Endovascular therapy in acute ischemic stroke with poor reperfusion is associated with worse outcomes compared with best medical management: a HERMES substudy

Background: Functional outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO) undergoing endovascular treatment (EVT) with poor reperfusion were compared with patients with AIS-LVO treated with best medical management only. Methods: Data are from the HERMES collaboration, a patient-level meta-analysis of seven randomized EVT trials. Baseline characteristics and functional outcomes (modified Rankin Scale (mRS) score at 90 days) were compared between patients with poor reperfusion (defined as modified Thrombolysis in Cerebral Infarction Score 0–1 on the final intracranial angiography run as assessed by the central imaging core laboratory) and patients in the control arm with multivariable logistic ordinal logistic regression adjusted for pre-specified baseline variables. Results: 972 of 1764 patients from the HERMES collaboration were included in the analysis: 893 in the control arm and 79 in the EVT arm with final mTICI 0–1. Patients with poor reperfusion who underwent EVT had higher baseline National Institutes of Health Stroke Scale than controls (median 19 (IQR 15.5–21) vs 17 (13–21), P=0.011). They also had worse mRS at 90 days compared with those in the control arm in adjusted analysis (median 4 (IQR 3–6) vs median 4 (IQR 2–5), adjusted common OR 0.59 (95% CI 0.38 to 0.91)). Symptomatic intracranial hemorrhage was not different between the two groups (3.9% vs 3.5%, P=0.75, adjusted OR 0.94 (95% CI 0.23 to 3.88)). Conclusion: Poor reperfusion after EVT was associated with worse outcomes than best medical management, although no difference in symptomatic intracranial hemorrhage was seen. These results emphasize the need for additional efforts to further improve technical EVT success rates

Disrupted structure and aberrant function of CHIP mediates the loss of motor and cognitive function in preclinical models of SCAR16

CHIP (carboxyl terminus of heat shock 70-interacting protein) has long been recognized as an active member of the cellular protein quality control system given the ability of CHIP to function as both a co-chaperone and ubiquitin ligase. We discovered a genetic disease, now known as spinocerebellar autosomal recessive 16 (SCAR16), resulting from a coding mutation that caused a loss of CHIP ubiquitin ligase function. The initial mutation describing SCAR16 was a missense mutation in the ubiquitin ligase domain of CHIP (p.T246M). Using multiple biophysical and cellular approaches, we demonstrated that T246M mutation results in structural disorganization and misfolding of the CHIP U-box domain, promoting oligomerization, and increased proteasome-dependent turnover. CHIP-T246M has no ligase activity, but maintains interactions with chaperones and chaperone-related functions. To establish preclinical models of SCAR16, we engineered T246M at the endogenous locus in both mice and rats. Animals homozygous for T246M had both cognitive and motor cerebellar dysfunction distinct from those observed in the CHIP null animal model, as well as deficits in learning and memory, reflective of the cognitive deficits reported in SCAR16 patients. We conclude that the T246M mutation is not equivalent to the total loss of CHIP, supporting the concept that disease-causing CHIP mutations have different biophysical and functional repercussions on CHIP function that may directly correlate to the spectrum of clinical phenotypes observed in SCAR16 patients. Our findings both further expand our basic understanding of CHIP biology and provide meaningful mechanistic insight underlying the molecular drivers of SCAR16 disease pathology, which may be used to inform the development of novel therapeutics for this devastating disease

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

Comparisons between nine-banded armadillo (Dasypus novemcinctus) populations in Brazil and the United States

We compared characteristics of a population of nine-banded armadillos (Dasypus novemcinctus) studied in the southern United States with a population found in the Atlantic coastal rainforest of Brazil. Adult armadillos in Brazil weighed less than those in the U.S., but when weight was accounted for, did not differ in other measures of body size. However, juveniles in the U.S. were proportionately bigger than those in Brazil. Armadillos in Brazil were less abundant (numbers sighted per h of observation) and were active later at night than those in the U.S. Adult sex-ratios were male-biased in both populations. Finally, there was no significant difference in the incidence of littermate associations observed in the two populations, but groups of juveniles (which included non-littermates) were observed more frequently in the U.S. Many of these differences may be due to the fact that armadillos are hunted extensively in Brazil but not in the United States

Dynamics of leprosy in Nine-Banded Armadillos: Net reproductive number and effects on host population dynamics

Leprosy (or Hansen’s disease) remains an important public health challenge globally, with an estimated 5.5 million total number of cases and 200,000–300,000 new cases reported annually. The nine-banded armadillo (Dasypus novemcinctus) is the only known natural non-human vertebrate host of Mycobacterium leprae, the causative agent of leprosy, in the Americas, yet gaps in knowledge remain regarding the dynamics of leprosy in wild populations. Here, we used data from a six-year study of a population of armadillos in Mississippi, USA to quantify the influence of leprosy on armadillo population dynamics, and to investigate leprosy dynamics within the host population. Leprosy reduced annual survival of adult armadillos by ∼15%, and growth rate of the population by ∼13%. The annual infection rate for adult armadillos (i.e., probability that a non-leprous adult armadillo seroconverts, conditional on survival) was 0.18, with no possibility of recovery. Assuming frequency-dependent transmission of leprosy, 18% to 25% of the adult armadillos will acquire leprosy infection in the long run. Finally, the basic reproductive ratio (R0) was 1.36, suggesting 36% increase in seroprevalence per leprosy generation. Assuming that leprosy generation time is 3–5 years, M. leprae will spread within the armadillo population at the rate of 7–12% per year. Our results are consistent with recent evidence that leprosy infection in armadillos in the USA is spreading rapidly with a concomitant increase in risk for zoonotic transmissions

A New Spanish Grammar, Or the Elements of the Spanish Language ...

Genetic data from polymorphic microsatellite loci were employed to estimate paternity and maternity in a local population of nine-banded armadillos (Dasypus novemcinctus) in northern Florida. The parentage assessments took advantage of maximum likelihood procedures developed expressly for situations when individuals of neither gender can be excluded a priori as candidate parents. The molecular data for 290 individuals, interpreted alone and in conjunction with detailed biological and spatial information for the population, demonstrate high exclusion probabilities and reasonably strong likelihoods of genetic parentage assignment in many cases; low mean probabilities of successful reproductive contribution to the local population by individual armadillo adults in a given year; and statistically significant microspatial associations of parents and their offspring. Results suggest that molecular assays of highly polymorphic genetic systems can add considerable power to assessments of biological parentage in natural populations even when neither parent is otherwise known