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2.
BMJ Open ; 11(11): e055003, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732503

RESUMO

OBJECTIVES: To investigate the associations of physical activity level with COVID-19 mortality risk across body mass index (BMI) categories, and to determine whether any protective association of a higher physical activity level in individuals with obesity may be explained by favourable levels of cardiometabolic and inflammatory biomarkers. DESIGN: Prospective cohort study (baseline data collected between 2006 and 2010). Physical activity level was assessed using the International Physical Activity Questionnaire (high: ≥3000 Metabolic Equivalent of Task (MET)-min/week, moderate: ≥600 MET-min/week, low: not meeting either criteria), and biochemical assays were conducted on blood samples to provide biomarker data. SETTING: UK Biobank. MAIN OUTCOME MEASURES: Logistic regressions adjusted for potential confounders were performed to determine the associations of exposure variables with COVID-19 mortality risk. Mortality from COVID-19 was ascertained by death certificates through linkage with National Health Service (NHS) Digital. RESULTS: Within the 259 397 included participants, 397 COVID-19 deaths occurred between 16 March 2020 and 27 February 2021. Compared with highly active individuals with a normal BMI (reference group), the ORs (95% CIs) for COVID-19 mortality were 1.61 (0.98 to 2.64) for highly active individuals with obesity, 2.85 (1.78 to 4.57) for lowly active individuals with obesity and 1.94 (1.04 to 3.61) for lowly active individuals with a normal BMI. Of the included biomarkers, neutrophil count and monocyte count were significantly positively associated with COVID-19 mortality risk. In a subanalysis restricted to individuals with obesity, adjusting for these biomarkers attenuated the higher COVID-19 mortality risk in lowly versus highly active individuals with obesity by 10%. CONCLUSIONS: This study provides novel evidence suggesting that a high physical activity level may attenuate the COVID-19 mortality risk associated with obesity. Although the protective association may be partly explained by lower neutrophil and monocyte counts, it still remains largely unexplained by the biomarkers included in this analysis.


Assuntos
COVID-19 , Doenças Cardiovasculares , Bancos de Espécimes Biológicos , Índice de Massa Corporal , Estudos de Coortes , Exercício Físico , Humanos , Inflamação , Obesidade/epidemiologia , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2 , Medicina Estatal , Reino Unido/epidemiologia
3.
BMC Med ; 19(1): 301, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34781951

RESUMO

BACKGROUND: With the increasing number of people infected with and recovered from coronavirus disease 2019 (COVID-19), the extent of major health consequences of COVID-19 is unclear, including risks of severe secondary infections. METHODS: Based on 445,845 UK Biobank participants registered in England, we conducted a matched cohort study where 5151 individuals with a positive test result or hospitalized with a diagnosis of COVID-19 were included in the exposed group. We then randomly selected up to 10 matched individuals without COVID-19 diagnosis for each exposed individual (n = 51,402). The life-threatening secondary infections were defined as diagnoses of severe secondary infections with high mortality rates (i.e., sepsis, endocarditis, and central nervous system infections) from the UK Biobank inpatient hospital data, or deaths from these infections from mortality data. The follow-up period was limited to 3 months after the initial COVID-19 diagnosis. Using a similar study design, we additionally constructed a matched cohort where exposed individuals were diagnosed with seasonal influenza from either inpatient hospital or primary care data between 2010 and 2019 (6169 exposed and 61,555 unexposed individuals). After controlling for multiple confounders, Cox models were used to estimate hazard ratios (HRs) of life-threatening secondary infections after COVID-19 or seasonal influenza. RESULTS: In the matched cohort for COVID-19, 50.22% of participants were male, and the median age at the index date was 66 years. During a median follow-up of 12.71 weeks, the incidence rate of life-threatening secondary infections was 2.23 (123/55.15) and 0.25 (151/600.55) per 1000 person-weeks for all patients with COVID-19 and their matched individuals, respectively, which corresponded to a fully adjusted HR of 8.19 (95% confidence interval [CI] 6.33-10.59). The corresponding HR of life-threatening secondary infections among all patients with seasonal influenza diagnosis was 4.50, 95% CI 3.34-6.08 (p for difference < 0.01). Also, elevated HRs were observed among hospitalized individuals for life-threatening secondary infections following hospital discharge, both in the COVID-19 (HR = 6.28 [95% CI 4.05-9.75]) and seasonal influenza (6.01 [95% CI 3.53-10.26], p for difference = 0.902) cohorts. CONCLUSION: COVID-19 patients have increased subsequent risks of life-threatening secondary infections, to an equal extent or beyond risk elevations observed for patients with seasonal influenza.


Assuntos
COVID-19 , Coinfecção , Bancos de Espécimes Biológicos , Teste para COVID-19 , Estudos de Coortes , Humanos , Masculino , SARS-CoV-2 , Reino Unido/epidemiologia
4.
Nutrients ; 13(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34684344

RESUMO

Previous studies have suggested that vitamin D (VD) was associated with psychiatric diseases, but efforts to elucidate the functional relevance of VD with depression and anxiety from genetic perspective have been limited. Based on the UK Biobank cohort, we first calculated polygenic risk score (PRS) for VD from genome-wide association study (GWAS) data of VD. Linear and logistic regression analysis were conducted to evaluate the associations of VD traits with depression and anxiety traits, respectively. Then, using individual genotype and phenotype data from the UK Biobank, genome-wide environment interaction studies (GWEIS) were performed to identify the potential effects of gene × VD interactions on the risks of depression and anxiety traits. In the UK Biobank cohort, we observed significant associations of blood VD level with depression and anxiety traits, as well as significant associations of VD PRS and depression and anxiety traits. GWEIS identified multiple candidate loci, such as rs114086183 (p = 4.11 × 10-8, LRRTM4) for self-reported depression status and rs149760119 (p = 3.88 × 10-8, GNB5) for self-reported anxiety status. Our study results suggested that VD was negatively associated with depression and anxiety. GWEIS identified multiple candidate genes interacting with VD, providing novel clues for understanding the biological mechanism potential associations between VD and psychiatric disorders.


Assuntos
Ansiedade/sangue , Ansiedade/genética , Depressão/sangue , Depressão/genética , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Vitamina D/sangue , Ansiedade/epidemiologia , Bancos de Espécimes Biológicos , Depressão/epidemiologia , Feminino , Genoma Humano , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Análise de Regressão , Fatores de Risco
5.
Nutrients ; 13(10)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34684543

RESUMO

Behavioral disinhibition is observed to be an important characteristic of many neurodevelopmental and psychiatric disorders. Recent studies have linked dietary quality to levels of behavioral inhibition. However, it is currently unclear whether brain factors might mediate this. The current study investigates whether cortical and subcortical brain volumes mediate part of the association between dietary composition and behavioral disinhibition. A total of 15,258 subjects from the UK Biobank project were included in the current study. Dietary composition and behavioral disinhibition were based on Principle Component Analyses of self-reported dietary composition). As a further data reduction step, cortical and subcortical volume segmentations were input into an Independent Component Analysis. The resulting four components were used as mediator variables in the main mediation analyses, where behavioral disinhibition served as the outcome variable and dietary components as predictors. Our results show: (1) significant associations between all dietary components and brain volume components; (2) brain volumes are associated with behavioral disinhibition; (3) the mediation models show that part of the variance in behavioral disinhibition explained by dietary components (for healthy diet, restricted diet, and high-fat dairy diet) is mediated through the frontal-temporal/parietal brain volume component. These results are in part confirming our hypotheses and offer a first insight into the underlying mechanisms linking dietary composition, frontal-parietal brain volume, and behavioral disinhibition in the general adult population.


Assuntos
Comportamento , Bancos de Espécimes Biológicos , Córtex Cerebral/patologia , Dieta , Comportamento Impulsivo , Adulto , Idoso , Córtex Cerebral/diagnóstico por imagem , Dieta Saudável , Análise Fatorial , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Reino Unido
6.
Nutrients ; 13(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684580

RESUMO

The association between nuts intake and cognitive function is inconclusive. We aimed to investigate the association between habitual nuts consumption and cognition among Qatari adults. Data from 1000 participants aged >20 years who attended Qatar Biobank (QBB) were used. Nuts consumption was assessed by a food frequency questionnaire (FFQ). Blood samples were measured for magnesium, lipids and glucose. Mean reaction time (MRT) was used as an indicator of cognitive function. Linear regression was used to assess the association. A total of 21.1% of the participants reported consuming nuts ≥4-6 times/week (high consumption) while 40.2% reported consuming ≤1 time/month (low consumption). The mean MRT was 715.6 milliseconds (SD 204.1). An inverse association was found between nuts consumption and MRT. Compared to those with a low consumption, high consumption of nuts had a regression coefficient of -36.9 (95% CI -68.1 to -5.8) after adjusting for sociodemographic and lifestyle factors. The inverse association between nuts and MRT was mainly seen among those >50 years. There was an interaction between nuts consumption and hypertension. The association between nuts consumption and MRT was not mediated by hypertension, diabetes, or serum magnesium. Habitual higher consumption of nuts is positively associated with cognitive function, especially among old adults.


Assuntos
Cognição/fisiologia , Comportamento Alimentar , Nozes , Adulto , Bancos de Espécimes Biológicos , Diabetes Mellitus/epidemiologia , Ingestão de Alimentos , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Catar/epidemiologia , Tempo de Reação
7.
PLoS One ; 16(10): e0258212, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618839

RESUMO

The ectodysplasin receptor (EDAR) is a tumor necrosis factor receptor (TNF) superfamily member. A substitution in an exon of EDAR at position 370 (EDARV370A) creates a gain of function mutant present at high frequencies in Asian and Indigenous American populations but absent in others. Its frequency is intermediate in populations of Mexican ancestry. EDAR regulates the development of ectodermal tissues, including mammary ducts. Obesity and type 2 diabetes mellitus are prevalent in people with Indigenous and Latino ancestry. Latino patients also have altered prevalence and presentation of breast cancer. It is unknown whether EDARV370A might connect these phenomena. The goals of this study were to determine 1) whether EDARV370A is associated with metabolic phenotypes and 2) if there is altered breast anatomy in women carrying EDARV370A. Participants were from two Latino cohorts, the Arizona Insulin Resistance (AIR) registry and Sangre por Salud (SPS) biobank. The frequency of EDARV370A was 47% in the Latino cohorts. In the AIR registry, carriers of EDARV370A (GG homozygous) had significantly (p < 0.05) higher plasma triglycerides, VLDL, ALT, 2-hour post-challenge glucose, and a higher prevalence of prediabetes/diabetes. In a subset of the AIR registry, serum levels of ectodysplasin A2 (EDA-A2) also were associated with HbA1c and prediabetes (p < 0.05). For the SPS biobank, participants that were carriers of EDARV370A had lower breast density and higher HbA1c (both p < 0.05). The significant associations with measures of glycemia remained when the cohorts were combined. We conclude that EDARV370A is associated with characteristics of the metabolic syndrome and breast density in Latinos.


Assuntos
Densidade da Mama/genética , Receptor Edar/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Hispano-Americanos/genética , Síndrome Metabólica/genética , Mutação/genética , Adulto , Comitês Consultivos , Arizona , Bancos de Espécimes Biológicos , Glicemia/metabolismo , Ectodisplasinas/genética , Feminino , Frequência do Gene/genética , Hemoglobina A Glicada/metabolismo , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Sistema de Registros
8.
PLoS One ; 16(10): e0258803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34665838

RESUMO

PURPOSE: To determine whether age-related macular degeneration (AMD) severity or the frequency of retinal pigment epithelium mitochondrial DNA lesions differ in human donor eyes that have undergone cataract surgery compared to phakic eyes. METHODS: Eyes from human donors aged ≥ 55 years were obtained from the Minnesota Lions Eye Bank. Cataract surgery status was obtained from history provided to Eye Bank personnel by family members at the time of tissue procurement. Donor eyes were graded for AMD severity using the Minnesota Grading System. Quantitative PCR was performed on DNA isolated from macular punches of retinal pigment epithelium to quantitate the frequency of mitochondrial DNA lesions in the donor tissue. Univariable and multivariable analyses were performed to evaluate for associations between (1) cataract surgery and AMD severity and (2) cataract surgery and mitochondrial DNA lesion frequency. RESULTS: A total of 157 subjects qualified for study inclusion. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that only age was associated with AMD grade. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that none of these factors were associated with retinal pigment epithelium mitochondrial DNA lesion frequency. CONCLUSIONS: In this study of human donor eyes, neither retinal pigment epithelium mitochondrial DNA damage nor the stage of AMD severity are independently associated with cataract surgery after adjusting for other AMD risk factors. These new pathologic and molecular findings provide evidence against a relationship between cataract surgery and AMD progression and support the idea that cataract surgery is safe in the setting of AMD.


Assuntos
Extração de Catarata/estatística & dados numéricos , Dano ao DNA , DNA Mitocondrial/genética , Degeneração Macular/genética , Idoso , Idoso de 80 Anos ou mais , Bancos de Espécimes Biológicos , Extração de Catarata/efeitos adversos , Progressão da Doença , Feminino , Humanos , Degeneração Macular/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Epitélio Pigmentado da Retina/química , Doadores de Tecidos
9.
Acta Reumatol Port ; 46(3): 218-229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34626462

RESUMO

OBJECTIVE: Biobanks for research (BBR) have enormous value for research, including those specifically oriented to chronic diseases. Knowing public attitudes and perceptions is key to design and implement patient-centered BBR. We assessed patient awareness, perception and choices among rheumatology outpatients regarding aging biobanking activities. METHODS: We conducted a cross-sectional survey of patients, aged 50 or older, attending an outpatient rheumatology tertiary department. Demographic data and perceptions about biobanking were collected and statistical analysis was performed. RESULTS: 132 valid questionnaires were obtained (mean age: 63,4; 68,2% female; mean education years: 8,35). 61,7% of respondents did not know the specific term "biobank", 57,7% knew they could donate biological material for BBR, 89,9% agreed with these infrastructures and 88,3% would consider participation Those participants with more years of education were more knowledgeable and prone to biobank participation. Willingness to participate in BBR was mainly related (86,4%) to the advancement of scientific knowledge and not individual gain. Scientific research institutes were indicated as the most adequate institutions to manage BBR. Informed consent, anonymity and confidentiality ranked as top requisites for biobank participation. 61,3% of respondents expressed their agreement with aging biobanks, considering these as a sign of respect for specific problems of people of older ages such as higher disease burdens. CONCLUSION: Knowledge of biobanks was found to be limited. Participants were positive toward the setting up of biobanks in general and patient-centered aging biobanks in particular. Knowledge about biobanks and acceptance were higher among participants with higher education years.


Assuntos
Bancos de Espécimes Biológicos , Reumatologia , Idoso , Envelhecimento , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Percepção
10.
Age Ageing ; 50(6): 2222-2229, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34657960

RESUMO

BACKGROUND: Weak grip strength is associated with a range of adverse health outcomes and an accelerated decline in grip strength confers an even greater risk. The factors associated with change in grip strength in mid-life remain to be fully determined. METHODS: We used data from 44,315 UK Biobank participants who had grip strength measured at baseline (2006-10) and a subsequent visit approximately nine years later. At baseline, participants' long-term conditions (LTCs) were categorised against a hierarchy, with multimorbidity characterised by the number of LTC categories. Lifestyle factors were assessed. Change in grip strength was grouped into four patterns: decline, stable low, stable high or reference (no change or increase) and used as the outcome in multinomial logistic regression. RESULTS: Most LTC categories were associated with adverse patterns of change in grip strength (stable low and/or decline): for example, musculoskeletal/trauma conditions were associated with an increased risk of the stable low pattern (Relative Risk Ratio [RRR] = 1.63; 95% confidence interval [CI]: 1.49-1.79). Multimorbidity and lifestyle factors had independent associations with grip strength change. Those with 3+ categories of LTCs were more likely to experience decline in grip strength (RRR = 1.18; 95% CI: 1.08-1.28) compared to those with none. Low physical activity was associated with adverse patterns of grip strength, while raised body mass index (BMI) had divergent associations. CONCLUSIONS: Individuals living with multimorbidity and those with lifestyle risk factors such as low physical activity are at increased risk of low muscle strength and the loss of strength over time.


Assuntos
Bancos de Espécimes Biológicos , Multimorbidade , Força da Mão , Humanos , Estilo de Vida , Reino Unido/epidemiologia
11.
Nat Commun ; 12(1): 6052, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663819

RESUMO

Polygenic risk prediction is a widely investigated topic because of its promising clinical applications. Genetic variants in functional regions of the genome are enriched for complex trait heritability. Here, we introduce a method for polygenic prediction, LDpred-funct, that leverages trait-specific functional priors to increase prediction accuracy. We fit priors using the recently developed baseline-LD model, including coding, conserved, regulatory, and LD-related annotations. We analytically estimate posterior mean causal effect sizes and then use cross-validation to regularize these estimates, improving prediction accuracy for sparse architectures. We applied LDpred-funct to predict 21 highly heritable traits in the UK Biobank (avg N = 373 K as training data). LDpred-funct attained a +4.6% relative improvement in average prediction accuracy (avg prediction R2 = 0.144; highest R2 = 0.413 for height) compared to SBayesR (the best method that does not incorporate functional information). For height, meta-analyzing training data from UK Biobank and 23andMe cohorts (N = 1107 K) increased prediction R2 to 0.431. Our results show that incorporating functional priors improves polygenic prediction accuracy, consistent with the functional architecture of complex traits.


Assuntos
Bancos de Espécimes Biológicos , Herança Multifatorial , Genoma , Genótipo , Humanos , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único , Reino Unido
12.
Comput Med Imaging Graph ; 93: 101994, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34624770

RESUMO

Along with rich health-related metadata, medical images have been acquired for over 40,000 male and female UK Biobank participants, aged 44-82, since 2014. Phenotypes derived from these images, such as measurements of body composition from MRI, can reveal new links between genetics, cardiovascular disease, and metabolic conditions. In this work, six measurements of body composition and adipose tissues were automatically estimated by image-based, deep regression with ResNet50 neural networks from neck-to-knee body MRI. Despite the potential for high speed and accuracy, these networks produce no output segmentations that could indicate the reliability of individual measurements. The presented experiments therefore examine uncertainty quantification with mean-variance regression and ensembling to estimate individual measurement errors and thereby identify potential outliers, anomalies, and other failure cases automatically. In 10-fold cross-validation on data of about 8500 subjects, mean-variance regression and ensembling showed complementary benefits, reducing the mean absolute error across all predictions by 12%. Both improved the calibration of uncertainties and their ability to identify high prediction errors. With intra-class correlation coefficients (ICC) above 0.97, all targets except the liver fat content yielded relative measurement errors below 5%. Testing on another 1000 subjects showed consistent performance, and the method was finally deployed for inference to 30,000 subjects with missing reference values. The results indicate that deep regression ensembles could ultimately provide automated, uncertainty-aware measurements of body composition for more than 120,000 UK Biobank neck-to-knee body MRI that are to be acquired within the coming years.


Assuntos
Bancos de Espécimes Biológicos , Imageamento por Ressonância Magnética , Composição Corporal , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Incerteza , Reino Unido
13.
Cells ; 10(10)2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34685505

RESUMO

The objective of this review is to describe the evolution of lung tissue-derived diploid progenitor cell applications, ranging from historical biotechnological substrate functions for vaccine production and testing to current investigations around potential therapeutic use in respiratory tract regenerative medicine. Such cell types (e.g., MRC-5 or WI-38 sources) were extensively studied since the 1960s and have been continuously used over five decades as safe and sustainable industrial vaccine substrates. Recent research and development efforts around diploid progenitor lung cells (e.g., FE002-Lu or Walvax-2 sources) consist in qualification for potential use as optimal and renewed vaccine production substrates and, alternatively, for potential therapeutic applications in respiratory tract regenerative medicine. Potentially effective, safe, and sustainable cell therapy approaches for the management of inflammatory lung diseases or affections and related symptoms (e.g., COVID-19 patients and burn patient severe inhalation syndrome) using local homologous allogeneic cell-based or cell-derived product administrations are considered. Overall, lung tissue-derived progenitor cells isolated and produced under good manufacturing practices (GMP) may be used with high versatility. They can either act as key industrial platforms optimally conforming to specific pharmacopoeial requirements or as active pharmaceutical ingredients (API) for potentially effective promotion of lung tissue repair or regeneration.


Assuntos
Biotecnologia/métodos , Diploide , Pulmão/citologia , Medicina Regenerativa/métodos , Infecções Respiratórias/terapia , Animais , Bancos de Espécimes Biológicos , Vacinas contra COVID-19 , Linhagem Celular , Terapia Baseada em Transplante de Células e Tecidos , História do Século XX , História do Século XXI , Humanos , Pulmão/fisiologia , Regeneração , Medicina Regenerativa/história , SARS-CoV-2 , Transplante de Células-Tronco , Células-Tronco/citologia , Transplante Homólogo
14.
Biopreserv Biobank ; 19(5): 394-398, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34610247

RESUMO

Background: The AIDS and Cancer Specimen Resource (ACSR) is a network of four regional biospecimen repositories and a technical core in the United States and South Africa. Its mission is to acquire, store, and distribute HIV-associated malignancy specimens and related clinical data to support translational research. At the outset of the COVID-19 pandemic, it became apparent that existing ACSR Standard Operating Procedures (SOPs) were not sufficient to ensure long-term maintenance and integrity of inventories during periods of extended shutdown. The ACSR needed an administrative SOP for situations pertaining to epidemics/pandemics. The ACSR Quality Working Group (QWG), comprised of representatives from each of the five ACSR sites and an external member who directs a large university medical center biorepository, addressed the issue. Methods: To understand the individual problems the sites faced, questions were developed to query each of the six QWG sites' contingency plans to cover this type of emergency, the amount of work allowed onsite and by whom, the challenges sites experienced, and the lessons learned to assist with future similar situations, while remaining consistent with the existing IRB protocols. Results: Reported challenges spanned all activities of classical biobanks and differed within the geographical locations of the sites and the local COVID-19 infection rate. Review of the responses to the questions revealed that the general shutdown of society external to the biorepositories presented them with a homogeneous collection of problems, limitations, and needs. This led to creating an SOP that addresses planning for pandemic emergencies, scaling down of activities, shutting down, and reopening plans. Conclusions: The ACSR QWG sites now have a structured response SOP for their sites, including guidance on how to develop and implement an emergency shutdown and reopening plan. The complete SOP is publicly available on the ACSR website.


Assuntos
COVID-19 , Pandemias , Bancos de Espécimes Biológicos , Emergências , Humanos , SARS-CoV-2 , Estados Unidos
15.
Artigo em Inglês | MEDLINE | ID: mdl-34639751

RESUMO

In previous studies, it has been documented that a short reproductive period is associated with a higher risk of diabetes, cardiovascular disease, and chronic kidney disease. This study aims to investigate the association of the reproductive period length with decreased renal function. This study obtained data from "the Shanghai Suburban Adult Cohort and Biobank". An estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 indicated decreased renal function during follow-up. Participants were grouped into quintiles by reproductive period. Logistic regression analysis was performed to examine the association between the reproductive period and decreased renal function. A total of 5503 menopausal women with baseline eGFR > 60 mL/min/1.73 m2 were included. Age, eGFR, and metabolic equivalent of task (MET) at baseline were 61.0 (range, 36.0-74.0) years, 92.2 (range, 60.1-194.5) mL/min/1.73 m2, and 1386 (range, 160-6678), respectively. A reproductive period of 37-45 years was associated with a lower risk of decreased eGFR (OR: 0.59, 95% CI: 0.35-1.00, p = 0.049) after adjusting for confounding variables. METs decreased the risk of decreased eGFR in women with a reproductive period of 37-45 years (OR: 0.43, 95% CI: 0.23-0.81, p = 0.010). Women with a longer reproductive period have a lower risk of decreased renal function. METs had an opposite influence on renal function in women with longer (decreased risk) or shorter (increased risk) reproductive periods.


Assuntos
Bancos de Espécimes Biológicos , Insuficiência Renal Crônica , Adulto , Idoso , China/epidemiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Menopausa , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Reprodução , Fatores de Risco
16.
Nat Genet ; 53(10): 1415-1424, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34594039

RESUMO

Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (ntotal = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Sistema ABO de Grupos Sanguíneos/genética , Bancos de Espécimes Biológicos , Loci Gênicos , Pleiotropia Genética , Estudo de Associação Genômica Ampla , Humanos , Complexo Principal de Histocompatibilidade/genética , Metanálise como Assunto , Mutação/genética , Fenótipo
17.
BMJ Open ; 11(10): e045871, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625411

RESUMO

OBJECTIVES: To investigate the association between shingles and dementia, and between Zostavax vaccination and dementia. DESIGN: Nested case-control study. SETTINGS: Data were drawn from the UK Biobank cohort study with a total of 228 223 participants with Hospital Episodes Statistics and primary care linkage health records. PARTICIPANTS: The analyses included 2378 incident dementia cases and 225 845 controls. Inclusion criteria for incident cases were a dementia diagnosis 3 years or more after the first assessment date derived from all sources including International Classification of Diseases (ICD)-10, ICD-9, self-report and primary care linkage records. Subjects with no dementia code from all sources were coded as controls. Both shingles and Zostavax vaccination were investigated for their association with dementia risk. RESULTS: There was a small but non-significant increase in the risk of dementia in subjects with shingles diagnosed 3 years or more prior to dementia diagnosis (OR: 1.088 with 95% CI: 0.978 to 1.211). In those subjects who had had Zostavax vaccination, the risk of dementia significantly decreased (OR: 0.808 with 95% CI: 0.657 to 0.993). CONCLUSION: A history of shingles was not associated with an increased risk of dementia. In subjects who were eligible for the immunisation and vaccinated with Zostavax, we saw reduced risk of developing dementia.


Assuntos
Demência , Vacina contra Herpes Zoster , Herpes Zoster , Bancos de Espécimes Biológicos , Estudos de Casos e Controles , Estudos de Coortes , Demência/epidemiologia , Humanos , Reino Unido/epidemiologia , Vacinação
18.
BMC Med ; 19(1): 240, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34629060

RESUMO

BACKGROUND: A greater understanding of the factors that are associated with favourable health may help increase longevity and healthy life expectancy. We examined sociodemographic, psychosocial, lifestyle and environmental exposures associated with multiple health indicators. METHODS: UK Biobank recruited > 500,000 participants, aged 37-73, between 2006 and 2010. Health indicators examined were 81 cancer and 443 non-cancer illnesses used to classify participants' health status; long-standing illness; and self-rated health. Exposures were sociodemographic (age, sex, ethnicity, education, income and deprivation), psychosocial (loneliness and social isolation), lifestyle (smoking, alcohol intake, sleep duration, BMI, physical activity and stair climbing) and environmental (air pollution, noise and residential greenspace) factors. Associations were estimated using logistic and ordinal logistic regression. RESULTS: In total, 307,378 participants (mean age = 56.1 years [SD = 8.07], 51.9% female) were selected for cross-sectional analyses. Low income, being male, neighbourhood deprivation, loneliness, social isolation, short or long sleep duration, low or high BMI and smoking were associated with poor health. Walking, vigorous-intensity physical activity and more frequent alcohol intake were associated with good health. There was some evidence that airborne pollutants (PM2.5, PM10 and NO2) and noise (Lden) were associated with poor health, though findings were not consistent across all models. CONCLUSIONS: Our findings highlight the multifactorial nature of health, the importance of non-medical factors, such as loneliness, healthy lifestyle behaviours and weight management, and the need to examine efforts to improve the health outcomes of individuals on low incomes.


Assuntos
Bancos de Espécimes Biológicos , Exposição Ambiental , Estudos Transversais , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia
19.
Yi Chuan ; 43(10): 972-979, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702709

RESUMO

China is facing a heavy burden of chronic diseases, so it is urgent to promote the relevant researches for early prevention of chronic diseases. Large population cohorts are one of the primary study designs for etiology evidence of chronic diseases, which are helpful to explore feasible intervention measures. Moreover, clarifying the genetic associations between risk factors and diseases from the genetic level of large population cohort can also open up a new way to the exploration of causality. This article aimed to introduce the study "China Kadoorie Biobank (CKB)" jointly carried out by the Chinese Academy of Medical Sciences, Peking University and University of Oxford, with emphasis on the construction progress of genetic resources and the recent published genetic studies, in order to provide reference for the in-depth mining and utilization of genetic resources in large population cohort in China.


Assuntos
Bancos de Espécimes Biológicos , Genética Humana , China , Humanos , Fatores de Risco
20.
Int J Mol Sci ; 22(19)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34639060

RESUMO

Glioblastoma (GBM) is highly resistant to treatment and invasion into the surrounding brain is a cancer hallmark that leads to recurrence despite surgical resection. With the emergence of precision medicine, patient-derived 3D systems are considered potentially robust GBM preclinical models. In this study, we screened a library of 22 anti-invasive compounds (i.e., NF-kB, GSK-3-B, COX-2, and tubulin inhibitors) using glioblastoma U-251 MG cell spheroids. We evaluated toxicity and invasion inhibition using a 3D Matrigel invasion assay. We next selected three compounds that inhibited invasion and screened them in patient-derived glioblastoma organoids (GBOs). We developed a platform using available macros for FIJI/ImageJ to quantify invasion from the outer margin of organoids. Our data demonstrated that a high-throughput invasion screening can be done using both an established cell line and patient-derived 3D model systems. Tubulin inhibitor compounds had the best efficacy with U-251 MG cells, however, in ex vivo patient organoids the results were highly variable. Our results indicate that the efficacy of compounds is highly related to patient intra and inter-tumor heterogeneity. These results indicate that such models can be used to evaluate personal oncology therapeutic strategies.


Assuntos
Bancos de Espécimes Biológicos , Neoplasias Encefálicas/patologia , Descoberta de Drogas , Glioblastoma/patologia , Organoides , Medicina de Precisão , Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Descoberta de Drogas/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Glioblastoma/tratamento farmacológico , Humanos , Invasividade Neoplásica , Medicina de Precisão/métodos , Esferoides Celulares , Técnicas de Cultura de Tecidos
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