Estudio Genético-Molecular de varias familias con Ataxia Dominante y ancestros en A Costa da Morte (Galicia, España)

La ataxia de A Costa da Morte es un tipo de ataxia espinocerebelosa (SCA) que hemos identificado en familias procedentes de Galicia. Esta enfermedad, denominada también SCA36, está causada por el aumento del número de repeticiones del repeat hexanucleotídico (GGCCTG)n situado en el intrón 1 del gen NOP56. El tamaño de los alelos normales es de 3 a 14 repeticiones GGCCTG, mientras que los alelos patológicos presentan expansiones de gran tamaño que van desde 650 a 2500 o más repeticiones. Hemos detectado la presencia de la mutación de NOP56 en 75 pacientes pertenecientes a 13 núcleos familiares de Galicia, lo que la convierte en el tipo de SCA más frecuente en nuestra comunidad (6% del total y 21% de las dominantes). El análisis detallado de la región de ligamiento en el brazo corto del cromosoma 20 reveló que todos los casos gallegos de SCA36 derivan de un ancestro común que probablemente vivió hace unos 700 años. Las características fenotípicas de la SCA36-Ataxia da Costa da Morte se resumen en un síndrome cerebeloso predominantemente de línea media, de inicio tardío y lenta progresión, asociado a hipoacusia neurosensorial, moderados signos de afectación piramidal y atrofia neurógena lingual. De forma independiente, se ha descrito la SCA36 en familias japonesas de la región Chugoku. Más recientemente se han reportado clústeres en Italia, Francia y Polonia, así como casos aislados españoles de fuera de Galicia. La expansión se comporta de manera inestable, con tendencia a aumentar de tamaño durante la transmisión y posible anticipación. La SCA36 se suma así al creciente número de síndromes neurodegenerativos asociados a grandes expansiones de zona

In vitro study of the therapeutic potential of brown crude fucoidans in osteoarthritis treatment

[Abstract] Osteoarthritis, one of the most common joint degenerative pathologies, still has no cure, and current treatments, such as nonsteroidal anti-inflammatory drugs, can cause serious adverse effects when taken for a long time. Brown seaweed crude fucoidans are used for the clinical treatment of several pathologies. In this study, the therapeutical potential of these biocompounds was analyzed in primary chondrocytes and the 260TT human chondrocyte cell line. Crude fucoidan from Undaria pinnatifida (Up) and Sargassum muticum (Sm) was obtained by different extraction techniques (microwave-assisted extraction, pressurized hot-water extraction, ultrasound-assisted extraction) and chemically and structurally characterized by Fourier transform infrared spectroscopy, high-performance size-exclusion chromatography, proton nuclear magnetic resonance, and scanning electron microscopy. Once cell viability was confirmed in chondrocytes treated with crude fucoidans, we evaluated their anti-inflammatory effects, observing a significant reduction in IL-6 production stimulated by IL-1β. Findings were confirmed by analysis of IL-6 and IL-8 gene expression, although only fucoidans from Up achieved a statistically significant reduction. Besides this, the antioxidant capacity of crude fucoidans was observed through the upregulation of Nrf-2 levels and the expression of its transcriptional target genes HO-1 and SOD-2, with compounds from Up again showing a more consistent effect. However, no evidence was found that crude fucoidans modulate senescence, as they failed to reduced β-galactosidase activity, cell proliferation, or IL-6 production in chondrocytes stimulated with etoposide. Thus, the findings of this research seem to indicate that the tested crude fucoidans are capable of partially alleviating OA-associated inflammation and oxidative stress, but fail to attenuate chondrocyte senescence

The rol of tics in e-informaion and guidance throught life: analysis of the european situation

La incorporación de las Tecnologías de la Información y Comunicación en la sociedad en general y en el sistema educativo, especialmente en la formación y orientación a lo largo de la vida de las personas, demanda cambios relevantes en los ámbitos tecnológicos y organizativos así como en los escenarios educativos y ambientes de aprendizaje y orientación formales y no formales. En el contexto europeo las transformaciones en amplios sectores sociales mediante las TIC no llegaron aún a generalizarse en los procesos formativos y orientadores. Entre las herramientas más innovadoras en el uso de las TIC en formación y orientación, además de las más conocidas como el teléfono, correo electrónico e Internet existen otras a subrayar como son la videoconferencia, chat y foro. Como instrumentos de software social se pueden citar el Blog, Twitter, Facebook, Flicker, Second Life, My Space… y otros recursos tecnológicos como son la pizarra interactiva, el portafolios y el sistema de gestión de contenidos (SGC). En las diversas conferencias europeas sobre el uso de las TIC en orientación se ha ido desplazando el centro de atención; se inicia por el tratamiento de los sistemas de orientación apoyados por el ordenador (Bruselas, 1985; Cambridge, 1989 y Nuremberg en 1992); se continúa por el uso de Internet en la conferencia de Dublín, 1996 y se considera la era digital en la de Gotemburg en 2001 y la tecnología Web 2.0 en Riga, en la 6ª Conferencia celebrada en el mes de septiembre de 2009The incorporation of Information and Communication Technologies in the society in general and in the education system, especially in training and guidance throughout the life of the people, demands significant changes in technological and organizational fields as well as the educational settings and learning and formal and informal guidance environments. In the European context the transformations in wide social sectors through ICT has not yet become generalized in the training and guidance process. Among the most innovative tools in the use of ICT for training and guidance, in addition to more familiar as the telephone, email and the Internet there are others to stress such as videoconferencing, chat and forum. As social software tools can cite the Blog, Twitter, Facebook, Flicker, Second Life, MySpace... and other technological resources such as interactive whiteboard, the portfolio and the content management system (CMS). In the various European conferences on the use of ICT in guidance has been shifting the center of attention; is begins by treating of guidance systems supported by the computer (Brussels, 1985, Cambridge, 1989 and Nuremberg in 1992); is continues by the use of Internet in the Dublin conference, 1996 and is considered the digital age in Gothenburg in 2001 and Web 2.0 technology in Riga, at the 6th Conference held in the moth of September 2009S

Dental caries in the stomatological emergency service in the area of the Polyclinic René Vallejo. Bayamo

Introducción: las caries dentales permanecen como un problema sobresaliente de salud pública, por su frecuencia, el daño causado, las posibilidades de actuación eficaz, el costo per cápita y el interés de la comunidad.Objetivo: determinar  la frecuencia de la caries dental en el  servicio de urgencias del policlínico René Vallejo Ortiz,  Bayamo, de noviembre 2011 a mayo 2012.Métodos: estudio descriptivo-prospectivo. El universo estuvo constituido por 1402 pacientes, seleccionando para nuestro estudio 922 casos cuya causa de urgencia fue la caries dental. Se estudiaron variables como edad, sexo, factores de riesgos,  además la presencia o no de enfermedades pulpares y periapicales  y  las conductas terapéuticas seguidas.Resultados: se corroboró que 65,8% de los casos presentaron caries dental como causa de urgencia, la edad de 35 – 59 años estuvo más afectada (71,2%) y el mayor número fue del sexo femenino (56,1%). Como factores de riesgo predominaron factores sociales, higiene bucal deficiente e ingestión de alimentos cariogénicos. Las enfermedades de mayor incidencia fueron las patologías pulpares (32,8%). La cura medicamentosa fue la terapia más empleada (64%).Conclusiones: las caries dentales fueron la causa que originó mayor cantidad de urgencias estomatológicas en esta área de salud, siendo el grupo de mayor incidencia el de 35- 59 años y el sexo femenino. Los factores de riesgo con más prevalencia fueron los sociales, higiene bucal deficiente y dieta cariogénica, Hubo más pacientes diagnosticados con enfermedades pulpares que periapicales y la conducta terapéutica más aplicada resultó ser los tratamientos que conservaron la vitalidad pulpar.Introduction: dental caries remains as a relevant health problem because of its frequency, damage caused, possibilities of effective performance, its cost per capita and the community interest.Objective: to determine the frequency of dental caries at the emergency services at René Vallejo Ortiz polyclinic in Bayamo, from November 2011 to May 2012. Methods: a descriptive prospective study was carried out. The universe was constituted by 1402 patients; only 922 cases were selected for our study, whose cause of emergency was the dental caries. We evaluated some variables like age, sex, risk factors, besides we also had the presence or not of pulpal and periapical diseases and the followed up therapeutic behaviors.Results: with the results it was confirmed that 65, 8% of the cases had dental caries, the most affected group of age was between 35-59 years (71, 2%), most of the patients were females (56, 1%). As risk factors prevailed social causes, the inefficient buccal hygiene and the ingestion of cariogenic food. The diseases with more incidences were the pulp pathologies (32.8%). The medical cure was the mostly used therapy (64%).Conclusions: dental caries originated most of the stomatological emergencies in this health area, prevailed the group of age from 35 to 59 years old and females. Risk factors that prevailed were social, inefficient buccal hygiene and cariogenic diet.   There were most diagnosed pulpal diseases rather than periapical ones, and the therapy conduct followed was conservation of pulpal vitality

A Shotgun Proteomics Approach to Reveal New Putative Therapeutical Targets in Nephropathic Cystinosis

Poster.-- Human Proteome Organization World Congress, HUPO 2023, 17-21 SeptemberNephropathic cystinosis is a rare autosomal recessive metabolic disease due to mutations in the CTNS gen codifying for cystinosin, a lysosomal symporter. It is characterized by the accumulation of cystine crystals in lysosomes causing end-stage renal damage and blindness in patients under ten years of age. Currently, there is no cure and the only palliative treatment, cysteamine, presents several limitations including the lack of cure for the disease, the adverse effects, and the complexity of the indicated treatment for life. Recent findings indicate that the intra-lysosomal accumulation of cystine alters key processes such as phagocytosis, redox balance, and autophagy, causing a molecular imbalance that, to date, has not been characterized in detail.N

Shotgun proteomics reveals new therapeutical targets in nephropathic cystinosis

Poster.-- Human Proteome Organization World Congress, HUPO 2023, 17-21 SeptemberTalento Senior Program-GAIN Xunta de Galicia, Fundación Mutua Madrileña, Asociación Cistinosis EspañaN

‘Costa da Morte’ ataxia is spinocerebellar ataxia 36: clinical and genetic characterization

Spinocerebellar ataxia 36 has been recently described in Japanese families as a new type of spinocerebellar ataxia with motor neuron signs. It is caused by a GGCCTG repeat expansion in intron 1 of NOP56. Family interview and document research allowed us to reconstruct two extensive, multigenerational kindreds stemming from the same village (Costa da Morte in Galicia, Spain), in the 17th century. We found the presence of the spinocerebellar ataxia 36 mutation co-segregating with disease in these families in whom we had previously identified an ∼0.8 Mb linkage region to chromosome 20 p. Subsequent screening revealed the NOP56 expansion in eight additional Galician ataxia kindreds. While normal alleles contain 5–14 hexanucleotide repeats, expanded alleles range from ∼650 to 2500 repeats, within a shared haplotype. Further expansion of repeat size was frequent, especially upon paternal transmission, while instances of allele contraction were observed in maternal transmissions. We found a total of 63 individuals carrying the mutation, 44 of whom were confirmed to be clinically affected; over 400 people are at risk. We describe here the detailed clinical picture, consisting of a late-onset, slowly progressive cerebellar syndrome with variable eye movement abnormalities and sensorineural hearing loss. There were signs of denervation in the tongue, as well as mild pyramidal signs, but otherwise no signs of classical amyotrophic lateral sclerosis. Magnetic resonance imaging findings were consistent with the clinical course, showing atrophy of the cerebellar vermis in initial stages, later evolving to a pattern of olivo-ponto-cerebellar atrophy. We estimated the origin of the founder mutation in Galicia to have occurred ∼1275 years ago. Out of 160 Galician families with spinocerebellar ataxia, 10 (6.3%) were found to have spinocerebellar ataxia 36, while 15 (9.4%) showed other of the routinely tested dominant spinocerebellar ataxia types. Spinocerebellar ataxia 36 is thus, so far, the most frequent dominant spinocerebellar ataxia in this region, which may have implications for American countries associated with traditional Spanish emigration

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). Methods: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (b-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Results: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with b-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. Conclusion: In patients with PCa and bone metastases treated with ZA, b-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially importantThis study was supported by Novartis Oncology Spai

Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions

Most monogenic disorders have a primary clinical presentation. Inherited ISG15 deficiency, however, has manifested with two distinct presentations to date: susceptibility to mycobacterial disease and intracranial calcifications from hypomorphic interferon-II (IFN-II) production and excessive IFN-I response, respectively. Accordingly, these patients were managed for their infectious and neurologic complications. Herein, we describe five new patients with six novel ISG15 mutations presenting with skin lesions who were managed for dermatologic disease. Cellularly, we denote striking specificity to the IFN-I response, which was previously assumed to be universal. In peripheral blood, myeloid cells display the most robust IFN-I signatures. In the affected skin, IFN-I signaling is observed in the keratinocytes of the epidermis, endothelia, and the monocytes and macrophages of the dermis. These findings define the specific cells causing circulating and dermatologic inflammation and expand the clinical spectrum of ISG15 deficiency to dermatologic presentations as a third phenotype co-dominant to the infectious and neurologic manifestations.Fil: Martin Fernandez, Marta. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia SauditaFil: Bravo García Morato, María. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Gruber, Conor. Icahn School Of Medicine At Mount Sinai; Estados Unidos. King Saud University; Arabia SauditaFil: Murias Loza, Sara. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Malik, Muhammad Nasir Hayat. Twincore; Alemania. University Of Lahore; Países Bajos. Leibniz Universitat Hannover; Alemania. Helmholtz Gemeinschaft; AlemaniaFil: Alsohime, Fahad. King Saud University; Arabia SauditaFil: Alakeel, Abdullah. King Saud University; Arabia SauditaFil: Valdez, Rita. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Buta, Sofija. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Buda, Guadalupe. Bitgenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; ArgentinaFil: Marti, Marcelo Adrian. Bitgenia; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Biología Celular e Histología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Larralde, Margarita. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Boisson, Bertrand. L'institut Des Maladies Génétiques Imagine; Francia. The Rockefeller University; Estados Unidos. Universite de Paris; FranciaFil: Feito Rodriguez, Marta. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Qiu, Xueer. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Chrabieh, Maya. L'institut Des Maladies Génétiques Imagine; FranciaFil: Al Ayed, Mohammed. Najran University; Arabia SauditaFil: Al Muhsen, Saleh. King Saud University; Arabia SauditaFil: Desai, Jigar V.. National Institutes of Health; Estados UnidosFil: Ferre, Elise M.N.. National Institutes of Health; Estados UnidosFil: Rosenzweig, Sergio D.. National Institutes of Health; Estados UnidosFil: Amador-Borrero, Blanca. Icahn School Of Medicine At Mount Sinai; Estados UnidosFil: Bravo-Gallego, Luz Yadira. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Olmer, Ruth. Hannover Medical School; Alemania. German Center for Lung Research; AlemaniaFil: Merkert, Sylvia. Hannover Medical School; Alemania. German Center for Lung Research; AlemaniaFil: Bret, Montserrat. Instituto de Investigacion del Hospital de la Paz.; EspañaFil: Sood, Amika K.. University of North Carolina; Estados UnidosFil: Al-rabiaah, Abdulkarim. King Saud University; Arabia SauditaFil: Temsah, Mohamad Hani. King Saud University; Arabia SauditaFil: Halwani, Rabih. University of Sharjah; Emiratos Arabes UnidosFil: Hernandez, Michelle Marilyn. University of North Carolina; Estados UnidosFil: Pessler, Frank. Twincore; Alemania. Helmholtz Centre for Infection Research; AlemaniaFil: Casanova, Jean Laurent. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Howard Hughes Medical Institute; Estados Unidos. Universite de Paris; FranciaFil: Bustamante, Jacinta. The Rockefeller University; Estados Unidos. Necker Hospital for Sick Children; Francia. Universite de Paris; FranciaFil: Lionakis, Michail S.. National Institutes of Health; Estados UnidosFil: Bogunovic, Dusan. Icahn School Of Medicine At Mount Sinai; Estados Unido

Clinical Predictors of Hyperperfusion Syndrome Following Carotid Stenting: Results From a National Prospective Multicenter Study

[Objectives] The aim of the HISPANIAS (HyperperfusIon Syndrome Post-carotid ANgIoplasty And Stenting) study was to define CHS rates and develop a clinical predictive model for cerebral hyperperfusion syndrome (CHS) after carotid artery stenting (CAS).[Background] CHS is a severe complication following CAS. The presence of clinical manifestations is estimated on the basis of retrospective reviews and is still uncertain.[Methods] The HISPANIAS study was a national prospective multicenter study with 14 recruiting hospitals. CHS was classified as mild (headache only) and moderate-severe (seizure, impaired level of consciousness, or development of focal neurological signs).[Results] A total of 757 CAS procedures were performed. CHS occurred in 22 (2.9%) patients, in which 16 (2.1%) had moderate-severe CHS and 6 (0.8%) had mild CHS (only headache). The rate of hemorrhages was 0.7% and was associated with high mortality (20%). Pre-operative predictors of moderate-severe CHS in multivariate analysis were female sex (odds ratio [OR]: 3.24; 95% confidence interval [CI]: 1.11 to 9.47; p = 0.03), older patients (OR: 1.09; 95% CI: 1.01 to 1.17; p = 0.02), left carotid artery treated (OR: 4.13; 95% CI: 1.11 to 15.40; p = 0.03), and chronic renal failure (OR: 6.29; 95% CI: 1.75 to 22.57; p = 0.005). The area under the curve of this clinical and radiological model was 0.86 (95% CI: 0.81 to 0.92; p = 0.001).[Conclusions] The rate of CHS in the HISPANIAS study was 2.9%, with moderate-severe CHS of 2.1%. CHS was independently associated with female sex, older age, history of chronic kidney disease, and a treated left carotid artery. Although further investigations are needed, the authors propose a model to identify high-risk patients and develop strategies to decrease CHS morbidity and mortality in the future.This study was supported by a Spanish grant from the Instituto de Salud Carlos III (ISCIII-FIS IP14/00971, 2014–2017). The ITRIBIS project has the registration number REGPOT-2013-1. Cooperative Cerebrovascular Disease Research Network (INVICTUS+) (RD16/0019/0015). Dr. Mancha is supported by a Río Hortega contract (CM16/00015). Abbott and Grifols have partial financial supported the conduction of the HISPANIAS project but had no role in the design of the study, interpretation of the data, or manuscript approval.Peer reviewe