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1.
JCI Insight ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600170

RESUMO

BACKGROUND: The presence of an early repolarization pattern (ERP) on the surface electrocardiogram (ECG) is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait but molecular genetic determinants are unknown. METHODS: To identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry. RESULTS: We identified a genome-wide significant (p<5E-8) locus in the KCND3 (potassium voltage gated channel subfamily D member 3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, p=7.7E-12), but did not reveal additional loci. Co-localization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery. CONCLUSIONS: In this study we identified for the first time a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene not only provide insights into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies. FUNDING: For detailed information per study, see Acknowledgments.

2.
Nat Commun ; 10(1): 4505, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582752

RESUMO

The human gut is inhabited by a complex and metabolically active microbial ecosystem. While many studies focused on the effect of individual microbial taxa on human health, their overall metabolic potential has been under-explored. Using whole-metagenome shotgun sequencing data in 1,004 twins, we first observed that unrelated subjects share, on average, almost double the number of metabolic pathways (82%) than species (43%). Then, using 673 blood and 713 faecal metabolites, we found metabolic pathways to be associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species showed less than 3,000 associations. Finally, we estimated that the microbiome was involved in a dialogue between 71% of faecal, and 15% of blood, metabolites. This study underlines the importance of studying the microbial metabolic potential rather than focusing purely on taxonomy to find therapeutic and diagnostic targets, and provides a unique resource describing the interplay between the microbiome and the systemic and faecal metabolic environments.

3.
Sci Rep ; 9(1): 15088, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31636301

RESUMO

Electrolytes have a crucial role in maintaining health and their serum levels are homeostatically maintained within a narrow range by multiple pathways involving the kidneys. Here we use metabolomics profiling (592 fasting serum metabolites) to identify molecular markers and pathways associated with serum electrolyte levels in two independent population-based cohorts. We included 1523 adults from TwinsUK not on blood pressure-lowering therapy and without renal impairment to look for metabolites associated with chloride, sodium, potassium and bicarbonate by running linear mixed models adjusting for covariates and multiple comparisons. For each electrolyte, we further performed pathway enrichment analysis (PAGE algorithm). Results were replicated in an independent cohort. Chloride, potassium, bicarbonate and sodium associated with 10, 58, 36 and 17 metabolites respectively (each P < 2.1 × 10-5), mainly lipids. Of all the electrolytes, serum potassium showed the most significant associations with individual fatty acid metabolites and specific enrichment of fatty acid pathways. In contrast, serum sodium and bicarbonate showed associations predominantly with amino-acid related species. In the first study to examine systematically associations between serum electrolytes and small circulating molecules, we identified novel metabolites and metabolic pathways associated with serum electrolyte levels. The role of these metabolic pathways on electrolyte homeostasis merits further studies.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31403758

RESUMO

Body site is highly relevant for melanoma: it affects prognosis and varies according to the patient's sex. The distribution of naevi, a major risk factor for melanoma, at different body sites also varies according to sex in childhood. Using naevus counts at different body sites in 492 unrelated adults from both sexes, we observed that women have an increased number of naevi on the lower limbs compared to men (p = 8.5 × 10-5 ), showing that a high naevus count on this site persists from childhood throughout life. Then, using data from 3,232 twins, we observed, in women, the lowest naevus count heritability on the trunk (26%), and the highest on the lower limbs (69%). Finally, we showed that, in 2,864 women, six genomic loci previously associated with both naevus count and melanoma risk (IRF4, DOCK8, MTAP, 9q31.2, KITLG and PLA2G6) have an effect on naevus count that is body site-specific, but whose effect sizes are predominantly stronger on the lower limbs. Sex-specific genetic influence on naevus count at different sites may explain differences in site-specific melanoma incidence as well as prognosis between sexes.

6.
Nat Commun ; 10(1): 3346, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431621

RESUMO

Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18-109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar in men and women and across different age strata. We subsequently show that the prediction accuracy of 5- and 10-year mortality based on a model containing the identified biomarkers and sex (C-statistic = 0.837 and 0.830, respectively) is better than that of a model containing conventional risk factors for mortality (C-statistic = 0.772 and 0.790, respectively). The use of the identified metabolic profile as a predictor of mortality or surrogate endpoint in clinical studies needs further investigation.

7.
Sci Rep ; 9(1): 11623, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31406173

RESUMO

Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10-6), methionine (p-value = 9.2 × 10-5), tyrosine (p-value = 2.1 × 10-4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10-4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10-4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10-4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality.

8.
Sci Rep ; 9(1): 9758, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278309

RESUMO

Both gut microbiota and diet have been shown to impact visceral fat mass (VFM), a major risk factor for cardiometabolic disease, but their relative contribution has not been well characterised. We aimed to estimate and separate the effect of gut microbiota composition from that of nutrient intake on VFM in 1760 older female twins. Through pairwise association analyses, we identified 93 operational taxonomic units (OTUs) and 10 nutrients independently linked to VFM (FDR < 5%). Conditional analyses revealed that the majority (87%) of the 93 VFM-associated OTUs remained significantly associated with VFM irrespective of nutrient intake correction. In contrast, we observed that the effect of fibre, magnesium, biotin and vitamin E on VFM was partially mediated by OTUs. Moreover, we estimated that OTUs were more accurate predictors of VFM than nutrients and accounted for a larger percentage of its variance. Our results suggest that while the role of certain nutrients on VFM appears to depend on gut microbiota composition, specific gut microbes may affect host adiposity regardless of dietary intake. The findings imply that the gut microbiota may have a greater contribution towards shaping host VFM than diet alone. Thus, microbial-based therapy should be prioritised for VFM reduction in overweight and obese subjects.

9.
Nat Commun ; 10(1): 2581, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197173

RESUMO

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.


Assuntos
Metilação de DNA/fisiologia , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Insulina/metabolismo , Obesidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Ilhas de CpG/genética , Diabetes Mellitus Tipo 2/metabolismo , Epigênese Genética/fisiologia , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Estudo de Associação Genômica Ampla/métodos , Homeostase/genética , Humanos , Masculino , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Obesidade/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto Jovem
10.
Nat Neurosci ; 22(7): 1196, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168101

RESUMO

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

11.
Gut Microbes ; : 1-8, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31030641

RESUMO

The gut microbiome has recently emerged as an important regulator of insulin resistance and abdominal obesity. The tryptophan metabolite generated by the gut microbiome, indoleproprionic acid (IPA) has been shown to predict the onset of type 2 diabetes. IPA is a metabolite produced by gut microbes from dietary tryptophan that exhibits a high degree of inter-individual variation. The microbiome composition parameters that are associated with circulating levels of this potent anti-oxidant have however not been investigated to date in human populations. In 1018 middle-aged women from the TwinsUK cohort, we assessed the relationship between serum IPA levels and gut microbiome composition targeting the 16S rRNA gene. Microbiome alpha-diversity was positively correlated with serum indoleproprionic acid levels (Shannon Diversity: Beta[95%CI] = 0.19[0.13;0.25], P = 6.41 × 10-10) after adjustment for covariates. Sixteen taxa and 12 operational taxonomic units (OTUs) associated with IPA serum levels. Among these are positive correlations with the butyrate-producing Faecalibacterium prausnitzii, the class Mollicutes and the order RF39 of the Tenericutes, and Coprococcus Negative correlations instead were observed with Eubacterium dolichum previously shown to correlate with visceral fat mass and several genera in the Lachnospiraceae family such as Blautia and Ruminococcus previously shown to correlate with obesity. Microbiome composition parameters explained ~20% of the variation in circulating levels of IPA, whereas nutritional and host genetic parameters explained only ~4%. Our data confirm an association between IPA circulating levels and metabolic syndrome parameters and indicate that gut microbiome composition influences IPA levels.

12.
Clin Epigenetics ; 11(1): 27, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760334

RESUMO

BACKGROUND: Genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism for mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease. METHODS: Self-reported gingival bleeding and history of gum disease, or tooth mobility, were used as indicators of periodontal disease. DNA methylation profiles were generated using the Infinium HumanMethylation450 BeadChip in whole blood, buccal, and adipose tissue samples from predominantly older female twins (mean age 58) from the TwinsUK cohort. Epigenome-wide association scans (EWAS) of gingival bleeding and tooth mobility were conducted in whole blood in 528 and 492 twins, respectively. Subsequently, targeted candidate gene analysis at 28 genomic regions was carried out testing for phenotype-methylation associations in 41 (tooth mobility) and 43 (gingival bleeding) buccal, and 501 (tooth mobility) and 556 (gingival bleeding) adipose DNA samples. RESULTS: Epigenome-wide analyses in blood identified one CpG-site (cg21245277 in ZNF804A) associated with gingival bleeding (FDR = 0.03, nominal p value = 7.17e-8) and 58 sites associated with tooth mobility (FDR < 0.05) with the top signals in IQCE and XKR6. Epigenetic variation at 28 candidate regions (247 CpG-sites) for chronic periodontitis showed an enrichment for association with periodontal traits, and signals in eight genes (VDR, IL6ST, TMCO6, IL1RN, CD44, IL1B, WHAMM, and CXCL1) were significant in both traits. The methylation-phenotype association signals validated in buccal samples, and a subset (25%) also validated in adipose tissue. CONCLUSIONS: Epigenome-wide analyses in adult female twins identified specific DNA methylation changes linked to self-reported periodontal disease. Future work will explore the environmental basis and functional impact of these results to infer potential for strategic personalized treatments and prevention of chronic periodontitis.


Assuntos
Metilação de DNA , Doenças em Gêmeos/genética , Estudo de Associação Genômica Ampla/métodos , Periodontite/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ilhas de CpG , Estudos Transversais , Epigênese Genética , Feminino , Humanos , Pessoa de Meia-Idade , Fenótipo , Análise de Sequência de RNA/métodos , Reino Unido
13.
Redox Biol ; 20: 349-353, 2018 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-30391827

RESUMO

Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Mechanisms involved in its homeostasis are not well understood, but associations between metabolic factors and IOP have been reported. To investigate the relationship between levels of circulating metabolites and IOP, we performed a metabolome-wide association using a machine learning algorithm, and then employing Mendelian Randomization models to further explore the strength and directionality of effect of the metabolites on IOP. We show that O-methylascorbate, a circulating Vitamin C metabolite, has a significant IOP-lowering effect, consistent with previous knowledge of the anti-hypertensive and anti-oxidative role of ascorbate compounds. These results enhance understanding of IOP control and may potentially benefit future IOP treatment and reduce vision loss from glaucoma.

14.
Clin Epigenetics ; 10(1): 126, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30342560

RESUMO

BACKGROUND: Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic health, remains unclear. METHODS: We investigated smoking-associated DNA methylation and gene expression variation in adipose tissue biopsies from 542 healthy female twins. Replication, tissue specificity, and longitudinal stability of the smoking-associated effects were explored in additional adipose, blood, skin, and lung samples. We characterized the impact of adipose tissue smoking methylation and expression signals on metabolic disease risk phenotypes, including visceral fat. RESULTS: We identified 42 smoking-methylation and 42 smoking-expression signals, where five genes (AHRR, CYP1A1, CYP1B1, CYTL1, F2RL3) were both hypo-methylated and upregulated in current smokers. CYP1A1 gene expression achieved 95% prediction performance of current smoking status. We validated and replicated a proportion of the signals in additional primary tissue samples, identifying tissue-shared effects. Smoking leaves systemic imprints on DNA methylation after smoking cessation, with stronger but shorter-lived effects on gene expression. Metabolic disease risk traits such as visceral fat and android-to-gynoid ratio showed association with methylation at smoking markers with functional impacts on expression, such as CYP1A1, and at tissue-shared smoking signals, such as NOTCH1. At smoking-signals, BHLHE40 and AHRR DNA methylation and gene expression levels in current smokers were predictive of future gain in visceral fat upon smoking cessation. CONCLUSIONS: Our results provide the first comprehensive characterization of coordinated DNA methylation and gene expression markers of smoking in adipose tissue. The findings relate to human metabolic health and give insights into understanding the widespread health consequence of smoking outside of the lung.

15.
Cell Metab ; 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30318341

RESUMO

Obesity is a heterogeneous phenotype that is crudely measured by body mass index (BMI). There is a need for a more precise yet portable method of phenotyping and categorizing risk in large numbers of people with obesity to advance clinical care and drug development. Here, we used non-targeted metabolomics and whole-genome sequencing to identify metabolic and genetic signatures of obesity. We find that obesity results in profound perturbation of the metabolome; nearly a third of the assayed metabolites associated with changes in BMI. A metabolome signature identifies the healthy obese and lean individuals with abnormal metabolomes-these groups differ in health outcomes and underlying genetic risk. Specifically, an abnormal metabolome associated with a 2- to 5-fold increase in cardiovascular events when comparing individuals who were matched for BMI but had opposing metabolome signatures. Because metabolome profiling identifies clinically meaningful heterogeneity in obesity, this approach could help select patients for clinical trials.

16.
J Bone Miner Res ; 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30320955

RESUMO

We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2 > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

17.
Sci Rep ; 8(1): 15249, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30323304

RESUMO

Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function-associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.

18.
Sci Rep ; 8(1): 14862, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30291282

RESUMO

Genome-wide DNA methylation has been implicated in complex human diseases. Here, we identified epigenetic biomarkers for type 2 diabetes (T2D) underlying obesogenic environments. In a blood-based DNA methylation analysis of 11 monozygotic twins (MZTW) discordant for T2D, we discovered genetically independent candidate methylation sites. In a follow-up replication study (17 MZTW pairs) for external validation, we replicated the T2D-association at a novel CpG signal in the ELOVL fatty acid elongase 5 (ELOVL5) gene specific to T2D-discordant MZTW. For concordant DNA methylation signatures in tissues, we further confirmed that a CpG site (cg18681426) was associated with adipogenic differentiation between human preadipocytes and adipocytes isolated from the same biopsy sample. In addition, the ELOVL5 gene was significantly differentially expressed in adipose tissues from unrelated T2D patients and in human pancreatic islets. Our results demonstrate that blood-derived DNA methylation is associated with T2D risk as a proxy for cumulative epigenetic status in human adipose and pancreatic tissues. Moreover, ELOVL5 expression was increased in cellular and mouse models of induced obesity-related diabetes. These findings may provide new insights into epigenetic architecture by uncovering methylation-based biomarkers.

19.
Cardiovasc Ultrasound ; 16(1): 21, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30249257

RESUMO

BACKGROUND: Interactions between the left ventricular (LV) and the arterial system, (ventricular-arterial coupling) are key determinants of cardiovascular function. However, most of studies covered multiple cardiovascular risk factors, which also contributed to the morphological and functional changes of LV. The aim of this study was to examine the relationship between arterial stiffness and LV structure and function in healthy women with a low burden of risk factors. METHODS: Healthy women from the Twins UK cohort (n = 147, mean age was 54.07 ± 11.90 years) were studied. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV). LV structure and function were assessed by two-dimensional speckle tracking echocardiography. RESULTS: cf-PWV was significantly associated with most measures of LV geometry and function, including relative wall thickness (RWT), E/e' ratio, global circumferential and radial strain, apical rotation and LV twist (each p <  0.05), but bore no relation to global longitudinal strain. After adjustment for age, body mass index, blood pressure and heart rate, cf-PWV was significantly correlated with RWT, global circumferential strain, apical rotation and LV twist (ß = 0.011, - 0.484, 1.167 and 1.089, respectively, each p ≤  0.05). CONCLUSIONS: In healthy women with a low burden of risk factors, elevated arterial stiffness was intimately interwoven with increased LV twisting even before LV dysfunction becomes clinically evident.


Assuntos
Aorta Torácica/fisiologia , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Rigidez Vascular/fisiologia , Função Ventricular Esquerda/fisiologia , Aorta Torácica/diagnóstico por imagem , Diástole , Feminino , Voluntários Saudáveis , Humanos , Pessoa de Meia-Idade , Análise de Onda de Pulso
20.
Appl Microbiol Biotechnol ; 102(20): 8629-8646, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30078138

RESUMO

Owing to the increased cost-effectiveness of high-throughput technologies, the number of studies focusing on the human microbiome and its connections to human health and disease has recently surged. However, best practices in microbiology and clinical research have yet to be clearly established. Here, we present an overview of the challenges and opportunities involved in conducting a metagenomic study, with a particular focus on data processing and analytical methods.


Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Metagenômica , Bactérias/classificação , Bactérias/genética , Protocolos Clínicos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenômica/métodos , Microbiologia
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