Preventive Veterinary Medicine

Background Rabies is a zoonotic neglected public health problem associated with animal bites, especially domestic carnivores claiming 59,000 deaths annually predominantly in developing countries of Africa and Asia. There is a high risk of exposure among rural communities endemic with animal rabies where adoption of prevention strategies is minimal. This study determined the prevalence of suspected rabies exposure, associated factors, and delayed post-exposure care-seeking among animal-bite human cases in Busia district, Uganda. Methods: This was a cross-sectional study that involved 332 consecutively sampled animal bite human cases that occurred within the period 2023 to 2024. Data for the bite cases from records were collected using a data abstraction tool. In addition, interviewer-administered semi-structured questionnaires were used to collect data on sociodemographic, animal-related and environmental characteristics. Approximate bite locations were collected using Global Positioning System (GPS) coordinates via Kobo collect. Analysis was carried out in STATA 17 using mixed effects modified Poisson regression for factors associated with suspected rabies exposure. Results: The median age of the bite cases was 18 (IQR: 9-36) with the male gender predominantly affected. The prevalence of suspected rabies exposure was 53.6% (95% Confidence interval - CI: 46.8-60.3). Factors associated were urban versus (vs) rural residence (adjusted prevalence ratio-aPR: 1.04, 95%CI: 1.00-1.08), being bitten by a stray animal (aPR: 1.28, 95% CI: 1.22-1.35) and wild animal (aPR: 1.22, 95% CI: 1.14-1.30) vs domestic animal, vaccination status of the biting animal i.e. vaccinated vs unvaccinated (aPR: 0.76, 95% CI: 0.69-0.85), provoked vs unprovoked bites (aPR: 0.82, 95% CI: 0.79-0.86), and distance to nearest river ([&ge;]5km) vs <5km (aPR: 0.93, 95% CI: 0.87-0.99). The prevalence of delayed post-exposure seeking was 23.0% (95% CI: 16.5-31.1) among the suspected rabies exposures. Conclusion: The study reveals a high prevalence of suspected rabies exposure. Factors associated are multidimensional i.e. are of human, animal and environmental origin. The one health paradigm should be emphasized during routine surveillance of rabies-related cases. The study observed that 1 in 5 bite cases delayed to seek care post bite exposure. We recommend collaborations between sectors, routine vaccination and awareness campaigns, and monitoring of wild carnivore populations and environmental dynamics in rabies-related surveillance.

Close to 50% of all bird species are reservoirs of potentially pathogenic fungi, including those listed as priority by the World Health Organization. In Malawi, data on diversity, pathogenic potential, and ecological avian sources of medically important yeast are scarce. A cross-sectional study using a descriptive approach was conducted in Blantyre, Southern Malawi, to characterise medically important yeasts recovered from environments contaminated with excreta/guano from synanthropic pigeons. A total of 20 samples were collected from 4 peri-urban areas, which yielded 71 yeast isolates. To assess the pathogenic potential of the environmental isolates, we compared their phenotypic virulence traits with those of 21 clinical yeast isolates collected from referral hospital laboratories. Pichia kudriavzevii (39%) and Candida orthopsilosis (30%) were the commonly isolated species in the pigeon-guano-contaminated environments. Candida parapsilosis sensu stricto (29%) and Candida albicans (24%) constituted most of the clinical yeast isolates. Half of the species isolated in the pigeon-guano-contaminated environments were also identified among the clinical isolates. A majority of the environmental isolates showed virulence traits similar to or stronger than clinical isolates. The findings underscore the critical need for integrated surveillance under the One Health framework, especially in bird-inhabited spaces close to human settlements.

Abstract Background: The sanitation crisis poses a significant public health risk, leading to diseases like diarrhea, cholera, and typhoid, which impede children's health and development in developing countries like Uganda. Improving sanitation infrastructure is crucial for safeguarding child health and future generations. However, the link between sanitation and children's health is complex, influenced by various factors. This investigation in Gulu scrutinizes the correlation between sanitation practices and child well-being, considering moderating factors such as age, climate, and consistent water accessibility. Methods: The study used a convergent parallel design with equal priority. The Social Ecological Model, Social Learning Theory, and Diffusion of Innovations Model guided it. Researchers collected data from 10 health facilities and 317 households, using purposive and simple random sampling. They used sampling proportions proportional to village size within strata. The researcher analyzed quantitative data using SPSS with factor analysis, structural equation modeling, and multivariate analysis. To analyze qualitative data, they used DQA Minor Lite software, which facilitated thematic analysis. Results: The finding shows 56.8% of households had low socio-economic status. Sanitation was poor; 24.9% household had improved latrines, 20.5% had handwashing facilities with soap, and 68.1% used basic anal cleansing. For nutrition, 38.5% of children were malnourished by MUAC; by Z-scores, 28.7% were stunted, 16.4% underweight, 13.6% wasted. Diarrhea affected 62% of children. Climate worsened sanitation: 48.3% had latrines collapse from floods, and 63.4% of waterborne diseases occurred in both dry and wet seasons. Moderation analysis on childhood diarrhea shows that sociocultural factors ({beta} = -0.20, p < 0.001), sanitation ({beta} = -0.15, p < 0.001), and health system response ({beta} = -0.18, p < 0.001) reduced diarrhea. Climate change increased risk ({beta} = 0.15, p < 0.001) and moderated sanitation effects ({beta} = 0.01, p < 0.05). Models explained 10-14% variance. Age and water access had no moderating effect. While childhood malnutrition shows that sociocultural factors ({beta} = -0.43, p < 0.001) and health system response ({beta} = -0.13, p < 0.001) reduced malnutrition. Sanitation had no effect ({beta} = 0.01, p > 0.05). Age increased malnutrition risk ({beta} = 0.28, p < 0.01) and moderated sociocultural effects ({beta} = 0.16, p < 0.001), but not sanitation. The model explained 21% variance, R{superscript 2} = 0.21, p < 0.001. Conclusion: Sociocultural improvements and health system responses lower both diarrhea and malnutrition. Climate worsens diarrhea and alters sanitation's impact. Age worsens malnutrition and changes sociocultural effects. These findings are valuable for policymakers, healthcare professionals, and researchers

Background: The 2026 FIFA World Cup may bring over one million visitors to North America from around the globe to participate in mass gathering events. The nature of the event and recent news have raised concerns for some that the tournament could lead to infectious disease outbreaks or fuel existing epidemics. Objective: To systematically assess the infectious disease threat posed to the United States by the tournament. Design: A multi-institutional team evaluated pathogen-specific risk across three dimensions: importation, outbreak potential, and impact to identify a priority pathogen list. A systematic screening protocol ensured common criteria and that pathogen information was collected when necessary to inform inclusion. Results: Increased risk from the World Cup is near zero for 63 of 77 evaluated pathogens. Pathogens were predominantly excluded as threats due to low excess importation risk and low outbreak potential if introduced. The remaining priority pathogens fall into five categories: (a) mosquito borne pathogens with the potential for sustained transmission in some host cities, (b) seasonal respiratory viruses, (c) chronic infections with high prevalence outside the United States, (d) pathogens present in the United States with likely increased transmission at World Cup activities, and (e) high-consequence infectious threats. Limitations: Data availability is variable across diseases. Impact calculations may not reflect actual costs to host cities. Disease incidence in World Cup travelers may differ from national incidence rates. Conclusion: While infectious disease outbreaks at the 2026 FIFA World Cup are possible, in an already highly connected world where large gatherings are frequent, the elevated risk from the tournament is not as extreme as it first may seem.

Abstract Objective To Estimate cost of integrating HBV, HCV, and HIV screening at Antenatal using Time-Driven Activity Based Costing (TDACB) Approach; A providers perspective comparing Intervention and standard of care at lower health facilities in West Nile sub region, Uganda Methods Design The Time Driven Activity-Based Costing (TDABC) approach was used to capture resource use and costs associated with delivering integrated HBV, HCV, and HIV screening among pregnant women. This study compared screening uptake among study participants in the intervention, and control group respectively. Five lower health facilities in Koboko and Maracha districts respectively in West Nile region of Uganda. A total of 1,338 study participants wo were pregnant mothers in first ANC, first trimester at the selected 10 facilities were enrolled in this study. Data were abstracted, and also collected on; Personnel/staff time; facility space utilisation; and Medical and non-medical equipment. Total cost per patient visit=Staff time costs+Space cost Equipment cost. Outcome Measure was the estimated provider-perspective costs of delivering integrated screening for HBV, HCV and HIV, using Integrated Care Model by comparing intervention and control groups. Results Staff CCRs demonstrated considerable variability across cadres and facilities, with an overall mean of USD 0.492 per minute (Range: USD 0.167 - 1.318). Laboratory technicians exhibited the highest mean CCR at USD 0.767 per minute for personnel CCRs per patient visit. the mean lowest CPP visit was noted for HBV in the intervention arm (USD 11.43) while HIV test was the lowest in the control arm (USD 0.43). HCV test had the highest cost in the control arm (USD 0.52). The CPP visit for positive clients were generally higher than those that were negative. Equipment CCRs were minimal and highly consistent across facilities, with a mean of USD 0.00069 per minute ({+/-}0.0002). HIV/Syphilis combo was the costliest test kits at USD 3.14 per test kit followed by viral hepatitis C test kit and Hep B at USD 2.47 and USD 0.28 respectively. Facility space CCRs exhibited moderate variation across facilities, ranging from USD 0.01593 to USD 0.03474 per minute. Overall mean CCR for the space for delivering HBV, HCV or HIV testing was USD 0.0256 (0.0066). Conclusion; Overall, the integration of screening resulted in: Cost efficiencies where the same staff and space were used for multiple simultaneous tests, reduced marginal costs for HIV tests due to larger procurement volumes, and higher marginal cost additions for HBV and HCV due to pricier reagents.

Background: Dengue is a major public health problem in Brazil, and Minas Gerais is one of the states with the highest burden. In January 2019, the Brumadinho dam collapse released about 12 million cubic meters of iron ore tailings into the Paraopeba River basin, causing environmental disturbance that could plausibly affect vector habitats and dengue transmission. We evaluated the spatiotemporal dynamics of dengue in Minas Gerais from 2014 to 2023 and tested whether the disaster was associated with changes in affected municipalities. Methods: We performed an ecological spatiotemporal analysis using dengue notifications from SINAN for all municipalities in Minas Gerais (2014-2023). Municipalities were classified as Paraopeba basin, regional controls, or state controls. Temporal similarity was assessed using Pearson correlation-based hierarchical clustering and non-metric multidimensional scaling (NMDS). Sources of variation were examined with PERMANOVA and principal component analysis (PCA). A linear mixed-effects model with municipality as a random effect was used to test changes after 2019, with pre/post contrasts estimated from marginal means. Results: Dengue showed strong temporal synchrony across the state, with major epidemic peaks in 2015-2016, 2019, and 2023. Health region explained 31.5% of the variation in temporal incidence profiles (p = 0.001), whereas Paraopeba basin status explained no significant variation (p = 0.998). No temporal cluster was enriched for municipalities in the Paraopeba basin. PCA identified 2023, 2019, and 2016 as the main years driving variability. In the mixed model, year was significant (p < 0.001), but Paraopeba basin status and its interaction with time were not. Incidence increased significantly after 2019 in non-exposed municipalities (p < 0.001), but not in basin municipalities (p = 0.088). Conclusions: Dengue dynamics in Minas Gerais were driven mainly by regional and state-wide epidemic processes, with no significant independent effect of the Brumadinho dam collapse on notified dengue patterns.

Background: Complicated acute appendicitis carries a higher risk of postoperative morbidity relative to uncomplicated cases. It remains unclear whether surgical timing (night vs. day; weekend vs. weekday) or surgeon seniority influence short-term outcomes in this high-risk population. Methods: This was a retrospective analysis of the RIFT Turkey dataset restricted to histologically confirmed cases of complicated appendicitis who had undergone laparoscopic appendectomy. Primary exposures were surgical timing (day [n=92] vs. night [n=123]; weekday [n=172] vs. weekend [n=43]) and surgeon seniority (trainee [n=89] vs. consultant [n=126]). The primary outcome was unplanned readmission and/or reintervention within 60 days. Secondary outcomes were conversion to open surgery and length of stay (LOS) >3 days. Propensity score matching (PSM) using RIPASA score (caliper 0.05, SMD <0.1) was performed as a pre-specified sensitivity analysis for each comparison. Results: Night-time surgery was associated with higher frequencies of unplanned readmission / reintervention (12.2% vs. 6.5%; OR 1.99 [95% CI 0.74-5.35], p=0.166) and surgical conversion (9.8% vs. 3.3%; OR 3.21 [0.88-11.72], p=0.064) compared with daytime surgery, neither reaching significance. Trainee surgeons had significantly higher readmission/reintervention rates than consultants (15.7% vs. 5.6%; OR 0.32 [0.12-0.82], p=0.013). PSM-adjusted results also showed similar relationships: night vs. day (readmission OR 2.45 [0.85-7.03], p=0.09; conversion OR 2.84 [0.73-11.1], p=0.13), weekend vs. weekday (readmission OR 1.53 [0.24-9.72], p=0.65), and trainee vs. consultant (readmission OR 0.25 [0.08-0.79], p=0.013). Conclusion: Surgical timing was not significantly associated with short-term outcomes in complicated appendicitis, though night-time surgery showed a consistent trend towards higher complication rates. Surgeon seniority was the only factor independently and significantly associated with unplanned readmission and reintervention in both primary and PSM analyses, indicating the need for senior supervision during out-of-hours procedures. Keywords: complicated appendicitis; surgical timing; night surgery; weekend effect; surgeon seniority; propensity score matching; RIFT Turkey

To evaluate the international interoperability of food composition databases, we assessed the compatibility of seven national food composition tables with USDA FoodData Central (FDC) using the LLM-based matching method reported previously (Nakagawa and Yamamoto, 2026). Databases from four English-speaking countries (Canada, United Kingdom, Australia, and New Zealand), South Korea, and Japan were compared with 8,158 USDA FDC entries (SR Legacy and Foundation Foods, excluding Survey/FNDDS). Match rates varied by country (62.0-89.7%) and food category. After excluding six USDA categories unsuitable for cross-national comparison, 45.2% of the remaining 6,290 entries were not matched by any country. Canada showed the highest concordance, reflecting shared North American food supply. Japan and South Korea showed similar low coverage for vegetables and spices. These findings suggest that while USDA FDC represents a practical foundation for a globally comprehensive food composition database given its breadth, systematic incorporation of country-specific foods and classification schemes will be necessary to achieve true international interoperability.

Background: Black and Latino adults in the United States experience a disproportionate burden of cardiometabolic conditions due to interacting behavioral, social, and structural drivers of health. Less is known about the impact of integrating digital health tools into CHW-led interventions to improve cardiometabolic health. This trial evaluates a multilevel community-digital health promotion model delivered by CHWs to improve service utilization, health behaviors and cardiometabolic health among Black and Latino adults. Methods: This community-partnered trial uses a randomized delayed-control group with a phased recruitment design. Four cohorts (N = 664) are enrolled through three community-based organizations (CBOs). Eligible participants are 18 years who self-identify as Black or Latino, and have prediabetes/diabetes, hypertension, or overweight/obesity. Participants are allocated to either (1) a multilevel intervention consisting of CBO and CHW capacity building combined with individualized CHW-led lifestyle coaching and group activities supported by digital tools, or (2) a delayed control group receiving SMS-only cardiometabolic health education. Data collected at baseline, 6, 9, and 18 months include surveys and health metrics. Qualitative data are collected from participants and community partners to assess intervention acceptability, implementation facilitators and barriers, and sustainability. Results: The primary outcome is health service utilization at 6 and 9 months. Secondary outcomes include health behaviors, health metrics, and social determinants of health. Sustainability of health behaviors and health metrics is assessed at 18 months. Conclusions: Findings will provide evidence to inform scalable, sustainable community-digital health models for CHW-supported cardiometabolic health interventions in underserved communities.

Biological aging is heterogeneous across organ systems, yet whether CT-derived abdominal aging provides prognostic value beyond routine clinical data and whether organ decomposition adds beyond a unified estimate remains untested. We developed and evaluated organ-specific and ensemble biological age models from radiomic features across five abdominal organs in 68,675 CT scans from 32,883 subjects, evaluated on alignment with chronological age of healthy subjects (nested cross validation: MAE=3.68 years, R^2=0.90). In sequential analyses restricted to adults aged 20-60 years which is the stratum of strongest BAG-disease association, ensemble biological age gaps provided incremental prognostic value beyond demographic covariates for all-cause disease and mortality (Delta C-index=0.141, 0.051) and beyond routine blood biomarkers (Delta C-index=0.048), confirming CT-derived aging captures structural information beyond laboratory markers. Organ-specific biological age added incremental prognostic value beyond ensemble selectively for focal diseases: cardiovascular (aorta, Delta C-index=0.091) and hepato-pancreatic (pancreas, Delta C-index=0.096). These findings establish a hierarchical organization of CT-derived biological aging, positioning routine CT as a source that adds prognostic value to existing clinical biomarkers.

Background: Frontotemporal dementia (FTD) lacks widely accessible disease-specific biomarkers. Optical coherence tomography (OCT) and OCT angiography (OCTA) may provide non-invasive measures of retinal changes associated with neurodegeneration. We conducted a systematic review and meta-analysis evaluating retinal biomarkers in FTD compared with Alzheimer disease (AD) and controls. Methods: A systematic search of PubMed and Embase was conducted through April 25, 2026 according to PRISMA guidelines. Studies evaluating OCT/OCTA biomarkers in FTD with comparator groups were included. Inverse weighted random-effects models, publication bias assessments, and meta-regressions were performed. Results: Ten studies involving 139 individuals with FTD, 87 with AD, 29 with mild cognitive impairment, 14 with TDP-43 proteinopathy, 5 with tauopathy, and 255 controls were included in the systematic review; five studies were eligible for meta-analysis. Compared with AD, individuals with FTD demonstrated significantly thinner retinal nerve fiber layer (RNFL) thickness (SMD = -0.61, 95% CI -0.98, -0.24). Compared with controls, individuals with FTD exhibited significantly thinner ganglion cell layer-inner plexiform layer (GCL-IPL) thickness (SMD = -0.55, 95% CI -1.02, -0.08), whereas pooled analyses across multiple retinal biomarkers were non-significant (SMD = -0.19, 95% CI -0.52, 0.14). RNFL thickness correlated negatively with female % in FTD and positively with age in both AD and controls. Conclusions: Individuals with FTD exhibit lower RNFL thickness than AD and lower GCL-IPL thickness than controls, suggesting retinal alterations may reflect neurodegeneration. However, larger longitudinal studies with standardized OCT/OCTA protocols are needed to determine the diagnostic and prognostic utility of retinal biomarkers in FTD

ABSTRACT OBJECTIVE: We performed a systematic review and meta-analysis (SRMA) of post-surgical outcomes, comparing chlorhexidine gluconate (CHG) versus povidone iodine (PI) for vaginal antisepsis of major gynecologic procedures. DATA SOURCES: Ovid Medline, Embase, Scopus, Embase, Cochrane, and Clinicaltrials.gov were searched between 1986 and December 2023, for studies comparing CHG with PI for vaginal antisepsis of major gynecologic operations. STUDY ELIGIBILITY CRITERIA: We included Randomized Controlled Trials (RCTs) and non-RCTs comparing CHG to PI for vaginal antisepsis of major gynecologic operations. The primary outcome was surgical site infections (SSIs) and the secondary outcome was urinary tract infections (UTIs) and vaginal irritation. METHODS: Summary estimates were calculated by fixed effects models when I2 [&le;] 25% and by random effects models when I2 > 25%. Statistical analysis was performed using RevMan 5.4.1. The protocol for this systematic review was registered on PROSPERO (ID CRD42022378101). RESULTS: Nine studies met the inclusion criteria, four of which were randomized controlled trials (RCTs). 9538 patients were included, 4300 (45%) of whom were allocated to CHG and 5238 (55%) to PI. No statistically significant difference in SSI incidence was found for vaginal antisepsis with CHG versus PI in pooled analyses (n= 9538 patients; RR 1.20; 95% CI 0.92-1.57; I2 =0%). In contrast, a significantly higher risk of UTIs was observed for vaginal antisepsis with CHG than with PI (n=6061 patients; RR 1.48 95% CI 1.03-2.14; I2 = 0%). CONCLUSION: In our SRMA, there were no significant differences in SSI risk when either CHG or PI was utilized for antiseptic vaginal preparation. Interestingly, vaginal antisepsis with PI was associated with a lower incidence of post-operative UTIs following major gynecologic surgery. Our findings support current guidelines that form of vaginal antisepsis can be used for SSI prevention. They also suggest that PI may result in fewer postoperative UTIs but further randomized studies are needed to support these findings. Key words: surgical site infection, surgical wound infection, urinary tract infection, urogynecologic surgery, Chlorhexidine, Povidone Iodine, surgical antiseptic,

Background Artificial intelligence-enhanced electrocardiography (AI-ECG) enables scalable, low-cost cardiac dysfunction screening, but existing models are annotation-intensive and predominantly adult-derived, leaving paediatric generalizability uncertain. Paediatric cohorts exhibit highly variable cardiac morphology and function compared to adults, which may be useful for learning generalizable AI-ECG models. Methods We pretrained ECG-Fyler on a predominantly paediatric, all-age cohort at Boston Children's Hospital (1992-2023), annotated with a cardiology-specific coding system (Fyler codes), and evaluated it on assessments from echocardiography (echo) and cardiac magnetic resonance (CMR) studies. We validated on an external adult cohort from Columbia University Irving Medical Center. Performance was benchmarked against several AI-ECG foundation models by AUROC across age groups, lesion types, and limited-data scenarios. Findings The pretraining cohort comprised 782,138 ECGs from 255,271 patients (median age: 10.9 years, IQR: [2.8-16.8]). Internal evaluation included 178,495 ECG-echo pairs (median age: 10.9 [3.7-17.0]) and 8,584 ECG-CMR pairs (median age: 20.7 [15.6-29.6]). External validation included 82,543 ECG-echo pairs from adults (median age: 64.0 [52.0-74.0]). ECG-Fyler improved AUROC across biventricular dysfunction and dilation tasks, with the largest gains in low-data settings. In internal validation, ECG-Fyler detected low left ventricular ejection fraction (LVEF [&le;] 40%) from only 100 fine-tuning samples (AUROC: 0.80, 95% CI: [0.78-0.80]), outperforming other models (AUROC < 0.65) and improving with additional fine-tuning (AUROC: 0.94 [0.93-0.94]). Similar improvements were observed for CMR-derived LVEF, RVEF, and ventricular dilation. In external validation on adults, ECG-Fyler exhibited an AUROC of 0.83 (CI: [0.82-0.85]) for LVEF [&le;] 40%. After fine-tuning on less than 10% of external data, LVEF [&le;] 45% performance (AUROC: 0.87 [0.86-0.88]) outperformed a fully trained, site-specific prior model (AUROC: 0.85 [0.84-0.87]). Interpretation Pretraining on richly annotated, paediatric-dominant ECGs yields models that transfer efficiently across institutions and ages, supporting AI-ECG screening and triage when labels or imaging access are limited. Funding National Institutes of Health (R01LM012973); Kostin Innovation Fund, Boston Children's Hospital

The Epic Sepsis Model version 2 (ESMv2) is a prediction model embedded into the electronic medical record used to warn clinicians which hospitalized patients are at risk for sepsis. We conducted a retrospective cohort study of 31,951 hospitalizations of 25,760 patients to compare analyses conducted at the commonly used patient-level (where a maximum prediction prior to the onset of sepsis is used to measure performance) vs novel prediction-level (where each prediction is used to measure performance). Sepsis, defined by the Sepsis 3 criteria occurred during 1,049 hospitalizations (3.3%). Patient-level analyses suggested excellent discrimination AUC 0.86; [IQR 0.85, 0.87], whereas prediction-level analyses demonstrated lower performance AUC 0.62; [IQR 0.57, 0.65]. Low estimates of the positive predictive value (14.5% at the patient level vs 4% at the prediction level) imply a high number of false alerts. Common evaluation approaches may overstate the performance of dynamic prediction models and mislead clinical decision-making.

Background: Despite the success of combination antiretroviral therapy (cART), vascular comorbidities, including cerebrovascular disease, are more prominent in people living with HIV (PLWH) compared to people without HIV (PWOH). However, quantitative assessments of cerebrovascular morphometry and their associations with cognitive outcomes in the context of HIV are still limited. In this study, we explore this missing link. Methods: Magnetic Resonance Angiography (MRA) data, blood markers, and neurocognitive assessments were collected from 73 PWOH subjects (male: 57, female: 16; age: 53 {+/-} 16) and 99 PLWH subjects (male: 66, female: 30, age: 53 {+/-} 11). Vessel morphometric features were quantified using intraCranial Artery Feature Extraction (iCafe) to investigate associations between vessel morphometry, markers of monocytes, endothelial cell activation, and cognitive performance. Results: HIV status predicted a lower total number of branches ({beta} = -0.224, p = 0.001, d = -0.517) and shorter total distal length ({beta} = -0.173, p = 0.021, d = -0.370) with a moderate effect size. Total branch number was found to be negatively associated with plasma levels of monocyte markers (sCD14: r = -0.167, p = 0.033; sCD163: r = -0.157, p = 0.045) and positively correlated with white matter cerebral blood flow (r = 0.550; p [&le;] 0.05). HIV status was the strongest predictor of overall cognitive performance in ANCOVA model ({beta} = -0.219, p = 0.006, d = -0.453). Conclusions: Our results suggest that cognitive impairment in PLWH is associated with vessel morphology metrics. Monocyte immune activation may contribute to changes in vessel morphology.

Patients with primary immunodeficiency (PID) often face prolonged diagnostic delays and may increasingly turn to large language models (LLMs) to interpret their symptoms during this period. We evaluated whether an LLM could recognize PID from symptom descriptions derived from interviews with 21 PID patients. In a prior study, we showed that GPT-4o identified PID in 96% of cases when prompted with physician-written patient histories (Rider et al., JACI, 2024). Here, when prompted with symptom descriptions in patients' own words, GPT-5 identified PID in only 7 cases (33%), although it more broadly suggested immune system issues in 18 cases (81%). The gap between these findings indicates that LLMs are sensitive to the language and framing of symptom descriptions, performing substantially worse when patients describe their own symptoms in everyday language than when clinicians summarize patient histories in structured medical terms. This study underscores the need to carefully evaluate how LLMs are used in patient-facing applications.

Pain in pancreatic ductal adenocarcinoma (PDAC) is associated with poor survival, but whether altered pain processing carries prognostic significance is unknown. We analyzed a prospective cohort of 143 patients with PDAC who underwent pancreatic quantitative sensory testing (PQST) after diagnosis. Patients were classified as having normal pain processing (n=84), segmental hyperalgesia (n=30), or widespread hyperalgesia (n=29). Survival was measured from the date of P-QST assessment. During follow-up, 70 deaths occurred. Widespread hyperalgesia was associated with increased mortality in unadjusted Cox analysis (HR 1.96, 95% CI 1.14,3.35) and after adjustment for age, sex, tumor stage, comorbidity, opioid treatment, and body mass index (adjusted HR 2.33, 95% CI 1.30,4.15). Segmental hyperalgesia was not associated with mortality. Kaplan Meier analysis demonstrated lower survival probability in the widespread hyperalgesia group (log rank p=0.025). These findings suggest that widespread hyperalgesia, reflecting altered central pain processing, identifies a subgroup of PDAC patients at increased risk of mortality independent of conventional clinical factors.

Intro: Characteristics of the pulse wave transmitted through the carotid arteries are predictive of cognitive decline and cerebrovascular health in humans. This study aimed to identify risk factor trajectories in childhood, adolescence and early adulthood that are associated with forward compression wave intensity (FCWI) in the common carotid artery in adults aged 28 years. Methods: Systolic blood pressure (SBP), body mass index (BMI) and fasting blood glucose (FBG) measured at multiple time-points when participants were aged between 8-20 years were included in a trajectory analysis. At age 28 years, FCWI was measured in 402 (M=206, F=196) participants who underwent a Duplex ultrasound assessment of the common carotid artery. Statistical analysis assessed differences in FCWI between each trajectory group for males and females separately. Results: In males, four trajectory groups were identified for BMI, three for SBP, and two for FBG. In females, three trajectory groups were identified for BMI, SBP, and FG. In males, having higher BMI (P=0.006), SBP (P=0.021) and FBG (P=0.002) from ages 8-20 years was associated with greater FCWI at age 28 years. In females, no associations were found between FCWI at age 28-years and trajectory groups for BMI (P=0.185), SBP (P=0.289) or FBG (P=0.070). Conclusion: Having high BMI, SBP and FBG throughout childhood, adolescence and early adulthood was associated with higher FCWI in the carotid artery at age 28 years in males, but not females. This may have a direct impact on the etiology of cognitive decline and cerebrovascular disease in later life.

Lead is a toxic metal ubiquitous in our environment. While dramatic reductions in lead sources have paralleled equivalent decreases in lead-poisoning rates, chronic lead exposure remains a critical public health concern. Childhood lead exposure (at its lowest levels) is liked to changes in cognitive development but less is known about lead's effects on children's brain structure, especially as a result of in utero exposure. We measured prenatal and early-postnatal lead exposure in shed deciduous teeth of 448 9- and 10-year-old children (from 20 United States cities) and linked those lead levels to childhood brain structure, cognition/behavior, and neighborhood- and family-level socioeconomic characteristics. Here we show negative associations between tooth-lead levels and the thickness of the brain's cortex, particularly in regions linked to language processing. With increasing tooth-lead levels, children of lower-income (versus higher-income) families showed steeper declines in receptive vocabulary. Caregiver-reported behavioral problems exhibited similar associations. With in utero exposure linked to adverse neurodevelopmental outcomes (well before lead exposure and its risks are evaluated by healthcare professionals), prenatal screening of maternal lead levels/exposure, coupled with recommended strategies to reduce its placental transmission, may help reduce lead's effects on future generations.

Background: Conventional psychiatric screening instruments summarize symptoms within individual scales and prioritize cases with high single-instrument additive score severity. This design treats items as independent within instruments and ignores cross-instrument covariance structure, making it insensitive to respondents whose responses are distributed across multiple domains in unusual combinations that remain below threshold on every individual scale. Methods: We analyzed two cohorts spanning older and younger adults. Item prompts from depression, stress, anxiety, and sleep instruments were embedded into a shared semantic space using a pretrained sentence encoder. Principal component analysis of the item-prompt embeddings alone---with no use of respondent data at this stage---was used to construct a low-dimensional subspace retaining 80\% of variance in the item embedding matrix. Normalized participant responses were then projected into this subspace, with Jaccard-based stability analysis used as a check on dimensional robustness. Multivariate deviation from the cohort norm was quantified with Mahalanobis distance using Ledoit-Wolf covariance regularization. Candidate outliers were defined by the empirical 95th percentile of the cohort-specific distance distribution. To isolate response configurations not already captured by conventional single-instrument extreme-value logic, we excluded all outlier respondents who had endorsed any individual item at the maximum value of its Likert scale on any instrument. For the remaining outliers, anomalous components were backtracked to their original item loadings for interpretation. Results: In the older-adult Health and Retirement Study (HRS) cohort, principal component analysis of 27 item-prompt embeddings showed that a 10-dimensional subspace provided a stable representation of cross-instrument semantic structure. In the younger-adult Xinxiang cohort the corresponding stable solution was 16-dimensional. In each cohort, seven respondents remained as multivariate outliers despite falling below every single-instrument extreme-value threshold. These cases were not characterized by uniformly severe symptom scores but by unusual cross-domain response configurations that became visible only in the shared semantic covariance subspace. The response structure of the retained configurations differed across cohorts: older-adult cases more often involved weak endorsement of mood-labeled items alongside nonzero body- and sleep-related responses, whereas younger-adult cases more often involved incomplete response configurations spanning mood, sleep, stress, and self-harm-related items. Conclusions: A semantically aligned, auditable covariance subspace provides a practical tool for flagging unusual multivariate response configurations that single-instrument additive screening may not flag. The method is interpretable at the level of original item contributions. It should be understood as a hypothesis-generating screen for unusual response configurations requiring further clinical assessment, not as a diagnostic instrument. Outcome validity remains to be established by prospective study.