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1.
J Affect Disord ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38772508

RESUMO

BACKGROUND: Mental health deteriorated in the early stages of the COVID-19 pandemic, but improved relatively quickly as restrictions were eased, suggesting overall resilience. However, longer-term follow-up of mental health in the general population is scarce. METHODS: We examined mental health trajectories in 5624 adults (58 % women; aged 18-97 years) from the Specchio-COVID19 cohort, using the Generalised Anxiety Disorder scale-2 and the Patient Health Questionnaire-2, administered each month from February to June 2021, and in Spring 2022 and 2023. RESULTS: Depressive and anxiety symptoms declined during a pandemic wave from February to May 2021 (ß = -0.06 [-0.07, -0.06]; -0.06 [-0.07, -0.05]), and remained lower at longer-term follow-up than at the start of the wave. Loneliness also declined over time, with the greatest decline during the pandemic wave (ß = -0.25 [-0.26, -0.24]). Many higher-risk groups, including socioeconomically disadvantaged individuals, those with a chronic condition, and those living alone had poorer mental health levels throughout the study period. Women and younger individuals had a faster improvement in mental health during the pandemic wave. Loneliness trajectories were associated with mental health trajectories throughout the study period. LIMITATIONS: We cannot definitively conclude that the observed changes in mental health were due to experiences of the pandemic. CONCLUSIONS: While there was a need for additional mental health support during stricter policy responses to COVID-19, overall, mental health improved relatively soon after measures were eased. Nevertheless, the persistence of mental health disparities highlights the need for further efforts from the government and healthcare practitioners to support vulnerable groups beyond the pandemic.

2.
J Gen Intern Med ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528233

RESUMO

BACKGROUND: Self-rated health is a subjective yet valuable indicator of overall health status, influenced by various factors including physical, psychological, and socio-economic elements. Self-rated health could be telling and used by primary care physicians to evaluate overall present and predictive health. DESIGN: This study investigates the longitudinal evolution of self-rated health in Switzerland during the COVID-19 pandemic, focusing on the association of persistently favorable self-rated health with various predictors. PARTICIPANTS: This study based on the Specchio cohort, a population-based digital study in Geneva Switzerland, involved participants completing questionnaires from 2021 to 2023. MAIN MEASURES: Self-rated health was assessed alongside factors like physical and mental health, socio-economic status, and lifestyle behaviors. KEY RESULTS: The study included 7006 participants in 2021, and 3888 participants who answered all three follow-ups (2021, 2022, and 2023). At baseline, 34.9% of individuals reported very good, 54.6% reported good, 9.6% reported average, and 1.0% reported poor to very poor self-rated health. Overall, 29.1% had a worsening in their self-rated health between 2021 and 2023. A subset of participants (12.1%) maintained very good self-rated health throughout, demonstrating persistently favorable self-rated health during the COVID-19 pandemic. Positive health behaviors were associated with persistently favorable self-rated health (exercise aOR 1.13 [1.03-1.24]; healthy diet aOR 2.14 [1.70-2.68]; less screen time aOR 1.28 [1.03-1.58]; and better sleep quality aOR 2.48 [2.02-3.04]). Mental health and social support also played significant roles. CONCLUSION: The study underscores the significance of healthy lifestyle choices and social support in maintaining favorable self-rated health, particularly during challenging times like the COVID-19 pandemic. Primary care physicians should focus on promoting these factors, integrating these actions in their routine consultations, and advising patients to undertake in socially engaging activities to improve overall health perceptions and outcomes.

3.
Sci Rep ; 14(1): 3538, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347020

RESUMO

Oilseed rape (Brassica napus) is an important global oil crop, with spring and winter varieties grown commercially. To understand the transcriptomic differences between these varieties, we collected transcriptomes from apex and leaf tissue from a spring variety, Westar, and a winter variety, Tapidor, before, during, and after vernalisation treatment, until the plants flowered. Large transcriptomic differences were noted in both varieties during the vernalisation treatment because of temperature and day length changes. Transcriptomic alignment revealed that the apex transcriptome reflects developmental state, whereas the leaf transcriptome is more closely aligned to the age of the plant. Similar numbers of copies of genes were expressed in both varieties during the time series, although key flowering time genes exhibited expression pattern differences. BnaFLC copies on A2 and A10 are the best candidates for the increased vernalisation requirement of Tapidor. Other BnaFLC copies show tissue-dependent reactivation of expression post-cold, with these dynamics suggesting some copies have retained or acquired a perennial nature. BnaSOC1 genes, also related to the vernalisation pathway, have expression profiles which suggest tissue subfunctionalisation. This understanding may help to breed varieties with more consistent or robust vernalisation responses, of special importance due to the milder winters resulting from climate change.


Assuntos
Brassica napus , Transcriptoma , Fatores de Tempo , Melhoramento Vegetal , Folhas de Planta/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas
4.
SSM Popul Health ; 23: 101472, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37560087

RESUMO

Background: Children and adolescents are highly vulnerable to the impact of sustained stressors during developmentally sensitive times. We investigated how demographic characteristics intersect with socioeconomic dimensions to shape the social patterning of quality of life and mental health in children and adolescents, two years into the COVID-19 pandemic. Methods: We used data from the prospective SEROCoV-KIDS cohort study of children and adolescents living in Geneva (Switzerland, 2022). We conducted an intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy by nesting participants within 48 social strata defined by intersecting sex, age, immigrant background, parental education and financial hardship in Bayesian multilevel logistic models for poor health-related quality of life (HRQoL, measured with PedsQL) and mental health difficulties (measured with the Strengths and Difficulties Questionnaire). Results: Among participants aged 2-17 years, 240/2096 (11.5%, 95%CI 10.1-12.9) had poor HRQoL and 105/2135 (4.9%, 95%CI 4.0-5.9) had mental health difficulties. The predicted proportion of poor HRQoL ranged from 3.4% for 6-11 years old Swiss girls with highly educated parents and no financial hardship to 34.6% for 12-17 years old non-Swiss girls with highly educated parents and financial hardship. Intersectional strata involving adolescents and financial hardship showed substantially worse HRQoL than their counterparts. Between-stratum variations in the predicted frequency of mental health difficulties were limited (range 4.4%-6.5%). Conclusions: We found considerable differences in adverse outcomes across social strata. Our results suggest that, post-pandemic, interventions to address social inequities in HRQoL should focus on specific intersectional strata involving adolescents and families experiencing financial hardship, while those aiming to improve mental health should target all children and adolescents.

5.
Swiss Med Wkly ; 153(4): 40049, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37011595

RESUMO

OBJECTIVE: We aimed to examine factors associated with parental willingness to vaccinate their children against COVID-19. METHODS: We surveyed adults included in a digital longitudinal cohort study composed of participants in previous SARS-CoV-2 serosurveys conducted in Geneva, Switzerland. In February 2022, an online questionnaire collected information on COVID-19 vaccination acceptance, parental willingness to vaccinate their children aged ≥5 years and reasons for vaccination preference. We used multivariable logistic regression to assess the demographic, socioeconomic and health-related factors associated with being vaccinated and with parental intention to vaccinate their children. RESULTS: We included 1,383 participants (56.8% women; 69.3% aged 35-49 years). Parental willingness to vaccinate their children increased markedly with the child's age: 84.0%, 60.9% and 21.2%, respectively, for parents of adolescents aged 16-17 years, 12-15 years and 5-12 years. For all child age groups, unvaccinated parents more frequently indicated not intending to vaccinate their children than vaccinated parents. Refusal to vaccine children was associated with having a secondary education (1.73; 1.18-2.47) relative to a tertiary education and with middle (1.75; 1.18-2.60) and low (1.96; 1.20-3.22) household income relative to high income. Refusal to vaccine their children was also associated with only having children aged 12-15 years (3.08; 1.61-5.91), aged 5-11 years (19.77; 10.27-38.05), or in multiple age groups (6.05; 3.22-11.37), relative to only having children aged 16-17 years. CONCLUSION: Willingness to vaccinate children was high for parents of adolescents aged 16-17 years but decreased significantly with decreasing child age. Unvaccinated, socioeconomically disadvantaged parents and those with younger children were less likely to be willing to vaccinate their children. These results are important for vaccination programs and developing communication strategies to reach vaccine-hesitant groups, both in the context of COVID-19 and in the prevention of other diseases and future pandemics.


Assuntos
COVID-19 , Adolescente , Adulto , Humanos , Criança , Feminino , Idoso de 80 Anos ou mais , Masculino , COVID-19/prevenção & controle , Suíça , SARS-CoV-2 , Vacinas contra COVID-19 , Estudos Transversais , Estudos Longitudinais , Pais , Vacinação
6.
BMC Public Health ; 23(1): 785, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37118691

RESUMO

BACKGROUND: Sport participation is an important component of a healthy lifestyle and is known to be more common among privileged individuals. However, few studies examined socio-demographic patterns of participation by type of activity. This study aims at quantifying socio-economic inequalities in sport participation by sport type, and to analyse their trend over 15 years. METHODS: We used 2005-2019 data from the Bus Santé study, a yearly population-based cross-sectional survey of Geneva adults. Sport participation was defined as reporting at least one sporting activity over the previous week; educational level, household income and occupational position were used as indicators of socio-economic position. Socio-economic inequalities in sport participation, and their trend over time, were examined using the relative and slope indexes of inequality (RII/SII). RESULTS: Out of 7769 participants (50.8% women, mean age 46 years old), 60% participated in a sporting activity. Results showed that the higher the socioeconomic circumstances, the higher the sport participation (RII = 1.78; 95% Confidence Interval (CI): 1.64-1.92; SII = 0.33; 95%CI: 0.29-0.37 for education). Relative inequalities varied per sport e.g., 0.68 (95%CI: 0.44-1.07) for football and 4.25 (95%CI: 2.68-6.75) for tennis/badminton for education. Yearly absolute inequalities in sport participation tended to increase between 2005 and 2019 for household income, especially among women and older adults. CONCLUSIONS: We observed strong socio-economic inequalities in sport participation in Geneva, with different magnitude depending on the sport type. These inequalities seemed to increase over the 2005-2019 period. Our results call for tailored measures to promote the participation of socially disadvantaged populations in sporting activities.


Assuntos
Esportes , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Fatores Socioeconômicos , Estudos Transversais , Escolaridade , Disparidades nos Níveis de Saúde
7.
J Psychiatr Res ; 158: 192-201, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36592533

RESUMO

There are concerns about acute and long-term mental health effects of the COVID-19 pandemic. This study examined the prevalence and predictors of psychological distress before, during, and after a pandemic wave in Switzerland, 2021. Prevalence of psychological distress was estimated in adults aged 35-96 years using the General Health Questionnaire-12 administered in June 2021 (Specchio-COVID19 cohort, N = 3965), and compared to values from 2003 to 2006 (CoLaus|PsyCoLaus cohort, N = 5667). Anxiety and depression were assessed from February to June 2021 using the Generalised Anxiety Disorder scale-2 and the Patient Health Questionnaire-2, respectively. Prevalence of psychological distress in June 2021, after the pandemic wave (16.0% [95% CI, 14.6%-17.4%]) was comparable to pre-pandemic levels (15.1% [14.0%-16.2%]). Anxiety and depression were highest at the start of the pandemic wave in February 2021, and declined from February to June with the relaxation of measures. Predictors of psychological distress included being younger, female, a single parent, unemployed, a change in working hours or job loss in the past 6 months, greater perceived severity and contagiousness of COVID-19, and self-reported post COVID-19. By June 2021, following a pandemic wave, prevalence of psychological distress in Switzerland was closer to pre-pandemic levels. These findings highlight the need for additional mental health support during times of stricter government policies relating to COVID-19; yet they also suggest that individuals can adapt relatively quickly to the changing context.


Assuntos
COVID-19 , Angústia Psicológica , Adulto , Feminino , Humanos , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Prevalência , Suíça/epidemiologia , Depressão/epidemiologia , Ansiedade/epidemiologia
8.
Lancet Reg Health Eur ; 24: 100547, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36474728

RESUMO

Background: More than two years into the COVID-19 pandemic, most of the population has developed anti-SARS-CoV-2 antibodies from infection and/or vaccination. However, public health decision-making is hindered by the lack of up-to-date and precise characterization of the immune landscape in the population. Here, we estimated anti-SARS-CoV-2 antibodies seroprevalence and cross-variant neutralization capacity after Omicron became dominant in Geneva, Switzerland. Methods: We conducted a population-based serosurvey between April 29 and June 9, 2022, recruiting children and adults of all ages from age-stratified random samples of the general population of Geneva, Switzerland. We tested for anti-SARS-CoV-2 antibodies using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein, and for antibody neutralization capacity against different SARS-CoV-2 variants using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. We estimated seroprevalence and neutralization capacity using a Bayesian modeling framework accounting for the demographics, vaccination, and infection statuses of the Geneva population. Findings: Among the 2521 individuals included in the analysis, the estimated total antibodies seroprevalence was 93.8% (95% CrI 93.1-94.5), including 72.4% (70.0-74.7) for infection-induced antibodies. Estimates of neutralizing antibodies in a representative subsample (N = 1160) ranged from 79.5% (77.1-81.8) against the Alpha variant to 46.7% (43.0-50.4) against the Omicron BA.4/BA.5 subvariants. Despite having high seroprevalence of infection-induced antibodies (76.7% [69.7-83.0] for ages 0-5 years, 90.5% [86.5-94.1] for ages 6-11 years), children aged <12 years had substantially lower neutralizing activity than older participants, particularly against Omicron subvariants. Overall, vaccination was associated with higher neutralizing activity against pre-Omicron variants. Vaccine booster alongside recent infection was associated with higher neutralizing activity against Omicron subvariants. Interpretation: While most of the Geneva population has developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, less than half has neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection confers the greatest neutralization capacity, including against Omicron. Funding: General Directorate of Health in Geneva canton, Private Foundation of the Geneva University Hospitals, European Commission ("CoVICIS" grant), and a private foundation advised by CARIGEST SA.

9.
BMJ Open ; 12(11): e063504, 2022 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-36410813

RESUMO

OBJECTIVES: To estimate the prevalence of children and adolescents reporting persistent symptoms after SARS-CoV-2 infection. DESIGN: A random sample of children and adolescents participated with their family members to a serological survey including a blood drawing for detecting antibodies targeting the SARS-CoV-2 nucleocapsid (N) protein and a questionnaire on COVID-19-related symptoms experienced since the beginning of the pandemic. SETTING: The study took place in the canton of Geneva, Switzerland, between June and July 2021. PARTICIPANT: 660 children aged between 2 and 17 years old. PRIMARY AND SECONDARY OUTCOME: The primary outcome was the persistence of symptoms beyond 4 weeks comparing seropositive and seronegative participants. The type of declared symptoms were also studied as well as associated risk factors. RESULTS: Among seropositive children, the sex-adjusted and age-adjusted prevalence of symptoms lasting longer than 2 weeks was 18.3%, compared with 11.1% among seronegatives (adjusted prevalence difference (ΔaPrev)=7.2%, 95% CI: 1.5% to 13.0%). Among adolescents aged 12-17 years, we estimated the prevalence of experiencing symptoms lasting over 4 weeks to be 4.4% (ΔaPrev,95% CI: -3.8% to 13.6%), whereas no seropositive child aged 2-11 reported symptoms of this duration. The most frequently declared symptoms were fatigue, headache and loss of smell. CONCLUSIONS: We estimated the prevalence of experiencing persistent symptoms lasting over 4 weeks to be around 4% among adolescents, which represents a large absolute number, and should raise awareness and concern. We did not observe meaningful differences of persistent symptoms between seropositive and seronegative younger children, suggesting that they may be less affected than their older counterparts.


Assuntos
COVID-19 , Adolescente , Criança , Humanos , Pré-Escolar , COVID-19/epidemiologia , Estudos Transversais , SARS-CoV-2 , Pandemias , Projetos de Pesquisa
10.
Front Public Health ; 10: 874252, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211707

RESUMO

Background: SARS-CoV-2 infection and its health consequences have disproportionally affected disadvantaged socio-economic groups globally. This study aimed to analyze the association between socio-economic conditions and having developed antibodies for-SARS-CoV-2 in a population-based sample in the canton of Geneva, Switzerland. Methods: Data was obtained from a population-based serosurvey of adults in Geneva and their household members, between November and December, 2020, toward the end of the second pandemic wave in the canton. Participants were tested for antibodies for-SARS-CoV-2. Socio-economic conditions representing different dimensions were self-reported. Mixed effects logistic regressions were conducted for each predictor to test its association with seropositive status as the main outcome. Results: Two thousand eight hundred and eighty-nine adults completed the study questionnaire and were included in the final analysis. Retired participants and those living in suburban areas had lower odds of a seropositive result when compared to employed participants (OR: 0.42, 95% CI: 0.20-0.87) and those living in urban areas (OR: 0.67, 95% CI: 0.46-0.97), respectively. People facing financial hardship for less than a year had higher odds of a seropositive result compared to those who had never faced them (OR: 2.23, 95% CI: 1.01-4.95). Educational level, occupational position, and household income were not associated with being seropositive, nor were ethnicity or country of birth. Discussion: While conventional measures of socio-economic position did not seem to be related to the risk of being infected in this sample, this study sheds lights on the importance of examining the broader social determinants of health when evaluating the differential impact of the pandemic within the population.


Assuntos
COVID-19 , Adulto , COVID-19/epidemiologia , Estudos Transversais , Humanos , SARS-CoV-2 , Fatores Socioeconômicos , Suíça/epidemiologia
11.
BMJ Open ; 12(1): e055515, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35105645

RESUMO

INTRODUCTION: The COVID-19 pandemic has affected billions of people around the world both directly through the infection itself and indirectly through its economic, social and sanitary impact. Collecting data over time is essential for the understanding of the disease spread, the incidence of COVID-19-like symptoms, the level and dynamics of immunity, as well as the long-term impact of the pandemic. The objective of the study was to set up a longitudinal follow-up of adult participants of serosurveys carried out in the canton of Geneva, Switzerland, during the COVID-19 pandemic. This follow-up aims at monitoring COVID-19 related symptoms and SARS-CoV-2 seroconversion, as well as the overall impact of the pandemic on several dimensions of health and on socioeconomic factors over a period of at least 2 years. METHODS AND ANALYSIS: Serosurvey participants were invited to create an account on the dedicated digital platform Specchio-COVID19 (https://www.specchio-covid19.ch/). On registration, an initial questionnaire assessed sociodemographic and lifestyle characteristics (including housing conditions, physical activity, diet, alcohol and tobacco consumption), anthropometry, general health and experience related to COVID-19 (symptoms, COVID-19 test results, quarantines, hospitalisations). Weekly, participants were invited to fill in a short questionnaire with updates on self-reported COVID-19-compatible symptoms, SARS-CoV-2 infection testing and vaccination. A more detailed questionnaire about mental health, well-being, risk perception and changes in working conditions was proposed monthly. Supplementary questionnaires were proposed at regular intervals to assess more in depth the impact of the pandemic on physical and mental health, vaccination adherence, healthcare consumption and changes in health behaviours. At baseline, serology testing allowed to assess the spread of SARS-CoV-2 infection among the general population and subgroups of workers. Additionally, seropositive participants and a sample of randomly selected participants were invited for serologic testing at regular intervals in order to monitor both the seropersistance of anti-SARS-CoV-2 antibodies and the seroprevalence of anti-SARS-CoV-2 antibodies in the population of the canton of Geneva. ETHICS AND DISSEMINATION: The study was approved by the Cantonal Research Ethics Commission of Geneva, Switzerland (CCER Project ID 2020-00881). Results will be disseminated in a variety of ways, via the Specchio-COVID-19 platform, social media posts, press releases and through regular scientific dissemination methods (open-access articles, conferences).


Assuntos
COVID-19 , Adulto , Estudos de Coortes , Seguimentos , Humanos , Pandemias , SARS-CoV-2 , Estudos Soroepidemiológicos , Suíça/epidemiologia
12.
PLoS One ; 17(1): e0262104, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35041708

RESUMO

Renal clinical chemistry only detects kidney dysfunction after considerable damage has occurred and is imperfect in predicting long term outcomes. Consequently, more sensitive markers of early damage and better predictors of progression are being urgently sought, to better support clinical decisions and support shorter clinical trials. Transglutaminase 2 (TG2) is strongly implicated in the fibrotic remodeling that drives chronic kidney disease (CKD). We hypothesized that urinary TG2 and its ε-(γ-glutamyl)-lysine crosslink product could be useful biomarkers of kidney fibrosis and progression. Animal models: a rat 4-month 5/6th subtotal nephrectomy model of CKD and a rat 8-month streptozotocin model of diabetic kidney disease had 24-hour collection of urine, made using a metabolic cage, at regular periods throughout disease development. Patients: Urine samples from patients with CKD (n = 290) and healthy volunteers (n = 33) were collected prospectively, and progression tracked for 3 years. An estimated glomerular filtration rate (eGFR) loss of 2-5 mL/min/year was considered progressive, with rapid progression defined as > 5 mL/min/year. Assays: TG2 was measured in human and rat urine samples by enzyme-linked immunosorbent assay (ELISA) and ε-(γ-glutamyl)-lysine by exhaustive proteolytic digestion and amino acid analysis. Urinary TG2 and ε-(γ-glutamyl)-lysine increased with the development of fibrosis in both animal model systems. Urinary TG2 was 41-fold higher in patients with CKD than HVs, with levels elevated 17-fold by CKD stage 2. The urinary TG2:creatinine ratio (UTCR) was 9 ng/mmol in HV compared with 114 ng/mmol in non-progressive CKD, 1244 ng/mmol in progressive CKD and 1898 ng/mmol in rapidly progressive CKD. Both urinary TG2 and ε-(γ-glutamyl)-lysine were significantly associated with speed of progression in univariate logistic regression models. In a multivariate model adjusted for urinary TG2, ε-(γ-glutamyl)-lysine, age, sex, urinary albumin:creatinine ratio (UACR), urinary protein:creatinine ratio (UPCR), and CKD stage, only TG2 remained statistically significant. Receiver operating characteristic (ROC) curve analysis determined an 86.4% accuracy of prediction of progression for UTCR compared with 73.5% for UACR. Urinary TG2 and ε-(γ-glutamyl)-lysine are increased in CKD. In this pilot investigation, UTCR was a better predictor of progression in patients with CKD than UACR. Larger studies are now warranted to fully evaluate UTCR value in predicting patient outcomes.


Assuntos
Biomarcadores/urina , Nefropatias Diabéticas/metabolismo , Nefrectomia/efeitos adversos , Proteína 2 Glutamina gama-Glutamiltransferase/urina , Insuficiência Renal Crônica/metabolismo , Estreptozocina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/urina , Dipeptídeos/urina , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Ratos , Análise de Regressão , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/urina
13.
J Med Chem ; 65(1): 757-784, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-34967602

RESUMO

A diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe 2 that was used to build target confidence, concerns over the ketone moiety led to the replacement of this group. The successful replacement of this moiety was achieved with pyrimidine carboxamides derived from cyclic secondary amines that were extensively characterized using biophysical and crystallographic methods as competitive inhibitors of vanin-1. Through optimization of potency and physicochemical and ADME properties, and guided by co-crystal structures with vanin-1, 3 was identified with a suitable profile for advancement into preclinical development.


Assuntos
Amidoidrolases/antagonistas & inibidores , Piridinas/síntese química , Piridinas/farmacologia , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Cristalografia por Raios X , Sulfato de Dextrana , Cães , Descoberta de Drogas , Feminino , Proteínas Ligadas por GPI/antagonistas & inibidores , Ensaios de Triagem em Larga Escala , Cetonas/química , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Piridinas/farmacocinética , Ratos , Relação Estrutura-Atividade
14.
Swiss Med Wkly ; 151: w30080, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34908389

RESUMO

OBJECTIVE: This study aimed to assess acceptance of COVID-19 vaccination as well as its sociodemographic and clinical determinants, 3 months after the launch of the vaccination programme in Geneva, Switzerland. METHODS: In March 2021, an online questionnaire was proposed to adults included in a longitudinal cohort study of previous SARS-CoV-2 serosurveys carried out in the canton of Geneva, which included former participants of a population-based health survey as well as individuals randomly sampled from population registries, and their household members. Questions were asked about COVID-19 vaccination acceptance, reasons for acceptance or refusal and attitudes to vaccination in general. Data on demographic (age, sex, education, income, professional status, living conditions) and health-related characteristics (having a chronic disease, COVID-19 diagnosis, smoking status) were assessed at inclusion in the cohort (December 2020). The overall vaccination acceptance was standardised according to the age, sex, and education distribution in the Geneva population. RESULTS: Overall, 4067 participants (completion rate of 77.4%) responded to the survey between 17 March and 1 April 2021. The mean age of respondents was 53.3 years and 56.0% were women. At the time of the survey, 17.2% of respondents had already been vaccinated with at least one dose or had made an appointment to get vaccinated, and an additional 58.5% intended or rather intended to get vaccinated. The overall acceptance of COVID-19 vaccination standardised to the age, sex and education distribution of the population of Geneva was 71.8%, with a higher acceptance among men than women, older adults compared with younger adults, high-income individuals compared with those with a low income, and participants living in urban and semi-urban areas compared with rural areas. Acceptance was lower among individuals having completed apprenticeships and secondary education than those with tertiary education. The most common reasons reported by participants intending to get vaccinated were the desire to "get back to normal", to protect themselves, their community and/or society,and their relatives or friends against the risk of infection by SARS-CoV-2, as well as the desire to travel. Less than half (45.6%) of participants having children were willing or rather willing to have their children vaccinated against COVID-19 if it were recommended by public health authorities. CONCLUSION: Although our study found a 71.8% weighted acceptance of COVID-19 vaccination, there were noticeable sociodemographic disparities in vaccination acceptance. These data will be useful for public health measures targeting hesitant populations when developing health communication strategies.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Idoso , Teste para COVID-19 , Criança , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinação
15.
Swiss Med Wkly ; 151: w30079, 2021 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-34846113

RESUMO

OBJECTIVE: This study aimed to assess the public perception of COVID-19 vaccination certificates as well as potential differences between individuals. METHODS: Between 17 March and 1 April 2021, a self-administered online questionnaire was proposed to all persons aged 18 years and older participating in the longitudinal follow-up of SARS-CoV-2 seroprevalence studies in Geneva, Switzerland. The questionnaire covered aspects of individual and collective benefits, and allowed participants to select contexts in which vaccination certificates should be presented. Results were presented as the proportion of persons agreeing or disagreeing with the implementation of vaccination certificates, selecting specific contexts where certificates should be presented, and agreeing or disagreeing with the potential risks related to certificates. Logistic regression was used to calculate odds ratios for factors associated with certificate non-acceptance. RESULTS: Overall, 4067 individuals completed the questionnaire (response rate 77.4%; mean age 53.3 ± standard deviation 14.4 years; 56.1% were women). About 61.0% of participants agreed or strongly agreed that a vaccination certificate was necessary in certain contexts and 21.6% believed there was no context where vaccination certificates should be presented. Contexts where a majority of participants perceived a vaccination certificate should be presented included jobs where others would be at risk of COVID-related complications (60.7%), jobs where employees would be at risk of getting infected (58.7%), or to be exempt from quarantine when travelling abroad (56.0%). Contexts where fewer individuals perceived the need for vaccination certificates to be presented were participation in large gatherings (36.9%), access to social venues (35.5%), or sharing the same workspace (21.5%). Younger age, no intent for vaccination, and not believing vaccination to be an important step in surmounting the pandemic were factors associated with certificate non-acceptance. CONCLUSION: This large population-based study showed that the general adult population in Geneva, Switzerland, agreed with the implementation of vaccination certificates in work-related and travel-related contexts. However, this solution was perceived as unnecessary for access to large gatherings or social venues, or to share the same workspace. Differences were seen with age, sex, education, socioeconomic status, and vaccination willingness and perception, highlighting the importance of taking personal and sociodemographic variation into consideration when predicting acceptance of such certificates.


Assuntos
COVID-19 , Viagem , Adulto , Vacinas contra COVID-19 , Feminino , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , Estudos Soroepidemiológicos , Suíça , Doença Relacionada a Viagens , Vacinação
16.
Euro Surveill ; 26(43)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34713799

RESUMO

BackgroundUp-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape and to guide public health decisions.AimWe estimate seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and 6 months into the vaccination campaign.MethodsWe conducted a population-based cross-sectional serosurvey between 1 June and 7 July 2021, recruiting participants from age- and sex-stratified random samples of the general population. We tested participants for anti-SARS-CoV-2 antibodies targeting the spike (S) or nucleocapsid (N) proteins using the Roche Elecsys immunoassays. We estimated the anti-SARS-CoV-2 antibodies seroprevalence following vaccination and/or infection (anti-S antibodies), or infection only (anti-N antibodies).ResultsAmong 3,355 individuals (54.1% women; 20.8% aged < 18 years and 13.4% aged ≥ 65 years), 2,161 (64.4%) had anti-S antibodies and 906 (27.0%) had anti-N antibodies. The total seroprevalence was 66.1% (95% credible interval (CrI): 64.1-68.0). We estimated that 29.9% (95% Crl: 28.0-31.9) of the population developed antibodies after infection; the rest having developed antibodies via vaccination. Seroprevalence estimates differed markedly across age groups, being lowest among children aged 0-5 years (20.8%; 95% Crl: 15.5-26.7) and highest among older adults aged ≥ 75 years (93.1%; 95% Crl: 89.6-96.0). Seroprevalence of antibodies developed via infection and/or vaccination was higher among participants with higher educational level.ConclusionMost of the population has developed anti-SARS-CoV-2 antibodies, despite most teenagers and children remaining vulnerable to infection. As the SARS-CoV-2 Delta variant spreads and vaccination rates stagnate, efforts are needed to address vaccine hesitancy, particularly among younger individuals and to minimise spread among children.


Assuntos
COVID-19 , SARS-CoV-2 , Adolescente , Idoso , Anticorpos Antivirais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Programas de Imunização , Lactente , Recém-Nascido , Masculino , Pandemias , Estudos Soroepidemiológicos , Suíça
17.
Nat Commun ; 12(1): 3455, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103517

RESUMO

Limited data exist on SARS-CoV-2 infection rates across sectors and occupations, hindering our ability to make rational policy, including vaccination prioritization, to protect workers and limit SARS-CoV-2 spread. Here, we present results from our SEROCoV-WORK + study, a serosurvey of workers recruited after the first wave of the COVID-19 pandemic in Geneva, Switzerland. We tested workers (May 18-September 18, 2020) from 16 sectors and 32 occupations for anti-SARS-CoV-2 IgG antibodies. Of 10,513 participants, 1026 (9.8%) tested positive. The seropositivity rate ranged from 4.2% in the media sector to 14.3% in the nursing home sector. We found considerable within-sector variability: nursing home (0%-31.4%), homecare (3.9%-12.6%), healthcare (0%-23.5%), public administration (2.6%-24.6%), and public security (0%-16.7%). Seropositivity rates also varied across occupations, from 15.0% among kitchen staff and 14.4% among nurses, to 5.4% among domestic care workers and 2.8% among journalists. Our findings show that seropositivity rates varied widely across sectors, between facilities within sectors, and across occupations, reflecting a higher exposure in certain sectors and occupations.


Assuntos
Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Tamanho da Amostra , Suíça/epidemiologia , Adulto Jovem
19.
Viruses ; 14(1)2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-35062247

RESUMO

The burden of COVID-19 has disproportionately impacted the elderly, who are at increased risk of severe disease, hospitalization, and death. This cross-sectional study aimed to assess the association between SARS-CoV-2 seroprevalence among nursing home staff, and cumulative incidence rates of COVID-19 cases, hospitalizations, and deaths among residents. Staff seroprevalence was estimated within the SEROCoV-WORK+ study between May and September 2020 across 29 nursing homes in Geneva, Switzerland. Data on nursing home residents were obtained from the canton of Geneva for the period between March and August 2020. Associations were assessed using Spearman's correlation coefficient and quasi-Poisson regression models. Overall, seroprevalence among staff ranged between 0 and 31.4%, with a median of 8.3%. A positive association was found between staff seroprevalence and resident cumulative incidence of COVID-19 cases (correlation coefficient R = 0.72, 95%CI 0.45-0.87; incidence rate ratio [IRR] = 1.10, 95%CI 1.07-1.17), hospitalizations (R = 0.59, 95%CI 0.25-0.80; IRR = 1.09, 95%CI 1.05-1.13), and deaths (R = 0.71, 95%CI 0.44-0.86; IRR = 1.12, 95%CI 1.07-1.18). Our results suggest that SARS-CoV-2 transmission between staff and residents may contribute to the spread of the virus within nursing homes. Awareness among nursing home professionals of their likely role in the spread of SARS-CoV-2 has the potential to increase vaccination coverage and prevent unnecessary deaths due to COVID-19.


Assuntos
COVID-19/epidemiologia , Casas de Saúde/estatística & dados numéricos , COVID-19/mortalidade , COVID-19/transmissão , Estudos Transversais , Pessoal de Saúde/estatística & dados numéricos , Hospitalização , Humanos , Incidência , Transmissão de Doença Infecciosa do Profissional para o Paciente , SARS-CoV-2/imunologia , Estudos Soroepidemiológicos , Suíça/epidemiologia
20.
Trends Cancer ; 7(1): 57-76, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32948502

RESUMO

Ribosome biogenesis (RiBi) is one of the most complex and energy demanding processes in human cells, critical for cell growth and proliferation. Strong causal links between inherited and acquired impairment in RiBi with cancer pathogenesis are emerging, pointing to RiBi as an attractive therapeutic target for cancer. Here, we will highlight new knowledge about causes of excessive or impaired RiBi and the impact of these changes on protein synthesis. We will also discuss how new knowledge about secondary consequences of dysregulated RiBi and protein synthesis, including proteotoxic stress, metabolic alterations, adaptive transcriptional and translational programs, and the impaired ribosome biogenesis checkpoint (IRBC) provide a foundation for the development of new anticancer therapies.


Assuntos
Benzotiazóis/farmacologia , Carcinogênese/efeitos dos fármacos , Naftiridinas/farmacologia , Neoplasias/tratamento farmacológico , RNA Polimerase I/antagonistas & inibidores , Ribossomos/metabolismo , Benzotiazóis/uso terapêutico , Carcinogênese/genética , Carcinogênese/patologia , Reparo do DNA/genética , Humanos , Mutação , Naftiridinas/uso terapêutico , Neoplasias/genética , Neoplasias/patologia , Biogênese de Organelas , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/genética , Proteólise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Polimerase I/metabolismo , Proteínas Ribossômicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Mutações Sintéticas Letais , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação/efeitos dos fármacos
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