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1.
Sci Rep ; 10(1): 1862, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024964

RESUMO

Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohn's disease (CD), some of which confer susceptibility to both diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two clinically distinct immune-mediated disorders. The fact that all these pleiotropic SNPs have opposite allelic effects in SSc and CD reveals the complexity of the molecular mechanisms by which polymorphisms affect diseases.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31894389

RESUMO

In recent years, there has been increasing consumer interest in carotenoids, particularly of marine sustainable origin with applications in the food, cosmeceutical, nutritional supplement and pharmaceutical industries. For instance, microalgae belonging to the genus Tetraselmis are known for their biotechnologically relevant carotenoid profile. The recently isolated marine microalgal strain Tetraselmis sp. CTP4 is a fast-growing, robust industrial strain, which has successfully been produced in 100-m3 photobioreactors. However, there are no reports on total carotenoid contents from this strain belonging to T. striata/convolutae clade. Although there are several reports on extraction methods targeting chlorophytes, extraction depends on the strength of cell coverings, solvent polarity and the nature of the targeted carotenoids. Therefore, this article evaluates different extraction methods targeting Tetraselmis sp. CTP4, a strain known to contain a mechanically resistant theca. Here, we propose a factorial experimental design to compare extraction of total carotenoids from wet and freeze-dried microalgal biomass using four different solvents (acetone, ethanol, methanol or tetrahydrofuran) in combination with two types of mechanical cell disruption (glass beads or dispersion). The extraction efficiency of the methods was assessed by pigment contents and profiles present in the extracts. Extraction of wet biomass by means of glass bead-assisted cell disruption using tetrahydrofuran yielded the highest amounts of lutein and ß-carotene (622 ± 40 and 618 ± 32 µg g-1 DW, respectively). Although acetone was slightly less efficient than tetrahydrofuran, it is preferable due to its lower costs and toxicity.

3.
Int J Mol Sci ; 21(3)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979077

RESUMO

Low stability of transgenes and high variability of their expression levels among the obtained transformants are still pending challenges in the nuclear genetic transformation of microalgae. We have generated a new multicistronic microalgal expression plasmid, called Phyco69, to make easier the large phenotypic screening usually necessary for the selection of high-expression stable clones. This plasmid contains a polylinker region (PLK) where any gene of interest (GOI) can be inserted and get linked, through a short viral self-cleaving peptide to the amino terminus of the aminoglycoside 3'-phosphotransferase (APHVIII) from Streptomyces rimosus, which confers resistance to the antibiotic paromomycin. The plasmid has been validated by expressing a second antibiotic resistance marker, the ShBLE gene, which confers resistance to phleomycin. It has been shown, by RT-PCR and by phenotypic studies, that the fusion of the GOI to the selective marker gene APHVIII provides a simple method to screen and select the transformants with the highest level of expression of both the APHVIII gene and the GOI among the obtained transformants. Immunodetection studies have shown that the multicistronic transcript generated from Phyco69 is correctly processed, producing independent gene products from a common promoter.

4.
Cerebrovasc Dis ; 48(3-6): 171-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31726450

RESUMO

INTRODUCTION: The current guidelines advocate the implementation of stroke networks to organize endovascular treatment (ET) for patients with acute ischemic stroke due to large vessel occlusion (LVO) after transfer from a Primary Stroke Centre (PSC) to a Comprehensive Stroke Centre (CSC). In France and in many other countries around the world, these transfers are carried out by a physician-led mobile medical team. However, with the recent broadening of ET indications, their availability is becoming more and more critical. Here, we retrospectively analysed data of patients transferred from a PSC to a CSC for potential ET to identify predictive factors of major complications (MC) at departure and during transport that absolutely require the presence of a physician during interhospital transfer. METHODS: This observational, single-centre study included patients with evidence of intracranial LVO transferred for ET from Perpignan to a 156 km-distant CSC between January 1, 2015 and -December 31, 2018. We compared 2 groups: MC group (patients who required emergency intervention by the medical team due to life-threatening complications, including need of mechanical ventilation at departure) and non-MC group (all other patients who experienced no or only minor complications that could be managed by the emergency paramedics alone). RESULTS: Among the 253 patients who were transferred to the CSC, 185 (73.1%) had no complication, 57 (22.6%) minor complications, and 11 (4.3%) had MC. In multivariate analysis, MC was associated with basilar artery (BA) occlusion (p < 0.0001), initial National Institute of Health Stroke Scale (NIHSS) score >22 (p < 0.005), and history of atrial fibrillation (p < 0.04). Among the 168 patients treated with intravenous thrombolysis (IVT), only 1 patient (0.6%) had MC due to an IVT-related adverse event during transfer. CONCLUSIONS: Physician-led inter-hospital transports are warranted for patients with BA occlusion, initial NIHSS score >22, or history of atrial fibrillation. For the other patients, transfer without a physician may be considered, even if treated with IVT.

5.
Korean J Intern Med ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31640337

RESUMO

Background/Aims: Myelodysplastic syndrome (MDS) is caused by genetic and epigenetic alteration of hematopoietic precursors and immune dysregulation. Approximately 20% of patients with MDS develop an autoimmune disease (AID). Here, we investigated whether particular genetic mutations are associated with AID in patients with MDS. Methods: Eighty-eight genetic mutations associated with myeloid malignancy were sequenced in 73 MDS patients. The association between these mutations and AID was then analyzed. Results: The median age of the 73 MDS patients was 70 years (interquartile range, 56 to 75), and 49 (67.1%) were male. AID was observed in 16 of 73 patients (21.9%). Mutations were detected in 57 (78.1%) patients. The percentage (68.8% vs. 80.7%, p = 0.32) and the mean number of mutations (1.8 ± 1.6 vs. 2.2 ± 1.8, p = 0.34) in MDS patients with or without AID were similar. However, the ten-eleven translocation- 2 (TET2) mutation rate was significantly higher in patients with AID than in those without (31.3% vs. 5.3%, respectively; p = 0.001). All TET2 mutations were variants of strong clinical significance. Conclusions: Mutation of TET2 in patients with MDS may be associated with increased risk of developing AID.

6.
Polymers (Basel) ; 11(9)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546862

RESUMO

The inclusion of electrospun nanofiber veils was revealed as an effective method for enhancing the mechanical properties of fiber-reinforced epoxy resin composites. These veils will eventually allow the incorporation of nanomaterials not only for mechanical reinforcement but also in multifunctional applications. Therefore, this paper investigates the effect of electrospun nanofibrous veils made of polyamide 6 modified with TiO2 nanoparticles on the mechanical properties of a carbon-fiber/epoxy composite. The nanofibers were included in the carbon-fiber/epoxy composite as a single structure. The effect of positioning these veils in different composite positions was investigated. Compared to the reference, the use of unmodified and TiO2 modified veils increased the flexural stress at failure and the fracture toughness of composites. When TiO2 modified veils were incorporated, new antibacterial properties were achieved due to the photocatalytic properties of the veils, widening the application area of these composites.

7.
Sensors (Basel) ; 19(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489881

RESUMO

In order to increase the sensitivity of a sensor, the relationship between its volume and the surface available to be functionalized is of great importance. Accordingly, porous materials are becoming very relevant, because they have a notable surface-to-volume ratio. Moreover, they offer the possibility to infiltrate the target substances on them. Among other porous structures, polymeric nanofibers (NFs) layers fabricated by electrospinning have emerged as a very promising alternative to low-cost and easy-to-produce high-performance photonic sensors. However, experimental results show a spectrum drift when performing sensing measurements in real-time. That drift is responsible for a significant error when trying to determine the refractive index variation for a target solution, and, because of that, for the detection of the presence of certain analytes. In order to avoid that problem, different chemical and thermal treatments were studied. The best results were obtained for thermal steps at 190 °C during times between 3 and 5 h. As a result, spectrum drifts lower than 5 pm/min and sensitivities of 518 nm/refractive index unit (RIU) in the visible range of the spectrum were achieved in different electrospun NFs sensors.

8.
J Pharm Biomed Anal ; 176: 112798, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31394303

RESUMO

PURPOSE: Salts of phenylacetic acid (PAA) and phenylbutyric acid (PBA) have been used for nitrogen elimination as a treatment for hyperammonaemia caused by urea cycle disorders (UCD). A new analytical method for PBA measurement in urine which helps to evaluate the drug adherence has been implemented. METHODS: Urine specimens from UCD patients receiving PBA were analysed by tandem mass spectrometry to measure urine phenylacetylglutamine (PAGln). Some clinical and biochemical data for each patient were collected. RESULTS: Our study included 87 samples from 40 UCD patients. The PAGln levels did not correlate with height, weight or age. However, the PAGln values showed correlation with PBA dose (r = 0.383, P = 0.015). Plasma glutamine and ammonia levels presented a positive correlation (r = 0.537, P < 0.001). The stability for PAGln in urine was determined at different storage temperatures. CONCLUSIONS: We have developed a simple method for the determination of PAGln in urine, which acts as useful biomarker of effective drug delivery. PAGln in urine is stable at room temperature at least for 15 days, and for several months when frozen at -20 °C. This procedure is useful for the optimization and monitorization of the drug dose allowing the use of spot urine samples.

9.
BMC Microbiol ; 19(1): 184, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395006

RESUMO

BACKGROUND: Helicobacter pylori recurrence after successful eradication is an important problem. Children are particularly vulnerable to reinfection, by intrafamilial transmission which facilitates the acquisition or recombination of new genetic information by this bacterium. We investigated the evolutionary dynamics of 80 H. pylori strains isolated from two paediatric patients with recurrent infection (recrudescence and reinfection). RESULTS: We characterized the virulence genes vacA (s1, m1, s2, and m2), cagA, cagE, and babA2 and performed multilocus sequence typing (MLST) on 7 housekeeping genes (atpA, efp, ureI, ppa, mutY, trpC, and yphC) to infer the evolutionary dynamics of the H. pylori strains through phylogenetic and genealogic inference analyses, genetic diversity analysis and the exploration of recombination events during recurrent infections. The virulence genotype vacAs1m1/cagA+/cagE+/babA2 was present at a high frequency, as were the EPIYA motifs EPIYA-A, -B and -C. Furthermore, the housekeeping genes of the H. pylori strains exhibited high genetic variation, comprising 26 new alleles and 17 new Sequence Type (ST). In addition, the hpEurope (76.5%) and hspWAfrica (23.5%) populations predominated among the paediatric strains. All strains, regardless of their ancestral affiliation, harboured western EPIYA motifs. CONCLUSIONS: This study provides evidence of the evolutionary dynamics of the H. pylori strains in two paediatric patients during recrudescence and reinfection events. In particular, our study shows that the strains changed during these events, as evidenced by the presence of different STs that emerged before and after treatment; these changes may be due to the accumulation of mutations and recombination events during the diversification process and recolonization of the patients by different genotypes.

10.
Front Immunol ; 10: 1796, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428096

RESUMO

Vasculitides are a heterogeneous group of low frequent disorders, mainly characterized by the inflammation of blood vessels that narrows or occlude the lumen and limits the blood flow, leading eventually to significant tissue and organ damage. These disorders are classified depending on the size of the affected blood vessels in large, medium, and small vessel vasculitis. Currently, it is known that these syndromes show a complex etiology in which both environmental and genetic factors play a major role in their development. So far, these conditions are not curable and the therapeutic approaches are mainly symptomatic. Moreover, a percentage of the patients do not adequately respond to standard treatments. Over the last years, numerous genetic studies have been carried out to identify susceptibility loci and biological pathways involved in vasculitis pathogenesis as well as potential genetic predictors of treatment response. The ultimate goal of these studies is to identify new therapeutic targets and to improve the use of existing drugs to achieve more effective treatments. This review will focus on the main advances made in the field of genetics and pharmacogenetics of vasculitis and their potential application for ameliorating long-term outcomes in patient management and in the development of precision medicine.

11.
Polymers (Basel) ; 11(5)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027371

RESUMO

This work has been focused on the one-step fabrication by electrospinning of polyamide 6 (PA6) nanofibre membranes modified with titanium dioxide nanoparticles (TiO2), where these TiO2 nanoparticles aggregates could induce a photocatalytic activity. The main potential application of these membranes could be the purification of contaminated water. Thus, it is important to analyse the contaminant degradation capability since in these membranes this is based on their photocatalytic activity. In this work, the effect of the photocatalysis has been studied both on the degradation of an organic model contaminant and on the removal of Escherichia coli and other coliform bacteria. As a result, it was observed that these membranes present excellent photocatalytic activity when they are irradiated under UV light, allowing a 70% reduction of an organic model pollutant after 240 min. In addition, these membranes successfully removed Escherichia coli and other coliform bacteria in artificially inoculated water after 24 h of contact with them. Moreover, the stand-alone structure of the membranes allowed for the reusing of the immobilized catalyst. The experimental evidence indicated that developed nanofibre membranes are a fast and efficient solution for polluted water decontamination based on photocatalysis. Their use could contribute to guarantee a fresh water level and quality, mitigating the water scarcity problem worldwide.

12.
Neurol Clin ; 37(2): 219-234, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30952406

RESUMO

"Vasculitides are a heterogeneous group of inflammatory diseases of blood vessels in which genetic variation plays an important role in their susceptibility and clinical spectrum. Because of the use of novel technologies and the increase of the sample size of the study cohorts, the knowledge of the genetic background of vasculitides has considerably expanded during the last years. However, few insights have been obtained regarding the genetics underlying severe clinical phenotypes, such as those related to the nervous system. In this review the authors provide an updated overview of the genetic landscape behind vasculitis predisposition and development of neurologic manifestations."


Assuntos
Predisposição Genética para Doença , Doenças do Sistema Nervoso/etiologia , Vasculite/complicações , Vasculite/genética , Humanos
13.
PLoS One ; 14(2): e0213073, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30818333

RESUMO

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Etanercepte/uso terapêutico , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Feminino , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos , Variantes Farmacogenômicos , Adulto Jovem
14.
Metabolites ; 9(3)2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871061

RESUMO

Genetic manipulation shows great promise to further boost the productivity of microalgae-based compounds. However, selection of microalgal transformants depends mainly on the use of antibiotics, which have raised concerns about their potential impacts on human health and the environment. We propose the use of a synthetic phytoene desaturase-encoding gene (CRTIop) as a selectable marker and the bleaching herbicide norflurazon as a selective agent for the genetic transformation of microalgae. Bacterial phytoene desaturase (CRTI), which, unlike plant and algae phytoene desaturase (PDS), is not sensitive to norflurazon, catalyzes the conversion of the colorless carotenoid phytoene into lycopene. Although the expression of CRTI has been described to increase the carotenoid content in plant cells, its use as a selectable marker has never been testedin algae or in plants. In this study, a version of the CRTI gene adapted to the codon usage of Chlamydomonas has been synthesized, and its suitability to be used as selectable marker has been shown. The microalgae were transformed by the glass bead agitation method and selected in the presence of norflurazon. Average transformation efficiencies of 550 colonies µg-1 DNA were obtained. All the transformants tested had incorporated the CRTIop gene in their genomes and were able to synthesize colored carotenoids.

15.
J Neurointerv Surg ; 11(6): 539-544, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30327386

RESUMO

BACKGROUND AND PURPOSE: Inter-hospital transfer for mechanical thrombectomy (MT) might result in the transfer of patients who finally will not undergo MT (ie, futile transfers [FT]). This study evaluated FT frequency in a primary stroke center (PSC) in a semi-rural area and at 156 km from the comprehensive stroke center (CSC). METHODOLOGY: Retrospective analysis of data collected in a 6-year prospective registry concerning patients admitted to our PSC within 4.5 hours of acute ischemic stroke (AIS) symptom onset, with MR angiography indicating the presence of large vessel occlusion (LVO) without large cerebral infarction (DWI-ASPECT ≥5), and selected for transfer to the CSC to undergo MT. Futile transfer rate and reasons were determined, and the relevant time measures recorded. RESULTS: Among the 529 patients screened for MT, 278 (52.6%) were transferred to the CSC. Futile transfer rate was 45% (n=125/278) and the three main reasons for FT were: clinical improvement and reperfusion on MRI on arrival at the CSC (58.4% of FT); clinical worsening and/or infarct growth (16.8%); and longer than expected inter-hospital transfer time (11.2%). Predictive factors of FT due to clinical improvement/reperfusion on MRI could not be identified. Baseline higher NIHSS (21 vs 17; P=0.01) and lower DWI-ASPECT score (5 vs 7; P=0.001) were associated with FT due to clinical worsening/infarct growth on MRI. CONCLUSIONS: In our setting, 45% of transfers for MT were futile. None of the baseline factors could predict FT, but the initial symptom severity was associated with FT caused byclinical worsening/infarct growth.


Assuntos
Hospitalização , Trombólise Mecânica/métodos , Transferência de Pacientes/métodos , Sistema de Registros , População Rural , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/epidemiologia , Infarto Cerebral/terapia , Feminino , Hospitalização/tendências , Hospitais/tendências , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
16.
Talanta ; 192: 301-307, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30348393

RESUMO

A dynamic headspace sorptive extraction (DHS) combined with thermal desorption (TD) and coupled with gas chromatography-mass spectrometry (GC/MS) was developed for the determination of forty-four volatile aroma metabolites (VAMs) which describe aroma fingerprints of wines. The response surface methodology (RSM) and a central composite design (CCD) was used to obtain the optimal values for the experimental extraction variables, and the results were assessed by an analysis of variance (ANOVA) and a principal component analysis (PCA). The VAMs exhibited optimal extraction with the high levels of salt concentration (1.5 g NaCl) and using an extraction temperature of 40 °C during 10 min, and a subsequent purge volume of 300 mL. Subsequently, the calibration curves were created for the quantification of each VAMs with seven levels of concentration obtaining a correlation coefficients (R2) above 0.9900 for all of them. The proposed method was successfully validated and showed good precision and accuracy values for all VAMs. Lastly, the method was applied to quantify VAMs, responsible for the aroma fingerprints of white and red wines, from different Denomination of Origin.

17.
Genome Med ; 10(1): 97, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572963

RESUMO

BACKGROUND: In recent years, research has consistently proven the occurrence of genetic overlap across autoimmune diseases, which supports the existence of common pathogenic mechanisms in autoimmunity. The objective of this study was to further investigate this shared genetic component. METHODS: For this purpose, we performed a cross-disease meta-analysis of Immunochip data from 37,159 patients diagnosed with a seropositive autoimmune disease (11,489 celiac disease (CeD), 15,523 rheumatoid arthritis (RA), 3477 systemic sclerosis (SSc), and 6670 type 1 diabetes (T1D)) and 22,308 healthy controls of European origin using the R package ASSET. RESULTS: We identified 38 risk variants shared by at least two of the conditions analyzed, five of which represent new pleiotropic loci in autoimmunity. We also identified six novel genome-wide associations for the diseases studied. Cell-specific functional annotations and biological pathway enrichment analyses suggested that pleiotropic variants may act by deregulating gene expression in different subsets of T cells, especially Th17 and regulatory T cells. Finally, drug repositioning analysis evidenced several drugs that could represent promising candidates for CeD, RA, SSc, and T1D treatment. CONCLUSIONS: In this study, we have been able to advance in the knowledge of the genetic overlap existing in autoimmunity, thus shedding light on common molecular mechanisms of disease and suggesting novel drug targets that could be explored for the treatment of the autoimmune diseases studied.


Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Artrite Reumatoide/genética , Doença Celíaca/genética , Diabetes Mellitus Tipo 1/genética , Estudo de Associação Genômica Ampla , Humanos , Anotação de Sequência Molecular , Escleroderma Sistêmico/genética
18.
PLoS One ; 13(12): e0209343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30586461

RESUMO

BACKGROUND: The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. METHODS: A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. RESULTS: No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.


Assuntos
Fator Ativador de Células B/genética , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Escleroderma Sistêmico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente) , Feminino , Redes Reguladoras de Genes/genética , Técnicas de Genotipagem , Arterite de Células Gigantes/patologia , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/patologia
19.
J Sports Sci Med ; 17(4): 668-679, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30479537

RESUMO

CrossFit® consists of workouts of the day (WODs) in which different exercises are conducted at high intensity with minimal or no rest periods. This study sought to quantify exercise intensity and muscular fatigue in the three CrossFit® session modalities: gymnastics (G), metabolic conditioning (M) and weightlifting (W). Thirty two, young, strength-trained, healthy men completed the three WODs: G ("Cindy"), M (double skip rope jumps) and W (power cleans). The variables measured in the sessions were: mean heart rate (HR), rate of perceived exertion (RPE), blood lactate [lactate], and jump height (H), average power (AP) and maximum take-off velocity (Vmax) in a counter movement jump test. In all three WODs, elevated HR values (≥90% of the theoretical HRmax) were recorded at the time points mid-session and end-session. Mean RPEs were 17.6 ± 1.6 (G WOD), 16.0 ± 2.3 (M WOD), and 15.7 ± 2.0 (W WOD). Postexercise [lactate] was higher than 10 mmol·L-1 for the three WODs. Following the G ("Cindy") and W (power cleans) WODs, respectively, significant muscular power losses were observed in H (7.3% and 8.1%), Vmax (13.8% and 3.3%), AP relative (4.6% and 8.3%) and AP total (4.2% and 8.2%) while losses in the M WOD were not significant (p > 0.05). A vigorous intensity of exercise was noted in all three WODs, with greater mean HRs detected in the "Cindy" and skip rope WODs than power clean WOD. Muscular fatigue was produced in response to the "Cindy" and power clean WODs but not the skip rope WOD.


Assuntos
Frequência Cardíaca , Fadiga Muscular , Condicionamento Físico Humano/métodos , Ginástica , Humanos , Ácido Láctico/sangue , Masculino , Consumo de Oxigênio , Esforço Físico , Levantamento de Peso , Adulto Jovem
20.
BMC Infect Dis ; 18(1): 463, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30219037

RESUMO

BACKGROUND: Helicobacter pylori is a major aetiologic agent associated with gastritis. H. pylori infections increase the expression of the Toll-like receptor (TLR), which in turn modulates the expression of microRNA (miRNA)-146a and miRNA-155. The objective of this study was to compare the expression of miRNA-146a and miRNA-155 in gastric lesions of paediatric and adult patients with different pathologies and in Mongolian gerbils (Meriones unguiculatus) infected with H. pylori 26,695. METHODS: Quantification of miRNA expression was performed by quantitative real-time polymerase chain reaction (qRT-PCR) of paraffin-embedded gastric lesions of children with or without an infection (n = 25), adults with follicular gastritis and metaplasia (n = 32) and eight-week-old M. unguiculatus males (Hsd:MON) infected with H. pylori 26,695 for 0, 3, 6, 12 and 18 months (n = 25). The genes RNU48 and RNU6 were used as endogenous controls for data normalization. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney, ANOVA and Student's t-test. RESULTS: The expression of miRNA-146a and miRNA-155 in infected children increased by 247.6- and 79.4-fold (on average), respectively, compared to that observed in the control group. However, these results were not significant (p = 0.12 and p = 0.07 respectively). In some children a gradual increase in expression was observed, while in others, expression was very high. Additionally, the expression levels of miRNA-146a and miRNA-155 increased by an average of 21.7- and 62-fold, respectively, in adult patients with follicular gastritis when compared to those of the controls. In M. unguiculatus infected with H. pylori 26,695, the expression of both miRNAs increased as the infection progressed. CONCLUSION: This is the first report to show differences in the expression of miRNA-146a and miRNA-155 in paediatric and adult patients with gastritis who were infected with H. pylori. In addition, in M. unguiculatus infected with H. pylori, miRNA expression was associated with the progression of infection and the ability of the bacteria to adapt to the host.


Assuntos
Gastrite/genética , Infecções por Helicobacter/genética , Helicobacter pylori/fisiologia , MicroRNAs/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Modelos Animais de Doenças , Progressão da Doença , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Perfilação da Expressão Gênica , Gerbillinae , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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