Craniodental Morphology and Systematics of a New Family of Hystricognathous Rodents (Gaudeamuridae) from the Late Eocene and Early Oligocene of Egypt

BACKGROUND: Gaudeamus is an enigmatic hystricognathous rodent that was, until recently, known solely from fragmentary material from early Oligocene sites in Egypt, Oman, and Libya. Gaudeamus' molars are similar to those of the extant cane rat Thryonomys, and multiple authorities have aligned Gaudeamus with Thryonomys to the exclusion of other living and extinct African hystricognaths; recent phylogenetic analyses have, however, also suggested affinities with South American caviomorphs or Old World porcupines (Hystricidae). METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the oldest known remains of Gaudeamus, including largely complete but crushed crania and complete upper and lower dentitions. Unlike younger Gaudeamus species, the primitive species described here have relatively complex occlusal patterns, and retain a number of plesiomorphic features. Unconstrained parsimony analysis nests Gaudeamus and Hystrix within the South American caviomorph radiation, implying what we consider to be an implausible back-dispersal across the Atlantic Ocean to account for Gaudeamus' presence in the late Eocene of Africa. An analysis that was constrained to recover the biogeographically more plausible hypothesis of caviomorph monophyly does not place Gaudeamus as a stem caviomorph, but rather as a sister taxon of hystricids. CONCLUSIONS/SIGNIFICANCE: We place Gaudeamus species in a new family, Gaudeamuridae, and consider it likely that the group originated, diversified, and then went extinct over a geologically brief period of time during the latest Eocene and early Oligocene in Afro-Arabia. Gaudeamurids are the only known crown hystricognaths from Afro-Arabia that are likely to be aligned with non-phiomorph members of that clade, and as such provide additional support for an Afro-Arabian origin of advanced stem and basal crown members of Hystricognathi

Factors affecting the outcome of surgically treated non-iatrogenic traumatic cervical esophageal perforation: 28 years experience at a single center

<p>Abstract</p> <p>Background</p> <p>We reviewed our experience with non-iatrogenic traumatic cervical esophageal perforations, paying particular attention to factors affecting the outcome of such cases.</p> <p>Methods</p> <p>In total, 30 patients treated surgically between 1980 and 2008 for non-iatrogenic traumatic cervical esophageal perforation in our clinic were reviewed.</p> <p>Results</p> <p>There were 25 male and 5 female patients with a median age of 27.5 years. The type of injury was external trauma in 21 (70%) patients and endoluminal injury in the remaining 9 (30%) patients. The mechanism of injury was gunshot in 16 patients, stabbing in 4, falling in 1 (extraluminal injury), and foreign body in 9 (endoluminal injuries). The overall mortality rate was 16.6% (5/30). The mortality rate for extraluminal injuries was 19%, and for endoluminal injuries was 11.1%. Mortality in patients treated within 24 h of sustaining injury was substantially less than in those for whom diagnosis and treatment were delayed (12.5 and 21.4%, respectively). The mortality rate was 33.3% (3/9) for patients with tracheal injuries and 9.5% (2/21) for those without tracheal injuries.</p> <p>Conclusions</p> <p>A treatment delay greater than 24 h, the presence of tracheal injury, or extraluminal perforation significantly affected the outcome of surgically treated non iatrogenic traumatic cervical esophageal perforation.</p

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial

Background For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. Methods/design The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Discussion Final results of RESTART will be analysed and disseminated in 2019. Trial registration ISRCTN71907627 (www.isrctn.com/ISRCTN71907627). Prospectively registered on 25 April 2013

A description of physical therapists' knowledge in managing musculoskeletal conditions

BACKGROUND: Physical therapists increasingly provide direct access services to patients with musculoskeletal conditions, and growing evidence supports the cost-effectiveness of this mode of healthcare delivery. However, further evidence is needed to determine if physical therapists have the requisite knowledge necessary to manage musculoskeletal conditions. Therefore, the purpose of this study was to describe physical therapists' knowledge in managing musculoskeletal conditions. METHODS: This study utilized a cross-sectional design in which 174 physical therapist students from randomly selected educational programs and 182 experienced physical therapists completed a standardized examination assessing knowledge in managing musculoskeletal conditions. This same examination has been previously been used to assess knowledge in musculoskeletal medicine among medical students, physician interns and residents, and across a variety of physician specialties. RESULTS: Experienced physical therapists had higher levels of knowledge in managing musculoskeletal conditions than medical students, physician interns and residents, and all physician specialists except for orthopaedists. Physical therapist students enrolled in doctoral degree educational programs achieved significantly higher scores than their peers enrolled in master's degree programs. Furthermore, experienced physical therapists who were board-certified in orthopaedic or sports physical therapy achieved significantly higher scores and passing rates than their non board-certified colleagues. CONCLUSION: The results of this study may have implications for health and public policy decisions regarding the suitability of utilizing physical therapists to provide direct access care for patients with musculoskeletal conditions

Rem2-Targeted shRNAs Reduce Frequency of Miniature Excitatory Postsynaptic Currents without Altering Voltage-Gated Ca2+ Currents

Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) plays important roles in neuronal cell development and function. Rem2 is a member of the RGK (Rad, Rem, Rem2, Gem/Kir) subfamily of small GTPases that confers potent inhibition upon VGCCs. The physiologic roles of RGK proteins, particularly in the brain, are poorly understood. Rem2 was implicated in synaptogenesis through an RNAi screen and proposed to regulate Ca2+ homeostasis in neurons. To test this hypothesis and uncover physiological roles for Rem2 in the brain, we investigated the molecular mechanisms by which Rem2 knockdown affected synaptogenesis and Ca2+ homeostasis in cultured rat hippocampal neurons. Expression of a cocktail of shRNAs targeting rat Rem2 (rRem2) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) measured 10 d after transfection (14 d in vitro), but did not affect mEPSC amplitude. VGCC current amplitude after rRem2-targeted knockdown was not different from that in control cells, however, at either 4 or 10 d post transfection. Co-expression of a human Rem2 that was insensitive to the shRNAs targeting rRem2 was unable to prevent the reduction in mEPSC frequency after rRem2-targeted knockdown. Over-expression of rRem2 resulted in 50% reduction in VGCC current, but neither the mEPSC frequency nor amplitude was affected. Taken together, the observed effects upon synaptogenesis after shRNA treatment are more likely due to mechanisms other than modulation of VGCCs and Ca2+ homeostasis, and may be independent of Rem2. In addition, our results reveal a surprising lack of contribution of VGCCs to synaptogenesis during early development in cultured hippocampal neurons

Myogenin Regulates Exercise Capacity but Is Dispensable for Skeletal Muscle Regeneration in Adult mdx Mice

Duchenne muscular dystrophy (DMD) is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenic regulatory factor, is best known for its role in embryonic myogenesis, but its role in adult muscle maintenance and regeneration is still poorly understood. Here, we generated an mdx:Myogflox/flox mouse harboring a tamoxifen-inducible Cre recombinase transgene, which was used to conditionally delete Myog during adult life. After tamoxifen treatment, three groups of mice were created to study the effects of Myog deletion: mdx:Myogflox/flox mice (mdx), Myogflox/flox mice (wild-type), and mdx:MyogfloxΔ/floxΔ:Cre-ER mice (mdx:Myog-deleted). mdx:Myog-deleted mice exhibited no adverse phenotype and behaved normally. When run to exhaustion, mdx:Myog-deleted mice demonstrated an enhanced capacity for exercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, we found that myogenin was dispensable for muscle regeneration. Factors associated with muscle fatigue, metabolism, and proteolysis were significantly altered in mdx:Myog-deleted mice, and this might contribute to their increased exercise capacity. Our results reveal novel functions for myogenin in adult muscle and suggest that reducing Myog expression in other muscle disease models may partially restore muscle function

Re-examining the effect of door-to-balloon delay on STEMI outcomes in the context of unmeasured confounders: a retrospective cohort study

Literature studying the door-to-balloon time-outcome relation in coronary intervention is limited by the potential of residual biases from unobserved confounders. This study re-examines the time-outcome relation with further consideration of the unobserved factors and reports the population average effect. Adults with ST-elevation myocardial infarction admitted to one of the six registry participating hospitals in Australia were included in this study. The exposure variable was patient-level door-to-balloon time. Primary outcomes assessed included in-hospital and 30 days mortality. 4343 patients fulfilled the study criteria. 38.0% (1651) experienced a door-to-balloon delay of >90 minutes. The absolute risk differences for in-hospital and 30-day deaths between the two exposure subgroups with balanced covariates were 2.81 (95% CI 1.04, 4.58) and 3.37 (95% CI 1.49, 5.26) per 100 population. When unmeasured factors were taken into consideration, the risk difference were 20.7 (95% CI −2.6, 44.0) and 22.6 (95% CI −1.7, 47.0) per 100 population. Despite further adjustment of the observed and unobserved factors, this study suggests a directionally consistent linkage between longer door-to-balloon delay and higher risk of adverse outcomes at the population level. Greater uncertainties were observed when unmeasured factors were taken into consideration