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

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Taller de Instrumento II - MS198 - 202102

Taller de Instrumento II es un curso práctico dirigido a los estudiantes de tercer ciclo de la carrera de música. Se dicta de manera individual y se fundamenta en la ejecución de un instrumento musical a partir de la aplicación de elementos teóricos del lenguaje musical tales como el ritmo, melodía y armonía profundizando en los modos de la escala mayor, las cuatriadas, el ejercicio de la lectura musical instrumental y la interpretación de géneros musicales peruanos y contemporáneos. El propósito del curso es dar al estudiante una base sólida para la ejecución instrumental a partir del trabajo técnico, el desarrollo de un repertorio y la aplicación de los fundamentos técnicos de ejecución en diversos géneros musicales contemporáneos. El curso se dicta en nivel 1 y trabaja dos competencias específicas: Destreza musical sobre el instrumento y destreza musical sobre el lenguaje musical. Tiene como prerrequisito el curso Taller de Instrumento I y Lectura 1y Entrenamiento Auditivo II. Es requisito para Taller de Instrumento III

Taller de Instrumento I - MS197 - 202101

Taller de Instrumento I es un curso práctico dirigido a los estudiantes de segundo ciclo de la carrera de música. Se dicta de manera individual y se fundamenta en la ejecución de un instrumento musical a partir de la aplicación de elementos teóricos del lenguaje musical tales como el ritmo, melodía y armonía profundizando en las escalas y triadas, el ejercicio de la lectura musical instrumental, y la interpretación de géneros musicales peruanos y contemporáneos. El estudiante puede escoger uno de los siguientes instrumentos que ofrece la carrera: guitarra, voz, batería, percusión, piano, bajo, violín, trompeta, trombón, saxofón. El curso se dicta en nivel 1 y trabaja una competencia específica: Destreza musical sobre el instrumento, tiene como prerrequisito el curso Clínica y Ensamble y es requisito para Taller de Instrumento II. El propósito del curso es dar al estudiante una base sólida para la ejecución instrumental, a partir del trabajo técnico, desarrollo 1de un repertorio y aplicación de los fundamentos musicales en distintos géneros musicales contemporáneos

Taller de Instrumento I - MS197 - 202102

Taller de Instrumento I es un curso práctico dirigido a los estudiantes de segundo ciclo de la carrera de música. Se dicta de manera individual y se fundamenta en la ejecución de un instrumento musical a partir de la aplicación de elementos teóricos del lenguaje musical tales como el ritmo, melodía y armonía profundizando en 1las escalas y triadas, el ejercicio de la lectura musical instrumental, y la interpretación de géneros musicales peruanos y contemporáneos. El estudiante puede escoger uno de los siguientes instrumentos que ofrece la carrera: guitarra, voz, batería, percusión, piano, bajo, violín, trompeta, trombón, saxofón. El curso se dicta en nivel 1 y trabaja una competencia específica: Destreza musical sobre el instrumento, tiene como prerrequisito el curso Clínica y Ensamble y es requisito para Taller de Instrumento II. El propósito del curso es dar al estudiante una base sólida para la ejecución instrumental, a partir del trabajo técnico, desarrollo de un repertorio y aplicación de los fundamentos musicales en distintos géneros musicales contemporáneos

Taller de Instrumento II - MS198 - 202101

Taller de Instrumento II es un curso práctico dirigido a los estudiantes de tercer ciclo de la carrera de música. Se dicta de manera individual y se fundamenta en la ejecución de un instrumento musical a partir de la aplicación de elementos teóricos del lenguaje musical tales como el ritmo, melodía y armonía profundizando en los modos de la escala mayor, las cuatriadas, el ejercicio de la lectura musical instrumental y la interpretación de géneros 1musicales peruanos y contemporáneos. El propósito del curso es dar al estudiante una base sólida para la ejecución instrumental a partir del trabajo técnico, el desarrollo de un repertorio y la aplicación de los fundamentos técnicos de ejecución en diversos géneros musicales contemporáneos. El curso se dicta en nivel 1 y trabaja dos competencias específicas: Destreza musical sobre el instrumento y destreza musical sobre el lenguaje musical. Tiene como prerrequisito el curso Taller de Instrumento I y Lectura y Entrenamiento Auditivo II. Es requisito para Taller de Instrumento III

How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort

CatedresBackground: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele