RESUMO
Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma, resulting in major global public health concerns. The HCV infection is unevenly distributed worldwide, with variations in prevalence across and within countries. The studies on molecular epidemiology conducted in several countries provide an essential supplement for a comprehensive knowledge of HCV epidemiology, genotypes, and subtypes, along with providing information on the impact of current and earlier migratory flows. HCV is phylogenetically classified into 8 major genotypes and 57 subtypes. HCV genotype and subtype distribution differ according to geographic origin and transmission risk category. Unless people with HCV infection are detected and treated appropriately, the number of deaths due to the disease will continue to increase. In 2015, 1.75 million new viral infections were mostly due to unsafe healthcare procedures and drug use injections. In the same year, access to direct-acting antivirals was challenging and varied in developing and developed countries, affecting HCV cure rates based on their availability. The World Health Assembly, in 2016, approved a global strategy to achieve the elimination of the HCV public health threat by 2030 (by reducing new infections by 90% and deaths by 65%). Globally, countries are implementing policies and measures to eliminate HCV risk based on their distribution of genotypes and prevalence.
Assuntos
Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , PrevalênciaRESUMO
The pathogenic mechanisms underlying Schizophrenia (SZ), one of the most frequent mental disorders, are complex and poorly understood. Several evidences suggest that inflammatory processes may underpin some of its neurobiological correlates. The aim of this study was: (i) to analyze the potential association between circulating levels of the C-reactive protein (CRP), a crucial inflammatory marker, and Schizophrenia in Tunisian patients and healthy controls (HC) cohorts; (ii) to investigate the genetic diversity of three CRP variants (rs1417938, rs1130864 and rs1205) and; (iii) to analyze a potential relationship between expression and genetic data and clinical and socio demographical characteristics. CRP polymorphisms were exanimated for 155 patients and 203 HC by taqMan5'-nuclease. High-sensitivity CRP (hs-CRP) serum level was measured in 128 clinically stable out-patient SZ patients and 63 HC subjects via an automated biochemical analyzer. We found that hs-CRP levels were significantly higher in SZ patients as compared to HC. No significant differences were found when the proportions of CRP variants were compared in patients and HC. Further analysis according to clinical and socio demographical characteristics revealed a positive association with age and hypertension. Our data on an original Tunisian sample confirm the previous finding in others population groups.
Assuntos
Proteína C-Reativa/análise , Esquizofrenia/sangue , Esquizofrenia/epidemiologia , Adolescente , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Estudos de Coortes , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Esquizofrenia/etiologia , Tunísia/epidemiologia , Adulto JovemRESUMO
Alzheimer's disease is the most common cause of dementia in the elderly population. Currently, there are no effective treatments to prevent or delay the natural course of the disease. Numerous studies have provided information about the molecular processes underlying biological ageing and, perhaps more importantly, potential interventions to slow ageing and promote healthy longevity in laboratory model systems. The main issue addressed in this review is whether an intervention that has anti-ageing properties can alter the appearance and/or progression of Alzheimer's disease, a disease in which age is the biggest risk factor. Different anti-ageing interventions have been shown to prevent (and in some cases possibly restore) several parameters recognised as central symptoms to the development of Alzheimer's disease. In addition, they are taking the first steps towards translating these laboratory discoveries into clinical applications.
Assuntos
Doença de Alzheimer/terapia , Idoso , Doença de Alzheimer/tratamento farmacológico , Terapia Genética , Humanos , Estilo de VidaRESUMO
Tumor suppressor genes and the immune system are critical players in inhibiting cancer initiation and/or progression. However, little is known about whether a tumor suppressor gene can function through both immune-dependent and -independent mechanisms. Retinoic acid receptor responder 2 (RARRES2) is transcriptionally downregulated in multiple cancer types. Previous studies suggested that it can serve as an immune-dependent tumor suppressor by acting as a chemoattractant to recruit anticancer immune cells expressing its receptor, the chemerin chemokine receptor 1 (CMKLR1), to sites of tumor. In this study, we investigated the role of RARRES2 in adrenocortical carcinoma (ACC), a rare lethal malignancy in which aberrant Wnt/ß-catenin signaling is frequently detected. We show that RARRES2 expression is downregulated in ACC as compared with normal and benign adrenocortical tissues, which is a result of CpG hypermethylation. Despite minimal CMKLR1 expression and lack of phenotypic tumor-suppressive effect with exogenous RARRES2 treatment, RARRES2 overexpression in ACC cell lines not only reduced cell proliferation, cell invasion and tumorigenicity in vitro, but also inhibited tumor growth in vivo in two immunodeficient mouse xenograft models. Mechanistically, RARRES2 overexpression in ACC cells inhibited Wnt/ß-catenin pathway activity by promoting ß-catenin phosphorylation and degradation, it also inhibited the phosphorylation of p38 mitogen-activated protein kinase. Thus our study identifies RARRES2 as a novel tumor suppressor for ACC, which can function through an immune-independent mechanism.
Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/metabolismo , Quimiocinas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteólise , Proteínas Supressoras de Tumor/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Animais , Linhagem Celular Tumoral , Quimiocinas/genética , Feminino , Xenoenxertos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Camundongos , Transplante de Neoplasias , Fosforilação/genética , Proteínas Supressoras de Tumor/genética , beta Catenina/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
Two way-communication between users and developers is a must when creating a truly functional computer-based patient record. The solution for tackling this daunting task may be to use structured requirements analysis supported by CASE tools.
Assuntos
Sistemas Computadorizados de Registros Médicos/normas , Software/normas , Análise de Sistemas , Relações Interprofissionais , Técnicas de Planejamento , Projetos de Pesquisa , Estados UnidosRESUMO
Designing a clinical information system offers a sense of accomplishment similar to that of a dramatic performance. The development of the data dictionary and proposed system description requires the same attention to detail as stage directions in a script. The people involved in daily system operation are of key importance in developing a clear understanding of how things actually happen in the information flow and decision process. Once the business rules are defined and edits and conditions are developed to ensure data integrity, it is time to step back and let the performance begin. The real power of the user-designed system, like that of a performance before a live audience, comes with the ability to query the data for answers to issues and problems decision makers did not face at the time of the initial system design.