Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study

More than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing cystinuria severity. In 2016, a second renal cystine transporter, AGT1, encoded by the SLC7A13 gene, was discovered. Although it was discarded as a causative gene for cystinuria, its possible effect as a modulatory gene remains unexplored. Thus, we analyzed its function in mouse models of cystinuria, screened the SLC7A13 gene in 34 patients with different lithiasic phenotypes, and functionally characterized the identified variants. Mice results showed that AGT1/rBAT may have a protective role against cystine lithiasis. In addition, among the four missense variants detected in patients, two exhibited a 25% impairment in AGT1/rBAT transport. However, no correlation between SLC7A13 genotypes and lithiasis phenotypes was observed in patients, probably because these variants were found in heterozygous states. In conclusion, our results, consistent with a previous study, suggest that AGT1/rBAT does not have a relevant effect on cystinuria patients, although an impact in patients carrying homozygous pathogenic variants cannot be discarded

Rúbrica para la evaluación de acciones y proyectos socioeducativos de empoderamiento juvenil. Proyecto HEBE

Proyecto HEBE: Universidades participantes Universitat de Girona. Projecte HEBE (coord,) Universitat de Barcelona. Projecte HEBE Universitat Pompeu Fabra. Projecte HEBE Universitat Autònoma de Barcelona. Projecte HEBE Universidad Autónoma de Madrid. Projecte HEBELa rúbrica de evaluación del empoderamiento juvenil que aquí se presenta es uno de los productos del “Proyecto Hebe. Una investigación sobre el empoderamiento juvenil”. Se trata de un trabajo que desde 2014 desarrolla un grupo de investigadores de cinco universidades (UdG, UB, UPF, UAB i UAM). Se pretende que este instrumento sea útil para el análisis de los proyectos de empoderamiento juvenil y, también, para planificar, implementar y analizar procesos socioeducativos que buscan incidir en el empoderamiento de las personas jóvenes. Se trata de un instrumento que consta de 9 dimensiones y 27 indicadores. La rúbrica está diseñada para ser aplicada tanto en los proyectos como en las acciones socioeducativas desarrolladas por un educador o un equipo educativo. Los resultados obtenidos de la aplicación de esta rúbrica permitirán conocer en qué medida el proyecto o las acciones desarrolladas por el equipo educativo facilitan el empoderamiento juvenil. Esto quiere decir que puede ser utilizada, también, para el aprendizaje y la mejora en la toma de decisiones sobre la programación y el desarrollo de acciones que ayuden a los jóvenes a empoderarse. La rúbrica para el análisis y evaluación de acciones y proyectos de empoderamiento juvenil pretende ser un recurso fácil de aplicar, que ayude a los educadores a reflexionar y mejorar sus acciones y proyectosinfo:eu-repo/grantAgreement/MINECO//EDU2013-42979-R/ES/PROYECTO HEBE. EL EMPODERAMIENTO DE LOS JOVENES: ANALISIS DE LOS MOMENTOS, ESPACIOS Y PROCESOS QUE CONTRIBUYEN AL EMPODERAMIENTO JUVENIL./info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/EDU2017-83249-R/ES/PROYECTO HEBE. IDENTIFICACION DE FACTORES POTENCIADORES Y LIMITADORES DEL EMPODERAMIENTO JUVENIL: ANALISIS DE DISCURSOS Y PRACTICAS DE EDUCADORES

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest

Background: Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA). Methods: Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university center. Serum levels of GDF-15 were measured on admission. Neurologic status was evaluated according to the cerebral performance category (CPC) scale. The relationship between GDF-15 levels and poor neurologic outcome at 6 months was analyzed. Results: Among 62 patients included, 32 (51.6%) presented poor outcome (CPC 3-5). Patients with CPC 3-5 exhibited significantly higher GDF-15 levels (median, 17.1 [IQR, 11.1-20.4] ng/mL) compared to those with CPC 1-2 (7.6 [IQR, 4.1-13.1] ng/mL; p = 0.004). Multivariable logistic regression analyses showed that age (OR, 1.09; 95% CI 1.01-1.17; p = 0.020), home setting arrest (OR, 8.07; 95% CI 1.61-40.42; p = 0.011), no bystander cardiopulmonary resuscitation (OR, 7.91; 95% CI 1.84-34.01; p = 0.005), and GDF-15 levels (OR, 3.74; 95% CI 1.32-10.60; p = 0.013) were independent predictors of poor outcome. The addition of GDF-15 in a dichotomous manner (≥ 10.8 vs. < 10.8 ng/mL) to the resulting clinical model improved discrimination; it increased the area under the curve from 0.867 to 0.917, and the associated continuous net reclassification improvement was 0.90 (95% CI 0.48-1.44), which allowed reclassification of 37.1% of patients. Conclusions: After an OHCA, increased GDF-15 levels were an independent, early predictor of poor neurologic outcome. Furthermore, when added to the most common clinical factors, GDF-15 improved discrimination and allowed patient reclassification

Diálogo de saberes : hacia una política de investigación para la implementación de la diversidad epistémica de la Universidad de Antioquia

RESUMEN: "Busca promover una cultura de la investigación basada en el diálogo de saberes para el Buen Vivir en la Universidad de Antioquia, la consolidación de su Sistema de Ciencia, Tecnología e Innovación, y la resignificación de su presencia en los territorios, que parta del reconocimiento de la diversidad en su más amplio espectro, con perspectiva interseccional, intercultural, decolonial e inter y transdisciplinar, a saber: cultural, étnica, social, epistémica, tecnológica, biológica, lingüística, sexual y de género."CONTENIDO: 1: Vemoj pa´traj, porque vamoj pa´lante. -- 1.1: El saber es común y solidario. -- 1.2: El saber, una germinación de colectividades. -- Metodologías empleadas en este dialogo de saberes. -- 2.1: Tonga. -- 2.2: Jíibibiri úai. -- 2.3: Seminario en dialogo de saberes. -- 3: Memoria del diálogo de saberes en la UdeA. -- 3.1: Sanar la memoria. -- 3.2: Otras diversidades, antiguas y modernas. -- 3.3: El caminar de la afrodescendía en la UdeA. -- 3.4: Los saberes indígenas en la UdeA. -- 3.5: Saberes raizales en la UdeA. -- 3.6: Epistemología feminista, genero, diversidades y disidencias sexuales en la UdeA. -- 3.7: Memoria de la discapacidad en la UdeA. -- 3.8: Memoria de la comida en la UdeA. -- 4: Dialogo de buenos vivieres: un caminar ético y político. -- 4.1: La traductibilidad del dialogo y los buenos saberes. -- 4.2: Tramas y urdimbres para un dialogo de vivieres. -- 4.3: Seminario en dialogo de saberes. -- 5: Ciencia, investigación y conocimientos con sabiduría. -- 5.1: Onoira kirigai, canastos del conocimiento. -- 5.2: Jai bia: investigadoras y sembradores de vida. -- 5.3: Vea vé: para qué investigamos en dialogo de saberes. -- 6: La comida: paradigma en dialogo de saberes. -- 6.1: Superar el modelo antropocéntrico. -- 6.2: Sentipensar las comida, un giro epistémico. -- 6.3: Aprender de la comida. -- 6.4: UdeA y las comprensiones de la comida. -- 7: Comunicar en diálogo de saberes. -- 7.1: El supuesto privilegio cognitivo de la escritura académica. -- 7.2: Comunicar la ciencia a través de las narrativas. -- 7.3: La ciencia expresada desde la nostredad comunicativa. -- 8: Con quién conversamos

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589