Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population

Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, >= 27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with >= 27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with = 27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype

Collagen XIX Alpha 1 improves prognosis in amyotrophic lateral sclerosis

The identification of more reliable diagnostic or prognostic biomarkers in age-related neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), is urgently needed. The objective in this study was to identify more reliable prognostic biomarkers of ALS mirroring neurodegeneration that could be of help in clinical trials. A total of 268 participants from three cohorts were included in this study. The muscle and blood cohorts were analyzed in two cross-sectional studies, while the serial blood cohort was analyzed in a longitudinal study at 6-monthly intervals. Fifteen target genes and fourteen proteins involved in muscle physiology and differentiation, metabolic processes and neuromuscular junction dismantlement were studied in the three cohorts. In the muscle biopsy cohort, the risk for a higher mortality in an ALS patient that showed high Collagen type XIX, alpha 1 (COL19A1) protein levels and a fast progression of the disease was 70.5% (P < 0.05), while in the blood cohort, this risk was 20% (P < 0.01). In the serial blood cohort, the linear mixed model analysis showed a significant association between increasing COL19A1 gene levels along disease progression and a faster progression during the follow-up period of 24 months (P < 0.05). Additionally, higher COL19A1 levels and a faster progression increased 17.9% the mortality risk (P < 0.01). We provide new evidence that COL19A1 can be considered a prognostic biomarker that could help the selection of homogeneous groups of patients for upcoming clinical trial and may be pointed out as a promising therapeutic target in ALS

Drinking patterns and effects of alcohol on instagram intimes of covid-19

Introducción: Compartir “eventos de la bebida” se ha convertido en una práctica habitual entre las personas jóvenes en redes como Instagram. La pandemia por el Covid-19 ha reestructurado tanto sus pautas de consumo de alcohol, como los usos que hacen de las redes sociales. Objetivos y Métodos: Describir en profundidad las pautas de consu- mo de alcohol y los efectos de este consumo que se muestran en Instagram en una muestra de 118 jóvenes y ado- lescentes en España a través de la etnografía digital. Resultados y Conclusiones: Instagram es parte de la fiesta, parte imbricada en la vida cotidiana de las personas jóvenes, en la que se comparten regularmente imágenes deseables de las pautas de consumo de alcohol y sus efectos. Adolescentes y jóvenes construyen un modelo online idealizado de pautas de consumo de alcohol en el que sólo son visibles los efectos de la fase de desinhibición tras el consumo y se obvian el resto de las fases de los efectos del alcohol en el organismo. Es fundamental incluir estas nuevas formas de transmisión de las pautas de consumo de alcohol en la normativa española que regula la venta y uso de alcoholIntroduction: Sharing “drinking events” has become a common practice among young people on Instagram. The Covid-19 pandemic has restructured both their alcohol consumption patterns and their use of social networks. Ob- jective and Methods: To describe in depth the patterns of alcohol consumption and the effects of this consumption shown on Instagram in a sample of 118 young people and adolescents in Spain through digital ethnography. Results and Conclusions: Instagram is part of the party, part embedded in the daily lives of young people, in which desirable images of drinking patterns and their effects are regularly shared. Adolescents and young people build an idealized online model of alcohol consumption patterns in which only the effects of the disinhibition phase after consumption are visible and the rest of the phases of the effects of alcohol on the body are ignored. It is essential to include these new forms of transmission of alcohol consumption patterns in the Spanish regulations that regulate the sale and use of alcoho

Pautas de consumo y efectos del alcohol en Instagram en tiempos de COVID-19

Introducción: Compartir “eventos de la bebida” se ha convertido en una práctica habitual entre las personas jóvenes en redes como Instagram. La pandemia por el Covid-19 ha reestructurado tanto sus pautas de consumo de alcohol, como los usos que hacen de las redes sociales. Objetivos y Métodos: Describir en profundidad las pautas de consu- mo de alcohol y los efectos de este consumo que se muestran en Instagram en una muestra de 118 jóvenes y ado- lescentes en España a través de la etnografía digital. Resultados y Conclusiones: Instagram es parte de la fiesta, parte imbricada en la vida cotidiana de las personas jóvenes, en la que se comparten regularmente imágenes deseables de las pautas de consumo de alcohol y sus efectos. Adolescentes y jóvenes construyen un modelo online idealizado de pautas de consumo de alcohol en el que sólo son visibles los efectos de la fase de desinhibición tras el consumo y se obvian el resto de las fases de los efectos del alcohol en el organismo. Es fundamental incluir estas nuevas formas de transmisión de las pautas de consumo de alcohol en la normativa española que regula la venta y uso de alcohol.Introduction: Sharing “drinking events” has become a common practice among young people on Instagram. The Covid-19 pandemic has restructured both their alcohol consumption patterns and their use of social networks. Ob- jective and Methods: To describe in depth the patterns of alcohol consumption and the effects of this consumption shown on Instagram in a sample of 118 young people and adolescents in Spain through digital ethnography. Results and Conclusions: Instagram is part of the party, part embedded in the daily lives of young people, in which desirable images of drinking patterns and their effects are regularly shared. Adolescents and young people build an idealized online model of alcohol consumption patterns in which only the effects of the disinhibition phase after consumption are visible and the rest of the phases of the effects of alcohol on the body are ignored. It is essential to include these new forms of transmission of alcohol consumption patterns in the Spanish regulations that regulate the sale and use of alcohol.Esta investigación está financiada por el Ministerio de Ciencia e Innovación. Programas Estatal de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i orientada a los Retos de la Sociedad. (PID2019-105122RB-I00/AEI/10.13039/501100011033)

Genetic Biomarkers for ALS Disease in Transgenic SOD1G93A Mice

The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS) are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1G93A mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1G93A mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10) could be considered potential genetic biomarkers of longevity in transgenic SOD1G93A mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

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

“Este tiempo me cambió la vida”: discursos y vivencias del tiempo de las empleadas de hogar durante la pandemia en Granada y Zaragoza, España

El objetivo de este artículo es analizar cómo la pandemia de la covid-19 ha afectado las percepciones y usos del tiempo de las empleadas de hogar en España, especialmente, nos concentramos en las ciudades de Granada y Zaragoza. Nuestro trabajo deriva del proyecto “El cuidado importa. Impacto de género en las cuidadoras/es de mayores y dependientes en tiempos de la Covid-19” (CUMADE) coordinado por la Universidad Rovira i Virgili de Tarragona-Cataluña (España), y llevado a cabo por equipos de investigación interdisciplinares de diez universidades españolas entre los meses de septiembre de 2020 y enero de 2021. La investigación fue de corte cualitativo basada en entrevistas en profundidad, cuyo objeto era indagar sobre el impacto de la covid-19 en el cuidado de mayores y dependientes y, más concretamente, en el sector de las trabajadoras del hogar. La temporalidad, cuya percepción social se ha visto tan afectada por la incertidumbre y la imprevisibilidad propias de la nueva situación, ofrece un interesante eje de análisis cualitativo de los discursos de las trabajadoras sobre la manera en que la pandemia ha condicionado su cotidianidad. Para ello partimos del trabajo de Ramón Ramos sobre las imágenes sociales del tiempo. Este enfoque supone un análisis original y novedoso de la realidad de las trabajadoras del hogar, al tiempo que dialoga con otros trabajos recientes sobre esta cuestión. Las imágenes del tiempo como recurso, escenario u horizonte nos sirven para analizar el discurso de nuestras entrevistadas y mostrar cómo el tiempo, entendido como categoría social, ha estructurado y organizado sus vidas, tanto en lo que han podido hacer, como en lo que no han podido hacer, en la distribución e intensificación de tareas, en sus planes a futuro y en el impacto físico y emocional de la pandemia.The purpose of this article is to analyze how the covid-19 pandemic affected the perceptions and uses of time of domestic workers in Spain, focu-sing, in particular, on the cities of Granada and Zaragoza. Our work derives from the project “El cuidado importa. Impacto de género en las cuidadoras/es de mayores y dependientes en tiempos de la Covid-19” (CUMADE) coordinated by Universidad Rovira I Virgili de Tarragona-Cataluña (Spain), and run by interdisciplinary research teams from ten Spanish universities between the months of September 2020 and January 2021. The research is qualitative, based on in-depth interviews, and designed to investigate the impact of covid-19 on the care of the elderly and dependents and, more specifically, on the domestic workers’ sector. Temporality, so severely affected by the uncertainty and unpredictability of the new situation, provides an interes-ting axis for qualitative analysis of the discourses of women workers on the way in which the pandemic has conditioned their daily lives. To undertake this analysis, we base ourselves on the work of Ramón Ramos on las imágenes sociales del tiempo (the social images of time). This approach represents an original and novel analysis of the reality of domestic workers, while at the same time dialoguing with other recent work on this issue. The images of time as a resource, scenario, or horizon serve to analyze the discourse of our inter-viewees and show how time, understood as a social category, has structured and organized their lives. We consider what they have been able to do and what they have not been able to do, the distribution and intensification of tasks, their plans for the future, and the physical and emotional impact of the pandemic.Proyecto de investigación “El cuidado importa. Impacto de género en las cuidadoras/es de mayores y dependientes en tiempos de la Covid-19” (CUMADE), financiado por el Fondo Supera Covid-19 (Santander Universidades, Consejo Superior de Investigaciones Científicas y Conferencia de Rectores de las Universidades Españolas)Proyecto “El modelo de cuidados de larga duración en transición: estrategias políti- cas, familiares y comunitarias para afrontar las consecuencias de la pandemia Covid-19” (CAREMODEL), financiado por el Ministerio de Innovación y Ciencia (PID2020-114887RB-C31

Torneo de la trucha (myxosomosis). Revisión

p. 5-28Se estudia el Torneo, vértigo o enfermedad del tambaleo de los salmónidos, sobre todo de las truchas arcoiris, producida por Myxosoma cerebralis (Protozoa, Myxosoporea), que invaden preferentemente el esqueleteo en su fase cartilaginosa, provocando deformidades cefálicas y caudales, pérdida del sentido del equilibrio (torneo) y pigmetación oscura intensa en la colaN