Capacitación y supervisión a equipos técnicos: saldando una deuda pendiente en temas de discapacidad y vejez

El presente trabajo hace referencia a la experiencia que surge de la implementación del proyecto aprobado y financiado en 2010 por Extensión Universitaria de la UNLP, denominado “Capacitación y Supervisión a equipos interdisciplinarios: saldando una deuda pendiente en temas de vejez y discapacidad”. Fueron partícipes de esta experiencia estudiantes avanzados, graduados y profesores de las Facultades de Humanidades y Ciencias de la Educación, Psicología y Trabajo Social (en carácter de Unidad Ejecutora), y como co-participantes la Comisión Universitaria sobre Discapacidad (CUD), el INSSJyP – Pami, la Red Mayor Nodo La Plata y la Dirección de Servicios Sociales de la UNLP. La implementación del proyecto implicó las instancias de capacitación y supervisión institucional, destinado a equipos técnicos y profesionales que se desempeñaban en centros de salud, áreas de acción social municipal, organizaciones específicas de adultos mayores e instituciones de personas con discapacidad. La implementación del proyecto dio lugar a que se establecieran tres aspectos a analizar al momento de realizar la evaluación final del mismo: a) la realización de trabajos finales de los diversos destinatarios que con sus diferentes matrices disciplinarias problematizaron la temática de la vejez y la discapacidad, la apropiación de nuevos conocimientos que potenciaron el cuestionamiento de las prácticas vigentes, la incorporación de metodologías de análisis diagnóstico, el conocimiento, diseño e implementación de modelos de gestión y el fortalecimiento del trabajo interdisciplinario; b) la función de Extensión Universitaria de responder a las demandas de la sociedad ante las carencias en la formación académica de los graduados; y finalmente c) impulsar la formación de estudiantes avanzados que a través de la extensión acompañaron el proyecto y participaron activamente en el cumplimiento del mismo. Por otro lado, se debe destacar que esta experiencia de intervención aporta a la política pública a partir del trabajo multidimensional de los diversos actores implicados en la propuesta (Universidad; Estado Nacional; Organizaciones de la Sociedad Civil; Ciudadanos), así como la intención del proyecto en sí mismo de buscar constantemente el conocimiento y la reflexión que permita mejorar la calidad de trabajo de los profesionales, generar ambientes laborales saludables en las diversas instituciones, y consecuentemente contribuir a la mejora de la calidad de vida de quienes reciben los aportes profesionales, en este caso, la población adulta mayor y las personas con discapacidad

Circadian and dark-pulse activation of orexin/hypocretin neurons

Temporal control of brain and behavioral states emerges as a consequence of the interaction between circadian and homeostatic neural circuits. This interaction permits the daily rhythm of sleep and wake, regulated in parallel by circadian cues originating from the suprachiasmatic nuclei (SCN) and arousal-promoting signals arising from the orexin-containing neurons in the tuberal hypothalamus (TH). Intriguingly, the SCN circadian clock can be reset by arousal-promoting stimuli while activation of orexin/hypocretin neurons is believed to be under circadian control, suggesting the existence of a reciprocal relationship. Unfortunately, since orexin neurons are themselves activated by locomotor promoting cues, it is unclear how these two systems interact to regulate behavioral rhythms. Here mice were placed in conditions of constant light, which suppressed locomotor activity, but also revealed a highly pronounced circadian pattern in orexin neuronal activation. Significantly, activation of orexin neurons in the medial and lateral TH occurred prior to the onset of sustained wheel-running activity. Moreover, exposure to a 6 h dark pulse during the subjective day, a stimulus that promotes arousal and phase advances behavioral rhythms, activated neurons in the medial and lateral TH including those containing orexin. Concurrently, this stimulus suppressed SCN activity while activating cells in the median raphe. In contrast, dark pulse exposure during the subjective night did not reset SCN-controlled behavioral rhythms and caused a transient suppression of neuronal activation in the TH. Collectively these results demonstrate, for the first time, pronounced circadian control of orexin neuron activation and implicate recruitment of orexin cells in dark pulse resetting of the SCN circadian clock

Island and Mountain Ecosystems as Testbeds for Biological Control in the Anthropocene

For centuries, islands and mountains have incited the interest of naturalists, evolutionary biologists and ecologists. Islands have been the cradle for biogeography and speciation theories, while mountain ranges have informed how population adaptation to thermal floors shapes the distribution of species globally. Islands of varying size and mountains’ altitudinal ranges constitute unique “natural laboratories” where one can investigate the effects of species loss or global warming on ecosystem service delivery. Although invertebrate pollination or seed dispersal processes are steadily being examined, biological control research is lagging. While observations of a wider niche breadth among insect pollinators in small (i.e., species-poor) islands or at high (i.e., colder) altitudes likely also hold for biological control agents, such remains to be examined. In this Perspective piece, we draw on published datasets to show that island size alone does not explain biological control outcomes. Instead, one needs to account for species’ functional traits, habitat heterogeneity, host community make-up, phenology, site history or even anthropogenic forces. Meanwhile, data from mountain ranges show how parasitism rates of Noctuid moths and Tephritid fruit flies exhibit species- and context-dependent shifts with altitude. Nevertheless, future empirical work in mountain settings could clarify the thermal niche space of individual natural enemy taxa and overall thermal resilience of biological control. We further discuss how global databases can be screened, while ecological theories can be tested, and simulation models defined based upon observational or manipulative assays in either system. Doing so can yield unprecedented insights into the fate of biological control in the Anthropocene and inform ways to reinforce this vital ecosystem service under global environmental change scenarios.The development of this manuscript was funded by the Food and Agriculture Organization FAO through LOA/RAP/2021/57, executed by The University of Queensland. AS was supported by the "Ramon y Cajal" program (RYC2020029407-I), financed by the Spanish "Ministerio de Ciencia e Innovacion".info:eu-repo/semantics/publishedVersio

EV-associated miRNAs from peritoneal lavage as potential diagnostic biomarkers in colorectal cancer

Background: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality worldwide. Current systematic methods for diagnosing have inherent limitations so development of a minimally-invasive diagnosis, based on the identification of sensitive biomarkers in liquid biopsies could therefore facilitate screening among population at risk. Methods: In this study, we aim to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the peritoneal lavage as a source of potential miRNA diagnostic biomarkers. We isolated EVs by ultracentrifugation from 25 ascitic fluids and 25 peritoneal lavages from non-cancer and CRC patients, respectively. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 371 miRNAs. Results: 210 miRNAs were significantly dysregulated (adjusted p value < 0.05 and abs(logFC) ≥ 1). The top-10 miRNAs, which had the AUC value higher than 0.95, were miRNA-199b-5p, miRNA-150-5p, miRNA-29c-5p, miRNA-218-5p, miRNA-99a-3p, miRNA-383-5p, miRNA-199a-3p, miRNA-193a-5p, miRNA-10b-5p and miRNA-181c-5p. Conclusions: This finding opens the avenue to the use of EV-associated miRNA of peritoneal lavages as an untapped source of biomarkers for CRC.EC hold a postdoctoral fellowship from the Departament de Salut of the Generalitat de Catalunya (SLT002/16/00274). This work was supported by grants: Discovery, validation and implementation of biomarkers for Precision Oncology (ISCIII PIE15/00029), CIBERONC (CB16/12/00231 and CB16/12/00328). Grups consolidats de la Generalitat de Catalunya (2017SGR1368 and 2017SGR1661). Work supported by IRBLleida BIOBANK (B.0000682) and Plataforma biobancos PT17/0015/0027

Detección y prevención de violencia contra la mujer en una muestra de estudiantes de enfermería

Justificación. Aunque la violencia durante el noviazgo ha sido poco estudiada, algunas investigaciones revelan que su incidencia puede ser elevada. Su detección precoz es fundamental para realizar una labor preventiva entre los jóvenes. Objetivo. El objetivo de este estudio fue identificar algunas conductas, actitudes y , valores que una muestra de mujeres estudiantes de enfermería atribuía a sus parejas masculinas y que podrían ser precursoras de violencia y abuso. Metodología. Se realizó un estudio descriptivo y transversal mediante encuesta autoadministrada a una muestra de estudiantes de 18 a 24 años, de cinco Escuelas de Enfermería de Cataluña. Se empleó una versión adaptada del Cuestionario de prevención y detección de la violencia durante el noviazgo de G. Ferreira. Las 48 preguntas se agruparon en 11 categorías por tratarse de formulaciones que exploraban cuestiones similares. Resultados principales. Se obtuvieron 390 respuestas. En el momento de la encuesta tenía pareja el 64% de la muestra. Los comportamientos en que el varón: 'Controla. Fiscaliza. Prohíbe', se confirmaron en el 13,9% de las encuestadas. Las 'Amenazas. Insultos' y las conductas en que él 'Aísla. Es antisocial', agruparon el mayor número (95%) de respuestas negativas. Conclusión. Según el estudio se descartan las conductas y actitudes que pueden considerarse precursoras de situaciones de mal trato contra la mujer. El cuestionario con preguntas cerradas puede que deba complementarse con otras técnicas (cualitativas) para obtener una información más fiable y válida

Autism care pathway in Europe

BACKGROUND: Autism is a lifelong complex neurodevelopmental condition that affects brain development and behaviour with significant consequences for everyday life. Despite its personal, familial, and societal impact, Europe-wide harmonised guidelines are still lacking for early detection, diagnosis, and intervention, leading to an overall unsatisfactory autistic person and carer journey. METHODS: The care pathway for autistic children and adolescents was analysed in Italy, Spain and the UK from the perspective of carers (using a survey aimed at caregivers of autistic children 0-18 years old), the autistic community, and professionals in order to identify major barriers (treatment gaps) preventing carers from receiving information, support, and timely screening/diagnosis and intervention. RESULTS: Across all three countries, analysis of the current care pathway showed: long waits from the time carers raised their first concerns about a child's development and/or behaviour until screening and confirmed diagnosis; delayed or no access to intervention once a diagnosis was confirmed; limited information about autism and how to access early detection services; and deficient support for families throughout the journey. CONCLUSIONS: These findings call for policy harmonisation in Europe to shorten long wait times for diagnosis and intervention and therefore, improve autistic people and their families' journey experience and quality of life

BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with IGH resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3-rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in CLL but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter 4 tumors transformed to a large B-cell lymphoma. We designed a novel FISH assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

High dose genistein in Sanfilippo syndrome: A randomised controlled trial

From Wiley via Jisc Publications RouterHistory: received 2021-02-09, rev-recd 2021-05-25, accepted 2021-05-27, pub-electronic 2021-06-13Article version: VoRPublication status: PublishedFunder: UK MPS SocietyFunder: National MPS society; Id: http://dx.doi.org/10.13039/100013927Funder: GEM AppealAbstract: The aim of this study was to evaluate the efficacy of high dose genistein aglycone in Sanfilippo syndrome (mucopolysaccharidosis type III). High doses of genistein aglycone have been shown to correct neuropathology and hyperactive behaviour in mice, but efficacy in humans is uncertain. This was a single centre, double‐blinded, randomised, placebo‐controlled study with open‐label extension phase. Randomised participants received either 160 mg/kg/day genistein aglycone or placebo for 12 months; subsequently all participants received genistein for 12 months. The primary outcome measure was the change in heparan sulfate concentration in cerebrospinal fluid (CSF), with secondary outcome measures including heparan sulfate in plasma and urine, total glycosaminoglycans in urine, cognitive and adaptive behaviour scores, quality of life measures and actigraphy. Twenty‐one participants were randomised and 20 completed the placebo‐controlled phase. After 12 months of treatment, the CSF heparan sulfate concentration was 5.5% lower in the genistein group (adjusted for baseline values), but this was not statistically significant (P = .26), and CSF heparan sulfate increased in both groups during the open‐label extension phase. Reduction of urinary glycosaminoglycans was significantly greater in the genistein group (32.1% lower than placebo after 12 months, P = .0495). Other biochemical and clinical parameters showed no significant differences between groups. High dose genistein aglycone (160 mg/kg/day) was not associated with clinically meaningful reductions in CSF heparan sulfate and no evidence of clinical efficacy was detected. However, there was a statistically significant reduction in urine glycosaminoglycans. These data do not support the use of genistein aglycone therapy in mucopolysaccharidosis type III. High dose genistein aglycone does not lead to clinically meaningful reductions in biomarkers or improvement in neuropsychological outcomes in mucopolysaccharidosis type III

Genistein Improves Neuropathology and Corrects Behaviour in a Mouse Model of Neurodegenerative Metabolic Disease

BACKGROUND: Neurodegenerative metabolic disorders such as mucopolysaccharidosis IIIB (MPSIIIB or Sanfilippo disease) accumulate undegraded substrates in the brain and are often unresponsive to enzyme replacement treatments due to the impermeability of the blood brain barrier to enzyme. MPSIIIB is characterised by behavioural difficulties, cognitive and later motor decline, with death in the second decade of life. Most of these neurodegenerative lysosomal storage diseases lack effective treatments. We recently described significant reductions of accumulated heparan sulphate substrate in liver of a mouse model of MPSIIIB using the tyrosine kinase inhibitor genistein. METHODOLOGY/PRINCIPAL FINDINGS: We report here that high doses of genistein aglycone, given continuously over a 9 month period to MPSIIIB mice, significantly reduce lysosomal storage, heparan sulphate substrate and neuroinflammation in the cerebral cortex and hippocampus, resulting in correction of the behavioural defects observed. Improvements in synaptic vesicle protein expression and secondary storage in the cerebral cortex were also observed. CONCLUSIONS/SIGNIFICANCE: Genistein may prove useful as a substrate reduction agent to delay clinical onset of MPSIIIB and, due to its multimodal action, may provide a treatment adjunct for several other neurodegenerative metabolic diseases