Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low-or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI).Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression.
Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl (1st dose 4.6 μg/kg followed by 0.07 μg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk.
Polymer PCF is used as a force transducer to measure orthodontic forces. The forces observed correspond to those necessary for tooth movement. It is a promising technique that can be applied in vivo.
Protein ubiquitination is an essential process that rapidly regulates protein synthesis, function, and fate in dynamic environments. Among its non-proteolytic functions, K63 ubiquitin accumulates in yeast cells exposed to oxidative stress, stalling ribosomes at elongation. K63 ubiquitin conjugates accumulate because of redox inhibition of the deubiquitinating enzyme Ubp2, however, the role and regulation of ubiquitin conjugating enzymes in this pathway remained unclear. Here we found that the E2 Rad6 binds and modifies elongating ribosomes during oxidative stress. We elucidated a mechanism by which Rad6 and its human homolog UBE2A are redox-regulated by forming reversible disulfides with the E1 activating enzyme, Uba1. We further showed that Rad6 activity is necessary to regulate translation, antioxidant defense, and adaptation to stress. Finally, we showed that Rad6 is required to induce phosphorylation of the translation initiation factor eIF2α, providing a novel link for K63 ubiquitin, elongation stalling, and the integrated stress response.
The health benefits of physical activity have been demonstrated. However, there is a growing debate over the potential adverse effects of strenuous physical activity, particularly at a professional level. The goal of this work is to investigate whether elite athletes live longer than general populations, by a comprehensive survival analysis of two populations of professional football players. Lifespan data of Portuguese and Spanish football players, who have repre-sented the national teams, were collected. The mortality of each cohort is then compared to that of the respective standard population, using data available in the Human Mortality Database and four different approaches. At the end, a comparison between the mortality of Portuguese and Spanish football players is also carried out. Keywords: elite football players, mortality measures, Portugal, Spain. Resumen Los beneficios para la salud derivados del ejercicio regular están científicamente probados. Sin embargo, cuando se trata de deportistas profesionales, cuya actividad física es muy intensa, los beneficios ya no son una evidencia clara. El objetivo de este trabajo es investigar si los deportistas de élite viven más tiempo que la población general. Se recogieron datos sobre la fecha de nacimiento y muerte (en su caso) de los jugadores portugueses y españoles que representaron su selección, así como otras variables de interés. Cada grupo de jugadores se compara con la población general del país respectivo, utilizando los datos disponibles en la Human Mortality Database y cuatro enfoques diferentes. Al final, también se compara la mortalidad de futbolistas portugueses y españoles. Palabras clave: futbolistas de élite, medidas de mortalidad, España, Portugal.
Primary biliary cirrhosis (PBC) is a chronic liver condition characterized by bile duct destruction, probably caused by a yet unknown immunological mechanism. Its association with several other autoimmune diseases has been described. The association of the limited cutaneous form of systemic scleroderma (lcSSc) and PBC is known as Reynolds syndrome. The authors describe a case of a 76 year old male patient with Raynaud's phenomenon complaints in 1999. The physical examination revealed sclerodactyly, cutaneous calcifi cations, digital ulcers and facial telangiectasias. Chest radiography showed signs of lung fi brosis. Dilated capillary loop were found in nailfold capillaroscopy. The autoimmunity pattern was compatible with limited systemic sclerosis (antinuclear and anticentromere antibodies were positive). In 2005 the autoimmunity pattern changed, with positive antimitochondrial antibodies. The patient presented with fatigue, pruritus and dyspnea on exertion complaints. Liver function tests showed elevation of alkaline phosphatase and gamma-glutamyl transpeptidase. Although the patient refused liver biopsy, PBC diagnosis was established. In 2008 the patient was admitted to the hospital with anorexia, dyspepsia, ascites, abdominal pain and weight loss. Endoscopy showed esophageal varices and abdominal computed tomography revealed cirrhotic liver. The patient died in 2009 with acute myocardial infarction.
Osteogenesis imperfecta (OI) is clinically and genetically heterogeneous. Defects in collagen type 1 are reportedly the main cause of OI (85-90%), but most available data has arisen from developed countries. Massively parallel sequencing (MPS) technologies now allow for systematic and comprehensive analysis of OI genes simultaneously. Our objective was to obtain the molecular diagnosis of OI through targeted MPS in a single tertiary center cohort of Brazilian adults with OI. After informed consent, DNA samples were obtained from 52 cases of OI (9 families and 43 sporadic; total of 64 sequenced individuals, 96% adults). Sixty-nine percent of the cohort had moderate to severe OI, and consanguinity was common (22%). Coding regions and 25-bp boundaries of 15 OI genes ( COL1A1, COL1A2, IFITM5 [plus 5’UTR], SERPINF1, CRTAP, P3H1, PPIB, SERPINH1, FKBP10, PLOD2, BMP1, SP7, TMEM38B, WNT1, CREB3L1 ) were captured with Agilent SureSelectXT and sequenced in Illumina NextSeq. Identified variants were classified according to ACMG/AMP guidelines and those considered to be disease-causing were confirmed by Sanger sequencing. Segregation analysis was pursued when familial samples were available. A molecular diagnosis was obtained in 92% of cases. Altogether, 55 variants were identified, 21 of which had never been previously reported in international databases. Variants in COL1A1 or COL1A2 were identified in 77%, whereas 23% had variants in other candidate genes. Amongst these, variants in SERPINF1, FKBP10 and PLOD2 were more prevalent. Only one case had the previously described IFITM5 c.-14C>T variant. A peculiar combination of four heterozygous P3H1 and WNT1 variants was detected in a non-consanguineous case, where one variant in each gene was inherited from each parent. In two cases, potentially modifier variants in LRP5 were identified. Surprisingly, in four consanguineous families the molecular cause was still related to COL1A1 or COL1A2 , and two non-consanguineous cases had compound heterozygous PLOD2 variants. In conclusion, targeted MPS has effectively allowed establishing the molecular basis of OI in this Brazilian cohort, unraveling novel disease-causing variants in 29% of cases, and potentially reflecting new aspects of OI pathogenesis in Brazil. Non-collagen defects were found in 23% of cases, with a higher prevalence of P3H1, FKBP10, PLOD2 and SERPINF1 defects, with potential digenic interactions, and a lower prevalence of IFITM5 -related OI. Inferring the molecular diagnosis from a family history of consanguinity was misleading in this setting. Obtaining a precise diagnosis of OI in underrepresented populations allows expanding our understanding of its...
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