Validation of the CALL score as a mortality prediction tool in a cohort of hospitalized COVID-19 patients in Chile

IntroductionThe CALL score is a predictive tool for respiratory failure progression in COVID-19. Whether the CALL score is useful to predict short- and medium-term mortality in an unvaccinated population is unknown.Materials and methodsThis is a prospective cohort study in unvaccinated inpatients with a COVID-19 pneumonia diagnosis upon hospital admission. Patients were followed up for mortality at 28 days, 3, 6, and 12 months. Associations between CALL score and mortality were analyzed using logistic regression. The prediction performance was evaluated using the area under a receiver operating characteristic curve (AUROC).ResultsA total of 592 patients were included. On average, the CALL score was 9.25 (±2). Higher CALL scores were associated with increased mortality at 28 days [univariate: odds ratio (OR) 1.58 (95% CI, 1.34–1.88), p < 0.001; multivariate: OR 1.54 (95% CI, 1.26–1.87), p < 0.001] and 12 months [univariate OR 1.63 (95% CI, 1.38–1.93), p < 0.001; multivariate OR 1.63 (95% CI, 1.35–1.97), p < 0.001]. The prediction performance was good for both univariate [AUROC 0.739 (0.687–0.791) at 28 days and 0.869 (0.828–0.91) at 12 months] and multivariate models [AUROC 0.752 (0.704–0.8) at 28 days and 0.862 (0.82–0.905) at 12 months].ConclusionThe CALL score exhibits a good predictive capacity for short- and medium-term mortality in an unvaccinated population

Cystic Fibrosis: A New Target for 4-Imidazo[2,1-b]thiazole-1,4-dihydropyridines

The pharmacology of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel has attracted significant interest in recent years with the aim to search for rational new therapies for diseases caused by CFTR malfunction. Mutations that abolish the function of CFTR cause the life-threatening genetic disease cystic fibrosis (CF). The most common cause of CF is the deletion of phenylalanine 508 (ΔF508) in the CFTR chloride channel. Felodipine, nifedipine, and other antihypertensive 1,4-dihydropyridines (1,4-DHPs) that block L-type Ca(2+) channels are also effective potentiators of CFTR gating, able to correct the defective activity of ΔF508 and other CFTR mutants ( Mol. Pharmacol. 2005 , 68 , 1736 ). For this purpose, we evaluated the ability of the previously and newly synthesized 4-imidazo[2,1-b]thiazoles-1,4-dihydropyridines without vascular activity and inotropic and/or chronotropic cardiac effects ( J. Med. Chem. 2008 , 51 , 1592 ) to enhance the activity of ΔF508-CFTR. Our studies indicate compounds 17, 18, 20, 21, 38, and 39 as 1,4-DHPs with an interesting profile of activity

‘Warrant’ revisited: Integrating mathematics teachers’ pedagogical and epistemological considerations into Toulmin’s model for argumentation

In this paper, we propose an approach to analysing teacher arguments that takes into account field dependence—namely, in Toulmin’s sense, the dependence of warrants deployed in an argument on the field of activity to which the argument relates. Freeman, to circumvent issues that emerge when we attempt to determine the field(s) that an argument relates to, proposed a classification of warrants (a priori, empirical, institutional and evaluative). Our approach to analysing teacher arguments proposes an adaptation of Freeman’s classification that distinguishes between: epistemological and pedagogical a priori warrants, professional and personal empirical warrants, epistemological and curricular institutional warrants, and evaluative warrants. Our proposition emerged from analyses conducted in the course of a written response and interview study that engages secondary mathematics teachers with classroom scenarios from the mathematical areas of analysis and algebra. The scenarios are hypothetical, grounded on seminal learning and teaching issues, and likely to occur in actual practice. To illustrate our proposed approach to analysing teacher arguments here, we draw on the data we collected through the use of one such scenario, the Tangent Task. We demonstrate how teacher arguments, not analysed for their mathematical accuracy only, can be reconsidered, arguably more productively, in the light of other teacher considerations and priorities: pedagogical, curricular, professional and personal

Analysis of Mandibular Fractures Caused by Work Related Accidents. Retrospective Descriptive Study

Indexación: Web of Science; Scielo.El objetivo de este estudio fue evaluar la tendencia de los pacientes con fracturas mandibulares asociados a accidentes laborales. Se realizó un estudio descriptivo retrospectivo en todos los casos de fracturas mandibulares que asistieron al servicio de cirugía maxilofacial del Hospital Clínico Mutual de Seguridad C.Ch.C., Santiago de Chile en un periodo de 4 años (enero 2009 - diciembre 2012). Todas las fracturas mandibulares fueron consignadas. La información fue recopilada a través de revisión de fichas clínicas electrónicas. Entre los años 2009 al 2012 se presentaron un total de 74 pacientes incluidos en el estudio con 102 rasgos de fracturas mandibulares. La fractura más común fue la de cóndilo mandibular (35 pacientes). Se observó una tasa de complicaciones del 8%. Los resultados mostrados en este estudio están en línea con la literatura y el análisis de este reporte provee información para el diseño de planes de prevención de riesgos, especialmente para desarrollar medidas de protección facial. Nivel de Evidencia: Tipo II. Estudio descriptivo.ABSTRACT: The objective of this study was to evaluate the tendency of patients with mandibular fractures associated with working accidents. A retrospective descriptive study was performed in all cases of mandibular fractures who attended the maxillofacial surgery service at the Clinical Hospital Mutual Seguridad C.CH.C. Santiago de Chile, in a 4-year period (January 2009 - December 2012). All mandibular fractures were recorded. The information was collected through review of electronic medical records. Between 2009 and 2012, 74 patients were included in the study with 102 lines of mandibular fractures. The most common fracture was the mandibular condyle (35 patients). The complication rate was 8%. The results shown in this study are in line with the literature and the analysis of this report provides information for the design of risk prevention plans, especially in developing measures of facial protection.http://ref.scielo.org/p5w48

Targeting of Ubiquitin E3 Ligase RNF5 as a Novel Therapeutic Strategy in Neuroectodermal Tumors

RNF5, an endoplasmic reticulum (ER) E3 ubiquitin ligase, participates to the ER-associated protein degradation guaranteeing the protein homeostasis. Depending on tumor model tested, RNF5 exerts pro-or anti-tumor activity. The aim of this study was to elucidate the controversial role of RNF5 in neuroblastoma and melanoma, two neuroectodermal tumors of infancy and adulthood, respectively. RNF5 gene levels are evaluated in publicly available datasets reporting the gene expression profile of melanoma and neuroblastoma primary tumors at diagnosis. The therapeutic effect of Analog-1, an RNF5 pharmacological activator, was investigated on in vitro and in vivo neuroblastoma and melanoma models. In both neuroblastoma and melanoma patients the high expression of RNF5 correlated with a better prognostic outcome. Treatment of neuroblastoma and melanoma cell lines with Analog-1 reduced cell viability by impairing the glutamine availability and energy metabolism through inhibition of F1Fo ATP-synthase activity. This latter event led to a marked increase in oxidative stress, which, in turn, caused cell death. Similarly, neuroblastoma-and melanoma-bearing mice treated with Analog-1 showed a significant delay of tumor growth in comparison to those treated with vehicle only. These findings validate RNF5 as an innovative drug target and support the development of Analog-1 in early phase clinical trials for neuroblastoma and melanoma patients

Compound climate-pollution extremes in Santiago de Chile

Cities in the global south face dire climate impacts. It is in socioeconomically marginalized urban communities of the global south that the effects of climate change are felt most deeply. Santiago de Chile, a major mid-latitude Andean city of 7.7 million inhabitants, is already undergoing the so-called “climate penalty” as rising temperatures worsen the effects of endemic ground-level ozone pollution. As many cities in the global south, Santiago is highly segregated along socioeconomic lines, which offers an opportunity for studying the effects of concurrent heatwaves and ozone episodes on distinct zones of affluence and deprivation. Here, we combine existing datasets of social indicators and climate-sensitive health risks with weather and air quality observations to study the response to compound heat-ozone extremes of different socioeconomic strata. Attributable to spatial variations in the ground-level ozone burden (heavier for wealthy communities), we found that the mortality response to extreme heat (and the associated further ozone pollution) is stronger in affluent dwellers, regardless of comorbidities and lack of access to health care affecting disadvantaged population. These unexpected findings underline the need of a site-specific hazard assessment and a community-based risk management.</p

Siting marine protected areas based on habitat quality and extent provides the greatest benefit to spatially structured metapopulations

Connectivity and its role in the persistence and sustainability of marine metapopulations are attracting increased attention from the scientific community and coastal resource managers. Whether protection should prioritize the connectivity structure or demographic characteristics of a given patch is still unclear. We design a three-stage population model to analyze the relative importance of sources, sinks, quality and extent of juvenile and adult habitat, and node centralities (eigenvector, degree, closeness, and betweenness) as a basis for prioritizing sites. We use a logistic-type stage-structured model to describe the local dynamics of a population with a sessile adult stage and network models to elucidate propagule-exchange dynamics. Our results show that the coupled states of habitat extent and quality, which determine population carrying capacity, are good criteria for protection strategy. Protecting sites on the basis of sources, sinks, or other centrality measures of connectivity becomes optimal only in limited situations, that is, when larval production is not dependent on the adult population. Our findings are robust to a diverse set of larval pathway structures and levels of larval retention, which indicates that the network topology may not be as important as carrying capacity in determining the fate of the metapopulation. Protecting extensive, good quality habitat can help achieve both conservation and fisheries objectives