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\u27s 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. CLINICALTRIALSGOV IDENTIFIER: NCT01590589

Association Between Insulin‐Like Growth Factor‐1 and Social Cognition in Huntington's Disease

Insulin-like growth factor 1 (IGF-1) seems to be involved in the neural circuits associated with social cognition and brain structure.Study funded by Gerencia Regional de Salud de Castilla y Leon (Sacyl GRS 1768/A/18)

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

Clinical manifestations of intermediate allele carriers in Huntington disease

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.status: publishe

Dosis diaria definida ajustada por peso: una propuesta para la medición de consumo antimicrobiano en pediatría

Introduction Antimicrobial defined daily dose (DDD), has limitations for antimicrobial consumption measurement in paediatrics. An alternative DDD design applicable for children is proposed. Methods Children (<16 years-old) from 10 Spanish hospitals during a 12-months period were included. Weight for age (50th percentile) was calculated for the median age of the cohort using standardized World Health Organization tables. DDD (g) for each antimicrobial was calculated by multiplying the obtained weight times the recommended dose (mg/kg) of the antimicrobial for the most common infectious indication. Results A total of 40,575 children were included. Median age was 4.17 (IQR: 1.36–8.98) and 4.81 (IQR: 1.42–9.60) years for boys and girls, respectively. Mean weight for this age was 17.08kg. Standardized DDD for representative antimicrobials were calculated. Conclusions A useful method for antimicrobial DDD measurement in paediatrics has been proposed and should be validated in future studies for its use in paediatric antimicrobial stewardship programmes.Introducción La dosis diaria definida (DDD), tiene limitaciones para la medición del consumo antimicrobiano en pediatría. Se propone un diseño aplicable en niños. Métodos Se incluyeron niños (<16 años) de 10 hospitales españoles durante un periodo de 12 meses. A partir de la mediana de edad de la cohorte, utilizando tablas estandarizadas de la OMS, se obtuvo el peso correspondiente al percentil P50 de esa edad. Se calculó la DDD (gr) multiplicando el peso obtenido por la dosis recomendada (mg/kg) de cada antimicrobiano para su indicación más común. Resultados Un total de 40575 niños fueron incluidos. La mediana de edad fue 4,17 (RIQ: 1,36–8,98) y 4,81 (RIQ: 1,42–9,60) años para niños y niñas, respectivamente. Peso medio para la edad: 17,08kg. DDD estandarizadas fueron calculadas para antimicrobianos representativos. Conclusiones Se ha propuesto un método útil para monitorizar consumo antimicrobiano en pediatría utilizando DDD adaptadas, que deberá validarse en futuros estudios.Sin financiación1.654 JCR (2019) Q4, 113/136 Microbiology0.317 SJR (2019) Q3, 83/129 Microbiology (medical)No data IDR 2019UE

Antimicrobial defined daily dose in neonatal population.

Antimicrobial defined daily dose (DDD), a standardized metric to assess antimicrobial consumption in adult population, has limitations hampering its use in neonatal patients. This study proposes an alternative DDD design applicable for neonates. Neonates ( A total of 4820 neonates were included. Mean age was 36.72 weeks of gestational age and Mean weight was 2.687kg. Standardized DDD (intravenous; oral route) for representative antimicrobials were: Amoxicillin (0.08; 0.08), amoxicillin-clavulanic acid (0.27; 0.08), ampicillin (0.27; x), cloxacillin (0.13; 0.13), penicillin G sodium (0.12), cefazolin (0.13), cefuroxime (0.27; x), cefotaxime (0.27), ceftazidime (0.27), ceftriaxone (0.13), cefepime (0.27) piperacillin-tazobactam (0.54), aztreonam (0.24), azithromycin (0.03; 0.03), clindamycin (0.04; 0.04), amikacin (0.04), gentamicin (0.01), metronidazole (0.04; 0.08), ciprofloxacin (0.04; 0.05), levofloxacin (x;x), fluconazole (0.02; 0.02), itraconazole (0.01; 0.01), fosfomycin (0.27). Restricted antimicrobials: meropenem (0.11), teicoplanin (0.02), vancomycin (0.08; 0.11), linezolid (0.08; 0.08), daptomycin (x), amphotericin B liposomal (0.01). A useful method for antimicrobial DDD measurement in neonatology has been designed to monitor antimicrobial consumption in hospital settings. It should be validated in further studies and thereby included in the design for neonatal antimicrobial stewardship programs in the future

Productos Turísticos para Sol y Playa, Naturaleza, Cultura y Patrimonio en el departamento de Sucre, Colombia

En Colombia, el Plan Nacional de Desarrollo 2010 - 2014 Prosperidad para Todos, incorporó el turismo como un pilar de desarrollo, hecho potencializado por el Plan Sectorial de Turismo 2014 – 2018, que tiene como uno de sus objetivos: Impulsar el desarrollo y consolidación de destinos y productos turísticos competitivos y sostenibles a nivel regional y territorial, a partir del aprovechamiento responsable de la diversidad natural, étnica y cultural. En ese sentido, el Ministerio de Cultura (2014) en asocio con Artesanías de Colombia señala que la artesanía es la actividad creativa de producción de objetos, realizada con predominio manual, ayuda de herramientas y maquinaria simples con un resultado final individualizado, determinado por el medio ambiente, el desarrollo histórico y resulta elemento clave del patrimonio cultural. (Baquero & González, Diseño de Ruta Turística artesanal, desde las asociaciones, en los municipios de Sincelejo, Morroa, Sampués y Coveñas, 2016) (Plan Nacional de Desarrollo Colombia, 2010-2014)

Estableciendo "puentes" entre la Universidad y el tejido social madrileño : cómo los estudiantes de la Asignatura Ciudad y Urbanismo pueden colaborar en la búsqueda de soluciones urbanísticas a históricas reclamaciones vecinales en el entorno de Puente de Vallecas

Publicación de los trabajos elaborados por los estudiantes del curso 2022/23 de la asignatura Ciudad y Urbanismo (35001304) de la Escuela Técnica Superior de Arquitectura de la Universidad Politécnica de Madrid en el marco de un proyecto de Aprendizaje-Servicio y reflexiones sobre el proceso tanto de los agentes sociales que formaron parte del mismo, como de los profesores que ha participado en la docencia