CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Tratamientos de reperfusión en el infarto cerebral agudo por disección de arterias cervicales

Resumen: Introducción: Las disecciones de arteriales cervicales (DAC) provocan hasta el 20% de los ictus isquémicos en menores de 45 años. El beneficio de los tratamientos de reperfusión en fase aguda no está plenamente clarificado. Métodos: Revisión retrospectiva de pacientes con DAC ingresados en un centro terciario de ictus desde 2010 hasta 2015. Recogemos las características basales, clínicas, los tratamientos, el pronóstico funcional y la mortalidad. Resultados: Se registraron 35 DAC (23 carotídeas/12 vertebrales). La edad media fue de 43,5 ± 9,5 años y el 67,7% fueron varones. En 10 casos (32,3%) hubo antecedente de un traumatismo. Los factores de riesgo más frecuentes fueron la hipertensión arterial (29%) y el tabaquismo (35,5%). La presentación clínica más frecuente fue el infarto cerebral en 29 pacientes (93,5%). La mediana de puntuación National Institute of Health Stroke Scale basal fue de 6 (0-41). El método diagnóstico más empleado fue la angio-TC (74,2%), seguido de resonancia magnética (64,5%) y arteriografía cerebral (45,6%). Siete pacientes (22,6%) fueron tratados con fibrinólisis intravenosa y 11 (35,5%) con tratamiento endovascular (TEV) ± fibrinólisis intravenosa. A los 3 meses, la independencia funcional (escala de Rankin 0-2) fue del 57,1% y del 63,6%, respectivamente. Falleció un paciente (3,2%). Conclusiones: La forma de presentación más frecuente de la DAC fue el infarto cerebral. Estos casos pueden beneficiarse de terapias de reperfusión, con un pronóstico similar al resto de enfermos con ictus isquémicos. Se requieren registros más extensos para conocer mejor la respuesta a los tratamientos de reperfusión en fase aguda en este grupo de pacientes. Abstract: Introduction: Cervical artery dissection (CAD) is responsible for up to 20% of all ischaemic strokes in patients younger than 45. The benefits of acute-phase reperfusion therapy in these patients have yet to be confirmed. Methods: We conducted a retrospective review of patients with CAD admitted to a comprehensive stroke centre between 2010 and 2015. We recorded baseline clinical characteristics, treatments, functional outcomes, and mortality. Results: We identified 35 cases of CAD (23 carotid/12 vertebral); mean age was 43.5  ±  9.5 years and 67.7% were men. Ten patients (32.3%) had a history of trauma. The most frequent risk factors were arterial hypertension (29%) and smoking (35.5%). The most common clinical presentation was ischaemic stroke (29 patients, 93.5%). The median baseline National Institute of Health Stroke Scale score was 6 (range, 0-41). The most frequently used diagnostic method was CT angiography (74.2%), followed by MRI (64.5%) and digital subtraction angiography (45.6%). Seven patients (22.6%) were treated with intravenous fibrinolysis and 11 (35.5%) with endovascular treatment plus intravenous fibrinolysis; at 3 months, functional independence (modified Rankin Scale scores 0-2) was achieved by 57.1% and 63.6% of these cases, respectively. One patient died (3.2%). Conclusions: In our sample, the most common form of presentation of CAD was ischaemic stroke. Reperfusion therapy seems to be a safe and effective option for these patients, and outcomes resemble those of other patients with ischaemic stroke. Larger comparative studies are necessary to better assess response to reperfusion therapy in acute ischaemic stroke. Palabras clave: Ictus isquémico, Disección carotídea, Disección vertebral, Disección arterial cervical, Fibrinólisis intravenosa, Tratamiento endovascular, Keywords: Ischaemic stroke, Carotid artery dissection, Vertebral artery dissection, Cervical artery dissection, Intravenous fibrinolysis, Endovascular treatmen

Reperfusion therapy in patients with acute ischaemic stroke caused by cervical artery dissection

Introduction: Cervical artery dissection (CAD) is responsible for up to 20% of all ischaemic strokes in patients younger than 45. The benefits of acute-phase reperfusion therapy in these patients have yet to be confirmed. Methods: We conducted a retrospective review of patients with CAD admitted to a comprehensive stroke centre between 2010 and 2015. We recorded baseline clinical characteristics, treatments, functional outcomes, and mortality. Results: We identified 35 cases of CAD (23 carotid/12 vertebral); mean age was 43.5 ± 9.5 years and 67.7% were men. Ten patients (32.3%) had a history of trauma. The most frequent risk factors were arterial hypertension (29%) and smoking (35.5%). The most common clinical presentation was ischaemic stroke (29 patients, 93.5%). The median baseline National Institute of Health Stroke Scale score was 6 (range, 0-41). The most frequently used diagnostic method was CT angiography (74.2%), followed by MRI (64.5%) and digital subtraction angiography (45.6%). Seven patients (22.6%) were treated with intravenous fibrinolysis and 11 (35.5%) with endovascular treatment plus intravenous fibrinolysis; at 3 months, functional independence (modified Rankin Scale scores 0-2) was achieved by 57.1% and 63.6% of these cases, respectively. One patient died (3.2%). Conclusions: In our sample, the most common form of presentation of CAD was ischaemic stroke. Reperfusion therapy seems to be a safe and effective option for these patients, and outcomes resemble those of other patients with ischaemic stroke. Larger comparative studies are necessary to better assess response to reperfusion therapy in acute ischaemic stroke. Resumen: Introducción: Las disecciones de arteriales cervicales (DAC) provocan hasta el 20% de los ictus isquémicos en menores de 45 años. El beneficio de los tratamientos de reperfusión en fase aguda no está plenamente clarificado. Métodos: Revisión retrospectiva de pacientes con DAC ingresados en un centro terciario de ictus desde 2010 hasta 2015. Recogemos las características basales, clínicas, los tratamientos, el pronóstico funcional y la mortalidad. Resultados: Se registraron 35 DAC (23 carotídeas/12 vertebrales). La edad media fue de 43,5 ± 9,5 años y el 67,7% fueron varones. En 10 casos (32,3%) hubo antecedente de un traumatismo. Los factores de riesgo más frecuentes fueron la hipertensión arterial (29%) y el tabaquismo (35,5%). La presentación clínica más frecuente fue el infarto cerebral en 29 pacientes (93,5%). La mediana de puntuación National Institute of Health Stroke Scale basal fue de 6 (0-41). El método diagnóstico más empleado fue la angio-TC (74,2%), seguido de resonancia magnética (64,5%) y arteriografía cerebral (45,6%). Siete pacientes (22,6%) fueron tratados con fibrinólisis intravenosa y 11 (35,5%) con tratamiento endovascular (TEV) ± fibrinólisis intravenosa. A los 3 meses, la independencia funcional (escala de Rankin 0-2) fue del 57,1% y del 63,6%, respectivamente. Falleció un paciente (3,2%). Conclusiones: La forma de presentación más frecuente de la DAC fue el infarto cerebral. Estos casos pueden beneficiarse de terapias de reperfusión, con un pronóstico similar al resto de enfermos con ictus isquémicos. Se requieren registros más extensos para conocer mejor la respuesta a los tratamientos de reperfusión en fase aguda en este grupo de pacientes. Keywords: Ischaemic stroke, Carotid artery dissection, Vertebral artery dissection, Cervical artery dissection, Intravenous fibrinolysis, Endovascular treatment, Palabras clave: Ictus isquémico, Disección carotídea, Disección vertebral, Disección arterial cervical, Fibrinólisis intravenosa, Tratamiento endovascula

Use of e-mail for Parkinson's disease consultations: Are answers just a click away?

Introduction: The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs). Methods: We retrospectively reviewed all consecutive emails sent and received over a period of 4 months, one year after implementation of the e-mail inquiry system. All patients received the e-mail address during consultations, and PCPs, during scheduled informative meetings. We recorded and later analysed the profile of the questioner, patients’ demographic and clinical data, number of queries, reason for consultation, and actions taken. Results: From 1 January 2015 to 30 April 2015, the service received 137 emails from 63 patients (43% male, mean age 71 ± 10.5) diagnosed with Parkinson's disease (76%), atypical parkinsonism (10%), and others (14%); 116 responses were sent. Twenty (32%) emails were written by patients, 38 (60%) by their caregivers, and 5 (8%) by their PCPs. The reasons for consultation were clinical in 50 cases (80%): 16 (32%) described clinical deterioration, 14 (28%) onset of new symptoms, and 20 (40%) side effects or concerns about medications. In 13 cases (20%), the query was bureaucratic: 11 were related to appointments (85%) and 2 were requests for clinical reports (15%). In response, new appointments were scheduled in 9 cases (14%), while the rest of the questions were answered by email. Patients were satisfied overall and the additional care burden on specialists was not excessive. Conclusions: Implementing an e-mail-based consultation system is feasible in MD units. It facilitates both communication between neurologists and patients and continued care in the primary care setting. Resumen: Introducción: La problemática de los trastornos del movimiento (TM) es compleja y la duración y frecuencia de las consultas presenciales puede estar limitada por problemas de espacio y tiempo. Analizamos el funcionamiento de un servicio de atención por correo electrónico institucional para médicos de Atención Primaria (MAP) y pacientes en la Unidad de Trastornos del Movimiento (UTM). Métodos: Se revisaron retrospectivamente los correos electrónicos enviados y recibidos en un periodo de 4 meses, un año tras su implantación. La dirección se proporcionaba en consulta y mediante sesiones informativas a los MAP del área. Se analizaron datos clínicos y demográficos de los pacientes, tipo de interlocutor, número de consultas, motivo y actuaciones derivadas de ellas. Resultados: Del 1 de enero al 30 de abril de 2015 se recibieron 137 correos de 63 pacientes (43% varones; edad 71 ± 10,5 años) diagnosticados de enfermedad de Parkinson (76%), parkinsonismos atípicos (10%) y otros (14%), y se enviaron 116 respuestas. En 20 casos (32%) fueron redactados por el paciente, en 38 (60%) por sus familiares y en 5 (8%) por MAP. Los motivos de consulta fueron clínicos en 50 casos (80%): deterioro clínico (16; 32%), nuevos síntomas (14; 28%), efectos secundarios o dudas sobre medicación (20; 40%). Como consecuencia, se adelantó una cita programada en 9 casos (14%), mientras que el resto se solucionaron por correo electrónico. En 13 (20%), el motivo de consulta fue burocrático: relacionado con citas (11, 85%) y solicitud de informe (2, 15%). La satisfacción fue generalizada, sin constituir una sobrecarga asistencial excesiva para los facultativos responsables. Conclusiones: La implantación de una consulta por correo electrónico es factible en UTM, facilita la comunicación médico-paciente y la continuidad asistencial con Atención Primaria. Keywords: E-consult, Email-based consultation, Telemedicine, Electronic consultation, Parkinson's disease, Palabras clave: Consulta electrónica, Atención por mail, Telemedicina, Atención electrónica, Parkinso

El correo electrónico en la consulta de Parkinson: ¿soluciones a un clic?

Resumen: Introducción: La problemática de los trastornos del movimiento (TM) es compleja y la duración y frecuencia de las consultas presenciales puede estar limitada por problemas de espacio y tiempo. Analizamos el funcionamiento de un servicio de atención por correo electrónico institucional para médicos de Atención Primaria (MAP) y pacientes en la Unidad de Trastornos del Movimiento (UTM). Métodos: Se revisaron retrospectivamente los correos electrónicos enviados y recibidos en un periodo de 4 meses, un año tras su implantación. La dirección se proporcionaba en consulta y mediante sesiones informativas a los MAP del área. Se analizaron datos clínicos y demográficos de los pacientes, tipo de interlocutor, número de consultas, motivo y actuaciones derivadas de ellas. Resultados: Del 1 de enero al 30 de abril de 2015 se recibieron 137 correos de 63 pacientes (43% varones; edad 71 ± 10,5 años) diagnosticados de enfermedad de Parkinson (76%), parkinsonismos atípicos (10%) y otros (14%), y se enviaron 116 respuestas. En 20 casos (32%) fueron redactados por el paciente, en 38 (60%) por sus familiares y en 5 (8%) por MAP. Los motivos de consulta fueron clínicos en 50 casos (80%): deterioro clínico (16; 32%), nuevos síntomas (14; 28%), efectos secundarios o dudas sobre medicación (20; 40%). Como consecuencia, se adelantó una cita programada en 9 casos (14%), mientras que el resto se solucionaron por correo electrónico. En 13 (20%), el motivo de consulta fue burocrático: relacionado con citas (11, 85%) y solicitud de informe (2, 15%). La satisfacción fue generalizada, sin constituir una sobrecarga asistencial excesiva para los facultativos responsables. Conclusiones: La implantación de una consulta por correo electrónico es factible en UTM, facilita la comunicación médico-paciente y la continuidad asistencial con Atención Primaria. Abstract: Introduction: The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs). Methods: We retrospectively reviewed all consecutive emails sent and received over a period of 4 months, one year after implementation of the e-mail inquiry system. All patients received the during consultations, and PCPs, during scheduled informative meetings. We recorded and later analysed the profile of the questioner, patients’ demographic and clinical data, number of queries, reason for consultation, and actions taken. Results: From 1 January 2015 to 30 April 2015, the service received 137 emails from 63 patients (43% male, mean age 71 ± 10.5) diagnosed with Parkinson's disease (76%), atypical parkinsonism (10%), and others (14%); 116 responses were sent. Twenty (32%) emails were written by patients, 38 (60%) by their caregivers, and 5 (8%) by their PCPs. The reasons for consultation were clinical in 50 cases (80%): 16 (32%) described clinical deterioration, 14 (28%) onset of new symptoms, and 20 (40%) side effects or concerns about medications. In 13 cases (20%), the query was bureaucratic: 11 were related to appointments (85%) and 2 were requests for clinical reports (15%). In response, new appointments were scheduled in 9 cases (14%), while the rest of the questions were answered by email. Patients were satisfied overall and the additional care burden on specialists was not excessive. Conclusions: Implementing an e-mail-based consultation system is feasible in MD units. It facilitates both communication between neurologists and patients and continued care in the primary care setting. Palabras clave: Consulta electrónica, Atención por mail, Telemedicina, Atención electrónica, Parkinson, Keywords: E-consult, Email-based consultation, Telemedicine, Electronic consultation, Parkinson's diseas

Impacts of diffuse urban stressors on stream benthic communities and ecosystem functioning: A review

Catchment urbanisation results in urban streams being exposed to a multitude of stressors. Notably, stressors originating from diffuse sources have received less attention than stressors originating from point sources. Here, advances related to diffuse urban stressors and their consequences for stream benthic communities are summarised by reviewing 92 articles. Based on the search criteria, the number of articles dealing with diffuse urban stressors in streams has been increasing, and most of them focused on North America, Europe, and China. Land use was the most common measure used to characterize diffuse stressor sources in urban streams (70.7 % of the articles characterised land use), and chemical stressors (inorganic nutrients, xenobiotics, metals, and water properties, including pH and conductivity) were more frequently reported than physical or biological stressors. A total of 53.3 % of the articles addressed the impact of urban stressors on macroinvertebrates, while 35.9 % focused on bacteria, 9.8 % on fungi, and 8.7 % on algae. Regarding ecosystem functions, almost half of the articles (43.5 %) addressed changes in community dynamics, 40.3 % addressed organic matter decomposition, and 33.9 % addressed nutrient cycling. When comparing urban and non-urban streams, the reviewed studies suggest that urbanisation negatively impacts the diversity of benthic organisms, leading to shifts in community composition. These changes imply functional degradation of streams. The results of the present review summarise the knowledge gained to date and identify its main gaps to help improve our understanding of urban streams.This study has received funding from the Iberian Association of Limnology (AIL) through the project URBIFUN (Urbanization effects on the relationship between microbial biodiversity and ecosystem functioning), awarded to Míriam Colls and Ferran Romero. Authors thank as well the Basque Government (Consolidated Research Group IT951-16) and the MERLIN project 101036337 – H2020-LC-GD-2020/H2020-LC-GD-2020-3.info:eu-repo/semantics/publishedVersio

Recent developments in chemistry, coordination, structure and biological aspects of 1-(acyl/aroyl)-3-(substituted) thioureas

1-(Acyl/aroyl)-3-(substituted)thioureas are privileged architectures that have received remarkable attention of researchers in view of their variable topological aspects, binding modes and broad spectrum promising pharmacological properties. Reactivity of acyl thiourea derivatives has presented various organic transformations into other demanding scaffolds and this is an attractive strategy for synthetic chemists to access heterocyclic cores. Multiple binding sites make them flexible ligands for complexation with transition metals thus occupying a distinct position in coordination chemistry. 1-(Acyl/aroyl)-3-(substituted)thioureas have also emerged as attractive candidates in various fields such as ion sensors, corrosion inhibitors, molecular electronics, in metal extraction and in pharmaceuticals. The medicinal chemistry of this organo-sulfur framework and the derived metal complexes has witnessed fantastic progress in the current era. In continuation of our efforts to compile data on the structural aspects and numerous applications of 1-(acyl/aroyl)-3-(substituted)thiourea analogs, continuous advances have prompted us to present an overview of the last 2 years literature on this exciting family of compounds through this review article.Fil: Saeed, Aamer. Quaid-i-Azam University; PakistánFil: Qamar, Rabia. Quaid-i-Azam University; PakistánFil: Fattah, Tanzeela Abdul. Quaid-i-Azam University; PakistánFil: Flörke, Ulrich. Universität Paderborn; AlemaniaFil: Erben, Mauricio Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentin