Development of a national registry of congenital anomalies in Argentine: a pilot feasibility study

INTRODUCCIÓN: el Sistema de Estadísticas de Salud de Argentina no registra datos sobre ocurrencia de anomalías congénitas (AC) en recién nacidos (RN). OBJETIVO: evaluar la confiabilidad de una nueva metodología de registro para el relevamiento de AC en nacidos vivos mediante su comparación con la estrategia de registro del Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC). MÉTODOS: se utilizaron dos metodologías independientes de recolección de datos: el ECLAMC y un formulario especial anexado al Informe Estadístico de Hospitalización (F-IEH). En el F-IEH los neonatólogos consignaron la presencia de AC en RN vivos y las describieron. RESULTADOS: Entre 18.491 RN vivos, se describieron 658 malformados en el ECLAMC (3,56%) y 587 en el F-IEH (3,17%); considerando sólo malformaciones mayores, la prevalencia fue 2,58% y 2,11%, respectivamente. Casi todas las categorías diagnósticas fueron más prevalentes en el ECLAMC que en el F-IEH. La confiabilidad, medida a través del Porcentaje de Concordancia Positiva (PCP), fue 62,2% para el total de casos con AC; 42,4%, para los casos con AC menores; y varió en un rango de 42,9%–88,9% entre diferentes categorías de AC mayores. CONCLUSIONES: el grado de concordancia entre el F-IEH y ECLAMC en la detección de AC fue mayor para las anomalías mayores que menores. Los diagnósticos fueron coincidentes en todos los casos detectados por ambas metodologías. Antes de extender el registro a escala nacional se recomienda capacitar a los neonatólogos para asegurar una adecuada detección de los casos.INTRODUCTION: the Health Statistics System in Argentina does not record data on the occurrence of congenital anomalies (CA) in newborns. OBJECTIVE: to evaluate the reliability of a new methodology for the record of CA in live births by comparison with the Latin American Collaborative Study of Congenital Malformations (ECLAMC, according to its Spanish acronym). METHODS: we used data from two independent methodologies: the ECLAMC and a special form attached to the Hospitalization Statistical Report (F-IEH, according to its Spanish acronym). On the F-IEH, neonatologists registered those newborns with CA and described the anomalies. RESULTS: in a population of 18,491 live births, the ECLAMC reported 658 (3.56%) malformed infants, while the F-IEH registered 587 (3.17%). The prevalence of major malformations was 2.58% and 2.11 %, respectively. Most diagnostic categories were more frequent in the ECLAMC than in the F-IEH. The reliability measured by the Percentage of Positive Agreement was 62.2%, in all the CA cases; 42.4%, in minor CA; and ranged from 42.9% to 88.9% among different categories of major CA. CONCLUSIONS: the degree of agreement between the F-IEH and the ECLAMC in the detection of CA is greater for major AC. The diagnoses were the same in all the cases detected by both methodologies. Before using the register nationwide, neonatologist’s training is required to ensure adequate case detection.Fil: Liascovich, Rosa. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Gili, Juan Antonio. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valdez, Rita. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital Materno Infantil Ramon Sarda; ArgentinaFil: Somaruga, Luis. Hospital General de Agudos Bernardino Rivadavia ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Goldshmidt, Ernesto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Bronberg, Ruben Adrian. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Ricagni, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Mussi, Margarita. Maternidad Martín; ArgentinaFil: Medina, Adriana. Hospital Municipal General de Agudos Doctor José Penna; ArgentinaFil: Deguer, Carlos. Hospital Municipal General de Agudos Doctor José Penna; ArgentinaFil: Menzio, Monica. Complejo Sanitario San Luis; ArgentinaFil: Guevel, Carlos. Dirección de Estadísticas e Información de Salud; ArgentinaFil: Fernández, Mercedes. Dirección de Estadísticas e Información de Salud; ArgentinaFil: Elida, Marconi. Dirección de Estadísticas e Información de Salud; ArgentinaFil: López Camelo, Jorge Santiago. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Unraveling the effect of silent, intronic and missense mutations on VWF splicing : contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. identifier:02869074

La ciudad como experiencia de conocimiento: nuevas metodologías de aprendizaje, iniciación a la investigación y extensión universitaria a partir de la historia urbana

Memoria que recoge las actividades desarolladas en el proyecto de Innovación docente 327 de 2020 con título La ciudad como experiencia de conocimiento: nuevas metodologías de aprendizaje, iniciación a la investigación y extensión universitaria a partir de la historia urbana y dirigido por Rubén Pallol Trigueros

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Transcriptome analysis in LRRK2 and idiopathic Parkinson's disease at different glucose levels

Type-2 diabetes (T2D) and glucose metabolic imbalances have been linked to neurodegenerative diseases, including Parkinson's disease (PD). To detect potential effects of different glucose levels on gene expression, by RNA-seq we analyzed the transcriptome of dermal fibroblasts from idiopathic PD (iPD) patients, LRRK2-associated PD (L2PD) patients, and healthy controls (total n = 21 cell lines), which were cultured at two different glucose concentrations (25 and 5 mM glucose). In PD patients we identified differentially expressed genes (DEGs) that were related to biological processes mainly involving the plasmatic cell membrane, the extracellular matrix, and also neuronal functions. Such pathway deregulation was largely similar in iPD or L2PD fibroblasts. Overall, the gene expression changes detected in this study were associated with PD independently of glucose concentration.This work was supported by CIBERNED / Instituto de Salud Carlos III (ISCIII) (grant PIE14/00061) (to M.-J.M.), and the Fondo de Investigaciones Sanitarias from ISCIII (grant PIE20/00259) (to M.E.). R.F.-S. was supported by a Jóvenes Investigadores (JIN) grant of the Spanish Ministry of Economy and Competitiveness (MINECO) and the Agencia Estatal de Investigación (AEI) (AEI/FEDER/UE) (grant #SAF2015-73508-JIN), and a Miguel Servet grant from the Instituto de Salud Carlos III (grant #CP19/00048). A.E-C. was funded by ISCIII /MINECO (PT17/0009/0019) and co-funded by FEDER. M.F. was funded through a María de Maeztu grant (#MDM-2017-0729). IDIBAPS receives funding from the CERCA Program from the Generalitat de Catalunya and the FEDER Program from the European Union

Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson's disease patients

Background: Parkinson’s disease (PD) is characterized by the loss of midbrain dopaminergic neurons (DAn). Previously, we described the presence of DNA hyper- and hypo-methylation alterations in induced pluripotent stem cells (iPSC)-derived DAn from PD patients using the Illumina 450K array which prominently covers gene regulatory regions. Methods: To expand and contextualize previous findings, we performed the first whole-genome DNA bisulfite sequencing (WGBS) using iPSC-derived DAn from representative PD subjects: one sporadic PD (sPD) patient, one monogenic LRRK2-associated PD patient (L2PD), and one control. Results: At the whole-genome level, we detected global DNA hyper-methylation in the PD which was similarly spread across the genome in both sPD and L2PD and mostly affected intergenic regions. Conclusion: This study implements previous epigenetic knowledge in PD at a whole genome level providing the first comprehensive and unbiased CpG DNA methylation data using iPSC-derived DAn from PD patients. Our results indicate that DAn from monogenic or sporadic PD exhibit global DNA hyper-methylation changes. Findings from this exploratory study are to be validated in further studies analyzing other PD cell models and patient tissues.This work was supported by the Fondo de Investigaciones Sanitarias of the Instituto de Salud Carlos III (ISCIII) to M.E. (grant # PI14/00426), the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) to the Movement Disorders Unit of the Neurology Service from the Hospital Clínic de Barcelona to E.T., M.-J.M., R.F.-S., and M.E. (grant # PRI-16-2017). R.F.S. was supported by a Jóvenes Investigadores grant (#SAF2015-73508-JIN) through the Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad (Plan Estatal de I+D+I 2013–2016) of the Spanish Ministry of Economy and Competitiveness (MINECO), and the Agencia Estatal de Investigación (AEI), which is cofunded by FEDER (AEI/FEDER/UE). Other funding included the grants BFU2013-49157-P, BFU2016-80870-P, and the European Research Council (ERC) 2012-StG (311736- PD-HUMMODEL) to A.C; ISCIII/FEDER (RD16/0011/0024) and Generalitat de Catalunya (iPS4BioMed SGR 2017–2019) to A.R.; and ISCIII/FEDER (PIE14/00061) to A.R