Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Vascular injuries of the upper extremity Lesões vasculares de membros superiores

OBJECTIVE: This study analyzes the causes of injuries, presentations, surgical approaches, outcome and complications of vascular trauma of the upper limbs, in spite of limited hospital resources. METHODS: A 5-year retrospective analysis. From 01/01/2001 to 31/12/2005, 165 patients were operated for vascular injuries at King Fahd Hospital, Medina, Saudi Arabia. Of all peripheral vascular trauma patients (115), upper limb trauma was present in 58. Diagnosis was made by physical examination and hand-held Doppler alone or in combination with Doppler scan/angiography. Primary vascular repair was performed whenever possible; otherwise, the interposition vein graft was used. Fasciotomy was considered when required. Patients with unsalvageable lower extremity injury requiring primary amputation were excluded from the study. RESULTS: Fifty patients were male (86%) and eight were female (14%), aged between 2.5-55 years (mean 23 years). Mean duration of presentation was 8 h after the injury. The most common etiological factor was road traffic accidents, accounting for 50.5% in the blunt trauma group and 33% among all penetrating and stab wound injuries. Incidence of concomitant orthopedic injuries was very high in our study (51%). The brachial artery was the most affected (51%). Interposition vein grafts were used in 53% of the cases. Limb salvage rate was 100%. CONCLUSION: Patients who suffer vascular injuries of the upper extremities should be transferred to vascular surgery centers as soon as possible. Decisive management of peripheral vascular trauma will maximize patient survival and limb salvage. Priorities must be established in the management of associated injuries, and delay must be avoided when ischemic changes are present.<br>OBJETIVO: Este estudo analisa as causas de lesões, apresentação, abordagens cirúrgicas, desfechos e complicações do trauma vascular de membros superiores, apesar de recursos hospitalares limitados. MÉTODOS: Análise retrospectiva de 5 anos. De 01/01/2001 a 31/12/2005, 165 pacientes foram operados devido a lesões vasculares no King Fahd Hospital, Medina, Arábia Saudita. De todos os pacientes com trauma vascular periférico (115), trauma de membros superiores esteve presente em 58. O diagnóstico foi realizado por exame físico e Doppler manual isoladamente ou associado com ultra-som Doppler/angiografia. A restauração vascular primária foi realizada sempre que possível; do contrário, utilizou-se a interposição de veia. A fasciotomia foi considerada quando necessário. Pacientes com lesão de membro inferior não resgatável necessitando de amputação foram excluídos do estudo. RESULTADOS: Cinqüenta pacientes eram homens (86%) e oito eram mulheres (14%), com idade entre 2,5 e 55 anos (média de 23 anos). A duração média de apresentação foi 8 h pós-lesão. O fator etiológico mais comum foi acidente em estradas, sendo responsável por 50,5% no grupo de trauma contuso e 33% entre as lesões penetrantes e por arma branca. A incidência de lesões ortopédicas concomitantes foi muito alta em nosso estudo (51%). A artéria braquial foi a mais afetada (51%). A interposição de veias foi utilizada em 53% dos casos. A taxa de preservação de membros foi de 100%. CONCLUSÃO: Pacientes que sofrem lesões vasculares de membros superiores devem ser transferidos para centros de cirurgia vascular o mais rápido possível. O tratamento imediato do trauma vascular periférico aumentará a sobrevida dos pacientes e a preservação dos membros. Devem-se estabelecer prioridades no tratamento de lesões associadas e evitar o atraso quando alterações isquêmicas estiverem presentes

Videotoracoscopia no trauma de tórax

OBJETIVOS: Com o intuito de definir a função da videotoracoscopia no diagnóstico e tratamento no trauma torácico, foram estudados 51 traumatizados por traumas penetrantes ocasionados por arma branca, ferimentos por projétil de arma de fogo ou traumas fechados do tórax, com suspeita diagnóstica por exame clínico e/ou radiológico de lesões torácicas. MÉTODOS: Foram selecionados doentes estáveis vítimas de trauma torácico (pressão arterial sistólica igual ou superior a 90mmHg) com diagnóstico de: hemotórax em 20 (cinco hemotórax estacionários, quatro hemotórax progressivos e 11 hemotórax coagulados), contusões e ferimentos precordiais (três), ferimentos da zona de transição tóraco-abdominal (24), corpo estranho no tórax (dois) e ferimentos transfixantes do mediastino (dois). Todos foram submetidos à videotoracoscopia. RESULTADOS: A videotoracoscopia se mostrou eficiente na investigação diagnóstica nos casos de hemotórax progressivo (quatro casos), hemotórax coagulado (11 casos), contusões e ferimentos precordiais (três casos), ferimentos da zona da transição tóraco-abdominal (confirmação de nove lesões diafragmáticas em 24 traumatizados examinados, 37,5%) e corpos estranhos no tórax, retirada do corpo estranho com sucesso (dois casos). O procedimento também foi eficiente, além do diagnóstico, no tratamento de hemotórax progressivo (ligadura de artéria mamária um caso, cauterização de vasos intercostais um caso), hemotórax coagulado (remoção de coágulos e decorticação, 11 casos) tendo evitado a realização de toracotomia em 33,3% dos traumatizados examinados. CONCLUSÕES: A videotoracoscopia é método eficiente para diagnóstico e tratamento no traumatismo do tórax e ainda pode evitar a toracotomia em expressivo número de pacientes submetidos ao procedimento

Prophylactic use of aspirin: systematic review of harms and approaches to mitigation in the general population

The review was sponsored by International Society of Cancer Prevention (ISCaP), Cancer Research UK (CRUK), British Heart Foundation (BHF) and American Cancer Society (ACS) and received funding from CRUK, BHF and AC

Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial

Background: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. We compared the selective thromboxane-prostaglandin receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event. &lt;p/&gt;Methods: This randomised, double-blind, parallel-group trial was undertaken in 802 centres in 46 countries. Patients who had an ischaemic stroke in the previous 3 months or a TIA in the previous 8 days were randomly allocated with a central interactive response system to 30 mg per day terutroban or 100 mg per day aspirin. Patients and investigators were masked to treatment allocation. The primary efficacy endpoint was a composite of fatal or non-fatal ischaemic stroke, fatal or non-fatal myocardial infarction, or other vascular death (excluding haemorrhagic death). We planned a sequential statistical analysis of non-inferiority (margin 1·05) followed by analysis of superiority. Analysis was by intention to treat. The study was stopped prematurely for futility on the basis of the recommendation of the Data Monitoring Committee. This study is registered, number ISRCTN66157730. &lt;p/&gt;Findings: 9562 patients were assigned to terutroban (9556 analysed) and 9558 to aspirin (9544 analysed); mean follow-up was 28·3 months (SD 7·7). The primary endpoint occurred in 1091 (11%) patients receiving terutroban and 1062 (11%) receiving aspirin (hazard ratio [HR] 1·02, 95% CI 0·94–1·12). There was no evidence of a difference between terutroban and aspirin for the secondary or tertiary endpoints. We recorded some increase in minor bleedings with terutroban compared with aspirin (1147 [12%] vs 1045 [11%]; HR 1·11, 95% CI 1·02–1·21), but no significant differences in other safety endpoints. &lt;p/&gt;Interpretation: The trial did not meet the predefined criteria for non-inferiority, but showed similar rates of the primary endpoint with terutroban and aspirin, without safety advantages for terutroban. In a worldwide perspective, aspirin remains the gold standard antiplatelet drug for secondary stroke prevention in view of its efficacy, tolerance, and cost