Retinitis pigmentosa and allied conditions today: a paradigm of translational research

Monogenic human retinal dystrophies are a group of disorders characterized by progressive loss of photoreceptor cells leading to visual handicap. Retinitis pigmentosa is a type of retinal dystrophy where degeneration of rod photoreceptors occurs at the early stages. At present, there are no available effective therapies to maintain or improve vision in patients affected with retinitis pigmentosa, but post-genomic studies are allowing the development of potential therapeutic approaches. This review summarizes current knowledge on genes that have been identified to be responsible for retinitis pigmentosa, the involvement of these genes in the different forms of the disorder, the role of the proteins encoded by these genes in retinal function, the utility of genotyping, and current efforts to develop novel therapies

La integridad científica: perspectiva de un investigador

La integridad científica: perspectiva de un investigador, Carmen Ayuso García. Directora del Instituto de Investigación Sanitaria. Fundación Jiménez Díaz (IIS-FJD, UAM).N

Activities of Daily Living and Categorization Skills of Elderly with Cognitive Deficit: A Preliminary Study

Cognitive dysfunction affects the performance of Activities of Daily Living (ADL) and the quality of life of people with these deficits and their caregivers. To the knowledge of the authors, to date, there are few studies that focus on knowing the relationship between personal autonomy and deductive reasoning and/or categorization skills, which are necessary for the performance of the ADL. The aim of this study was to explore the relationships between ADL and categorization skills in older people. The study included 51 participants: 31 patients with cognitive impairment and 20 without cognitive impairment. Two tests were administered to assess cognitive functions: (1) the Montreal Cognitive Assessment (MoCA); and (2) the digital version of Riska Object Classification test (ROC-d). In addition, the Routine Tasks Inventory-2 (RTI-2) was applied to determine the level of independence in activities of daily living. People with cognitive impairment performed poorly in categorization tasks with unstructured information (p = 0.006). Also, the results found a high correlation between cognitive functioning and the performance of ADLs (Physical ADL: r = 0.798; p < 0.001; Instrumental ADL: r = 0.740; p < 0.001), a moderate correlation between Physical ADLs and categorization skills (unstructured ROC-d: r = 0.547; p < 0.001; structured ROC-d: r = 0.586; p < 0.001) and Instrumental ADLs and categorization skills in older people (unstructured ROC-d: r = 0.510; p < 0.001; structured ROC-d: r = 0.463; p < 0.001). The ROC-d allows the assessment of categorization skills to be quick and easy, facilitating the assessment process by OT, as well as the accuracy of the data obtained.Ministerio de Ciencia, Innovación y Universidades (Spain) RTI2018-099942-B-100Junta de Comunidades de Castilla-La Mancha SBPLY/17/180501/00049

Iridoids as DNA topoisomerase I poisons

The discovery of new topoisomerase I inhibitors is necessary since most of the antitumor drugs are targeted against type II and only a very few can specifically affect type I. Topoisomerase poisons generate toxic DNA damage by stabilization of the covalent DNA-topoisomerase cleavage complex and some have therapeutic efficacy in human cancer. Two iridoids, aucubin and geniposide, have shown antitumoral activities, but their activity against topoisomerase enzymes has not been tested. Here it was found that both compounds are able to stabilize covalent attachments of the topoisomerase I subunits to DNA at sites of DNA strand breaks, generating cleavage complexes intermediates so being active as poisons of topoisomerase I, but not topoisomerase II. This result points to DNA damage induced by topoisomerase I poisoning as one of the possible mechanisms by which these two iridoids have shown antitumoral activity, increasing interest in their possible use in cancer chemoprevention and therapy.Ministerio de Ciencia y Tecnología de España. SAF 2000-016

El Entremés de la venta, de Quevedo

Los autores publican en este artículo una edición crítica del Entremés de la venta de don Francisco de Quevedo. El principal objetivo del artículo es la fijación textual y la redacción del aparato de notas. Análisis literarios más demorados se incluirán en un volumen de teatro completo que están preparando. The authors of this article publish a critical edition of Quevedo’s Entremés de la Venta. The main purpose of this article is the textual fixation and notes. A more detailed analysis of this interlude will be included in the volume of Quevedo’s theater that Arellano and García Valdés are preparing

Androgen receptor polyQ alleles and COVID-19 severity in men: A replication study.

Background Ample evidence indicates a sex-related difference in severity of COVID-19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID-19 severity. Objective To test the association between the androgen receptor polyQ polymorphism and COVID-19 severity in a large cohort of COVID-19 male patients. Materials and methods This study included 1136 male patients infected with SARS-CoV-2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short (<23 repeats) or long (≥23 repeats) allele carriers. The association between polyQ alleles (short or long) and COVID-19 severity was assessed by Chi-squared (Chi2) and logistic regression analysis. Results The mean number of polyQ CAG repeats was 22 (±3). Patients were classified as oligosymptomatic (15.5%), hospitalized (63.2%), and severe patients (21.3%) requiring substantial respiratory support. PolyQ alleles distribution did not show significant differences between severity classes in our cohort (Chi2 test p > 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis). Discussion Androgen sensitivity may be a critical factor in COVID-19 disease severity. However, we did not find an association between the polyQ polymorphism and the COVID-19 severity. Additional studies are needed to clarify the mechanism underlying the association between androgens and COVID-19 outcome. Conclusions The results obtained in our study do not support the role of this polymorphism as biomarker of COVID-19 severity.post-print253 K

Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID‑19.

Rare variants afecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n= 44). To this end, diferent etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodefciencies or blood coagulation were studied. We detected 44 diferent variants of interest, in 29 diferent patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially infuence COVID-19 outcome in our cohort of patients. Further studies are needed to confrm the ultimate role of the genetic variants described in the present study on COVID-19 severitypost-print2807 K

Identification Of Mitotically Competent SOX2+ Cells In White Matter Of Normal Human Adult Brain

SOX2 expression is linked to the undifferentiated state of stem cells in mammalian neurogenic niches. While its expression has been reported in the adult human subventricular zone (SVZ), to date it has not been detected in adult human white matter. Here we describe a population of SOX2+ cells from the white matter of the adult human temporal lobe, which proliferate and express glial markers in vitro