We describe two patients with variably protease-sensitive prionopathy (VPSPr) who developed progressive upper motor neuron symptoms, insomnia, behavioral and cognitive decline, compatible with primary lateral sclerosis associated with frontotemporal dementia (FTD). Neuropathology revealed a spongiform encephalopathy with frontotemporal and pronounced thalamic involvement, associated with fine synaptic abnormal prion protein conformer (PrP^Sc) deposits, microplaques, and intraneuronal aggregates. Western blot analysis revealed a characteristic VPSPr proteolytic profile, lacking the diglycosylated band. Both patients were methionine homozygous at PRNP codon 129 and carried no pathogenic mutations. These cases illustrate that VPSPr can present with a prominent motor neuron syndrome and FTD features.

Loneliness is a critical mental health issue among university students, yet the mechanisms linking physical activity (PA) to loneliness remain underexplored. This study examines whether core self-evaluation (CSE) mediates the PA-loneliness relationship, and whether only-child status moderates this pathway.

Using random cluster sampling from a Chinese university, 558 valid questionnaires were collected.

This cross-sectional study collected self-reported data on PA levels, loneliness, and CSE among Chinese university students. The data underwent normality tests. Independent samples t-tests were used to examine differences in these variables by sex, grade, and only-child status. Pearson's correlation analyses were employed to assess the relationships among loneliness, PA, and CSE. We used the PROCESS macro for hierarchical regression analysis to test the mediation effect of CSE and the moderation effect of only-child status.

PA was negatively correlated with loneliness (r = -.154, P < .001) and positively with CSE (r = .263, P < .001). CSE fully mediated the PA-loneliness relationship (indirect effect = -0.001, 95% CI [-0.0007, -0.0003]). Only-child status moderated the direct path, the interaction term between PA and only-child status had a significant effect on loneliness (B= -0.0006, P = .016), The model explained 35.5% of the variance in loneliness.

CSE serves as a complete mediator between PA and loneliness, and only-child status moderates this association. These findings highlight the importance of tailoring PA-based mental health interventions to students' family backgrounds.

Glioblastoma is the most common and aggressive malignant brain tumor, characterized by poor response to current therapies and inevitable recurrence. Novel therapeutic strategies are urgently needed. Lansbermin-I, a disintegrin isolated from the venom of Porthidium lansbergii lansbergii, was purified, sequenced, structurally modeled, and evaluated for its antitumor potential against the human Glioblastoma cell line T98G. Cytotoxicity assays revealed a dose-dependent effect, with Lansbermin-I inducing up to 38.1% cell death at 100 μg/mL, surpassing the activity of temozolomide (34.9%) while exhibiting lower toxicity on non-tumorigenic human astrocytes (28% vs. 37%). Lansbermin-I also inhibited T98G adhesion to fibronectin by nearly 80% (p < 0.0001), suggesting interference with integrin-mediated interactions. Flow cytometry demonstrated a significant increase in apoptotic cells (60% vs. 36% in control) and cell cycle arrest at the G1 phase. In silico docking studies supported a strong interaction of Lansbermin-I with integrin αvβ3, comparable to that of fibronectin, reinforcing its potential mechanism of action through the disruption of adhesion and survival signaling. Collectively, these findings highlight Lansbermin-I as a promising selective prototype for Glioblastoma therapy. Further studies are warranted to elucidate its molecular targets and evaluate its efficacy in preclinical models.

The detection of neutralizing antibodies (NAbs) is crucial for evaluating immune protection against viral infections. This study assessed two ELISA-based surrogate virus neutralization tests (sVNTs): the novel GeneTex U-OK SARS-CoV-2 Neutralizing Antibody Detection ELISA kit and the FDA-authorized GenScript cPass SARS-CoV-2 Neutralization Antibody Detection kit. The GeneTex U-OK kit contains recombinant spike proteins from the wild-type strain and Omicron subvariants BA.1, BA.2, and BA.4/BA.5. A total of 115 serum samples were analyzed, including 75 from SARS-CoV-2 unvaccinated individuals and 40 from vaccinated individuals. No participant had evidence of prior SARS-CoV-2 infection, as confirmed by negative anti-nucleocapsid antibody tests. Compared with the GenScript cPass kit, the GeneTex U-OK kit demonstrated 100% positive agreement (95% CI: 90.4-100.0%) and 100% negative agreement (95% CI: 95.4-100.0%) in detecting NAbs against the wild-type strain, corresponding to 100% sensitivity and 100% specificity. When compared with viral neutralization assays, it achieved 100% concordance for Omicron BA.1, BA.2, and BA.4/BA.5 subvariants, with correlation coefficients (R) of 0.85, 0.98, and 0.46, respectively. These findings highlight the accuracy and reliability of the GeneTex U-OK kit, indicating its potential as a valuable tool for monitoring vaccine effectiveness and identifying individuals with protective NAbs against vaccinated individuals, including Omicron variants.

Heart failure (HF) is still an important disease with high mortality rates worldwide. HF treatment is also difficult due to different phenotypes. Diuretic response (DR) is one of the main differences across these subgroups. Novel urinary parameters are used for DR prediction. We sought to determine whether the MELD score could be used as an additional parameter for predicting the DR.

Eighty-one consecutive patients diagnosed with decompensated HF between June and October 2020 were included. The second hour urine sodium (UNa) level after the first intravenous diuretic administration and serum parameters were recorded. All patients underwent a comprehensive echocardiographic examination. MELD score derivatives were tested to assess the DR.

A total of 81 patients (mean age: 66.4 ± 13.5; mean ejection fraction: 29.6 ± 12.7%) were divided into two groups according to UNa. 26 (32%) patients had poor DR. MELD Na score was independently associated with DR (OR = 0.88 [-0.21 to (-0.03)]; p = 0.008). Furthermore, MELD Na score was correlated with urinary sodium (r = -0.354; p = 0.004). Daily furosemide dose was higher (237.9 ± 204.7 vs. 129.3 ± 83.5 mg; p = 0.001) and length of hospital stay was longer (15.6 ± 10.8 vs. 8.5 ± 6.1 days; p < 0.01) in the low UNa group.

The MELD score derivative was associated with DR according to urinary sodium and may be used as an additional parameter to predict the DR.

Latinos have seen a 30% increase in autism spectrum disorder (ASD) since 2018. However, Latino children are diagnosed later and remain underdiagnosed compared to Whites. Later diagnosis of autism or failure to receive a diagnosis of autism into adulthood is associated with negative outcomes. From 2012 to 2022, in specialty clinic diagnosing autism in adulthood, Latino adults (n = 31) were older than White adults (n = 323) and, using 2020 Census data, severely underrepresented despite experiencing similar distress and symptoms of autism to White adults. Latino adults with a first-time diagnosis of autism were also nearly 2.5 years older than White adults. Recommendations are provided to service providers to improve access to services for Latinos. Recommendations provided include making changes at an organizational level to improve access to high quality healthcare services for Latinos. Other recommendations include translating services for Spanish-speaking Latinos and advertising these services. Finally, service providers should culturally adapt services to ensure they are appropriate for Latinos.

People with HIV face a constellation of social and structural barriers, including unstable housing, discrimination, lack of identification documents, immigration issues, and denial of public benefits, that impede access to and retention in care. These health-harming legal needs are rarely addressed systematically in HIV service settings, despite longstanding calls for structural interventions. This study examines the role and impact of a Medical-Legal Partnership (MLP) embedded within The Philadelphia AIDS Consortium, in collaboration with the Legal Clinic for the Disabled. As part of a larger feasibility and acceptability trial, we conducted follow-up interviews with 95 participants who engaged with the on-site attorney. Recruitment was conducted via venue-based outreach, online ads, and peer referral. Participants reported a substantial reduction in legal needs over time, with more than half reporting no health-harming legal needs (HHLNs) by the 3- and 6-month follow-ups. The most common concerns at baseline, transportation, care planning, and food access, declined significantly. Thematic analysis revealed six key domains of impact: (1) empowerment and knowledge-building; (2) trust, respect, and cultural competence; (3) accessibility and integration of legal services; (4) practical legal resolution; (5) emotional relief and therapeutic benefit; and (6) limitations in legal scope or access. Findings underscore the transformative potential of MLPs in HIV care. When embedded in trusted, culturally responsive settings, legal services can help dismantle structural barriers, foster trust, and support both practical legal resolution and improved mental health outcomes.

White matter alterations are increasingly implicated in neurological diseases and their progression. Diffusion-weighted magnetic resonance imaging (DW-MRI) has been included in many international-scale studies to identify alterations in white matter microstructure and connectivity. Yet, quantitative investigation of DW-MRI data is hindered by a lack of consistency due to variations in acquisition protocols, sites, and scanners. Specifically, there is a need to harmonize the preprocessing of DW-MRI datasets to ensure that compatible and reproducible quantitative metrics are derived from each site, including (1) bundle-wise microstructure measures, (2) features of white matter fiber bundles, and (3) connectomics measures. In the MICCAI CDMRI 2023 QuantConn challenge, participants are provided raw data from the same individuals taken with two different acquisition protocols on a single 4 tesla scanner in the same scanning session and asked to preprocess the data in order to minimize acquisition differences while retaining biological variation. Here, we outline the testing framework, provide baseline pre-harmonized results, and discuss the learning implications of this challenge.

Background & objectives Sudden death, defined as death occurring within one hour of symptom onset in witnessed cases or within 24 h of last being seen alive in unwitnessed cases, remains a major public health concern. This study aimed to evaluate the incidence, causes, and risk factors associated with sudden death in young adults. Methods A cross-sectional study was conducted over one year at a tertiary care centre in New Delhi. Cases meeting the definition of sudden death were included, excluding trauma, suicide, homicide, and drug abuse. Each case underwent whole-body imaging, autopsy, and histopathological examination. A multidisciplinary team comprising forensic experts, pathologists, radiologists, and clinicians determined the cause of death. Comparative analysis was performed between sudden death in young adults (18-45 yr) and older adults (46-65 yr). Results Out of 2214 autopsies, 180 cases (8.1%) met the criteria for sudden death. Sudden death in young accounted for 103 (57.2%) cases. Mean age was 33.6 yr in sudden death in young (IQR=10) and 53.8 years in sudden death in old, with male predominance in both. Cardiovascular causes were most common in young (n=40, 42.6%), followed by respiratory causes (n=20, 21.3%) and sudden unexplained deaths (n=20, 21.3%), where no pathology was identified. Other causes included gastrointestinal, central nervous system, and genitourinary pathologies. Smoking and alcohol intake was equally prevalent in those who died young and at old age. Interpretation & conclusions Sudden death in young adults is a significant concern requiring targeted public health strategies. Coronary artery disease remains the leading cause. Respiratory and unexplained deaths warrant further investigation.

Cancer and diabetes are the second and eighth leading causes of death in the United States (US), respectively. There are associations between diabetes and development of certain cancers yet a spatial analysis of their association has not been performed. This study examined the relationship between county-level diabetes prevalence and diabetes-associated cancer mortality in the US to identify disease hotspots and socioeconomic disparities.

In this cross-sectional study of 3,108 counties in the continental US, we characterized county-level diabetes prevalence and diabetes-associated cancer mortality rates by conducting hotspot analyses using the Getis-Ord G* statistic to identify county clusters with similar high/low values of diabetes prevalence and cancer mortality rates. We compared demographic and socioeconomic factors among hotspot and coldspot overlaps.

Hotspots of diabetes prevalence were in the Mississippi Delta, Appalachian Kentucky and West Virginia, southeastern Virginia, southern Texas, New Mexico, and tribal areas of Arizona and South Dakota. Hotspots for diabetes-associated cancer mortality were in the Mississippi Delta, Appalachian Kentucky, south central Texas, and South Dakota tribal areas. Hot-hot overlaps occupied the Mississippi Delta, Appalachian Kentucky, southern Texas, and South Dakota tribal areas. Compared to cold-cold overlaps, hot-hot cluster counties were more rural with higher percentages of poorly educated, impoverished, and unemployed citizens. Racial economic segregation data suggest that hot-hot clusters are significantly disadvantaged.

Diabetes incidence and diabetes-associated cancer mortality share geographic, demographic, and socioeconomic risk factors. Providers should promote eligible cancer screenings and control of other risk factors among patients with diabetes to reduce mortality.