Citations

Introduction Pulmonary hypertension (PH) is a devastating, progressive disease with increasingly debilitating symptoms and usually shortened overall life expectancy due to a narrowing of the pulmonary vasculature and consecutive right heart failure. Little is known about PH in Africa, but limited reports suggest that PH is more prevalent in Africa compared with developed countries due to the high prevalence of risk factors in the region. Methods and analysis A multinational multicentre registry-type cohort study was established and tailored to resource-constraint settings to describe disease presentation, disease severity and aetiologies of PH, comorbidities, diagnostic and therapeutic management, and the natural course of PH in Africa. PH will be diagnosed by specialist cardiologists using echocardiography (right ventricular systolic pressure >35 mm Hg, absence of pulmonary stenosis and acute right heart failure), usually accompanied by shortness of breath, fatigue, peripheral oedema and other cardiovascular symptoms, ECG and chest X-ray changes in keeping with PH as per guidelines (European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines). Additional investigations such as a CT scan, a ventilation/perfusion scan or right heart catheterisation will be performed at the discretion of the treating physician. Functional tests include a 6 min walk test and the Karnofsky Performance Score. The WHO classification system for PH will be applied to describe the different aetiologies of PH. Several substudies have been implemented within the registry to investigate specific types of PH and their outcome at up to 24 months. Data will be analysed by an independent institution following a data analyse plan. Ethics and dissemination All local ethics committees of the participating centres approved the protocol. The data will be disseminated through peer-reviewed journals at national and international conferences and public events at local care providers.

Fat-specific protein 27 (FSP27) plays a pivotal role in controlling the formation of large lipid droplet and energy metabolism. The cellular levels of FSP27 are tightly regulated through the proteasomal ubiquitin-mediated degradation. However, the upstream signals that trigger FSP27 degradation and the underlying mechanism(s) have yet to be identified. Here we show that AMP-activated protein kinase (AMPK) activation by AICAR (5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide) or phenformin induced the ubiquitination of FSP27 and promoted its degradation in 3T3-L1 adipocytes. The levels of FSP27 protein could be maintained by either knocking down AMPKα1 or blocking proteasomal pathway. Moreover, AICAR treatment induced multilocularization of LDs in 3T3-L1 adipocytes, reminiscent of the morphological changes in cells depleted of FSP27. Furthermore, mass spectrometry-based proteomic analysis identified heat shock cognate 70 (HSC70) as a novel binding protein of FSP27. The specific interaction was confirmed by co-immunoprecipitation of both ectopically expressed and endogenous proteins. Importantly, knockdown of HSC70 by small interference RNA resulted in increased half-life of FSP27 in cells treated with a protein synthesis inhibitor cycloheximide (CHX) or AICAR. However, silencing of the E3 ubiquitin ligase CHIP (COOH terminus of HSC70-interacting protein) failed to alter the stability of FSP27 protein under both conditions. Taken together, our data indicate that AMPK is a negative regulator of FSP27 stability through the proteasomal ubiquitin-dependent protein catabolic process. Promotion of FSP27 degradation may be an important factor responsible for the beneficial effect of AMPK activators on energy metabolism.

We use administrative data from Wisconsin to determine the fraction of new Medicaid enrollees who have private health insurance at the time of enrollment in the program. Through the linkage of several administrative data sources not previously used for research, we are able to observe coverage status directly for a large fraction of enrollees and indirectly for the remainder. We provide strict bounds for the percentages in each status and find that the percentage of new enrollees with private insurance coverage at the time of enrollment lies between 16 percent and 29 percent, and the percentage that dropped private coverage in favor of public insurance lies between 4 percent and 18 percent. Our point estimates indicate that, among all new enrollees, 21 percent had private health insurance at the time of enrollment and that 10 percent dropped this coverage. Our results show substantially lower rates than previous studies of crowd-out following public health insurance expansions and significant rates of dual coverage, whereby new enrollees into public insurance retain their previously held private insurance coverage.

AbstractProsthodontics has a rich history related to the principles embedded in evidence‐based health care. This paper reviews the evidence‐based prosthodontics activity over the past 3 decades. It also discusses the impact of health care reform on evidence‐based medicine as it relates to broader context of care outcomes. Finally, the value associated with an Evidence Stewardship emphasis in prosthodontics is presented. This emphasis suggests that combining evidence from clinical trials with evidence from clinical practice environments best equips clinicians for the management of patients in the future. Adoption of a strategic Evidence Stewardship direction is an extended commitment to change that recognizes health care reform aims and seeks to be an accountable provider group in the broader health care arena. The vision to form a representative network of prosthodontic practitioners that augments a commitment to Cochrane “clinical trial” data demonstrates a responsibility to professional transparency about who we are, adds value for patients and oral health care providers, impacts teachers and students in dental education, and provides a measure of care accountability unique in dentistry.

Background Proximal pole scaphoid fractures are less common than waist fractures, and successful management can be difficult. We hypothesize that time to union is increased by delays in surgical fixation, greater initial displacement, and higher energy mechanisms of injury. Methods A retrospective review was conducted of all patients undergoing open reduction internal fixation (ORIF) of acute proximal pole scaphoid fractures at our institution over a 19-year period. A review of clinical as well as radiographic data was undertaken. The mechanism of injury, patient demographics, timing of surgery, initial displacement, fixation method, smoking status, and lunate morphology were recorded. Functional outcome measures were recorded when available. Univariate analysis using Kaplan-Meier survival curves was performed. Results A total of 10 out of 23 patients (43 %) showed evidence of union at 14 weeks post-injury. Rates of early union were higher in non-displaced fractures (70 %) when compared to displaced fractures (23 %). Similarly, fractures sustained via low energy mechanisms had a higher rate of early union compared to high energy mechanisms (69 versus 10 %). A delay in ORIF did not appear to influence rate of union. Conclusions Initial displacement and mechanism of injury have the most significant effects on early rates of union. Delay in ORIF of up to 28 days did not affect the rate of initial union, but the authors recommend early fixation of these fractures to prevent further displacement. Patients with widely displaced fractures or those with high energy mechanisms should be counseled regarding prolonged healing time. Level of Evidence: IV—therapeutic

A proof of principle pharmacogenomic translational study was used as a case example to explore Biobank Community Advisory Board (CAB) member views about placing genomic information into the medical record and to establish how CAB input could affect research design. CAB members expressed enthusiasm for the potential benefit of the research discussed, yet voiced concerns regarding the recruitment and consent materials. They discussed the value of genomic research and its clinical utility; the risk of genetic discrimination; and personal ownership of genomic data. Members distinguished between indirect benefits to future generations and individual risk to research participants. Feedback was used to revise the recruitment and consent materials. Results highlight tensions reported between the public’s support for genomic research and concerns with genomic information in the medical record and its use in medical decision-making.