Association of allostatic load with overall survival in epithelial ovarian cancer.

OBJECTIVE: Elevated allostatic load (AL), an integrated, cumulative marker of physiologic damage due to socioenvironmental stress, is associated with increased mortality in patients with breast, lung, and other cancers. The relationship between allostatic load and mortality in ovarian cancer patients remains unknown. We examined the relationship between allostatic load and overall survival in ovarian cancer patients. METHODS: This cross-sectional study used data from 201 patients enrolled in a prospective observational ovarian cancer cohort study at a National Cancer Institute-designated Comprehensive Cancer Center from October 2012 through June 2022. All patients underwent debulking surgery and completed a full course of standard-of-care platinum-based chemotherapy. Follow-up was completed through January 2024. Allostatic load was calculated as a summary score by assigning one point to the worst sample quartile for each of ten biomarkers measured within 45 days before the ovarian cancer diagnosis. High allostatic load was defined as having an allostatic load in the top quartile of the summary score. A Cox proportional hazard model with robust variance tested the association between allostatic load and overall survival. RESULTS: There were no associations between allostatic load and ovarian cancer clinical characteristics. After accounting for demographic, clinical, and treatment factors, high allostatic load was associated with a significant increase in mortality (hazard ratio 2.17 [95%CI, 1.13-4.15]; P = 0.02). CONCLUSION: Higher allostatic load is associated with worse survival among ovarian cancer patients. Allostatic load could help identify patients at risk for poorer outcomes who may benefit from greater socioenvironmental support during treatment.

A Reinterpretation of the Relationship Between Persistent and Resurgent Sodium Currents.

The resurgent sodium current (INaR) activates on membrane repolarization, such as during the downstroke of neuronal action potentials. Due to its unique activation properties, INaR is thought to drive high rates of repetitive neuronal firing. However, INaR is often studied in combination with the persistent or non-inactivating portion of sodium currents (INaP). We used dynamic clamp to test how INaR and INaP individually affect repetitive firing in adult cerebellar Purkinje neurons from male and female mice. We learned INaR does not scale repetitive firing rates due to its rapid decay at subthreshold voltages, and that subthreshold INaP is critical in regulating neuronal firing rate. Adjustments to the Nav conductance model used in these studies revealed INaP and INaR can be inversely scaled by adjusting occupancy in the slow inactivated kinetic state. Together with additional dynamic clamp experiments, these data suggest the regulation of sodium channel slow inactivation can fine-tune INaP and Purkinje neuron repetitive firing rates.Significance Statement Across neuronal cell types, the resurgent sodium current (INaR-) is often implicated in driving high rates of repetitive firing. Using dynamic clamp, we determined INaR is ineffective at driving subsequent action potentials, and that the subthreshold persistent sodium current (INaP) is the critical parameter for scaling repetitive firing rates. We propose INaR measured in native neurons may reflect a mechanism by which the magnitude of INaP is fine-tuned.

Electronic structure orientation as a map of in-plane antiferroelectricity in ß'-In2Se3.

Antiferroelectric (AFE) materials are excellent candidates for sensors, capacitors, and data storage due to their electrical switchability and high-energy storage capacity. However, imaging the nanoscale landscape of AFE domains is notoriously inaccessible, which has hindered development and intentional tuning of AFE materials. Here, we demonstrate that polarization-dependent photoemission electron microscopy can resolve the arrangement and orientation of in-plane AFE domains on the nanoscale, despite the absence of a net lattice polarization. Through direct determination of electronic transition orientations and analysis of domain boundary constraints, we establish that antiferroelectricity in ß'-In2Se3 is a robust property from the scale of tens of nanometers to tens of micrometers. Ultimately, the method for imaging AFE domain organization presented here opens the door to investigations of the influence of domain formation and orientation on charge transport and dynamics.

Abnormal Heart Rate Recovery and Chronotropic Incompetence With Exercise in Patients With Interstitial Lung Disease With and Without Pulmonary Hypertension.

Introduction Chronotropic incompetence (CI) and heart rate (HR) recovery at one minute post-exercise (HRR1) have been proposed as indicators of autonomic imbalance. We retrospectively studied the presence of CI and HRR1 attained on cardiopulmonary exercise testing (CPET) in patients with interstitial lung disease (ILD) and those with interstitial lung disease with pulmonary hypertension (ILD-PHTN). Methods A total of 32 patients (21 had ILD alone; 11 had ILD-PHTN) underwent CPET performed per American Thoracic Society protocol on a manually-braked bicycle. HRR1 was defined as the difference between peak HR and HR after one minute post-exercise. The utilization of HR reserve recovery at peak exercise was expressed as Chronotropic Response Index (CRI) and was calculated as (peak HR-resting HR)/(220-age-resting HR). CI was defined by failure to reach 85% of the age-predicted maximum heart rate (APMHR = 200-Age) and CRI<0.80 (80%). Results VO2max was lower in patients with ILD-PHTN compared to ILD alone (14.15± 5.00 vs. 18.11± 4.48, p<0.05). Mean CRI (0.468± 0.179 versus 0.691± 0.210, p<0.05) and HRR1 (10± 7 versus 18± 9, p<0.05) were lower in patients with ILD-PHTN compared to ILD alone. Twenty out of a total of 32 patients (62.5%) met the criteria for CI. In the ILD group, 10 out of 21 patients (47.62%) and in the ILD-PHTN group 10 of 11 patients (90.90%) had CI. Conclusion Chronotropic Incompetence and abnormal heart rate recovery at one minute post-exercise are notable in patients with ILD and are more severe in patients with ILD-PHTN. These findings may contribute to our understanding of dyspnea due to these conditions.

Transcranial focused ultrasound to the posterior cingulate cortex modulates default mode network and subjective experience: an fMRI pilot study.

Background: Transcranial focused ultrasound (TFUS) is an emerging neuromodulation tool for temporarily altering brain activity and probing network functioning. The effects of TFUS on the default mode network (DMN) are unknown. Objective: The study examined the effects of transcranial focused ultrasound (TFUS) on the functional connectivity of the default mode network (DMN), specifically by targeting the posterior cingulate cortex (PCC). Additionally, we investigated the subjective effects of TFUS on mood, mindfulness, and self-related processing. Methods: The study employed a randomized, single-blind design involving 30 healthy subjects. Participants were randomly assigned to either the active TFUS group or the sham TFUS group. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted before and after the TFUS application. To measure subjective effects, the Toronto Mindfulness Scale, the Visual Analog Mood Scale, and the Amsterdam Resting State Questionnaire were administered at baseline and 30 min after sonication. The Self Scale and an unstructured interview were also administered 30 min after sonication. Results: The active TFUS group exhibited significant reductions in functional connectivity along the midline of the DMN, while the sham TFUS group showed no changes. The active TFUS group demonstrated increased state mindfulness, reduced Global Vigor, and temporary alterations in the sense of ego, sense of time, and recollection of memories. The sham TFUS group showed an increase in state mindfulness, too, with no other subjective effects. Conclusions: TFUS targeted at the PCC can alter DMN connectivity and cause changes in subjective experience. These findings support the potential of TFUS to serve both as a research tool and as a potential therapeutic intervention.

Multi-Level Thrombotic/Embolic Burden and Its Role in Sex-Related Outcomes in Acute Limb Ischemia (ALI).

INTRODUCTION: The impact of sex upon outcomes in acute limb ischemia (ALI) remains disputed. We aim to quantify the effect of sex upon amputation-free survival (AFS) after a percutaneous-first approach for ALI. METHODS: Two-center retrospective review of ALI managed via a percutaneous-first approach. Demographics, comorbidities, and clinical characteristics were analyzed (Table I). The Kaplan-Meier and Cox regression were used to estimate AFS, limb-salvage and overall survival. RESULTS: Over nine years, 170 patients (87, 51% males; median age 67 IQR 59, 77 years) presented with ALI. Rutherford Classification was I in 56 (33%); IIa in 85 (50%); IIb in 20 (12%) and III in 9 (5%). Thirty-day mortality, major amputation rate and fasciotomy rates were 8% (N=13); 6.5% (N=11), and 4.7% (N=8), respectively. Among revascularized limbs, 92% were patent at 30 days. Length of stay was 7 (IQR 3-11) days. Complications included 13 bleeding episodes (8%), 4 cases of atrial fibrillation (2%), and 3 re-thrombosis/clot extension events (1.7%). No differences were noted in complication rates when stratified by sex. Females were older than males (median age 70 IQR 62, 79 vs 65 IQR 56, 76 years; p=0.02) and more likely to present with atrial fibrillation (20.5% vs 8%, p 0.02); and hyperlipidemia (72% vs 57%, p = 0.04). Females also more frequently presented with multi-level thrombotic/embolic burden compared to males (56% vs 43%; p=0.03), and required both aspiration thrombectomy and thrombolysis (27% versus 14%; p 0.02). Kaplan-Meier estimated median AFS, limb salvage, and overall survival were 425 (IQR 140, 824 days); 314 (IQR 72, 727 days); and 342 (IQR 112, 762 days). When stratified by sex, females had worse survival (median 270 IQR 92, 636 versus 406 IQR 140, 937 days; p=0.005); and limb salvage (median 241 IQR 88, 636 versus 363 IQR 49, 822 days; p=0.04) compared to males. Univariate Cox regression showed female sex (HR = 1.46 95% CI 1.04-2.05; p=0.03); multi-level thrombotic/embolic burden (HR 1.64 95% CI 1.17-2.31; p=0.004) and Rutherford Class (HR 1.37 95% CI 1.08-1.73; p=0.009) predicted major amputation/death. By multivariable Cox regression, multi-level thrombotic/embolic burden (HR 1.54 95% CI 1.09-2.17; p=0.01), Rutherford Class (HR 1.34 95% CI 1.07-1.69; p=0.01), and female Sex (HR = 1.45 95% CI 1.03-2.05; p=0.03) were each independently predictive of major amputation/death. CONCLUSIONS: A percutaneous-first strategy is safe and efficacious in the overall ALI population. Similar to prior works, female versus male ALI patients in our cohort have higher rates of mortality and major amputation. In our multivariable model, multi-level thrombotic/embolic burden was independently associated with a greater than 45% increased hazard of major amputation/ death at last follow up. Further prospective analysis is warranted to elucidate the underlying factors contributing to the higher prevalence of multi-level thrombotic/embolic burden in female ALI patients, and to further define the optimal percutaneous-first approach for ALI in consideration of patient sex and extent of clot burden.

Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations.

BACKGROUND: Canine and human osteosarcoma are similar in clinical presentation and tumor genomics. Giant breed dogs experience elevated osteosarcoma incidence, and taller stature remains a consistent risk factor for human osteosarcoma. Whether evolutionarily conserved genes contribute to both human and canine osteosarcoma predisposition merits evaluation. METHODS: A multi-center sample of childhood osteosarcoma patients and controls underwent genome-wide genotyping and imputation. Ancestry-adjusted SNP associations were calculated within each dataset using logistic regression, then meta-analyzed across the three datasets, totaling 1091 patients and 3026 controls. Ten regions previously associated with canine osteosarcoma risk were mapped to the human genome, spanning ∼6 Mb. We prioritized association testing of 5985 human SNPs mapping to candidate osteosarcoma risk regions detected in Irish wolfhounds, the largest dog breed studied. Secondary analyses explored 6289 additional human SNPs mapping to candidate osteosarcoma risk regions identified in Rottweilers and greyhounds. RESULTS: Fourteen SNPs were associated with human osteosarcoma risk after adjustment for multiple comparisons, all within a 42 kb region of human Chromosome 7p12.1. The lead variant was rs17454681 (OR=1.25, 95 %CI: 1.12-1.39; P=4.1×10-5), and independent risk variants were not observed in conditional analyses. While the associated region spanned 2.1 Mb and contained eight genes in Irish wolfhounds, associations were localized to a 50-fold smaller region of the human genome and strongly implicate GRB10 (growth factor receptor-bound protein 10) in canine and human osteosarcoma predisposition. PheWAS analysis in UK Biobank data identified noteworthy associations of the rs17454681 risk allele with varied measures of height and pubertal timing. CONCLUSIONS: Our comparative oncology analysis identified a novel human osteosarcoma risk allele near GRB10, a growth inhibitor that suppresses activated receptor tyrosine kinases including IGF1R, PDGFRB, and EGFR. Epidemiologists may benefit from leveraging cross-species comparisons to identify haplotypes in highly susceptible but genetically homogenous populations of domesticated animals, then fine-mapping these associations in diverse human populations.

Patient Characteristics and Postoperative Outcomes of Surgically Treated Inferior Pole Patellar Sleeve Fractures.

BACKGROUND: Despite representing over half of all pediatric patella fractures, inferior pole patellar sleeve fractures (PSFs) are a relatively uncommon pediatric injury. As a result, existing literature on PSFs is limited to case reports and small case series. The purpose of this study was to evaluate the radiographic and clinical characteristics of operatively treated PSFs as well as outcomes following surgical management. METHODS: A retrospective review of all inferior pole PSFs requiring surgery from 2007 to 2023 was performed at a single urban tertiary care children's hospital. Cases were identified using diagnostic and billing codes. Patient demographics, injury characteristics, surgical techniques, and postoperative rehabilitation practices were recorded. Regional skeletal maturity, fracture characteristics, and postreduction patellar height were recorded. Postoperative complications were recorded and categorized using the modified Clavien-Dindo Classification System (CDS). RESULTS: Thirty-eight inferior pole PSFs were identified meeting study criteria. The majority of patients were male (86.8%), and the mean age at injury was 11.0 years (range: 7.2 to 15.0). Mean BMI was 21.1. Radiographically, the majority of patients were Epiphyseal Fusion Stage 0 (nonunion), with a median postreduction Caton-Deschamps index (CDI) of 1.2 (IQR: 1.1 to 1.3). These fractures were predominantly treated with suture-based fixation (84%). Postoperative immobilization varied within the cohort, and the initiation of knee ROM was permitted at a median of 3.5 (IQR: 2.0 to 4.6) weeks. All patients regained full range of motion and straight leg raise without extensor lag, and return-to-sport was achieved by a median of 17.6 weeks (IQR: 12.8 to 30.3). Complications occurred in 10 (26.3%) patients, with 3 (7.9%) requiring a return to the OR (CDS Grade III). CONCLUSIONS: Inferior pole PSFs appear to occur most commonly among prepubertal males of normal BMI and normal patellar height. Despite variable rehabilitation protocols, operative management resulted in restoration of extensor mechanism function. Eight percent of patients experienced complications requiring unplanned surgery. This large series improves our understanding of the epidemiology, injury characteristics, and postoperative outcomes of an operatively treated cohort of a rare injury pattern. LEVEL OF EVIDENCE: Level IV.

Comparative mitochondrial genomics in Nematoda reveal astonishing variation in compositional biases and substitution rates indicative of multi-level selection.

BACKGROUND: Nematodes are the most abundant and diverse metazoans on Earth, and are known to significantly affect ecosystem functioning. A better understanding of their biology and ecology, including potential adaptations to diverse habitats and lifestyles, is key to understanding their response to global change scenarios. Mitochondrial genomes offer high species level characterization, low cost of sequencing, and an ease of data handling that can provide insights into nematode evolutionary pressures. RESULTS: Generally, nematode mitochondrial genomes exhibited similar structural characteristics (e.g., gene size and GC content), but displayed remarkable variability around these general patterns. Compositional strand biases showed strong codon position specific G skews and relationships with nematode life traits (especially parasitic feeding habits) equal to or greater than with predicted phylogeny. On average, nematode mitochondrial genomes showed low non-synonymous substitution rates, but also high clade specific deviations from these means. Despite the presence of significant mutational saturation, non-synonymous (dN) and synonymous (dS) substitution rates could still be significantly explained by feeding habit and/or habitat. Low ratios of dN:dS rates, particularly associated with the parasitic lifestyles, suggested the presence of strong purifying selection. CONCLUSIONS: Nematode mitochondrial genomes demonstrated a capacity to accumulate diversity in composition, structure, and content while still maintaining functional genes. Moreover, they demonstrated a capacity for rapid evolutionary change pointing to a potential interaction between multi-level selection pressures and rapid evolution. In conclusion, this study helps establish a background for our understanding of the potential evolutionary pressures shaping nematode mitochondrial genomes, while outlining likely routes of future inquiry.

Brain gray matter volume of reward-related structures in Inuit adolescents pre- and postnatally exposed to lead, mercury and polychlorinated biphenyls.

This study aimed to assess associations between prenatal and postnatal exposure to lead (Pb), mercury (Hg) and polychlorinated biphenyls (PCBs) and gray matter volume of key regions of the brain reward circuit, namely the caudate nucleus, putamen, nucleus accumbens (nAcc), the amygdala, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC). Structural magnetic resonance imaging (MRI) was conducted in 77 Inuit adolescents (mean age = 18.39) from Nunavik, Canada, who also completed the Brief Sensation Seeking Scale (BSSS-4) and Sensation Seeking - 2 (SS-2), two self-report questionnaires evaluating the tendency toward sensation seeking, which is a proxy of reward-related behaviors. Exposures to Pb, Hg and PCBs were measured in cord blood at birth, in blood samples at 11 years old and at time of testing (18 years old). Multivariate linear regressions were corrected for multiple comparisons and adjusted for potential confounders, such as participants' sociodemographic characteristics and nutrient fish intake. Results showed that higher cord blood Pb levels predicted smaller gray matter volume in the bilateral nAcc, caudate nucleus, amygdala and OFC as well as in left ACC. A moderating effect of sex was identified, indicating that the Pb-related reduction in volume in the nAcc and caudate nucleus was more pronounced in female. Higher blood Hg levels at age 11 predicted smaller right amygdala independently of sex. No significant associations were found between blood PCBs levels at all three times of exposure. This study provides scientific support for the detrimental effects of prenatal Pb and childhood Hg blood concentrations on gray matter volume in key reward-related brain structures.

Otology and Audiology: Complications, Challenges, and Concerns in the Patient With Cleft Lip and/or Palate.

Cleft lip and/or palate, a treatable congenital condition, affects around 1 in 700 births, placing a large burden of care on those affected. A multidisciplinary approach to treating the patient involves not only cleft surgery but also a wide array of treatments and preventative therapies to prevent further disease. In this review, the otolaryngology subspecialties, otology and audiology, are discussed in relation to orofacial clefts. As patients with clefts carry a higher risk of permanent hearing loss and speech complications caused by the pathology of their cleft, management of additional diseases such as otitis media with effusion, conductive hearing loss, or infections requires timely evaluation, treatment, and follow-up. The current practice in otology and audiology is discussed with the challenges faced in delivering timely care-in any setting, low or higher income. Lack of consensus and controversies surrounding the use and timing of tympanostomy tubes are reviewed, as well as the palatoplasty types that show significant benefit for otitis media with effusion, audiometry, and speech outcomes. Lastly, a call for further research in clefts and otology and the urgency for its awareness and advocacy in low and middle-income countries is imperative.

A Switch from Glial to Neuronal Gene Expression Alterations in the Spinal Cord of SIV-infected Macaques on Antiretroviral Therapy.

Despite antiretroviral therapy (ART), HIV-associated peripheral neuropathy remains one of the most prevalent neurologic manifestations of HIV infection. The spinal cord is an essential component of sensory pathways, but spinal cord sampling and evaluation in people with HIV has been very limited, especially in those on ART. The SIV/macaque model allows for assessment of the spinal cord at key time points throughout infection with and without ART. In this study, RNA was isolated from the spinal cord of uninfected, SIV+, and SIV + ART animals to track alterations in gene expression using global RNA-seq. Next, the SeqSeek platform was used to map changes in gene expression to specific cell types. Pathway analysis of differentially expressed genes demonstrated that highly upregulated genes in SIV-infected spinal cord aligned with interferon and viral response pathways. Additionally, this upregulated gene set significantly overlapped with those expressed in myeloid-derived cells including microglia. Downregulated genes were involved in cholesterol and collagen biosynthesis, and TGF-b regulation of extracellular matrix. In contrast, enriched pathways identified in SIV + ART animals included neurotransmitter receptors and post synaptic signaling regulators, and transmission across chemical synapses. SeqSeek analysis showed that upregulated genes were primarily expressed by neurons rather than glia. These findings indicate that pathways activated in the spinal cord of SIV + ART macaques are predominantly involved in neuronal signaling rather than proinflammatory pathways. This study provides the basis for further evaluation of mechanisms of SIV infection + ART within the spinal cord with a focus on therapeutic interventions to maintain synaptodendritic homeostasis.

Folate metabolism and risk of childhood acute lymphoblastic leukemia: a genetic pathway analysis from the Childhood Cancer and Leukemia International Consortium.

BACKGROUND: Prenatal folate supplementation has been consistently associated with a reduced risk of childhood lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity, and led to inconclusive results. METHODS: We evaluated whether ~2,900 single nucleotide polymorphisms (SNPs) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control-studies in the Childhood Cancer and Leukemia International Consortium (n=9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data, and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software. RESULTS: None of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni p-value of 5x10-6 and less stringent p-value of 3.5x10-5 accounting for the number of "independent" SNPs). None of the 10 top (non-significant) SNPs and corresponding genes overlapped across ancestry groups. CONCLUSION: This large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups. IMPACT: Genetic variants in the folate pathway alone do not appear to substantially influence childhood ALL risk. Other mechanisms such as gene-folate interaction, DNA methylation or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.

Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR-T therapies in autoimmunity.

Given the global surge in autoimmune diseases, it is critical to evaluate emerging therapeutic interventions. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leveraged advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of autoantibody profiles, proteome-wide, in both health and disease. Using a custom set of over 730,000 human derived peptides, we demonstrated that each individual, regardless of disease state, possesses a distinct and complex constellation of autoreactive antibodies. For each individual, the set of resulting autoreactivites constituted a unique immunological fingerprint, or "autoreactome," that was remarkably stable over years. Using the autoreactome as a primary output, we evaluated the relative effectiveness of various immunomodulatory therapies in altering autoantibody repertoires. We found that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly altered an individual's autoreactome, while anti-CD19 and CD20 therapies had minimal effects. These data both confirm that the autoreactome is comprised of autoantibodies secreted by plasma cells, and strongly suggest that BCMA or other plasma cell targeting therapies may be highly effective in treating currently refractory autoantibody mediated diseases.

Pandemic Planning, Response, and Recovery for Pediatricians: A Focus on Health Equity and Social Determinants of Health.

This article summarizes how pediatricians may be uniquely positioned to mitigate the long-term trajectory of COVID-19 on the health and wellness of pediatric patients especially with regard to screening for social determinants of health that are recognized drivers of disparate health outcomes. Health inequities, that is, disproportionately deleterious health outcomes that affect marginalized populations, have been a major source of vulnerability in past public health emergencies and natural disasters. Recommendations are provided for pediatricians to collaborate with disaster planning networks and lead strategies for public health communication and community engagement in pediatric pandemic and disaster planning, response, and recovery efforts.

Self-injurious unnatural death among Veterans with HIV: a nested case-control study.

OBJECTIVE: People living with HIV (PWH) are at increased risk of suicide and death from unintentional causes compared with people living without HIV. Broadening the categorization of death from suicide to self-injurious unnatural death (SIUD) may better identify a more complete set of modifiable risk factors that could be targeted for prevention efforts among PWH. DESIGN: We conducted a nested case-control study using data from the Veterans Aging Cohort Study (VACS), a longitudinal, observational cohort of Veterans from 2006-2015. A total of 5,036 Veterans with HIV, of whom 461 died by SIUD, were included in the sample. METHODS: SIUD was defined using the International Classification of Disease 10th revision cause of death codes. Cases (n = 461) included individuals who died by SIUD (intentional, unintentional, and undetermined causes of death). Controls (n = 4,575) were selected using incidence density sampling, matching on date of birth ± one year, race, sex, and HIV status. SIUD and suicide was estimated using conditional logistic regression. RESULTS: A previous suicide attempt, a diagnosis of an affective disorder, recent use of benzodiazepines, psychiatric hospitalization, and living in the western US significantly increased the risk of suicide and SIUD. Risk factors that appear more important for SIUD than for suicide included a drug use disorder, alcohol use disorder, Hepatitis C, VACS Index 2.0, current smoking, and high pain levels (7-10). CONCLUSION: Limiting studies to known suicides obscures the larger public health burden of excess deaths from self-injurious behavior. Our findings demonstrate the benefit of expanding the focus to SIUD for the identification of modifiable risk factors that could be targeted for treatment.

Estimation of the causal effect of sex on neonatal intensive care unit outcomes among very low birth weight infants.

OBJECTIVE: Estimate the causal effect of sex on outcomes in the neonatal intensive care unit (NICU) among very low birth weight (VLBW) infants. STUDY DESIGN: Retrospective cohort study using Vermont Oxford Network data to compare NICU outcomes for VLBW males versus females. Odds ratios (OR) for outcomes that differed significantly by sex were computed using standard unweighted analysis and inverse probability weighted (IPW) analysis to correct for selection bias. RESULTS: Using standard analysis, males were significantly more likely to die before discharge and experience six other adverse outcomes. From IPW analysis, male sex caused a 56% increase in the odds of death before discharge (OR = 1.56, 95% confidence interval: 1.18-1.94). Standard unweighted results were significantly biased towards increased risk of adverse outcomes for males (p = 0.005) compared to IPW results for which three outcomes were no longer significantly associated with male sex. CONCLUSION: Standard statistical methods generally overestimate the casual effect of sex among VLBW infants.

Sexual and Gender Minority Status and Suicide Mortality: An Explainable Artificial Intelligence Analysis.

Objectives: Suicide risk is elevated in lesbian, gay, bisexual, and transgender (LGBT) individuals. Limited data on LGBT status in healthcare systems hinder our understanding of this risk. This study used natural language processing to extract LGBT status and a deep neural network (DNN) to examine suicidal death risk factors among US Veterans. Methods: Data on 8.8 million veterans with visits between 2010 and 2017 was used. A case-control study was performed, and suicide death risk was analyzed by a DNN. Feature impacts and interactions on the outcome were evaluated. Results: The crude suicide mortality rate was higher in LGBT patients. However, after adjusting for over 200 risk and protective factors, known LGBT status was associated with reduced risk compared to LGBT-Unknown status. Among LGBT patients, black, female, married, and older Veterans have a higher risk, while Veterans of various religions have a lower risk. Conclusion: Our results suggest that disclosed LGBT status is not directly associated with an increase suicide death risk, however, other factors (e.g., depression and anxiety caused by stigma) are associated with suicide death risks.

Stressors in Atopic Dermatitis.

As with other inflammatory skin disorders, atopic dermatitis has a tendency to cause stress and also be exacerbated by it. Patients with atopic dermatitis have several disease-associated stressors, some of which include physical discomfort due to itching and altered appearance due to flare-ups. These stressors have been shown to effect patients psychosocially by altering sleep patterns, decreasing self-esteem, and interfering with interpersonal relationships. In combination with its direct effect on patients, atopic dermatitis also causes stress for parents and caregivers. Studies suggest that atopic dermatitis is strongly correlated with co-sleeping habits, which can negatively impact the health and mood of parents or caregivers. It has also been reported to interfere with the formation of a strong mother-child relationship. In order to optimize treatment for patients with atopic dermatitis, it is important to note the impact that it has on quality of life. By implementing patient counseling, sleep-targeted therapies, and the use of quality of life (QoL) indices, atopic dermatitis patients and caregivers have the potential to experience greater satisfaction with treatment.