits and that the neighborhood may impact diet in ways other than through access to healthy food.

Increasing access to healthful foods: a qualitative study with residents of low-income communities.

BACKGROUND: Inadequate access to healthful foods has been identified as a significant barrier to healthful dietary behaviors among individuals who live in low-income communities. The purpose of this study was to gather low-income community members' opinions about their food purchasing choices and their perceptions of the most effective ways to increase access to healthful foods in their communities. METHODS: Spanish and English focus groups were conducted in low-income, ethnically-diverse communities. Participants were asked about their knowledge, factors influencing their food purchasing decisions, and their perceptions regarding solutions to increase access to healthful foods. RESULTS: A total of 148 people participated in 13 focus groups. The majority of participants were female and ethnically diverse (63% Hispanic, 17% African American, 16% Caucasian, and 4% "other"). More than 75% of the participants reported making less than $1999 USD per month. Participants reported high levels of knowledge and preference for healthful foods. The most important barriers influencing healthful shopping behaviors included high price of healthful food, inadequate geographical access to healthful food, poor quality of available healthful food, and lack of overall quality of the proximate retail stores. Suggested solutions to inadequate access included placement of new chain supermarkets in their communities. Strategies implemented in convenience stores were not seen as effective. Farmers' markets, with specific stipulations, and community gardens were regarded as beneficial supplementary solutions. CONCLUSION: The results from the focus groups provide important input from a needs assessment perspective from the community, identify gaps in access, and offer potential effective solutions to provide direction for the future.

Implementing a free school-based fruit and vegetable programme: barriers and facilitators experienced by pupils, teachers and produce suppliers in the Boost study.

BACKGROUND: Multi-component interventions which combine educational and environmental strategies appear to be most effective in increasing fruit and vegetable (FV) intake in adolescents. However, multi-component interventions are complex to implement and often poorly implemented. Identification of barriers and facilitators for implementation is warranted to improve future interventions.This study aimed to explore implementation of two intervention components which addressed availability and accessibility of FV in the multi-component, school-based Boost study which targeted FV intake among Danish 13-year-olds and to identify barriers and facilitators for implementation among pupils, teachers and FV suppliers. METHODS: We conducted focus group interviews with 111 13-year-olds and 13 teachers, completed class observations at six schools, and conducted telephone interviews with all involved FV suppliers. Interviews were transcribed, coded and analysed using qualitative analytical procedures. RESULTS: FV suppliers affected the implementation of the FV programme at schools and thereby pupils' intake through their timing of delivery and through the quality, quantity and variety of the delivered FV. Teachers influenced the accessibility and appearance of FV by deciding if and when the pupils could eat FV and whether FV were cut up. Different aspects of time acted as barriers for teachers' implementation of the FV programme: time spent on having a FV break during lessons, time needed to prepare FV and time spent on pupils' misbehaviour and not being able to handle getting FV. Teacher timing of cutting up and serving FV could turn into a barrier for pupils FV intake due to enzymatic browning. The appearance of FV was important for pupils' intake, especially for girls. FV that did not appeal to the pupils e.g. had turned brown after being cut up were thrown around as a part of a game by the pupils, especially boys. Girls appreciated the social dimension of eating FV together to a larger extent than boys. CONCLUSIONS: Limited time and pupils' misbehaviour were barriers for teachers' implementation. Establishing FV delivery to schools as a new routine challenged FV suppliers' implementation. Food aesthetics were important for most pupils' FV intake while the social dimension of eating FV together seemed more important to girls than boys. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11666034.

Effects of cannabidiol, with and without ∆9-tetrahydrocannabinol, on anxiety-like behavior following alcohol withdrawal in mice.

Introduction: Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function. Methods: We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor. Results: We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100ß and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects.. Discussion: These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.

Conceptualizing, implementing, and monitoring a structural health promotion intervention in an organizational setting.

This article presents a framework for developing and carrying out an implementation monitoring plan of a complex structural intervention in an organizational setting and describes seven steps for analyzing and reporting results for fidelity and completeness of implementation. This process is illustrated using the Environmental Interventions in Children's Homes (ENRICH) Wellness Project. ENRICH aimed to promote physical activity and healthful nutrition behaviors among children residing in children's group homes by working collaboratively with organizational staff. A comprehensive implementation monitoring plan was developed based on the particulars of the setting, context, and the program framework and used multiple data sources, criteria for evidence of implementation, and data triangulation to examine evidence for organizational implementation. Eleven of 17 organizations (65%) met the criteria for nutrition implementation whereas 9 of 17 (53%) met the criteria for physical activity implementation. Implementation data can be used descriptively, as described here, and may also be used in future outcome analyses to better understand project outcomes. The framework and evaluation approach are applicable to complex interventions in other organizational settings.

Comparative toxicology of syringe exchange and postmortem blood samples in the District of Columbia: Trends and affinity analysis.

This cross-sectional analysis aimed to understand the similarities and differences between drugs detected in syringes collected from syringe service providers in the District of Columbia and fatal overdose deaths captured by the State Unintentional Drug Overdose Reporting System. Substance exposures for these fatal and non-fatal drug use outcomes have not been previously compared. Substance distributions were examined and a paired significance test was used to compare changes over time. Affinity analysis was employed to reveal substance co-occurrences. Between September 2020 and September 2022, 1,118 postmortem blood samples (PBSs) and 3,646 syringes exchange samples (SESs) were processed, with fatal overdoses increasing 24.1%. Polysubstance use was more commonly found in postmortem blood (82.5%) than in syringe samples (48.6%). Of samples containing opioids, 94.8% of blood samples and 86.3% of syringes contained fentanyl, fentanyl analogs or fentanyl precursors/metabolites. PBSs had double the frequency of co-occurring stimulants and opioids (43.9%) as SESs (21.8%). Major changes in occurrence frequency over time were found for opioid and stimulant exposure in both groups, especially in the increased occurrence of fluorofentanyl (>400%), methamphetamine (>90%) and xylazine (>60%), while the incidence of fentanyl, heroin and metabolite morphine declined. These results indicate that while fatal use and syringe exchange populations have distinct substance exposures, which may contribute to differences in mortality rate, their substance distributions have similar change magnitudes. This study highlights the utility of using multiple data sources to provide a comprehensive description of drug use patterns and discusses the limitations in reporting data from each source.

Sleep disturbance as a transdiagnostic marker of psychiatric risk in children with neurodevelopmental risk genetic conditions.

Children with rare neurodevelopmental genetic conditions (ND-GCs) are at high risk for a range of neuropsychiatric conditions. Sleep symptomatology may represent a transdiagnostic risk indicator within this patient group. Here we present data from 629 children with ND-GCs, recruited via the United Kingdom's National Health Service medical genetic clinics. Sibling controls (183) were also invited to take part. Detailed assessments were conducted to characterise the sleep phenotype of children with ND-GCs in comparison to controls. Latent class analysis was conducted to derive subgroups of children with an ND-GC based on sleep symptomatology. Assessment of cognition and psychopathology allowed investigation of whether the sleep phenotypic subgroup was associated with neuropsychiatric outcomes. We found that children with an ND-GC, when compared to control siblings, were at elevated risk of insomnia (ND-GC = 41% vs Controls = 17%, p < 0.001) and of experiencing at least one sleep symptom (ND-GC = 66% vs Controls = 39%, p < 0.001). On average, insomnia was found to have an early onset (2.8 years) in children with an ND-GC and to impact across multiple contexts. Children in subgroups linked to high sleep symptomatology were also at high risk of psychiatric outcomes (OR ranging from 2.0 to 21.5 depending on psychiatric condition). Our findings demonstrate that children with high genetic vulnerability for neurodevelopmental outcomes exhibit high rates of insomnia and sleep symptomatology. Sleep disruption has wide-ranging impacts on psychosocial function, and indexes those children at greater neuropsychiatric risk. Insomnia was found to onset in early childhood, highlighting the potential for early intervention strategies for psychiatric risk informed by sleep profile.

Adolescent alcohol disrupts development of noradrenergic neurons in the nucleus of the tractus solitarius and enhances stress behaviors in adulthood in mice in a sex specific manner.

Alcohol use disorders (AUDs) are common mental health issues worldwide and can lead to other chronic diseases. Stress is a major factor in the development and continuation of AUDs, and adolescent alcohol exposure can lead to enhanced stress-responsivity and increased risk for AUD development in adulthood. The exact mechanisms behind the interaction between adolescence, stress, and alcohol are not fully understood and require further research. In this regard, the nucleus of the tractus solitarius (NTS) provides dense norepinephrine projections to the extended amygdala, providing a key pathway for stress-related alcohol behaviors. While NTS norepinephrine neurons are known to be alcohol sensitive, whether adolescent alcohol disrupts NTS-norepinephrine neuron development and if this is related to altered stress-sensitivity and alcohol preference in adulthood has not previously been examined. Here, we exposed male and female C57Bl/6J mice to the commonly used adolescent intermittent ethanol (AIE) vapor model during postnatal day 28-42 and examined AIE effects on: 1) tyrosine hydroxylase (TH) mRNA expression in the NTS across various ages (postnatal day 21-90), 2) behavioral responses to acute stress in the light/dark box test in adulthood, 3) NTS TH neuron responses to acute stress and ethanol challenges in adulthood, and 4) ethanol conditioned place preference behavior in adulthood. Overall the findings indicate that AIE alters NTS TH mRNA expression and increases anxiety-like behaviors following acute stress exposure in a sex-dependent manner. These mRNA expression and behavioral changes occur in the absence of AIE-induced changes in NTS TH neuron sensitivity to either acute stress or acute alcohol exposure or changes to ethanol conditioned place preference.