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

Doença meningocócica: comparação entre formas clínicas Meningococcal disease: comparison between clinical forms

Visando avaliar formas clínicas da doença meningocócica, foram revistos 201 casos diagnosticados como doença meningocócica, em Hospital Universitário da Universidade Federal Fluminense; durante o período de 1971 a 1996, dos quais 185 preencheram os critérios de inclusão. A caracterização clínico-laboratorial permitiu reagrupá-los nas formas de doença meningocócica com meningite, 18%, meningite e septicemia, 62%, e septicemia, 20%. Dados epidemiológicos disponíveis não diferenciaram formas clínicas. Na meningite meningocócica foi significativamente maior: tempo de história clínica; freqüência de manifestações neurológicas; e positividade da bacterioscopia, cultura e teste do látex no líquor. Na septicemia menigocócica, houve predomínio significativamente de: choque; letalidade e níveis maiores de tempo parcial de tromboplastina. Septicemia meningogócica e septicemia com meningite se diferenciaram da meningite meningocócica quanto a: tempo de história clínica; ocorrência de sinais neurológicos focais; coagulação intravascular disseminada e artrite. Dados clínico-laboratoriais levam a admitir meningite como forma localizada de doença meningocócica, e septicemia com meningite e septicemia como variações de gravidade da forma sistêmica da doença.<br>In order to asses the clinical forms of meningococcal disease, we reviewed 201 cases diagnosed as meningococcal disease in the University Hospital of the Fluminense Federal University in Rio de Janeiro, 185 of which met the inclusion criteria. Clinical and laboratorial characterization allowed for grouping of the cases as follows: meningococcal meningitis, 18%; meningitis with septicemia, 62%; and septicemia, 20%. Available epidemiological data did not differentiate clinical forms. The following were significantly greater in meningococcal meningitis: duration of clinical history; frequency of neurological manifestations; positive bacterioscopy; culture and latex test in cerebrospinal fluid. The following were significantly predominant in septicemia: shock; fatal outcome and higher partial thromboplastin time. Septicemia and meningitis with septicemia were differentiated from meningococcal meningitis in the following: duration of clinical history; occurrence of focal neurological signs; disseminated intravascular coagulation; and arthritis. Clinical and laboratory data lead us to admit meningococcal meningitis as a localized form of Meningococcal disease, and meningitis with septicemia and septicemia as variations in severity of the systemic form of the disease