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1.
Aging (Albany NY) ; 12(11): 10687-10703, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532929

RESUMO

INTRODUCTION: To investigate the independent and joint effects of leisure activities on disability in activities of daily living (ADL) among the oldest-old Chinese population (aged ≥ 80 years). RESULTS: A total of 3696 participants with ADL disability were identified during the median follow-up period of 3.1 years. Compared to the participants who "never" watched TV or listened to the radio and who "never" kept domestic animals or pets, those who engaged in these activities "almost every day" had a significantly lower ADL disability risk (adjusted hazard ratios were 0.74 and 0.66, respectively; both P < 0.001). Furthermore, participants engaging in multiple leisure activities showed a reduced risk of ADL disability (P for trend < 0.001). CONCLUSIONS: Frequently watching TV or listening to the radio and keeping domestic animals or pets was associated with a lower risk of ADL disability among the oldest-old Chinese population. METHODS: We included 12,331 participants (aged ≥ 80 years) (mean [SD] age: 89.5 [7.0] years) who managed to perform ADL independently at baseline in the Chinese Longitudinal Healthy Longevity Survey 1998-2014 waves. Cox proportional hazards models were used to examine whether leisure activities were associated with ADL disability.

2.
J Diabetes ; 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32500961

RESUMO

BACKGROUND: Previous epidemiological evidence on the sex-specific association of obesity, particularly abdominal obesity, as reflected by larger waist circumference (WC), with incident diabetic neuropathy (DN) remains limited. METHODS: We used data from a patient cohort with a median 10-year history of type 2 diabetes mellitus at the time of recruitment. A composite outcome of four types of predefined DN (Neuro 1-4) was used as the outcome of interest. Because of sex differences in abdominal obesity, analyses were conducted separately for men and women. RESULTS: Among the 7442 participants (4551 men and 2891 women) recruited in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, 3999 cases of incident DN were documented (1413 in men and 853 in women). Larger WCs were associated with a higher risk of DN among both men and women. Compared with the lowest quintile, the HR for the highest quintile was 1.30 (95% CI 1.13-1.49) among men (P-trend <0.001). For women, the HR for the lowest vs highest quintile was 1.25 (95% CI 1.04-1.51) (P-trend <0.001). A linear relationship between WC and DN was observed in men, and in women, the risk of DN increased as the WC quintile increased before it appeared to plateau. The relationship between BMI and incident DN was similar to the results observed for WC. CONCLUSION: General and abdominal obesity were both associated with an increased risk of incident DN among individuals with type 2 diabetes mellitus, regardless of sex. This article is protected by copyright. All rights reserved.

3.
Int J Infect Dis ; 96: 288-290, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32437933

RESUMO

Data are limited on the viral load, viral shedding patterns, and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). This study included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in the incubation period (APIs); the other nine patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The median cycle threshold (Ct) value of APs (39.0, interquartile range (IQR) 37.5-39.5) was significantly higher than that of APIs (34.5, IQR 32.2-37.0), indicating a lower viral load in APs. However, the duration of viral shedding remained similar in the two groups (7 days, IQR 5-14 days vs. 8 days, IQR 5-16 days). The study findings demonstrated that although APs with COVID-19 have a lower viral load, they still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid testing are warranted.

4.
Ann Rheum Dis ; 79(6): 829-836, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32253185

RESUMO

OBJECTIVES: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort. METHODS: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables. RESULTS: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080). CONCLUSIONS: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

5.
Viruses ; 12(4)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276428

RESUMO

Enterovirus A71 (EV-A71) is a major pathogen that causes severe and fatal cases of hand-foot-and-mouth disease (HFMD). HFMD caused by EV-A71 seriously endangers children's health. Although autophagy is an important antiviral defense mechanism, some viruses have evolved strategies to utilize autophagy to promote self-replication. EV-A71 can utilize autophagy vesicles as replication scaffolds, indicating that EV-A71 infection is closely related to its autophagy induction mechanism. VP1, a structural protein of EV-A71, has been reported to induce autophagy, but the underlying mechanism is still unclear. In this study, we found that the C-terminus (aa 251-297) of VP1 induces autophagy. Mass spectrometry analysis suggested that prohibitin 2 (PHB2) interacts with the C-terminus of the EV-A71 VP1 protein, and this was further verified by coimmunoprecipitation assays. After PHB2 knockdown, EV-A71 replication, viral particle release, and viral protein synthesis were reduced, and autophagy was inhibited. The results suggest that PHB2 interaction with VP1 is essential for induction of autophagy and the infectivity of EV-A71. Furthermore, we confirmed that EV-A71 induced complete autophagy that required autolysosomal acidification, thus affecting EV-A71 infection. In summary, this study revealed that the host protein PHB2 is involved in an autophagy mechanism during EV-A71 infection.

6.
BMJ ; 368: m456, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131999

RESUMO

OBJECTIVES: To evaluate the associations of habitual fish oil supplementation with cardiovascular disease (CVD) and mortality in a large prospective cohort. DESIGN: Population based, prospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 427 678 men and women aged between 40 and 69 who had no CVD or cancer at baseline were enrolled between 2006 and 2010 and followed up to the end of 2018. MAIN EXPOSURE: All participants answered questions on the habitual use of supplements, including fish oil. MAIN OUTCOME MEASURES: All cause mortality, CVD mortality, and CVD events. RESULTS: At baseline, 133 438 (31.2%) of the 427 678 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.87 (95% confidence interval 0.83 to 0.90) for all cause mortality, 0.84 (0.78 to 0.91) for CVD mortality, and 0.93 (0.90 to 0.96) for incident CVD events. For CVD events, the association seemed to be stronger among those with prevalent hypertension (P for interaction=0.005). CONCLUSIONS: Habitual use of fish oil seems to be associated with a lower risk of all cause and CVD mortality and to provide a marginal benefit against CVD events among the general population.


Assuntos
Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais/estatística & dados numéricos , Óleos de Peixe/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia
7.
J Gerontol A Biol Sci Med Sci ; 75(4): 739-746, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30946444

RESUMO

BACKGROUND: Little is known about the role of specific leisure activities in affecting cognitive functions. We aim to examine the associations of specific leisure activities with the risk of cognitive impairment among oldest-old people in China. METHODS: This community-based prospective cohort study included 10,741 cognitively normal Chinese individuals aged 80 years or older (median age 88 years) from the Chinese Longitudinal Healthy Longevity Survey. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Cox proportional hazards models were utilized to estimate the effects of specific leisure activities on cognitive impairment outcome. RESULTS: During a median follow-up time of 3.4 years (41,760 person-years), 2,894 participants developed cognitive impairment. Compared to those who "never" engaged in watching TV or listening to radio, reading books or newspapers, and playing cards or mah-jong, those who engaged in such activities "almost every day" reduced their risk of cognitive impairment, the fully-adjusted hazard ratios were 0.56 (0.51-0.61), 0.64 (0.53-0.78), and 0.70 (0.56-0.86), respectively. The association between the risk of cognitive impairment and watching TV and listening to the radio, playing cards or mah-jong, and reading books or newspapers were stronger among those who had two or more years of education. Moreover, the association between risk of cognitive impairment and watching TV and listening to radio was stronger in men than in women. CONCLUSIONS: In conclusion, a greater frequency of TV watching or radio listening, reading books or newspapers, and playing cards or mah-jong may decrease the risk of cognitive impairment among the oldest-old.

8.
Immun Ageing ; 16: 28, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708993

RESUMO

Background: The association of high-sensitivity C-reactive protein (hsCRP) with mortality is controversial. We aimed to investigate the associations of hsCRP concentrations with the risks of all-cause and cause-specific mortality and identify potential modifying factors affecting these associations among middle-aged and elderly individuals. Methods: This community-based prospective cohort study included 14,220 participants aged 50+ years (mean age: 64.9 years) from the Health and Retirement Study. Cox proportional hazard models were employed to estimate the associations between the hsCRP concentrations and the risk of all-cause and cause-specific mortality with adjustment for sociodemographic and lifestyle factors, self-reported medical history, and other potential confounders. Results: In total, 1730 all-cause deaths were recorded, including 725 cardiovascular- and 417 cancer-related deaths, after an 80,572 person-year follow-up (median: 6.4 years; range: 3.6-8.1 years). The comparisons of the groups with the highest (quartile 4) and lowest (quartile 1) hsCRP concentrations revealed that the adjusted hazard ratios and 95% confidence intervals were 1.50 (1.31-1.72) for all-cause mortality, 1.44 (1.13-1.82) for cardiovascular mortality, and 1.67 (1.23-2.26) for cancer mortality. The associations between high hsCRP concentrations and the risks of all-cause, cardiovascular, and cancer mortality were similar in the men and women (P for interaction > 0.05). Conclusions: Among middle-aged and older individuals, elevated hsCRP concentration could increase the risk of all-cause, cardiovascular, and cancer mortality in men and women.

9.
BMJ Open ; 9(10): e026513, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31601581

RESUMO

PURPOSE: The Chinese Longitudinal Healthy Longevity Survey Biomarkers Cohort (Healthy Ageing and Biomarkers Cohort Study (HABCS)) was established to investigate the determinants of healthy aging and mortality among the oldest old in China. Besides collecting health status, behavioural and sociodemographic circumstances, the present study also gathers comprehensive data for the elderly by simultaneously collecting, detecting, analysing blood and urine, respectively. PARTICIPANTS: HABCS is a community-based longitudinal multiwave study of older men and women aged 65 or above. Baseline survey and the follow-up surveys with replacement for deceased elderly were conducted in eight longevity areas in China, which cover the northern, middle and southern parts of China. Between 2008 and 2017, 6333 participants were included in HABCS, comprising 1385 centenarians, 1350 nonagenarians, 1294 octogenarians, 1577 younger elderly (aged 65-79). FINDINGS TO DATE: We have found that higher baseline levels of (1) total cholesterol, (2) low-density lipoprotein cholesterol (LDL-C) and (3) superoxide dismutase activity were associated with greater cognitive decline. While (4) higher LDL-C level was associated with lower risk of all-cause mortality. There was a reverse association between (5) plasma vitamin D and cognitive impairment in cross-sectional and prospective study. FUTURE PLANS: We are currently exploring the relationships between various biomarkers and different outcomes such as cognitive function and mortality. This longitudinal cohort study will be continued in the future.

10.
J Am Med Dir Assoc ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31588027

RESUMO

OBJECTIVE: To investigate associations between leisure activities, examining each activity separately and in combination, and all-cause mortality among the Chinese oldest-old (≥80 years) population. DESIGN: Prospective cohort study. SETTING: Community-living, the oldest-old from 22 provinces in China. PARTICIPANTS: We included 30,070 Chinese individuals aged ≥80 years (mean age: 92.7 years) from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. MEASUREMENTS: Cox proportional hazards models were used to estimate relationships between leisure activities and all-cause mortality, adjusting for covariates including sociodemographic and lifestyle factors, self-reported medical history, and other potential confounders. RESULTS: During 110,278 person-years of follow-up, 23,661 deaths were documented. Participants who engaged in watching TV or listening to the radio, playing cards or mah-jong, reading books or newspapers, gardening, keeping domestic animals or pets, or attending religious activities "almost every day" had a significantly lower mortality risk (adjusted hazard ratios ranged from 0.82 to 0.89; P < .01 for all) than did participants who "never" engaged in those activities. Furthermore, engagement in multiple leisure activities was associated with a reduced risk of all-cause mortality (P for the trend < .001). CONCLUSIONS AND IMPLICATIONS: Frequent participation in leisure activities might help decrease the risk of death in the Chinese oldest-old population. This finding has important implications for public health policy and encourages the incorporation of a broad range of leisure activities into the daily lives of oldest-old individuals.

11.
Nutr Metab (Lond) ; 16: 66, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528185

RESUMO

Background: Current evidence remains equivocal as to whether and how consumption of coffee may be associated with risk of bladder cancer, and potential influence of confounding by smoking on this association is yet to be elucidated. We conducted an updated meta-analysis of prospective studies to address these issues. Methods: Relevant studies were identified by searching PubMed and EMBASE databases from inception to April 2019. A random-effects model was used to estimate summary relative risk (RR) with corresponding 95% confidence interval (CI) of bladder cancer associated with coffee consumption. Results: The final analysis included 16 prospective studies comprising 2,122,816 participants and 11,848 bladder cancer cases. Overall, coffee consumption was not associated with risk of bladder cancer (RR high-vs-low = 1.07, 95% CI: 0.96-1.20). The lack of association persisted in the strata defined by sex or participants' smoking status. Meta-regression analyses identified the number cases (P difference = 0.06) and the degree of adjustment for smoking (P difference = 0.04) as potential sources of heterogeneity. There was an increased risk of bladder cancer related to higher coffee consumption among studies with fewer cases (RR high-vs-low = 1.38, 95% CI: 1.05-1.81) and among those with poorer adjustment for smoking (RR high-vs-low = 1.48, 95% CI: 1.14-1.93). Results were similar in the dose-response analyses (RR 1 cup/d = 1.01, 95% CI: 0.98-1.03). Conclusion: Best evidence available to date does not support an independent association between coffee consumption and bladder cancer risk. Some direct associations observed in individual studies may be a result of residual confounding by smoking. Supplementary information: Supplementary information accompanies this paper at 10.1186/s12986-019-0390-3.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31435643

RESUMO

BACKGROUND: The aim of this study was to examine the trends in impairment regarding activities of daily living (ADL), physical performance and cognitive function among the oldest-old (those aged ≥80 years) in China between 1998 and 2014. METHODS: We used data on 34,297 oldest-old individuals from the seven waves of the Chinese Longitudinal Healthy Longevity Study. We estimated age, period and cohort effects on the prevalence of self-reported ADL impairment, tested physical performance and cognitive function impairment using the age-period-cohort (APC) model. RESULTS: Regarding age, the prevalence of ADL, physical and cognitive impairment were highest in the centenarians, but they did not increase with age in this population. Among the literate subgroup, the prevalence of cognitive impairment increased more rapidly with age than that in the illiterate subgroup. Regarding period, the prevalence of self-reported and tested physical impairment slowly increased between 1998 and 2014, but cognitive impairment remained stable. Regarding cohort, ADL impairment continuously decreased. However, physical and cognitive impairment remained stable after a brief decline in the early birth cohorts. CONCLUSIONS: The results suggest that the age effect is still the most obvious effect regarding several types of functional impairment. The likelihood of a younger person experiencing functional impairment may not change significantly, but ADL is likely to be amenable to improvement resulting from improved medical and social care. Therefore, increased care for the elderly may considerably improve their quality of life, particularly regarding their basic activities of daily living.

13.
mSystems ; 4(4)2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387931

RESUMO

Cronobacter sakazakii is an important pathogen associated with the development of necrotizing enterocolitis (NEC), infant sepsis, and meningitis. Several randomized prospective clinical trials demonstrated that oral probiotics could decrease the incidence of NEC. Previously, we isolated and characterized a novel probiotic, Bacteroides fragilis strain ZY-312. However, it remains unclear how ZY-312 protects the host from the effects of C. sakazakii infection. To understand the underlying mechanisms triggering the probiotic effects, we tested the hypothesis that there was cross talk between probiotics/probiotics-modulated microbiota and the local immune system, governed by the permeability of the intestinal mucosa, using in vitro and in vivo models for the intestinal permeability. The probiotic effects of ZY-312 on intestinal epithelial cells were first examined, and the results revealed that ZY-312 inhibited C. sakazakii invasion, C. sakazakii-induced dual cell death (pyroptosis and apoptosis), and epithelial barrier dysfunction in vitro and in vivo The presence of ZY-312 also resulted in decreased expression of an inflammasome (NOD-like receptor family member pyrin domain-containing protein 3 [NLRP3]), caspase-3, and serine protease caspase-1 in a neonatal rat model. Furthermore, ZY-312 significantly modulated the compositions of the intestinal bacterial communities and decreased the relative abundances of Proteobacteria and Gammaproteobacteria but increased the relative abundances of Bacteroides and Bacillus in neonatal rats. In conclusion, our findings have shown for the first time that the probiotic B. fragilis ZY-312 suppresses C. sakazakii-induced NEC by modulating the proinflammatory response and dual cell death (apoptosis and pyroptosis).IMPORTANCE Cronobacter sakazakii is an opportunistic pathogenic bacterium that can cause necrotizing enterocolitis (NEC). However, the mechanism of pathogenicity of C. sakazakii is largely unknown. Here we have now demonstrated that apoptotic and pyroptotic stimuli are effectors of C. sakazakii-induced NEC. Previously, we isolated a novel probiotic strain candidate from fecal samples from healthy infants and characterized it as Bacteroides fragilis strain ZY-312. Functional characterization reveals that ZY-312 inhibited C. sakazakii invasion, restoring epithelial barrier dysfunction, decreasing the expression of inflammatory cytokines, and reducing dual cell death (pyroptosis and apoptosis). Furthermore, the presence of ZY-132 was sufficient to hinder the adverse reaction seen with C. sakazakii in a C. sakazakii-induced NEC model. Taking the results together, our study demonstrated the utility of ZY-312 as a promising probiotic agent for the prevention of NEC.

14.
Viruses ; 11(5)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121933

RESUMO

Vimentin (VIM) is a surface receptor for enterovirus-A71, mediating the initial binding and subsequent increase in EV-A71 infectivity. The caspid protein VP1 variation, A289T, is reportedly closely associated with less severe central nervous system (CNS) infections in humans. However, it is unclear whether VIM is associated with a reduction in CNS infections of EV-A71 in the presence of A289T. We investigated whether VIM served as a receptor for EV-A71 in the presence of an A298T substitution in VP1. EV-A71-289A and EV-A71-289T were used to infect human rhabdomyosarcoma cells, control human brain microvascular endothelial cells (HBMECs), and VIM-knockout (KO) HBMECs and inoculated BALB/c mice, SV129 mice, and VIM-KO SV129 mice. Furthermore, we cloned VP1-289A-Flag and VP1-289T-Flag proteins for co-immunoprecipitation analysis. Analysis of viral function revealed that the capacity of viral attachment, replication, and protein synthesis and secretion decreased in HBMECs during an EV-A71-289A infection, the infectivity being higher than that of EV-A71-289T upon VIM-KO. Histopathological and immunohistochemical analyses of brain tissue revealed that cerebral cortical damage was more extensive in EV-A71-289A than in EV-A71-289T infections in control SV129 mice; however, no significant difference was observed upon VIM-KO. Co-immunoprecipitation analysis revealed an interaction between VP1 and VIM, which was attenuated in VP1 harboring A289T; however, this attenuation was reversed by VIM (1-58) peptide. The A289T variation of VP1 specifically decreased the virulence of EV-A71 in HBMECs, and the attenuated interaction between VP1 harboring the A289T variation and VIM essentially decreased the CNS infectivity of EV-A71 in vitro and vivo.

15.
J Nutr ; 149(6): 1056-1064, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30949685

RESUMO

BACKGROUND: High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ≥80 y (oldest old) remains unclear. OBJECTIVE: We investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 y. DESIGN: The present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs. RESULTS: The median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend <0.01). Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. The observed associations were broadly consistent across age and other subgroups. Sensitivity analyses generated similar results after excluding participants who died within 2 y of follow-up or after further adjustment for ethnicity and chronic diseases. CONCLUSIONS: A higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ≥80 y. This observed inverse association warrants further investigation in randomized controlled trials testing vitamin D supplementation in this age group.


Assuntos
Mortalidade , Vitamina D/análogos & derivados , Fatores Etários , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Biomarcadores/sangue , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Longevidade/fisiologia , Estudos Longitudinais , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Vitamina D/sangue
16.
J Clin Endocrinol Metab ; 104(8): 3345-3354, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30896760

RESUMO

CONTEXT: The patterns of associations between glycated Hb (HbA1c) and mortality are still unclear. OBJECTIVE: To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes. DESIGN, SETTING, AND PATIENTS: This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for mortality. RESULTS: A total of 2133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was <5.6% or >7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When the HbA1c level was <5.0%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 5.4%. However, we did not observe a statistically significant elevated risk of all-cause mortality above an HbA1c level of 5.4%. CONCLUSIONS: A U-shaped and reverse J-shaped association for all-cause mortality was found among participants with and without diabetes. The corresponding optimal ranges for overall survival are predicted to be 5.6% and 7.4% and 5.0% and 6.5%, respectively.

17.
J Clin Endocrinol Metab ; 104(8): 3370-3378, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30869791

RESUMO

CONTEXT: The patterns of the association between high-density lipoprotein cholesterol (HDL-C) concentrations and mortality among the elderly are still unclear. OBJECTIVE: To examine the association of HDL-C concentrations with mortality and to identify the optimal HDL-C concentration range that predicts the lowest risk of all-cause mortality among the elderly. DESIGN: This was a nationwide, community-based, prospective cohort study. PARTICIPANTS: This study included 7766 elderly individuals (aged ≥65 years; mean age: 74.4 years) from the Health and Retirement Study. Cox proportional hazards models and Cox models with penalized smoothing splines were used to estimate hazard ratios (HRs) with 95% CI for all-cause and cause-specific mortality. RESULTS: During a median follow-up of 5.9 years, 1921 deaths occurred. After a full adjustment for covariates, a nonlinear (P < 0.001 for nonlinearity) association was found between HDL-C and all-cause mortality [minimum mortality risk at 71 mg/dL (1.84 mM)]; the risk for all-cause mortality was significantly higher in the groups with HDL-C concentration <61 mg/dL (1.58 mM; HR: 1.18; 95% CI: 1.05 to 1.33) and with HDL-C concentration >87 mg/dL (2.25 mM; HR: 1.56; 95% CI: 1.17 to 2.07) than in the group with HDL-C concentrations ranging from 61 to 87 mg/dL (1.58 to 2.25 mM). Nonlinear associations of HDL-C concentrations with both cardiovascular and noncardiovascular mortality were also observed (both P < 0.001 for nonlinearity). CONCLUSIONS: Among the elderly, nonlinear associations were found between HDL-C and all-cause and cardiovascular mortality. The single optimal HDL-C concentration and range were 71 mg/dL and 61 to 87 mg/dL, respectively.

18.
BMC Bioinformatics ; 20(1): 11, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30616589

RESUMO

BACKGROUND: Skewed X chromosome inactivation (XCI), which is a non-random process, is frequently observed in both healthy and affected females. Furthermore, skewed XCI has been reported to be related to many X-linked diseases. However, no statistical method is available in the literature to measure the degree of the skewness of XCI for case-control design. Therefore, it is necessary to develop methods for such a task. RESULTS: In this article, we first proposed a statistical measure for the degree of XCI skewing by using a case-control design, which is a ratio of two logistic regression coefficients after a simple reparameterization. Based on the point estimate of the ratio, we further developed three types of confidence intervals (the likelihood ratio, Fieller's and delta methods) to evaluate its variation. Simulation results demonstrated that the likelihood ratio method and the Fieller's method have more accurate coverage probability and more balanced tail errors than the delta method. We also applied these proposed methods to analyze the Graves' disease data for their practical use and found that rs3827440 probably undergoes a skewed XCI pattern with 68.7% of cells in heterozygous females having the risk allele T active, while the other 31.3% of cells keeping the normal allele C active. CONCLUSIONS: For practical application, we suggest using the Fieller's method in large samples due to the non-iterative computation procedure and using the LR method otherwise for its robustness despite its slightly heavy computational burden.


Assuntos
Cromossomos Humanos X/genética , Genes Ligados ao Cromossomo X , Heterozigoto , Modelos Estatísticos , Inativação do Cromossomo X , Alelos , Estudos de Casos e Controles , Feminino , Humanos
19.
BMC Genet ; 19(1): 109, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518319

RESUMO

BACKGROUND: X chromosome inactivation (XCI) is an important gene regulation mechanism in females to equalize the expression levels of X chromosome between two sexes. Generally, one of two X chromosomes in females is randomly chosen to be inactivated. Nonrandom XCI (XCI skewing) is also observed in females, which has been reported to play an important role in many X-linked diseases. However, there is no statistical measure available for the degree of the XCI skewing based on family data in population genetics. RESULTS: In this article, we propose a statistical approach to measure the degree of the XCI skewing based on family trios, which is represented by a ratio of two genotypic relative risks in females. The point estimate of the ratio is obtained from the maximum likelihood estimates of two genotypic relative risks. When parental genotypes are missing in some family trios, the expectation-conditional-maximization algorithm is adopted to obtain the corresponding maximum likelihood estimates. Further, the confidence interval of the ratio is derived based on the likelihood ratio test. Simulation results show that the likelihood-based confidence interval has an accurate coverage probability under the situations considered. Also, we apply our proposed method to the rheumatoid arthritis data from USA for its practical use, and find out that a locus, rs2238907, may undergo the XCI skewing against the at-risk allele. But this needs to be further confirmed by molecular genetics. CONCLUSIONS: The proposed statistical measure for the skewness of XCI is applicable to complete family trio data or family trio data with some paternal genotypes missing. The likelihood-based confidence interval has an accurate coverage probability under the situations considered. Therefore, our proposed statistical measure is generally recommended in practice for discovering the potential loci which undergo the XCI skewing.


Assuntos
Cromossomos Humanos X , Inativação do Cromossomo X , Alelos , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Genótipo , Humanos , Funções Verossimilhança , Polimorfismo de Nucleotídeo Único
20.
Front Microbiol ; 9: 1180, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29922263

RESUMO

Human adenovirus type 55 (HAdV-B55) is a recently identified acute respiratory disease (ARD) pathogen in HAdV species B with a recombinant genome between renal HAdV-B11 and respiratory HAdV-B14. Since HAdV-B55 first appeared in China school in 2006, no more ARD cases associated with it had been reported until 2011, when there was an outbreak of adult severe community-acquired pneumonia (CAP) in Beijing, China. Reported here is the bioinformatics analysis of the re-emergent HAdV-B55 responsible for this outbreak. Recombination and protein sequence analysis re-confirmed that this isolate (BJ01) was a recombinant virus with the capsid hexon gene from HAdV-B11. The selection pressures for the three capsid proteins, i.e., hexon, penton base, and fiber genes, were all negative, along with very low non-synonymous (dN) and synonymous (dS) substitutions/site (<0.0007). Phylogenetic analyses of the whole genome and the three major capsid genes of HAdV-B55 revealed the close phylogenetic relationship among all HAdV-B55 strains. Comparative genomic analysis of this re-emergent HAdV-B55 strain (BJ01; 2011) with the first HAdV-B55 strain (QS-DLL; 2006) showed the high genome identity (99.87%), including 10 single-nucleotide non-synonymous substitutions, 11 synonymous substitutions, 3 insertions, and one deletion in non-coding regions. The major non-synonymous substitutions (6 of 10) occurred in the protein pVI in its L3 region, which protein has different functions at various stages of an adenovirus infection, and may be associated with the population distribution of HAdV-B55 infection. No non-synonymous substitutions were found in the three major capsid proteins, which proteins are responsible for type-specific neutralizing antibodies. Comparative genomic analysis of the re-emergent HAdV-B55 strains associated with adult severe CAP revealed conserved genome and capsid proteins, providing the foundation for the development of effective vaccines against this pathogen. This study also facilitates the further investigation of HAdV-B55 epidemiology, molecular evolution, patterns of pathogen emergence and re-emergence, and the predication of genome recombination between adenoviruses.

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