Primera aproximación al uso de la ocupación del tapir (Tapirella bairdii Gill, 1865) como indicador de la integridad ecológica en la Reserva de la Biosfera Maya, Guatemala

La Reserva de la Biosfera Maya (RBM) es un área protegida de relevancia nacional, regional y mundial por la diversidad biológica  asociada  y  los  beneficios  que  se  obtienen  de  esta.  En  su  plan  maestro  se  plantea  el  conjunto  de  elementos  de conservación a partir de los cuales se orientan estrategias y se evalúa la efectividad de manejo de dicha reserva, entre los cuales se incluye a Tapirella  bairdii  (tapir), por lo que es importante contar con un monitoreo de esta especie como una  herramienta para la administración de esta reserva. En el 2015 se inició el desarrollo de un protocolo de monitoreo basado en la estimación de  la  probabilidad de  ocupación  y el  presente  estudio constituye  la  continuación de  esta  iniciativa  a  través de la implementación de las  temporadas  de muestreo en 2017 y 2018. Se registró la presencia del tapir en cinco zonas núcleo de la RBM empleando trampas cámara y se estimó la probabilidad de ocupación. Los valores estimados sugieren una relación  de la ocupación con la integridad ecológica, en la cual hay una mayor ocupación en áreas con menor perturbación. Se generaron modelos con cinco covariables relacionadas con amenazas potenciales, sin embargo fue el modelo nulo el que se  seleccionó  de  acuerdo  al  criterio  definido.  Los  resultados  sugieren  que  la  integridad  ecológica  en  las  áreas  de  estudio  está siendo afectada  como consecuencia  de  las presiones antrópicas por lo que  es necesario el  fortalecimiento de  aquellas con menores valores de ocupación.

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

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

Contribución al mecanismo de formación de poros de sticholisina I, una proteína formadora de poros de la anémona Stichodactyla helianthus, mediante el empleo de mutantes de Cys en zonas funcionalmente relevantes de la proteína

Sticholisina I (St I) es una citolisina producida por la anémona marina Stichodactyla helianthus, que se caracteriza por formar poros oligoméricos en membranas naturales y artificiales. En este trabajo se describe la obtención por vía recombinante en Escherichia coli (E. coli) de una variante recombinante de St I (St Ir), así como su caracterización conformacional y funcional. Estos trabajos permitieron reducir el impacto ecológico que provoca la obtención de St I a partir de las anémonas como fuente natural y además realizar mutagénesis sitio-específica para su caracterización funcional. La ausencia de Cys en St I facilitó la introducción de este residuo aminoacídico, por mutagénesis dirigida, en zonas funcionalmente importantes de la toxina. En el trabajo se sustituyeron por Cys en St Ir de forma independiente, los aminoácidos Glu2 y Phe15 (localizados en el segmento de los primeros treinta aminoácidos que participan en la formación del canal) y la Arg52, Pro80 y Trp111 (en la región de interacción con las membranas). Así, se obtuvieron y purificaron de E. coli cinco proteínas mutadas: StI E2C, StI F15C, StI R52C, StI P80C y StI W111C. Los estudios de caracterización espectroscópicos permitieron establecer que las sustituciones aminoacídicas no provocaron cambios conformacionales en los mutantes con respecto a St Ir. Los monómeros de StI E2C, StI R52C y StI P80C mostraron capacidades similares de unión a las membranas en comparación con la variante recombinante. StI F15C mostró un ligero incremento en su capacidad de interacción con las membranas mientras que StI W111C resultó la de menor capacidad de unión. La capacidad formadora de poros de los monómeros, medida en vesículas liposomales y membrana eritrocitaria, resultó similar entre StI E2C, StI F15C y St Ir. Sin embargo, la actividad lítica de StI R52C, StI P80C y StI W111C disminuyó con respecto a St Ir. Los agregados diméricos por enlace disulfuro en StI R52C y StI W111C disminuyeron la actividad biológica de las proteínas. Una de las novedades científicas más importante del presente trabajo radica en que se demuestra que la presencia de agregados diméricos estabilizados por enlace disulfuro, en StI E2C, incrementa la actividad biológica formadora de poros tanto en vesículas liposomales como en eritrocitos. Estos resultados demuestran, por primera vez, que la unión covalente de los extremos aminos de St I potencia la formación de poros funcionales por un mecanismo hasta ahora desconocido. En la investigación se aportan nuevos elementos sobre la importancia de los residuos Glu2, Phe15, Arg52, Pro80 y Trp111 en las etapas de unión inicial a las membranas y de formación de poros durante el mecanismo lítico. Por último, la obtención de los mutantes de Cys abre las posibilidades para el marcaje de St I con sondas de espín o sondas fluorescentes para estudiar el mecanismo de formación de poros mediante las espectroscopias de resonancia paramagnética electrónica (EPR) y de fluorescencia, y sustentan otras aplicaciones nanobiotecnológicas actualmente en desarrollo en nuestro grupo de trabajo.Sticholisin I (St I) is a cytolysin produced by the sea anemone Stichodactyla helianthus, which is characterized by forming oligomeric pores in natural and artificial membranes. This work describes the recombinant production in Escherichia coli (E. coli) of a recombinant variant of St I (St Ir), as well as its conformational and functional characterization. These works allowed us to reduce the ecological impact caused by obtaining St I from anemones as a natural source and also perform site-specific mutagenesis for its functional characterization. The absence of Cys in St I facilitated the introduction of this amino acid residue, by directed mutagenesis, into functionally important areas of the toxin. In the work, the amino acids Glu2 and Phe15 (located in the segment of the first thirty amino acids that participate in the formation of the channel) and Arg52, Pro80 and Trp111 (in the interaction region) were independently replaced by Cys in St Ir. with the membranes). Thus, five mutated proteins were obtained and purified from E. coli: StI E2C, StI F15C, StI R52C, StI P80C and StI W111C. Spectroscopic characterization studies allowed us to establish that amino acid substitutions did not cause conformational changes in the mutants with respect to St Ir. The monomers of StI E2C, StI R52C and StI P80C showed similar binding capacities to membranes compared to the recombinant variant. StI F15C showed a slight increase in its interaction capacity with membranes while StI W111C had the lowest binding capacity. The pore-forming capacity of the monomers, measured in liposomal vesicles and erythrocyte membrane, was similar between StI E2C, StI F15C and St Ir. However, the lytic activity of StI R52C, StI P80C and StI W111C decreased with respect to St Ir The dimeric aggregates by disulfide bond in StI R52C and StI W111C decreased the biological activity of the proteins. One of the most important scientific novelties of the present work is that it is demonstrated that the presence of dimeric aggregates stabilized by disulfide bond, in StI E2C, increases the pore-forming biological activity in both liposomal vesicles and erythrocytes. These results demonstrate, for the first time, that covalent attachment of the amino termini of St I enhances the formation of functional pores by a previously unknown mechanism. The research provides new elements on the importance of residues Glu2, Phe15, Arg52, Pro80 and Trp111 in the stages of initial binding to membranes and pore formation during the lytic mechanism. Finally, obtaining the Cys mutants opens the possibilities for labeling St I with spin probes or fluorescent probes to study the mechanism of pore formation through electron paramagnetic resonance (EPR) and fluorescence spectroscopies, and support other nanobiotechnological applications currently under development in our working group.Universidad Nacional, Costa RicaAcademia de Ciencias de Cuba, CubaEscuela de Ciencias Biológica

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research