Kenneth S. O'Rourke

Altered editing in RNA editing adenosine deaminase ADAR2 gene transcripts of systemic lupus erythematosus T lymphocytes

Adenosine Deaminases that act on RNA (ADARs) edit gene transcripts through site‐specific conversion of adenosine to inosine by hydrolytic deamination at C6 of the adenosine. ADAR2 gene transcripts are substrates for the ADAR1 and ADAR2 enzymes and their expression is regulated by editing at the − 1 and − 2 sites. Our previous experiments demonstrated up‐regulation of type I interferon (IFN) inducible 150 kDa ADAR1 in systemic lupus erythematosus (SLE) T cells. In this study we investigate the role of ADAR1 and ADAR2 in editing of ADAR2 gene transcripts of healthy controls and SLE patients. The ADAR2 gene transcripts were cloned into pCR2.1‐TOPO vectors. A total of 150 clones from SLE and 150 clones from controls were sequenced. Sequence analysis demonstrated A to I editing at − 1, + 10, + 23 and + 24 in normal T cells. In SLE clones site‐selective editing of the − 2 site was observed as a result of type I IFN‐inducible 150 kDa ADAR1 expression. These results are confirmed by analysing ADAR2 transcripts of normal T cells activated with type I IFN‐α. Editing of the + 23 and + 24 sites was decreased in SLE T cells compared to normal controls. In addition to A to G changes, U to C discrepancies were observed in normal and SLE T cells. In SLE cells, positions − 6 and + 30 were frequently edited from U to C compared to normal controls. Taken together, these results demonstrate altered and site‐selective editing in ADAR2 transcripts of SLE patients. Based on these results, it is proposed that altered transcript editing contributes to the modulation of gene expression and immune functions in SLE patients.

Rheumatologists’ recommendations on what to do in the dermatology office to evaluate and manage psoriasis patients’ joint symptoms

Background: Psoriasis patients presenting to the dermatologist for skin disease management may have joint symptoms related to psoriatic arthritis. Dermatologists should ask psoriasis patients about these, yet may not be sure about how to best collaborate with rheumatologists in the management of these patients. Objective: To describe how rheumatologists view the role of dermatologists in addressing and identifying signs and symptoms of psoriatic arthritis in psoriasis patients. Methods: A questionnaire was developed concerning the evaluation and management of joint complaints in a dermatology setting. The survey was sent to rheumatologists interested in psoriatic arthritis. Results: Rheumatologists recommended dermatologists ask psoriasis patients about joint pain, stiffness, swelling, and fatigue to evaluate for psoriatic arthritis. Rheumatology referral was recommended if patients had signs of inflammatory joint disease that were unrelieved by non-prescription non-steroidal anti-inflammatory drugs (NSAIDs). Patients with disabling joint symptoms, no improvement on (disease-modifying antirheumatic drug; DMARD) therapy, or with other causes of joint pain should be referred to rheumatology. Rheumatologists recommended that dermatologists only provide DMARD therapy for joint symptoms if concomitant skin disease warrants such treatment. Conclusions: Dermatologists play a pivotal role in preventing joint destruction in psoriasis patients by screening for signs of psoriatic arthritis, initiating treatment, and referring patients to a rheumatologist when appropriate.

Competency-based goals, objectives, and linked evaluations for rheumatology training programs: a standardized template of learning activities from the Carolinas Fellows Collaborative.

American Council on Graduate Medical Education program requirements mandate that rheumatology training programs have written goals, objectives, and performance evaluations for each learning activity. Since learning activities are similar across rheumatology programs, we aimed to create competency‐based goals and objectives (CBGO) and evaluations that would be generalizable nationally.

Pilot Study of the Effect of Ultraviolet Light on Pain and Mood in Fibromyalgia Syndrome

BACKGROUND There is a lack of effective systemic or adequate symptomatic treatment for pain associated with fibromyalgia syndrome (FMS). Anecdotes suggest ultraviolet (UV) light may be of some benefit. PURPOSE The purpose of the present study was to determine if UV is effective in ameliorating chronic pain in persons with FMS. METHODS Nineteen subjects with FMS were enrolled in a controlled trial of UV and non-UV (control) tanning beds for 2 weeks, followed by randomization to receive UV or non-UV (control) exposure for 6 additional weeks. A follow-up interview was conducted 4 weeks after the last treatment. Pain was assessed with an 11-point numerical pain rating (Likert scale), a visual analogue pain scale (VAS), and the McGill Pain Questionnaire. Mood variables were also assessed. RESULTS During the initial 2 weeks when subjects received both UV and non-UV (control) exposures, the 11-point Likert scale pain score decreased 0.44 points after exposure to UV from pre-exposure levels (S.E. = .095). Additionally, UV exposure resulted in greater positive affect, well-being, relaxation, and reduced pain levels when compared to non-UV (control) exposure (Odds Ratio [OR] = 2.80, p = 0.0059). Following the randomized treatment period, there was slight improvement in pain as measured by the McGill Pain Questionnaire in the UV group compared to the non-UV (control) group (12.2 versus 14.1; p = 0.049); the other pain scales yielded nonsignificant results. Assessment 4 weeks after the last treatment showed no significant differences in scores in the adjusted means for outcomes. CONCLUSIONS Results from this pilot study suggest that tanning beds may have some potential in reducing pain in persons with FMS.

Induction of 150-kDa adenosine deaminase that acts on RNA (ADAR)-1 gene expression in normal T lymphocytes by anti-CD3-ε and anti-CD28

We and other investigators have demonstrated up‐regulation of the expression of the RNA‐editing gene 150‐kDa adenosine deaminase that acts on RNA (ADAR1) in systemic lupus erythematosus (SLE) T cells and B cells, peripheral blood mononuclear cells (PBMC), natural killer (NK) cells. The presence of a small proportion of activated T cells is the hallmark of SLE. Therefore, it was hypothesized that 150‐kDa ADAR1 gene expression is induced by the physiological activation of T cells. To examine this hypothesis, normal T cells were activated by anti‐CD3‐ε plus anti‐CD28 for various time periods from 0 to 48 hr. The expression of 110‐kDa and 150‐kDa ADAR1, and interleukin (IL)‐2 and β‐actin gene transcripts was analysed. An approximately fourfold increase in 150‐kDa ADAR1 gene expression was observed in activated T cells. ADAR2 gene transcripts are substrates for ADAR1 and ADAR2 enzymes. Therefore, we assessed the role of the 150‐kDa ADAR enzyme in editing of ADAR2 gene transcripts. In activated T cells, site‐selective editing of the −2 site was observed. Previous studies indicate that this site is predominantly edited by ADAR1. In addition to this, novel editing sites at base positions −56, −48, −45, −28, −19, −15, +46 and +69 were identified in activated T cells. On the basis of these results, it is proposed that 150‐kDa ADAR1 gene expression is selectively induced in T cells by anti‐CD3‐ε and anti‐CD28 stimulation and that it may play a role in site‐selective editing of gene transcripts and in altering the functions of several gene products of T cells during activation and proliferation.

What Is a Rheumatologist and How Do We Make One

Graduate medical education is a critical time in the training of a rheumatologist, and purposeful evaluation of abilities during this time is essential for long‐term success as an independent practitioner. The internal medicine subspecialties collectively developed a uniform set of reporting milestones by which trainees can be assessed and receive formative feedback, providing clarity of accomplishment as well as areas for improvement in training. Furthermore, the reporting milestones provide a schema for assessment and evaluation of fellows by supervisors. The internal medicine subspecialties were also tasked with considering entrustable professional activities (EPAs), which define the abilities of a subspecialty physician who has attained sufficient mastery of the field to be accountable to stakeholders and participate in independent practice. Although EPAs have been established for a few specialties, they had not yet been described for rheumatology. EPAs have value as descriptors of the comprehensive abilities, knowledge, and skills of a practicing rheumatologist. The rheumatology EPAs have a role in defining a specialist in rheumatology upon completion of training, and also represent the ways our specialty defines our abilities that are enduring throughout practice.

MYOPATHIES IN THE ELDERLY

Muscle disease symptoms and myopathies are not uncommon in the elderly. Inflammatory and noninflammatory myopathies lead to proximal extremity or axial weakness and are superimposed on the intrinsic changes that occur in muscle with aging (sarcopenia). This article surveys the more common myopathies in the elderly based on a review of the process of sarcopenia, and how these age-related changes in muscle structure and function affect the results of the standard assessments of muscle disease in the elderly.

Expert panel consensus on assessment checklists for a rheumatology objective structured clinical examination.

While several regional fellowship groups conduct rheumatology objective structured clinical examinations (ROSCEs), none have been validated for use across programs. We aimed to establish agreement among subspecialty experts regarding checklist items for several ROSCE stations.

The Fellow as Clinical Teacher Curriculum: Improving Rheumatology Fellows' Teaching Skills During Inpatient Consultation

Enhancing rheumatology fellows’ teaching skills in the setting of inpatient consultation may have a broad positive impact. Such efforts may improve fellows’ clinical skills and overall patient care. Most importantly, effective resident‐fellow teaching interactions may not only increase residents’ knowledge of rheumatology but may influence their career choice. However, a number of barriers to the resident‐fellow teaching interaction have been identified, including fellows’ teaching skills. We developed the Fellow As Clinical Teacher (FACT) curriculum in order to enhance fellows’ teaching skills during inpatient consultation.

New Roadmap for the Journey From Internist to Rheumatologist

Measurement is necessary to gauge improvement. US training programs have not previously used shared standards to assess trainees’ mastery of the knowledge, skills, and attitudes necessary to practice rheumatology competently. In 2014, the Accreditation Council for Graduate Medical Education (ACGME) Next Accreditation System began requiring semiannual evaluation of all medicine subspecialty fellows on 23 internal medicine subspecialty reporting milestones. Since these reporting milestones are not subspecialty specific, rheumatology curricular milestones were needed to guide rheumatology fellowship training programs and fellows on the training journey from internist to rheumatologist.