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1.
Sci Rep ; 11(1): 23261, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853337

RESUMO

The most promising way to prevent the explosive spread of COVID-19 infection is to achieve herd immunity through vaccination. It is therefore important to motivate those who are less willing to be vaccinated. To address this issue, we conducted an online survey of 6232 Japanese people to investigate age- and gender-dependent differences in attitudes towards COVID-19 vaccination and the underlying psychological processes. We asked participants to read one of nine different messages about COVID-19 vaccination and rate their willingness to be vaccinated. We also collected their 17 social personality trait scores and demographic information. We found that males 10-20 years old were least willing to be vaccinated. We also found that prosocial traits are the driving force for young people, but the motivation in older people also depends on risk aversion and self-interest. Furthermore, an analysis of 9 different messages demonstrated that for young people (particularly males), the message emphasizing the majority's intention to vaccinate and scientific evidence for the safety of the vaccination had the strongest positive effect on the willingness to be vaccinated, suggesting that the "majority + scientific evidence" message nudges young people to show their prosocial nature in action.

2.
Leg Med (Tokyo) ; 54: 101993, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34808562

RESUMO

Based on the screening results of mass analyses using gas chromatography- mass spectrometry (GC-MS) and liquid chromatograph-tandem mass spectrometry (LC-MS/MS), we assessed the performance of Status DS10 (Status) and DRIVEN-FLOW® M8-Z (DF8), and compared the results with those of Triage DOA® (Triage) using 356 autopsy urine samples within one month of death. The sensitivity to benzodiazepines was 0.52 in Triage, 0.59 in Status, and 0.58 in DF8 with few false-positive cases. Triage detected triazolo-derivatives more easily than DF8. DF8 detected diazepam and nitro-benzodiazepines more easily than Status and Triage, with Status performing better than Triage. However, lorazepam detection with Status was difficult. There were 11 false-positive cases for amphetamines in Triage and 12 for Status-AMP at more than one week after death, but there were no false-positive in Status-MET and DF8. Tricyclic antidepressant (TCA) was detected in five cases by mass analysis, while there were 6 false-positive cases in Triage and 10 in both Status and DF8. In the TCA false-positive cases, tricyclic psychotics such as quetiapine, chlorpromazine, and carbamazepine existed. There were 23 true-positive and 6 false-positive cases for zolpidem in DF8 without false-negative cases. The accuracy of Status and DF8 for barbiturates or opiates was almost 1, but Triage was 0.98. There were no samples containing cocaine, THC, phencyclidine, or methadone. Based on the above, we conclude that Status and DF8 are comparable or slightly better than Triage, with fewer false-positive and fewer false-negative cases, except for TCA.

4.
BMC Med ; 19(1): 280, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34814922

RESUMO

BACKGROUND: Dietary biomarkers may complement dietary intake assessment made by dietary questionnaires. We developed an a-posteriori dietary biomarkers score based on Mediterranean diet food groups and evaluated its association with mortality. METHODS: 642 participants (56% female), aged ≥65 years, with complete data on dietary biomarkers were followed during 20 years in the InCHIANTI cohort study (Tuscany, Italy). The main outcomes were all-cause, cardiovascular, and cancer mortality. Dietary biomarkers were selected from literature and from correlation analyses with dietary intakes of Mediterranean diet food groups in the study. The baseline levels of the following dietary biomarkers were chosen: urinary total polyphenols and resveratrol metabolites, and plasma carotenoids, selenium, vitamin B12, linolenic, eicosapentaenoic and docosahexaenoic acids, and the mono-unsaturated/saturated fatty acid ratio. Associations of the Mediterranean diet score using dietary biomarkers and a validated food frequency questionnaire (FFQ) (as tertiles) with mortality were assessed through Cox regression. RESULTS: During the 20-year follow-up [median (Q1-Q3), 14 (8-18) years], and 435 deaths occurred (139 from cardiovascular diseases and 89 from cancer-related causes). In the fully adjusted models, the dietary biomarker-Mediterranean diet score was inversely associated with all-cause (HRT3vs.T1 0.72; 95%CI 0.56-0.91) and cardiovascular (HRT3vs.T1 0.60; 95%CI 0.38-0.93), but not with cancer mortality. Associations between the FFQ-Mediterranean diet score and mortality were not statistically significant. CONCLUSIONS: A greater adherence at baseline to a Mediterranean diet assessed by a dietary biomarker score was associated with a lower risk of mortality in older adults during a 20-year follow-up. The measurement of dietary biomarkers may contribute to guide individualized dietary counseling to older people. TRIAL REGISTRATION: NCT01331512.

5.
Am J Clin Nutr ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637504

RESUMO

BACKGROUND: Diet quality may be protective of physical function and muscle strength during aging. OBJECTIVES: We aimed to investigate associations of the Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet with physical function and grip strength. METHODS: Data were obtained from men and women in the Baltimore Longitudinal Study of Aging (mean ± SD age: 68 ± 14 y at first diet visit; n = 1358). Diet was assessed by FFQ. MIND diet score was calculated from 15 food groups, with a higher score indicating better diet quality; tertile categories of averaged MIND score across visits were used. Physical function was assessed using the Short Physical Performance Battery (SPPB), with a score < 10 indicative of impaired function, and the Health, Aging and Body Composition Physical Performance Battery (HABCPPB). The highest value of grip strength over 3 trials was used. Multivariable logistic and linear mixed-effects models were examined with repeated measurements of physical function and grip strength, respectively. RESULTS: MIND score was inversely associated with physical function impairment (per 1-point increment: OR: 0.81; 95% CI: 0.71, 0.93; P < 0.01), and with each SPPB component, over a median 6 y of follow-up. Participants in the highest compared with the lowest tertile of MIND diet score had 57% lower odds of functional impairment (OR: 0.43; 95% CI: 0.25, 0.73; P < 0.01), and slower decline by the HABCPPB. Men and women in the highest compared with the lowest tertiles of MIND score had 1.86-kg (95% CI: 0.33, 3.40 kg; P < 0.05) and 1.24-kg (95% CI: 0.04, 2.45 kg; P < 0.05) greater grip strength, respectively. CONCLUSIONS: Adherence to the MIND dietary pattern was associated with lower odds of physical function impairment and decline, and with better muscle strength, indicating that the MIND dietary pattern may be protective of physical functional health in older adults.

6.
Immunity ; 54(11): 2465-2480.e5, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34706222

RESUMO

Epigenetic reprogramming underlies specification of immune cell lineages, but patterns that uniquely define immune cell types and the mechanisms by which they are established remain unclear. Here, we identified lineage-specific DNA methylation signatures of six immune cell types from human peripheral blood and determined their relationship to other epigenetic and transcriptomic patterns. Sites of lineage-specific hypomethylation were associated with distinct combinations of transcription factors in each cell type. By contrast, sites of lineage-specific hypermethylation were restricted mostly to adaptive immune cells. PU.1 binding sites were associated with lineage-specific hypo- and hypermethylation in different cell types, suggesting that it regulates DNA methylation in a context-dependent manner. These observations indicate that innate and adaptive immune lineages are specified by distinct epigenetic mechanisms via combinatorial and context-dependent use of key transcription factors. The cell-specific epigenomics and transcriptional patterns identified serve as a foundation for future studies on immune dysregulation in diseases and aging.

7.
Aging (Albany NY) ; 13(20): 23471-23516, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34718232

RESUMO

It is widely thought that individuals age at different rates. A method that measures "physiological age" or physiological aging rate independent of chronological age could therefore help elucidate mechanisms of aging and inform an individual's risk of morbidity and mortality. Here we present machine learning frameworks for inferring individual physiological age from a broad range of biochemical and physiological traits including blood phenotypes (e.g., high-density lipoprotein), cardiovascular functions (e.g., pulse wave velocity) and psychological traits (e.g., neuroticism) as main groups in two population cohorts SardiNIA (~6,100 participants) and InCHIANTI (~1,400 participants). The inferred physiological age was highly correlated with chronological age (R2 > 0.8). We further defined an individual's physiological aging rate (PAR) as the ratio of the predicted physiological age to the chronological age. Notably, PAR was a significant predictor of survival, indicating an effect of aging rate on mortality. Our trait-based PAR was correlated with DNA methylation-based epigenetic aging score (r = 0.6), suggesting that both scores capture a common aging process. PAR was also substantially heritable (h2~0.3), and a subsequent genome-wide association study of PAR identified significant associations with two genetic loci, one of which is implicated in telomerase activity. Our findings support PAR as a proxy for an underlying whole-body aging mechanism. PAR may thus be useful to evaluate the efficacy of treatments that target aging-related deficits and controllable epidemiological factors.

8.
J Nutr ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550359

RESUMO

BACKGROUND: Although diets rich in carotenoids are associated with reduced risk of cardiovascular disease, age-related macular degeneration, disability, and other adverse aging outcomes, the underlying biological mechanisms are not fully elucidated. OBJECTIVES: To characterize the plasma proteome fingerprint associated with circulating carotenoid and retinol concentrations in older adults. METHODS: In 728 adults, ≥65 years, participating in the Invecchiare in Chianti (InCHIANTI) Study, plasma α-carotene, ß-carotene, ß-cryptoxanthin, lutein, zeaxanthin, and lycopene were measured using high performance liquid chromatography. The SOMAscan assay was used to measure 1301 plasma proteins. Multivariable linear regression models were used to examine the relationship of individual carotenoids and retinol with plasma proteins. A false discovery rate approach was used to deal with multiple comparisons using a q-value <0.05. RESULTS: Plasma ß-carotene, ß-cryptoxanthin, lutein, zeaxanthin, and lycopene were associated with 85, 39, 4, 2, and 5 plasma proteins, respectively, in multivariable linear regression models adjusting for potential confounders (q<0.05). No proteins were associated with α-carotene or retinol. Two or more carotenoids were positively associated with ferritin, 6-phosphogluconate dehydrogenase (decarboxylating), hepcidin, thrombospondin-2, and choline/ethanolamine kinase. The proteins associated with circulating carotenoids were related to energy metabolism, sirtuin signaling, inflammation and oxidative stress, iron metabolism, proteostasis, innate immunity, and longevity. CONCLUSIONS: The plasma proteomic fingerprint associated with elevated circulating carotenoids in older adults provide insight into the mechanisms underlying the protective role of carotenoids on health.

9.
Nat Commun ; 12(1): 5647, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561431

RESUMO

Comparing transcript levels between healthy and diseased individuals allows the identification of differentially expressed genes, which may be causes, consequences or mere correlates of the disease under scrutiny. We propose a method to decompose the observational correlation between gene expression and phenotypes driven by confounders, forward- and reverse causal effects. The bi-directional causal effects between gene expression and complex traits are obtained by Mendelian Randomization integrating summary-level data from GWAS and whole-blood eQTLs. Applying this approach to complex traits reveals that forward effects have negligible contribution. For example, BMI- and triglycerides-gene expression correlation coefficients robustly correlate with trait-to-expression causal effects (rBMI = 0.11, PBMI = 2.0 × 10-51 and rTG = 0.13, PTG = 1.1 × 10-68), but not detectably with expression-to-trait effects. Our results demonstrate that studies comparing the transcriptome of diseased and healthy subjects are more prone to reveal disease-induced gene expression changes rather than disease causing ones.


Assuntos
Algoritmos , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Transcriptoma/genética , Causalidade , Estudos de Associação Genética/métodos , Humanos , Análise da Randomização Mendeliana/métodos , Fenótipo , Locos de Características Quantitativas/genética
10.
Nat Hum Behav ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426670

RESUMO

Dietary intake is a major contributor to the global obesity epidemic and represents a complex behavioural phenotype that is partially affected by innate biological differences. Here, we present a multivariate genome-wide association analysis of overall variation in dietary intake to account for the correlation between dietary carbohydrate, fat and protein in 282,271 participants of European ancestry from the UK Biobank (n = 191,157) and Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 91,114), and identify 26 distinct genome-wide significant loci. Dietary intake signals map exclusively to specific brain regions and are enriched for genes expressed in specialized subtypes of GABAergic, dopaminergic and glutamatergic neurons. We identified two main clusters of genetic variants for overall variation in dietary intake that were differently associated with obesity and coronary artery disease. These results enhance the biological understanding of interindividual differences in dietary intake by highlighting neural mechanisms, supporting functional follow-up experiments and possibly providing new avenues for the prevention and treatment of prevalent complex metabolic diseases.

11.
J UOEH ; 43(2): 197-203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34092764

RESUMO

We gave mice a 540 mg/kg dose of LD50 acephate, followed by an assessment of acephate, methamidophos (MP), and choline esterase (ChE) activity for up to 4 hours (hr) in order to investigate the time course of acephate intoxication. At 1 hr, the blood acephate and MP levels were 428 ± 90 µg/ml (mean ± SEM) and 4.2 ± 0.4 µg/ ml, respectively. The liver acephate levels were similar to those in the blood, but the liver MP levels were approximately 3.5 times that of the blood at 1 hr. The brain MP level tended to be higher than the blood MP at 1 hr. These levels decreased gradually over 4 hr, but the brain acephate and MP levels surpassed the blood levels significantly at 4 hr, and after 2 hr, respectively. Serum, liver, cerebrum, cerebellum, and brainstem cholinesterase activity (ChE) were inhibited at 1 hr, and remained inhibited in all but the cerebellum until the end of the experiment. The obtained data were applied to previously reported autopsy cases of acephate intake. Experimental data suggest that brain MP is involved in acute acephate-induced poisoning, even after a reduction in blood acephate. In autopsy cases with suspected acephate poisoning, the MP level in the brain should be considered in addition to the ChE activity to diagnose the cause of death.


Assuntos
Inibidores da Colinesterase , Inseticidas , Animais , Encéfalo , Camundongos , Compostos Organotiofosforados , Fosforamidas
12.
Front Physiol ; 12: 674013, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135771

RESUMO

Human aging is associated with a decline of physical and cognitive function and high susceptibility to chronic diseases, which is influenced by genetics, epigenetics, environmental, and socio-economic status. In order to identify the factors that modulate the aging process, established measures of aging mechanisms are required, that are both robust and feasible in humans. It is also necessary to connect these measures to the phenotypes of aging and their functional consequences. In this review, we focus on how this has been addressed from an epidemiologic perspective using proteomics. The key aspects of epidemiological models of aging can be incorporated into proteomics and other omics which can provide critical detailed information on the molecular and biological processes that change with age, thus unveiling underlying mechanisms that drive multiple chronic conditions and frailty, and ideally facilitating the identification of new effective approaches for prevention and treatment.

13.
Forensic Sci Med Pathol ; 17(3): 465-468, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34106422

RESUMO

An 86-year-old female was found unconscious the day after taking a prescribed tablet containing a combination of tramadol and acetaminophen. At admission to the hospital, marked hypoglycemia (blood glucose: 4 mg/dL) was confirmed, but serum insulin and C-peptide were within the normal range, which suggested that neither endogenous hyperinsulinemia nor exogenous insulin administration was responsible for the hypoglycemia. Despite resuscitation efforts, the woman subsequently died. At autopsy, there was renal disorder, but any pathological abnormalities that could have caused hypoglycemia were not observed. Blood tramadol and acetaminophen were in the therapeutic range. We speculate that the cause of fatal hypoglycemia was tramadol intake at the therapeutic dose. Older age and renal insufficiency are factors that could have potentially caused the fatal hypoglycemia in this case despite tramadol having been taken at a therapeutic dose. This is the first case report of fatal hypoglycemia following ingestion of a therapeutic dose of tramadol.


Assuntos
Hipoglicemia , Tramadol , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Autopsia , Ingestão de Alimentos , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Tramadol/efeitos adversos
14.
Nutrients ; 13(4)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808076

RESUMO

Identifying modifying protective factors to promote healthy aging is of utmost public health importance. The frailty index (FI) reflects the accumulation of health deficits and is one widely used method to assess health trajectories in aging. Adherence to a Mediterranean-type diet (MTD) has been associated with favorable health trajectories. Therefore, this study explored whether adherence to a MTD is negatively associated with FI in the InCHIANTI study. Participants (n = 485) included individuals over 65 years of age at baseline with complete data over a follow-up period of 10 years. MTD was computed on a scale of 0-9 and categorized based on these scores into three groups of low (≤3), medium (4-5), and high (≥6) adherence. Being in a high or medium adherence group was associated with 0.03 and 0.013 unit lower FI scores over the follow-up period, compared to the low adherence group. In participants with a low FI at baseline, being in a high or medium MTD-adherence group had 0.004 and 0.005 unit/year slower progression of FI compared to the low adherence group. These study results support adherence to a MTD as a protective strategy to maintain a lower FI.


Assuntos
Dieta Mediterrânea , Fragilidade/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
15.
Aging Cell ; 20(4): e13325, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33730416

RESUMO

The identification of plasma proteins that systematically change with age and, independent of chronological age, predict accelerated decline of health is an expanding area of research. Circulating proteins are ideal translational "omics" since they are final effectors of physiological pathways and because physicians are accustomed to use information of plasma proteins as biomarkers for diagnosis, prognosis, and tracking the effectiveness of treatments. Recent technological advancements, including mass spectrometry (MS)-based proteomics, multiplexed proteomic assay using modified aptamers (SOMAscan), and Proximity Extension Assay (PEA, O-Link), have allowed for the assessment of thousands of proteins in plasma or other biological matrices, which are potentially translatable into new clinical biomarkers and provide new clues about the mechanisms by which aging is associated with health deterioration and functional decline. We carried out a detailed literature search for proteomic studies performed in different matrices (plasma, serum, urine, saliva, tissues) and species using multiple platforms. Herein, we identified 232 proteins that were age-associated across studies. Enrichment analysis of the 232 age-associated proteins revealed metabolic pathways previously connected with biological aging both in animal models and in humans, most remarkably insulin-like growth factor (IGF) signaling, mitogen-activated protein kinases (MAPK), hypoxia-inducible factor 1 (HIF1), cytokine signaling, Forkhead Box O (FOXO) metabolic pathways, folate metabolism, advance glycation end products (AGE), and receptor AGE (RAGE) metabolic pathway. Information on these age-relevant proteins, likely expanded and validated in longitudinal studies and examined in mechanistic studies, will be essential for patient stratification and the development of new treatments aimed at improving health expectancy.

16.
Clin Epigenetics ; 13(1): 60, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752734

RESUMO

BACKGROUND: DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. RESULTS: We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. CONCLUSIONS: Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.

18.
Geroscience ; 43(2): 619-627, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33462706

RESUMO

Levels of angiotensin-converting enzyme 2 (ACE2), the gateway for COVID-19 virus into the cells, have been implicated in worse COVID-19 outcomes associated with aging and cardiovascular disease (CVD). Data on age-associated differences in circulating ACE2 levels in humans and the role of CVD and medications is limited. We analyzed data from 967 participants of the InCHIANTI study, a community-dwelling cohort in the Chianti region, Italy. Relative abundance of ACE2 in plasma was assessed using a proteomics platform. CVD diagnoses, use of renin-angiotensin-aldosterone system (RAAS) antagonists: ACEi, ARBs, and aldosterone antagonists, were ascertained. Multiple linear analyses were performed to examine the independent association of ACE2 with age, CVD, and RAAS antagonist use. Age was independently associated with lower log (ACE2) in persons aged ≥ 55 years (STD ß = - 0.12, p = 0.0002). ACEi treatment was also independently associated with significantly lower ACE2 levels, and ACE2 was inversely associated with weight, and positively associated with peripheral artery disease (PAD) status. There was a trend toward higher circulating ACE2 levels in hypertensive individuals, but it did not reach statistical significance. In a stratified analysis, the association between log (ACE2) and log (IL-6) was more evidenced in participants with PAD. Circulating ACE2 levels demonstrate curvilinear association with age, with older individuals beyond the sixth decade age having lower levels. ACEi was associated with greater circulating ACE2 levels. Interestingly, ACE2 was elevated in PAD and positively associated with inflammatory markers, suggesting compensatory upregulation in the setting of chronic inflammation. Further studies are needed to comprehensively characterize RAAS components with aging and disease, and assess its prognostic role in predicting COVID-19 outcomes.


Assuntos
COVID-19 , Peptidil Dipeptidase A , Idoso , Antagonistas de Receptores de Angiotensina , Enzima de Conversão de Angiotensina 2 , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Humanos , Itália/epidemiologia , SARS-CoV-2
19.
Leg Med (Tokyo) ; 49: 101847, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33465569

RESUMO

A man and a woman were rescued from a room that had exploded. Many empty cassette gas cylinders were found in the room. The man and woman were hospitalized immediately for the treatment of burns. The woman died 6 days later, and the man died 31 days later without regaining consciousness. Carbonization and hardening of the frontal facial skin and parts of the left and right fingers were observed on the man's body. In both cases, systemic burns had led to progressive systemic edema and markedly suppressed circulation. Analytical samples for butanes obtained from their bodies at autopsy were stored at -20 °C for 14 and 25 days, respectively, before analysis. Normal butane and isobutane were quantified in the brain and subcutaneous adipose tissue of the woman. Only the isobutane was quantified in the adipose tissue of the man. The evidence suggests that the man lit a cigarette while breathing gas and the entire room exploded. Our results also suggest that butane can be detected in the adipose tissue of autopsy cases long after inhalation even under the present storage conditions, and isobutane may remain in adipose tissue longer than n-butane.


Assuntos
Tecido Adiposo/metabolismo , Autopsia/métodos , Queimaduras/metabolismo , Queimaduras/patologia , Butanos/análise , Medicina Legal/métodos , Adulto , Queimaduras/complicações , Córtex Cerebral/metabolismo , Edema/etiologia , Edema/patologia , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Preservação de Tecido/métodos
20.
Nat Commun ; 12(1): 654, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510174

RESUMO

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10-17), arthritis (GDF5 p = 4 × 10-13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Debilidade Muscular/genética , Sarcopenia/genética , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Estudos de Coortes , Europa (Continente) , Feminino , Fator 5 de Diferenciação de Crescimento/genética , Cadeias alfa de HLA-DQ/genética , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/genética , Força Muscular/fisiologia , Debilidade Muscular/fisiopatologia , Polimorfismo de Nucleotídeo Único , Sarcopenia/fisiopatologia
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