Variability in Phelan-McDermid Syndrome in a Cohort of 210 Individuals

Phelan-McDermid syndrome; Intellectual disabilities; Subtelomeric deletion syndromeSíndrome de Phelan-McDermid; Discapacidades intelectuales; Síndrome de deleción subteloméricaSíndrome de Phelan-McDermid; Discapacitats intel·lectuals; Síndrome de deleció subtelomèricaPhelan-McDermid syndrome (PMS, OMIM# 606232) results from either different rearrangements at the distal region of the long arm of chromosome 22 (22q13.3) or pathogenic sequence variants in the SHANK3 gene. SHANK3 codes for a structural protein that plays a central role in the formation of the postsynaptic terminals and the maintenance of synaptic structures. Clinically, patients with PMS often present with global developmental delay, absent or severely delayed speech, neonatal hypotonia, minor dysmorphic features, and autism spectrum disorders (ASD), among other findings. Here, we describe a cohort of 210 patients with genetically confirmed PMS. We observed multiple variant types, including a significant number of small deletions (<0.5 Mb, 64/189) and SHANK3 sequence variants (21 cases). We also detected multiple types of rearrangements among microdeletion cases, including a significant number with post-zygotic mosaicism (9.0%, 17/189), ring chromosome 22 (10.6%, 20/189), unbalanced translocations (de novo or inherited, 6.4%), and additional rearrangements at 22q13 (6.3%, 12/189) as well as other copy number variations in other chromosomes, unrelated to 22q deletions (14.8%, 28/189). We compared the clinical and genetic characteristics among patients with different sizes of deletions and with SHANK3 variants. Our findings suggest that SHANK3 plays an important role in this syndrome but is probably not uniquely responsible for all the spectrum features in PMS. We emphasize that only an adequate combination of different molecular and cytogenetic approaches allows an accurate genetic diagnosis in PMS patients. Thus, a diagnostic algorithm is proposed.REDES/FIBHULP08. FIBHULP PI: 2735. FIBHULP Auchan Reserch Project. FIBHULP. Raregenomics (B2017/BMD-3721)

Effect of Size, Shape, and Composition on the Interaction of Different Nanomaterials with HeLa Cells

The application of nanomaterials in the fields of medicine and biotechnology is of enormous interest, particularly in the areas where traditional solutions have failed. Unfortunately, there is very little information on how to optimize the preparation of nanomaterials for their use in cell culture and on the effects that these can trigger on standard cellular systems. These data are pivotal in nanobiotechnology for the development of different applications and to evaluate/compare the cytotoxicity among the different nanomaterials or studies. The lack of information drives many laboratories to waste resources performing redundant comparative tests that often lead to partial answers due to differences in (i) the nature of the start-up material, (ii) the preparation, (iii) functionalization, (iv) resuspension, (v) the stability/dose of the nanomaterial, etc. These variations in addition to the different analytical systems contribute to the artefactual interpretation of the effects of nanomaterials and to inconsistent conclusions between different laboratories. Here, we present a brief review of a wide range of nanomaterials (nanotubes, various nanoparticles, graphene oxide, and liposomes) with HeLa cells as a reference cellular system. These human cells, widely used as cellular models for many studies, represent a reference system for comparative studies between different nanomaterials or conditions and, in the last term, between different laboratories.This work has been supported by the Spanish MINECO and European FEDER under Project ref. PI16/000496, the NanoBioApp Network Ref. MINECO-17-MAT2016-81955-REDT. We thank IDIVAL for INNVAL15/16, INNVAL 17/11, PREVAL 16/03, 16/02, 17/04, and the Raman4clinics BMBS COST Actions BM1401 and TD1402. We also thank Débora Muñoz for her technical assistance. We are grateful to the Nikon A1R Laser Microscopy Unit and the TEM Unit of the IDIVAL Institute

Genetic structure of Cannabis sativa var. indica cultivars based on genomic SSR (gSSR) markers: implications for breeding and germplasm management

[EN] Cannabis saliva L. is cultivated for its fiber or seeds (var. saliva; hemp), or for its high content in cannabinoids (var. indica; marijuana). Knowledge of the genetic structure of C. sativa var. indica is important for selection and breeding of cultivars with medicinal interest. We used six genomic SSRs (gSSRs) for genotyping 154 individual plants of 20 cultivars of C. sativa var. indica, plus two cultivars of C. sativa var. sativa. A very high polymorphism was observed, with an average of 17 alleles and 23.8 genotypes per locus. Expected (H-e) and observed (H-o) heterozygosities were high, with average values of 0.753 and 0.429, respectively. In some cultivars H-e and H-o presented similar values, while in others H-e was considerably higher than H-o suggesting that consanguinity and fixation had taken place during its development. In addition, some cultivars had a reduced number of alleles per locus (in some cases only two) indicating that a genetic bottleneck had taken place during its development. Gene flow (Nm) between both botanical varieties was high, with Nm = 1.736. The molecular analysis of variance (AMOVA) revealed that only 31.94% of the molecular variation observed was caused by differences among cultivars, while the variation among plants of the same cultivar was of 37.11%, and within individual variation, due to heterozygosity, was of 30.96%. This indicates that a large variation exists within cultivars, which can be exploited for selection, but also complicates germplasm management and regeneration. The population structure analysis identified 14 genetic clusters, with most individuals of a single cultivar clustering together. This analysis, together with UPGMA cluster analysis shows that the two C. saliva var. saliva cultivars studied are differentiated from C. sativa var. indica, and that some cultivars of C. saliva var. indica seem to represent different selections from a common original cultivar. Our results represent the first comprehensive study of intra-varietal diversity in C. sativa var. indica and provide information of relevance for selection, breeding, and germplasm conservation, as well as for forensic studies in this crop.Soler Aleixandre, S.; Gramazio, P.; Figás-Moreno, MDR.; Vilanova Navarro, S.; Rosa-Martínez, E.; Llosa, ER.; Borràs-Palomares, D.... (2017). Genetic structure of Cannabis sativa var. indica cultivars based on genomic SSR (gSSR) markers: implications for breeding and germplasm management. Industrial Crops and Products. 104:171-178. doi:10.1016/j.indcrop.2017.04.043S17117810

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Adelante / Endavant

Séptimo desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d’Estudis Feministes i de Gènere "Purificación Escribano" de la Universitat Jaume

Desarrollo de nanopartículas multifuncionales para el tratamiento y diagnóstico de precisión de cáncer de cabeza y cuello

RESUMEN: El cáncer de cabeza y cuello es el sexto cáncer más común a nivel mundial, es de naturaleza generalmente localizado y su mortalidad por fallo loco-regional puede reducirse significativamente si se detecta precozmente. Por ello, surge la necesidad de explorar estrategias alternativas que puedan contribuir al diagnóstico temprano y al tratamiento local, contexto donde la nanotecnología puede aportar soluciones únicas. A lo largo de esta Tesis se desarrollan nanosistemas híbridos multifuncionales fotoactivables para su potencial aplicación en el diagnóstico de precisión y el tratamiento a demanda de esta patología. Se han sintetizado nanomateriales con un núcleo de oro y de óxido de hierro, capaces de calentarse al irradiarse con luz láser infrarroja, recubiertos de una capa de sílice fluorescente que sirve como plataforma para su funcionalización y además permite su detección aplicando luz visible. Para su direccionamiento, se han imitado los mecanismos de invasión celular utilizados por la toxina de la Shiga, cuyo receptor, el glucoesfingolípido Gb3, está sobreexpresado en el cáncer cabeza y cuello entre otros. Con este fin, se ha diseñado genéticamente y producido una proteína quimera recombinante conteniendo el dominio de interacción de la toxina fusionado a una secuencia de unión a nanomateriales. Este estudio demuestra el posicionamiento controlado, la estabilidad y eficiencia de este recubrimiento, y cómo los nanomateriales funcionalizados con esta proteína, se unen específicamente al receptor Gb3 en células tumorales de cabeza y cuello, invadiendo éstas siguiendo una ruta biomimética “no canónica”, vía aparato de Golgi y/o retículo endoplásmico, que permite evitar el paso por los lisosomas. Finalmente, esta tesis idea un recubrimiento a modo de nano-termómetro, y demuestra cómo la irradiación de células expuestas a estas nanopartículas con un láser de 808 nm provoca la muerte celular a demanda en escasos minutos.Proyecto PREVAL16/02, correspondiente con la ayuda recibida bajo la convocatoria del “Programa de Personal Investigador en Formación Predoctoral en el Área de la Biomedicina, Biotecnología y Ciencias de la Salud (2015, BOC NÚM. 188)”. Proyectos INNVAL16/15, INNVAL17/11, INNVAL18/28, todos ellos del Instituto de Investigación Marqués de Valdecilla (IDIVAL) • Proyecto de investigación PI16/00496; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Fondos FEDER. • Proyectos MINECO. MAT2015-69508-P, MAT2016-81955-REDT y MAT2017-83631-C3-3-R

Método de recubrimiento proteico de materiales mediante bioconjugación electrostática

La presente invención se refiere a un método de recubrimiento proteico de materiales mediante bioconjugación electrostática entre el material y un complejo proteico mediado por cargas electrostáticas opuestas entre la superficie del material y el complejo proteico, generando así una corona proteica biocompatible dispuesta de manera uniforme sobre la superficie del material. El método permite además mantener la funcionalidad del complejo proteico para poder emplear así el material recubierto obtenido en clínica.Solicitud: 201930734 (07.08.2019)Nº Pub. de Solicitud: ES2804578A1 (08.02.2021