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1.
J Diabetes Res ; 2024: 7459628, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38343427

RESUMEN

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.


Asunto(s)
COVID-19 , Diabetes Mellitus , Hipertensión , Persona de Mediana Edad , Humanos , Femenino , Anciano , Masculino , Jubilación , Síndrome Post Agudo de COVID-19 , Estudios Prospectivos , COVID-19/epidemiología , Envejecimiento , Diabetes Mellitus/epidemiología , Encuestas y Cuestionarios , Hipertensión/epidemiología , Europa (Continente)/epidemiología
2.
Can J Neurol Sci ; : 1-9, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38312043

RESUMEN

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.

3.
Int J Biol Macromol ; 262(Pt 2): 130136, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38354926

RESUMEN

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.


Asunto(s)
Alphavirus , Proteínas de la Cápside , Humanos , Proteínas de la Cápside/química , Cápside/química , Cápside/metabolismo , Virus O'nyong-nyong/metabolismo , Péptido Hidrolasas/metabolismo , Ideación Suicida , Triptófano/metabolismo , Alphavirus/metabolismo , Endopeptidasas/metabolismo
4.
Int J Obes (Lond) ; 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38287094

RESUMEN

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.

5.
Qual Life Res ; 33(1): 169-181, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37776401

RESUMEN

PURPOSE: The increased burden of multimorbidity is restricting individuals' ability to live autonomously, leading to a poorer quality of life. This study estimated trajectories of functional limitation and quality of life among middle-aged (ages 50 to 64 years) and older (aged 65 years and older) individuals with and without multimorbidity. We also assessed differences in the relationship between these two trajectories by multimorbidity status and separately for each age cohort. METHODS: Data originated from the Survey of Health, Ageing, and Retirement in Europe (SHARE). In Luxembourg, data were obtained between 2013 and 2020, involving 1,585 respondents ≥ 50 years of age. Multimorbidity was defined as a self-reported diagnosis of two or more out of 16 chronic conditions; functional limitation was assessed by a combined (Instrumental) Activities of Daily Living (ADL/IADLI) scale; and to measure quality of life, we used the Control, Autonomy, Self-Realization, and Pleasure (CASP-12) scale. Latent growth curve modelling techniques were used to conduct the analysis where repeated measures of quality of life and functional limitation were treated as continuous and zero-inflated count variables, respectively. The model was assessed separately in each age cohort, controlling for the baseline covariates, and the estimates from the two cohorts were presented as components of a synthetic cohort covering the life course from the age of 50. RESULTS: Middle-aged and older adults living with multimorbidity experienced poorer quality of life throughout the life course and were at a higher risk of functional limitation than those without multimorbidity. At baseline, functional limitation had a negative impact on quality of life. Furthermore, among middle-aged adults without multimorbidity and older adults with multimorbidity, an increase in the number of functional limitations led to a decline in quality of life. These results imply that the impact of multimorbidity on functional limitation and quality of life may vary across the life course. CONCLUSION: Using novel methodological techniques, this study contributes to a better understanding of the longitudinal relationship between functional limitation and quality of life among individuals with and without multimorbidity and how this relationship changes across the life course. Our findings suggest that lowering the risk of having multimorbidity can decrease functional limitation and increase quality of life.


Asunto(s)
Calidad de Vida , Jubilación , Persona de Mediana Edad , Humanos , Anciano , Calidad de Vida/psicología , Multimorbilidad , Actividades Cotidianas , Envejecimiento , Europa (Continente)/epidemiología , Estudios Longitudinales
6.
Sleep Health ; 10(1): 104-113, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37977986

RESUMEN

OBJECTIVES: Sleep health inequities likely contribute to disparities in health outcomes. Our objective was to identify social determinants of sleep health among middle-aged/older adults in Canada, where prior evidence is limited. METHODS: We analyzed cross-sectional data from the Canadian Longitudinal Study on Aging, a survey of over 30,000 community-dwelling adults aged 45-85years. Self-reported measures included sleep duration, sleep satisfaction, and sleep efficiency. We explored associations between sleep measures and social determinants of health. We used modified Poisson regression to estimate prevalence ratios for sleep satisfaction and sleep efficiency, and linear regression for sleep duration. Estimates were adjusted for all social, lifestyle, and clinical covariates. We explored effect modification by sex. RESULTS: Of the 11 social determinants explored, all were significantly associated with at least one domain of sleep health. These associations were reduced to 9 variables with adjustment for all social variables, and 7 with further adjustment for lifestyle and clinical covariates, including differences by sex, age, education, marital status, employment, race/ethnicity, and sexual orientation. Better sleep health in >1 domain was observed among males, older age groups (65 and older), higher income groups, the retired group, and homeowners with adjustment for social variables, and only in males and older age groups with additional adjustment for lifestyle and clinical variables. Only sleep duration associations were modified by sex. CONCLUSIONS: Sleep health disparities among Canadian adults exist across socioeconomic gradients and racial/ethnic minority groups. Poor sleep health among disadvantaged groups warrants increased attention as a public health problem in Canada.


Asunto(s)
Etnicidad , Determinantes Sociales de la Salud , Persona de Mediana Edad , Humanos , Masculino , Femenino , Anciano , Estudios Longitudinales , Estudios Transversales , Canadá/epidemiología , Grupos Minoritarios , Envejecimiento , Sueño
7.
Age Ageing ; 52(12)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38124254

RESUMEN

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.


Asunto(s)
Síndrome Post Agudo de COVID-19 , Anciano , Humanos , Masculino , Persona de Mediana Edad , Europa (Continente)/epidemiología , Análisis Multinivel , Multimorbilidad , Síndrome Post Agudo de COVID-19/epidemiología , Estudios Prospectivos , Factores de Riesgo , Factores Socioeconómicos , Encuestas y Cuestionarios , Factores de Edad
8.
JAMA Netw Open ; 6(11): e2342663, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37938843

RESUMEN

Importance: Governments and others continue to use financial incentives to influence citizen health behaviors like physical activity. However, when delivered on a population scale they can be prohibitively costly, suggesting more sustainable models are needed. Objectives: To evaluate the association of incomplete financial incentive withdrawal ("schedule thinning") with physical activity after more than a year of incentive intervention and to explore whether participant characteristics (eg, app engagement and physical activity) are associated with withdrawal outcomes. Design, Setting, and Participants: This case-control study with a pre-post quasi-experimental design included users of a government-funded health app focused on financial incentives. Eligible participants were residents in 3 Canadian provinces over 25 weeks in 2018 and 2019. Data were analyzed from July 2021 to December 2022. Exposure: Due to fiscal constraints, financial incentives for daily physical activity goals were withdrawn in Ontario in December 2018 (case)-representing a 90% reduction in incentive earnings-but not in British Columbia or Newfoundland and Labrador (controls). Main Outcome and Measures: The primary outcome was objectively assessed weekly mean daily step count. Linear regression models were used to compare pre-post changes in daily step counts between provinces (a difference-in-differences approach). Separate models were developed to examine factors associated with changes in daily step count (eg, app engagement and physical activity). Clinically meaningful initial effect sizes were previously reported (approximately 900 steps/d overall and 1800 steps/d among the physically inactive). Results: In total there were 584 760 study participants (mean [SD] age, 34.3 [15.5] years; 220 388 women [63.5%]), including 438 731 from Ontario, 124 101 from British Columbia, and 21 928 from Newfoundland and Labrador. Significant physical activity declines were observed when comparing pre-post changes in Ontario to British Columbia (-198 steps/d; 95% CI, -224 to -172 steps/d) and Newfoundland and Labrador (-274 steps/d; 95% CI, -323 to -225 steps/d). The decrease was most pronounced for highly engaged Ontario users (-328 steps/d; 95% CI, -343 to -313 steps/d). Among physically inactive Ontario users, physical activity did not decline following withdrawal (107 steps/d; 95% CI, 90 to 124 steps/d). Conclusions and Relevance: In this case-control study of incomplete financial incentive withdrawal, statistically significant daily step count reductions were observed in Ontario; however, these declines were modest and not clinically meaningful. Amidst substantial program savings, the physical activity reductions observed here may be acceptable to decision-makers working within finite budgets.


Asunto(s)
Ejercicio Físico , Motivación , Humanos , Femenino , Adulto , Estudios de Casos y Controles , Conductas Relacionadas con la Salud , Ontario
9.
Int J Popul Data Sci ; 8(1): 2152, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37670954

RESUMEN

Introduction: Knowledge of the sociodemographic, behavioural, and clinical characteristics of children visiting emergency departments (EDs) for mental health or substance use concerns in Ontario, Canada is lacking. Objectives: Using data from a population-based survey linked at the individual level to administrative health data, this study leverages a provincially representative sample and quasi-experimental design to strengthen inferences regarding the extent to which children's sociodemographic, behavioural, and clinical characteristics are associated with the risk of a mental health or substance use related ED visit. Methods: 9,301 children aged 4-17 years participating in the 2014 Ontario Child Health Study were linked retrospectively (6 months) and prospectively (12 months) with administrative health data on ED visits from the National Ambulatory Care Reporting System. Modified Poisson regression was used to examine correlates of mental health and substance use related ED visits among children aged 4-17 years over a 12-month period following their survey completion date, adjusting for ED visits in the 6 months prior to their survey completion date. Subgroup analyses of youths aged 14-17 years who independently completed survey content related to peer victimisation, substance use, and suicidality were also conducted. Results: Among children aged 4-17 years, older age, parental immigrant status, internalising problems, and perceived need for professional help were statistically significant correlates that increased the risk of a mental health or substance use related ED visit; low-income and suicidal ideation with attempt were statistically significant only among youths aged 14-17 years. Conclusions: Knowledge of the sociodemographic, behavioural, and clinical characteristics of children visiting EDs for mental health and substance use related concerns is required to better understand patient needs to coordinate effective emergency mental health care that optimises child outcomes, and to inform the development and targeting of upstream interventions that have the potential to prevent avoidable ED visits. Highlights: Growing rates of child mental health and substance use related ED visits have been observed internationally.A population-based survey linked at the individual level to administrative health data was used to examine the extent to which children's sociodemographic, behavioural, and clinical characteristics are associated with the risk of a mental health or substance use related ED visit in Ontario, Canada.Older age, low-income, parental immigrant status, perceived need for professional help, internalising problems, and suicidality increase the risk of an ED visit.Knowledge of the characteristics of children visiting EDs can be used to coordinate effective emergency mental health care that optimises child outcomes, and to inform the development and targeting of upstream interventions that have the potential to prevent avoidable ED visits.


Asunto(s)
Salud Mental , Trastornos Relacionados con Sustancias , Adolescente , Humanos , Niño , Ontario , Estudios Retrospectivos , Servicio de Urgencia en Hospital
10.
Nutrition ; 111: 112053, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37167923

RESUMEN

The aim of this review was to map the literature on the double burden of malnutrition (DBM) among women of reproductive age (WRA) and preschool children in low- and middle-income countries (LMICs). The study aimed to provide an understanding of how DBM construct has been defined in the current literature and to elucidate plausible mechanisms underlying DBM development and its common risk factor among the two subgroups. We systematically searched for literature from the following databases: EMBASE, CINAHL, MEDLINE, LILACS, Scopus and ProQuest Dissertations & Thesis Global and identified articles that specifically reported on the coexistence of undernutrition and overnutrition sequalae at the population, household, or individual levels among WRA and preschool children in LMICs. A thematic analysis using the Braun and Clarke approach was conducted on excerpts from the articles to reveal emerging themes underlying the occurrence of DBM from the included studies. Of the initial 15 112 articles found, 720 met the inclusion criteria. Anthropometric measures for overnutrition and undernutrition including body mass index for WRA and height-for-age, weight-for-age, and weight-for-height Z-scores for preschool children were frequently used indicators for defining DBM across all levels of assessment. In fewer cases, DBM was defined by the pairing of cardiometabolic risk factors (e.g., hypertension) as measures for overnutrition and micronutrient deficiency (e.g., iron deficiency) as measures for undernutrition. The following themes emerged as plausible mechanisms for DBM development: nutrition transition, breastfeeding, diet behavior, biological mechanism, and statistical artifact. Factors such as child age, child sex, maternal age, maternal education, maternal occupation, household food security, household wealth, urbanicity, and economic development were commonly associated with most of the DBM phenotypes. Our review findings showed that the understanding of the DBM in current literature is very ambiguous. There is need for future research to better understand the DBM construct and its etiology.


Asunto(s)
Desnutrición , Hipernutrición , Femenino , Humanos , Países en Desarrollo , Desnutrición/complicaciones , Desnutrición/epidemiología , Estado Nutricional , Hipernutrición/complicaciones , Hipernutrición/epidemiología , Sobrepeso/epidemiología , Prevalencia , Factores Socioeconómicos
11.
Can J Public Health ; 114(4): 613-628, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36976487

RESUMEN

OBJECTIVE: We investigated the impact of mandatory school nutrition policy on diet quality of Canadian school children using a quasi-experimental study design. METHODS: Using 24-h dietary recall data from the 2004 Canadian Community Health Survey (CCHS) Cycle 2.2 and 2015 CCHS - Nutrition, we constructed the Diet Quality Index (DQI). We used multivariable difference-in-differences regressions to quantify the DQI scores associated with school nutrition policy. We conducted stratified analyses by sex, school grade, household income, and food security status to gain additional insights into the impact of nutrition policy. RESULTS: We found that mandatory school nutrition policy was associated with an increased DQI score by 3.44 points (95% CI: 1.1, 5.8) during school-hours in intervention provinces relative to control provinces. DQI score was higher among males (3.8 points, 95% CI: 0.6, 7.1) than among females (2.9 points, 95% CI: -0.5, 6.3), and the score among students in elementary schools was higher (5.1 points, 95% CI: 2.3, 8.0) than that among high school students (0.4 points, 95% CI: -3.6, 4.5). We also found that DQI scores were higher for middle-high income and food secure households. CONCLUSION: Provincial mandatory school nutrition policy was associated with better diet quality among children and youth in Canada. Our findings suggest that other jurisdictions may consider implementing mandatory school nutrition policy.


RéSUMé: OBJECTIF: Nous avons étudié l'effet des politiques nutritionnelles en milieu scolaire sur la qualité du régime des enfants canadiens d'âge scolaire à l'aide d'un protocole d'étude quasi expérimental. MéTHODE: En utilisant les données des rappels alimentaires de 24 heures du cycle 2.2 de l'Enquête sur la santé dans les collectivités canadiennes (ESCC) de 2004 et de l'ESCC ­ Nutrition de 2015, nous avons construit un « indice de qualité du régime ¼ (IQR). Au moyen de régressions multivariées de la différence dans les différences, nous avons chiffré les valeurs de l'IQR associées aux politiques nutritionnelles en milieu scolaire. Nous avons mené des analyses stratifiées selon le sexe, le niveau scolaire, le revenu du ménage et l'état de sécurité alimentaire pour en savoir plus sur l'effet des politiques nutritionnelles. RéSULTATS: Nous avons constaté que les politiques nutritionnelles obligatoires en milieu scolaire étaient associées à des valeurs d'IQR de 3,44 points plus élevées (IC de 95 % : 1,1, 5,8) pendant les heures de classe dans les provinces ayant de telles politiques par rapport aux provinces témoins. La valeur d'IQR était plus élevée chez les garçons (3,8 points, IC de 95 % : 0,6, 7,1) que chez les filles (2,9 points, IC de 95 % : -0,5, 6,3), et la valeur chez les élèves des écoles primaires était plus élevée (5,1 points, IC de 95 % : 2,3, 8,0) que celle chez les élèves des écoles secondaires (0,4 points, IC de 95 % : -3,6, 4,5). Nous avons aussi constaté que les valeurs d'IQR étaient supérieures pour les ménages de revenu moyen à élevé et pour les ménages à l'abri de l'insécurité alimentaire. CONCLUSION: Les politiques nutritionnelles provinciales obligatoires en milieu scolaire étaient associées à un régime de meilleure qualité chez les enfants et les jeunes au Canada. Nos constatations indiquent que d'autres provinces et territoires pourraient envisager la mise en œuvre de politiques nutritionnelles en milieu scolaire.


Asunto(s)
Dieta , Instituciones Académicas , Masculino , Femenino , Humanos , Niño , Adolescente , Canadá , Estudiantes , Política Nutricional
12.
Nat Commun ; 14(1): 1698, 2023 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-36973244

RESUMEN

Hypusination is a unique post-translational modification of the eukaryotic translation factor 5A (eIF5A) that is essential for overcoming ribosome stalling at polyproline sequence stretches. The initial step of hypusination, the formation of deoxyhypusine, is catalyzed by deoxyhypusine synthase (DHS), however, the molecular details of the DHS-mediated reaction remained elusive. Recently, patient-derived variants of DHS and eIF5A have been linked to rare neurodevelopmental disorders. Here, we present the cryo-EM structure of the human eIF5A-DHS complex at 2.8 Å resolution and a crystal structure of DHS trapped in the key reaction transition state. Furthermore, we show that disease-associated DHS variants influence the complex formation and hypusination efficiency. Hence, our work dissects the molecular details of the deoxyhypusine synthesis reaction and reveals how clinically-relevant mutations affect this crucial cellular process.


Asunto(s)
Enfermedades Neurodegenerativas , Trastornos del Neurodesarrollo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH , Factores de Iniciación de Péptidos , Humanos , Microscopía por Crioelectrón , Factores de Iniciación de Péptidos/química , Procesamiento Proteico-Postraduccional , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/química , Factor 5A Eucariótico de Iniciación de Traducción
13.
J Am Heart Assoc ; 12(4): e026790, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36789849

RESUMEN

Background The environment plays a large role in the health of individuals; however, more research is needed to better understand aspects of the environment that most influence health. Specifically, our study examines how the social environment influences cardiovascular health (CVH). Methods and Results The social environment was characterized using measures of belonging and life and work stress in individuals, as well as nationally derived measures of marginalization, deprivation, economic status, and community well-being in neighborhoods. CVH was defined by the American Heart Association's Cardiovascular Health Index-a summed score of 7 clinical and behavioral components known to have the greatest impact on CVH. Data were obtained from the Canadian Community Health Survey 2015 to 2016 and multiple national data sources. Multilevel regression models were used to analyze the associations between CVH and the social environment. Overall, 27% of Canadians reported ideal CVH (6-7 score points), 68% reported intermediate CVH (3-5 score points), and 5% reported poor CVH (0-2 score points). The neighborhood environment contributed up to 7% of the differences in CVH between individuals. Findings indicated that residing in a neighborhood with greater community well-being (odds ratio [OR], 1.33 [95% CI, 1.26-1.41]) was associated with achieving higher odds of ideal CVH, while weaker community belonging (OR, 0.67 [95% CI, 0.62-0.72]) and residing in a neighborhood with greater marginalization (OR, 0.87 [95% CI, 0.82-0.91]) and deprivation (OR, 0.67 [95% CI, 0.64-0.69]) were associated with achieving lower odds of ideal CVH. Conclusions Aspects of individual-level social environment and residing in a neighborhood with a more favorable social environment were both independently and significantly associated with achieving ideal CVH.


Asunto(s)
Enfermedades Cardiovasculares , Sistema Cardiovascular , Humanos , Estados Unidos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Estado de Salud , Canadá/epidemiología , Medio Social , Factores de Riesgo
14.
Environ Res ; 219: 114999, 2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36565843

RESUMEN

OBJECTIVE: Ambient extreme temperatures have been associated with mental and behavior disorders (MBDs). However, few studies have assesed whether vulnerability factors such as ambient air pollution, pre-existing mental health conditions and residential environmental factors increase susceptibility. This study aims to evaluate the associations between short-term variations in outdoor ambient extreme temperatures and MBD-related emergency department (ED) visits and how these associations are modified by vulnerability factors. METHODS: We conducted a case-crossover study of 9,958,759 MBD ED visits in Alberta and Ontario, Canada made between March 1st, 2004 and December 31st, 2020. Daily average temperature was assigned to individual cases with ED visits for MBD using gridded data at a 1 km × 1 km spatial resolution. Conditional logistic regression was used to estimate associations between extreme temperatures (i.e., risk of ED visit at the 2.5th percentile temperature for cold and 97.5th percentile temperature for heat for each health region compared to the minimal temperature risk) and MBD ED visits. Age, sex, pre-existing mental health conditions, ambient air pollution (i.e. PM2.5, NO2 and O3) and residential environmental factors (neighborhood deprivation, residential green space exposure and urbanization) were evaluated as potential effect modifiers. RESULTS: Cumulative exposure to extreme heat over 0-5 days (odds ratio [OR] = 1.145; 95% CI: 1.121-1.171) was associated with ED visits for any MBD. However, cumulative exposure to extreme cold was associated with lower risk of ED visits for any MBD (OR = 0.981; 95% CI: 0.976-0.987). We also found heat to be associated with ED visits for specific MBDs such as substance use disorders, dementia, neurotic disorders, schizophrenia and personality behavior disorder. Individuals with pre-existing mental health conditions, those exposed to higher daily concentrations of NO2 and O3 and those residing in neighborhoods with greater material and social deprivation were at higher risk of heat-related MBD ED visits. Increasing tree canopy coverage appeared to mitigate risks of the effect of heat on MBD ED visits. CONCLUSIONS: Findings provide evidence that the impacts of heat on MBD ED visits may vary across different vulnerability factors.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Trastornos Mentales , Humanos , Contaminantes Atmosféricos/análisis , Temperatura , Calor , Estudios Cruzados , Dióxido de Nitrógeno/análisis , Trastornos Mentales/epidemiología , Alberta/epidemiología , Factores de Riesgo , Servicio de Urgencia en Hospital
15.
Can J Aging ; 42(2): 230-240, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36408684

RESUMEN

International studies have demonstrated associations between sleep problems and poor psychological well-being; however, Canadian data are limited. This study investigated this association using cross-sectional baseline data from the Canadian Longitudinal Study on Aging, a national survey of 30,097 community-dwelling adults, 45-85 years of age. Short sleep duration, sleep dissatisfaction, insomnia symptoms, and daytime impairment were consistently associated with a higher prevalence of dissatisfaction with life, psychological distress, and poor self-reported mental health. Long sleep duration was associated with a higher prevalence of psychological distress and poor self-reported mental health, but not with dissatisfaction with life. Associations between sleep problems and psychological distress were 11-18 per cent stronger in males. With each 10-year increase in age, the association between daytime impairment and life dissatisfaction increased by 11 per cent, and insomnia symptoms and poor mental health decreased by 11 per cent. Sleep problems in middle-aged and older adults warrant increased attention as a public health problem in Canada.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Masculino , Humanos , Persona de Mediana Edad , Anciano , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Bienestar Psicológico , Estudios Longitudinales , Estudios Transversales , Canadá/epidemiología , Envejecimiento/psicología , Trastornos del Sueño-Vigilia/epidemiología
16.
J Public Health (Oxf) ; 45(2): 295-303, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-35460257

RESUMEN

BACKGROUND: Weight status and weight perception have a significant impact on life satisfaction. As overweight prevalence increases in Canada, it is important to understand how accuracy of weight perception (AWP) is associated with life satisfaction. This study explored the association between AWP and life satisfaction among Canadian adults with and without anxiety and/or mood disorders. METHODS: Using data from the 2015-2018 cycles of the Canadian Community Health Survey, an indicator of AWP was created to capture concordance between perceived weight and actual weight status. Univariate and multivariate Gaussian generalized linear models were assessed while stratifying by sex and presence of anxiety and/or mood disorders. RESULTS: Our sample included 88 814 males and 106 717 females. For both sexes, perceiving oneself as overweight or underweight, regardless of actual weight status, was associated with lower life satisfaction (ß = -0.93 to -0.30), compared to those who accurately perceived their weight as 'just about right'. Perceiving oneself as overweight or underweight was associated with more pronounced differences in life satisfaction scores in those with anxiety and/or mood disorders (ß = -1.49 to -0.26) than in those without these disorders (ß = -0.76 to -0.25). CONCLUSION: Weight perception is more indicative of life satisfaction than actual weight status, especially in those with anxiety and/or mood disorders.


Asunto(s)
Sobrepeso , Percepción del Peso , Masculino , Femenino , Humanos , Adulto , Sobrepeso/epidemiología , Estudios Transversales , Trastornos del Humor/epidemiología , Delgadez , Salud Pública , Canadá/epidemiología , Índice de Masa Corporal , Ansiedad/epidemiología , Satisfacción Personal , Peso Corporal
17.
Artículo en Inglés | MEDLINE | ID: mdl-36141512

RESUMEN

The primary objective of this review was to synthesize studies assessing the relationships between high temperatures and cardiovascular disease (CVD)-related hospital encounters (i.e., emergency department (ED) visits or hospitalizations) in urban Canada and other comparable populations, and to identify areas for future research. Ovid MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, and Scopus were searched between 6 April and 11 April 2020, and on 21 March 2021, to identify articles examining the relationship between high temperatures and CVD-related hospital encounters. Studies involving patients with pre-existing CVD were also included. English language studies from North America and Europe were included. Twenty-two articles were included in the review. Studies reported an inconsistent association between high temperatures and ischemic heart disease (IHD), heart failure, dysrhythmia, and some cerebrovascular-related hospital encounters. There was consistent evidence that high temperatures may be associated with increased ED visits and hospitalizations related to total CVD, hyper/hypotension, acute myocardial infarction (AMI), and ischemic stroke. Age, sex, and gender appear to modify high temperature-CVD morbidity relationships. Two studies examined the influence of pre-existing CVD on the relationship between high temperatures and morbidity. Pre-existing heart failure, AMI, and total CVD did not appear to affect the relationship, while evidence was inconsistent for pre-existing hypertension. There is inconsistent evidence that high temperatures are associated with CVD-related hospital encounters. Continued research on this topic is needed, particularly in the Canadian context and with a focus on individuals with pre-existing CVD.


Asunto(s)
Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Infarto del Miocardio , Canadá/epidemiología , Enfermedades Cardiovasculares/epidemiología , Humanos , Revisiones Sistemáticas como Asunto , Temperatura
18.
EMBO J ; 41(20): e111318, 2022 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-36102610

RESUMEN

Post-translational modifications by ubiquitin-like proteins (UBLs) are essential for nearly all cellular processes. Ubiquitin-related modifier 1 (Urm1) is a unique UBL, which plays a key role in tRNA anticodon thiolation as a sulfur carrier protein (SCP) and is linked to the noncanonical E1 enzyme Uba4 (ubiquitin-like protein activator 4). While Urm1 has also been observed to conjugate to target proteins like other UBLs, the molecular mechanism of its attachment remains unknown. Here, we reconstitute the covalent attachment of thiocarboxylated Urm1 to various cellular target proteins in vitro, revealing that, unlike other known UBLs, this process is E2/E3-independent and requires oxidative stress. Furthermore, we present the crystal structures of the peroxiredoxin Ahp1 before and after the covalent attachment of Urm1. Surprisingly, we show that urmylation is accompanied by the transfer of sulfur to cysteine residues in the target proteins, also known as cysteine persulfidation. Our results illustrate the role of the Uba4-Urm1 system as a key evolutionary link between prokaryotic SCPs and the UBL modifications observed in modern eukaryotes.


Asunto(s)
Ubiquitina , Ubiquitinas , Anticodón , Proteínas Portadoras/metabolismo , Cisteína , Peroxirredoxinas , Azufre/metabolismo , Ubiquitina/metabolismo , Ubiquitinas/metabolismo
19.
Acad Emerg Med ; 29(11): 1329-1337, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36043233

RESUMEN

OBJECTIVES: This study had two objectives: (1) to estimate the prevalence of preventable emergency department (ED) visits during the 2016-2020 time period among those living in 19 large urban centers in Alberta and Ontario, Canada, and (2) to assess if the definition of preventable ED visits matters in estimating the prevalence. METHODS: A retrospective, population-based study of ED visits that were reported to the National Ambulatory Care Reporting System from April 1, 2016, to March 31, 2020, was conducted. Preventable ED visits were operationalized based on the following approaches: (1) Canadian Triage and Acuity Scale (CTAS), (2) ambulatory care-sensitive conditions (ACSC), (3) family practice-sensitive conditions (FPSC), and (4) sentinel nonurgent conditions (SNC). The overall proportion of ED visits that were preventable was estimated. We also estimated the adjusted relative risks of preventable ED visits by patients' sex and age, fiscal year, province of residence, and census metropolitan area (CMA) of residence. RESULTS: There were 20,171,319 ED visits made by 8,919,618 patients ages 1 to 74 who resided in one of the 19 CMAs in Alberta or Ontario. On average, there were 2.26 visits per patient over the period of 4 fiscal years; most patients made one (44.22%) or two ED visits (20.72%). The overall unadjusted prevalence of preventable ED visits varied by definition; 35.33% of ED visits were defined as preventable based on CTAS, 12.88% based on FPSC, 3.41% based on SNC, and 2.33% based on ACSC. CONCLUSIONS: There is a substantial level of variation in prevalence estimates across definitions of preventable ED visits, and care should be taken when interpreting these estimates as each has a different meaning and may lead to different conclusions. The conceptualization and measurement of preventable ED visits is complex and multifaceted and may not be adequately captured by a single definition.


Asunto(s)
Atención Ambulatoria , Servicio de Urgencia en Hospital , Humanos , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Ontario/epidemiología , Alberta/epidemiología
20.
Age Ageing ; 51(8)2022 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-35930724

RESUMEN

INTRODUCTION: multimorbidity has become an increasingly important issue for many populations around the world, including Canada. The objectives of this study were to estimate the prevalence of multimorbidity at first follow-up and to identify factors associated with multimorbidity using data from the Canadian Longitudinal Study on Aging (CLSA). METHODS: this study included 27,701 community-dwelling participants in the first follow-up of the CLSA. Multimorbidity was operationalised using two definitions (Public Health and Primary Care), as well as the cut-points of two or more chronic conditions (MM2+) and three or more chronic conditions (MM3+). The prevalence of multimorbidity was calculated at first follow-up and multivariable regression models were used to identify correlates of multimorbidity occurrence. RESULTS: the prevalence of multimorbidity at first follow-up was 32.3% among males and 39.3% among females when using the MM2+ Public Health definition, whereas the prevalence was 67.2% among males and 75.8% among females when using the MM2+ Primary Care definition. Older age, lower alcohol consumption, lower physical activity levels, dissatisfaction with sleep quality, dissatisfaction with life and experiencing social limitations due to health conditions were significantly associated with increased odds of multimorbidity for both males and females, regardless of the definition of multimorbidity used. CONCLUSION: various sociodemographic, behavioural and psychosocial factors are associated with multimorbidity. Future research should continue to examine how the prevalence of multimorbidity changes with time and how these changes may be related to specific risk factors. This future research should be supplemented with studies examining the longitudinal impacts of multimorbidity over time.


Asunto(s)
Vida Independiente , Multimorbilidad , Anciano , Envejecimiento/psicología , Canadá/epidemiología , Enfermedad Crónica , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Prevalencia
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