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

Immature and mature sperm morphometry in fresh and frozen-thawed falcon ejaculates

Sperm morphometry is one characteristic which may be useful in prediction of fertility and sperm freezability in a species. Knowledge of the sperm characteristics of the ejaculate and the morphometric descriptors is necessary to effectively develop sperm cryopreservation. The aim of the current study was to provide a general description of the sperm from two falcon species (Peregrine falcon Falco peregrinus peregrinus/brookei and Gyrfalcon Falco rusticolus) including immature sperm, sperm head morphometric descriptors, and the existence of mature sperm subpopulations. Semen samples were collected by massage and voluntary false copulation and diluted with Lake and Ravie medium. Smears were prepared of the diluted samples, stained with Hemacolor, and subjected to: 1) morphological analysis (bright field optical microscopy), and 2) computerised morphometric analysis; each sperm head was measured for length, width, area and perimeter. In addition, in the Gyrfalcon, pooled semen was frozen in pellets using DMA as a cryoprotectant and the analyses repeated after thawing. The mean percentage of immature sperm (spermatocytes and spermatids) was similarly high in all species/subspecies: Brookei Peregrine falcon (F. p. brookei) 55.5%, European Peregrine falcon (F. p. peregrinus) 65.5% and Gyrfalcon 64.7%. Clustering analyses identified four subpopulations of mature spermatozoa with different morphometric characteristics (P < 0.001). The relative proportions of these subpopulations were similar in all three species. The mean values recorded for the morphometric variables of the four subpopulations were, however, lower (P < 0.001) in the thawed Gyrfalcon samples than in fresh samples. The results support the idea of pleiomorphy as a characteristic of raptor mature sperm. This finding, plus that of the existence of four sperm subpopulations with different morphometric characteristics, may be important in the future development of cryopreservation protocols for falcon sperm.This work was funded by INIA grant RZ2012-00013-C02., and GAMESA grant Cryoraptor.Peer Reviewe

Characterization of natural ejaculates and sperm cryopreservation in a golden eagle (Aquila chrysaetus)

This paper describes the sperm characteristics and response to cooling and freezing of naturally ejaculated semen from a captive, adult golden eagle (Aquila chrysaetus) trained to allow sperm recovery via cooperative copulation. A basic spermiogram was prepared, and sperm motility and morphometric variables recorded using a computer-aided system. For sperm storage, the effects of a polyvinylpyrrolidone-based extender were evaluated at 5°C. The same extender was also used in freezing procedures in which glycerol (11%) and dimethylacetamide (6%) were compared as cryoprotectants. The extender preserved sperm viability over storage periods of up to 6 days. Although sperm motility and percentage live sperm values were poorer for frozen-thawed (5.8-14.6% and 44-42%, respectively) than for fresh samples (46.7 and 74.6%, respectively), no differences were seen between the effects of the two cryoprotectants. These results could be of use when attempting to store the sperm of golden eagles and other raptors. © 2015 American Association of Zoo Veterinarians

Impact of COVID-19 outbreak on ischemic stroke admissions and in-hospital mortality in North-West Spain

Background and purpose Spain has been one of the countries heavily stricken by COVID-19. But this epidemic has not affected all regions equally. We analyzed the impact of the COVID-19 pandemic on hospital stroke admissions and in-hospital mortality in tertiary referral hospitals from North-West Spain.Methods Spanish multicenter retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. We recorded the number of patients admitted for ischemic stroke between 30 December 2019 and 3 May 2020, the number of IVT and EVT procedures, and in-hospital mortality.Results In the study period, 2737 patients were admitted with ischemic stroke. There was a decrease in the weekly mean admitted patients during the pandemic (124 vs. 173, p<0.001). In-hospital mortality of stroke patients increased significantly (9.9% vs. 6.5%, p = 0.003), but there were no differences in the proportion of IVT (17.3% vs. 16.1%, p = 0.405) or EVT (22% vs. 23%, p = 0.504).Conclusion We found a decrease in the number of ischemic stroke admissions and an increase in in-hospital mortality during the COVID-19 epidemic in this large study from North-West Spain. There were regional changes within the network, not fully explained by the severity of the pandemic in different regions.Peer reviewe

Oral Anticoagulation and Risk of Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Mechanical Thrombectomy: Data From the Nordictus Registry

Introduction: We aimed to evaluate if prior oral anticoagulation (OAC) and its type determines a greater risk of symptomatic hemorrhagic transformation in patients with acute ischemic stroke (AIS) subjected to mechanical thrombectomy. Materials and Methods: Consecutive patients with AIS included in the prospective reperfusion registry NORDICTUS, a network of tertiary stroke centers in Northern Spain, from January 2017 to December 2019 were included. Prior use of oral anticoagulants, baseline variables, and international normalized ratio (INR) on admission were recorded. Symptomatic intracranial hemorrhage (sICH) was the primary outcome measure. Secondary outcome was the relation between INR and sICH, and we evaluated mortality and functional outcome at 3 months by modified Rankin scale. We compared patients with and without previous OAC and also considered the type of oral anticoagulants. Results: About 1.455 AIS patients were included, of whom 274 (19%) were on OAC, 193 (70%) on vitamin K antagonists (VKA), and 81 (30%) on direct oral anticoagulants (DOACs). Anticoagulated patients were older and had more comorbidities. Eighty-one (5.6%) developed sICH, which was more frequent in the VKA group, but not in DOAC group. OAC with VKA emerged as a predictor of sICH in a multivariate regression model (OR, 1.89 [95% CI, 1.01-3.51], p = 0.04) and was not related to INR level on admission. Prior VKA use was not associated with worse outcome in the multivariate regression model nor with mortality at 3 months. Conclusions: OAC with VKA, but not with DOACs, was an independent predictor of sICH after mechanical thrombectomy. This excess risk was associated neither with INR value by the time thrombectomy was performed, nor with a worse functional outcome or mortality at 3 months

Impact of COVID‐19 outbreak in reperfusion therapies of acute ischemic stroke in North‐West Spain

Since the first reported case in early December 2019, severe acute respiratory coronavirus 2 (SARS‐CoV‐2) infection, known as Coronavirus Disease 2019 (COVID‐19), has spread all over the world (1‐3). As of June 4th, more than 6 million cases and 350,000 deaths have been reported worldwide (4). Treating these patients and containing the outbreak has become the main priority in any center, arising the risk of possible collateral damage on patients with other acute diseases due to the collapse of the pre‐ and intra‐hospital emergency care systems.Peer reviewe

CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype

[Purpose]: CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. Here we tested the hypothesis that, although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism.[Methods]: We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from 9 patients using high-throughput, deep sequencing.[Results]: We identified five activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders.[Conclusion]: We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO. We also report an update of the phenotype and natural history of the syndrome.This research was supported by the project “Genetics of vascular and lymphatic malformations” financed with funds donated by Asociación Ultrafondo and Villareal FC, cofinanced by project IP-17 from the funding call “Todos Somos Raros” (Telemaraton TVE promoted by Fundación Isabel Gemio, Federación ASEM, and Federación Española de Enfermedades Raras), cofinanced by the Instituto de Salud Carlos III, FEDER FUNDS FIS PI15/01481, and IIS-Fundación Jiménez Díaz UAM Genome Medicine Chair.Peer reviewe