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1.
Acta Otolaryngol ; 141(11): 989-993, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34694199

RESUMO

BACKGROUND: The effect of Covid-19 infection on nasal mucociliary clearance (MCC) is unknown. AIMS/OBJECTIVES: The aim of this study is to investigate the relationship between Covid-19 and nasal MCC in terms of smoking, Covid-19 symptoms and treatment. METHODS: Thirty-six patients who were hospitalized in the pandemic ward due to Covid-19 and 36 volunteers (Covid-19 negative test result) who presented to the otolaryngology outpatient clinic with non-nasal symptoms were included in this study. The Saccharin test was performed in both groups to evaluate nasal MCC. RESULTS: The patients and control groups were not significantly different in terms of age and gender. The nasal MCC time was significantly higher in the patient group compared to the control group (19.18 ± 10.84 min and 13.78 ± 8.18 min, p = .003). CONCLUSIONS AND SIGNIFICANCE: In this study, we found that Covid-19 prolonged nasal MCC time regardless of age. We suggest that corticosteroids should be included in the treatment of Covid-19, both with its symptom reduction and its positive effect on MCC duration.


Assuntos
COVID-19/fisiopatologia , Depuração Mucociliar/fisiologia , Mucosa Nasal/fisiopatologia , Fumar/fisiopatologia , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Adulto , Amidas/uso terapêutico , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/tratamento farmacológico , Estudos de Casos e Controles , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Depuração Mucociliar/efeitos dos fármacos , Pirazinas/uso terapêutico
2.
Nat Commun ; 12(1): 5945, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642315

RESUMO

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.


Assuntos
Antígenos HLA/imunologia , Papillomavirus Humano 16/imunologia , Imunidade Humoral , Neoplasias Bucais/imunologia , Neoplasias Orofaríngeas/imunologia , Infecções por Papillomavirus/imunologia , Idoso , Anticorpos Antivirais/biossíntese , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos HLA/classificação , Antígenos HLA/genética , Haplótipos , Papillomavirus Humano 16/patogenicidade , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Locos de Características Quantitativas , Proteínas Repressoras/genética , Proteínas Repressoras/imunologia , Fatores de Risco , Fumar/fisiopatologia
3.
Nat Commun ; 12(1): 5431, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521849

RESUMO

Small cell lung cancer (SCLC) is a highly malignant tumor which is eventually refractory to any treatment. Intratumoral heterogeneity (ITH) may contribute to treatment failure. However, the extent of ITH in SCLC is still largely unknown. Here, we subject 120 tumor samples from 40 stage I-III SCLC patients to multi-regional whole-exome sequencing. The most common mutant genes are TP53 (88%) and RB1 (72%). We observe a medium level of mutational heterogeneity (0.30, range 0.0~0.98) and tumor mutational burden (TMB, 10.2 mutations/Mb, range 1.1~51.7). Our SCLC samples also exhibit somatic copy number variation (CNV) across all patients, with an average CNV ITH of 0.49 (range 0.02~0.99). In terms of mutation distribution, ITH, TMB, mutation clusters, and gene signatures, patients with combined SCLC behave roughly the same way as patients with pure SCLC. This condition also exists in smoking patients and patients with EGFR mutations. A higher TMB per cluster is associated with better disease-free survival while single-nucleotide variant ITH is linked to worse overall survival, and therefore these features may be used as prognostic biomarkers for SCLC. Together, these findings demonstrate the intratumoral genetic heterogeneity of surgically resected SCLC and provide insights into resistance to treatment.


Assuntos
Heterogeneidade Genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Proteínas de Ligação a Retinoblastoma/genética , Carcinoma de Pequenas Células do Pulmão/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Variações do Número de Cópias de DNA , Receptores ErbB/genética , Receptores ErbB/metabolismo , Exoma , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Proteínas de Ligação a Retinoblastoma/metabolismo , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/cirurgia , Fumar/fisiopatologia , Análise de Sobrevida , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
4.
Rev Med Virol ; 31(6): e2288, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34472152

RESUMO

SARS Coronavirus-2 is one of the most widespread viruses globally during the 21st century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.


Assuntos
COVID-19/patologia , Tosse/patologia , Dispneia/patologia , Fadiga/patologia , Febre/patologia , SARS-CoV-2/patogenicidade , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/mortalidade , COVID-19/virologia , Comorbidade , Tosse/tratamento farmacológico , Tosse/mortalidade , Tosse/virologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatologia , Dispneia/tratamento farmacológico , Dispneia/mortalidade , Dispneia/virologia , Fadiga/tratamento farmacológico , Fadiga/mortalidade , Fadiga/virologia , Febre/tratamento farmacológico , Febre/mortalidade , Febre/virologia , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Fatores Imunológicos/uso terapêutico , Prognóstico , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/fisiopatologia , Índice de Gravidade de Doença , Fumar/fisiopatologia , Análise de Sobrevida
5.
PLoS One ; 16(8): e0255692, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34351990

RESUMO

INTRODUCTION: In the absence of a universally accepted association between smoking and COVID-19 health outcomes, we investigated this relationship in a representative cohort from one of the world's highest tobacco consuming regions. This is the first report from the Middle East and North Africa that tackles specifically the association of smoking and COVID-19 mortality while demonstrating a novel sex-discrepancy in the survival rates among patients. METHODS: Clinical data for 743 hospitalized COVID-19 patients was retrospectively collected from the leading centre for COVID-19 testing and treatment in Lebanon. Logistic regression, Kaplan-Meier survival curves and Cox proportional hazards model adjusted for age and stratified by sex were used to assess the association between the current cigarette smoking status of patients and COVID-19 outcomes. RESULTS: In addition to the high smoking prevalence among our hospitalized COVID-19 patients (42.3%), enrolled smokers tended to have higher reported ICU admissions (28.3% vs 16.6%, p<0.001), longer length of stay in the hospital (12.0 ± 7.8 vs 10.8 days, p<0.001) and higher death incidences as compared to non-smokers (60.5% vs 39.5%, p<0.001). Smokers had an elevated odds ratio for death (OR = 2.3, p<0.001) and for ICU admission (OR = 2.0, p<0.001) which remained significant in a multivariate regression model. Once adjusted for age and stratified by sex, our data revealed that current smoking status reduces survival rate in male patients ([HR] = 1.9 [95% (CI), 1.029-3.616]; p = 0.041) but it does not affect survival outcomes among hospitalized female patients([HR] = 0.79 [95% CI = 0.374-1.689]; p = 0.551). CONCLUSION: A high smoking prevalence was detected in our hospitalized COVID-19 cohort combined with worse prognosis and higher mortality rate in smoking patients. Our study was the first to highlight potential sex-specific consequences for smoking on COVID-19 outcomes that might further explain the higher vulnerability to death from this disease among men.


Assuntos
COVID-19/mortalidade , Fumar/efeitos adversos , Adulto , Idoso , COVID-19/epidemiologia , Teste para COVID-19 , Estudos de Coortes , Comorbidade/tendências , Feminino , Mortalidade Hospitalar , Hospitalização/tendências , Humanos , Estimativa de Kaplan-Meier , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/patogenicidade , Fatores Sexuais , Fumar/fisiopatologia , Taxa de Sobrevida
6.
Thorax ; 76(6): 618-620, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34157671

RESUMO

Tobacco habit still represents the leading preventable cause of morbidity and mortality worldwide. Heat-not-burn cigarettes (HNBCs) are considered as an alternative to traditional combustion cigarettes (TCCs) due to the lack of combustion and the absence of combustion-related specific toxicants. The aim of this observational study was to assess the effect of HNBC on endothelial function, oxidative stress and platelet activation in chronic adult TCC smokers and HNBC users. The results showed that both HNBC and TCC display an adverse phenotype in terms of endothelial function, oxidative stress and platelet activation. Future randomised studies are strongly warranted to confirm these data.


Assuntos
Endotélio Vascular/fisiopatologia , Temperatura Alta , Estresse Oxidativo , Ativação Plaquetária/fisiologia , Fumar/metabolismo , Produtos do Tabaco/estatística & dados numéricos , Vaping , Idoso , Sistemas Eletrônicos de Liberação de Nicotina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/fisiopatologia
7.
Medicine (Baltimore) ; 100(23): e26266, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115020

RESUMO

ABSTRACT: Waon therapy (WT) has been used as a thermal therapy in chronic heart failure patients. However, its effect in patients with hypertension is unclear. This study aimed to reveal the hypotensive effect of WT in patients with hypertension. WT was performed on 31 patients with hypertension (63.9 ±â€Š11.9 years, male: 17) on standard hypertension treatment focusing on lifestyle modification and medication. Systolic and diastolic blood pressures were measured before and after WT using an upper arm automated sphygmomanometer. We investigated the effect of single and repeated (1 time/d, >5 times) WT sessions on blood pressure and further compared its effect between current smoking (n = 11, 55.4 ±â€Š6.4 years, 8.5 ±â€Š2.4 times) and non-smoking (n = 11, 66.9 ±â€Š8.5 years, 12.2 ±â€Š5.9 times) groups. A total of 370 sessions of WT were conducted. Systolic and diastolic blood pressures significantly decreased after a single WT session (systolic blood pressure: 118.5 ±â€Š10.1 to 115.1 ±â€Š9.0 mm Hg, P < .001; diastolic blood pressure: 70.5 ±â€Š6.4 to 65.9 ±â€Š5.3 mm Hg, P < .001). The blood pressure decrease following repeated WT was not significant when all participants were considered (systolic blood pressure: 122.3 ±â€Š15.2 to 116.9 ±â€Š19.6 mm Hg; diastolic blood pressure: 73.8 ±â€Š16.7 to 68.2 ±â€Š13.2 mm Hg); however, it was significant in the non-smoking group (systolic blood pressure: 124.2 ±â€Š11.3 to 108.8 ±â€Š13.4 mm Hg, P < .001; diastolic blood pressure: 73.6 ±â€Š4.9 to 62.1 ±â€Š7.6 mm Hg, P < .001). Repeated WT (at least 5 sessions) decreased blood pressure in patients with hypertension, especially in non-smokers. WT is a simple method to reduce blood pressure in non-smoking patients with hypertension.


Assuntos
Determinação da Pressão Arterial/métodos , Hipertensão , Hipertermia Induzida/métodos , Fumar , Pressão Sanguínea/fisiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertensão/psicologia , Hipertensão/terapia , Japão , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , não Fumantes/estatística & dados numéricos , Fumar/efeitos adversos , Fumar/fisiopatologia , Resultado do Tratamento
8.
PLoS One ; 16(5): e0251888, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34014988

RESUMO

BACKGROUND: The smoking-paradox of a better outcome in ischemic stroke patients who smoke may be due to increased efficacy of thrombolysis. We investigated the effect of smoking on outcome following endovascular therapy (EVT) with mechanical thrombectomy alone versus in combination with intra-arterial (IA-) thrombolysis. METHODS: The primary endpoint was defined by three-month modified Rankin Scale (mRS). We performed a generalized linear model and reported relative risks (RR) for smoking (adjustment for age, sex, hypertension, atrial fibrillation, stroke severity, time to EVT) in patient data stemming from the Virtual International Stroke Trials Archive-Endovascular database. RESULTS: Among 1,497 patients, 740(49.4%) were randomized to EVT; among EVT patients, 524(35.0%) received mechanical thrombectomy alone and 216(14.4%) received it in combination with IA-thrombolysis. Smokers (N = 396) had lower mRS scores (mean 2.9 vs. 3.2; p = 0.02) and mortality rates (10% vs. 17.3%; p<0.001) in univariate analysis. In all patients and in patients treated with mechanical thrombectomy alone, smoking had no effect on outcome in regression analyses. In patients who received IA-thrombolysis (N = 216;14%), smoking had an adjusted RR of 1.65 for an mRS≤1 (95%CI 0.77-3.55). Treatment with IA-thrombolysis itself led to reduced RR for favorable outcome (adjusted RR 0.30); interaction analysis of IA-thrombolysis and smoking revealed that non-smokers with IA-thrombolysis had mRS≤2 in 47 cases (30%, adjusted RR 0.53 [0.41-0.69]) while smokers with IA-thrombolysis had mRS≤2 in 23 cases (38%, adjusted RR 0.61 [0.42-0.87]). CONCLUSIONS: Smokers had no clear clinical benefit from EVT that incorporates IA-thrombolysis.


Assuntos
AVC Isquêmico/terapia , Trombólise Mecânica/métodos , Fumar/efeitos adversos , Terapia Trombolítica/métodos , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/fisiopatologia , Procedimentos Endovasculares/métodos , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/reabilitação , Masculino , Pessoa de Meia-Idade , Fumar/fisiopatologia , Trombectomia/efeitos adversos , Fumar Tabaco/efeitos adversos , Resultado do Tratamento
9.
Mayo Clin Proc ; 96(7): 1770-1781, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33775420

RESUMO

OBJECTIVE: To evaluate the contemporary geographic trends in cardiovascular health in the United States and its relationship with geographic distribution of cardiovascular mortality. METHODS: By use of a retrospective cross-sectional design, the 2011-2017 Behavioral Risk Factor Surveillance System (BRFSS) was queried to determine the age-adjusted prevalence of cardiovascular health index (CVHI) metrics (sum of ideal blood pressure, blood glucose concentration, lipid levels, body mass index, smoking, physical activity, and diet). Cardiovascular health was estimated as both continuous (0 to 7 points) and categorical (ideal, intermediate, poor) variables from the BRFSS. Age-adjusted cardiovascular mortality for 2017 was obtained from the Centers for Disease Control and Prevention WONDER database. RESULTS: Among 1,362,529 American adult participants of the BRFSS 2011-2017 and all American residents in 2017, the CVHI score increased from 3.89±0.004 in 2011 to 3.96±0.005 in 2017 (Ptrend<.001) nationally, with modest improvement across all regions (Ptrend<.05 for all). Ideal cardiovascular health prevalence improved in the northeastern (Ptrend=.03) and southern regions (Ptrend=.002). In 2017, the prevalence of coronary heart disease (6.8%; 95% CI, 6.5% to 7.1%) and stroke (3.7%; 95% CI, 3.4% to 3.9%) was highest in the southern region. The CVHI score (3.81±0.01) and the prevalence of ideal cardiovascular health (12.2%; 95% CI, 11.7% to 12.7%) were lowest in the southern United States. This corresponded to the higher cardiovascular mortality in the southern region (233.0 [95% CI, 232.2- to 33.8] per 100,000 persons). CONCLUSION: Despite a modest improvement in CVHI, only 1 in 6 Americans has ideal cardiovascular health with significant geographic differences. These differences correlate with the geographic distribution of cardiovascular mortality. An urgent unmet need exists to mitigate the geographic disparities in cardiovascular morbidity and mortality.


Assuntos
Glicemia/análise , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares , Sistema Cardiovascular , Nível de Saúde , Fumar , Sistema de Vigilância de Fator de Risco Comportamental , Índice de Massa Corporal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/psicologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Estudos Transversais , Dieta/psicologia , Dieta/estatística & dados numéricos , Exercício Físico/fisiologia , Exercício Físico/psicologia , Feminino , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Prevalência , Fatores de Risco , Fumar/epidemiologia , Fumar/fisiopatologia , Estados Unidos/epidemiologia
10.
J Toxicol Environ Health A ; 84(13): 536-552, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-33715603

RESUMO

Workers in swine operations may be at increased risk of developing respiratory problems. These respiratory conditions are more prevalent among workers who are smokers. Tumor necrosis factor (TNF) genes play an important role in human immune responses to various respiratory hazards. This study aimed to investigate whether polymorphisms in TNF genes might alter the effects of smoking on lung function among workers in swine operations. Three hundred and seventy-four full-time workers from large swine operations and 411 non-farming rural dwellers in Saskatchewan were included in this study. Information on demographic and lifestyle characteristics, pulmonary function, and blood samples were obtained. Multiple linear regression analyses were used in the statistical analysis. Three promoter polymorphisms (rs1799724, rs361525, and rs1800629) in the TNF gene were investigated. Only the interaction term between smoking status and rs1799724 was significant in the multiple regression models. Among workers with the rs1799724 polymorphism (TT+TC), current smokers exhibited significantly lower lung function than nonsmokers. These associations were not observed among workers with the wild-type (CC). These findings were not observed among non-farming rural dwellers. Data demonstrated the possible involvement of TNF gene in (1) development of adverse respiratory conditions among workers who are smokers, (2) importance of smoking cessation among workers, especially those with polymorphisms in the TNF gene, and (3) potential implications in treatment, screening, and prevention.


Assuntos
Fazendeiros/estatística & dados numéricos , Pulmão/fisiologia , Polimorfismo de Nucleotídeo Único , Fumar/fisiopatologia , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Criação de Animais Domésticos , Animais , Feminino , Humanos , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Saskatchewan , Sus scrofa , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
11.
PLoS One ; 16(3): e0247746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651799

RESUMO

The purpose of this study was to clarify the odds ratio for association between working hours and obesity in Korean male wage workers and investigate the role of sleep duration. This study is a cross-sectional one using large-scale national data from the Korea National Health and Nutrition Examination Survey collected between 2010 and 2015 to evaluate 2,592 male wage workers (between the ages of 19 and 60 years). Obesity was defined as 25kg/m2 or more and working hours per week were categorized into <40, 40-49, 50-59, and ≥60 hours. Multiple regression analysis was performed to examine the odds ratio for association between working hours and obesity, after controlling for age, education, income, marital status, smoking, drinking, physical activity, daily energy intake, sleep duration, hypertension, diabetes, dyslipidemia, work schedule, and job category. Next, to study the mediating effect of sleep duration on the association between working hours and obesity, an analysis was performed using the Baron and Kenny method and the Sobel test. Results showed that workers with 50 to 59 hours had 1.4 times higher odds (odds ratio [OR] = 1.4, confidence interval [CI]: 1.11-1.85) of obesity and workers with 60 hours or more had 1.4 times higher odds (OR = 1.4, CI: 1.06-1.90) of obesity than workers with less than 40 hours. Sleep was found to have a mediating effect on the association between working time and body mass index. Therefore, the results of this analysis suggest that practitioners should identify potential factors such as working time and sleeping time when preventing work-related obesity.


Assuntos
Emprego/estatística & dados numéricos , Inquéritos Nutricionais/estatística & dados numéricos , Obesidade/epidemiologia , Admissão e Escalonamento de Pessoal/estatística & dados numéricos , Sono/fisiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Dislipidemias/epidemiologia , Dislipidemias/fisiopatologia , Escolaridade , Emprego/economia , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Renda/estatística & dados numéricos , Masculino , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Obesidade/prevenção & controle , Razão de Chances , Análise de Regressão , República da Coreia/epidemiologia , Fatores de Risco , Fumar/epidemiologia , Fumar/fisiopatologia
12.
Drug Alcohol Depend ; 221: 108593, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33611027

RESUMO

BACKGROUND: Craving is a major contributor to drug-seeking and relapse. Although the ventral striatum (VS) is a primary neural correlate of craving, strategies aimed at manipulating VS function have not resulted in efficacious treatments. This incongruity may be because the VS does not influence craving in isolation. Instead, craving is likely mediated by communication between the VS and other neural substrates. Thus, we examined how striatal functional connectivity (FC) with key nodes of networks involved in addiction affects relief of craving, which is an important step in identifying viable treatment targets. METHODS: Twenty-four nicotine-dependent non-abstinent women completed two resting-state (rs) fMRI scans, one before and one following smoking a cigarette in the scanner, and provided craving ratings before and after smoking the cigarette. A seed-based approach was used to examine rsFC between the VS, putamen and germane craving-related brain regions; the dorsolateral prefrontal cortex (dlPFC), the posterior cingulate cortex, and the anterior ventral insula. RESULTS: Smoking a cigarette was associated with a decrease in craving. Relief of craving correlated with increases in right dlPFC- bilateral VS (r = 0.57, p = 0.003, corrected) as did increased right dlPFC-left putamen coupling (r = 0.62, p = 0.001, corrected). CONCLUSIONS: Smoking-induced relief of craving is associated with enhanced rsFC between the dlPFC, a region that plays a pivotal role in decision making, and the striatum, the neural structure underlying motivated behavior. These findings are highly consistent with a burgeoning literature implicating dlPFC-striatal interactions as a neurobiological substrate of craving.


Assuntos
Fissura , Nicotina , Córtex Pré-Frontal/fisiologia , Tabagismo/fisiopatologia , Adulto , Comportamento Aditivo , Encéfalo/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Corpo Estriado , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/fisiopatologia , Fumar/fisiopatologia , Fumar Tabaco
13.
Medicina (Kaunas) ; 57(1)2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33435185

RESUMO

Effective platelet inhibition is the main goal of the antiplatelet therapy recommended as a standard treatment in the secondary prevention of non-embolic ischemic stroke. Acetylsalicylic acid (aspirin) and clopidogrel are commonly used for this purpose worldwide. A low biological response to antiplatelet agents is a phenomenon that significantly reduces the therapeutic and protective properties of the therapy. The mechanisms leading to high on-treatment platelet reactivity are still unclear and remain multifactorial. The aim of the current review is to establish the background of resistance to antiplatelet agents commonly used in the secondary prevention of ischemic stroke and to explain the possible mechanisms. The most important factors influencing the incidence of a low biological response were demonstrated. The similarities and the differences in resistance to both drugs are emphasized, which may facilitate the selection of the appropriate antiplatelet agent in relation to specific clinical conditions and comorbidities. Despite the lack of indications for the routine assessment of platelet reactivity in stroke subjects, this should be performed in selected patients from the high-risk group. Increasing the detectability of low antiaggregant responders, in light of its negative impact on the prognosis and clinical outcomes, can contribute to a more individualized approach and modification of the antiplatelet therapy to maximize the therapeutic effect in the secondary prevention of stroke.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Resistência a Medicamentos/fisiologia , AVC Isquêmico/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Disponibilidade Biológica , Interações Medicamentosas , Resistência a Medicamentos/genética , Humanos , Falência Renal Crônica/fisiopatologia , Síndrome Metabólica/fisiopatologia , Variantes Farmacogenômicos/genética , Ativação Plaquetária , Testes de Função Plaquetária , Medição de Risco , Prevenção Secundária , Fumar/fisiopatologia , Acidente Vascular Cerebral/prevenção & controle
14.
Hum Genet ; 140(6): 849-861, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33385171

RESUMO

Mitochondrial (MT) dysfunction is a hallmark of aging and has been associated with most aging-related diseases as well as immunological processes. However, little is known about aging, lifestyle and genetic factors influencing mitochondrial DNA (mtDNA) abundance. In this study, mtDNA abundance was estimated from the weighted intensities of probes mapping to the MT genome in 295,150 participants from the UK Biobank. We found that the abundance of mtDNA was significantly elevated in women compared to men, was negatively correlated with advanced age, higher smoking exposure, greater body-mass index, higher frailty index as well as elevated red and white blood cell count and lower mortality. In addition, several biochemistry markers in blood-related to cholesterol metabolism, ion homeostasis and kidney function were found to be significantly associated with mtDNA abundance. By performing a genome-wide association study, we identified 50 independent regions genome-wide significantly associated with mtDNA abundance which harbour multiple genes involved in the immune system, cancer as well as mitochondrial function. Using mixed effects models, we estimated the SNP-heritability of mtDNA abundance to be around 8%. To investigate the consequence of altered mtDNA abundance, we performed a phenome-wide association study and found that mtDNA abundance is involved in risk for leukaemia, hematologic diseases as well as hypertension. Thus, estimating mtDNA abundance from genotyping arrays has the potential to provide novel insights into age- and disease-relevant processes, particularly those related to immunity and established mitochondrial functions.


Assuntos
Envelhecimento/genética , DNA Mitocondrial/genética , Genoma Mitocondrial , Doenças Hematológicas/genética , Hipertensão/genética , Leucemia/genética , Idoso , Envelhecimento/imunologia , Bancos de Espécimes Biológicos , Índice de Massa Corporal , DNA Mitocondrial/imunologia , Contagem de Eritrócitos , Feminino , Estudo de Associação Genômica Ampla , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/imunologia , Doenças Hematológicas/patologia , Humanos , Hipertensão/epidemiologia , Hipertensão/imunologia , Hipertensão/patologia , Imunidade Inata , Padrões de Herança/imunologia , Leucemia/epidemiologia , Leucemia/imunologia , Leucemia/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/imunologia , Polimorfismo de Nucleotídeo Único , Fumar/genética , Fumar/fisiopatologia , Reino Unido/epidemiologia
15.
Nucleic Acids Res ; 49(D1): D1358-D1364, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33151297

RESUMO

A multitude of pharmacokinetics studies have been published. However, due to the lack of an open database, pharmacokinetics data, as well as the corresponding meta-information, have been difficult to access. We present PK-DB (https://pk-db.com), an open database for pharmacokinetics information from clinical trials. PK-DB provides curated information on (i) characteristics of studied patient cohorts and subjects (e.g. age, bodyweight, smoking status, genetic variants); (ii) applied interventions (e.g. dosing, substance, route of application); (iii) pharmacokinetic parameters (e.g. clearance, half-life, area under the curve) and (iv) measured pharmacokinetic time-courses. Key features are the representation of experimental errors, the normalization of measurement units, annotation of information to biological ontologies, calculation of pharmacokinetic parameters from concentration-time profiles, a workflow for collaborative data curation, strong validation rules on the data, computational access via a REST API as well as human access via a web interface. PK-DB enables meta-analysis based on data from multiple studies and data integration with computational models. A special focus lies on meta-data relevant for individualized and stratified computational modeling with methods like physiologically based pharmacokinetic (PBPK), pharmacokinetic/pharmacodynamic (PK/PD), or population pharmacokinetic (pop PK) modeling.


Assuntos
Bases de Dados Factuais , Modelos Estatísticos , Anotação de Sequência Molecular , Medicamentos sob Prescrição/farmacocinética , Área Sob a Curva , Peso Corporal , Cafeína/farmacocinética , Ensaios Clínicos como Assunto , Anticoncepcionais Orais/administração & dosagem , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Ontologia Genética , Meia-Vida , Humanos , Fumar/fisiopatologia
16.
J Nucl Med ; 62(3): 405-411, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32764123

RESUMO

Chronic obstructive pulmonary disease (COPD) is the most common noninfectious pulmonary disease among people living with HIV, independent of smoking. However, the cause for this enhanced susceptibility remains unclear, and the effects of HIV on pulmonary perfusion and ventilation are unknown. Methods: We used PET/CT in 46 smokers and nonsmokers, 23 of whom had documented HIV infection. Emphysema was assessed by CT and perfusion by 13N (13NN) PET scans. After removal of image noise, vertical and axial gradients in perfusion were calculated. We tested for differences in the total spatial heterogeneity of perfusion (CV2 Qtotal) and its components (CV2 Qtotal = CV2 Qvgrad [vertical gradient] + CV2 Qzgrad [axial gradient] + CV2 Qr [residual heterogeneity]) among groups. Results: There were no significant differences in demographic parameters among groups, and all subjects had minimal radiographic evidence of emphysema. Compared with controls, nonsmokers living with HIV had a significantly greater CV2 Qr/CV2 Qtotal (0.48 vs. 0.36, P = 0.05) and reduced CV2 Qvgrad/CV2 Qtotal (0.46 vs. 0.65, P = 0.038). Smokers also had a reduced CV2 Qvgrad/CV2 Qtotal, however, there was no significant difference in CV2 Qvgrad/CV2 Qtotal between smokers living with and without HIV (0.39 vs. 0.34, P = 0.58), despite a decreased vertical perfusion gradient (Qvgrad) in smokers living with HIV. Conclusion: In nonsmokers living with well-controlled HIV and minimal radiographic emphysema, HIV infection contributes to pulmonary perfusion abnormalities similar to smokers. These data indicate the onset of subclinical pulmonary perfusion abnormalities that could herald the development of significant lung disease in these susceptible individuals.


Assuntos
Infecções por HIV/diagnóstico por imagem , Infecções por HIV/fisiopatologia , Tomografia por Emissão de Pósitrons , Circulação Pulmonar , Fumar/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Am J Med Sci ; 361(1): 75-82, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32988598

RESUMO

BACKGROUND: Individuals with cystic fibrosis (CF) have difficulty maintaining optimal vitamin D status due to pancreatic insufficiency-induced malabsorption, inadequate sunlight exposure, and poor intake of vitamin D containing foods. Vitamin D deficiency may increase the risk of pulmonary exacerbations of CF. The objective of this study was to assess factors impacting vitamin D status in patients with CF recently hospitalized for a pulmonary exacerbation of CF. METHODS: This was a pre-planned analysis of vitamin D intake in patients enrolled in a multi-center, double-blind, randomized controlled study examining vitamin D therapy for pulmonary exacerbation of CF. Demographic information, responses from a habitual sun exposure questionnaire and food frequency questionnaire, and vitamin D supplement usage were queried and compared to serum 25-hydroxyvitamin D (25(OH)D) concentrations. RESULTS: A total of 48 subjects were included in this analysis. Subjects were taking approximately 1,200 IU of vitamin D daily. Reported vitamin D intake, age, race, employment, and education were not significantly associated with vitamin D status in this population. However, smoking status, sunlight exposure in the last 3 years, and skin type (in the bivariate model) were all significantly associated with vitamin D status (all p<0.05). CONCLUSIONS: Sunlight exposure was the most predictive determinant of vitamin D status in patients with CF prior to pulmonary exacerbation. Subjects reported vitamin D intake below the recommended amounts. The role and mode of optimizing vitamin D status prior to a pulmonary exacerbation needs further investigation.


Assuntos
Fibrose Cística/etiologia , Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Vitaminas/sangue , Adulto , Feminino , Georgia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Fatores de Risco , Fenômenos Fisiológicos da Pele , Fumar/fisiopatologia , Luz Solar , Vitamina D/sangue , Deficiência de Vitamina D/sangue
18.
Nicotine Tob Res ; 23(2): 390-396, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-32804236

RESUMO

INTRODUCTION: Little is known about the natural use behavior of new and emerging tobacco products due to the limited availability of reliable puff topography monitors suitable for ambulatory deployment. An understanding of use behavior is needed to assess the health impact of emerging tobacco products and inform realistic standardized topography profiles for emissions studies. The purpose of this study is to validate four monitors: the wPUM cigalike, vapepen, hookah, and cigarette monitors. AIMS AND METHODS: Each wPUM monitor was characterized and validated for range, accuracy, and resolution for puff flow rate, duration, volume, and interpuff gap in a controlled laboratory environment. Monitor repeatability was assessed for each wPUM monitor using four separate week-long natural environment monitoring studies including cigalike, vapepen, hookah, and cigarette users. RESULTS: The valid flow rate range was 10 to 100 mL/s for cigalike and cigarette monitors, 10 to 95 mL/s for vapepen monitors, and 50 to 400 mL/s hookah monitors. Flow rate accuracy was within ±2 mL/s for cigalike, vapepen, and cigarette monitors and ±6 mL/s for the hookah monitor. Durations and interpuff gaps as small as 0.2 s were measured to within ±0.07 s. Monitor calibrations changed by 4.7% (vapepen), 1.5% (cigarette), 0.5% (cigalike), and 0.1% (hookah) after 1 week of natural environment use. CONCLUSIONS: The wPUM topography monitors were demonstrated to be reliable when deployed in the natural environment for a range of emerging tobacco products. IMPLICATIONS: The current study addresses the lack of available techniques to reliably monitor topography in the natural environment, across multiple emerging tobacco products. Natural environment topography data will inform standardized puffing protocols for premarket tobacco product applications. The ability to quantify topography over extended periods of time will lead to a better understanding of use behavior and better-informed regulations to protect public health.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Monitorização Fisiológica/normas , Cachimbos de Água/estatística & dados numéricos , Fumar/fisiopatologia , Produtos do Tabaco/estatística & dados numéricos , Vaping/psicologia , Calibragem , Meio Ambiente , Humanos , Monitorização Fisiológica/métodos , Saúde Pública , Fumar/epidemiologia , Fumar/psicologia , Topografia Médica , Vaping/tendências
19.
J Crohns Colitis ; 15(1): 74-87, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-32621742

RESUMO

BACKGROUND AND AIMS: Cigarette smoking worsens prognosis of Crohn's disease [CD]. We conducted a systematic review and meta-analysis to examine the association between smoking and induction of clinical response or remission with anti-tumour necrosis factor [TNF] therapy. METHODS: MEDLINE, EMBASE, PubMed, and Cochrane CENTRAL [June 2019] were searched for studies reporting the effect of smoking on short-term clinical response and remission to anti-TNF therapy [≤16 weeks following the first treatment] in patients with CD. Risk ratios [RR] with 95% confidence intervals [CI] were calculated using random-effects models. RESULTS: Eighteen observational studies and three randomised controlled trials [RCT] were included. Current smokers and non-smokers [never or former] had similar rates of clinical response [observational studies RR: 0.96; 95% CI: 0.88, 1.05; RCTs RR: 1.09; 95% CI: 0.84, 1.41]. When restricted to studies clearly defining the smoking exposure, smokers treated with anti-TNF were less likely to achieve clinical response than non-smokers [smokers defined as having ≥5 cigarettes/day for ≥6 months RR: 0.63; 95% CI: 0.48, 0.83; lifetime never smokers vs ever smokers excluding former smokers RR: 0.81; 95% CI: 0.71, 0.93]. Current smokers were also less likely to achieve clinical remission in observational studies [RR: 0.75; 95% CI: 0.57, 0.98], though this association was not seen in RCTs [RR: 1.04; 95% CI: 0.89, 1.21]. CONCLUSIONS: Smoking is significantly associated with a reduction in the ability of infliximab or adalimumab to induce short-term clinical response and remission when pooling studies where smoking status was clearly defined. When patients with CD are treated with highly effective therapy, including anti-TNF agents, concurrent smoking cessation may improve clinical outcomes.


Assuntos
Adalimumab/farmacologia , Doença de Crohn , Infliximab/farmacologia , Fumar , Doença de Crohn/tratamento farmacológico , Doença de Crohn/psicologia , Humanos , Medição de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Fumar/fisiopatologia , Falha de Tratamento , Inibidores do Fator de Necrose Tumoral/farmacologia
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