The M694V mutation in Armenian‐Americans: a 10‐year retrospective study of MEFV mutation testing for familial Mediterranean fever at UCLA

Familial Mediterranean fever (FMF), inherited in an autosomal recessive manner, is a systemic auto‐inflammatory disorder characterized by recurrent attacks of fever with peritonitis, pleuritis, synovitis and erysipeloid rash. The marenostrin‐encoding fever (MEFV) gene, located on chromosome 16p13.3, is the only gene in which mutations are currently known to cause FMF. To correlate specific genotypes with adverse phenotypes of affected populations residing in the Western United States, a retrospective case series review was conducted of all MEFV gene mutation testing completed at UCLA Clinical Molecular Diagnostic Laboratory between February 2002 and February 2012, followed by clinical chart review of all subjects who either have a single or double mutation. All 12 common mutations in the MEFV gene were analyzed and the M694V variant was found to be associated with an adverse FMF clinical outcome in the Armenian‐American population, manifested by earlier onset of disease, increased severity of disease, and renal amyloidosis.     

Motivations for Contributing to Health-Related Articles on Wikipedia: An Interview Study

BackgroundWikipedia is one of the most accessed sources of health information online. The current English-language Wikipedia contains more than 28,000 articles pertaining to health.ObjectiveThe aim was to characterize individuals’ motivations for contributing to health content on the English-language Wikipedia.MethodsA set of health-related articles were randomly selected and recent contributors invited to complete an online questionnaire and follow-up interview (by Skype, by email, or face-to-face). Interviews were transcribed and analyzed using thematic analysis and a realist grounded theory approach.ResultsA total of 32 Wikipedians (31 men) completed the questionnaire and 17 were interviewed. Those completing the questionnaire had a mean age of 39 (range 12-59) years; 16 had a postgraduate qualification, 10 had or were currently studying for an undergraduate qualification, 3 had no more than secondary education, and 3 were still in secondary education. In all, 15 were currently working in a health-related field (primarily clinicians). The median period for which they have been an active editing Wikipedia was 3-5 years. Of this group, 12 were in the United States, 6 were in the United Kingdom, 4 were in Canada, and the remainder from another 8 countries. Two-thirds spoke more than 1 language and 90% (29/32) were also active contributors in domains other than health. Wikipedians in this study were identified as health professionals, professionals with specific health interests, students, and individuals with health problems. Based on the interviews, their motivations for editing health-related content were summarized in 5 strongly interrelated categories: education (learning about subjects by editing articles), help (wanting to improve and maintain Wikipedia), responsibility (responsibility, often a professional responsibility, to provide good quality health information to readers), fulfillment (editing Wikipedia as a fun, relaxing, engaging, and rewarding activity), and positive attitude to Wikipedia (belief in the value of Wikipedia). An additional factor, hostility (from other contributors), was identified that negatively affected Wikipedians’ motivations.ConclusionsContributions to Wikipedia’s health-related content in this study were made by both health specialists and laypeople of varying editorial skills. Their motivations for contributing stem from an inherent drive based on values, standards, and beliefs. It became apparent that the community who most actively monitor and edit health-related articles is very small. Although some contributors correspond to a model of “knowledge philanthropists,” others were focused on maintaining articles (improving spelling and grammar, organization, and handling vandalism). There is a need for more people to be involved in Wikipedia’s health-related content.     

Aging leads to increased levels of protein O-linked <Emphasis Type="Italic">N</Emphasis>-acetylglucosamine in heart,aorta, brain and skeletal muscle in Brown-Norway rats

Changes in the levels of O-linked N-acetyl-glucosamine (O-GlcNAc) on nucleocytoplasmic protein have been associated with a number of age-related diseases such as Alzheimer’s and diabetes; however, there is relatively little information regarding the impact of age on tissue O-GlcNAc levels. Therefore, the goal of this study was to determine whether senescence was associated with alterations in O-GlcNAc in heart, aorta, brain and skeletal muscle and if so whether there were also changes in the expression of enzymes critical in regulating O-GlcNAc levels, namely, O-GlcNAc transferase (OGT), O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase (GFAT). Tissues were harvested from 5- and 24-month old Brown-Norway rats; UDP-GlcNAc, a precursor of O-GlcNAc was assessed by HPLC, O-GlcNAc and OGT levels were assessed by immunoblot analysis and GFAT1/2, OGT, O-GlcNAcase mRNA levels were determined by RT-PCR. In the 24-month old animals serum insulin and triglyceride levels were significantly increased compared to the 5-month old group; however, glucose levels were unchanged. Protein O-GlcNAc levels were significantly increased with age (30–107%) in all tissues examined; however, paradoxically the expression of OGT, which catalyzes O-GlcNAc formation, was decreased by ∼30% in the heart, aorta and brain. In the heart increased O-GlcNAc was associated with increased UDP-GlcNAc levels and elevated GFAT mRNA while in other tissues we found no difference in UDP-GlcNAc or GFAT mRNA levels. These results demonstrate that senescence is associated with increased O-GlcNAc levels in multiple tissues and support the notion that dysregulation of pathways leading to O-GlcNAc formation may play an important role in the development of age-related diseases.     

Clinically significant valvular heart disease in systemic lupus erythematosus

PURPOSE: Clinically significant valvular heart disease due to systemic lupus erythematosus (SLE) has generally been considered rare, and Libman-Sacks endocarditis has been thought to be predominantly an autopsy finding. With the declining prevalence of rheumatic heart disease, however, the spectrum of valvular heart disease is changing. We retrospectively analyzed our experience with SLE between 1975 and 1987 for the presence of hemodynamically significant valvular heart disease. PATIENTS AND METHODS: An existing data base of 421 patients with SLE was selected for review. Patients were selected for inclusion in the study if they met four or more of the criteria of the American Rheumatism Association for SLE, they had clinically significant valvular heart disease, and tissue from the involved valve was available for review. The etiology of the valve lesion was determined by assessment of the clinical history, chart review, gross morphology, and valve histology. RESULTS: Of 14 cases with pathologic material available for review, six had anatomic features of SLE valvular heart disease such as verrucous vegetations or valvulitis with necrosis and vasculitis. Two of these patients underwent successful valve replacements and four died from complications of their valve disease. CONCLUSION: We suggest that significant morbidity and mortality may result from SLE valvular heart disease in about 1 to 2 percent of SLE patients and that the pathogenetic mechanisms underlying valve dysfunction in SLE patients are multifactorial.