Ancient papillomavirus-host co-speciation in Felidae

The evolutionary rate of feline papillomaviruses is inferred from the phylogenetic analysis of their hosts, providing evidence for long-term virus-host co-speciatio

Genomic Legacy of the African Cheetah, Acinonyx jubatus

Background Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. Results Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one \u3e100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p\u3c0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah’s extremely high (\u3e80 %) pleiomorphic sperm. Conclusions The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Analysis of the initiation of spontaneous monomorphic ventricular tachycardia by stored intracardiac electrograms

AbstractObjectives. This study was designed to analyze stored intracardiac electrograms generated during spontaneous monomorphic ventricular tachycardia to examine the possible mechanisms responsible for the initiation of ventricular tachycardia in a group of postinfarction patients.Background. Implantable cardioverter-defibrillators capable of storing electrograms during an arrhythmic event provide an intracardiac electrogram analog to Holter ambulatory electrocardiographic monitoring. Such electrograms are of value in arrhythmia diagnosis and in determining the appropriateness of implantable cardioverter-defibrillator therapy and may aid in understanding the initiation of ventricular arrhythmias.Methods. We studied 73 stored electrograms in 22 postinfarction patients with spontaneous monomorphic ventricular tachycardia. Premature depolarizations before tachycardia were classified by morphology and number. Electrogram morphology was compared with the morphology of the baseline rhythm and ventricular tachycardia. Prematurity was assessed by the coupling interval and a calculated prematurity ratio.Results. During baseline rhythm, ectopic activity was present in 30 (41%) of 73 stored episodes. Ventricular tachycardia was preceded by a short-long-short sequence in 14% of episodes and by a rapid ventricular rhythm in 5.5% of episodes. The onset of ventricular tachycardia was marked by single premature depolarizations in 33 episodes (45%), by pairs in 16 (22%) and by multiple complexes in 24 (33%). Morphology was similar to that of the ensuing tachycardia in 35 episodes (48%). The mean coupling interval was 364 ms, and the mean prematurity ratio was 0.56. In all 10 episodes (14%) where the prematurity ratio was <0.40, a short-long-short sequence was responsible. When classified by morphology, the mean prematurity ratio of depolarizations dissimilar to ventricular tachycardia (0.53) was significantly less than that of the morphologically similar group (0.60, p = 0.035).Conclusions. In this select group of postinfarction patients with recurrent sustained monomorphic ventricular tachycardia treated with implanteble cardioverter-defbrillators, ventricular tachycardia was most often preceded by late-coupled premature depolarizations. Not infrequently, a short-long-short sequence occurred before tachycardia. Premature depolarizations with a morphology different from that of the tachycardia occurred earlier in the cardiac cycle than did those with a morphology similar to that of the tachycardia. These indings may reflect different mechanisms of ventricular tachycardia initiation

RECOVER: Researching COVID to Enhance Recovery

HOW WILL RECOVER ACHIEVE ITS GOALS? NIH has selected health care institutions across the nation, including MaineHealth , to conduct this study, which is anticipated to enroll a total of 15,000 participants who have or had SARS CoV 2 infection and 2,680 control participants without a SARS CoV 2 infection.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2022/1020/thumbnail.jp

Multi-generational benefits of genetic rescue

Abstract Genetic rescue—an increase in population fitness following the introduction of new alleles—has been proven to ameliorate inbreeding depression in small, isolated populations, yet is rarely applied as a conservation tool. A lingering question regarding genetic rescue in wildlife conservation is how long beneficial effects persist in admixed populations. Using data collected over 40 years from 1192 endangered Florida panthers (Puma concolor coryi) across nine generations, we show that the experimental genetic rescue implemented in 1995—via the release of eight female pumas from Texas—alleviated morphological, genetic, and demographic correlates of inbreeding depression, subsequently preventing extirpation of the population. We present unequivocal evidence, for the first time in any terrestrial vertebrate, that genetic and phenotypic benefits of genetic rescue remain in this population after five generations of admixture, which helped increase panther abundance (> fivefold) and genetic effective population size (> 20-fold). Additionally, even with extensive admixture, microsatellite allele frequencies in the population continue to support the distinctness of Florida panthers from other North American puma populations, including Texas. Although threats including habitat loss, human-wildlife conflict, and infectious diseases are challenges to many imperiled populations, our results suggest genetic rescue can serve as an effective, multi-generational tool for conservation of small, isolated populations facing extinction from inbreeding