Curso temporal de la expresión de proteínas antioxidantes, Trx1 y Nrf2, inducidas por la exposición a rayos X en un modelo murino

Se diseñó un modelo murino de irradiación a cuerpo entero con rayos X (RX), para estudiar el curso tempo-ral de la expresión de mRNA de Nrf2 y de Trx1, dos proteínas que participan en la respuesta antioxidante, en distintos órganos con diferente radiosensibilidad

Assessment of pre-clinical liver models based on their ability to predict the liver-tropism of adeno-associated virus vectors

The liver is a prime target for in vivo gene therapies using recombinant adeno-associated viral vectors (rAAV). Multiple clinical trials have been undertaken for this target in the past 15 years, however we are still to see market approval of the first liver-targeted AAV-based gene therapy. Inefficient expression of the therapeutic transgene, vector-induced liver toxicity and capsid, and/or transgene-mediated immune responses reported at high vector doses are the main challenges to date. One of the contributing factors to the insufficient clinical outcomes, despite highly encouraging preclinical data, is the lack of robust, biologically- and clinically-predictive preclinical models. To this end, this study reports findings of a functional evaluation of six AAV vectors in twelve preclinical models of the human liver, with the aim to uncover which combination of models is the most relevant for the identification of AAV capsid variant for safe and efficient transgene delivery to primary human hepatocytes. The results, generated by studies in models ranging from immortalized cells, iPSC-derived and primary hepatocytes, and primary human hepatic organoids to in vivo models, increased our understanding of the strengths and weaknesses of each system. This should allow the development of novel gene therapies targeting the human liver

Dislipidemias e alguns fatores de risco associados em uma população periférica da Região Metropolitana de São Paulo, SP - Brasil. um estudo piloto Lipemic disorders and some associated risk factors in a population on the outs kirts of Greater S. Paulo, SP, Brazil

Realizou-se levantamento da prevalência de dislipidemias e alguns fatores de risco (hipertensão, obesidade e alcoolismo), em uma população típica da periferia do Município de São Paulo, SP (Brasil). A prevalência de um ou mais fatores de risco foi maior do que 50% em todos os grupos etários. No que concerne às dislipidemias propriamente ditas, foi de aproximadamente 49%, 58% e 57% nos grupos etários de 20 a 39 anos, 40 a 59 anos e 60 anos e mais, respectivamente. A dislipidemia mais freqüente foi devido a baixos níveis de HDL-colesterol, principalmente nos mais jovens, entre 29 e 39 anos. Nos outros dois grupos etários houve prevalência maior de "outras dislipidemias". A obesidade isolada ou associada foi o fator de risco mais relevante na população estudada. Levanta-se a hipótese de que as dislipidemias podem constituir-se em grave problema de Saúde Pública nas populações periféricas da cidade de São Paulo.<br>A survey of the prevalence of lipemic disorders and some risk factors associated with them (obesity, hypertension and alcoholism), in a representative sample of the population of 20 years of age and over in a locality typical of the peripheral zone of the Greater S. Paulo Region, Brazil, both in terms of the poverty of the population and with regard to the lack of public sources such as sewage, transport and housing, is undertaken. The following results were obtained: a) the prevalence of one risk factor was of about 55%, and of two or more associated risk factors was of approximately 9% in the age group from 20 to 39. There was found to be a prevalence of about 51% and 57%, respectively of two or more associated risk factors for the age groups from 40 to 59 and 60 years of age and over; b) the prevalence of lipemic disorders proper was of about 49%, 58% and 57% respectively, for the age groups of 20 to 39, 40 to 59 and 60 years of age and over. In these cases the most prevalent risk factors among men were alcoholism and hypertension, either isolatedly or associated with obesity, and among women the most prevalent was obesity, alone or associated with hypertension; c) the most prevalent lipemic disorder was due to HDL-cholesterol, mainly among the younger people. The prevalence lower-than-normal HDL-cholesterol, was of about 28% and of "other lipemic disorders" was of 22% in the age group between 20 and 39 years of age. For those between 40 and 59 years of age the prevalence of low HDL-cholesterol and "other lipemic disorders" was of about 20% and 38% respectively. Among those above 60 years of age, the prevalence of HDL-cholesterol below normal was of about 7% and "other lipemic disorders" was of aproximately 50%; d) obesity whether isolated or associated, was the most significant with higher "prevalence risk ratio". The lipemic disorders and risk factors studied probably represent a severe public health problem for the population of the peripheral zone of the city of S. Paulo

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module

•We report INICC device-associated module data of 50 countries from 2010-2015.•We collected prospective data from 861,284 patients in 703 ICUs for 3,506,562 days.•DA-HAI rates and bacterial resistance were higher in the INICC ICUs than in CDC-NHSN's.•Device utilization ratio in the INICC ICUs was similar to CDC-NHSN's. Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically