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Abstract Background Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions. Methods In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks. Results We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-nucleus data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case–control gene expression studies suggests a female molecular predisposition towards Alzheimer’s disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis. Conclusion Overall, these analyses highlight mechanisms by which sex differences may interact with sex-biased conditions in the brain. Furthermore, we provide region-specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences. Graphical Abstract

Summary: Background: Physiological-based cord clamping (PBCC) in preterm infants is beneficial for cardiovascular transition at birth and may optimize placental transfusion. Whether PBCC can improve clinical outcomes is unknown. The aim of the Aeration, Breathing, Clamping (ABC3) trial was to test whether PBCC results in improved intact survival in very preterm infants. Methods: The ABC3 trial was a parallel-group, multicentre, randomised, controlled superiority clinical trial conducted in all Dutch tertiary referral centers for perinatal care involving infants born before 30 weeks of gestation. Infants were randomised to either PBCC or time-based delayed cord clamping (TBCC), stratified by gestational age and treatment center. Infants receiving PBCC were stabilised with umbilical cord intact, which was clamped after reaching cardiorespiratory stability (heart rate >100 bpm and SpO2 >85% while supplemental oxygen

PurposeThe aim of this study is to determine the prospective associations between baseline screen time and obsessive-compulsive disorder (OCD) at 2-year follow-up in a national (United States) cohort of 9- to 10-year-old children.MethodsWe analyzed prospective cohort data from the Adolescent Brain Cognitive Development study (n = 9,208). Logistic regression analyses were used to determine the associations between baseline self-reported screen time (exposure) and OCD, based on the Kiddie Schedule for Affective Disorders and Schizophrenia (outcome), at 2-year-follow-up, adjusting for race/ethnicity, sex, household income, parent education, family history of psychopathology, and study site, excluding participants with baseline OCD.ResultsThe sample was 48.9% female and racially and ethnically diverse (43.5% non-White). Each additional hour of total screen time was prospectively associated with 1.05 higher odds of OCD at 2-year follow-up (95% confidence interval [CI] 1.01-1.09). For specific screen time modalities, each additional hour of playing video games (adjusted odds ratio 1.15, 95% CI 1.03-1.28) and watching videos (adjusted odds ratio 1.11, 95% CI 1.01-1.23) was associated with a subsequent OCD diagnosis.ConclusionVideo games and watching videos are prospectively associated with new-onset OCD in early adolescents. Future research should examine mechanisms linking these specific screen modalities to OCD development to inform future prevention and intervention efforts.

BackgroundCross-sectional studies have demonstrated associations between screen time and disruptive behavior disorders (conduct disorder and oppositional defiant disorder); however, prospective associations remain unknown. This study's objective was to determine the prospective associations of contemporary screen time modalities with conduct and oppositional defiant disorder in a national cohort of 9-11-year-old children.MethodsWe analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,875). Modified Poisson regression analyses were conducted to estimate the associations between baseline child-reported screen time (total and by modality) and parent-reported conduct or oppositional defiant disorder based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) at 1-year follow-up, adjusting for potential confounders.ResultsParticipants reported an average of 4 hr of total screen time per day at baseline. Each hour of total screen time per day was prospectively associated with a 7% higher prevalence of conduct disorder (95% CI 1.03-1.11) and a 5% higher prevalence of oppositional defiant disorder (95% CI 1.03-1.08) at 1-year follow-up. Each hour of social media per day was associated with a 62% higher prevalence of conduct disorder (95% CI 1.39-1.87). Each hour of video chat (prevalence ratio [PR] 1.21, 95% CI 1.06-1.37), texting (PR 1.19, 95% CI 1.07-1.33), television/movies (PR 1.17, 95% CI 1.10-1.25), and video games (PR 1.14, 95% CI 1.07-1.21) per day was associated with a higher prevalence of the oppositional defiant disorder. When examining thresholds, exposure to >4 hr of total screen time per day was associated with a higher prevalence of conduct disorder (69%) and oppositional defiant disorder (46%).ConclusionsHigher screen time was prospectively associated with a higher prevalence of new-onset disruptive behavior disorders. The strongest association was between social media and conduct disorder, indicating that future research and interventions may focus on social media platforms to prevent conduct disorder.

BackgroundBinge-eating disorder (BED) is the most common eating disorder phenotype and is linked to several negative health outcomes. Yet, little is known about the social epidemiology of BED, particularly in early adolescence. The objective of this study was to examine the associations between sociodemographic characteristics and BED and binge-eating behaviors in a large, national cohort of 10-14-year-old adolescents in the United States (U.S.) METHODS: We conducted a cross-sectional analysis of two-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study (2018 - 2020) that included 10,197 early adolescents (10 - 14 years, mean 12 years) in the U.S. Multivariable logistic regression models were used to assess the associations between sociodemographic characteristics and BED and binge-eating behaviors, defined based on the Kiddie Schedule for Affective Disorders and Schizophrenia.ResultsIn this early adolescent sample (48.8% female, 54.0% White, 19.8% Latino/Hispanic, 16.1% Black, 5.4% Asian, 3.2% Native American, 1.5% Other), the prevalence of BED and binge-eating behaviors were 1.0% and 6.3%, respectively. Identifying as gay or bisexual (compared to heterosexual; adjusted odds ratio [AOR]: 2.25, 95% CI 1.01-5.01) and having a household income of less than $75,000 (AOR: 2.05, 95% CI: 1.21-3.46) were associated with greater odds of BED. Being male (AOR: 1.28, 95% CI: 1.06-1.55), of Native American (AOR: 1.60, 95% CI: 1.01-2.55) descent, having a household income less than $75,000 (AOR: 1.34, 95% CI: 1.08-1.65), or identifying as gay or bisexual (AOR for 'Yes' Response: 1.95, 95% CI: 1.31-2.91 and AOR for 'Maybe' Response: 1.81, 95% CI: 1.19-2.76) were all associated with higher odds of binge-eating behaviors.ConclusionSeveral sociodemographic variables showed significant associations with binge-eating behaviors, which can inform targeted screening, prevention, and education campaigns for BED among early adolescents.

We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9-4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9-4.5 μm. PEARLS is designed to be of lasting benefit to the community.

Chronic cough is a frequent disorder that is defined by cough of more than 8 weeks duration. Despite extensive investigation, some patients exhibit no aetiology and others do not respond to specific treatments directed against apparent causes of cough. Such patients are identified as having unexplained or refractory chronic cough. Recently, a high proportion of patients with chronic cough in the context of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) was highlighted. CANVAS is a rare neurological disorder with a biallelic variation in the replication factor C subunit 1 (RFC1) gene corresponding mostly to an intronic AAGGG repeat expansion. Chronic cough in patients with CANVAS shares similar characteristics with cough hypersensitivity syndrome. The high prevalence of chronic cough in CANVAS gives the opportunity to better understand the neurogenic mechanism of chronic cough. In this review, we will describe the characteristics and mechanisms of CANVAS. We will also address the potential mechanisms responsible for chronic cough in CANVAS. Finally, we will address chronic cough management in the context of CANVAS.

Recent years have seen an increase in interest with regard to offering music industry undergraduate programs at institutes of higher learning. Such programs typically cover a mix of courses in both music and business areas. An emerging trend in the music industry is the rising application of digital technologies in all business aspects. This makes it necessary to enhance the curriculum with opportunities that familiarize students with various digital technologies and the possibilities they offer, so graduates are well-prepared for their future careers. This paper presents a case study conducted at the State University of New York--Fredonia. It revealed a need to enhance the school's Music Industry program, in terms of course content, with information and communication technologies. A proposal of novel courses to enhance music industry student acquisition of technology competencies resulted from the study. Additionally, opportunities for the possible enrichment of existing courses with material on digital technologies applications are provided. This work is aimed not only at music industry educators but also at instructors in other disciplines willing to make their students aware of the latest technological trends.

BackgroundRecent research has emphasized a growing trend of weight gain attempts, particularly among adolescents and boys and young men. Little research has investigated these efforts among adults, as well as the specific diet modifications individuals who are trying to gain weight engage in. Therefore, the aims of this study were to characterize the diet modification efforts used by adults across five countries who reported engaging in weight gain attempts and to determine the associations between weight gain attempts and concerted diet modification efforts.MethodsCross-sectional data from the 2018 and 2019 International Food Policy Study, including participants from Australia, Canada, Mexico, the United Kingdom, and the United States (N = 42,108), were analyzed. In reference to the past 12 months, participants reported on weight gain attempts and diet modification efforts related to increased consumption of calories, protein, fiber, fruits and vegetables, whole grains, dairy products, all meats, red meat only, fats, sugar/added sugar, salt/sodium, and processed foods. Unadjusted (chi-square tests) and adjusted (modified Poisson regressions) analyses were conducted to examine associations between weight gain attempts and diet modification efforts.ResultsWeight gain attempts were significantly associated with higher likelihood of each of the 12 forms of diet modification efforts among male participants, and 10 of the diet modification efforts among female participants. Notably, this included higher likelihood of efforts to consume more calories (males: adjusted prevalence ratio [aPR] 3.25, 95% confidence interval [CI] 2.94-3.59; females: aPR 4.05, 95% CI 3.50-4.70) and fats (males: aPR 2.71, 95% CI 2.42-3.03; females: aPR 3.03, 95% CI 2.58-3.55).ConclusionsOverall, the patterns of association between weight gain attempts and diet modification efforts may be indicative of the phenomenon of muscularity-oriented eating behaviors. Findings further highlight the types of foods and nutrients adults from five countries may try to consume in attempts to gain weight.

BackgroundAnorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations-a critical component of hedonic responding-has never been studied in AN.MethodsThis multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12-22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired.DiscussionThis study will be the first to interrogate appetitive conditioning in AN-a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward.Trial registrationPending.Intended registryClinicaltrials.gov.

ObjectiveTo determine the prevalence and sociodemographic correlates of cyberbullying victimization and perpetration among a racially, ethnically and socioeconomically diverse population-based sample of 11-12-year-old early adolescents.MethodsWe analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study (Year 2; N = 9429). Multiple logistic regression analyses were used to estimate associations between sociodemographic factors (sex, race/ethnicity, sexual orientation, country of birth, household income, parental education) and adolescent-reported cyberbullying victimization and perpetration.ResultsIn the overall sample, lifetime prevalence of cyberbullying victimization was 9.6%, with 65.8% occurring in the past 12 months, while lifetime prevalence of cyberbullying perpetration was 1.1%, with 59.8% occurring in the past 12 months. Boys reported higher odds of cyberbullying perpetration (AOR 1.71, 95% CI 1.01-2.92) but lower odds of cyberbullying victimization (AOR 0.80, 95% CI 0.68-0.94) than girls. Sexual minorities reported 2.83 higher odds of cyberbullying victimization (95% CI 1.69-4.75) than nonsexual minorities. Lower household income was associated with 1.64 (95% CI 1.34-2.00) higher odds of cyberbullying victimization than higher household income, however household income was not associated with cyberbullying perpetration. Total screen time, particularly on the internet and social media, was associated with both cyberbullying victimization and perpetration.ConclusionsNearly one in 10 early adolescents reported cyberbullying victimization. Pediatricians, parents, teachers, and online platforms can provide education to support victims and prevent perpetration for early adolescents at the highest risk of cyberbullying.

ObjectiveTo determine sociodemographic correlates of problematic screen use (social media, video games, mobile phones) among a racially/ethnically and socioeconomically diverse population-based sample of 10-14-year-old early adolescents.Study designWe analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 2, 2018-2020; N = 8753). Multiple linear regression analyses were used to estimate associations between sociodemographic factors (age, sex, race/ethnicity, primary language, household income, parental education) and adolescent-reported problematic video game (Video Game Addiction Questionnaire), social media (Social Media Addiction Questionnaire), and mobile phone use (Mobile Phone Involvement Questionnaire).ResultsBoys reported higher problematic video game use while girls reported higher problematic social media and mobile phone use. Native American, black, and Latinx adolescents reported higher scores across all problematic screen measures compared to non-Latinx white adolescents. Having unmarried/unpartnered parents was associated with higher problematic social media use. Although higher household income was generally protective against problematic video game use, these associations were weaker for black than white adolescents (p for interaction

Abstract Background Infants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial). Design The PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4–8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved. Trial registration ClinicalTrials.gov NCT04373902 (registered April 2020).

Abstract Chaperone‐mediated autophagy (CMA) is a lysosome‐dependent degradation pathway that eliminates proteins that are damaged, partially unfolded, or targeted for selective proteome remodeling. CMA contributes to several cellular processes, including stress response and proteostasis. Age‐associated increase in cellular stressors and decrease in CMA contribute to pathologies associated with aging in various tissues. CMA contributes to bone homeostasis in young mice. An age‐associated reduction in CMA was reported in osteoblast lineage cells; however, whether declining CMA contributes to skeletal aging is unknown. Herein we show that cellular stressors stimulate CMA in UAMS‐32 osteoblastic cells. Moreover, the knockdown of an essential component of the CMA pathway, LAMP2A, sensitizes osteoblasts to cell death caused by DNA damage, ER stress, and oxidative stress. As elevations in these stressors are thought to contribute to age‐related bone loss, we hypothesized that declining CMA contributes to the age‐associated decline in bone formation by sensitizing osteoblast lineage cells to elevated stressors. To test this, we aged male CMA‐deficient mice and controls up to 24 months of age and examined age‐associated changes in bone mass and architecture. We showed that lack of CMA did not alter age‐associated decline in bone mineral density as measured by dual x‐ray absorptiometry (DXA). Moreover, microCT analysis performed at 24 months of age showed that vertebral cancellous bone volume, cortical thickness, and porosity of CMA‐deficient and control mice were similar. Taken together, these results suggest that reduction of CMA does not contribute to age‐related bone loss.

Abstract Background Understanding of pain in osteoarthritis, its genesis, and perception is still in its early stages. Identification of precise ligand-receptor pairs that transduce pain and the cells and tissues in which they reside will elucidate new therapeutic approaches for pain management. Our recent studies had identified an inflammation-amplifying (Inf-A) cell population that is expanded in human OA cartilage and is distinctive in the expression of both IL1R1 and TNF-R2 receptors and active Jnk signaling cascade. Methods In this study, we have tested the function of the cartilage-resident IL1R1+TNF-R2+ Inf-A cells in OA. We have identified that the IL1R1+TNF-R2+ Inf-A cells expand in aged mice as well as after anterior cruciate ligament tear upon tibia loading and OA initiation in mice. We targeted and modulated the Jnk signaling cascade in InfA through competitive inhibition of Jnk signaling in mice and human OA explants and tested the effects on joint structure and gait in mice. Results Modulation of Jnk signaling led to attenuation of inflammatory cytokines CCL2 and CCL7 without showing any structural improvements in the joint architecture. Interestingly, Jnk inhibition and lowered CCL2 and 7 are sufficient to significantly improve the gait parameters in treated PTOA mice demonstrating reduced OA-associated pain. Consistent with the mice data, treatment with JNK inhibitor did not improve human OA cartilage explants. Conclusion These studies demonstrate that Inf-A, an articular-cartilage resident cell population, contributes to pain in OA via secretion of CCL2 and 7 and can be targeted via inhibition of Jnk signaling.

Aims: Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice. Methods: We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR). Results: Local delivery of NF-κB decoy ODN in vivo increased osteogenesis in males, but not females, in the presence of chronic inflammation induced by cPE. Bone resorption activity was decreased in both sexes. In vitro osteogenic and osteoclastic differentiation assays during inflammatory conditions did not reveal differences among the groups. Receptor activator of nuclear factor kappa Β ligand (Rankl) gene expression by osteoblasts was significantly decreased only in males when treated with ODN. Conclusion: We demonstrated that NF-κB decoy ODN increased osteogenesis in male mice and decreased bone resorption activity in both sexes in preclinical models of chronic inflammation. NF-κB signalling could be a therapeutic target for chronic inflammatory diseases involving bone, especially in males. Cite this article: Bone Joint Res 2024;13(1):28–39.

Advancements in genomics and machine learning have significantly enhanced the study of Salmonella epidemiology. Whole-genome sequencing has revolutionized bacterial genomics, allowing for detailed analysis of genetic variation and aiding in outbreak investigations and source tracking. Short-read sequencing technologies, such as those provided by Illumina, have been instrumental in generating draft genomes that facilitate serotyping and the detection of antimicrobial resistance. Long-read sequencing technologies, including those from Pacific Biosciences and Oxford Nanopore Technologies, offer the potential for more complete genome assemblies and better insights into genetic diversity. In addition to these sequencing approaches, machine learning techniques like decision trees and random forests provide powerful tools for pattern recognition and predictive modeling. Importantly, the study of bacteriophages, which interact with Salmonella, offers additional layers of understanding. Phages can impact Salmonella population dynamics and evolution, and their integration into Salmonella genomics research holds promise for novel insights into pathogen control and epidemiology. This review revisits the history of Salmonella and its pathogenesis and highlights the integration of these modern methodologies in advancing our understanding of Salmonella.

Abstract Introduction Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations in both reward processing and dopaminergic activity. Neuromelanin‐sensitive magnetic resonance imaging (MRI) is an emerging method to index midbrain neuromelanin—a by‐product of dopaminergic synthesis. The assessment of midbrain neuromelanin, and its association with AN psychopathology and reward‐related processes, may provide critical insights into reward circuit function in AN. Methods This study will incorporate neuromelanin‐sensitive MRI into an existing study of appetitive conditioning in those with AN. Specifically, those with acute and underweight AN (N = 30), those with weight‐restored AN (N = 30), and age‐matched healthy controls (N = 30) will undergo clinical assessment of current and previous psychopathology, in addition to structural neuromelanin‐sensitive MRI, diffusion MRI, and functional MRI (fMRI) during appetitive conditioning. Conclusion This study will be among the first to interrogate midbrain neuromelanin in AN—a disorder characterized by altered dopaminergic activity. Results will help establish whether abnormalities in the midbrain synthesis of dopamine are evident in those with AN and are associated with symptomatic behavior and reduced ability to experience pleasure and reward.

Summary: Memory has been identified as the least heritable cognitive trait in canines, suggesting a significant influence of non-genetic factors. We observed a trend that overall memory scores (OMS) improve with age in a cohort of 27 young dogs, but considerable plasticity exists. Employing linear discriminant analysis of gut microbiome data from dogs exhibiting low and high OMS, a single bacterial species, Bifidobacterium pseudolongum, was identified and confirmed to be correlated with elevated OMS. Subsequent analysis using a random forest regression model revealed that sex, litter, and breed identity had minimal predictive importance. Age had some predictive value but failed to achieve statistical significance in this dataset. In sharp contrast, the abundance of 17 bacterial taxa in the microbiome showed a stronger predictive capacity for memory performance. Our findings provide insights into microbiome underpinnings of mammalian cognitive functions and suggest avenues for developing psychobiotics to enhance canine memory and learning.

Influenza A virus (IAV) is a common respiratory pathogen and a global cause of significant and often severe morbidity. Although inflammatory immune responses to IAV infections are well described, little is known about how neuroimmune processes contribute to IAV pathogenesis. In the present study, we employed surgical, genetic, and pharmacological approaches to manipulate pulmonary vagal sensory neuron innervation and activity in the lungs to explore potential crosstalk between pulmonary sensory neurons and immune processes. Intranasal inoculation of mice with H1N1 strains of IAV resulted in stereotypical antiviral lung inflammation and tissue pathology, changes in breathing, loss of body weight and other clinical signs of severe IAV disease. Unilateral cervical vagotomy and genetic ablation of pulmonary vagal sensory neurons had a moderate effect on the pulmonary inflammation induced by IAV infection, but significantly worsened clinical disease presentation. Inhibition of pulmonary vagal sensory neuron activity via inhalation of the charged sodium channel blocker, QX-314, resulted in a moderate decrease in lung pathology, but again this was accompanied by a paradoxical worsening of clinical signs. Notably, vagal sensory ganglia neuroinflammation was induced by IAV infection and this was significantly potentiated by QX-314 administration. This vagal ganglia hyperinflammation was characterized by alterations in IAV-induced host defense gene expression, increased neuropeptide gene and protein expression, and an increase in the number of inflammatory cells present within the ganglia. These data suggest that pulmonary vagal sensory neurons play a role in the regulation of the inflammatory process during IAV infection and suggest that vagal neuroinflammation may be an important contributor to IAV pathogenesis and clinical presentation. Targeting these pathways could offer therapeutic opportunities to treat IAV-induced morbidity and mortality.

This study examined relationship status (e.g., single versus not single) and number of sexual partners in relation to muscularity- and disordered eating-related attitudes and behaviors among 1090 cisgender gay men enrolled in The PRIDE Study in 2018. Participants completed measures assessing muscle dysmorphia (MD) symptoms, disordered eating attitudes and behaviors, and appearance- and performance-enhancing drug or supplement (APEDS) use. In linear regression models adjusting for theoretically relevant covariates, neither relationship status nor number of past-month sexual partners was associated with disordered eating attitudes. In terms of MD symptoms, single (versus not single) relationship status was associated with greater appearance intolerance, and a greater number of sexual partners was associated with greater drive for size and functional impairment. In adjusted logistic regression models, a greater number of past-month sexual partners was associated with use of anabolic-androgenic steroids, synthetic performance-enhancing substances, protein supplements, and creatine supplements, as well as greater likelihood of engaging in compelled/driven exercise. Across all associations, effect sizes were generally small. Overall, results support that inquiring about sexual partners may have utility in evaluating risk for muscularity-oriented attitudes and behaviors among cisgender gay men. Future work will need to replicate these findings, particularly in more diverse samples.

ObjectivesTo determine the prevalence of muscle-enhancing behaviors in adolescents and young adults using a nationally representative sample in the USA and to examine differences by sex, race/ethnicity, age, socioeconomic status, body mass index, and participation in team sports.MethodsProspective cohort data from the National Longitudinal Study of Adolescent to Adult Health, Waves I through III (1994-2002) were analyzed. Engagement in muscle-enhancing behaviors including dietary changes, exercise and weightlifting, supplement use, performance-enhancing substances, and anabolic androgenic steroids were recorded. Multiple logistic regression models using generalized estimating equations, incorporating robust standard errors with clustering by school and within persons, and using national sample weighting, were used to determine associations with muscle-enhancing behaviors across three data collection waves.ResultsOf the 18,924 adolescents at baseline, 29.2% of males and 7.0% of females reported weight gain attempts, while 25.2% of males and 3.8% of females reported any muscle-enhancing behavior. All muscle-enhancing behaviors were more common in males compared to females (p

Abstract The function of regulatory elements is highly dependent on the cellular context, and thus for understanding the function of elements associated with psychiatric diseases these would ideally be studied in neurons in a living brain. Massively Parallel Reporter Assays (MPRAs) are molecular genetic tools that enable functional screening of hundreds of predefined sequences in a single experiment. These assays have not yet been adapted to query specific cell types in vivo in a complex tissue like the mouse brain. Here, using a test-case 3′UTR MPRA library with genomic elements containing variants from autism patients, we developed a method to achieve reproducible measurements of element effects in vivo in a cell type-specific manner, using excitatory cortical neurons and striatal medium spiny neurons as test cases. This targeted technique should enable robust, functional annotation of genetic elements in the cellular contexts most relevant to psychiatric disease.

Abstract Background Binge-eating disorder (BED) is the most common eating disorder phenotype and is linked to several negative health outcomes. Yet, little is known about the social epidemiology of BED, particularly in early adolescence. The objective of this study was to examine the associations between sociodemographic characteristics and BED and binge-eating behaviors in a large, national cohort of 10–14-year-old adolescents in the United States (U.S.) Methods We conducted a cross-sectional analysis of two-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study (2018 − 2020) that included 10,197 early adolescents (10 − 14 years, mean 12 years) in the U.S. Multivariable logistic regression models were used to assess the associations between sociodemographic characteristics and BED and binge-eating behaviors, defined based on the Kiddie Schedule for Affective Disorders and Schizophrenia. Results In this early adolescent sample (48.8% female, 54.0% White, 19.8% Latino/Hispanic, 16.1% Black, 5.4% Asian, 3.2% Native American, 1.5% Other), the prevalence of BED and binge-eating behaviors were 1.0% and 6.3%, respectively. Identifying as gay or bisexual (compared to heterosexual; adjusted odds ratio [AOR]: 2.25, 95% CI 1.01–5.01) and having a household income of less than $75,000 (AOR: 2.05, 95% CI: 1.21–3.46) were associated with greater odds of BED. Being male (AOR: 1.28, 95% CI: 1.06–1.55), of Native American (AOR: 1.60, 95% CI: 1.01–2.55) descent, having a household income less than $75,000 (AOR: 1.34, 95% CI: 1.08–1.65), or identifying as gay or bisexual (AOR for ‘Yes’ Response: 1.95, 95% CI: 1.31–2.91 and AOR for ‘Maybe’ Response: 1.81, 95% CI: 1.19–2.76) were all associated with higher odds of binge-eating behaviors. Conclusion Several sociodemographic variables showed significant associations with binge-eating behaviors, which can inform targeted screening, prevention, and education campaigns for BED among early adolescents.

As current psychosocial and pharmacological interventions show limited efficacy in the treatment of anorexia nervosa (AN), interest in the potential value of neurosurgical intervention and neuromodulation in managing severe and enduring illness has grown. We conducted a systematic review of 20 trials of neurosurgical and neuromodulatory treatments for AN, including neurosurgical ablation, deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Overall, there is evidence to support the role of stereotactic ablation and DBS in the treatment of AN. In contrast, results for rTMS and tDCS have been modest and generally more mixed. Neurosurgical treatment may offer important new avenues for the treatment of AN. Additional randomized clinical trials with comparable patient populations will be needed, in which change in affective, cognitive, and perceptual symptom phenomena, and interrogation of targeted circuits, pre- and post-intervention, are carefully documented.

Sexually dimorphic tissues are formed by cells that are regulated by sex hormones. While a number of systemic hormones and transcription factors are known to regulate proliferation and differentiation of osteoblasts and osteoclasts, the mechanisms that determine sexually dimorphic differences in bone regeneration are unclear. To explore how sex hormones regulate bone regeneration, we compared bone fracture repair between adult male and female mice. We found that skeletal stem cell (SSC) mediated regeneration in female mice is dependent on estrogen signaling but SSCs from male mice do not exhibit similar estrogen responsiveness. Mechanistically, we found that estrogen acts directly on the SSC lineage in mice and humans by up-regulating multiple skeletogenic pathways and is necessary for the stem cell's ability to self- renew and differentiate. Our results also suggest a clinically applicable strategy to accelerate bone healing using localized estrogen hormone therapy.

BackgroundAdverse childhood experiences (ACEs) are common and linked to negative health outcomes. Previous studies have found associations between ACEs and binge-eating disorder (BED), though they have mainly focused on adults and use cross-sectional data. The objective of this study was to examine the associations between ACEs and BED in a large, national cohort of 9-14-year-old early adolescents in the US.MethodsWe analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 10,145, 2016-2020). Logistic regression analyses were used to determine the associations between self-reported ACEs and BED based on the Kiddie Schedule for Affective Disorders and Schizophrenia at two-year follow-up, adjusting for sex, race/ethnicity, baseline household income, parental education, site, and baseline binge-eating disorder.ResultsIn the sample, (49% female, 46% racial/ethnic minority), 82.8% of adolescents reported at least one ACE and 1.2% had a diagnosis of BED at two-year follow-up. The mean number of ACEs was higher in those with a diagnosis of BED compared to those without (2.6 ± 0.14 vs 1.7 ± 0.02). The association between number of ACEs and BED in general had a dose-response relationship. One ACE (adjusted odds ratio [aOR] 3.48, 95% confidence interval [CI] 1.11-10.89), two ACEs (aOR 3.88, 95% CI 1.28-11.74), and three or more ACEs (aOR 8.94, 95% CI 3.01-26.54) were all associated with higher odds of BED at two-year follow-up. When stratified by types of ACEs, history of household mental illness (aOR 2.18, 95% 1.31-3.63), household violence (aOR 2.43, 95% CI 1.42-4.15), and criminal household member (aOR 2.14, 95% CI 1.23-3.73) were most associated with BED at two-year follow-up.ConclusionsChildren and adolescents who have experienced ACEs, particularly household challenges, have higher odds of developing BED. Clinicians may consider screening for ACEs and providing trauma-focused care when evaluating patients for BED.