Mechanical behaviour and rupture of normal and pathological human ascending aortic wall

The mechanical properties of aortic wall, both healthy and pathological, are needed in order to develop and improve diagnostic and interventional criteria, and for the development of mechanical models to assess arterial integrity. This study focuses on the mechanical behaviour and rupture conditions of the human ascending aorta and its relationship with age and pathologies. Fresh ascending aortic specimens harvested from 23 healthy donors, 12 patients with bicuspid aortic valve (BAV) and 14 with aneurysm were tensile-tested in vitro under physiological conditions. Tensile strength, stretch at failure and elbow stress were measured. The obtained results showed that age causes a major reduction in the mechanical parameters of healthy ascending aortic tissue, and that no significant differences are found between the mechanical strength of aneurysmal or BAV aortic specimens and the corresponding age-matched control group. The physiological level of the stress in the circumferential direction was also computed to assess the physiological operation range of healthy and diseased ascending aortas. The mean physiological wall stress acting on pathologic aortas was found to be far from rupture, with factors of safety (defined as the ratio of tensile strength to the mean wall stress) larger than six. In contrast, the physiological operation of pathologic vessels lays in the stiff part of the response curve, losing part of its function of damping the pressure waves from the heart

Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections.

Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far, the only known X-linked gene is FLNA, which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene explain only a small number of X-linked TAAD families. We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands. Subsequently, Sanger sequencing of BGN in 360 male and 155 female molecularly unexplained TAAD probands was performed. We found five individuals with loss-of-function mutations in BGN encoding the small leucine-rich proteoglycan biglycan. The clinical phenotype is characterized by early-onset aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia. Fluorescent staining revealed an increase in TGF-β signaling, evidenced by an increase in nuclear pSMAD2 in the aortic wall. Our results are in line with those of prior reports demonstrating that Bgn-deficient male BALB/cA mice die from aortic rupture. In conclusion, BGN gene defects in humans cause an X-linked syndromic form of severe TAAD that is associated with preservation of elastic fibers and increased TGF-β signaling.Genet Med 19 4, 386-395

Challenges of scaling up and of knowledge transfer in an action research project in Burkina Faso to exempt the worst-off from health care user fees

<p>Abstract</p> <p>Background</p> <p>Systems to exempt the indigent from user fees have been put in place to prevent the worst-off from being excluded from health care services for lack of funds. Yet the implementation of these mechanisms is as rare as the operational research on this topic. This article analyzes an action research project aimed at finding an appropriate solution to make health care accessible to the indigent in a rural district of Burkina Faso.</p> <p>Research</p> <p>This action research project was initiated in 2007 to study the feasibility and effectiveness of a community-based, participative and financially sustainable process for exempting the indigent from user fees. A interdisciplinary team of researchers from Burkina Faso and Canada was mobilized to document this action research project.</p> <p>Results and knowledge sharing</p> <p>The action process was very well received. Indigent selection was effective and strengthened local solidarity, but coverage was reduced by the lack of local financial resources. Furthermore, the indigent have many other needs that cannot be addressed by exemption from user fees. Several knowledge transfer strategies were implemented to share research findings with residents and with local and national decision-makers.</p> <p>Partnership achievements and difficulties</p> <p>Using a mixed and interdisciplinary research approach was critical to grasping the complexity of this community-based process. The adoption of the process and the partnership with local decision-makers were very effective. Therefore, at the instigation of an NGO, four other districts in Burkina Faso and Niger reproduced this experiment. However, national decision-makers showed no interest in this action and still seem unconcerned about finding solutions that promote access to health care for the indigent.</p> <p>Lessons learned</p> <p>The lessons learned with regard to knowledge transfer and partnerships between researchers and associated decision-makers are: i) involve potential users of the research results from the research planning stage; ii) establish an ongoing partnership between researchers and users; iii) ensure that users can participate in certain research activities; iv) use a variety of strategies to disseminate results; and v) involve users in dissemination activities.</p

What are the important components of the clinical assessment of hand problems in older adults in primary care? Results of a Delphi study

<p>Abstract</p> <p>Background</p> <p>To identify clinical questions and assessments regarded by health care practitioners as important when assessing undifferentiated hand pain or problems in adults aged 50 years and over presenting to primary care.</p> <p>Methods</p> <p>A purposively selected panel of 26 UK-based Health Care Practitioners comprising occupational therapists, physiotherapists, rheumatologists and general practitioners, were invited to take part in a consensus study involving three postal rounds of a Delphi questionnaire with accompanying case scenarios. Participants were asked to generate questions and assessments (round 1), rate their importance (round 2), and vote on which items were most important (round 3).</p> <p>Results</p> <p>Sixteen Health Care Practitioners agreed to participate with 11 completing all three rounds. The first round of the Delphi study generated 156 questions and 143 assessments. After three rounds agreement was reached on the importance of 25 questions and 19 assessments. Questions were weighted towards current symptoms, but also included the history of previous hand problems, self-reported hand function, co-morbidity and general health. Observation and palpation of features predominated in the choice of assessment, but specific tests, grip strength, evaluation of sensation and hand function were also included.</p> <p>Conclusions</p> <p>A pool of clinical questions and assessments were generated by Health Care Practitioners, and those considered most important for assessing older adults presenting with undifferentiated hand pain and hand problems in primary care were identified. Further evaluation is required to establish the reliability and feasibility of using these questions and assessments in primary care. In particular, the relative contribution of these questions and assessments in evaluating the nature and severity of hand problems, assisting diagnosis, indicating appropriate management, and predicting future course requires further investigation.</p