There is strong evidence for brain-related abnormalities in COVID-19 1-13 . It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51-81) imaged twice, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan, and 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.

Key Points Question Is regular consumption of soft drinks associated with a greater risk of all-cause and cause-specific mortality? Findings In this population-based cohort study of 451 743 individuals from 10 countries in Europe, greater consumption of total, sugar-sweetened, and artificially sweetened soft drinks was associated with a higher risk of all-cause mortality. Consumption of artificially sweetened soft drinks was positively associated with deaths from circulatory diseases, and sugar-sweetened soft drinks were associated with deaths from digestive diseases. Meaning Results of this study appear to support ongoing public health measures to reduce the consumption of soft drinks.

The purpose of this study was to evaluate the effectiveness of the influenza vaccine during the 2024-2025 respiratory viral season. Employees of Cleveland Clinic in employment in Ohio on October 1, 2024, were included. The cumulative incidence of influenza among those in the vaccinated and unvaccinated states was compared over the following 25 weeks. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. Among 53402 employees, 43857 (82.1%) had received the influenza vaccine by the end of the study. Influenza occurred in 1079 (2.02%) during the study. The cumulative incidence of influenza was similar for the vaccinated and unvaccinated states early, but over the course of the study the cumulative incidence of influenza increased more rapidly among the vaccinated than the unvaccinated. In an analysis adjusted for age, sex, clinical nursing job, and employment location, the risk of influenza was significantly higher for the vaccinated compared to the unvaccinated state (HR, 1.27; 95% C.I., 1.07 – 1.51; P = 0.007), yielding a calculated vaccine effectiveness of −26.9% (95% C.I., −55.0 to −6.6%). This study found that influenza vaccination of working-aged adults was associated with a higher risk of influenza during the 2024-2025 respiratory viral season, suggesting that the vaccine has not been effective in preventing influenza this season. Among 53402 working-aged Cleveland Clinic employees, we were unable to find that the influenza vaccine has been effective in preventing infection during the 2024-2025 respiratory viral season.

Objective To investigate the potential of voice analysis as a prescreening or monitoring tool for type 2 diabetes mellitus (T2DM) by examining the differences in voice recordings between nondiabetic and T2DM individuals. Patients and Methods Total 267 participants diagnosed as nondiabetic (79 women and 113 men) or T2DM (18 women and 57 men) on the basis of American Diabetes Association guidelines were recruited in India between August 30, 2021 and June 30, 2022. Using a smartphone application, participants recorded a fixed phrase up to 6 times daily for 2 weeks, resulting in 18,465 recordings. Fourteen acoustic features were extracted from each recording to analyze differences between nondiabetic and T2DM individuals and create a prediction methodology for T2DM status. Results Significant differences were found between voice recordings of nondiabetic and T2DM men and women, both in the entire dataset and in an age-matched and body mass index (BMI [calculated as the weight in kilograms divided by the height in meters squared])-matched sample. The highest predictive accuracy was achieved by pitch (P<.0001), pitch SD (P<.0001), and relative average pertubation jitter (P=.02) for women, and intensity (P<.0001) and 11-point amplitude perturbation quotient shimmer (apq11, P<0.0001) for men. Incorporating these features with age and BMI, the optimal prediction models achieved accuracies of 0.75±0.22 for women and 0.70±0.10 for men through 5-fold cross-validation in the age-matched and BMI-matched sample. Conclusion Overall, vocal changes occur in individuals with T2DM compared with those without T2DM. Voice analysis shows potential as a prescreening or monitoring tool for T2DM, particularly when combined with other risk factors associated with the condition. Trial Registration clinicaltrials.gov Identifier: CTRI/2021/08/035957

Here we report a conserved transcriptomic signature of reduced fatty acid and lipid metabolism gene expression in a Drosophila model of C9orf72 repeat expansion, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), and in human postmortem ALS spinal cord. We performed lipidomics on C9 ALS/FTD Drosophila, induced pluripotent stem (iPS) cell neurons and postmortem FTD brain tissue. This revealed a common and specific reduction in phospholipid species containing polyunsaturated fatty acids (PUFAs). Feeding C9 ALS/FTD flies PUFAs yielded a modest increase in survival. However, increasing PUFA levels specifically in neurons of C9 ALS/FTD flies, by overexpressing fatty acid desaturase enzymes, led to a substantial extension of lifespan. Neuronal overexpression of fatty acid desaturases also suppressed stressor-induced neuronal death in iPS cell neurons of patients with both C9 and TDP-43 ALS/FTD. These data implicate neuronal fatty acid saturation in the pathogenesis of ALS/FTD and suggest that interventions to increase neuronal PUFA levels may be beneficial.

Abstract IMPORTANCE Post-acute sequelae of SARS-CoV-2 infection (PASC) remains a major public health challenge. While previous studies have focused on characterizing PASC and identifying its subphenotypes in children and adolescents following an initial SARS-CoV-2 infection, the risks of PASC with Omicron-variant reinfections remain unclear. Using a real-world data approach, this study investigates the risks of PASC following reinfections during the Omicron phase in the pediatric population. OBJECTIVE To investigate the risks of PASC diagnosis and 24 PASC symptoms and conditions after reinfection of SARS-CoV-2 during Omicron period in the pediatric population. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data from the RECOVER consortium comprising 40 children’s hospitals and health institutions in U.S. between January 2022 and October 2023. EXPOSURES A second SARS-CoV-2 infection, confirmed by a positive polymerase-chain-reaction (PCR) or antigen tests, or a diagnose of COVID-19, occurring at least 60 days after the initial infection, compared to the initial infection. MAIN OUTCOMES AND MEASURES PASC was identified using two approaches: (1) the ICD-10- CM diagnosis code U09.9 and (2) a symptom-based definition including 24 physician-identified symptoms and conditions. Absolute risks of incident PASC were reported, and relative risks (RRs) were calculated by comparing the second infection episode with the first infection episode groups using a modified Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through exact matching and propensity scoring matching. RESULTS A total of 465,717 individuals under 21 years old (mean [SD] age 8.17 [6.58] years; 52% male) were included. Compared to the first infection, a second infection was associated with significantly increased risk of an overall PASC diagnosis (RR, 2.08; 95% confidence interval [CI], 1.68-2.59), and with many specific conditions including: myocarditis (RR, 3.60; 95% CI, 1.46-8.86); changes in taste and smell (RR, 2.83; 95% CI, 1.41-5.67); thrombophlebitis and thromboembolism (RR, 2.28; 95% CI, 1.71-3.04); heart disease (RR, 1.96; 95% CI, 1.69 to 2.28); acute kidney injury (RR, 1.90; 95% CI, 1.38 to 2.61); fluid and electrolyte (RR, 1.89; 95% CI, 1.62 to 2.20); generalized pain (RR, 1.70; 95% CI, 1.48 to 1.95); arrhythmias (RR, 1.59; 95% CI, 1.45-1.74); abnormal liver enzyme (RR, 1.56; 95% CI, 1.24 to 1.96); fatigue and malaise (RR, 1.50; 95% CI, 1.38 to 1.64); musculoskeletal pain (RR, 1.45; 95% CI, 1.37 to 1.54); abdominal pain (RR, 1.42; 95% CI, 1.34 to 1.50); postural orthostatic tachycardia syndromes (POTS)/dysautonomia (RR, 1.35; 95% CI, 1.20 to 1.51); cognitive functions (RR, 1.32; 95% CI, 1.15 to 1.50); and respiratory signs and symptoms (RR, 1.29; 95% CI, 1.25 to 1.33). The risks were consistent across various organ systems, including cardiovascular, respiratory, gastrointestinal, neurological, and musculoskeletal systems. CONCLUSIONS AND RELEVANCE Children and adolescents face significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings suggest a cumulative risk of PASC and highlight the urgent need for targeted prevention strategies to reduce reinfections, which includes an increased emphasis on initial or re-vaccination of children. Key Points Question Do children and adolescents face an increased risk of post-acute sequelae of SARS-CoV-2 infection (PASC) following reinfection during the Omicron era? Findings During the post-acute phase, children and adolescents with reinfection are at statistically significant increased risk of incident PASC outcomes, including an overall PASC diagnosis and 24 most commonly complaints/symptoms/diagnoses associated with PASC. The risks remained consistent across different demographic and clinical subgroups. Meaning These findings underscore the significant long-term health risks associated with SARS-CoV-2 reinfection in children and adolescents. Public health strategies should prioritize reinfection prevention, including enhanced vaccination efforts, to mitigate the burden of PASC in the pediatric population.