Exploring Resilience Models in a Sample of Combat-Exposed Military Service Members and Veterans: A Comparison and Commentary

Background: The term resilience is applied in numerous ways in the mental health field, leading to different perspectives of what constitutes a resilient response and disparate findings regarding its prevalence following trauma. Objective: illustrate the impact of various definitions on our understanding and prevalence of resilience, we compared various resilience definitions (absence of PTSD, absence of current mental health diagnosis, absence of generalized psychological distress, and an alternative trauma load–resilience discrepancy model of the difference between actual and predicted distress given lifetime trauma exposure) within a combat-exposed military personnel and veteran sample. Method: In this combat-trauma exposed sample (N = 849), of which approximately half were treatment seeking, rates of resilience were determined across all models, the kappa statistic was used to determine the concordance and strength of association across models, and t-tests examined the models in relation to a self-reported resilience measure. Results: Prevalence rates were 43.7%, 30.7%, 87.4%, and 50.1% in each of the four models. Concordance analyses identified 25.7% (n = 218) considered resilient by all four models (kappa = .40, p \u3c .001). Correlations between models and self-reported resilience were strong, but did not fully overlap. Conclusions:The discussion highlights theoretical considerations regarding the impact of various definitions and methodologies on resilience classifications, links current findings to a systems-based perspective, and ends with suggestions for future research approaches on resilience

Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration

Mutations in the vacuolar protein sorting 35 homolog (VPS35) gene at the PARK17 locus, encoding a key component of the retromer complex, were recently identified as a new cause of late-onset, autosomal dominant Parkinson's disease (PD). Here we explore the pathogenic consequences of PD-associated mutations in VPS35 using a number of model systems. VPS35 exhibits a broad neuronal distribution throughout the rodent brain, including within the nigrostriatal dopaminergic pathway. In the human brain, VPS35 protein levels and distribution are similar in tissues from control and PD subjects, and VPS35 is not associated with Lewy body pathology. The common D620N missense mutation in VPS35 does not compromise its protein stability or localization to endosomal and lysosomal vesicles, or the vesicular sorting of the retromer cargo, sortilin, SorLA and cation-independent mannose 6-phosphate receptor, in rodent primary neurons or patient-derived human fibroblasts. In yeast we show that PD-linked VPS35 mutations are functional and can normally complement VPS35 null phenotypes suggesting that they do not result in a loss-of-function. In rat primary cortical cultures the overexpression of human VPS35 induces neuronal cell death and increases neuronal vulnerability to PD-relevant cellular stress. In a novel viral-mediated gene transfer rat model, the expression of D620N VPS35 induces the marked degeneration of substantia nigra dopaminergic neurons and axonal pathology, a cardinal pathological hallmark of PD. Collectively, these studies establish that dominant VPS35 mutations lead to neurodegeneration in PD consistent with a gain-of-function mechanism, and support a key role for VPS35 in the development of PD

Complement factor I deficiency: a potentially treatable cause of fulminant cerebral inflammation

Objective To raise awareness of complement factor I (CFI) deficiency as a potentially treatable cause of severe cerebral inflammation. Methods Case report with neuroradiology, neuropathology, and functional data describing the mutation with review of literature. Results We present a case of acute, fulminant, destructive cerebral edema in a previously well 11-year-old, demonstrating massive activation of complement pathways on neuropathology and compound heterozygote status for 2 pathogenic mutations in CFI which result in normal levels but completely abrogate function. Conclusions Our case adds to a very small number of extant reports of this phenomenon associated with a spectrum of inflammatory histopathologies including hemorrhagic leukoencephalopathy and clinical presentations resembling severe acute disseminated encephalomyelitis. CFI deficiency can result in uncontrolled activation of the complement pathways in the brain resulting in devastating cerebral inflammation. The deficit is latent, but the catastrophic dysregulation of the complement system may be the result of a C3 acute phase response. Diagnoses to date have been retrospective. Diagnosis requires a high index of suspicion and clinician awareness of the limitations of first-line clinical tests of complement activity and activation. Simple measurement of circulating CFI levels, as here, may fail to diagnose functional deficiency with absent CFI activity. These diagnostic challenges may mean that the CFI deficiency is being systematically under-recognized as a cause of fulminant cerebral inflammation. Complement inhibitory therapies (such as eculizumab) offer new potential treatment, underlining the importance of prompt recognition, and real-time whole exome sequencing may play an important future role

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

Fueling the gender gap? Oil and women's labor and marriage market outcomes

This paper analyzes the effect of resource-based economic specialization on women's labor market outcomes. Using information on the location and discovery of major oil fields in the Southern United States coupled with a county-level panel derived from US Census data for 1900-1940, we specifically test the hypothesis that the presence of mineral resources can induce changes in the sectoral composition of the local economy that are detrimental to women's labor market outcomes. We find evidence that the discovery of oil at the county level may constitute a substantial male biased demand shock to local labor markets, as it is associated with a higher gender pay gap. However, we find no evidence that oil wealth lowers female labor force participation or has any impact on local marriage and fertility patterns. While our results are consistent with oil shocks limiting female labor market opportunities in some sectors (mainly manufacturing), this effect tends to be compensated by the higher availability of service sector jobs for women who are therefore not driven out of the labor market

Deep Learning for Automated Boundary Detection and Segmentation in Organ Donation Photography

Background: Medical photography is ubiquitous and plays an increasingly important role in the fields of medicine and surgery. Any assessment of these photographs by computer vision algorithms requires first that the area of interest can accurately be delineated from the background. We aimed to develop deep learning segmentation models for kidney and liver retrieval photographs where accurate automated segmentation has not yet been described. Methods: Two novel deep learning models (Detectron2 and YoloV8) were developed using transfer learning and compared against existing tools for background removal (macBGRemoval, remBGisnet, remBGu2net). Anonymized photograph datasets comprised training/internal validation sets (821 kidney and 400 liver images) and external validation sets (203 kidney and 208 liver images). Each image had two segmentation labels: whole organ and clear view (parenchyma only). Intersection over Union (IoU) was the primary outcome, as the recommended metric for assessing segmentation performance. Results: In whole kidney segmentation, Detectron2 and YoloV8 outperformed other models with internal validation IoU of 0.93 and 0.94, and external validation IoU of 0.92 and 0.94, respectively. Other methods—macBGRemoval, remBGisnet, and remBGu2net—scored lower, with highest internal validation IoU at 0.54 and external validation at 0.59. Similar results were observed in liver segmentation, where Detectron2 and YoloV8 both showed internal validation IoU of 0.97 and external validation of 0.92 and 0.91, respectively. The other models showed a maximum internal validation and external validation IoU of 0.89 and 0.59 respectively. All image segmentation tasks with Detectron2 and YoloV8 completed within 0.13 to 1.5 seconds per image. Conclusions: Accurate, rapid, and automated image segmentation in the context of surgical photography is possible with open-source deep-learning software. These outperform existing methods, and could impact the field of surgery, enabling similar advancements seen in other areas of medical computer vision

Replication of the Interaction of PRKG1 and Trauma Exposure on Alcohol Misuse in an Independent African American Sample.

In the present study, we sought to replicate recent findings of Polimanti et al. (2017), who conducted a genome-wide gene-by-environment interaction study (GEWIS) and identified a gene-by-trauma interaction that predicts alcohol misuse among African Americans.  Consistent with the findings published by Polimanti and colleagues, results of the current study demonstrated an interaction effect, b = 0.41, of trauma exposure and rs1729578 in the intron of PRKG1 on alcohol misuse in a subsample of ancestral African Americans. The minor allele (rs1729578*C) was positively associated with increased alcohol use disorder symptoms in trauma-exposed subjects and negatively associated in non-trauma-exposed subjects.  This effect, however, was only significant for one out of three alcohol outcome measures we investigated, suggesting the interaction may be most salient when predicting higher severity of alcohol misuse. Additionally, the effect did not remain significant after we accounted for testing the effect on three different outcome variables. Also in line with the original study, the gene-by-environment effect was not demonstrated among the ancestral European subsample.  The findings suggest this gene variant may increase an individual's susceptibility to environmental influences, both adverse and supportive.AMSUNY DownstatePsychiatry and Behavioral SciencesInstitute for Genomics in HealthN/

Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosis

Background: Catalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals. The effects of catalase deficiency on albuminuria and progressive glomerulosclerosis have not yet been fully elucidated. The adriamycin (ADR) nephropathy model is considered to be an experimental model of focal segmental glomerulosclerosis. A functional catalase deficiency was hypothesized to exacerbate albuminuria and the progression of glomerulosclerosis in this model. Methods: ADR was intravenously administered to both homozygous acatalasemic mutant mice (C3H/AnLCs(b)Cs(b)) and control wild-type mice (C3H/AnLCs(a)Cs(a)). The functional and morphological alterations of the kidneys, including albuminuria, renal function, podocytic, glomerular and tubulointerstitial injuries, and the activities of catalase were then compared between the two groups up to 8 weeks after disease induction. Moreover, the presence of a mutation of the toll-like receptor 4 (tlr4) gene, which was previously reported in the C3H/HeJ strain, was investigated in both groups. Results: The ADR-treated mice developed significant albuminuria and glomerulosclerosis, and the degree of these conditions in the ADR-treated acatalasemic mice was higher than that in the wild-type mice. ADR induced progressive renal fibrosis, renal atrophy and lipid peroxide accumulation only in the acatalasemic mice. In addition, the level of catalase activity was significantly lower in the kidneys of the acatalasemic mice than in the wild-type mice during the experimental period. The catalase activity increased after ADR injection in wild-type mice, but the acatalasemic mice did not have the ability to increase their catalase activity under oxidative stress. The C3H/AnL strain was found to be negative for the tlr4 gene mutation. Conclusions: These data indicate that catalase deficiency plays an important role in the progression of renal injury in the ADR nephropathy model