Persistent bradycardia after hypoglycaemia: a case report and a brief literature review

Hypoglycaemia can cause cardiac arrhythmias such as QT interval prolongation and ventricular arrhythmias. Supraventricular arrhythmias and sinus bradycardia were rarely reported. We present the clinical case of an 84- year-old man who developed a persistent bradycardia after a hypoglycaemic episode. After restoration of normoglycaemia, bradycardia persisted for almost eighteen hours, without QT prolongation or any symptoms. Hypoglycaemia is an unusual cause of bradyarrhytmias mainly mediated by neurologic and endocrine systems. Our clinical case supports recent recommendations for more relaxed inpatient glycaemic targets in frail older adults who may be particularly vulnerable to hypoglycaemia and its consequences

A Gigantic, Exceptionally Complete Titanosaurian Sauropod Dinosaur from Southern Patagonia, Argentina

Titanosaurian sauropod dinosaurs were the most diverse and abundant large-bodied herbivores in the southern continents during the final 30 million years of the Mesozoic Era. Several titanosaur species are regarded as the most massive land-living animals yet discovered; nevertheless, nearly all of these giant titanosaurs are known only from very incomplete fossils, hindering a detailed understanding of their anatomy. Here we describe a new and gigantic titanosaur, Dreadnoughtus schrani, from Upper Cretaceous sediments in southern Patagonia, Argentina. Represented by approximately 70% of the postcranial skeleton, plus craniodental remains, Dreadnoughtus is the most complete giant titanosaur yet discovered, and provides new insight into the morphology and evolutionary history of these colossal animals. Furthermore, despite its estimated mass of about 59.3 metric tons, the bone histology of the Dreadnoughtus type specimen reveals that this individual was still growing at the time of death

A new large-bodied oviraptorosaurian theropod dinosaur from the Latest Cretaceous of Western North America

The oviraptorosaurian theropod dinosaur clade Caenagnathidae has long been enigmatic due to the incomplete nature of nearly all described fossils. Here we describe Anzu wyliei gen. et sp. nov., a new taxon of large-bodied caenagnathid based primarily on three well-preserved partial skeletons. The specimens were recovered from the uppermost Cretaceous (upper Maastrichtian) Hell Creek Formation of North and South Dakota, and are therefore among the stratigraphically youngest known oviraptorosaurian remains. Collectively, the fossils include elements from most regions of the skeleton, providing a wealth of information on the osteology and evolutionary relationships of Caenagnathidae. Phylogenetic analysis reaffirms caenagnathid monophyly, and indicates that Anzu is most closely related to Caenagnathus collinsi, a taxon that is definitively known only from a mandible from the Campanian Dinosaur Park Formation of Alberta. The problematic oviraptorosaurs Microvenator and Gigantoraptor are recovered as basal caenagnathids, as has previously been suggested. Anzu and other caenagnathids may have favored well-watered floodplain settings over channel margins, and were probably ecological generalists that fed upon vegetation, small animals, and perhaps eggs

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Perspectives on precision cut lung slices—powerful tools for investigation of mechanisms and therapeutic targets in lung diseases

Precision cut lung slices (PCLS) have emerged as powerful experimental tools for respiratory research. Pioneering studies using mouse PCLS to visualize intrapulmonary airway contractility have been extended to pulmonary arteries and for assessment of novel bronchodilators and vasodilators as therapeutics. Additional disease-relevant outcomes, including inflammatory, fibrotic, and regenerative responses, are now routinely measured in PCLS from multiple species, including humans. This review provides an overview of established and innovative uses of PCLS as an intermediary between cellular and organ-based studies and focuses on opportunities to increase their application to investigate mechanisms and therapeutic targets to oppose excessive airway contraction and fibrosis in lung diseases

Calibrated phylogeny of oviraptorosaurian theropods showing hypothesized position of <i>Anzu wyliei</i> gen. et sp. nov.

<p>Depicted topology is the strict consensus of seven most parsimonious trees of 498 steps resulting from an analysis of 34 taxa (31 oviraptorosaurs) scored for 230 morphological characters (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092022#pone-0092022-g006" target="_blank">Figure 6B</a>). Numbers adjacent to each node are Bremer support values; named nodes are indicated with black dots. Thick black bars indicate stratigraphic ranges of each taxon; small crossbars at ends of some bars indicate taxa that are especially poorly stratigraphically constrained (e.g., most Asian Late Cretaceous forms). Time scale follows <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092022#pone.0092022-Walker1" target="_blank">[98]</a>. Sources for stratigraphic ranges of included taxa are provided in Table S9 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092022#pone.0092022.s001" target="_blank">File S1</a>.</p

Craniomandibular skeleton of <i>Anzu wyliei</i> gen. et sp. nov.

<p>(<b>A</b>) Reconstructed skull and mandible in left lateral view, with preserved bones in gray. (<b>B</b>) Left premaxilla of CM 78001 in lateral view. (<b>C</b>) Left maxilla of CM 78001 in lateral view. (<b>D</b>) Left jugal of CM 78001 in lateral view. (<b>E</b>) Braincase with articulated quadrates and pterygoids of CM 78001 in posterior view. Reconstructed mandible of CM 78000 in left lateral (<b>F</b>) and dorsal (<b>G</b>) views (hatching indicates broken areas, dashed lines indicate restoration). Abbreviations: ang, angular; aof, antorbital fenestra; ap, ascending process; bpt, basipterygoid process; d, dentary; emf, external mandibular fenestra; fm, foramen magnum; lf, lateral flange; lg, lateral groove; lgl, lateral facet of mandibular glenoid; lr, lingual ridge; mgl, medial facet of mandibular glenoid; oc, occipital condyle; pdp, posterodorsal process; pop, paroccipital process; por, postorbital process; pt, pterygoid; pvp, posteroventral process; q, quadrate; qjp, quadratojugal process; r, retroarticular process; sac, surangular–articular–coronoid complex. Scale bars  = 10 cm in A; 1 cm in B–G.</p

MRF 319, a partial oviraptorosaurian skeleton referred to <i>Anzu wyliei</i> gen. et sp. nov.

<p>(<b>A</b>) Skeletal reconstruction in left lateral view, with preserved bones in gray and bones represented in other <i>Anzu</i> specimens in white (hatching indicates heavily reconstructed portions of the ilia of CM 78001). Middle-posterior (ninth?) cervical vertebra in (<b>B</b>) anterior, (<b>C</b>) left lateral, and (<b>D</b>) dorsal views. Posterior (11^th?) cervical vertebra in (<b>E</b>) anterior, (<b>F</b>) left lateral, and (<b>G</b>) dorsal views. Posterior (12^th?) cervical vertebra in (<b>H</b>) anterior, (<b>I</b>) left lateral, and (<b>J</b>) dorsal views. Anteroposteriorly crushed left radius in lateral (<b>K</b>) and anterior (<b>L</b>) views. Mediolaterally crushed left ulna in lateral (<b>M</b>) and anterior (<b>N</b>) views. (<b>O</b>) Partial left scapulocoracoid in lateral view. Dorsal rib in anterior (<b>P</b>) and posterior (<b>Q</b>) views. Abbreviations: acr, acromial process; cr, cervical rib; dip, distal processes; pat, pathology; pf, pneumatic fossa. Scale bars  = 50 cm in A; 1 cm in B–Q.</p