RESUMO
Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 × 10(-8)) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.
Assuntos
Cromossomos Humanos Par 13/genética , Predisposição Genética para Doença/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Osteoartrite/genética , Anticorpos Monoclonais/uso terapêutico , Estudo de Associação Genômica Ampla , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Fator de Crescimento Neural/imunologia , Fator de Crescimento Neural/metabolismo , Razão de Chances , Osteoartrite/imunologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Troca de Nucleotídeo Guanina Rho , População Branca/genéticaRESUMO
OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. METHODS: We performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. RESULTS: We accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis). CONCLUSIONS: Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
Assuntos
Osteoartrite do Quadril/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Proteínas HMGN/genética , Proteínas de Homeodomínio/genética , Humanos , Proteínas Imediatamente Precoces/genética , Masculino , Coativador 3 de Receptor Nuclear/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Fatores Sexuais , População Branca/genética , Quinases DyrkRESUMO
OBJECTIVES: Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale. METHODS: We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls. RESULTS: We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI. CONCLUSIONS: We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.
Assuntos
Estatura/genética , Índice de Massa Corporal , Obesidade/genética , Osteoartrite/genética , Proteínas/genética , Adulto , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The coronavirus disease-19 pandemic changed rheumatology practice with remote consultations being increasingly utilized where appropriate. We evaluated patient experiences with telephone consultations and report on patient attitudes toward current health care delivery and perspectives of telemedicine in a UK National Health Service rheumatology outpatient department. We analyzed 297 questionnaires from a postal survey conducted during the summer of 2020 after a telephone follow-up consultation. The mean age of respondents was 67 years and 68% were female. The 161 respondents (54%) reported it was their first telephone consultation and overall, 239 (84%) were satisfied with their health assessment. 60% would be happy to have future routine follow-up telephone consultations. Patients advised to shield shared similar satisfaction to the whole sample. However, with increasing age we identified a higher proportion were dissatisfied with telephone consultations and unlikely to have accessibility to video consultation or preferentially opt for this modality.
RESUMO
The present investigation was carried out to isolate and characterize bioactive components from Mirabilis jalapa L. radix ( zÇ mò lì gen). Thin-layer chromatography was used for the separation of spots from fractions of the crude extract. Separated spots were collected for identification of their activities. Free-radical scavenging activity was evaluated by spraying thin-layer chromatography plates (spotted with fractions) with 0.2% of 2,2-diphenyl-1-picrylhydrazyl solution. Activity against human pathogens such as Staphylococcus aureus and Candida albicans were determined using the agar diffusion method. Potential spots were subjected to infrared (IR) analysis and gas chromatography for characterization. Two spots (5F1 and 1F3) showed free-radical scavenging activity. The 1F3 spot was active against both S. aureus and C. albicans, whereas the 5F1 spot was active against S. aureus only. IR spectral analysis indicated that 5F1 spot to be a triterpenoid. Using IR spectral analysis and an IR library search, the 1F3 spot was identified to be a flavone, which may have a hydroxyl group in ring "A" of the flavone nucleus. Our results indicated that the 1F3 and 5F1 spots are potential free-radical scavengers. Both 1F3 and 5F1 exhibited antimicrobial activity. IR spectral analysis coupled with an IR library search indicated 1F3 and 5F1 to be a flavone and a triterpenoid, respectively.
RESUMO
The study was designed to evaluate the effects of hydromethanolic extract of tuberous root of M. jalapa and its terpenoid and flavonoid fractions on cutaneous wound healing in Wistar Albino rats. The hydromethanolic extract was subfractionated by sequential extraction in solvents (moderately nonpolar to polar). The extract and its (terpenoid and flavonoid) fractions were used for cutaneous wound healing studies by using excision wound model on rat. Their effects on wound contraction rate, biochemical and histological changes, and expression of growth factors such as collagen 3A, basic fibroblast growth factor, and vascular endothelial growth factor were investigated. The results indicated that flavonoid treated group showed significant decrease (P < 0.05) in antioxidant enzyme level as compared to control in wound healing process, whereas terpenoid fraction showed significant increase (P < 0.05) in expression of growth factor levels but regeneration and remodeling stages were delayed due to formation of thicker ulcus layer and also there were no hair follicle-like blood capillaries formation which ultimately may lead to formation of hypertrophic scar of wound. Therefore, from this study, it can be concluded that terpenoid fraction prolongs proliferation phase and hence may have tendency to convert the wound into hypertrophic wound.
RESUMO
Acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV). The integrase (IN) enzyme of HIV interacts with several cellular and viral proteins during the integration process. Thus, it represents an appropriate target for antiretroviral drugs (ARVs). We performed virtual screening of database compounds and designed analogues using Elvitegravir (EVG) as a standard compound. The 378 screened compounds were retrieved from ZINC, ChemSpider, PubChem, and ChemBank Chemical Databases based on chemical similarity and literature searches related to the structure of EVG. The Physiochemical properties, Bioactivity, Toxicity and Absorption, Distribution, Metabolism and Excretion of Molecules (ADME) of these compounds were predicted and docking Experiments were conducted using Molegro Virtual Docker software. The docking and ADME suggested very significant results in regard to EVG. The MolDock and Rerank scores were used to analyze the results. The compounds ZINC26507991 (-84.22), Analogue 9 (-68.49), ZINC20731658 (-66.79), ZINC00210363 (-43.44) showed better binding orientation with IN receptor model with respect to EVG (182.52). The ZINC26507991 has showed significant ADME result.
RESUMO
One common thread to health care reform in the United States is an emphasis on effectively managing the care of patients with chronic conditions. A landmark study by McGlynn et al demonstrated that patients receive about 55% of the treatment they need. While technological advances allow automated means for identifying and reaching out to patients in need of treatment, few studies have evaluated their impact. The purpose of this study is to measure how an automated outreach program can be used to improve the quality of care for patients with diabetes and hypertension. Billing and electronic medical records data from a large health system in Wisconsin were studied, identifying patients with a history of diabetes and hypertension but no visits recorded in billing data related to their condition in the past 6 months. The outcomes of interest were the occurrence of a chronic care-related visit and a necessary test within 6 months of the nonadherence date. Diabetes patients who were successfully contacted were significantly more likely to have both a chronic care-related visit and an HbA1c test (odds ratio [OR] = 4.61, 95% confidence interval [CI] 3.87-5.49) than their counterparts who were not contacted. As well, hypertension patients were significantly more likely to have both a chronic care-related visit and a systolic blood pressure reading recorded in an electronic medical record (OR = 3.18, 95% CI 2.90-3.48). An automated patient identification and outreach program can be an effective means to supplement existing practice patterns to ensure that patients with chronic conditions in need of care receive the necessary treatment.