Protein kinase CK2 inhibition suppresses neointima formation via a proline-rich homeodomain-dependent mechanism

Neointimal hyperplasia is a product of VSMC replication and consequent accumulation within the blood vessel wall. In this study, we determined whether inhibition of protein kinase CK2 and the resultant stabilisation of proline-rich homeodomain (PRH) could suppress VSMC proliferation. Both silencing and pharmacological inhibition of CK2 with K66 antagonised replication of isolated VSMCs. SiRNA-induced knockdown as well as ectopic overexpression of proline-rich homeodomain indicated that PRH disrupts cell cycle progression. Mutation of CK2 phosphorylation sites Ser163 and Ser177 within the PRH homeodomain enabled prolonged cell cycle arrest by PRH. Concomitant knockdown of PRH and inhibition of CK2 with K66 indicated that the anti-proliferative action of K66 required the presence of PRH. Both K66 and adenovirus-mediated gene transfer of S163C:S177C PRH impaired neointima formation in human saphenous vein organ cultures. Importantly, neither intervention had notable effects on cell cycle progression, cell survival or migration in cultured endothelial cells

Scaling Peak Oxygen Consumption for Body Size and Composition in People With a Fontan Circulation

This is the final version. Available on open access from Wiley via the DOI in this recordBACKGROUND: Peak oxygen consumption (peak ̇ VO2) is traditionally divided (“ratio- scaled”) by body mass (BM) for clinical interpretation. Yet, it is unknown whether ratio- scaling to BM can produce a valid size- independent expression of peak VO2 in people with a Fontan circulation. Furthermore, people with a Fontan circulation have deficits in lean mass, and it is unexplored whether using different measures of body composition may improve scaling validity. The objective was to assess the validity of different scaling denominators (BM, stature, body surface area, fat- free mass, lean mass, and appendicular lean mass using ratio and allometric scaling). ̇ METHODS AND RESULTS: Eighty- nine participants (age: 23.3±6.7 years; 53% female) with a Fontan circulation had their cardiorespiratory fitness and body composition measured by cardiopulmonary exercise testing and dual- energy x- ray absorptiometry. Ratio and allometric (log- linear regression) scaling was performed and Pearson correlations assessed scaling validity. Scaling denominators BM (r=−0.25, P=0.02), stature (r=0.46, P<0.001), and body surface area (0.23, P=0.03) were significantly correlated with their respective ratio- scaled expressions of peak ̇ VO2, but fat- free mass, lean mass, or appendicular Downloaded from http://ahajournals.org by on December 14, 2022 lean mass were not (r≤0.11; R2=1%). Allometrically expressed peak denominator (r=≤0.23; R2=≤4%). ̇ ̇ VO2 resulted in no significant correlation with any scaling CONCLUSIONS: The traditional and accepted method of ratio- scaling to BM is invalid because it fails to create a size- independent expression of peak VO2 in people with a Fontan circulation. However, ratio- scaling to measures of body composition (fat- free mass, lean mass, and appendicular lean mass) and allometric techniques can produce size- independent expressions of peak ̇ VO2 in people with a Fontan circulation.Canon Medical Systems UK Ltd.University of ExeterMedical Research Future Fun

Real patient learning integrated in a preclinical block musculoskeletal disorders. Does it make a difference?

Although musculoskeletal disorders are the most common reason for general practitioner visits, training did not keep pace. Implementation of learning from patients with rheumatologic disorders linked together with the teaching of theoretical knowledge in the preclinical medical education might be an important step forward in the improvement of quality of care for these patients. The Leiden Medical School curriculum has implemented two non-obligatory real patient learning (RPL) practicals integrated within the preclinical block musculoskeletal disorders. This study investigates the educational effectiveness of the practicals, the expectations students have of RPL, and students’ satisfaction. Participants’ grades on the end-of-block test served as the test results of the educational effectiveness of the practicals and were compared with those of the non-participants. Qualitative data was collected by means of questionnaires generated by focus groups. The participants in practicals scored significantly higher at the end-of-block test. The expected effects of the contact with real patients concerned positive effects on cognition and skills. ‘Contextualizing of the theory’, ‘better memorizing of clinical pictures’, and ‘understanding of the impact of the disease’ were the most frequently mentioned effects of the practicals. Overall, the participants were (very) enthusiastic about this educational format. The RPL practicals integrated within a preclinical block musculoskeletal disorders are a valuable addition to the Leiden medical curriculum. This relatively limited intervention exhibits a strong effect on students’ performance in tests. Future research should be directed towards the long-term effects of this intervention

Canadian physiotherapists' views on certification, specialisation, extended role practice, and entry-level training in rheumatology

<p>Abstract</p> <p>Background</p> <p>Since the last decade there has been a gradual change of boundaries of health professions in providing arthritis care. In Canada, some facilities have begun to adopt new arthritis care models, some of which involve physiotherapists (PT) working in extended roles. However, little is known about PTs' interests in these new roles. The primary objective of this survey was to determine the interests among orthopaedic physiotherapists (PTs) in being a certified arthritis therapist, a PT specialized in arthritis, or an extended scope practitioner in rheumatology, and to explore the associated factors, including the coverage of arthritis content in the entry-level physiotherapy training.</p> <p>Methods</p> <p>Six hundred PTs practicing in orthopaedics in Canada were randomly selected to receive a postal survey. The questionnaire covered areas related to clinical practice, perceptions of rheumatology training received, and attitudes toward PT roles in arthritis care. Logistic regression models were developed to explore the associations between PTs' interests in pursuing each of the three extended scope practice designations and the personal/professional/attitudinal variables.</p> <p>Results</p> <p>We received 286 questionnaires (response rate = 47.7%); 258 contained usable data. The average length of time in practice was 15.4 years (SD = 10.4). About 1 in 4 PTs agreed that they were interested in assuming advanced practice roles (being a certified arthritis therapist = 28.9%, being a PT specialized in rheumatology = 23.3%, being a PT practitioner = 20.9%). Having a caseload of ≥ 40% in arthritis, having a positive attitude toward advanced practice roles in arthritis care and toward the formal credentialing process, and recognizing the difference between certification and specialisation were associated with an interest in pursing advanced practice roles.</p> <p>Conclusion</p> <p>Orthopaedic PTs in Canada indicated a fair level of interest in pursuing certification, specialisation and extended scope practice roles in arthritis care. Future research should focus on the effectiveness and cost-effectiveness of the emerging health service delivery models involving certified, specialized or extended scope practice PTs in the management of arthritis.</p

Elite Refereeing in Professional Soccer: A Case Study of Mental Skills Support

Refereeing a high-profile soccer game requires a unique blend of sports-specific knowledge, physical abilities, and mental skills. While mental skills instruction has been seen as an integral element of performance enhancement in elite sport, the application of sport psychology intervention for referees and match officials is far less prominent. This case study briefly describes the levels of stress associated with refereeing elite soccer matches and the impact of stress on officiating performance and subsequent self-confidence of soccer referees. The work then outlines the program of mental skills intervention that was delivered to an elite soccer referee working within the Scottish professional soccer leagues. The program of mental skills embraced five stages: (1) Education; (2) Assessment/ profiling; (3) Mental skill learning; (4) Application of mental skills in context; and (5) Evaluation, and this article centers on the way in which each of these stages was carried out. The case study describes how the mental skills instruction program was associated with improved refereeing performance, and provides some tentative advice for sport psychology practitioners who may wish to provide consultancy services within the domain of sports officiating

A Review of Surgical Informed Consent: Past, Present, and Future. A Quest to Help Patients Make Better Decisions

Contains fulltext : 87422.pdf (publisher's version ) (Closed access)BACKGROUND: Informed consent (IC) is a process requiring a competent doctor, adequate transfer of information, and consent of the patient. It is not just a signature on a piece of paper. Current consent processes in surgery are probably outdated and may require major changes to adjust them to modern day legislation. A literature search may provide an opportunity for enhancing the quality of the surgical IC (SIC) process. METHODS: Relevant English literature obtained from PubMed, Picarta, PsycINFO, and Google between 1993 and 2009 was reviewed. RESULTS: The body of literature with respect to SIC is slim and of moderate quality. The SIC process is an underestimated part of surgery and neither surgeons nor patients sufficiently realize its importance. Surgeons are not specifically trained and lack the competence to guide patients through a legally correct SIC process. Computerized programs can support the SIC process significantly but are rarely used for this purpose. CONCLUSIONS: IC should be integrated into our surgical practice. Unfortunately, a big gap exists between the theoretical/legal best practice and the daily practice of IC. An optimally informed patient will have more realistic expectations regarding a surgical procedure and its associated risks. Well-informed patients will be more satisfied and file fewer legal claims. The use of interactive computer-based programs provides opportunities to improve the SIC process.1 juli 201

Quantum chemical calculations of X-ray emission spectroscopy

The calculation of X-ray emission spectroscopy with equation of motion coupled cluster theory (EOM-CCSD), time dependent density functional theory (TDDFT) and resolution of the identity single excitation configuration interaction with second order perturbation theory (RI-CIS(D)) is studied. These methods can be applied to calculate X-ray emission transitions by using a reference determinant with a core-hole, and they provide a convenient approach to compute the X-ray emission spectroscopy of large systems since all of the required states can be obtained within a single calculation removing the need to perform a separate calculation for each state. For all of the methods, basis sets with the inclusion of additional basis functions to describe core orbitals are necessary, particularly when studying transitions involving the 1s or- bitals of heavier nuclei. EOM-CCSD predicts accurate transition energies when compared with experiment, however, its application to larger systems is restricted by its computational cost and difficulty in converging the CCSD equations for a core-hole reference determinant, which become increasing problematic as the size of the system studied increases. While RI-CIS(D) gives accurate transition energies for small molecules containing first row nuclei, its application to larger systems is limited by the CIS states providing a poor zeroth order reference for perturbation theory which leads to very large errors in the computed transition energies for some states. TDDFT with standard exchange-correlation functionals predicts transition energies that are much larger than experiment. Optimization of a hybrid and short-range cor- rected functional to predict the X-ray emission transitions results in much closer agreement with EOM-CCSD. The most accurate exchange-correlation functional identified is a modified B3LYP hybrid functional with 66% Hartree-Fock exchange, denoted B66LYP, which predicts X-ray emission spectra for a range of molecules including fluorobenzene, nitrobenzene, ace- tone, dimethyl sulfoxide and CF3Cl in good agreement with experiment

The ability of societies to adapt to twenty-first-century sea-level rise

Against the background of potentially substantial sea-level rise, one important question is to what extent are coastal societies able to adapt? This question is often answered in the negative by referring to sinking islands and submerged megacities. Although these risks are real, the picture is incomplete because it lacks consideration of adaptation. This Perspective explores societies' abilities to adapt to twenty-first-century sea-level rise by integrating perspectives from coastal engineering, economics, finance and social sciences, and provides a comparative analysis of a set of cases that vary in terms of technological limits, economic and financial barriers to adaptation and social conflicts