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

Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Background: Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods: The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings: 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; p<0·0001). Of 2844 patients in the entire cohort, the main clinical syndromes were pneumonia (511 [18·0%] patients), CNS infection (469 [16·5%]), and skin and soft tissue infection (247 [8·7%]). The causal microorganism was identified in 1359 (47·8%) children, with the most prevalent ones being Neisseria meningitidis (in 259 [9·1%] patients), followed by Staphylococcus aureus (in 222 [7·8%]), Streptococcus pneumoniae (in 219 [7·7%]), and group A streptococcus (in 162 [5·7%]). 1070 (37·6%) patients required admission to a paediatric intensive care unit. Of 2469 patients with outcome data, 57 (2·2%) deaths occurred: seven were in patients with severe focal infections and 50 in those with sepsis. Interpretation: Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Memoria del evento : XVI congreso latinoamericano y caribeño de extensión y acción social universitaria

Congreso latinoamericano y caribeño de extensión y acción social universitaria (16 : 2021 : Costa Rica)El XVI Congreso Latinoamericano y Caribeño de Extensión y Acción Social Universitaria llama a conjuntar ideas para plantear nuevas perspectivas de una sociedad latinoamericana más justa. Instó a las universidades inscritas en la jornada académica desarrollada en octubre, a trabajar por una sociedad más justa, menos desigual y violenta, renovando el compromiso para aprender de los procesos de base social y comunitaria, que se desarrollan con fuerza en la región. Tiene como objetico el contribuir con la reflexión crítica del quehacer de extensión y la acción social de las universidades latinoamericanas, mediante el intercambio de saberes y experiencias de distintos actores de la comunidad universitaria y civil latinoamericana a propósito de los desafíos del contexto regional.The XVI Latin American and Caribbean Congress of Extension and University Social Action calls for joining ideas to propose new perspectives of a fairer Latin American society. He urged the universities enrolled in the academic session held in October to work for a fairer, less unequal and violent society, renewing their commitment to learn from social and community-based processes that are strongly developing in the region. Its objective is to contribute to the critical reflection of the extension work and social action of Latin American universities, through the exchange of knowledge and experiences of different actors of the Latin American university and civil community regarding the challenges of the regional context.Universidad Nacional, Costa RicaEscuela de Planificación y Promoción Socia

Ischemic heart disease in women La cardiopatía isquémica en la mujer A cardiopatia isquêmica na mulher

Nowadays, Coronary Diseases (CDs) represent the main mortality cause in men and women, but there are gender differences regarding their presentation, progression and the way the disease is tackled. This study mainly focuses on reviewing literature about the CD and its gender approach. The authors carried out a search of texts that use qualitative methodology, published between 2003 and 2009 in the following databases: PUBMED, IME, CUIDEN and CINAHL. Factors that hinder the early diagnosis of Ischemic Heart Disease in women are identified as the main findings, and the possible consequences are pointed out. In the fifty-six texts that were selected initially, we can see the difficulty women face to recognize early symptoms of the CD and their low risk perception of this disease. Greater awareness on Ischemic Heart Disease is needed, so that the high morbidity and mortality rates can be reduced.<br>Las Enfermedades Coronarias (EC) suponen la principal causa de mortalidad en el sexo femenino y masculino, pero existen diferencias de género en aspectos como la presentación, evolución o el abordaje de la enfermedad. Este trabajo se centra principalmente en revisar la literatura sobre la EC y el enfoque de género. Los autores han realizado una búsqueda de artículos que utilizan metodología cualitativa publicados entre 2003 y 2009 en las bases de datos PUBMED, IME, CUIDEN y CINAHL. Como hallazgos principales se identifican los factores que dificultan el diagnóstico precoz de la cardiopatía isquémica en la mujer, y se apuntan las posibles consecuencias que puede comportar. En los 56 textos seleccionados, inicialmente se evidencia la dificultad de la mujer para reconocer los síntomas iniciales de EC, así como la baja percepción de riesgo sobre dicha enfermedad. Es necesaria una mayor concienciación sobre la CI con la finalidad de reducir las altas cifras de morbimortalidad.<br>As doenças coronárias (DC) são o principal motivo de mortalidade no sexo feminino e masculino. Existem diferenças de gênero na apresentação, na evolução e na maneira como a doença é abordada. Este trabalho teve como objetivo principal revisar a literatura sobre a DC e o seu enfoque de gênero. Os autores pesquisaram diferentes textos caracterizados por uma abordagem qualitativa, publicados entre 2003 e 2009, nas bases de dados PubMed, IME, CUIDEN e CINAHL. Como principais resultados são identificados os fatores que dificultam o diagnóstico precoce da doença isquêmica nas mulheres, e as possíveis consequências desse diagnóstico tardio são apontadas. Nos 56 textos selecionados, inicialmente mostra-se a dificuldade da mulher relacionada ao reconhecimento dos primeiros sintomas da doença coronária, e a baixa percepção do risco dessa doença. É necessária maior sensibilização sobre a cardiopatia isquêmica (CI), para se reduzir o elevado índice de morbidade e mortalidade

Pulmonary tuberculosis is associated with biomass fuel use among rural women in Pakistan: An age- and residence-matched case-control study

Facility-based, age- and residential area-matched case-control study was conducted in Sindh, Pakistan to determine association between biomass fuel use for cooking and pulmonary tuberculosis (TB). Cases were women with pulmonary TB, and controls were those suffering from other diseases. Current users of biomass fuel were at higher risk of pulmonary TB (adjusted matched odds ratio [mOR] = 3.0; 95% CI = 1.1-4.9) compared with nonusers. In comparison with former biomass users (women not using biomass for \u3e10 years), recent biomass users (women who switched from biomass to nonbiomass ≤10 years ago), and current (lifetime) users were at a higher risk in a dose-response manner (adjusted mOR = 2.8, 95% CI = 0.9-8.2 and adjusted mOR = 3.9, 95% CI = 1.4-10.7, respectively). Population attributable fraction for TB related to biomass fuel use was 40.6% (95% CI = 35.5%-45.7%). This study strengthens the evidence that biomass fuel use for cooking is associated with pulmonary TB and risk increases with duration of exposure