A shared role for sonic hedgehog signalling in patterning chondrichthyan gill arch appendages and tetrapod limbs.

Chondrichthyans (sharks, skates, rays and holocephalans) possess paired appendages that project laterally from their gill arches, known as branchial rays. This led Carl Gegenbaur to propose that paired fins (and hence tetrapod limbs) originally evolved via transformation of gill arches. Tetrapod limbs are patterned by asonic hedgehog(Shh)-expressing signalling centre known as the zone of polarising activity, which establishes the anteroposterior axis of the limb bud and maintains proliferative expansion of limb endoskeletal progenitors. Here, we use loss-of-function, label-retention and fate-mapping approaches in the little skate to demonstrate that Shh secretion from a signalling centre in the developing gill arches establishes gill arch anteroposterior polarity and maintains the proliferative expansion of branchial ray endoskeletal progenitor cells. These findings highlight striking parallels in the axial patterning mechanisms employed by chondrichthyan branchial rays and paired fins/limbs, and provide mechanistic insight into the anatomical foundation of Gegenbaur's gill arch hypothesis.This research was supported by a Royal Society University Research Fellowship [UF130182 to JAG], by Plum foundation John E. Dowling and Laura and Arthur Colwin Endowed Summer Research Fellowships at the Marine Biological Laboratory to JAG, by a grant from the University of Cambridge Isaac Newton Trust to [14.23z to JAG], and by a grant from the Natural Sciences and Engineering Research Council of Canada [A5056 to BKH].This is the final version of the article. It first appeared from The Company of Biologists via http://dx.doi.org/10.1242/dev.13388

Association between osteoarthritis and cardiovascular disease: systematic review and meta-analysis

Background: To examine for a possible relationship between osteoarthritis and cardiovascular disease (CVD). Design: A systematic review and meta-analysis Methods: Published and unpublished literature from: MEDLINE, EMBASE, CINAHL, the Cochrane Library, OpenGrey and clinical trial registers. Search to 22nd November 2014. Cohort, case-control, randomised and non-randomised controlled trial papers reporting the prevalence of CVD in osteoarthritis were included. Results: Fifteen studies with 32,278,744 individuals were eligible. Pooled prevalence for overall CVD pathology in people with osteoarthritis was 38.4% (95% Confidence interval (CI): 37.2% to 39.6%). Individuals with osteoarthritis were almost three times as likely to have heart failure (Relative Risk (RR): 2.80; 95% CI: 2.25 to 3.49) or ischaemic heart disease (RR: 1.78; 95% CI: 1.18 to 2.69) compared to matched non-osteoarthritis cohorts. No significant difference was detected between the two groups for the risk of experiencing myocardial infarction or stroke. There was a three-fold decrease in the risk of experiencing a transient ischaemic attack in the osteoarthritis cohort compared to the non-osteoarthritis group. Conclusions: Prevalence of CVD in patients with OA is significant. There was an observed increased risk of incident heart failure and ischaemic heart disease in people with OA compared to matched controls. However the relationship between OA and CVD is not straight-forward and there is a need to better understand the potential common pathways linking pathophysiological mechanisms

Does quality of care in hip fracture vary by day of admission?

Open Access via Springer CompactPeer reviewedPublisher PD

Environmentally co-occurring mercury resistance plasmids are genetically and phenotypically diverse and confer variable context-dependent fitness effects

Plasmids are important mobile elements that can facilitate genetic exchange and local adaptation within microbial communities. We compared the sequences of four co-occurring pQBR-family environmental mercury resistance plasmids and measured their effects on competitive fitness of a Pseudomonas fluorescens SBW25 host, which was isolated at the same field site. Fitness effects of carriage differed between plasmids and were strongly context dependent, varying with medium, plasmid status of competitor and levels of environmental mercury. The plasmids also varied widely in their rates of conjugation and segregational loss. We found that few of the plasmid-borne accessory genes could be ascribed functions, although we identified a putative chemotaxis operon, a type IV pilus-encoding cluster, and a region encoding putative arylsulfatase enzymes, which were conserved across geographically distant isolates. One plasmid, pQBR55, conferred the ability to catabolise sucrose. Transposons, including the mercury resistance Tn5042, appeared to have been acquired by the different pQBR plasmids by recombination, indicating an important role for horizontal gene transfer in the recent evolution of pQBR plasmids. Our findings demonstrate extensive genetic and phenotypic diversity amongst co-occurring members of a plasmid community and suggest a role for environmental heterogeneity in the maintenance of plasmid diversity

Évaluation des compétences en réanimation en séance de simulation et en milieu de travail : analyse descriptive et comparative de trois spécialités

Background: Simulation-based assessment can complement workplace-based assessment of rare or difficult to assess Entrustable Professional Activities (EPAs). We aimed to compare the use of simulation-based assessment for resuscitation-focused EPAs in three postgraduate medical training programs and describe faculty perceptions of simulation-based assessment. Methods: EPA assessment scores and setting (simulation or workplace) were extracted from 2017-2020 for internal medicine, emergency medicine, and surgical foundations residents at the transition to discipline and foundations of discipline stages. A questionnaire was distributed to clinical competency committee members. Results: Eleven percent of EPA assessments were simulation-based. The proportion of simulation-based assessment did not differ between programs but differed between transition (38%) and foundations (4%) stages within surgical foundations only. Entrustment scores differed between settings in emergency medicine at the transition level only (simulation: 4.82 ± 0.60 workplace: 3.74 ± 0.93). 70% of committee members (n=20) completed the questionnaire. Of those that use simulation-based assessment, 45% interpret them differently than workplace-based assessments. 73% and 100% trust simulation for high-stakes and low-stakes assessment, respectively. Conclusions: The proportion of simulation-based assessment for resuscitation focused EPAs did not differ between three postgraduate medical training programs. Interpretation of simulation-based assessment data between committee members was inconsistent. All respondents trust simulation-based assessment for low-stakes, and the majority for high-stakes assessment. These findings have practical implications for the integration simulation into programs of assessment.Contexte : Pour les activités professionnelles confiables (APC) qui sont rarement observées ou difficiles à évaluer, l’évaluation dans les séances de simulation peut compléter l’évaluation en milieu de travail. Nous avons comparé l’utilisation de l’évaluation lors de simulations pour les APC axées sur la réanimation dans trois programmes de formation médicale postdoctorale et décrit les perceptions de membres du corps professoral concernant cette modalité d’évaluation. Méthodes : Nous avons extrait les scores et le cadre (simulation ou lieu de travail) d’évaluation des APC de 2017 à 2020 pour les résidents en médecine interne, en médecine d’urgence et en fondements chirurgicaux aux étapes de transition vers la discipline et de fondements de la discipline. Un questionnaire a été distribué aux membres du comité des compétences cliniques. Résultats : Onze pour cent des évaluations d’APC étaient faites lors de séances de simulation. Cette proportion était la même pour tous les programmes, mais dans le cadre des fondements chirurgicaux, elle était différente selon qu’il s’agissait de l’étape de transition (38 %) ou de l’étape des fondements (4 %). Les scores de confiance différaient selon le cadre de l’évaluation uniquement pour les résidents en médecine d’urgence à l’étape de la transition (simulation : 4,82 ± 0,60; lieu de travail : 3,74 ± 0,93). Le questionnaire a été rempli par 70 % des membres du comité (n=20). Parmi ceux qui avaient utilisé l’évaluation en séance de simulation, 45 % avaient interprété les données de l’évaluation différemment de la façon dont ils interprètent les données d’évaluation en milieu de travail. Soixante-treize pour cent et 100 % d’entre eux font confiance à la simulation pour les évaluations à enjeux élevés et à faibles enjeux, respectivement. Conclusions : La proportion d’évaluations en séance de simulation pour les APC axées sur la réanimation était la même pour trois programmes de formation médicale postdoctorale. Les membres du comité n’ont pas interprété les données de ce type d’évaluation de manière uniforme. Tous les répondants font confiance à l’évaluation en séance de simulation pour les évaluations à faible enjeu, et la plupart d’entre eux pour les évaluations à enjeu élevé. Ces résultats ont des incidences pratiques sur l’intégration de la simulation dans les programmes d’évaluation

Comparing Measures Of Functional Difficulty With Self-Identified Disability: Implications For Health Policy

The Affordable Care Act mandated data collection standards to identify people with disabilities in federal surveys to better understand and address health disparities within this population. Most federal surveys use six questions from the American Community Survey (ACS-6) to identify people with disabilities, whereas many international surveys use the six-item Washington Group Short Set (WG-SS). The National Survey on Health and Disability (NSHD), which focuses on working-age adults ages 18–64, uses both question sets and contains other disability questions. We compared ACS-6 and WG-SS responses with self-reported disability types. The ACS-6 and WG-SS failed to identify 20 percent and 43 percent, respectively, of respondents who reported disabilities in response to other NSHD questions (a broader WG-SS version missed 4.4 percent of respondents). The ACS-6 and the WG-SS performed especially poorly in capturing respondents with psychiatric disabilities or chronic health conditions. Researchers and policy makers must augment or strengthen federal disability questions to improve the accuracy of disability prevalence counts, understanding of health disparities, and planning of appropriate services for a diverse and growing population

Optimization and Validation of a Human <i>Ex Vivo</i> Femoral Head Model for Preclinical Cartilage Research and Regenerative Therapies

OBJECTIVE: Articular cartilage is incapable of effective repair following injury or during osteoarthritis. While there have been developments in cartilage repair technologies, there is a need to advance biologically relevant models for preclinical testing of biomaterial and regenerative therapies. This study describes conditions for the effective ex vivo culture of the whole human femoral head. DESIGN: Fresh, viable femoral heads were obtained from femoral neck fractures and cultured for up to 10 weeks in (a) Dulbecco’s modified Eagle’s medium (DMEM); (b) DMEM + mixing; (c) DMEM + 10% human serum (HS); (d) DMEM + 10% HS + mixing. The viability, morphology, volume, and density of fluorescently labelled in situ chondrocytes and cartilage surface roughness were assessed by confocal microscopy. Cartilage histology was studied for glycosaminoglycan content using Alcian blue and collagen content using picrosirius red. RESULTS: Chondrocyte viability remained at >95% in DMEM + 10% HS. In DMEM alone, viability remained high for ~4 weeks and then declined. For the other conditions, superficial zone chondrocyte viability fell to 0.05). CONCLUSIONS: In this ex vivo model, chondrocyte viability was maintained in human femoral heads for up to 10 weeks in culture, a novel finding not previously reported. This human model could prove invaluable for the exploration, development, and assessment of preclinical cartilage repair and regenerative therapies