Educación afectivo- sexual en personas con discapacidad intelectual

Este estudio se enfoca en la educación afectivo-sexual en personas con discapacidad intelectual. Explora la evolución legislativa que ha influido en su abordaje, y presenta una propuesta de intervención basada en la revisión de literatura y buenas prácticas. Además, analiza tablas y gráficos relevantes para ofrecer una visión visual del panorama actual y los desafíos en la educación sexual adaptada. La inclusión educativa y social emerge como un concepto fundamental, examinando cómo se traduce en la adaptación curricular y en la creación de ambientes de aprendizaje inclusivos, con el fin de garantizar una educación afectivo-sexual y respetuosa para las personas con discapacidad intelectual<br /

Application of a Clinical Workflow May Lead to Increased Diagnostic Precision in Hereditary Spastic Paraplegias and Cerebellar Ataxias: A Single Center Experience

The molecular characterization of Hereditary Spastic Paraplegias (HSP) and inherited cerebellar ataxias (CA) is challenged by their clinical and molecular heterogeneity. The recent application of Next Generation Sequencing (NGS) technologies is increasing the diagnostic rate, which can be influenced by patients\u2019 selection. To assess if a clinical diagnosis of CA/HSP received in a third-level reference center might impact the molecular diagnostic yield, we retrospectively evaluated the molecular diagnostic rate reached in our center on 192 unrelated families (90 HSP and 102 CA) (i) before NGS and (ii) with the use of NGS gene panels. Overall, 46.3% of families received a genetic diagnosis by first-tier individual gene screening: 43.3% HSP and 50% spinocerebellar ataxias (SCA). The diagnostic rate was 56.7% in AD-HSP, 55.5% in AR-HSP, and 21.2% in sporadic HSP. On the other hand, 75% AD-, 52% AR- and 33% sporadic CA were diagnosed. So far, 32 patients (24 CA and 8 HSP) were further assessed by NGS gene panels, and 34.4% were diagnosed, including 29.2% CA and 50% HSP patients. Eleven novel gene variants classified as (likely) pathogenic were identified. Our results support the role of experienced clinicians in the diagnostic assessment and the clinical research of CA and HSP even in the next generation era

A Multifunctional Conjugated Polymer Developed as an Efficient System for Differentiation of SH-SY5Y Tumour Cells

Polymer-based systems have been demonstrated in novel therapeutic and diagnostic (theranostic) treatments for cancer and other diseases. Polymers provide a useful scaffold to develop multifunctional nanosystems that combine various beneficial properties such as drug delivery, bioavailability, and photosensitivity. For example, to provide passive tumour targeting of small drug molecules, polymers have been used to modify and functionalise the surface of water-insoluble drugs. This approach also allows the reduction of adverse side effects, such as retinoids. However, multifunctional polymer conjugates containing several moieties with distinct features have not been investigated in depth. This report describes the development of a one-pot approach to produce a novel multifunctional polymer conjugate. As a proof of concept, we synthesised polyvinyl alcohol (PVA) covalently conjugated with rhodamine B (a tracking agent), folic acid (a targeting agent), and all-trans retinoic acid (ATRA, a drug). The obtained polymer (PVA@RhodFR) was characterised by MALDI-TOF mass spectrometry, gel permeation chromatography, thermal analysis, dynamic light-scattering, NMR, UV-Vis, and fluorescence spectroscopy. Finally, to evaluate the efficiency of the multifunctional polymer conjugate, cellular differentiation treatments were performed on the neuroblastoma SH-SY5Y cell line. In comparison with standard ATRA-based conditions used to promote cell differentiation, the results revealed the high capability of the new PVA@RhodFR to induce neuroblastoma cells differentiation, even with a short incubation time and low ATRA concentration

Freeze-Dried Secretome (Lyosecretome) from Mesenchymal Stem/Stromal Cells Promotes the Osteoinductive and Osteoconductive Properties of Titanium Cages

Titanium is one of the most frequently used materials in bone regeneration due to its good biocompatibility, excellent mechanical properties, and great osteogenic performance. However, osseointegration with host tissue is often not definite, which may cause implant failure at times. The present study investigates the capacity of the mesenchymal stem cell (MSC)-secretome, formulated as a ready-to-use and freeze-dried medicinal product (the Lyosecretome), to promote the osteoinductive and osteoconductive properties of titanium cages. In vitro tests were conducted using adipose tissue-derived MSCs seeded on titanium cages with or without Lyosecretome. After 14 days, in the presence of Lyosecretome, significant cell proliferation improvement was observed. Scanning electron microscopy revealed the cytocompatibility of titanium cages: the seeded MSCs showed a spread morphology and an initial formation of filopodia. After 7 days, in the presence of Lyosecretome, more frequent and complex cellular processes forming bridges across the porous surface of the scaffold were revealed. Also, after 14 and 28 days of culturing in osteogenic medium, the amount of mineralized matrix detected by alizarin red was significantly higher when Lyosecretome was used. Finally, improved osteogenesis with Lyosecretome was confirmed by confocal analysis after 28 and 56 days of treatment, and demonstrating the production by osteoblast-differentiated MSCs of osteocalcin, a specific bone matrix protein

Sirt3 deficiency shortens lifespan and impairs cardiac mitochondrial function rescued by Opa1 gene transfer

Aims: Sirtuins, a family of NAD+-dependent deacetylases, are recognized as non-dispensable regulators of aging processes. Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase that maintains mitochondrial bioenergetics, an essential prerequisite for healthy aging. Here using Sirt3 knock-out (Sirt3-/-) mice we sought to establish whether Sirt3 deficiency affected lifespan, an endpoint that has never been tested formally in mammals, and uncover the mechanisms involved in organ damage associated with aging. Results: Sirt3-/- mice experienced a shorter lifespan than wild-type mice and severe cardiac damage, characterized by hypertrophy and fibrosis, as they aged. No alterations were found in organs other than the heart. Sirt3 deficiency altered cardiac mitochondrial bioenergetics and caused hyperacetylation of optic atrophy 1 (OPA1), a SIRT3 target. These changes were associated with aberrant alignment of trans-mitochondrial cristae in cardiomyocytes, and cardiac dysfunction. Gene transfer of deacetylated Opa1 restored cristae alignment in Sirt3-/- mice, ameliorated cardiac reserve capacity and protected the heart against hypertrophy and fibrosis. The translational relevance of these findings is in the data showing that SIRT3 silencing in human induced pluripotent stem cellderived cardiomyocytes led to mitochondrial dysfunction and altered contractile phenotype, both rescued by Opa1 gene transfer. Innovation: Our findings indicate that future approaches to heart failure could include SIRT3 as a plausible therapeutic target. Conclusion: SIRT3 has a major role in regulating mammal lifespan. Sirt3 deficiency leads to cardiac abnormalities, due to defective trans-mitochondrial cristae alignment and impaired mitochondrial bioenergetics. Correcting cardiac OPA1 hyperacetylation through gene transfer diminished heart failure in Sirt3-/- mice during aging

Reconstitution of an Ultradian Oscillator in Mammalian Cells by a Synthetic Biology Approach

The Notch effector gene <i>Hes1</i> is an ultradian clock exhibiting cyclic gene expression in several progenitor cells, with a period of a few hours. Because of the complexity of studying Hes1 in the endogenous setting, and the difficulty of imaging these fast oscillations <i>in vivo</i>, the mechanism driving oscillations has never been proven. Here, we applied a “build it to understand it” synthetic biology approach to construct simplified “hybrid” versions of the Hes1 ultradian oscillator combining synthetic and natural parts. We successfully constructed a simplified synthetic version of the <i>Hes1</i> promoter matching the endogenous regulation logic. By mathematical modeling and single-cell real-time imaging, we were able to demonstrate that Hes1 is indeed able to generate stable oscillations by a delayed negative feedback loop. Moreover, we proved that introns in <i>Hes1</i> contribute to the transcriptional delay but may not be strictly necessary for oscillations to occur. We also developed a novel reporter of endogenous Hes1 oscillations able to amplify the bioluminescence signal 5-fold. Our results have implications also for other ultradian oscillators

Freeze-Dried Mesenchymal Stem Cell-Secretome Pharmaceuticalization: Optimization of Formulation and Manufacturing Process Robustness

Producing mesenchymal stem cell (MSC)-secretome for dose escalation studies and clinical practice requires scalable and good manufacturing practice (GMP)-compliant production procedures and formulation into a standardized medicinal product. Starting from a method that combines ultrafiltration and freeze-drying to transform MSC-secretome into a pharmaceutical product, the lyosecretome, this work aims to: (i) optimize the lyosecretome formulation; (ii) investigate sources of variability that can affect the robustness of the manufacturing process; (iii) modify the ultrafiltration step to obtain a more standardized final product. Design of experiments and principal component analysis of the data were used to study the influence of batch production, lyophilization, mannitol (M)/sucrose (S) binary mixture, selected as cryoprotectant excipients, and the total amount of excipients on the extracellular vesicles (EV) particle size, the protein and lipid content and the in vitro anti-elastase. The different excipients ratios did not affect residual moisture or EV particle size; simultaneously, proteins and lipids were better preserved in the freeze-dried product using the maximum total concentration of excipients (1.5% w/v) with a M:S ratio of about 60% w/w. The anti-elastase activity was instead better preserved using 0.5% w/w of M as excipient. The secretome batch showed to be the primary source of variability; therefore, the manufacturing process has been modified and then validated: the final product is now concentrated to reach a specific protein (and lipid) concentration instead of cell equivalent concentration. The new standardization approach led to a final product with more reproducible quali-quantitative composition and higher biological activity

Diagnóstico y tratamiento de la pancreatitis aguda en la Argentina. Resultados de un estudio prospectivo en 23 centros

En la Argentina no existen trabajos multicéntricos que eva-lúen el manejo de los pacientes con pancreatitis aguda (PA)a nivel nacional.Objetivos.El objetivo principal de estetrabajo es conocer el manejo de los pacientes con PA en la Argentina. El objetivo secundario es evaluar si los resultadosobtenidos cumplen con los postulados de la Guía Internacio-nal del Colegio Americano de Gastroenterología.Material ymétodos.Participaron 23 centros que ingresaron, en formaprospectiva y consecutiva, a todos los pacientes con diagnós-tico de PA a una base de datos alojada en Internet desdejunio de 2010 a junio de 2013.Resultados.Ingresaron alestudio 854 pacientes (495 mujeres, 58%), edad mediana:47 años (rango: 15-91). La causa más frecuente de PA fue labiliar (88,2%), en el 99% de los pacientes se utilizó un sis-tema pronóstico, el más frecuente fue el de Ranson (74,5%). Fueron clasificados como PA leves 714 pacientes (83,6%) yPA graves 140 (16,4%). Se registraron 43 complicacionessistémicas y 21 locales. A 86 pacientes se les realizó tomogra-fía dinámica y se registraron 73 pacientes con necrosis pan-creática y/o peripancreática. La mortalidad fue de 1,5%. Nohubo diferencia en la mortalidad en relación al volumen,complejidad o afiliación del centro. El cumplimiento de lasprincipales recomendaciones de la guía del Colegio America-no de Gastroenterología fue superior al 80%.Conclusiones.El diagnóstico y el tratamiento de los pacientes con PA en 23centros de salud distribuidos en todo el país fueron óptimos.El manejo cumple con la mayoría de las recomendaciones dela Guía del Colegio Americano de Gastroenterología

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction