Stroke risk among patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis

Increased stroke risk among chronic obstructive pulmonary disease patients has not yet been established. In this study, we conducted a systematic review and meta-analysis to assess stroke risk among chronic obstructive pulmonary disease patients. PubMed, EMBASE, and the Cochrane Library were systematically searched from database inception until December 31, 2016 to identify longitudinal observational studies that investigated the association between chronic obstructive pulmonary disease and stroke. Stroke risk was quantified by overall and subgroup analyses, and a pooled hazard ratio was calculated. Study quality was evaluated using the Newcastle-Ottawa Scale. Publication bias was assessed using Begg’s rank correlation test. Eight studies met the inclusion criteria. In a random-effects model, significantly increased stroke risk was observed among chronic obstructive pulmonary disease patients (hazard ratio, 1.30; 95% confidence interval, 1.18-1.43). In subgroup analyses stratified by stroke subtype, study quality, and adjustment by socioeconomic status, the association between increased stroke risk and chronic obstructive pulmonary disease patients was robust. Statistically significant publication bias was not detected. In summary, chronic obstructive pulmonary disease was found to be associated with increased stroke risk. Additional prospective studies are required to elucidate the mechanisms underlying the increase in stroke risk and identify effective preventive interventions

Biallelic variants in FLII cause pediatric cardiomyopathy by disrupting cardiomyocyte cell adhesion and myofibril organization

Pediatric cardiomyopathy (CM) represents a group of rare, severe disorders that affect the myocardium. To date, the etiology and mechanisms underlying pediatric CM are incompletely understood, hampering accurate diagnosis and individualized therapy development. Here, we identified biallelic variants in the highly conserved flightless-I (FLII) gene in 3 families with idiopathic, early-onset dilated CM. We demonstrated that patient-specific FLII variants, when brought into the zebrafish genome using CRISPR/Cas9 genome editing, resulted in the manifestation of key aspects of morphological and functional abnormalities of the heart, as observed in our patients. Importantly, using these genetic animal models, complemented with in-depth loss-of-function studies, we provided insights into the function of Flii during ventricular chamber morphogenesis in vivo, including myofibril organization and cardiomyocyte cell adhesion, as well as trabeculation. In addition, we identified Flii function to be important for the regulation of Notch and Hippo signaling, crucial pathways associated with cardiac morphogenesis and function. Taken together, our data provide experimental evidence for a role for FLII in the pathogenesis of pediatric CM and report biallelic variants as a genetic cause of pediatric CM.</p

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Displasia fibrosa do clivus: relato de caso Fibrous dysplasia of the clivus: case report

Relatamos o caso de uma paciente de 43 anos com história de cefaléia crônica e diplopia. O exame neurorradiológico demonstrou aumento de volume e alteração na densidade óssea do clivus. Foi submetida a cirurgia e o exame anatomopatológico evidenciou displasia fibrosa. Foram relatados na literatura outros 14 casos de displasia fibrosa envolvendo o clivus. Discutimos essa rara apresentação da doença segundo o quadro clínico, exames de imagem, histologia e tratamento.<br>We describe the case of a 43 year-old woman with chronic headache and diplopia. The neurorradiologic exam showed volume increase and alteration in the bone density of the clivus. She was submitted to surgery and the anatomopathologic evidenced fibrous dysplasia. Other 14 of about fibrous dysplasia involving the clivus are related in the literature. We discuss clinical aspects, image exams, histology and treatment of this rare presentation of the disease