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The 2021 meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was titled "Role of Parental Experiences in Offspring Outcomes". The theme was reflected in the presentations of two keynote speakers: Edward Levin, Ph.D., who spoke about the role of paternal exposures in offspring development, and Catherine Monk, Ph.D., who spoke about the effects of maternal exposures and maternal mental health on offspring development. The conference included updates from three government agencies, short presentations by junior and senior investigators showcasing late-breaking FASD research, a report on international efforts to streamline FASD classifications for research, a presentation of observations from adults with FASD, a short film of people with FASDs describing their experiences, and a poster session. The conference was capped by awarding the 2021 Henry Rosett award for career-long contributions to the field to Cynthia J.M. Kane, Ph.D.

Introduction Fetal alcohol spectrum disorders (FASD) are highly prevalent developmental disabilities associated with prenatal alcohol exposure. In addition to varied strengths and unique talents, people with FASD experience significant challenges, including in adaptive functioning. Adaptive functioning refers to skills related to everyday life such as communication, practical skills, and social skills. For the current review we aimed to understand how adaptive functioning in FASD compares to that of nonexposed individuals and those with attention deficit-hyperactivity disorder (ADHD). Additionally, we investigated how this relationship may change based on IQ, executive functioning, and age. Method The current review was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Studies were eligible for inclusion if they measured adaptive functioning and included an FASD group and at least one eligible comparison group. Articles available in May 2021 in PubMed, PsycInfo, Scopus, and ProQuest Dissertations were searched. Publication bias was assessed using Egger's regression and three-level random effects models were computed for all domains of adaptive functioning. Possible moderation of IQ, executive functioning, and age were investigated if heterogeneity analyses were significant. A post-hoc moderation analysis of recruitment method was also completed. Results Thirty studies were included. Individuals with FASD had significantly lower adaptive functioning relative to other groups, with effect sizes ranging from 1.04-1.35 compared to nonexposed groups and .30-.43 compared to ADHD groups. No significant moderating effects were found for IQ, or age; executive functioning significantly moderated communication skills in FASD compared to the nonexposed group. Recruitment method significantly affected this relationship, with larger effect sizes on average found for clinically-identified samples compared to at-risk or population samples. Conclusions Individuals with FASD have impairments in adaptive functioning relative to nonexposed and ADHD groups, regardless of IQ, executive functioning, or age. Limitations include low sample sizes in some comparisons and limited age range.

Background Informal caregivers providing unpaid assistance may be vulnerable to changes in health behaviors due to modifications in caregiving during the COVID-19 pandemic. Therefore, this cross-sectional study explored self-reported changes in physical activity (PA), sedentary behavior, and screen time among informal caregivers providing care for older adults aged 50+ during the pandemic. Methods Study participants were recruited via Amazon’s Mechanical Turk and reported their perceived changes (increased a lot, increased a little, remained the same, decreased a little, decreased a lot) in moderate-intensity PA (MPA), vigorous-intensity PA (VPA), sedentary behavior, and screen time (weekday and weekend) during the pandemic. For analytic purposes, response categories were categorized into three-level ordinal variables—increased (increased a lot, increased a little), no change (remained the same), decreased (decreased a little, decreased a lot). Multinomial logistic regression models assessed the likelihood of changes (vs. no change) in MPA, VPA, sedentary behavior, and screen time (weekday, weekend) based on caregiving and demographic characteristics. Results In total, 2574 individuals accessed the study link, 464 of whom did not meet eligibility requirements. In addition, people who completed 80% or less of the survey (n = 1171) and/or duplicate IP addresse (n = 104) were excluded, resulting in an analytic sample of n = 835. The sample was 69% male, had a mean age of 34 (SD = 9.7), and 48% reported increased VPA, while 55% reported increased MPA. The majority also reported increased sedentary behavior, as well as increased screen time. Respondents living with their care recipient were more likely to report increased weekday screen time (Odds Ratio [OR] = 1.55, 95% CI 1.11–2.16) and sedentary behavior (OR = 1.80, 95% CI 1.28–2.53) than respondents not living with the care recipient. Those living with their care recipient were also more likely to reported increased MPA (OR = 1.64, 95% CI 1.16–2.32), and VPA (OR = 1.53, 95% CI 1.09–2.15), but also more likely to report a decrease in VPA (OR = 1.75, 95% CI 1.14–2.70). Conclusion The majority of respondents reported that their MPA, VPA PA, sedentary behavior, and screen time had changed during the pandemic. Living with the care recipient was associated with both positive and negative changes in behavior. Future research can explore factors associated with these reported changes in behavior.

This large cross-sectional study examined the impact of COVID-19 emergency measures on child/adolescent mental health for children/adolescents with and without pre-existing psychiatric diagnoses. Using adapted measures from the CRISIS questionnaire, parents of children aged 6–18 (N = 1013; 56% male; 62% pre-existing psychiatric diagnosis) and self-reporting children/adolescents aged 10–18 (N = 385) indicated changes in mental health across six domains: depression, anxiety, irritability, attention, hyperactivity, and obsessions/compulsions. Changes in anxiety, irritability, and hyperactivity were calculated for children aged 2–5 years using the Strengths and Difficulties Questionnaire. COVID-19 exposure, compliance with emergency measures, COVID-19 economic concerns, and stress from social isolation were measured with the CRISIS questionnaire. Prevalence of change in mental health status was estimated for each domain; multinomial logistic regression was used to determine variables associated with mental health status change in each domain. Depending on the age group, 67–70% of children/adolescents experienced deterioration in at least one mental health domain; however, 19–31% of children/adolescents experienced improvement in at least one domain. Children/adolescents without and with psychiatric diagnoses tended to experience deterioration during the first wave of COVID-19. Rates of deterioration were higher in those with a pre-exiting diagnosis. The rate of deterioration was variable across different age groups and pre-existing psychiatric diagnostic groups: depression 37–56%, anxiety 31–50%, irritability 40–66%, attention 40–56%, hyperactivity 23–56%, obsessions/compulsions 13–30%. Greater stress from social isolation was associated with deterioration in all mental health domains (all ORs 11.12–55.24). The impact of pre-existing psychiatric diagnosis was heterogenous, associated with deterioration in depression, irritability, hyperactivity, obsession/compulsions for some children (ORs 1.96–2.23) but also with improvement in depression, anxiety, and irritability for other children (ORs 2.13–3.12). Economic concerns were associated with improvement in anxiety, attention, and obsessions/compulsions (ORs 3.97–5.57). Children/adolescents with and without pre-existing psychiatric diagnoses reported deterioration. Deterioration was associated with increased stress from social isolation. Enhancing social interactions for children/adolescents will be an important mitigation strategy for current and future COVID-19 waves. Supplementary Information The online version contains supplementary material available at 10.1007/s00787-021-01744-3.

Contains fulltext : 248656.pdf (Publisher’s version ) (Closed access) BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

Intravascular hemolysis is relatively rare but can lead to acute kidney injury (AKI), from increased destruction of erythrocytes and release of free hemoglobin. Since hemolysis and hemoglobinuria are known causes of acute kidney injury we sought to define clinicopathologic findings and outcomes of patients with hemolysis-associated hemoglobin cast nephropathy through a retrospective analysis of 27 cases. The mean patient age was 47 years (range 19-79) and the female-to-male ratio was 1.3:1. All patients presented with AKI with a mean serum creatinine of 8.0 (range 2.9-17.0) mg/dL. Etiologies included autoimmune hemolytic anemia (30%), medication (26%), paroxysmal nocturnal hemoglobinuria (7%), procedural/mechanical causes (7%), transfusion of incompatible blood (4%), toxin ingestion (4%), disseminated intravascular coagulation (4%), and hemoglobinopathy (4%). All biopsies showed acute tubular injury and pigmented, proteinaceous casts characterized by positive hemoglobin immunohistochemistry. After a mean follow-up of nine months (range 0.5-26), the mean serum creatinine was 1.3 (range 0.6-3.3) mg/dL, with 78% of patients returning to normal kidney function. Thus, based on our clinicopathologic case series, hemolysis-associated hemoglobin cast nephropathy is an important entity for clinicians and pathologists to recognize as treatment hinges upon elimination of the pathogenic driver of intravascular hemolysis.

The 2018 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting was entitled “Sex Differences and Vulnerability.” The theme reflected the ongoing NIH initiative to address sex differences in both clinical and preclinical research. The first keynote speaker, Jill Becker, Ph.D., addressed sex differences in addiction in preclinical studies. The second keynote speaker, Meeyoung Min, Ph.D., discussed effects of gender on adolescent outcomes in poly-drug exposed children. The conference presented updates from three government agencies, a discussion panel of new data on FASD prevalence, and short presentations by junior and senior investigators showcasing late-breaking FASD research. The conference was capped by the presentation of Dr. Sarah Mattson, Ph.D., the recipient of the 2018 Henry Rosett award for career-long contributions to the field.

Diseases have no borders, and global health operates from both within and beyond. Global health informatics can adopt an assets-oriented approach to mitigate concerns by maximizing global health data, principles, and resources combined with geographic information systems' use case mapping. This exploratory study utilizes an assets-oriented approach to analyze four global social determinants of health indicators, including Skilled Birth Attendance, Measles Immunization Coverage, Education (Female), and the Healthcare Access and Quality Index in relation to countries' income and geographical region. Data were extracted and analyzed from two publicly available datasets. Positive trends and variations were detected among all variables aggregated by countries' income category and geographical region. These findings pinpoint potential health assets that the discipline of nursing can leverage to build healthier global health communities.

BackgroundThe origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations across these traits, we tested for a sex-differentiated genetic architecture within and between traits.MethodsUsing genome-wide association study (GWAS) summary statistics for 20 neuropsychiatric and behavioral traits, we tested for differences in SNP-based heritability (h2) and genetic correlation (rgResultsWith current sample sizes (and power), we found no significant, consistent sex differences in SNP-based h2. Between-sex, within-trait genetic correlations were consistently high, although significantly less than 1 for educational attainment and risk-taking behavior. We identified genome-wide significant genes with sex-differentiated effects for eight traits. Several trait pairs shared sex-differentiated effects. The top 0.1% of genes with sex-differentiated effects across traits overlapped with neuron- and synapse-related gene sets. Most between-trait genetic correlation estimates were similar across sex, with several exceptions (e.g. educational attainment & risk-taking behavior).ConclusionsSex differences in the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic, requiring large sample sizes. Genes with sex-differentiated effects are enriched for neuron-related gene sets. This work motivates further investigation of genetic, as well as environmental, influences on sex differences.

BACKGROUND: When the primary disabilities associated with fetal alcohol spectrum disorders (FASD) are not well supported, individuals are at higher risk for mental health problems and other secondary conditions. The Families on Track intervention was designed to prevent secondary conditions and improve family functioning in children with FASD. Promising results from a pilot study demonstrated positive effects on child and caregiver outcomes immediately following the intervention. The objective of this study was to examine the sustainability of these effects 6-months post-intervention. METHODS: Thirty children (ages 4 to 8) with prenatal alcohol exposure and their caregivers were enrolled in the original study. Families were randomized to the Families on Track intervention or an active comparison group that provided comprehensive assessment and individualized feedback. The intervention integrated a positive parenting curriculum and a child skills group. Families were assessed at baseline, post-intervention, and 6-month follow up visits. Follow up data were available for 24 families on child and caregiver outcomes. Data were analyzed using effect size calculations and analysis of variance techniques. RESULTS: Relative to the comparison group, intervention families showed continued gains in parenting efficacy and maintained prior improvements in FASD knowledge over the follow-up period. Although intervention families reported a decrease in their needs being met over the follow up period, they continued to report their needs being met to greater extent than those in the comparison group. Consistent with post-intervention outcomes, children in both groups exhibited similar decreases in child disruptive behavior 6 months following the intervention. Unfortunately, positive gains seen at post-intervention for child self-esteem and emotion regulation were attenuated at follow-up. CONCLUSIONS: This pilot study yielded promising effects on important areas of caregiver functioning. However, the intervention’s impact on child functioning waned over time, suggesting the need for sustained or alternate child intervention.

To describe the course of intermittent exotropia (IXT) in children followed up without treatment for 3 years.Observation arm from randomized trial of short-term occlusion versus observation.One hundred eighty-three children 3 to 10 years of age with previously untreated IXT and 400 seconds of arc (arcsec) or better near stereoacuity.Participants were to receive no treatment unless deterioration criteria were met at a follow-up visit occurring at 3 months, 6 months, or 6-month intervals thereafter for 3 years.The primary outcome was deterioration by 3 years, defined as meeting motor criterion (constant exotropia ≥10 prism diopters [Δ] at distance and near) or near stereoacuity criterion (≥2-octave decrease from best previous measure). For the primary analysis, participants also were considered to have deteriorated if treatment was prescribed without meeting either deterioration criterion.The cumulative probability of protocol-specified deterioration by 3 years was 15% (95% confidence interval, 10%-22%), but that was likely an overestimate, partly because of misclassification. Among 25 deteriorations, 2 met motor deterioration, 11 met stereoacuity deterioration, and 12 started treatment without meeting either criteria (7 for social concern, 1 for diplopia, 4 for other reasons). Among the 132 participants who completed the 3-year visit and had not been treated during the study, only 1 (1%) met motor or stereoacuity deterioration criteria at 3 years. Of the 4 participants completing the 3-year visit who met deterioration criteria previously and had not started treatment, none still met deterioration criteria. Between the baseline and 3-year examination for these 132 patients, improvement occurred in distance and near stereoacuity (mean improvement, 0.14 and 0.14 logarithm of arcsec; P ≤ 0.001 and P ≤ 0.001, respectively), distance exotropia control (mean improvement, 0.6 points; P ≤ 0.001), and distance exodeviation magnitude (mean improvement, 2.2 Δ; P = 0.002).Among children 3 to 10 years of age with IXT for whom surgery was not considered to be the immediately necessary treatment, stereoacuity deterioration or progression to constant exotropia over 3 years was uncommon, and exotropia control, stereoacuity, and magnitude of deviation remained stable or improved slightly.

BACKGROUND: Bronchopulmonary dysplasia (BPD), a major source of morbidity in premature neonates, has been associated with intrauterine infection and preterm birth. Both preterm premature rupture of membranes (PPROM) and spontaneous preterm labor (sPTL) are linked with intrauterine inflammation. Whether PPROM and sPTL, as two phenotypic categories of preterm birth, are associated with exposure to different degrees and durations of inflammation that might impact fetal lung development is unknown. PPROM may be associated with longer latency until delivery, which is beneficial for neonatal mortality, but may impart greater injury risk to the developing fetal lungs. It is unknown if PPROM is associated with a greater risk of adverse neonatal respiratory outcomes than sPTL. OBJECTIVE: The objective of this study was to determine if PPROM imparts a differentially greater risk for neonatal BPD than sPTL. A secondary objective was to determine if PPROM was associated with a greater risk of adverse neonatal respiratory outcomes other than BPD and whether gestational latency following PPROM or sPTL diagnosis constitutes a risk factor for fetal lung injury. STUDY DESIGN: We conducted a retrospective secondary analysis of a large cohort of women at risk for spontaneous preterm birth, who were originally enrolled in a randomized controlled trial of magnesium sulfate versus placebo examining neuroprotection. For our study, we included women with a singleton pregnancy complicated by PPROM or sPTL and delivery between 24 and 34 weeks gestational age. Cases with multiple gestation, congenital anomalies, maternal seropositivity for human immunodeficiency virus, or hypertensive diseases of pregnancy (including preeclampsia) were excluded. The primary outcome was BPD. Secondary outcomes were respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), requirement for mechanical ventilation, pneumonia, neonatal sepsis, fetal or neonatal death, and a composite of adverse neonatal respiratory outcomes including (BPD, pneumonia, RDS, and TTN). Statistical analyses included chi-square, Student’s t-test and logistic and multiple regression. RESULTS: A total of 1,729 women were included in this analysis including 1,554 with PPROM and 175 with sPTL. Women in the PPROM group were more likely to be older, not of Hispanic race, married, more educated, have smoked during pregnancy and have a greater body mass index (See Table 1). The BPD rate was not significantly different following PPROM versus sPTL. Neonates in the PPROM group experienced a lower rate of pneumonia (p=0.001), neonatal sepsis (p=0.009) and patent ductus arterious (PDA) requiring either medical or surgical therapy (p

Individuals with fetal alcohol spectrum disorders (FASD) have high rates of health care service utilization. It is vital that health care professionals understand FASD and associated family experiences to strengthen their ability to respond to family needs and tailor family-focused interventions. This study included 24 foster and adoptive parents of children and adults (aged 3-33 years) with FASD. Data were collected via individual interviews and focus groups and analyzed thematically. Consistent with a developmental psychopathology perspective, parents’ experiences interacted with the individual (with FASD), family, and broader systems ecological levels. Parents undertook protective actions in an attempt to prevent secondary conditions, support their child and family, and mitigate systems barriers. They also experienced stressors at each level, and stress was increased by protective actions. The overall parenting experience was fueled by a protective parenting attitude. Findings can strengthen family-focused care practices with individuals with FASD and their families and inform novel family interventions.

Background Attention-deficit/hyperactivity disorder (ADHD) is a major sequela of traumatic brain injury (TBI) in youths. The objective of this study was to examine whether ADHD symptoms are differentially associated with genetic risk and brain structure in youths with and without a history of TBI. Methods Medical history, ADHD symptoms, genetic data, and neuroimaging data were obtained from a community sample of youths. ADHD symptom severity was compared between those with and without TBI (TBI n = 418, no TBI n = 3193). The relationship of TBI history, genetic vulnerability, brain structure, and ADHD symptoms was examined by assessing 1) ADHD polygenic score (discovery sample ADHD n = 19,099, control sample n = 34,194), 2) basal ganglia volumes, and 3) fractional anisotropy in the corpus callosum and corona radiata. Results Youths with TBI reported greater ADHD symptom severity compared with those without TBI. Polygenic score was positively associated with ADHD symptoms in youths without TBI but not in youths with TBI. The negative association between the caudate volume and ADHD symptoms was not moderated by a history of TBI. However, the relationship between ADHD symptoms and structure of the genu of the corpus callosum was negative in youths with TBI and positive in youths without TBI. Conclusions The identification of distinct ADHD etiology in youths with TBI provides neurobiological insight into the clinical heterogeneity in the disorder. Results indicate that genetic predisposition to ADHD does not increase the risk for ADHD symptoms associated with TBI. ADHD symptoms associated with TBI may be a result of a mechanical insult rather than neurodevelopmental factors.

BackgroundFew studies have investigated the partner's influence on risk factors such as alcohol consumption and depression during pregnancy. Partner substance use and lower relationship satisfaction predict higher maternal alcohol use and depressive symptoms. Because prenatal alcohol use and maternal depression affect infant outcomes, it is imperative to examine how the partner affects these maternal risk factors. The current study examined the effect of a latent construct of partner influence on maternal alcohol use and depressive symptoms, and the effects on infant development of these maternal factors.MethodsParticipants were 246 pregnant women from 2 sites in Western Ukraine from whom longitudinal data were collected as part of a multisite study. In the first trimester, mothers reported on relationship satisfaction, partner substance use, and socioeconomic status (SES). In the third trimester, they reported on alcohol use and depressive symptoms. Infants were assessed using the Bayley Scale of Infant Development (average age=6.93months). A latent construct titled partner influence was formed using partner substance use and measures of relationship satisfaction, including the frequency of quarreling, happiness in the relationship, and the ease of talking with the partner. Using structural equation modeling, a model was specified in which partner influence and SES predicted maternal alcohol use and depressive symptoms, which in turn predicted infant neurodevelopmental outcomes.ResultsHigher partner influence significantly predicted lower prenatal alcohol use and lower depressive symptoms, controlling for the effect of SES. Higher maternal prenatal alcohol use significantly predicted lower infant mental and psychomotor development. Maternal depressive symptoms did not predict infant development over and above the effect of alcohol use.ConclusionsPartner influence is an important contributor to prenatal alcohol use and maternal depressive symptoms, over and above the effect of SES. The significant paths from prenatal alcohol exposure to infant neurodevelopmental outcomes underscore the importance of partner influence during pregnancy.

During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood.This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State.Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State.A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3-23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2-7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3-2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3-20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96-1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%).The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states.

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients, mostly consisting of a variety of essential oils and botanical extracts. This publication, seventh in the series, re-evaluates NFCs with constituent profiles dominated by phenolic derivatives including carvacrol, thymol and related compounds using a constituent-based procedure first published in 2005 and updated in 2018. The procedure is based on the chemical characterization of each NFC as intended for commerce and the estimated intake of the constituent congeneric groups. The procedure applies the threshold of toxicological concern (TTC) concept and evaluates relevant data on absorption, metabolism, genotoxic potential and toxicology of the constituent congeneric groups and the NFC under evaluation. Herein, the FEMA Expert Panel affirmed the generally recognized as safe (GRAS) status of seven phenolic derivative-based NFCs, Origanum Oil (Extractive) (FEMA 2828), Savory Summer Oil (FEMA 3013), Savory Summer Oleoresin (FEMA 3014), Savory Winter Oil (FEMA 3016), Savory Winter Oleoresin (FEMA 3017), Thyme Oil (FEMA 3064) and Thyme White Oil (FEMA 3065) under their conditions of intended use as flavor ingredients.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior., ADHD is often found to be comorbid with disruptive behavior disorders, but the genetic loci underlying this comorbidity are unknown. Here, the authors have performed a GWAS meta-analysis of ADHD with disruptive behavior disorders, finding three genome-wide significant loci in Europeans, and replicating one in a Chinese cohort.

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a program for the re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, the sixth in the series, will summarize the re-evaluation of eight NFCs whose constituent profiles are characterized by significant amounts of eucalyptol and/or other cyclic ethers. This re-evaluation was based on a procedure first published in 2005 and subsequently updated in 2018 that evaluates the safety of naturally occurring mixtures for their intended use as flavoring ingredients. The procedure relies on a complete chemical characterization of the NFC intended for commerce and the organization of its chemical constituents into well-defined congeneric groups. The safety of the NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of the constituents of the congeneric groups and the NFC under evaluation. Eight NFCs derived from the Eucalyptus, Melaleuca, Origanum, Laurus, Rosmarinus and Salvia genera were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.

People with disabilities have not been adequately represented in strengths-based research. This study is the first to examine strengths and positive influences of young children with fetal alcohol spectrum disorder (FASD). Thirty adoptive and relative caregivers of children with FASD reported their children's strengths and positive influences and completed measures on family functioning. Using a conversion mixed design, we described themes in strengths and influences, degree of caregiver positivity and relationships with child and family functioning. Caregivers reported wide-ranging strengths and positive influences. Frequency of adaptive strengths correlated with measures of family functioning, but thematic strengths and positive influences did not. Strengths and positive influences are distinct from measures of functioning and are not well captured in deficit-focused research.

BACKGROUND: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown. OBJECTIVE: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery. RESULTS: The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019-associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3-5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257-3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7-43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, -0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P

ObjectivesTo determine if adults with overweight or obesity received counselling from their healthcare providers (HCPs) to lose weight and/or adopt healthful behaviours associated with weight loss, and whether they took action on their HCPs’ recommendations.DesignCross-sectional analysis of 2011–2018 National Health and Nutrition Examination Survey (NHANES) data.SampleNHANES respondents aged 18+ who were overweight/obese and had seen an HCP in the previous 12 months (n=13 158).MethodsRespondents reported if their HCPs recommended they control/lose weight, increase exercise/physical activity (PA) and/or reduce fat/calorie intake, and if they adopted the offered recommendation(s). Weighted logistic regression models examined receipt of HCP counselling by sex, age, race/ethnicity, and weight status accounting for demographic characteristics and complex sampling. Similar analyses examined reported adoption of HCPs’ recommendations.ResultsThe sample was 53.1% women, 45.0% were overweight and 55.0% had obesity. In total, 40.4% received counselling to control/lose weight, 49.5% to increase exercise/PA and 38.9% to reduce fat/calorie intake. The following groups were less likely (pConclusionMost respondents did not receive HCP counselling, and approximately half of those who received counselling reported taking action. HCPs may need training to provide counselling and to offer recommendations tailored to the social contexts of populations less likely to adopt weight control related recommendations.

The androgen receptor (AR) is known for masculinization of behavior and brain. To better understand the role that AR plays, mice bearing humanizedArgenes with varying lengths of a polymorphic N-terminal glutamine (Q) tract were created (Albertelli et al 2006). The length of the Q tract is inversely proporitional to AR activity. Biological studies of the Q tract length may also provide a window into potential AR contributions to sex-biases in disease risk.Here we take a multi-pronged approach to characterizing AR signaling effects on brain and behavior in mice using the humanizedArQ tract model. We first map effects of Q tract length on regional brain anatomy, and consider if these are modified by gonadal sex. We then test the notion that spatial patterns of anatomical variation related to Q tract length could be organized by intrinsic spatiotemporal patterning of AR gene expression in the mouse brain. Finally, we test influences of Q tract length on four behavioral tests.Altering Q tract length led to neuroanatomical differences in a non-linear dosage-dependent fashion. Gene expression analyses indicated that adult neuroanatomical changes due to Q tract length are only associated with neurodevelopment (as opposed to adulthood). No significant effect of Q tract length was found on the behavior of the three mouse models. These results indicate that AR activity differentially mediates neuroanatomy and behavior, that AR activity alone does not mediate sex differences, and that neurodevelopmental processes are associated with spatial patterns of volume changes due to Q tract length in adulthood. They also indicate that androgen sensitivity in adulthood does not directly lead to autism-related behaviors or neuroanatomy, although neurodevelopmental processes may play a role earlier. Further study into sex differences, development, other behaviors, and other sex-specific mechanisms are needed to better understand AR sensitivity, neurodevelopmental disorders, and the sex difference in their prevalence.

Background In tropically-adapted beef heifers, application of genomic prediction for age at puberty has been limited due to low prediction accuracies. Our aim was to investigate novel methods of pre-selecting whole-genome sequence (WGS) variants and alternative analysis methodologies; including genomic best linear unbiased prediction (GBLUP) with multiple genomic relationship matrices (MGRM) and Bayesian (BayesR) analyses, to determine if prediction accuracy for age at puberty can be improved. Methods Genotypes and phenotypes were obtained from two research herds. In total, 868 Brahman and 960 Tropical Composite heifers were recorded in the first population and 3695 Brahman, Santa Gertrudis and Droughtmaster heifers were recorded in the second population. Genotypes were imputed to 23 million whole-genome sequence variants. Eight strategies were used to pre-select variants from genome-wide association study (GWAS) results using conditional or joint (COJO) analyses. Pre-selected variants were included in three models, GBLUP with a single genomic relationship matrix (SGRM), GBLUP MGRM and BayesR. Five-way cross-validation was used to test the effect of marker panel density (6 K, 50 K and 800 K), analysis model, and inclusion of pre-selected WGS variants on prediction accuracy. Results In all tested scenarios, prediction accuracies for age at puberty were highest in BayesR analyses. The addition of pre-selected WGS variants had little effect on the accuracy of prediction when BayesR was used. The inclusion of WGS variants that were pre-selected using a meta-analysis with COJO analyses by chromosome, fitted in a MGRM model, had the highest prediction accuracies in the GBLUP analyses, regardless of marker density. When the low-density (6 K) panel was used, the prediction accuracy of GBLUP was equal (0.42) to that with the high-density panel when only six additional sequence variants (identified using meta-analysis COJO by chromosome) were included. Conclusions While BayesR consistently outperforms other methods in terms of prediction accuracies, reasonable improvements in accuracy can be achieved when using GBLUP and low-density panels with the inclusion of a relatively small number of highly relevant WGS variants.

Zika virus (ZIKV) is a mosquito-transmitted flavivirus, recently linked to microcephaly and central nervous system anomalies following infection in pregnancy. Striking findings of disproportionate growth with a smaller than expected head relative to body length have been observed more commonly among fetuses with exposure to ZIKV in utero compared to pregnancies without ZIKV infection regardless of other signs of congenital infection including microcephaly. This study's objective was to determine the diagnostic accuracy of femur-sparing profile of intrauterine growth restriction for the identification of ZIKV-associated congenital injuries on postnatal testing. A retrospective cohort study of pregnant women with possible or confirmed ZIKV infection between January 1, 2016 and December 31, 2017 were included. Subjects were excluded if no prenatal ultrasound was available. A femur-sparing profile of growth restriction determined using INTERGROWTH-21st sonographic standard for head circumference to femur length (HC: FL). Congenital injuries were determined postnatally by imaging, comprehensive eye exam and standard newborn hearing screen. A total of 111 pregnant women diagnosed with ZIKV infection underwent fetal ultrasound and 95 neonates had complete postnatal evaluation. Prenatal microcephaly was detected in 5% of fetuses (6/111). Postnatal testing detected ZIKV-associated congenital injuries in 25% of neonates (24/95). A HC: FL Z-score ≤ -1.3 had a 52% specificity (95% CI 41-63%), 82% negative predictive value (NPV, 95% CI 73-88%) for the detection of ZIKV-associated congenital injuries in the neonatal period. A more stringent threshold with a Z-score ≤ -2 was associated with a 90% specificity (95% CI 81-95%), 81% NPV (95% CI 77-85%). Excluding cases of fetal microcephaly, HC: FL (Z-score ≤ -2) demonstrated a similar specificity (89%, 95% CI 81-95%) with superior NPV (87%, 95% CI 84-90%). The sonographic recognition of a normally proportioned fetus may be useful prenatally to exclude a wider spectrum of ZIKV-associated congenital injuries detected postnatally.

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a program for the re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, fifth in the series, evaluates the safety of NFCs containing linalool and/or other characteristic mono- and sesquiterpenoid tertiary alcohols and esters using the safety evaluation procedure published by the FEMA Expert Panel in 2005 and updated in 2018. The procedure relies on a complete chemical characterization of the NFC intended for commerce and organization of the chemical constituents of each NFC into well-defined congeneric groups. The safety of each NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of both the constituent congeneric groups and the NFCs. Sixteen NFCs, derived from the Lavandula, Aniba, Elettaria, Daucus, Salvia, Coriandrum, Ribes, Guaiacum/Bulnesia, Citrus, Pogostemon, Melaleuca and Michelia genera, were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association initiated the safety re-evaluation of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, 4th in a series focusing on the safety evaluation of NFCs, presents an evaluation of NFCs rich in hydroxyallylbenzene and hydroxypropenylbenzene constituents using a procedure initially published in 2005 and updated in 2018 that evaluates the safety of naturally occurring mixtures for their intended use as flavoring ingredients. The procedure requires the characterization of the chemical composition for each NFC and subsequent organization of the constituents into defined congeneric groups. The safety of each NFC is evaluated using the conservative threshold of toxicological concern (TTC) approach together with studies on absorption, metabolism and toxicology of the NFC and its constituent congeneric groups. By the application of this procedure, seven NFCs, derived from clove, cinnamon leaf and West Indian bay leaf were affirmed as “generally recognized as safe (GRAS)” under their conditions of intended use as flavor ingredients. An eighth NFC, an oleoresin of West Indian bay leaf, was affirmed based on its estimated intake, which is below the TTC of 0.15 μg/person per day for compounds with structural alerts for genotoxicity.

The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number of diseases, but it has not been investigated in ophthalmic diseases. Here, we evaluated the functional hierarchy of interleukin-1β (IL-1β), IL-6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular inflammation.We delivered adeno-associated virus (AAV) vectors expressing IL-1β, IL-6, IL-17A, or TNF intravitreally in naïve C57/BL6 mice and compared and contrasted the inflammatory effects in the eye 5 weeks after AAV-mediated gene transfer. We also used an in vitro human system to test the effect of cytokines on barrier function.We found that IL-1β had the highest ability to initiate ocular inflammation. The continuous overexpression of IL-1β resulted in a significant upregulation of additional proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and optical coherence tomography imaging techniques, we showed that a low dose of AAVIL-1β was sufficient and was as pathogenic as a high dose of TNF in inducing vascular leakage, retinal degeneration, and cellular infiltration. Furthermore, only a marginal increase in IL-1β was enough to cause cellular infiltration, thus confirming the highly pathogenic nature of IL-1β in the eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the eye. To examine the clinical relevance of our findings, we used an impedance assay to show that IL-1β alone or TNF alone was able to cause primary human retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL-17A alone had no effect on barrier function; however, in the presence of IL-1β or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects.Our studies demonstrate the existence of a functional hierarchy of proinflammatory cytokines in the eye, and we show that IL-1β is the most pathogenic when it is continuously expressed in the eye.

To examine whether exposure to general anesthesia for procedures at age ≥40 years is associated with prevalent mild cognitive impairment (MCI) in the elderly.A case-control study nested within a population-based cohort. Olmsted County, Minnesota, residents, aged 70-91 years, underwent baseline evaluations that included the Clinical Dementia Rating scale, a neurologic evaluation, and neuropsychologic testing. Individuals identified with MCI (cases) at enrollment were matched 1:2 on age, sex, education, and apolipoprotein genotype with participants who were cognitively normal at the time of the index visit. Medical records from age 40 years until the index visit were reviewed to determine exposures to general anesthesia. Conditional logistic regression, taking into account the matched set study design and adjusting for MCI risk factors, was used to assess whether exposure to anesthesia after the age of 40 years was associated with prevalent MCI.A total of 387 Mayo Clinic Study of Aging participants (219 males, 168 females) were diagnosed with MCI at enrollment with mean age of 81 ± 5 years. Exposure to general anesthesia after the age of 40 years was not significantly associated with prevalent MCI when analyzed as a dichotomous variable (any versus none, adjusted odds ratio, 0.97 [95% confidence interval, 0.68-1.40]) or the number of exposures (odds ratio, 1.13 [0.74-1.72], 0.81 [0.53-1.22], and 1.03 [0.67-1.58] for 1, 2-3, and ≥4 exposures, respectively, with no exposure as the reference). Similar results were obtained for exposure to anesthesia after the age of 60 years and during 5, 10, and 20 years before the first visit.Exposure to general anesthesia for procedures at age ≥40 years was not associated with prevalent MCI in the elderly.

Copyright © 2016 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.Objectives: To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Design: Secondary analysis of a prospective, cross-sectional, point prevalence study. Setting: International, multicenter PICUs. Patients: Pediatric patients with severe sepsis identified on five separate days over a 1-year period. Interventions: None. Measurements and Main Results: Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Conclusions: Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

Objectives The relationship between components of body composition and physical function is not well characterized among middle-aged women. This cross-sectional study examined the strength of the associations between lean mass and percent fat and physical function in middle-aged women. Study Design Body composition, physical function and physical activity were objectively measured in 80 women (mean age 52.58 ± 6.10 years; range = 40−63 years). Main Outcome Measures Adiposity (%Fat) and lean mass were measured via dual-energy x-ray absorptiometry. Steps/day and minutes of low-, moderate- and vigorous-intensity physical activity were assessed via accelerometer. Physical function was measured via a seated transfer task, 30-second chair stand, a six-minute walk task, 8-foot timed up and go, and a lift and carry task. Results: When controlling for steps/day, measures of lean mass were related to performance on the seated transfer task (r = .25) and 30-second chair stand (−.26) (both p > 0.05), while %Fat was related to performance on the seated transfer task (r = .53), 8-foot timed up and go (r = .32), 30-second chair stand (r = −.35), and six-minute walk (r = −.48; all p ≤ 0.05). Linear regression analyses revealed: (1) age, steps/day, and %Fat were independently related to performance on the seated transfer task and 30-second chair stand (both p ≤ 0.05), (2) %Fat was associated with six-minute walk and 8-foot up-and-go performance (p ≤ 0.01); none of the variables included were associated with lift and carry. Conclusions Adiposity but not lean mass was associated with objectively measured physical function in middle-aged women. Interventions that focus on reducing body fat may be an effective method for improving functional performance among women in this age group.

Background Hoarding, originally only considered a symptom of obsessive-compulsive disorder (OCD), is now categorized as a separate disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). We studied candidate serotonergic genes and the distinctness of hoarding in children and adolescents and hypothesized that unique gene variants would be associated with hoarding alone. Methods We examined obsessive-compulsive (OC) traits, including hoarding, in a total of 5,213 pediatric participants in the community. We genotyped candidate serotonin genes (5-HTTLPR polymorphism in SLC6A4 for 2,018 individuals and single nucleotide polymorphisms [SNPs] across genes SLC6A4, HTR2A, and HTR1B for 4,711 individuals). In a previous study conducted by our group in the same sample, we identified a significant association between 5-HTTLPR and hoarding in males. In this study, we examined hoarding more closely by testing the association between serotonin gene variants and hoarding traits with and without other accompanying OC traits. Results The [LG +S] variant in 5-HTTLPR was significantly associated with hoarding alone in males (p-value of 0.009). There were no significant findings for 5-HTTLPR in females. There were no significant findings after correction for multiple comparisons using SNP array data, but top SNP findings suggested that variation downstream of HTR1B may be implicated in hoarding alone in females. Conclusions Our results suggest specific serotonin gene variants are associated with hoarding traits alone, differing between sexes. Top findings are in line with our former study, suggesting that individuals with hoarding alone were driving previous results. Our paper supports hoarding disorder's new designation.

Obsessive-compulsive disorder (OCD) is phenotypically heterogeneous and genetically complex. This study aimed to reduce heterogeneity using structural brain imaging to study putative intermediate phenotypes for OCD. We hypothesized that select serotonin gene variants would differ in their relationship with brain volume in specific regions of the cortico-striato-thalamo-cortical (CSTC) circuits between OCD patients and controls. In a total of 200 pediatric subjects, we genotyped candidate serotonin genes (SLC6A4, HTR2A, HTR1B, and HTR2C) and conducted structural magnetic resonance imaging (sMRI) to measure regional brain volumes within CSTC circuits. In males and females separately, we first tested the association between serotonin gene variants and OCD and the effect of serotonin gene variants on brain volume irrespective of diagnosis. We then carried out a series of analyses to assess the effect of genotype-diagnosis interaction on brain volume. In females, but not in males, we identified a statistically significant genotype-diagnosis interaction for two single nucleotide polymorphisms (SNPs) in HTR2C, rs12860460 (interaction term estimate of 5.45 cc and interaction P value of 9.70e-8) and rs12854485 (interaction term estimate of 4.28 cc and interaction P value of 2.07e-6). The tested allele in each SNP was associated with decreased anterior cingulate cortex (ACC) volume in controls and with increased ACC volume in OCD patients. Our findings suggest that, in females, sequence variation in HTR2C influences ACC volume in pediatric OCD. The variants may contribute to differences in ACC volume and to OCD in a sex-specific manner when acting together with other genetic, biological, and/or environmental factors.

Two independent 90-day GLP-compliant studies were conducted in Sprague-Dawley rats with β-caryophyllene or β-caryophyllene epoxide, two common flavoring and fragrance materials. Dietary concentrations of β-caryophyllene were 3500; 7000; and 21,000 ppm for males and 3500; 14,000; and 56,000 ppm for females. Dietary concentrations of β-caryophyllene epoxide were 1750; 10,500; and 21,000 ppm. There were no deaths or clinical toxicity attributable to either substance administration. Statistically significant, dose-dependent reductions in body weight, body weight gain, food consumption, and food efficiency at the highest dietary concentrations of β-caryophyllene, but not of β-caryophyllene epoxide, were attributed to palatability issues. Neither β-caryophyllene nor β-caryophyllene epoxide influenced estrus cyclicity or sperm parameters. Macroscopic and microscopic findings were primarily related to changes in the kidneys of male rats, consistent with α2u-globulin nephropathy, and in the liver of male and female rats, including hepatocyte hypertrophy at the middle and high intake levels. These changes correlated with increased absolute and relative organ weights. Since the kidney findings were a species- and sex-specific effect, the NOAEL in each study was based on hepatocyte hypertrophy at the two highest dietary concentrations and were determined to be 222 mg/kg bw/day for β-caryophyllene and 109 mg/kg bw/day for β-caryophyllene epoxide.

Background Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. Methods Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. Results The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6). Conclusions This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group.

Purpose: Weight loss is advantageous for individuals with obesity and arthritis. Therefore, this study was conducted to determine if there are differences by rural-urban status among older adults with these conditions who reported being advised by a health care provider to lose weight for arthritis or to ameliorate arthritis symptoms. Methods: A cross-sectional analysis of 2011 Behavioral Risk Factor Surveillance System (BRFSS) data. Respondents reported if they had been diagnosed with arthritis and if they received a provider weight loss recommendation (WLR). The analytic sample was limited to older adults aged 60&ndash, 79 living in the five states that administered the examined BRFSS arthritis module who had body mass index &ge, 30 kg/m2 and reported having arthritis (n = 2920). The respondent&rsquo, s county of residence was linked to the corresponding county-level population density from the US Decennial Census to determine rural-urban status. A generalized linear model examined the association between receipt of a WLR and population density, controlling for demographics. Results: The sample was 83.6% white, 57.8% female, and 63.2% received a WLR. Respondents from more urban counties were more likely to receive a WLR (p value for trend &lt, 0.001). Additionally, older respondents, men, individuals with less than a high school education, and whites had a decreased likelihood of receiving a WLR. Conclusions: The analysis identified notable rural-urban differences with respondents in more urban counties being more likely to receive a WLR. Furthermore, there were differences in those who received a WLR by age, sex, and education. Reasons for these differences should be explored.

Background Population-based samples with valid, quantitative and genetically informative trait measures of psychopathology could be a powerful complement to case/control genetic designs. We report the convergent and predictive validity of the parent- and self-report versions of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN). We tested if SWAN scores were associated with ADHD diagnosis, ADHD polygenic risk, as well as traits and polygenic risk for disorders that co-occur with ADHD: anxiety and obsessive-compulsive disorder (OCD). Methods We collected parent- and self-report SWAN scores in a sample of 15,560 children and adolescents (6-17 years) recruited at a science museum (Spit for Science sample). We established age and sex norms for the SWAN. Sensitivity-specificity analyses determined SWAN cut-points that discriminated those with and without a reported ADHD diagnosis. These cut-points were validated in a clinic sample (266 ADHD cases; 36 controls). Convergent validity was established using the Conners' parent- and self-report scales. Using Spit for Science participants with genome-wide data (n = 5,154), we tested if low, medium and high SWAN scores were associated with polygenic risk for ADHD, OCD and anxiety disorders. Results Parent- and self-report SWAN scores showed high convergent validity with Conners' scales and distinguished ADHD participants with high sensitivity and specificity in the Spit for Science sample. In a clinic sample, the Spit for Science cut-points discriminated ADHD cases from controls with a sensitivity of 84% and specificity of 92%. High SWAN scores and scores above the Spit for Science cut-points were significantly associated with polygenic risk for ADHD. SWAN scores were not associated with polygenic risk for OCD or anxiety disorders. Conclusions Our study supports the validity of the parent- and self-report SWAN scales and their potential in ADHD population-based genetic research.

Background Recent investigations have questioned the role of hydration and electrolytes in cramp susceptibility and thus the efficacy of consuming electrolyte-rich carbohydrate beverages (EB) to control/prevent cramping. Methods Nine euhydrated, cramp-prone participants had their cramp susceptibility assessed by measuring the nerve stimulation threshold frequency at which cramping occurs (TF) before and after consumption of an EB (kCal: 120, Na: 840 mg, K: 320 mg, Mg: 5 mg) and placebo beverage (PB: kCal: 5, Na: 35 mg). Cramp intensity was assessed using a verbal pain scale and poststimulation electromyography (EMG). Results TF was greater in EB (14.86 ± 7.47 Hz) than PB (14.00 ± 5.03 Hz; P = .038) and reported pain was lower in EB (2.0 ± 0.6) than PB (2.7 ± 0.8; P = .025) while EMG was similar (P = .646). Discussion EB consumption decreased cramp susceptibility and pain but did not prevent cramping in any participants. These results suggest that electrolyte consumption independent of hydration can influence cramp susceptibility in young people.

Five hundred eighty renal biopsies from a pool of 27850 archived cases were identified in which a myoglobin stain was performed because of atypical casts. Two hundred and thirty-eight (41%) of these biopsies were found to be positive for myoglobin casts. The morphology of the myoglobin casts ranged from light, almost translucent and refractile, to pink, to dark red and slightly brown granular casts by hematoxylin and eosin, to beaded globular casts that stained brightly fuchsinophilic with Masson trichrome and partially argyrophilic with silver methenamine. All biopsies displayed acute tubular injury associated with intratubular debris and thinning and vacuolization of tubular epithelium. Approximately 20% of myoglobin-positive biopsies showed calcium oxalate or phosphate deposition. Positive myoglobin staining was present in casts, proximal tubular epithelial cells without casts, and also dehisced epithelial cells. Collecting ducts and occasionally the distal tubular epithelium also stained positive. One case showed concurrent myeloma cast nephropathy with "fractured" casts and translucent myoglobin-positive casts. Herein, we describe the morphologic spectrum of myoglobin-positive casts. We conclude that utilization of myoglobin immunohistochemistry is advantageous and, when not available, knowledge of the morphologic spectrum is important.

This study's objective is to assess differences in dietary intakes in breast cancer survivors (n = 13) and women without a history of breast cancer (controls, n = 71). In a cross-sectional design, intake of foods, food groups, nutrients, and non-nutritive sweeteners was assessed using participant-completed three-day food records. All women were postmenopausal (mean age (SD) 58.5 (±3.8) y, 95% White, 2.4% Asian Pacific, and 2.4% Black). The two groups did not differ in age, energy intake, or body mass index (p > 0.05). Compared to controls, survivors consumed less dairy products, animal protein, total protein, and calcium, but more legumes, noncitrus fruit, and carbohydrates (p ≤ 0.05). Calcium intakes were of particular concern in survivors who consumed an average of 686 mg calcium/d, which is

OBJECTIVE Greater muscle strength and power are associated with better physical function in middle-aged and older women. The aim of the present study was to determine whether accelerometer-measured physical activity was associated with muscle strength and power in middle-aged postmenopausal women. METHODS Postmenopausal women (N = 60; mean [SD] age, 58.9 [3.9] y) were assessed for physical activity (step count and moderate to vigorous physical activity [MVPA]) via accelerometer, for body composition via dual-energy x-ray absorptiometry, for concentric isokinetic knee torque at 60°/s and 180°/s using isokinetic dynamometry, and for leg extensor power with the Nottingham power rig. RESULTS In linear regression analysis, daily step count was independently associated with isokinetic knee torque at 60°/s (standardized β = 0.32, P = 0.01), isokinetic knee torque at 180°/s (standardized β = 0.32, P = 0.01), and total leg extensor power (β = 0.36, P = 0.01) after adjustment for covariates. Daily MVPA had similar associations with isokinetic knee torque at 60°/s (β = 0.38, P

Background Fetal alcohol spectrum disorders (FASD) affect approximately 2% to 5% of the US population. However, most families are unable to access FASD-informed interventions. Barriers to care include the lack of a knowledgeable and skilled workforce and family-level barriers such as limited financial resources, inability to access childcare, and stigma. As a result, families often try peer-to-peer and self-help support strategies. However, they often take these strategies from disparate sources, which have quite variable intervention quality and empirical support. Objective This study aimed to initiate systematic development and evaluation of a mobile health intervention (app) for caregivers raising children with FASD. Focus groups were conducted to elicit participant perspectives on app design and functionalities to inform further app development. Methods The app, called FMF Connect, was derived from the scientifically validated Families Moving Forward (FMF) Program, a clinician-delivered behavioral consultation intervention. FMF Connect was intended for caregiver self-delivery and included five main components: (1) Learning Modules, (2) Family Forum, (3) Library, (4) Notebook, and (5) Dashboard. Focus group methods were used to solicit perspectives from diverse families during the early stages of app development. Questions were asked about interface design, relevance of components and content, and perceived barriers and facilitators of use. A total of 25 caregivers participated in 7 focus groups across 5 US cities. Data were analyzed thematically. Results Focus group participants were generally enthusiastic about the app interface design and components. Four global positive impression themes emerged, including (1) ease of access, (2) how the app guides and organizes information, (3) connection to other users and information, and (4) ability to share some content with others. Themes arose not only in discussions relating to positive app features but also when participants were asked about motivators for app use. Participants related how these positive global themes could address some system-level barriers, such as limited access to services, feeling isolated, and increased advocacy needs related to the societal lack of FASD knowledge. Participants identified many positive features about individual app components and functionalities. They also communicated potential barriers to use and raised important concerns and considerations relating to several app components. These included recognizability of the app based on the logo, and the balance of following the planned intervention sequence versus obtaining immediate answers. Also mentioned were privacy and dynamics within the Family Forum. Conclusions FMF Connect is a promising novel intervention with potential to reach many families in need and reduce significant barriers to care, resulting in a broader public health impact. Study findings will guide further app development both in terms of content and technological advances to optimize intervention effects. FMF Connect app development provides useful directions for other apps aimed at changing parenting practices.