Golimumab as rescue therapy for refractory immune-mediated uveitis: a three-center experience

OBJECTIVE: To evaluate, in three Spanish tertiary referral centres, the short-term safety and efficacy of golimumab (GLM) for treatment of immune-mediated uveitis resistant to previous immunosuppressive therapy. METHODS: Nonrandomized retrospective interventional case series. Thirteen patients with different types of uveitis that were resistant to treatment with at least 2 previous immunosuppressors were included in this study. All included patients were treated with GLM (50 mg every four weeks) during at least 6 months. Clinical evaluation and treatment-related side effects were assessed at least four times in all included patients. RESULTS: Eight men and 5 women (22 affected eyes) with a median age of 30 years (range 20-38) and active immune-mediated uveitides were studied. GLM was used in combination with conventional immunosuppressors in 7 patients (53.8%). GLM therapy achieved complete control of inflammation in 12/13 patients (92.3%) after six months of treatment. There was a statistically significant improvement in mean BCVA (0.60 versus 0.68, P = 0.009) and mean 1 mm central retinal thickness (317 versus 261.2 µ, P = 0.05) at the six-month endpoint when compared to basal values. No major systemic adverse effects associated with GLM therapy were observed. CONCLUSIONS: GLM is a new and promising therapeutic option for patients with severe and refractory uveitis

Extinction risk of Mesoamerican crop wild relatives

Ensuring food security is one of the world's most critical issues as agricultural systems are already being impacted by global change. Crop wild relatives (CWR)—wild plants related to crops—possess genetic variability that can help adapt agriculture to a changing environment and sustainably increase crop yields to meet the food security challenge. Here we report the results of an extinction risk assessment of 224 wild relatives of some of the world's most important crops (i.e. chilli pepper, maize, common bean, avocado, cotton, potato, squash, vanilla and husk tomato) in Mesoamerica—an area of global significance as a centre of crop origin, domestication and of high CWR diversity. We show that 35% of the selected CWR taxa are threatened with extinction according to The International Union for Conservation of Nature (IUCN) Red List demonstrates that these valuable genetic resources are under high anthropogenic threat. The dominant threat processes are land use change for agriculture and farming, invasive and other problematic species (e.g. pests, genetically modified organisms) and use of biological resources, including overcollection and logging. The most significant drivers of extinction relate to smallholder agriculture—given its high incidence and ongoing shifts from traditional agriculture to modern practices (e.g. use of herbicides)—smallholder ranching and housing and urban development and introduced genetic material. There is an urgent need to increase knowledge and research around different aspects of CWR. Policies that support in situ and ex situ conservation of CWR and promote sustainable agriculture are pivotal to secure these resources for the benefit of current and future generations

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

Golimumab as rescue therapy for refractory immune-mediated uveitis: a three-center experience

Objective. To evaluate, in three Spanish tertiary referral centres, the short-term safety and efficacy of golimumab (GLM) for treatment of immune-mediated uveitis resistant to previous immunosuppressive therapy. Methods. Nonrandomized retrospective interventional case series. Thirteen patients with different types of uveitis that were resistant to treatment with at least 2 previous immunosuppressors were included in this study. All included patients were treated with GLM (50 mg every four weeks) during at least 6 months. Clinical evaluation and treatment-related side effects were assessed at least four times in all included patients. Results. Eight men and 5 women (22 affected eyes) with a median age of 30 years (range 20-38) and active immune-mediated uveitides were studied. GLM was used in combination with conventional immunosuppressors in 7 patients (53.8%). GLM therapy achieved complete control of inflammation in 12/13 patients (92.3%) after six months of treatment. There was a statistically significant improvement in mean BCVA (0.60 versus 0.68, P - 0.009) and mean 1 mm central retinal thickness (317 versus 261.2 mu, P -0.05) at the six-month endpoint when compared to basal values. No major systemic adverse effects associated with GLM therapy were observed. Conclusions. GLM is a new and promising therapeutic option for patients with severe and refractory uveitis

Experiencias ganaderas, agrícolas y forestales en la conservación de los recursos naturales

La producción agrícola y ganadera es un desafío en la actualidad por diversas razones, entre las que se encuentran el cambio climático, la degradación de los suelos y la contaminación. En algunas zonas, estas actividades se llevan a cabo en áreas destinadas a la conservación de la naturaleza, por lo que tienen el reto de garantizar la producción de alimentos para una población creciente, y a su vez de conservar la biodiversidad y los servicios ecosistémicos en México.GIZ, SEMARNAT, CONANP, GFA, ICA

Estudios multidisciplinarios en Ciencias de la Salud

Es una distinción, como miembro de la Comisión del Programa del Doctorado en Ciencias de la Salud de la Universidad Autónoma del Estado de México, presentar el libro titulado Estudios multidisciplinarios en Ciencias de la Salud, en el que distinguidos y reconocidos investigadores, entusiastas y comprometidos alumnos del programa nos dan a conocer los resultados de sus proyectos de investigación, trabajos que forman parte de los requisitos para acceder al grado de doctor. Entre las razones que invitan a la lectura del libro destaca su contenido conformado con la participación de autores en cuatro áreas en el campo de la salud: Odontología, Ciencias Médicas y Nutrición, Ciencias de la Conducta, y Enfermería y Obstetricia, quienes contribuyen a incrementar el acervo del conocimiento en cada área, en favor de la ciencia, la tecnología, y la salud física y mental de la población.Universidad Autónoma del Estado de México

Non-motor symptoms burden, mood, and gait problems are the most significant factors contributing to a poor quality of life in non-demented Parkinson's disease patients: Results from the COPPADIS Study Cohort

[Objective] To identify factors related to a poor health-related and global quality of life (QoL) in a cohort of non-demented Parkinson's disease (PD) patients and compare to a control group.[Methods] The data correspond to the baseline evaluation of the COPPADIS-2015 Study, an observational, 5-year follow-up, multicenter, evaluation study. Three instruments were used to assess QoL: (1) the 39-item Parkinson's disease Questionnaire (PDQ-39), (2) a subjective rating of global QoL (PQ-10), and (3) the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Multiple linear regression methods were used to evaluate the direct impact of different variables on these QoL measures.[Results] QoL was worse in PD patients (n = 692; 62.6 ± 8.9 years old, 60.3% males) than controls (n = 206; 61 ± 8.3 years old, 49.5% males): PDQ-39, 17.1 ± 13.5 vs 4.4 ± 6.3 (p < 0.0001); PQ-10, 7.3 ± 1.6 vs 8.1 ± 1.2 (p < 0.0001); EUROHIS-QOL8, 3.8 ± 0.6 vs 4.2 ± 0.5 (p < 0.0001). A high correlation was observed between PDQ-39 and Non-Motor Symptoms Scale (NMSS) (r = 0.72; p < 0.0001), and PDQ-39 and Beck Depression Inventory-II (BDI-II) (r = 0.65; p < 0.0001). For health-related QoL (PDQ-39), non-motor symptoms burden (NMSS), mood (BDI-II), and gait problems (Freezing Of Gait Questionnaire [FOGQ]) provided the highest contribution to the model (β = 0.32, 0.28, and 0.27, respectively; p < 0.0001); whereas mood and gait problems contributed the most to global QoL (PQ-10, β = -0.46 and −0.21, respectively; EUROHIS-QOL8, β = -0.44 and −0.23, respectively).[Conclusions] QoL is worse in PD patients than in controls. Mood, non-motor symptoms burden, and gait problems seem to be the most relevant factors affecting health-related and global perceived QoL in non-demented PD patients.Peer reviewe

Voces de la gestión territorial. Estrategias complementarias para la conservación de la biodiversidad en Colombia

Colombia es un país con una alta riqueza biológica y cultural, tan diverso en su territorio como en las estrategias de conservación que en él se implementan. Sin embargo, muchas de estas estrategias no se han dado a conocer lo suficiente, lo que hace difícil su articulación a los procesos de gestión y ordenamiento del territorio. Existen algunos avances en su identificación como los ejercicios que se han realizado en los sistemas regionales de áreas protegidas para recopilar la información sobre estrategias complementarias de conservación en sus jurisdicciones, la articulación que realizan organizaciones privadas para identificar las iniciativas de conservación voluntaria por parte de la sociedad civil y el trabajo realizado por comunidades campesinas, indígenas y afrodescendientes para visibilizar sus áreas de conservación. Este libro, por lo tanto, tiene como objetivo visibilizar experiencias de conservación y gestión de la biodiversidad, diferentes a las áreas protegidas, teniendo en cuenta que el Convenio de Diversidad Biológica a través de la Meta Aichi 11 introduce el concepto de otras medidas efectivas de conservación basadas en áreas (OMEC) o áreas conservadas como instrumentos para lograr sistemas de conservación más completos, representativos y efectivamente gestionados (UNEP CDB, 2010). Esperamos sea un aporte para llenar un vacío de conocimiento acerca de dichas estrategias, mostrando sus principales características, los diferentes tipos de gobernanza con los que cuentan, sus mecanismos de implementación, fortalezas y debilidades, aprendizajes y cómo estos pueden ser aplicados a la gestión de la biodiversidad en el territorio.Servicios ecosistémicosGobernanzaManejo de territoriosDeforestación de bosquesPérdida y degradaciónEcosistemasComunidades localesConservación de la biodiversida

NMDA receptor gene variations as modifiers in Huntington disease: a replication study.

Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the entire cohort. Yet, when subjects were stratified by AO subtypes, we found nominally significant evidence for an association of the GRIN2A rs1969060 variation and the GRIN2B rs1806201 variation. These findings further implicate the N-methyl D-aspartate receptor subtype genes as loci containing variation associated with AO in HD