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Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Abstract Altered functioning of the bed nucleus of the stria terminalis (BNST) may play a critical role in the etiology of posttraumatic stress disorder (PTSD). Chronic stressors such as racial discrimination and lifetime trauma are associated with an increased risk for PTSD, but it is unknown whether they influence the relationship between BNST functioning and PTSD. We investigated acute post-trauma BNST resting-state functional connectivity (rsFC) as a predictor of future PTSD symptoms in Black trauma survivors. We also examined whether racial discrimination and lifetime trauma moderated the relationship between BNST rsFC and PTSD symptoms. Black adults (N = 95; 54.7% female; mean age = 34.04) were recruited from an emergency department after experiencing a traumatic injury (72.6% were motor vehicle accidents). Two-weeks post-injury, participants underwent a resting-state fMRI scan and completed questionnaires evaluating their PTSD symptoms as well as lifetime exposure to racial discrimination and trauma. Six-months post-injury, PTSD symptoms were reassessed. Whole brain seed-to-voxel analyses were conducted to examine BNST rsFC patterns. Greater rsFC between the BNST and the posterior cingulate cortex, precuneus, left angular gyrus, and hippocampus prospectively predicted six-month PTSD symptoms after adjusting for sex, age, education, and baseline PTSD symptoms. Acute BNST rsFC was a stronger predictor of PTSD symptoms in individuals who experienced more racial discrimination and lifetime trauma. Thus, in the acute aftermath of a traumatic event, the BNST could be a key biomarker of risk for PTSD in Black Americans, particularly for individuals with a greater history of racial discrimination or previous trauma exposure.

Abstract Background Influenza infections pose significant risks for nursing home (NH) residents. Our aim was to evaluate the impact of the cantonal influenza campaign, and influenza vaccination coverage of residents and healthcare workers (HCWs) on influenza burden in NHs in a context of enhanced infection prevention and control measures (IPC) during the SARS-CoV-2 pandemic. Methods We extracted data from epidemic reports provided by our unit to NHs over two consecutive winter seasons (2021-22 and 2022-23) and used linear regression to assess the impact of resident and HCW vaccination coverage, and participation in the campaign, on residents’ cumulative influenza incidence and mortality. Results Thirty-six NHs reported 155 influenza cases and 21 deaths during the two winter seasons corresponding to 6.2% of infected residents and a case fatality ratio of 13.5%. Median vaccination coverage was 83% for residents, 25.8% for HCWs, while 87% of NHs participated in the campaign. Resident vaccination was significantly associated with a decrease in odds of death (odds ratio (OR) 0.96, 95% confidence interval (CI): 0.93–0.99). There was no significant effect of HCW vaccination coverage on resident infections and deaths. Campaign participation was associated with decreased odds of infection and death among residents (OR: 0.17, 95% CI: 0.06–0.47 and OR: 0.06, 95% CI: 0.02–0.17 respectively). Conclusion Our analysis suggests that in a context of reinforced IPC measures, influenza still represents a significant burden for NH residents. The most effective measures in decreasing resident influenza burden in NHs was participation in the cantonal influenza vaccination campaign and resident vaccination.

Among the letters written and received by Aldus Manutius, the ones held in the Archivio di Stato in Mantua are very interesting and rich in rare Aldus’s autographs. These letters testify both the commercial relationship between a book printer and seller and a very prestigious costumer, Isabella d’Este, and the curious episode of Aldus’s detention during his return to Venice in 1506. This contribution aims to present these precious texts and to analyse their edition by Armand Baschet in 1867, in view of a future critical edition of the whole known Aldus’s correspondence.

BACKGROUND AND OBJECTIVES: Ectopic intracerebral calcifications (EICs) in the basal ganglia, thalamus, cerebellum, or white matter are seen in a variety of disease states or may be found incidentally on brain imaging. The clinical significance and proportion of cases attributable to an underlying genetic cause is unknown. METHODS: This retrospective cohort study details the clinical, imaging, and genomic findings of 44 patients with EICs who had no established diagnosis despite extensive medical workup. RESULTS: In total, 15 of 44 patients received a diagnosis through genomic testing explaining their calcifications, and 2 more received a diagnosis that has not been previously associated with EICs. Six of the 15 were found to have one of the 4 genes (PDGFB, PDGFRB, SLC20A2, and XPR1) conventionally associated with the phenotypic term idiopathic basal ganglia calcifications. DISCUSSION: These findings support the use of genomic testing for symptomatic patients with EICs.

Career selection in medicine is a complex and underexplored process. Most medical career studies performed in the U.S. focused on the effect of demographic variables and medical education debt on career choice. Considering ongoing U.S. physician workforce shortages and the trilateral adaptive model of career decision making, a robust assessment of professional attitudes and work-life preferences is necessary. The objective of this study was to explore and define the dominant viewpoints related to career choice selection in a cohort of U.S. IM residents. We administered an electronic Q-sort in which 218 IM residents sorted 50 statements reflecting the spectrum of opinions that influence postgraduate career choice decisions. Participants provided comments that explained the reasoning behind their individual responses. In the final year of residency training, we ascertained participating residents' chosen career. Factor analysis grouped similar sorts and revealed four distinct viewpoints. We characterized the viewpoints as "Fellowship-Bound-Academic," "Altruistic-Longitudinal-Generalist," "Inpatient-Burnout-Aware," and "Lifestyle-Focused-Consultant." There is concordance between residents who loaded significantly onto a viewpoint and their ultimate career choice. Four dominant career choice viewpoints were found among contemporary U.S. IM residents. These viewpoints reflect the intersection of competing priorities, personal interests, professional identity, socio-economic factors, and work/life satisfaction. Better appreciation of determinants of IM residents' career choices may help address workforce shortages and enhance professional satisfaction.

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

Background: Childhood abuse (physical, emotional, and sexual) is associated with aberrant connectivity of the amygdala, a key threat-processing region. Heightened amygdala activity also predicts adult anxiety and posttraumatic stress disorder (PTSD) symptoms, as do experiences of childhood abuse. The current study explored whether amygdala resting-state functional connectivity may explain the relationship between childhood abuse and anxiety and PTSD symptoms following trauma exposure in adults. Methods: Two weeks posttrauma, adult trauma survivors (n = 152, mean age [SD] = 32.61 [10.35] years; women = 57.2%) completed the Childhood Trauma Questionnaire and underwent resting-state functional magnetic resonance imaging. PTSD and anxiety symptoms were assessed 6 months posttrauma. Seed-to-voxel analyses evaluated the association between childhood abuse and amygdala resting-state functional connectivity. A mediation model evaluated the potential mediating role of amygdala connectivity in the relationship between childhood abuse and posttrauma anxiety and PTSD. Results: Childhood abuse was associated with increased amygdala connectivity with the precuneus while covarying for age, gender, childhood neglect, and baseline PTSD symptoms. Amygdala-precuneus resting-state functional connectivity was a significant mediator of the effect of childhood abuse on anxiety symptoms 6 months posttrauma (B = 0.065; 95% CI, 0.013–0.130; SE = 0.030), but not PTSD. A secondary mediation analysis investigating depression as an outcome was not significant. Conclusions: Amygdala-precuneus connectivity may be an underlying neural mechanism by which childhood abuse increases risk for anxiety following adult trauma. Specifically, this heightened connectivity may reflect attentional vigilance for threat or a tendency toward negative self-referential thoughts. Findings suggest that childhood abuse may contribute to longstanding upregulation of attentional vigilance circuits, which makes one vulnerable to anxiety-related symptoms in adulthood.

Background This project analyzed risk factors for emergency department (ED) utilization without readmission within 2 weeks post-discharge for survivors of gun violence.Methods A hundred gun violence survivors admitted to a Level 1 trauma center were surveyed. Descriptive analyses and group comparisons were conducted between patients who did and did not use the ED. Factors analyzed are rooted in social determinants of health and clinical care related to the index hospitalization.Results Of the 100 patients, 31 had an ED visit within 6 weeks, although most (87.1%) returned within 2 weeks of discharge. Factors significantly associated (p≤0.05) with a return ED visit included: not having an identified primary care provider, not having friends or family to count on for help, not having enough money to support themselves before return to work, and not feeling able to read discharge instructions.Conclusion Lack of a primary care provider, low health literacy and social support were associated with increased ED visits without readmission post-discharge.Level of Evidence Level III, Prognostic and Epidemiological

A desinformação é um problema crescente na contemporaneidade, e a fotografia tem sido usada como uma ferramenta para credibilizar peças desinformativas. Este artigo discute a importância de compreender os mecanismos complexos por trás da desinformação imagética e como a fotografia pode ser usada para influenciar e formar opiniões. Para analisar a fotografia como estratégia de desinformação, é necessário compreender suas características e estrutura verossímil. Neste sentido, foram selecionadas duas peças desinformativas: “Julgamento de Dilma no período da ditadura militar” e “Povos yanomami no Brasil”, que foram analisadas de acordo com o método de Barthes (1990). Os resultados mostram como a fotografia pode ser usada para manipular a opinião pública sobre governos, crises e atores políticos, e como é importante que jornalistas, educadores e cidadãos estejam atentos a esses mecanismos para navegar com discernimento em um mundo onde a desinformação visual desempenha um papel cada vez mais influente.

Abstract Background Ectoparasites of dogs and cats are implicated to be responsible for life‐threatening anaemia, allergic dermatitis and pruritic and non‐pruritic skin disorders. In Ethiopia, few studies have been conducted on the arthropods of dogs and cats. Objectives In order to shed light on some of these aspects, a survey was conducted to investigate the presence of ectoparasites in dogs and cats living in sympatry in the urban and rural areas of Gamo Zone, Ethiopia. Methods A total of 297 dogs and 110 cats were examined for ectoparasites, and questionnaires were employed to obtain information concerning owner's knowledge about arthropods and vector‐borne diseases (VBDs). Results The overall prevalence of ticks, fleas and lice in dogs was 36.7%, 69.7% and 4.7%, respectively. Similarly, on cats, an overall prevalence of 2.7% ticks and 21.8% fleas was recorded. On dogs, fleas (Ctenocephalides felis 69.4%, Echidnophaga gallinacea 1.3%, Ctenocephalides canis 1.0% and Pulex irritans 0.3%), ticks (Amblyomma variegatum 22.9%, Rhipicephalus sanguineus 14.1%, Haemaphysalis leachi 8.8%, Rhipicephalus praetextatus 4.0% and Rhipicephalus pulchellus 3.4%) and lice (Heterodoxus spiniger 4.0% and Trichodectes canis 0.7%) were identified. Likewise, on cats, fleas (C. felis [15.5%] and E. gallinacea [7.3%]) and ticks (H. leachi [2.7%]) were identified. The abundance of C. felis was significantly higher (p

BackgroundStructural racism produces mental health disparities. While studies have examined the impact of individual factors such as poverty and education, the collective contribution of these elements, as manifestations of structural racism, has been less explored. Milwaukee County, Wisconsin, with its racial and socioeconomic diversity, provides a unique context for this multifactorial investigation. ObjectiveThis research aimed to delineate the association between structural racism and mental health disparities in Milwaukee County, using a combination of geospatial and deep learning techniques. We used secondary data sets where all data were aggregated and anonymized before being released by federal agencies. MethodsWe compiled 217 georeferenced explanatory variables across domains, initially deliberately excluding race-based factors to focus on nonracial determinants. This approach was designed to reveal the underlying patterns of risk factors contributing to poor mental health, subsequently reintegrating race to assess the effects of racism quantitatively. The variable selection combined tree-based methods (random forest) and conventional techniques, supported by variance inflation factor and Pearson correlation analysis for multicollinearity mitigation. The geographically weighted random forest model was used to investigate spatial heterogeneity and dependence. Self-organizing maps, combined with K-means clustering, were used to analyze data from Milwaukee communities, focusing on quantifying the impact of structural racism on the prevalence of poor mental health. ResultsWhile 12 influential factors collectively accounted for 95.11% of the variability in mental health across communities, the top 6 factors—smoking, poverty, insufficient sleep, lack of health insurance, employment, and age—were particularly impactful. Predominantly, African American neighborhoods were disproportionately affected, which is 2.23 times more likely to encounter high-risk clusters for poor mental health. ConclusionsThe findings demonstrate that structural racism shapes mental health disparities, with Black community members disproportionately impacted. The multifaceted methodological approach underscores the value of integrating geospatial analysis and deep learning to understand complex social determinants of mental health. These insights highlight the need for targeted interventions, addressing both individual and systemic factors to mitigate mental health disparities rooted in structural racism.

Background Outpatient follow-up represents a crucial opportunity to re-engage with gun violence survivors (GVS) and to facilitate positive health outcomes. Current outpatient models for firearm-related injuries and trauma care are inconsistent and unstandardized across trauma centers. This project describes the patient population served by the multidisciplinary Trauma Quality of Life (TQoL) Clinic for GVS. Also of primary interest was the outpatient follow-up services used by patients prior to their clinic appointment. Subsequent referrals placed during Clinic, as well as rate of attendance, was a secondary aim.Methods This was a descriptive retrospective analysis of a quality improvement project of the TQoL Clinic. Data were extracted from the electronic medical record and were supplemented with information from the trauma registry and the hospital-based violence intervention program database. Descriptive statistics characterized the patient population served. A Χ2 analysis was used to compare no-show rates for the TQoL Clinic against two historical cohorts of trauma clinic attendees.Results Most attendees were young (M=32.0, SD=1.8, range=15–88 years), Black (80.1%), and male (82.0%). Of the 306 total TQoL Clinic attendees, 82.3% attended their initial scheduled appointment. Most non-attendee patients rescheduled their appointments (92.1%), and 89.5% attended the rescheduled appointment. TQoL Clinic demonstrated a significantly lower no-show rate than the traditional trauma clinic model, including after the implementation of the hospital’s inpatient violence intervention program (χ2(2)=75.52, p

The endocannabinoid system is a highly conserved and ubiquitous signalling pathway with broad-ranging effects. Despite critical pathway functions, gene variants have not previously been conclusively linked to human disease. We identified nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All children displayed paroxysms of nystagmus or eye deviation accompanied by compensatory head posture and worsened incoordination most frequently after waking. RNA sequencing showed clear expression of the truncated transcript and no differences were found between mutant and wild-type DAGLA activity. Immunofluorescence staining of patient-derived fibroblasts and HEK cells expressing the mutant protein showed distinct perinuclear aggregation not detected in control samples. This report establishes truncating variants in the last DAGLA exon as the cause of a unique paediatric syndrome. Because enzymatic activity was preserved, the observed mislocalization of the truncated protein may account for the observed phenotype. Potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect. To our knowledge, this is the first report directly linking an endocannabinoid system component with human genetic disease and sets the stage for potential future therapeutic avenues.

PurposeDiphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).MethodsMolecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) was created for a DPH5 p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate-ribosylation assays in DPH5-knockout human and yeast cells and in silico modeling were performed for the identified DPH5 potential pathogenic variants.ResultsDPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2.ConclusionWe provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.

Summary: Background: Insufficient infection prevention and control (IPC) practices in healthcare settings increase the SARS-CoV-2 infection risk among health workers. This study aimed to examine the level of preparedness for future outbreaks. Methods: We modelled the experience from the COVID-19 pandemic and assessed the return on investment on a global scale of three IPC interventions to prevent SARS-CoV-2 infections among health workers: enhancing hand hygiene; increasing access to personal protective equipment (PPE); and combining PPE, with a scale-up of IPC training and education (PPE+). Our analysis covered seven geographic regions, representing a combination of World Health Organization (WHO) regions and the Organisation for Economic Co-operation and Development (OECD) countries. Across all regions, we focused on the first 180 days of the pandemic in 2020 between January 1st and June 30th. We used an extended version of a susceptible-infectious-recovered compartmental model to measure the level of IPC preparedness. Data were sourced from the WHO COVID-19 Detailed Surveillance Database. Findings: In all regions, the PPE + intervention would have averted the highest number of new SARS-CoV-2 infections compared to the other two interventions, ranging from 6562 (95% CI 4873–8779) to 38,170 (95% CI 33,853–41,901) new infections per 100,000 health workers in OECD countries and in the South-East Asia region, respectively. Countries in the South-East Asia region and non-OECD countries in the Western Pacific region were poised to achieve the highest level of savings by scaling up the PPE + intervention. Interpretation: Our results not only support efforts to make an economic case for continuing investments in IPC interventions to halt the COVID-19 pandemic and protect health workers, but could also contribute to efforts to improve preparedness for future outbreaks. Funding: This work was funded by WHO, with support by the German Federal Ministry of Health for the WHO Research and Development Blueprint for COVID-19.

Recently, we described a phenomenon whereby apoptotic cells generate and release CrkI-containing microvesicles, which stimulate proliferation in surrounding cells upon contact to compensate for their own demise. We termed these microvesicles ACPSVs for Apoptotic Compensatory Proliferation Signaling microvesicles. As immune cells and a majority of current cancer therapeutics destroy tumor cells primarily by apoptosis, we conducted a small pilot study to assess the possibility that ACPSVs may also be generated in squamous cell carcinomas. We first evaluated a primary and a metastatic squamous cell carcinoma cancer cell lines for their ability to produce ACPSVs under normal and apoptotic conditions. We next conducted a pilot study to assess the occurrence of ACPSVs in solid tumors extracted from 20 cancer patients with squamous cell carcinomas. Both cancer cell lines produced copious amounts of ACPSVs under apoptotic conditions. Interestingly, the metastatic squamous cell carcinoma cancer cell line also produced high levels of ACPSVs under healthy condition, suggesting that the ability to generate ACPSVs may be hijacked by these cells. Importantly, ACPSVs were also abundant in the solid tumors of all squamous cell carcinoma cancer patients. Detection of ACPSVs in cancer has potentially important ramifications in tumor biology and cancer therapeutics which warrants further investigation.

Environmental and anthropogenic factors may significantly affect the diffusion of wild animals, enhancing the interface of human–wildlife interactions and driving the spread of pathogens and vector-borne diseases between animals and humans. However, in the last decade, the involvement of citizens in scientific research (the so-called citizen science approach, henceforth abbreviated as CS) provided a network of large-scale and cost-effective surveillance programmes of wildlife populations and their related arthropod species. Therefore, this review aims to illustrate different methods and tools used in CS studies, by arguing the main advantages and considering the limitations of this approach. The CS approach has proven to be an effective method for establishing density and distribution of several wild animal species, in urban, peri-urban and rural environments, as well a source of information regarding vector–host associations between arthropods and wildlife. Extensive efforts are recommended to motivate citizens to be involved in scientific projects to improve both their and our knowledge of the ecology and diseases of wildlife. Following the One Health paradigm, collaborative and multidisciplinary models for the surveillance of wildlife and related arthropod species should be further developed by harnessing the potentiality of the CS approach.