Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe.

BACKGROUND: Research on Long COVID risk factors is ongoing. High body mass index (BMI) may increase Long COVID risk, yet no evidence has been established regarding sex differences in the relationship between BMI and the risk of Long COVID. Investigating the nature of this relationship was the main objective of this study. METHODS: A population-based prospective study involving a sample of respondents aged 50 years and older (n = 4004) from 27 European countries that participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe's (SHARE) Corona Surveys and in Waves 7 and 8 of the main SHARE survey. Logistic regression models were estimated to produce unadjusted and adjusted estimates of the sex differences in the relationship between BMI and Long COVID. RESULTS: Linear relationship for females, with probability of Long COVID increasing with BMI (68% at BMI = 18, 93% at BMI = 45). Non-linear relationship for males, with probability of Long COVID of 27% at BMI = 18, 68% at BMI = 33, and 40% at BMI = 45. Relationships remained significant after adjusting for known Long COVID risk factors (age and COVID-19 hospitalization), presence of chronic diseases, and respondents' place of residence. CONCLUSION: Sex differences appear to play an important role in the relationship between BMI and risk of Long COVID. Overall, females were more likely to have Long COVID, regardless of their BMI. Males at the higher end of the BMI spectrum had a lower risk of Long COVID as opposed to their female counterparts. Sex-specific research is recommended for better understanding of Long COVID risk factors.

Association of outdoor air and noise pollution with unprovoked seizures and new onset epilepsy: A systematic review and meta-analysis.

Research has indicated that certain environmental exposures may increase the risk of unprovoked seizures and new onset epilepsy. This study aimed to synthesize the literature that has estimated the associations between short- and long-term exposure to outdoor air and noise pollution and the risk of unprovoked seizures and new onset epilepsy. We searched Embase, MEDLINE, Scopus, Web of Science, BIOSIS Previews, Latin American and Caribbean Health Sciences Literature, Proquest Dissertations and Theses, conference abstracts, and the gray literature and conducted citation tracing in June 2023. Observational and ecological studies assessing the associations of air and noise pollution with unprovoked seizures or new onset epilepsy were eligible. One reviewer extracted summary data. Using fixed and random effects models, we calculated the pooled risk ratios (RRs) for the studies assessing the associations between short-term exposure to air pollution and unprovoked seizures. Seventeen studies were included, 16 assessing the association of air pollution with seizures and one with epilepsy. Eight studies were pooled quantitatively. Ozone (O3; RR = .99, 95% confidence interval [CI] = .99-.99) and nitrogen dioxide (NO2) exposure adjusted for particulate matter (RR = 1.02, 95% CI = 1.01-1.02) on the same day, and carbon monoxide (CO) exposure 2 days prior (RR = 1.12, 95% CI = 1.02-1.22), were associated with seizure risk. A single study of air pollution and epilepsy did not report a significant association. The risk of bias and heterogeneity across studies was moderate or high. Short-term exposure to O3, NO2, and CO may affect the risk of seizures; however, the effect estimates for O3 and NO2 were minimal. Additional research should continue to explore these and the associations between outdoor air pollution and epilepsy and between noise pollution and seizures and epilepsy.

Incidence of First-Episode Status Epilepticus and Risk Factors in Ontario, Canada.

BACKGROUND: Status epilepticus (SE) is a neurological emergency characterized by prolonged seizures. However, the incidence of first-episode SE is unclear, as estimates vary greatly among studies. Additionally, SE risk factors have been insufficiently explored. Therefore, the objectives of this study were to estimate the incidence of first-episode SE in Ontario, Canada, and estimate the associations between potential sociodemographic and health-related risk factors and first-episode SE. METHODS: We conducted a population-based retrospective cohort study using linked health administrative datasets. We included individuals who completed Canada's 2006 Census long-form questionnaire, lived in Ontario, were between 18 and 105, and had no history of SE. A Cox proportional hazards regression model was used to estimate the hazard ratios for SE within three years associated with each potential risk factor. RESULTS: The final sample included 1,301,700 participants, 140 of whom were hospitalized or had an emergency department visit for first-episode SE during follow-up (3.5 per 100,000 person-years). Older age was the only significant sociodemographic SE risk factor (HR = 1.35, 95% CI = 1.33, 1.37), while health-related risk factors included alcohol or drug abuse (HR = 1.05, 95% CI = 1.02, 1.08), brain tumour or cancer (HR = 1.14, 95% CI = 1.12, 1.15), chronic kidney disease (HR = 1.32, 95% CI = 1.29, 1.36), dementia (HR = 1.42, 95% CI = 1.36, 1.48), diabetes (HR = 1.11, 95% CI = 1.09, 1.12), epilepsy or seizures (HR = 1.05, 95% CI = 1.01, 1.09) and stroke (HR = 1.08, 95% CI = 1.05, 1.11). CONCLUSION: The estimated incidence of SE in a sample of Ontario residents was 3.5 per 100,000 person-years. Older age and several comorbid conditions were associated with higher first-episode SE risk.

The role of multimorbidity and socio-economic characteristics as potential risk factors for Long Covid: evidence from the multilevel analysis of the Survey of Health, Ageing and Retirement in Europe's corona surveys (2020-2021).

BACKGROUND: A substantial proportion of individuals continue experiencing persistent symptoms following the acute stage of their Covid-19 illness. However, there is a shortage of population-based studies on Long Covid risk factors. OBJECTIVE: To estimate the prevalence of Long Covid in the population of middle-aged and older Europeans having contracted Covid-19 and to assess the role of multimorbidity and socio-economic characteristics as potential risk factors of Long Covid. METHODS: A population-based longitudinal prospective study involving a sample of respondents 50 years and older (n = 4,004) from 27 countries who participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe (SHARE), in particular the Corona Surveys. Analyses were conducted by a multilevel (random intercept) hurdle negative binomial model. RESULTS: Overall, 71.6% (95% confidence interval = 70.2-73.0%) of the individuals who contracted Covid-19 had at least one symptom of Long Covid up to 12 months after the infection, with an average of 3.06 (standard deviation = 1.88) symptoms. There were significant cross-country differences in the prevalence of Long Covid and number of symptoms. Higher education and being a man were associated with a lower risk of Long Covid, whilst being employed was associated with a higher risk of having Long Covid. Multimorbidity was associated with a higher number of symptoms and older age was associated with a lower number of symptoms. CONCLUSION: Our results provide evidence on the substantial burden of Long Covid in Europe. Individuals who contracted Covid-19 may require long-term support or further medical intervention, putting additional pressure on national health care systems.

Does Pre-existing Diabetes Correlate with Long COVID-19 in Europe? Evidence from the Analysis of the Survey of Health, Ageing and Retirement in Europe's Corona Surveys.

Background: A substantial proportion of those infected with COVID-19 are presenting with persistent symptoms, referred to as long COVID-19. Emerging evidence suggests that the presence of pre-existing chronic conditions, such as diabetes, may increase the risk of long COVID-19. Objectives: To investigate whether having pre-existing diabetes increases the risk of developing long COVID-19 in the population of middle-aged and older adults (≥50 years old) in Europe, while assessing if this relationship can be accounted for or is modified by the known long COVID-19 and diabetes risk factors (age, sex, hospitalization, pre-existing hypertension, and weight status). Methods: A population-based longitudinal prospective study involving a sample of respondents aged 50 years and older (n = 4,004) with probable or confirmed COVID-19 infection from 27 countries that participated in both waves 7 and 8 of the Survey of Health, Ageing and Retirement in Europe and its 2020 and 2021 Corona Surveys. Logistic regression modeling was performed. Results: Overall, 66.8% of the respondents affected by COVID-19 infection reported at least one long COVID-19 symptom; 55.2% were female, and the average age was 64.6 years; 13.2% had pre-existing diabetes. Respondents with pre-existing diabetes had significantly higher odds of developing long COVID-19, compared to those without diabetes (OR = 1.37; 95% CI = 1.12, 1.68). This relationship remained significant (OR = 2.00; 98% CI = 0.25, 1.14) after adjusting for sex (OR = 1.64 for females; 95% CI = 1.43, 1.88), hospitalization for COVID-19 illness (OR = 3.19; 95% CI = 2.41, 4.23), pre-existing hypertension (OR = 1.17; 95% CI = 1.01, 1.36), and overweight (OR = 1.31; 95% CI = 1.11, 1.56) and obese (OR = 1.77; 95% CI = 1.44, 2.19) weight status. The effect of pre-existing diabetes on the risk of long COVID-19 is moderated by age; it was highest at the age of 50 (OR = 2.00; 95% CI = 1.28, 3.14), and then, it declined with age. Conclusions: There is a relationship between pre-existing diabetes and long COVID-19, even after controlling for literature-based confounding factors, with age having a moderating effect on this relationship.

Structural characterization of the (deoxy)hypusination in Trichomonas vaginalis questions the bifunctionality of deoxyhypusine synthase.

Trichomonas vaginalis, the causative agent of trichomoniasis, is a prevalent anaerobic protozoan parasite responsible for the most common nonviral sexually transmitted infection globally. While metronidazole and its derivatives are approved drugs for this infection, rising resistance necessitates the exploration of new antiparasitic therapies. Protein posttranslational modifications (PTMs) play crucial roles in cellular processes, and among them, hypusination, involving eukaryotic translation factor 5A (eIF5A), has profound implications. Despite extensive studies in various organisms, the role of hypusination in T. vaginalis and its potential impact on parasite biology and pathogenicity remain poorly understood. This study aims to unravel the structural basis of the hypusination pathway in T. vaginalis using X-ray crystallography and cryo-electron microscopy. The results reveal high structural homology between T. vaginalis and human orthologs, providing insights into the molecular architecture of eIF5A and deoxyhypusine synthase (DHS) and their interaction. Contrary to previous suggestions of bifunctionality, our analyses indicate that the putative hydroxylation site in tvDHS is nonfunctional, and biochemical assays demonstrate exclusive deoxyhypusination capability. These findings challenge the notion of tvDHS functioning as both deoxyhypusine synthase and hydroxylase. The study enhances understanding of the hypusination pathway in T. vaginalis, shedding light on its functional relevance and potential as a drug target, and contributing to the development of novel therapeutic strategies against trichomoniasis.

Autoinhibition of suicidal capsid protease from O'nyong'nyong virus.

Alphaviruses pose a significant threat to public health. Capsid protein encoded in the alphaviral genomes constitutes an interesting therapy target, as it also serves as a protease (CP). Remarkably, it undergoes autoproteolysis, leading to the generation of the C-terminal tryptophan that localizes to the active pocket, deactivating the enzyme. Lack of activity hampers the viral replication cycle, as the virus is not capable of producing the infectious progeny. We investigated the structure and function of the CP encoded in the genome of O'nyong'nyong virus (ONNV), which has instigated outbreaks in Africa. Our research provides a high-resolution crystal structure of the ONNV CP in its active state and evaluates the enzyme's activity. Furthermore, we demonstrated a dose-dependent reduction in ONNV CP proteolytic activity when exposed to indole, suggesting that tryptophan analogs may be a promising basis for developing small molecule inhibitors. It's noteworthy that the capsid protease plays an essential role in virus assembly, binding viral glycoproteins through its glycoprotein-binding hydrophobic pocket. We showed that non-aromatic cyclic compounds like dioxane disrupt this vital interaction. Our findings provide deeper insights into ONNV's biology, and we believe they will prove instrumental in guiding the development of antiviral strategies against arthritogenic alphaviruses.