Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches

The Schuurs–Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopment Disorder (PACS1-NDD) is a rare autosomal dominant disease caused by mutations in the PACS1 gene. To date, only 87 patients have been reported and, surprisingly, most of them carry the same variant (c.607C>T; p.R203W). The most relevant clinical features of the syndrome include neurodevelopment delay, seizures or a recognizable facial phenotype. Moreover, some of these characteristics overlap with other syndromes, such as the PACS2 or Wdr37 syndromes. The encoded protein phosphofurin acid cluster sorting 1 (PACS-1) is able to bind to different client proteins and direct them to their subcellular final locations. Therefore, although its main function is protein trafficking, it could perform other roles related to its client proteins. In patients with PACS1-NDD, a gain-of-function or a dominant negative mechanism for the mutated protein has been suggested. This, together with the fact that most of the patients carry the same genetic variant, makes it a good candidate for novel therapeutic approaches directed to decreasing the toxic effect of the mutated protein. Some of these strategies include the use of antisense oligonucleotides (ASOs) or targeting of its client proteins

Ewing sarcoma of the bone. Multidisciplinary approach and oncological results in 88 patients

El sarcoma de Ewing óseo es un tumor poco frecuente, agresivo, que afecta principalmente a niñosy adultos jóvenes. Existe ausencia de registros en nuestro país respecto de la prevalencia de estaenfermedad, los esquemas de tratamiento utilizados y sus resultados. El objetivo fue analizar, en un grupode pacientes con sarcoma de Ewing óseo tratados con quimioterapia y cirugía de conservación de miembro,las tasas de supervivencia global, de recurrencia local y los factores de riesgo oncológicos. Se incluyó a 88pacientes. La edad media de la serie fue de 14.5 años y el seguimiento promedio de 8.8 años. La tasa de supervivencia global fue de 79.5% a los 2 años, de 69% a 5 años y de 64% a 10 años. Los factores pronósticosnegativos asociados a menor supervivencia fueron: mala respuesta a la quimioterapia, edad ≥ de 16 años,localización central, y recurrencia local. En el análisis multivariable únicamente la respuesta a la quimioterapiatuvo significancia estadística. La tasa libre de recurrencia local a 2 y 5 años fue del 87%. La mala respuesta ala quimioterapia fue el único factor significativo para la recurrencia local. Consideramos que la cirugía de conservación de miembro asociada a quimioterapia pre y postoperatoria debe ser el tratamiento para el sarcomade Ewing óseo, alcanzando de esta manera una supervivencia global a 5 años del 69%. En nuestra serie, larespuesta a la quimioterapia ha sido el factor pronóstico más relevante para supervivencia y recurrencia local.Ewing sarcoma of the bone is a rare, highly aggressive tumor that typically affects children and young adults. In Argentina, the lack of Ewing’s sarcoma registries reflects in the absence of information regarding prevalence, treatment protocols and patient´s outcome. The purpose of this study was to analyze, in a group of patients diagnosed with Ewing sarcoma of the bone, treated with chemotherapy and limb-conserving surgery, their overall survival rate, local recurrence rate, and oncological risk factors. A retrospective research was conducted between 1990 and 2017. Eighty-eight patients with Ewing sarcoma of the bone matched the inclusion criteria. Median age was 14.5 years and median follow-up was 8.8 years. Overall survival rate was 79.5%, 69% and 64% at 2, 5 and 10 years respectively. Negative prognostic factors, associated with less survival rate after univariate analysis, were: bad response to chemotherapy (tumoral necrosis 0-89%), age > 16 years-old, central tumor localization and local recurrence. Gender and tumor size were not significant prognostic factors. After multivariate analysis, response to chemotherapy remained statistical significant. Local recurrence-free survival rate at 2 and 5 years was 87%. Tumor response to chemotherapy (0-89%) was the only significant factor for local recurrence. We consider that limb-salvage surgery, with neoadjuvant and adjuvant chemotherapy, are the mainstays of treatment for Ewing’s sarcoma, with an overall survival rate, at 5 years, of 69%. In this population, response to chemotherapy is the most relevant prognostic factor, being associated with both local recurrence and overall survival.Fil: Sanchez Saba, Javier E.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Abrego, Mariano O.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Albergo, José I.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Farfalli, Germán Luis. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Aponte Tinao, Luis A.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Ayerza, Miguel A.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Cayol, Federico. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Streitenberger, Patricia. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Risk, Marcelo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Roitman, Pablo Daniel. Instituto Universidad Escuela de Medicina del Hospital Italiano; Argentin

Development and characterization of 22 polymorphic microsatellites of the Andean frog Telmatobius chusmisensis (Anura, Telmatobius) and cross amplification in seven Chilean species of the genus

© 2018, Springer Nature B.V. The genus Telmatobius Wiegmann, 1834 is composed of a wide variety of species and is one of the most diverse native components of the high-altitude Andean environments. The species of the genus present in Chile are considered as endangered, critically endangered or data deficient. We isolated and evaluated 44 microsatellites in 80 individuals of 8 species of Telmatobius present in Chile, obtaining 22 polymorphic microsatellite loci for Telmatobius chusmisensis. The cross-amplification test was successful in all other species tested. For the first time, microsatellite markers are described for Telmatobius. The description of these primers will be useful for further genetic studies for T. chusmisensis and other species of the same genus; allowing further analyses of population structuring, dispersal patterns, recent demographic history and population effective size. This information is also significant to undertake conservation actions for the species of th

Latest Judgments of the Court of Justice of the European Union on Wolves (Canis lupus) and their Potential Impact on the Species Management in Spain

El lobo (Canis lupus), al igual que otros grandes carnívoros, está recuperando su antiguo territorio en el continente europeo. Esta situación supone una mayor interacción con el ser humano, por lo que es necesario establecer un nuevo paradigma en la relación entre seres humanos y lobos. La doctrina del Tribunal de Justicia de la Unión Europea (TJUE) determina en gran parte la aplicación efectiva y uniforme de la legislación de la Unión Europea ante cualquier tipo de situaciones inéditas. Este artículo supone una aproximación a la situación jurídica del lobo en Europa. Se analizan, pues, las dos últimas sentencias pronunciadas por el TJUE en 2019 y 2020, donde se consideran cuestiones relacionadas con la aplicación de la caza para llevar a cabo su gestión en un Estado miembro de la UE, y con la conservación de la especie independientemente de dónde se encuentre, incluyendo paisajes humanizados. Estas sentencias tienen consecuencias para la gestión de la especie en los Estados miembros de la Unión Europea. Además, nos centramos en sus repercusiones en España, donde la especie se encuentra bajo un escenario de gestión complejo.The wolf (Canis lupus), like other apex carnivores, is recovering its former territory in the European continent. This situation implies a greater interaction with humans, so it is necessary to establish a new paradigm in the relationship between humans and wolves. The doctrine of the Court of Justice of the European Union (CJEU) largely determines the effective and uniform application of the European Union legislation in any type of unprecedented situation. This article approaches the legal situation of the wolf in Europe. We therefore analyze the last two judgments of the CJEU in 2019 and 2020, which consider issues related to the application of wolf culling management within an EU member State, and to the conservation of the species wherever it may be found, including humanized landscapes. These judgments have consequences for the management of the species within the member States of the European Union. Furthermore, we discuss its repercussions in Spain, where the species is under a complex management scenario.El estudio fue parcialmente financiado por el Ministerio de Ciencia, Innovación y Universidades y el Fondo Europeo de Desarrollo Regional FEDER (proyecto “TRASCAR” RTI2018-099609-B-C21). Z.M.-R. fue financiado por un contrato postdoctoral cofinanciado por la Generalitat Valenciana y el Fondo Social Europeo (APOSTD/2019/016)

Aprovechamiento humano de aves marinas durante el Holoceno medio en el litoral árido del norte de Chile

Artículo de publicación ISISe identifi có y analizó la osteofauna aviar del sitio arqueológico Copaca 1, ubicado en el litoral árido de la segunda Región de Chile. La muestra estuvo compuesta por 685 fragmentos extraídos desde nueve capas con dataciones que cubren un rango entre 8000 - 5000 años cal. a.p. Los resultados indican que el ensamble de aves marinas encontrado en este sitio conserva actualmente su rango de distribución en la zona de estudio, siendo dominantes los órdenes Suliformes, Procellariiformes y Pelecaniformes. Los análisis sugieren un aprovechamiento principalmente sobre Puffi nus sp., Pelecanus thagus y Phalacrocorax sp., identifi cándose un mínimo número de individuos de 74 aves. Además, se estimó la masa corporal utilizable aportada por cada taxón y se determinó una representación diferencial de elementos anatómicos apendiculares junto con diversos grados de fraccionamiento y marcas culturales, que indicarían obtención de alimento y elaboración de artefactos. Nuestros resultados apoyan el aprovechamiento de aves marinas durante el Holoceno medio en la costa suroccidental de Sudamérica

A new endemic lineage of the Andean frog genus Telmatobius (Anura, Telmatobiidae) from the western slopes of the central Andes

The amphibian genus Telmatobius is a diverse group of species that inhabits the Andes. This study analysed the phylogenetic relationships of 19 species described from the central Andes of Chile and Bolivia, and 12 undescribed populations of Chile. A molecular phylogeny based on mitochondrial DNA16S and cytochrome b shows that the Chilean species belong to three groups: (1) the Telmatobius marmoratus group, widespread in the Chilean and Bolivian Altiplano; (2) the Telmatobius hintoni group, including the species Telmatobius philippii, Telmatobius fronteriensis, and Telmatobius huayra, occurring in the south-western Altiplano of Chile and Bolivia, and (3) the Telmatobius zapahuirensis group, a new clade which also includes Telmatobius chusmisensis, Telmatobius dankoi, and Telmatobius vilamensis, restricted to western slopes of the Andes, and which was recovered as more closely related to the T.hintoni group than the T.marmoratus group. The divergence times between clades were traced to

Optic neuritis: our experience

Optic Neuritis (ON) is an acute inflammatory disorder of the optic nerve. The general characteristics of isolated ON include unilateral, subacute, and painful visual loss without systemic or other neurological symptoms.[1] In the literature, acute typical optic neuritis is the most common optic neuropathy with an estimated lifetime prevalence of 0.6/1000 with age-adjusted and sex-adjusted incidence. In its typical form, optic neuritis presents as an inflammatory demyelinating disorder of the optic nerve, which can be associated with multiple sclerosis. (MS). Atypical forms of optic neuritis can occur, either in association with other inflammatory disorders or in isolation.[2]. This review shows our incidence of ON, the demographic distribution and the main causes

Ocular Myasthenia Gravis: AChR Seropositivy and Generalization

Ocular Myasthenia Gravis (OMG) is an autoimmune disorder of the neuromuscular junction characterized by fatigable weakness of extraocular muscles, levator palpebrae, and orbicularis oculi resulting in fatigable ptosis and binocular diplopia. The predominant auto-antibodies in Myasthenia Gravis are, among others, those against acethylcholine receptors. Multiples studies reported a seropositivity between 40% and 60% f or OMG. Some patients may develop weakness in their limbs, bulbar or respiratory muscles,that is, Generalized Myasthenia Gravis (GMG). The purpose of this study is to report the frequency of Acetylcholine Receptor Antibody (AChR) seropositivity i n patients with clinical suspicion of OMG and the percentage of these patients who developed GMG during the follow up