ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Several neurodegenerative diseases are influenced by the innate immune response in the central nervous system (CNS). Microglia, have pro-inflammatory and subsequently neurotoxic actions as well as anti-inflammatory functions that promote recovery and repair. Very little is known about the transcriptional control of these specific microglial behaviors. We have previously shown that in HIV associated neurocognitive disorders (HAND), the transcription factor p53 accumulates in microglia and that microglial p53 expression is required for the in vitro neurotoxicity of the HIV coat glycoprotein gp120. These findings suggested a novel function for p53 in regulating microglial activation. Here we report that in the absence of p53, microglia demonstrate a blunted response to interferon-γ, failing to increase expression of genes associated with classical macrophage activation or secrete pro-inflammatory cytokines. Microarray analysis of global gene expression profiles revealed increased expression of genes associated with anti-inflammatory functions, phagocytosis and tissue repair in p53 knockout (p53−/−) microglia compared with those cultured from strain matched p53 expressing (p53+/+) mice. We further observed that p53−/− microglia demonstrate increased phagocytic activity in vitro and expression of markers for alternative macrophage activation both in vitro and in vivo. In HAND brain tissue, the alternative activation marker CD163 was expressed in a separate subset of microglia than those demonstrating p53 accumulation. These data suggest that p53 influences microglial behavior, supporting the adoption of a pro-inflammatory phenotype, while p53 deficiency promotes phagocytosis and gene expression associated with alternative activation and anti-inflammatory functions.

BackgroundBoth research and clinical medicine requires similar attributes of efficiency, diligence and effective teamwork. Furthermore, residents must succeed at scholarship and patient care to be competitive for fellowship training. It is unknown whether research productivity among residents is related to broad measures of clinical achievement. Our goal was to examine associations between the quantity of internal medicine residents’ publications and validated measures of their knowledge, skills and multi-source evaluations of performance.MethodsThis was a longitudinal study of 308 residents graduating from Mayo Clinic from 2006 to 2012. We identified peer-reviewed articles in Ovid MEDLINE between July of each resident’s match year and the end of their graduation. Outcomes included American Board of Internal Medicine (ABIM) certification examination scores, mini clinical examination (mini-CEX) scores, and validated assessments of clinical performance by resident-peers, faculty and non-physicians. Performance assessments were averaged to form an overall score ranging from 1 to 5. Associations between quantity of resident publications – and ABIM, mini-CEX and performance assessment scores – were determined using multivariate linear regression.ResultsThe residents published 642 papers, of which 443 (69.0 %) were research papers, 198 (30.8 %) were case reports, and 380 (59.2 %) were first-authored. On adjusted analysis, multi-source clinical performance evaluations were significantly associated (beta; 99 % CI; p-value) with the numbers of research articles (0.012; 0.001–0.024; 0.007), and overall publications (0.012; 0.002–0.022; 0.002).ConclusionsTo our knowledge, this is the first study to demonstrate that scholarly productivity based on journal publication is associated with clinical performance during residency training. Our findings suggest that residents who invest substantial efforts in research are not compromised in their abilities to learn medicine and care for patients.

You are seeing Mr Roberts, a 69-year-old retired office manager referred from the emergency department for treatment of atrial fibrillation (AF). He presented the previous night to the emergency department with shortness of breath and palpitations and was found to be in AF with a rapid ventricular response and a heart rate of 140 bpm. He was treated with intravenous diltiazem and spontaneously converted to sinus rhythm. He was then discharged from the emergency department with an outpatient cardiology appointment. He has a background history of hypertension but no other cardiac disease. His only medication is a thiazide diuretic. On questioning, he reports experiencing several episodes of palpitations over the last 2 to 3 years; typically, these are brief and self-limited. His transthoracic echocardiogram, thyroid studies, and electrolytes are all within normal limits. His ECG shows sinus rhythm with no other significant abnormality. His CHADS 2 score is 1 and CHA 2 DS 2 -Vasc score is 2. He has a family history of gastrointestinal hemorrhage-associated death and is uncomfortable about long-term anticoagulation. Additionally, he is reluctant about taking a daily medication plus his blood pressure pill. How might you present current best practice while ensuring that his treatment program is consistent with his goals, values, and preferences? Introduction AF is the most common arrhythmia requiring treatment, affecting ≈5 million Americans, with the prevalence expected to double by 2050.1-3 AF accounts for more than a third of all hospitalizations for cardiac rhythm disturbances. Hospitalization for AF has risen dramatically over the past 20 years and is projected to continue to rise as the population ages. 4 Importantly, AF is associated with a doubling in patient-matched and adjusted mortality.5 Atrial fibrillation can range from completely asymptomatic to highly symptomatic and can negatively affect patients' quality of life if left untreated. 6 Studies have demonstrated significant gaps in AF patient's knowledge about their condition, as well as knowledge of the risks and benefits of the treatment they are currently taking for their AF despite their disease being treated for several years. 7A landmark study in 2007 observed multidisciplinary groups of clinicians and patients discussing AF management and noted that all groups recognized the difficulties in managing the disease, but no group agreed with the other on the optimal way to improve patient care.8 A meta-synthesis of qualitative studies from 2012 examined the perspectives of both clinicians and patients and found that patients often experienced a paternalistic model of decision making, whereas clinicians involved in these same conversations reported that a shared decision making (SDM) model was used. 9 This discordance has been reported by other studies and indicates that patients wish for more information about their treatment options and that clinician bias and practice style, not patient preferences, influenced the outcome of starting oral anticoagul...

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