Obtención de modelos 3D de nuevos prototipos de hisopos nasofaríngeos mediante la tecnología de impresión 3D en materiales biocompatibles

Este estudio nace de la necesidad de dar respuesta a la falta de suministro de material sanitario durante las etapas más críticas de la pandemia de Covid-19. En el panorama mundial de escasez de material para hacer frente a la lucha contra la enfermedad de Covid-19 durante la etapa más agresiva de la pandemia desencadenada por la presencia del virus SARS-CoV-2, surgió la imperiosa necesidad de buscar alternativas de fabricación in situ de material requerido tanto para el tratamiento, como para diagnosis de pacientes, al igual que ocurrió con elementos de seguridad o equipos de protección individual para personal clínico y de a pie. En el caso base de estudio de este trabajo se precisó en concreto de elementos para toma de muestras a analizar mediante técnicas de PCR, ya que hubo una falta de stock a nivel mundial de este tipo de material sanitario. Por este motivo desde muchos centros de investigación e instituciones se emprendió una búsqueda de soluciones a partir de iniciativas públicas y privadas que permitieran obtener elementos eficaces para la toma de muestras con las que determinar el contagio de este virus. Desde el SEDIC de la UPCT, teniendo en cuenta estudios previos, se obtuvieron diseños de hisopos nasofaríngeos como material de último recurso útil para estos fines, que podían ser fabricados mediante técnicas de impresión 3D.Al Departamento de microbiología del Hospital Reina Sofía de Murcia, a Rosa Blázquez, al SMS, UPCT y todas las personas, grupos de investigación y entidades que lo hicieron posible y que formaron parte del entorno colaborativo con sus pequeñas y grandes aportaciones

Adaptación de pieza para tubos de respirador: tubuladora segura para la ventilación no invasiva

El estudio llevado a cabo por el Servicio de Diseño Industrial y Cálculo Científico SEDIC del Servicio de Apoyo a la Investigación Tecnológica SAIT de la Universidad Politécnica de Cartagena UPCT, responde a la necesidad de disponer de conexiones de tipo estándar para equipos de ventilación asistida. Esta demanda parte de personal médico, que en periodo de pandemia (Covid-19) identificó un déficit en cuanto a falta de stock de estas válvulas de conexión y un problema en cuanto a la ausencia de estandarización que las hicieran útiles para cualquier tipo de ventilador fuera de la marca y modelo que fuera. Se ha llevado a cabo para ello, el diseño y obtención de un prototipo, mediante técnicas de fabricación aditiva con materiales biocompatibles, de una pieza de adaptación para tubos de respirador para la ventilación por Terapia de presión positiva continua en las vías respiratorias (CPAP), que además ofrece la ventaja de mejorar los requerimientos que son de aplicación para el tratamiento de enfermos que necesitan ventilación asistida a la vez que posibilitar el suministro de medicación desde la misma válvula. El prototipo final ha sido revisado por especialistas clínicos del Sistema de Salud y propuesto para su evaluación mediante investigación clínica

Methods for assessing DNA repair and repeat expansion in Huntington's Disease

Huntington’s disease (HD) is caused by a CAG repeat expansion in the HTT gene. Repeat length can change over time, both in individual cells and between generations, and longer repeats may drive pathology. Cellular DNA repair systems have long been implicated in CAG repeat instability but recent genetic evidence from humans linking DNA repair variants to HD onset and progression has reignited interest in this area. The DNA damage response plays an essential role in maintaining genome stability, but may also license repeat expansions in the context of HD. In this chapter we summarize the methods developed to assay CAG repeat expansion/contraction in vitro and in cells, and review the DNA repair genes tested in mouse models of HD. While none of these systems is currently ideal, new technologies, such as long-read DNA sequencing, should improve the sensitivity of assays to assess the effects of DNA repair pathways in HD. Improved assays will be essential precursors to high-throughput testing of small molecules that can alter specific steps in DNA repair pathways and perhaps ameliorate expansion or enhance contraction of the HTT CAG repeat

Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing.

Expanded CAG/CTG repeat disorders affect over 1 in 2500 individuals worldwide. Potential therapeutic avenues include gene silencing and modulation of repeat instability. However, there are major mechanistic gaps in our understanding of these processes, which prevent the rational design of an efficient treatment. To address this, we developed a novel system, ParB/ANCHOR-mediated Inducible Targeting (PInT), in which any protein can be recruited at will to a GFP reporter containing an expanded CAG/CTG repeat. Previous studies have implicated the histone deacetylase HDAC5 and the DNA methyltransferase DNMT1 as modulators of repeat instability via mechanisms that are not fully understood. Using PInT, we found no evidence that HDAC5 or DNMT1 modulate repeat instability upon targeting to the expanded repeat, suggesting that their effect is independent of local chromatin structure. Unexpectedly, we found that expanded CAG/CTG repeats reduce the effectiveness of gene silencing mediated by targeting HDAC5 and DNMT1. The repeat-length effect in gene silencing by HDAC5 was abolished by a small molecule inhibitor of HDAC3. Our results have important implications on the design of epigenome editing approaches for expanded CAG/CTG repeat disorders. PInT is a versatile synthetic system to study the effect of any sequence of interest on epigenome editing

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study

Background: Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone. Methods: Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP. Results: A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95% CI 0.53-1.43), p = 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0-2.5) vs 2 IQR 1.0-3.0] days (p = 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95% CI 0.40-2.72), p = 0.92]. Conclusion: In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality