Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Profilaxia antimicrobiana em cirurgia vascular periférica: cefalosporina ainda é o padrão-ouro? Antimicrobial prophylaxis in peripheral vascular surgery: is cephalosporin still the gold standard?

Nas cirurgias vasculares periféricas, as cefalosporinas têm seu uso consagrado como agente antimicrobiano profilático de escolha. Recentemente, observamos uma mudança nos padrões de colonização, prevalência de patógenos e suscetibilidade geral aos antimicrobianos. Os patógenos multirresistentes vêm se tornando cada vez mais freqüentes nas infecções de ferida cirúrgica vascular, demonstrando variações regionais e locais quanto à suscetibilidade aos antimicrobianos profiláticos utilizados na rotina cirúrgica. Os dados e a literatura disponível até o momento demonstram que não existe evidência suficiente para uma mudança na rotina profilática perioperatória. Entretanto, devemos levar em consideração os padrões regionais e institucionais de prevalência de patógenos resistentes e padrões de suscetibilidade aos antimicrobianos para estabelecer guias e orientações específicas para a utilização de antimicrobianos profiláticos alternativos.<br>In peripheral vascular surgery, cephalosporins are nowadays regarded as the first choice for operative antibiotic prophylaxis. We have recently observed changes in colonizing patterns, pathogen prevalence and antibiotic susceptibility to antimicrobials. Multiresistant pathogens are becoming more frequent in vascular surgical wound infections, showing regional and local variations as to prophylactic antibiotic susceptibility. Data from the available literature so far have shown no strong evidence for a change in routine surgical antibiotic prophylaxis. We must consider regional and institutional prevalence of pathogen resistance and patterns of antibiotic susceptibility to establish specific guidelines for the use of alternative antibiotics

Standard abdominal wound edge protection with surgical dressings vs coverage with a sterile circular polyethylene drape for prevention of surgical site infections (BaFO): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Postoperative surgical site infections cause substantial morbidity, prolonged hospitalization, costs and even mortality and remain one of the most frequent surgical complications. Approximately 14% to 30% of all patients undergoing elective open abdominal surgery are affected and methods to reduce surgical site infection rates warrant further investigation and evaluation in randomized controlled trials.</p> <p>Methods/design</p> <p>To investigate whether the application of a circular plastic wound protector reduces the rate of surgical site infections in general and visceral surgical patients that undergo midline or transverse laparotomy by 50%. BaFO is a randomized, controlled, patient-blinded and observer-blinded multicenter clinical trial with two parallel surgical groups. The primary outcome measure will be the rate of surgical site infections within 45 days postoperative assessed according to the definition of the Center for Disease Control. Statistical analysis of the primary endpoint will be based on the intention-to-treat population. The global level of significance is set at 5% (2 sided) and sample size (n = 258 per group) is determined to assure a power of 80% with a planned interim analysis for the primary endpoint after the inclusion of 340 patients.</p> <p>Discussion</p> <p>The BaFO trial will explore if the rate of surgical site infections can be reduced by a single, simple, inexpensive intervention in patients undergoing open elective abdominal surgery. Its pragmatic design guarantees high external validity and clinical relevance.</p> <p>Trial registration</p> <p><url>http://www.clinicaltrials.gov</url> NCT01181206. Date of registration: 11 August 2010; date of first patient randomized: 8 September 2010</p