The purpose of this study is to investigate whether sex plays a role in donor-site dysfunction after head and neck reconstruction.

In this retrospective case series, 76 patients were assessed for donor-site morbidity using the Short Form 36, Short Musculoskeletal Function Assessment, disabilities of the arm, shoulder, and hand, and lower-limb core scale. Differences by sex were compared using t-tests. Multivariable linear regression analysis was conducted to adjust for potential confounders.

Females observed significantly greater disability for the SF-36 mental component summary score with a mean of 45.9 (standard deviation 10.5) compared to males, with a mean of 51.8 (standard deviation 10.2), p = 0.02. Sex is significantly related to SF-36 mental component summary score after controlling for neuropsychiatric disease and tracheostomy status.

Females reported significantly worse mental component scores compared to males undergoing free flap reconstruction of the head and neck.

Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations.

This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples.

We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18–0.34, p = 8.5 × 10−6). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI −0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06–0.08), female sex (beta = 0.160, 95% CI 0.15–0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03–0.07), while neither the depression PGS (beta = 0.004, 95% CI −0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI −0.01 to 0.03) were strongly associated with MDD.

Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.

Nonsuicidal self-injury (NSSI) is defined as deliberate and direct damage to one’s body tissues without any suicidal intent. NSSI is now recognized as a major risk factor for suicide and is prevalent among adolescents, with prevalence rates ranging from 7.5% to 46.5%, leading to increased interest in the pathophysiology of NSSI. This study aimed to examine cortical gyrification morphology, a neurobiological index of cortical folding and patterning, among unmedicated individuals with NSSI, which is prevalent in adolescents and young adults.

The main objective of this study is to compare cortical morphological abnormalities between individuals with NSSI and controls in terms of the local gyrification index (LGI), the ratio of the smooth cortical surface area at each vertex to the corresponding sulcal folds. In addition, we hypothesized that the LGI, a stable neurodevelopmental marker of cortical and subcortical circuit intergrity, would correlate with clinical measures in youth with NSSI.

A total of 101 individuals with NSSI and 100 age-, gender-, and handedness-matched controls completed self-report questionnaires and structural magnetic resonance imaging (MRI) data were acquired on a 3T Siemens scanner. A surface-based analysis was conducted using the Computational Anatomy Toolbox (CAT12) in Statistical Parametric Mapping (SPM12). Partial correlation analysis was also performed using R software to investigate the association between the LGI values extracted from the region of interest (ROI) and clinical symptoms, including depression, anxiety, emotion dysregulation, and anhedonia in individuals with NSSI.

Individuals with NSSI showed significantly increased LGI in the right insula sulcus and left superior temporal sulcus (STS), along with decreased LGI in the right calcarine and left superior parietal sulcus (SPS), compared to controls (5000 permutation correction, threshold-free cluster enhancement with a threshold of p < .05). In addition, higher LGI in left STS was correlated with greater scores of the Beck Anxiety Inventory (r = 0.22, p < .05) and of the Impulse Control Difficulties subscale of the Difficulties in Emotion Regulation Scale (r = 0.34, p < .001). Conversely, reduced LGI of the right calcarine was associated with a higher score on the Anhedonia subscale of the Beck Depression Inventory (r = -0.23, p < .05) within individuals with NSSI.

This study identified hypergyria in the right insular and left STS and hypogyria in the right calcarine and left SPS in individuals with NSSI. The former pattern was associated with anxiety and impulse control difficulties, and the latter was with anhedonia. This study is the first to alter distinct neurodevelopmental patterns of local gyrification and their correlations with clinical manifestations in individuals with NSSI.

None Declared

The focus on social determinants of health (SDOH) and their impact on health outcomes is evident in U.S. federal actions by Centers for Medicare & Medicaid Services and Office of National Coordinator for Health Information Technology. The disproportionate impact of COVID-19 on minorities and communities of color heightened awareness of health inequities and the need for more robust SDOH data collection. Four Clinical and Translational Science Award (CTSA) hubs comprising the Texas Regional CTSA Consortium (TRCC) undertook an inventory to understand what contextual-level SDOH datasets are offered centrally and which individual-level SDOH are collected in structured fields in each electronic health record (EHR) system potentially for all patients.

Hub teams identified American Community Survey (ACS) datasets available via their enterprise data warehouses for research. Each hub’s EHR analyst team identified structured fields available in their EHR for SDOH using a collection instrument based on a 2021 PCORnet survey and conducted an SDOH field completion rate analysis.

One hub offered ACS datasets centrally. All hubs collected eleven SDOH elements in structured EHR fields. Two collected Homeless and Veteran statuses. Completeness at four hubs was 80%–98%: Ethnicity, Race; < 10%: Education, Financial Strain, Food Insecurity, Housing Security/Stability, Interpersonal Violence, Social Isolation, Stress, Transportation.

Completeness levels for SDOH data in EHR at TRCC hubs varied and were low for most measures. Multiple system-level discussions may be necessary to increase standardized SDOH EHR-based data collection and harmonization to drive effective value-based care, health disparities research, translational interventions, and evidence-based policy.

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD).

To investigate the genomic architecture of ASD in terms of non-coding de novo mutations and 3-dimensional chromatin interactions

We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions.

Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development.

Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

None Declared

Nurses are at an increased risk for work-related stress resulting in post-traumatic stress disorder (PTSD). They are susceptible due to frequent exposure to traumatic situations providing care for patients.

The purpose of this systematic review is to comprehensively review the content and characteristics of intervention programs for reducing the post-traumatic stress of nurses or nursing students, providing a basis for developing a standardized protocol for programs to promote the integrated health of nurses and protect them from stress events in clinical environments.

This is a systematic review. Participants (P) targeted nurses or nursing students; Intervention (I) included intervention programs for reducing post-traumatic stress; Comparison (C) was control groups provided with usual or no interventions ; and Outcomes (O) referred to changes in physical or emotional reactions toward post-traumatic stress. Two researchers searched four databases including PubMed, CINAHL, PsycINFO, and EMBASE with keywords such as “nurse,” “post-trumatic stress disorder,” “program,” and “intervention”. A total of 7,523 studies were searched and 10 studies were included for final analysis (Image 1). The Risk of Bias2 (Image 2) and the Risk of Bias for Non-randomized Study I (Image 3) were used to evaluate the quality the included studies.

The number of studies is increasing, with four studies published before 2020, and six studies published since, of which three in 2022. Definitions of trauma situations to which nurses are exposed included diverse elements such as patient death, workplace violence, the COVID-19 pandemic, and complex trauma experiences due to working environments. Most studies have provided multiple intervention sessions, which is appropriate considering the characteristics of PTSD. Most studies examined the secondary effects on mental health such as anxiety, depression, and burnout caused by stress rather than evaluating stress itself. The quality of the study was generally highly biased. The risk of bias increased for the two randomized controlled trials in terms of measurement outcomes and outcome description. The other eight non-randomized studies all included a self-reporting questionnaire of participants, leading to a risk of bias in terms of measurement outcomes.

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Studies have been conducted to confirm the effectiveness of interventions given heightened concerns about PTSD in nurses. However, the concept of the trauma experienced by nurses was not integrally defined, and information on interventions was often limited. Efforts are required to improve the quality of research in terms of experimental study design.

None Declared

Lamina-specific alterations of inhibitory circuitries have been considered the crucial pathogenesis of perceptual, cognitive and behavioral symptoms presented in schizophrenia and mood disorders. Especially, with emerging evidences indicating the close lamina-specific relationship between synaptic defects and γ-Aminobutyric acid (GABA)-related gene dysfunctions, it has been suggested the mRNA dysregulations of Tyrosine kinase B (TrkB) and Glutamate decarboxylase 67 (GAD67) could particularly be implicated in middle and deep layers of neocortex of patients with major psychiatric disorders.

Giving inquiries of whether defects of these mRNA levels in Orbitofrontal cortex (OFC) would be involved as lamina-specific patterns in individuals with schizophrenia and mood disorders.

We examined mRNA levels of BDNF, TrkB and GAD67 in each OFC layer I through VI. We analyzed data from postmortem brain tissue of the Stanley Neuropathology Consortium Integrative Database (SNCID). SNCID consists of 15 subjects in each of four groups (schizophrenia, bipolar disorder, major depression without psychotic features, and unaffected controls). All groups were matched for age, sex, race, brain pH and post-mortem interval.

We found TrkB mRNA levels to be significantly reduced in layer VI in both groups with schizophrenia (25.8%) and bipolar disorder (35.7%) compared with controls. GAD67 mRNA levels were also significantly reduced in layer III and IV in patients with schizophrenia (23.4% and 22.7%, respectively) and bipolar disorder (31.2% and 24.9%, respectively) compared with controls. Individuals with major depression showed only trends toward decreased mRNA levels of GAD67 in layer III and IV and of TrkB in layer VI compared with controls. TrkB mRNA levels in layer VI were significantly correlated with GAD67 mRNA levels in layer III (ρ=0.581, p=0.037) and IV (ρ=0.857, p<0.001) in subjects with bipolar disorder, but not in those with schizophrenia. When analyzed with partial correlation controlling the effects of pH and PMI, significance of correlation remained only between GAD67 mRNA in layer IV and TrkB mRNA in layer VI in individuals with bipolar disorder (ρ=0.768, p=0.006).

The resulting lamina-specific decreases in inhibitory tone across layers of OFC may contribute to the unrestrained irritability and violent behaviors in common shared by both patients with schizophrenia and bipolar disorder. Nonetheless, our findings indicate the obvious correlations between lamina-specifically altered TrkB and GAD67 mRNA levels in OFC might be a candidate for endophenotype of bipolar disorder.

None Declared

Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.

Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.

In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.

This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.