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BackgroundSex 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.MethodsWe 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.ResultsAcross 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).ConclusionsIn 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.

Introduction: The coronavirus 2019 pandemic caused a shortage of disposable N95 respirators, prompting healthcare entities to extend the use of these masks beyond their intended single-use manufacturer recommendation with a paucity of supporting research.Methods: We performed a prospective cohort study of ED healthcare workers (HCW) (“subjects”) required to use respirators at an academic, Level I trauma center. Subjects had been previously fit tested and assigned an appropriately sized N95 mask per hospital protocol. Per study protocol, subjects were fit tested periodically throughout their shifts and on multiple shifts over the eight-week study period. Data points collected included the age of the mask, subjective assessment of mask seal quality, and fit test results. We analyzed the data using Fisher’s exact test, and calculated odds ratios (OR) to determine the failure rate of disposable N95 masks following reuse.Results: A total of 130 HCWs underwent fit testing and 127 were included for analysis. Mask failure rate climbed after day 2 of use, with 33.3% of masks failing at day 3, 42.9% at day 4, and 50% at ≥ day 5. Categorizing the masks into those being used for two or fewer days vs those in use for three or more, failure was more common on day 3 of use or older compared to those in the first two days of use (41.8% vs 8.3%, P < 0.0001) with an OR of failure with an older mask of 7.9 (confidence interval [CI], 2.8-22.3). The healthcare workers’ assessment of poor seal was 33.3% sensitive (CI, 18.6-51.9) and 95.7% specific (CI, 88.8-98.6) for fit test failure.Conclusion: Disposable N95 masks have significant failure rates following reuse in clinical practice. Healthcare personnel also performed poorly in assessing the integrity of the seal of their disposable respirators.

The purpose of this article was to explore how family chaos, parenting processes, parent-child relationship qualities, and sibling relationship qualities changed before versus the early months of the COVID-19 pandemic. Participants included one parent and two adolescent-aged children from 682 families (2,046 participants). Parents and youth participating in an ongoing longitudinal study in five Midwestern states in the United States completed an additional web-based assessment of family processes and family relationship qualities during the May-June 2020 pandemic-related shutdowns. A series of two-wave latent change score models indicated that family chaos increased with the onset of pandemic-related shutdowns and that the level of chaos within a family during the shutdowns had implications for changes in several parenting processes and family relationship qualities. Specifically, higher levels of family chaos during the pandemic mitigated observed increases in parental knowledge and were associated with declines in parental autonomy granting. Family chaos during pandemic-related shutdowns also was associated with increases in maternal-child conflict, paternal-child conflict, and sibling conflict as well as decreases in paternal-child intimacy, sibling intimacy, and sibling disclosure. Overall, consistent with a family stress perspective, the onset of the COVID-19 pandemic was associated with increased strain and commotion within many households, and these changes had implications for multiple family relationships.

We performed a transcriptome-wide meta-analysis and gene co-expression network analysis to identify genes and gene networks dysregulated in the peripheral blood of bipolar disorder (BD) cases relative to unaffected comparison subjects, and determined the specificity of the transcriptomic signatures of BD and schizophrenia (SZ). Nineteen genes and 4 gene modules were significantly differentially expressed in BD cases. Thirteen gene modules were shown to be differentially expressed in a combined case-group of BD and SZ subjects called "major psychosis", including genes biologically linked to apoptosis, reactive oxygen, chromatin remodeling, and immune signaling. No modules were differentially expressed between BD and SZ cases. Machine-learning classifiers trained to separate diagnostic classes based solely on gene expression profiles could distinguish BD cases from unaffected comparison subjects with an area under the curve (AUC) of 0.724, as well as BD cases from SZ cases with AUC = 0.677 in withheld test samples. We introduced a novel and straightforward method called "polytranscript risk scoring" that could distinguish BD cases from unaffected subjects (AUC = 0.672) and SZ cases (AUC = 0.607) significantly better than expected by chance. Taken together, our results highlighted gene expression alterations common to BD and SZ that involve biological processes of inflammation, oxidative stress, apoptosis, and chromatin regulation, and highlight disorder-specific changes in gene expression that discriminate the major psychoses.

BackgroundSacroiliac (SI) joint pathology may result in low-back pain, which causes substantial disability. Treatment failure with operative management of SI pain may be related to incomplete fusion of the joint and to fixation failure. The objective of this study was to evaluate the initial biomechanical stability of SI joint fixation with a novel implantable device in an in vitro human cadaveric model.MethodsThe right and left sides of 3 cadaveric L4-pelvis specimens were tested (1) intact, (2) destabilized, and (3) instrumented with an implantable SI joint fixation device using a simulated single-stance load condition. Right-leg and left-leg stance data were grouped together for a sample size of 6, and angular range of motion (ROM) was determined during application of flexion-extension, lateral bending, and axial rotation bending moments to a limit of 7.5 Nm.ResultsFollowing intact testing, destabilization by severing the posterior SI joint capsule and ligaments and the pubic symphysis reliably produced a significantly destabilized joint with the mean angular ROM more than doubling in flexion-extension and lateral bending and more than tripling in axial rotation (P ≤ .003) compared to the intact condition. Instrumentation with the SI screw fixation device significantly reduced mean joint ROM compared to the destabilized condition in all 3 anatomic planes tested (P < .001). When compared to the intact condition, the SI-instrumented condition significantly reduced lateral bending (P = .01) and had a similar ROM in flexion-extension (P = .14) and axial rotation (P = .85).ConclusionsInstrumentation with the SI screw fixation device significantly reduced mean joint ROM compared to the destabilized condition, with similar ROM in flexion-extension and axial rotation, and it significantly reduced ROM in lateral bending compared to that for the intact joint. The ROM values observed with the instrumented condition were comparable to levels of mobility considered favorable for spinal fusion.

DSGN110 was a multidisciplinary course teaching first year students enrolled in in a variety of majors about design thinking. The course is offered for the majors of architecture, landscape architecture, interior design, community and regional planning, along with computer science and business students. By blending face-to-face and online instructional strategies, desired practices and learning outcomes associated with the more intimate nature of studio-based learning and learning through action were scaled and achieved in the large enrollment course. The quantitative analysis of the pre and post survey revealed significant change across all constructs and the qualitative data analysis supported these findings, demonstrating that a blended course design utilizing collaborative technology platforms offered an innovative solution to teaching and learning in a manner reflective of a studio-based pedagogy.

To fill a gap in research on the incorporation of neuroscience in social work education, this article describes Master of Social Work (MSW) student and alumni experiences learning a neuroscience-informed model for practice with clients who have endured developmental trauma. The Neurosequential Model of Therapeutics (NMT) is a clinical decision-making tool that provides an estimate of how a client's current neurobiological functioning may have been impacted by trauma during the developmental period in order to inform the selection and sequencing of interventions. MSW students and alumni participated in focus groups exploring their perspectives on learning the NMT, the utility of the model in their work, and the fit between the model and social work theory and practice. Participants found the model helpful in conceptualizing client cases and applicable to their work, but challenging to implement due to others' lack of familiarity with the model, and insufficient infrastructure. These findings suggest the NMT may be a valuable tool for teaching neuroscience within schools of social work.

To identify risk factors for relaxing a strict e-cigarette ban in households with adolescents. Youth (ages 12–17) in the Population Assessment of Tobacco and Health (PATH) Study whose parents held a strict vaping ban in 2016 (n = 6,514; 51.5% male) and their parents provided follow-up data on up to four occasions through 2020 on whether the ban was relaxed. 13.5% of households with strict vaping bans relaxed them in a subsequent wave. Results from a logistic regression model showed that the odds of relaxing strict bans were higher if, at baseline, parents vaped (OR = 2.20; 95% CI: 1.22–3.97; p <.01), parents smoked tobacco (OR = 2.55; CI: 2.00–3.26; p <.001), youth smoked tobacco (OR = 2.27; CI: 1.29–4.00; p <.01), parents reported no smoking ban (OR = 2.68; CI: 1.88–3.81; p <.001), youth did not know that their household had a vaping ban (OR = 1.95; CI: 1.50–2.54; p <.001), and parents perceived low harm from vaping (OR = 1.60; CI: 1.16–2.19; p <.01). Although most sociodemographic controls were not independently associated, parents were less likely to relax bans if they had a college degree (OR = 0.71; CI: 0.51–0.998; p <.05), graduate degree (OR = 0.50; CI: 0.43–0.72; p <.001), or children who were non-Hispanic Black (OR = 0.69; CI: 0.49–0.96; p <.05) or Hispanic (OR = 0.62; CI: 0.47–0.81; p <.001). While most households with adolescents prohibited e-cigarette use indoors, nearly one in seven relaxed prior strict vaping bans. Parents need support to maintain clear, consistent, and continuous restrictions that communicate that vaping is not safe or permissible for youth. [ABSTRACT FROM AUTHOR]

The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n=315) and from ex-vivo blood tissues (n=578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia.

Many genes involved in brain development have been associated with human neurodevelopmental disorders, but underlying pathophysiological mechanisms remain undefined. Human genetic and mouse behavioral analyses suggest that ENGRAILED-2 (EN2) contributes to neurodevelopmental disorders, especially autism spectrum disorder. In mouse, En2 exhibits dynamic spatiotemporal expression in embryonic mid-hindbrain regions where monoamine neurons emerge. Considering their importance in neuropsychiatric disorders, we characterized monoamine systems in relation to forebrain neurogenesis in En2-knockout (En2-KO) mice. Transmitter levels of serotonin, dopamine and norepinephrine (NE) were dysregulated from Postnatal day 7 (P7) to P21 in En2-KO, though NE exhibited the greatest abnormalities. While NE levels were reduced ∼35% in forebrain, they were increased 40 -: 75% in hindbrain and cerebellum, and these patterns paralleled changes in locus coeruleus (LC) fiber innervation, respectively. Although En2 promoter was active in Embryonic day 14.5 -: 15.5 LC neurons, expression diminished thereafter and gene deletion did not alter brainstem NE neuron numbers. Significantly, in parallel with reduced NE levels, En2-KO forebrain regions exhibited reduced growth, particularly hippocampus, where P21 dentate gyrus granule neurons were decreased 16%, suggesting abnormal neurogenesis. Indeed, hippocampal neurogenic regions showed increased cell death (+77%) and unexpectedly, increased proliferation. Excess proliferation was restricted to early Sox2/Tbr2 progenitors whereas increased apoptosis occurred in differentiating (Dcx) neuroblasts, accompanied by reduced newborn neuron survival. Abnormal neurogenesis may reflect NE deficits because intra-hippocampal injections of β-adrenergic agonists reversed cell death. These studies suggest that disruption of hindbrain patterning genes can alter monoamine system development and thereby produce forebrain defects that are relevant to human neurodevelopmental disorders.

There has been recent interest in the relationship between socioeconomic status and the diagnosis of autism in children. Studies in the United States have found lower rates of autism diagnosis associated with lower socioeconomic status, while studies in other countries report no association, or the opposite. This article aims to contribute to the understanding of this relationship in the United Kingdom. Using data from the Born in Bradford cohort, comprising 13,857 children born between 2007 and 2011, it was found that children of mothers educated to A-level or above had twice the rate of autism diagnosis, 1.5% of children (95% confidence interval: 1.1%, 1.9%) compared to children of mothers with lower levels of education status 0.7% (95% confidence interval: 0.5%, 0.9%). No statistically significant relationship between income status or neighbourhood material deprivation was found after controlling for mothers education status. The results suggest a substantial level of underdiagnosis for children of lower education status mothers, though further research is required to determine the extent to which this is replicated across the United Kingdom. Tackling inequalities in autism diagnosis will require action, which could include increased education, awareness, further exploration of the usefulness of screening programmes and the provision of more accessible support services.