Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency

Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-κB activity through the downregulation of inhibitor of apoptosis proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immunity. Our data demonstrate that by activating NF-κB, MOMP can exert additional signalling functions besides triggering cell death. Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies

Conventional vs. tubeless percutaneous nephrolithotomy. Is the urinary diversion really necessary?

Introducción La nefrolitotomía percutánea (NLP) convencional utiliza derivación con nefrostomía para mejorar el drenaje de orina, facilitar la hemostasia postoperatoria y permitir un trayecto seguro para intervenciones adicionales futuras. Sin embargo, en los últimos años el procedimiento de NLP se ha modificado: ahora permite el retiro del uso del catéter de nefrostomía o de derivación urinaria, procedimiento conocido como tubeless. El presente estudio pretende evaluar la experiencia institucional en cuanto a seguridad, eficacia y ventajas de la NLP tubeless. Materiales y métodos Entre agosto de 2012 y mayo de 2014 se reclutó a 51 pacientes del Hospital Universitario San Ignacio y Clínica Fundadores para manejo con nefrolitotomía percutánea. Se incluyó a 49 pacientes con litiasis renal menor de 5cm de diámetro y mayor de 2cm con punción única o múltiple. Se aleatorizaron en 2 grupos: grupo A sin derivación (no nefrostomía no catéter doble J) 26 pacientes, grupo B con derivación (nefrostomía sonda Foley 18 Fr) 23 pacientes. Los desenlaces evaluados fueron: efectividad verificada mediante revisión de imágenes postoperatorias y definida como cálculo residual menor de 5mm, sangrado postoperatorio con medición de hemoglobina durante las primeras 24 h después de cirugía, valoración de dolor con escala visual análoga, necesidad de analgésicos durante las primeras 4 h, cantidad de rescates de analgésico durante las primeras 24 h de cirugía. Los datos se analizaron mediante el paquete estadístico IBM SPSS versión 20, utilizando estadística no paramétrica con la prueba de Wilcoxon Mann-Whitney una vez se determinó que la muestra no tenía una distribución normal. Las variables dicotómicas se analizaron utilizando la prueba de Chi2. Resultados Las características de base de los pacientes son comparables: la edad promedio en el grupo A fue de 44,73 años y en el B de 50,26 años (p=0,186), el peso en el grupo A fue de 75,96 kg y en el B de 71,96 kg (p=0,054), el tamaño de los cálculos en el A fue de 28,23mm en promedio y en el B de 29,69mm, sin diferencia estadísticamente significativa (p=0,517). No hubo diferencias significativas en cuanto a efectividad en ambos grupos: en el A el porcentaje de lito residual fue de 1,15% y en el B de 0,87% (p=0,713). No hubo diferencias estadísticamente significativas en cuanto a sangrado postoperatorio (p=0,566), pero sí se observó mayor dolor, requerimiento de analgésicos y mayor número de rescates en los pacientes a los cuales se les dejó derivación mediante nefrostomía. Discusión Nuestro trabajo demuestra que la NLP sin derivación urinaria es una técnica segura en aquellos pacientes en los cuales se logra una extracción completa del cálculo, con sangrado comparable a la cirugía convencional y, adicionalmente, con el beneficio de menor dolor y menor requerimiento de analgésico postoperatorio.Q4Artículo original5-9Introduction Conventional percutaneous nephrolithotomy (PNL) uses a nephrostomy derivation to improve the drainage of urine, facilitate postoperative hemostasis and allow a safe course for future additional surgical interventions. However, in recent years the PNL procedure has been modified to avoid the use of a nephrostomy catheter or any other urinary diversion. This procedure is known as tubeless. This study aims to assess the institutional experience in safety, efficiency and advantages of tubeless PNL. Materials and methods Between August 2012 and May 2014, 51 patients were recruited in San Ignacio University Hospital and Fundadores Clinic to be treated with PNL. Forty-nine patients with kidney lithiasis less than 5cm of diameter and greater than 2cm with single or multiple puncture were included. They were randomised into 2 groups: group A no derivation (no nephrostomy catheter, no double J) 26 patients, group B with derivation (18 Fr Foley nephrostomy catheter) 23 patients. The evaluated outcomes were: Effectiveness verified by reviewing postoperative images and defined as a residual stone less than 5mm of diameter, postoperative bleeding with hemoglobin measurement during the first 24h after surgery, pain assessment with the visual analog scale, need for analgesics during the first 4h, amount of analgesic rescues during the first 24h of surgery. Data were analyzed using the statistical package SPSS version 20, using the nonparametric statistical test Wilcoxon Mann-Whitney 11 it was determined that the sample does not have a normal distribution, the dichotomous variables were analyzed using Chi2 test. Results Baseline characteristics of patients are comparable: The average age in the group A was 44.73 and 50.26 years in the group B (P=.186), average weight in group A and B was 75.96kg and 71.96kg, respectively (P=.054), the average size of the stones in group A was 28.23mm and 29.69mm in group B with no statistically significant difference (P=.517). There were no significant differences in effectiveness in both groups, in group A the percentage of residual lithiasis was 1.15% and 0.87% in group B (P=.713). There were no statistically significant differences in postoperative bleeding (P=.566), although pain, analgesic requirement and number of rescues needed were greater in patients who were left with a nephrostomy derivation. Discussion Our work shows that percutaneous nephrolithotomy without urinary diversion is a safe procedure in patients in whom a complete stone removal is achieved, with bleeding comparable to conventional surgery, and additionally with the benefit of less pain and less postoperative analgesic requirement

In vitro activity of ten medicinal plants on ten Streptococcus pneumoniae strains

Introducción: El portador sano es el principal diseminador de las infecciones neumocócicas por la nasofaringe. Una alternativa para combatirlo son las plantas medicinales. Objetivos: Determinar la efectividad de diez plantas medicinales frente a Streptococcus pneumoniae. Diseño: Estudio experimental in vitro. Material biológico: Plantas medicinales y cepas de Streptococcus pneumoniae. Intervenciones: Los extractos de 10 plantas medicinales fueron puestos en contacto in vitro con 10 cepas de Streptococcus pneumoniae. Principales medidas de resultados: Actividad de las plantas medicinales sobre las cepas de Streptococcus pneumoniae. Resultados: almendro y Bellaco caspi fueron las únicas plantas que dieron pequeño halo de inhibición con algunas cepas; con almendro se inhibió dos cepas y con Bellaco caspi, se inhibió siete cepas y tres resultaron resistentes. Estos resultados no tuvieron relación con el serotipo de neumococo ni con los antibióticos utilizados en los antibiogramas realizados previamente. Conclusiones: El Bellaco caspi podría ser una alternativa para atacar al neumococo en la nasofaringe. Pero, por haber presentado resistencia a tres cepas de Streptococcus pneumoniae, antes de usarlo sería conveniente desarrollar un antibiograma de los neumococos contra las plantas medicinales.Introduction: The healthy carrier is the main disseminator of pneumococcal infections through nasopharynx; an alternative for treatment is a medicinal plant. Objectives: To determine the effectivity of ten medicinal plants against Streptococcus pneumoniae. Design: In vitro experimental study. Biologic materials: Medicinal plant extracts and Streptococcus pneumoniae strains. Interventions: Ten medicinal plant extracts were put in contact in vitro with 10 different Streptococcus pneumonia strains. Main outcome measures: Medicinal plant extracts activity against Streptococcus pneumoniae strains. Results: Only almendro y Bellaco caspi showed small inhibition halos with some strains; with almendro two of 10 Pneumococcus strains were inhibited and with Bellaco caspi seven strains were inhibited and three were resistant. These results had no relation either with Pneumococcus serotype or with antibiotics used according to antibiograms. Conclusions: Bellaco caspi could be an alternative for treating nasopharynx Pneumococcus, but due to resistance to three Streptococcus pneumonia strains there is no total guarantee and an antibiogram for pneumococci against medicinal plants is needed

Global Island Monitoring Scheme (GIMS): a proposal for the long-term coordinated survey and monitoring of native island forest biota

Islands harbour evolutionary and ecologically unique biota, which are currently disproportionately threatened by a multitude of anthropogenic factors, including habitat loss, invasive species and climate change. Native forests on oceanic islands are important refugia for endemic species, many of which are rare and highly threatened. Long-term monitoring schemes for those biota and ecosystems are urgently needed: (i) to provide quantitative baselines for detecting changes within island ecosystems, (ii) to evaluate the effectiveness of conservation and management actions, and (iii) to identify general ecological patterns and processes using multiple island systems as repeated ‘natural experiments’. In this contribution, we call for a Global Island Monitoring Scheme (GIMS) for monitoring the remaining native island forests, using bryophytes, vascular plants, selected groups of arthropods and vertebrates as model taxa. As a basis for the GIMS, we also present new, optimized monitoring protocols for bryophytes and arthropods that were developed based on former standardized inventory protocols. Effective inventorying and monitoring of native island forests will require: (i) permanent plots covering diverse ecological gradients (e.g. elevation, age of terrain, anthropogenic disturbance); (ii) a multiple-taxa approach that is based on standardized and replicable protocols; (iii) a common set of indicator taxa and community properties that are indicative of native island forests’ welfare, building on, and harmonized with existing sampling and monitoring efforts; (iv) capacity building and training of local researchers, collaboration and continuous dialogue with local stakeholders; and (v) long-term commitment by funding agencies to maintain a global network of native island forest monitoring plots

Naturaleza y cultura en Ámerica Latina

La concreción del XVIII Foro de Estudiantes Latinoamericanos de Antrología y Arqueología: Cultura y naturaleza en América Latina: escenarios para un modelo de desarrollo no civilizatorio, efectuado en Quito desde el 17 al 23 de julio del 2011, se constituyó en un acontecimiento sumamente significativo para la antropología latinoamericana debido a dos motivos. Primero porque coincidió con la emergencia del movimiento universitario estudiantil latinoamericano que expresaba sus tendencias, propuestas y exigencias de cambios tanto de las prácticas académicas como de los patrones civilizatorios que rigen las relaciones actuales. Segundo, porque se inscribía en un contexto de consolidación de las nuevas democracias de los países andinos, de carácter antineoliberal y basadas en los sujetos de derecho entre los cuales se incluye la naturaleza. Estos contextos determinaron que el Foro no ponga en escena certidumbres teóricas o metodológicas, ni se preste al exhibicionismo estéril de los avances disciplinares. Más bien, la convocatoria de la antropología y la arqueología fue apenas un pretexto para hablar, con su lenguaje, de nosotros mismos, de lo que somos, de lo que pensamos, de lo que aspiramos y sentimos sobre nuestra Latinoamérica. Lo que hemos visto, oído y compartido, en realidad, no han sido solamente ideas o conceptos sino opciones y toma de posiciones respecto a múltiples encrucijadas. Posición ante situaciones que amenazan la vida, la justicia y los derechos de todos, un desafío epistemológico todavía en ciernes y que no termina de cuajar aún en nuestras prácticas académicas

A miniature world in decline: European Red List of Mosses, Liverworts and Hornworts

AimThis Red List is a summary of the conservation status of the European species of mosses, liverworts and hornworts, collectively known as bryophytes, evaluated according to IUCN’s Guidelines for Application of IUCN Red List Criteria at Regional Level. It provides the first comprehensive, region-wide assessment of bryophytes and it identifies those species that are threatened with extinction at a European level, so that appropriate policy measures and conservation actions, based on the best available evidence, can be taken to improve their status.ScopeAll bryophytes native to or naturalised in Europe (a total of 1,817 species), have been included in this Red List. In Europe, 1,796 species were assessed, with the remaining 21 species considered Not Applicable (NA). For the EU 28, 1,728 species were assessed, with a remaining 20 species considered NA and 69 species considered Not Evaluated (NE). The geographical scope is continentwide, extending from Iceland in the west to the Urals in the east, and from Franz Josef Land in the north to theCanary Islands in the south. The Caucasus region is not included. Red List assessments were made at two regional levels: for geographical Europe and for the 28 Member States of the European Union.ResultsOverall, 22.5% of European bryophyte species assessed in this study are considered threatened in Europe, with two species classified as Extinct and six assessed as Regionally Extinct (RE). A further 9.6% (173 species) are considered Near Threatened and 63.5% (1,140 species) are assessed as Least Concern. For 93 species (5.3%), there was insufficient information available to be able to evaluate their risk of extinction and thus they were classified as Data Deficient (DD). The main threats identified were natural system modifications (i.e., dam construction, increases in fire frequency/intensity, and water management/use), climate change (mainly increasing frequency of droughts and temperature extremes), agriculture (including pollution from agricultural effluents) and aquaculture.RecommendationsPolicy measures• Use the European Red List as the scientific basis to inform regional/national lists of rare and threatened species and to identify priorities for conservation action in addition to the requirements of the Habitats Directive, thereby highlighting the conservation status of bryophytes at the regional/local level.• Use the European Red List to support the integration of conservation policy with the Common Agricultural Policy (CAP) and other national and international policies. For example, CAP Strategic Plans should include biodiversity recovery commitments that could anticipate, among others, the creation of Important Bryophyte Areas. An increased involvement of national environmental agencies in the preparation of these strategic plans, and more broadly in ongoing discussions on the Future CAP Green Architecture, would likely also ensure the design of conservation measures better tailored to conserve bryophytes in agricultural landscapes.• Update the European Red List every decade to ensure that the data remains current and relevant.• Develop Key Biodiversity Areas for bryophytes in Europe with a view to ensuring adequate site-based protection for bryophytes.Research and monitoring• Use the European Red List as a basis for future targeted fieldwork on possibly extinct and understudied species.• Establish a monitoring programme for targeted species (for example, threatened species and/or arable bryophytes).• Use the European Red List to obtain funding for research into the biology and ecology of key targeted species.Action on the ground• Use the European Red List as evidence to support multi-scale conservation initiatives, including designation of protected areas, reform of agricultural practices and land management, habitat restoration and rewilding, and pollution reduction measures.• Use the European Red List as a tool to target species that would benefit the most from the widespread implementation of the solutions offered by the 1991 Nitrates Directive (Council Directive 91/676/EEC), including the application of correct amounts of nutrients for each crop, only in periods of crop growth under suitable climatic conditions and never during periods of heavy rainfall or on frozen ground, and the creation of buffer zones to protect waters from run-off from the application of fertilizers.Ex situ conservation• Undertake ex situ conservation of species of conservation concern in botanic gardens and spore and gene banks, with a view to reintroduction where appropriate.</p

Colombian consensus recommendations for diagnosis, management and treatment of the infection by SARS-COV-2/ COVID-19 in health care facilities - Recommendations from expert´s group based and informed on evidence

La Asociación Colombiana de Infectología (ACIN) y el Instituto de Evaluación de Nuevas Tecnologías de la Salud (IETS) conformó un grupo de trabajo para desarrollar recomendaciones informadas y basadas en evidencia, por consenso de expertos para la atención, diagnóstico y manejo de casos de Covid 19. Estas guías son dirigidas al personal de salud y buscar dar recomendaciones en los ámbitos de la atención en salud de los casos de Covid-19, en el contexto nacional de Colombia

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Acción in vitro de diez plantas medicinales sobre diez cepas diferentes de Streptococcus pneumoniae

Introducción: El portador sano es el principal diseminador de las infecciones neumocócicas por la nasofaringe. Una alternativa para combatirlo son las plantas medicinales. Objetivos: Determinar la efectividad de diez plantas medicinales frente a Streptococcus pneumoniae. Diseño: Estudio experimental in vitro. Material biológico: Plantas medicinales y cepas de Streptococcus pneumoniae. Intervenciones: Los extractos de 10 plantas medicinales fueron puestos en contacto in vitro con 10 cepas de Streptococcus pneumoniae. Principales medidas de resultados: Actividad de las plantas medicinales sobre las cepas de Streptococcus pneumoniae. Resultados: almendro y Bellaco caspi fueron las únicas plantas que dieron pequeño halo de inhibición con algunas cepas; con almendro se inhibió dos cepas y con Bellaco caspi, se inhibió siete cepas y tres resultaron resistentes. Estos resultados no tuvieron relación con el serotipo de neumococo ni con los antibióticos utilizados en los antibiogramas realizados previamente. Conclusiones: El Bellaco caspi podría ser una alternativa para atacar al neumococo en la nasofaringe. Pero, por haber presentado resistencia a tres cepas de Streptococcus pneumoniae, antes de usarlo sería conveniente desarrollar un antibiograma de los neumococos contra las plantas medicinales