Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 80
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eklem Hastalik Cerrahisi ; 30(3): 289-95, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31650927

RESUMO

OBJECTIVES: This study aims to assess the effects of the hematopoietic stem cells and endothelial progenitor cells in peripheral blood and monocyte cluster of differentiation (CD) 34, CD133 and CD309 expression levels on maturation at the repair site in patients who underwent forearm arterial repair. PATIENTS AND METHODS: This prospective study included 30 patients (23 males, 7 females; mean age 28.9±1.8 years; range, 18 to 49 years) with a well-defined cut at the wrist due to a stabbing injury but no comorbid condition who presented to the emergency department of our hospital between November 2014 and November 2017. Vascular patency was assessed by Doppler sonography in patients who underwent forearm arterial repair via micro-vascular techniques. The relationships between patency and hematopoietic stem and endothelial progenitor cell markers such as CD34, CD133 and CD309 were assessed by flow cytometry. RESULTS: The patients were divided into two groups according to presence of sufficient flow in the arteries repaired. The mean CD34 expression level was 72.09±3.00 in the group with maturation whereas it was 54.64±7.34 in the group without maturation, indicating a statistically significant difference (p<0.05). In addition, the likelihood of sufficient flow was increased by 1.075 per one unit increase in CD34 level. Resistive index values were significantly lower in the group with maturation and CD34 level was predictive for maturation of arterial repair. CONCLUSION: In the present study, the findings demonstrated that high CD34 expression level has favorable effects on maturation after arterial repair.

3.
Nat Commun ; 10(1): 3653, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409800

RESUMO

Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over-represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits.

4.
Methods Mol Biol ; 2037: 453-470, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31463860

RESUMO

NMR data from large studies combining multiple cohorts is becoming common in large-scale metabolomics. The data size and combination of cohorts with diverse properties leads to special problems for data processing and analysis. These include alignment, normalization, detection and removal of outliers, presence of strong correlations, and the identification of unknowns. Nonetheless, these challenges can be addressed with suitable algorithms and techniques, leading to enhanced data sets ripe for further data mining.

5.
Nat Hum Behav ; 3(9): 950-961, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31358974

RESUMO

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.

6.
Ann Ital Chir ; 90: 264-268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354154

RESUMO

AIMS: This study aimed to examine the correlation between DTI, clinical assessment, and electromyography results in patients who underwent primary median nerve repair. METHODS: Ten patients who underwent primary repair of the complete median nerve transection were included. Study assessments were performed on both the traumatized and non-traumatized extremities and patients were followed up for a minimum duration of 11 months. Clinical assessments, (Tinnel test, static 2-point discrimination test, motor and quality of life assessments), electromyography and DTI were performed. RESULTS: None of the clinical or electromyographic parameters correlated significantly with any of the diffusion tensor imaging parameters, i.e. fractional anisotropy (FA) or apparent diffusion coefficient (ADC) (p>0.05 for all). In addition, The Disabilities of the Arm, Shoulder and Hand (DASH) scores did not correlate with either FA (r=0.55, p=0.098) or ADC (r=0.40, p=0.260) values. However, Tinnel positive cases (n=3) had lower relative FA when compared to Tinnel negative cases (n=7) (-0.11±0.19 vs. 0.05±0.04, p=0.033). CONCLUSION: Our findings do not support the presence of relations between DTI parameters and electromyographic or most of the clinical parameters. Further MRI studies with larger numbers of patients with complete transection of the median nerve using the novel imaging parameters are warranted. KEY WORDS: Diffusion Tensor Imaging (DTI), Electromyography (EMG), Median nerve, Nerve injury, Nerve repair.

7.
Eur Heart J ; 40(34): 2883-2896, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31102408

RESUMO

AIMS: To characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). METHODS AND RESULTS: We used untargeted one-dimensional (1D) serum metabolic profiling by proton nuclear magnetic resonance spectroscopy (1H NMR) among 3867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3569 participants from the Rotterdam and LOLIPOP studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 1H NMR measured metabolites were associated with CAC and/or IMT, P = 1.3 × 10-14 to 1.0 × 10-6 (discovery) and P = 5.6 × 10-10 to 1.1 × 10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched chain, and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine, and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide, and lactate as well as apolipoprotein B (P < 0.05). CONCLUSION: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclerosis.

8.
J Am Heart Assoc ; 8(9): e010810, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31017036

RESUMO

Background Identifying associations between serum metabolites and visceral adipose tissue ( VAT ) could provide novel biomarkers of VAT and insights into the pathogenesis of obesity-related diseases. We aimed to discover and replicate metabolites reflecting pathways related to VAT . Methods and Results Associations between fasting serum metabolites and VAT area (by computed tomography or magnetic resonance imaging) were assessed with cross-sectional linear regression of individual-level data from participants in MESA (Multi-Ethnic Study of Atherosclerosis; discovery, N=1103) and the NEO (Netherlands Epidemiology of Obesity) study (replication, N=2537). Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed in MESA, and metabolites were replicated in the NEO study using targeted 1H nuclear magnetic resonance spectroscopy. A total of 30 590 metabolomic spectral variables were evaluated. After adjustment for age, sex, race/ethnicity, socioeconomic status, smoking, physical activity, glucose/lipid-lowering medication, and body mass index, 2104 variables representing 24 nonlipid and 49 lipid/lipoprotein subclass metabolites remained significantly associated with VAT ( P=4.88×10-20-1.16×10-3). These included conventional metabolites, amino acids, acetylglycoproteins, intermediates of glucose and hepatic metabolism, organic acids, and subclasses of apolipoproteins, cholesterol, phospholipids, and triglycerides. Metabolites mapped to 31 biochemical pathways, including amino acid substrate use/metabolism and glycolysis/gluconeogenesis. In the replication cohort, acetylglycoproteins, branched-chain amino acids, lactate, glutamine (inversely), and atherogenic lipids remained associated with VAT ( P=1.90×10-35-8.46×10-7), with most associations remaining after additional adjustment for surrogates of VAT (glucose level, waist circumference, and serum triglycerides), reflecting novel independent associations. Conclusions We identified and replicated a metabolite panel associated with VAT in 2 community-based cohorts. These findings persisted after adjustment for body mass index and appear to define a metabolic signature of visceral adiposity.

9.
Gigascience ; 8(2)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30535405

RESUMO

BACKGROUND: Metabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organism's metabolism. The research field is dynamic and expanding with applications across biomedical, biotechnological, and many other applied biological domains. Its computationally intensive nature has driven requirements for open data formats, data repositories, and data analysis tools. However, the rapid progress has resulted in a mosaic of independent, and sometimes incompatible, analysis methods that are difficult to connect into a useful and complete data analysis solution. FINDINGS: PhenoMeNal (Phenome and Metabolome aNalysis) is an advanced and complete solution to set up Infrastructure-as-a-Service (IaaS) that brings workflow-oriented, interoperable metabolomics data analysis platforms into the cloud. PhenoMeNal seamlessly integrates a wide array of existing open-source tools that are tested and packaged as Docker containers through the project's continuous integration process and deployed based on a kubernetes orchestration framework. It also provides a number of standardized, automated, and published analysis workflows in the user interfaces Galaxy, Jupyter, Luigi, and Pachyderm. CONCLUSIONS: PhenoMeNal constitutes a keystone solution in cloud e-infrastructures available for metabolomics. PhenoMeNal is a unique and complete solution for setting up cloud e-infrastructures through easy-to-use web interfaces that can be scaled to any custom public and private cloud environment. By harmonizing and automating software installation and configuration and through ready-to-use scientific workflow user interfaces, PhenoMeNal has succeeded in providing scientists with workflow-driven, reproducible, and shareable metabolomics data analysis platforms that are interfaced through standard data formats, representative datasets, versioned, and have been tested for reproducibility and interoperability. The elastic implementation of PhenoMeNal further allows easy adaptation of the infrastructure to other application areas and 'omics research domains.


Assuntos
Metabolômica/métodos , Software , Computação em Nuvem , Humanos , Fluxo de Trabalho
11.
Nat Genet ; 50(10): 1412-1425, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30224653

RESUMO

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

12.
J Med Ultrason (2001) ; 45(1): 59-64, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28547388

RESUMO

PURPOSE: The gold standard for the diagnosis of malrotation is barium contrast study of the upper gastrointestinal system (UGCS), while color Doppler ultrasonography (CDUS) is another method used in the diagnosis. We investigated the value of CDUS for the diagnosis of malrotation in this study. METHODS: UGCS images, CDUS images, plain abdominal images, demographic data, and symptoms of 82 patients who were investigated for presumed malrotation during a 7-year period were evaluated, retrospectively. RESULTS: All patients underwent CDUS, and 18% of these patients were diagnosed with malrotation as the superior mesenteric vein was seen to be on the left of the superior mesenteric artery. We found that 16% of the 75 patients who underwent UGCS were diagnosed with malrotation. The sensitivity and specificity of CDUS in the diagnosis of malrotation was found to be 93.8 and 100%, respectively. The respective values for UGCS were 91.7 and 98.4%. CONCLUSION: Current data in the literature and our results underline that UGCS may yield false-positive and false-negative results. Although CDUS was found to be a reliable method for the diagnosis of malrotation in our study, the limitations of UGCS are also recognized for CDUS. Prospective studies are needed to determine the more valuable method.


Assuntos
Anormalidades do Sistema Digestório/diagnóstico por imagem , Artéria Mesentérica Superior/diagnóstico por imagem , Veias Mesentéricas/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Adolescente , Criança , Pré-Escolar , Anormalidades do Sistema Digestório/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Volvo Intestinal/diagnóstico , Volvo Intestinal/diagnóstico por imagem , Masculino , Artéria Mesentérica Superior/anormalidades , Veias Mesentéricas/anormalidades , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
Metabolomics ; 14(3): 32, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30830335

RESUMO

INTRODUCTION: Differences in the metabolite profiles between serum and plasma are incompletely understood. OBJECTIVES: To evaluate metabolic profile differences between serum and plasma and among plasma sample subtypes. METHODS: We analyzed serum, platelet rich plasma (PRP), platelet poor plasma (PPP), and platelet free plasma (PFP), collected from 8 non-fasting apparently healthy women, using untargeted standard 1D and CPMG 1H NMR and reverse phase and hydrophilic (HILIC) UPLC-MS. Differences between metabolic profiles were evaluated using validated principal component and orthogonal partial least squares discriminant analysis. RESULTS: Explorative analysis showed the main source of variation among samples was due to inter-individual differences with no grouping by sample type. After correcting for inter-individual differences, lipoproteins, lipids in VLDL/LDL, lactate, glutamine, and glucose were found to discriminate serum from plasma in NMR analyses. In UPLC-MS analyses, lysophosphatidylethanolamine (lysoPE)(18:0) and lysophosphatidic acid(20:0) were higher in serum, and phosphatidylcholines (PC)(16:1/18:2, 20:3/18:0, O-20:0/22:4), lysoPC(16:0), PE(O-18:2/20:4), sphingomyelin(18:0/22:0), and linoleic acid were lower. In plasma subtype analyses, isoleucine, leucine, valine, phenylalanine, glutamate, and pyruvate were higher among PRP samples compared with PPP and PFP by NMR while lipids in VLDL/LDL, citrate, and glutamine were lower. By UPLC-MS, PE(18:0/18:2) and PC(P-16:0/20:4) were higher in PRP compared with PFP samples. CONCLUSIONS: Correction for inter-individual variation was required to detect metabolite differences between serum and plasma. Our results suggest the potential importance of inter-individual effects and sample type on the results from serum and plasma metabolic phenotyping studies.


Assuntos
Metaboloma , Plasma/química , Soro/química , Adulto , Aminoácidos/análise , Glicemia/análise , Feminino , Humanos , Lipídeos/análise , Lipoproteínas/análise , Espectrometria de Massas , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância Magnética
15.
J Proteome Res ; 16(10): 3623-3633, 2017 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-28823158

RESUMO

1H NMR spectroscopy of biofluids generates reproducible data allowing detection and quantification of small molecules in large population cohorts. Statistical models to analyze such data are now well-established, and the use of univariate metabolome wide association studies (MWAS) investigating the spectral features separately has emerged as a computationally efficient and interpretable alternative to multivariate models. The MWAS rely on the accurate estimation of a metabolome wide significance level (MWSL) to be applied to control the family wise error rate. Subsequent interpretation requires efficient visualization and formal feature annotation, which, in-turn, call for efficient prioritization of spectral variables of interest. Using human serum 1H NMR spectroscopic profiles from 3948 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), we have performed a series of MWAS for serum levels of glucose. We first propose an extension of the conventional MWSL that yields stable estimates of the MWSL across the different model parameterizations and distributional features of the outcome. We propose both efficient visualization methods and a strategy based on subsampling and internal validation to prioritize the associations. Our work proposes and illustrates practical and scalable solutions to facilitate the implementation of the MWAS approach and improve interpretation in large cohort studies.


Assuntos
Aterosclerose/sangue , Metaboloma/genética , Metabolômica , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/epidemiologia , Aterosclerose/patologia , Glicemia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância Magnética
16.
Int J Surg Case Rep ; 34: 32-35, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28415025

RESUMO

INTRODUCTION: Traumatic hip dislocation associated with femur intertrocanteric fracture is a rare and severe injury and it frequently occurs following a high energy trauma, Associated acetabular fractures with this injury are even more rare and potentially cause devastating consequences including avascular necrosis of the femoral head and subsequent early secondary osteoarthritis of the hip joint. PRESENTATION OF CASE: In this case report, we present a 20year old polytraumatized patient with traumatic hip dislocation associated with ipsilateral acetabulum fracture and simultaneous fractures of the ipsilateral femur. DISCUSSION: Traumatic hip dislocation associated with femur intertrochanteric fracture is a rare and severe injury and it frequently occurs following a high energy trauma. In polytraumatized patients, musculoskeletal injuries are the most common lesions requiring surgical intervention frequently presenting challenging scenarios in terms of functional outcome and quality of life. Osteonecrosis of the femoral head is a serious and unpredictable complication that may occur after displaced femoral neck fracture and traumatic hip dislocation due to the disturbed blood supply of the femoral head. CONCLUSION: A staged treatment strategy may be useful managing an unstable polytraumatized patient or a patient who requires prolonged transfer to receive definitive care.

17.
Sci Rep ; 7: 46707, 2017 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-28429796

RESUMO

We demonstrate a method to achieve local control of 3-dimensional thermal history in a metallic alloy, which resulted in designed spatial variations in its functional response. A nickel-titanium shape memory alloy part was created with multiple shape-recovery stages activated at different temperatures using the selective laser melting technique. The multi-stage transformation originates from differences in thermal history, and thus the precipitate structure, at various locations created from controlled variations in the hatch distance within the same part. This is a first example of precision location-dependent control of thermal history in alloys beyond the surface, and utilizes additive manufacturing techniques as a tool to create materials with novel functional response that is difficult to achieve through conventional methods.

18.
Adv Exp Med Biol ; 965: 145-161, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28132179

RESUMO

From data acquisition to statistical analysis, metabolomics data need to undergo several processing steps, which are crucial for the data quality and interpretation of the results. In this chapter, methods for preprocessing, normalization, and pretreatment of metabolomics data generated from nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are presented and discussed. Preprocessing is reported for both NMR and MS analysis. The challenges in preprocessing such complex data are highlighted. Subsequently, normalization methods such as total area normalization, probabilistic quotient normalization, and quantile normalization are explained. Finally, several scaling and data transformation methods are discussed for metabolomics data pretreatment, which is an important step prior to statistical analysis.


Assuntos
Interpretação Estatística de Dados , Metabolômica/métodos , Processamento Eletrônico de Dados , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Controle de Qualidade
19.
Nat Genet ; 49(3): 403-415, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28135244

RESUMO

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.


Assuntos
Pressão Sanguínea/genética , Doenças Cardiovasculares/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Adulto , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
20.
Sci Rep ; 6: 35523, 2016 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-27752106

RESUMO

The prospect of extending existing metal-ceramic composites to those with the compositions that are far from thermodynamic equilibrium is examined. A current and pressure-assisted, rapid infiltration is proposed to fabricate composites, consisting of reactive metallic and ceramic phases with controlled microstructure and tunable properties. An aluminum (Al) alloy/Ti2AlC composite is selected as an example of the far-from-equilibrium systems to fabricate, because Ti2AlC exists only in a narrow region of the Ti-Al-C phase diagram and readily reacts with Al. This kind of reactive systems challenges conventional methods for successfully processing corresponding metal-ceramic composites. Al alloy/Ti2AlC composites with controlled microstructures, various volume ratios of constituents (40/60 and 27/73) and metallic phase sizes (42-83 µm, 77-276 µm, and 167-545 µm), are obtained using the Ti2AlC foams with different pore structures as preforms for molten metal (Al alloy) infiltration. The resulting composites are lightweight and display exceptional mechanical properties at both ambient and elevated temperatures. These structures achieve a compressive strength that is 10 times higher than the yield strength of the corresponding peak-aged Al alloy at ambient temperature and 14 times higher at 400 °C. Possible strengthening mechanisms are described, and further strategies for improving properties of those composites are proposed.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA