Progressive multifocal leukoencephalopathy in patients with systemic lupus erythematosus: a systematic literature review.

OBJECTIVE: To determine risk factors for progressive multifocal leukoencephalopathy (PML) in systemic lupus erythematosus (SLE) patients, and understand how underlying disease or treatment for SLE may be associated with PML in this population. METHODS: Studies published in English between January 1, 1984 and October 31, 2014 that reported PML in adult SLE patients were included. Immunosuppression was defined as exposure to ≥1 immunosuppressant drug of interest at PML diagnosis: belimumab, rituximab, mycophenolate mofetil, azathioprine, cyclophosphamide, methotrexate and high-dose corticosteroids (>15 mg/day). Minimal immunosuppression was defined as low-dose corticosteroids (≤15 mg/day) and/or anti-malarials. RESULTS: Thirty-five publications met our inclusion criteria: four observational studies, two large case series, and 29 case reports that described 35 cases. Reported PML incidence rates among SLE patients based on observational studies ranged from 1.0 to 2.4 cases/100,000 person-years. Of the 35 case reports, three cases were exposed to no immunosuppressant drugs at PML diagnosis, five cases had minimal immunosuppression, 23 cases had immunosuppression, and four cases were indeterminate. CONCLUSIONS: The evidence from this literature review suggests that, while PML is a very rare disease in SLE patients, there does appear to be an increased risk of PML associated with SLE compared to the general population, potentially due to immunosuppression, other contributing factors in their underlying disease, treatments prescribed to manage disease, or some combination of these factors. Additional large observational studies, designed to assess exposure to drugs of interest and complicated treatment histories, are needed to provide further evidence about potential mechanisms contributing to the onset of PML in SLE patients.

Melatonin modulates M4-type ganglion-cell photoreceptors.

In the retina, melatonin is secreted at night by rod/cone photoreceptors and serves as a dark-adaptive signal. Melatonin receptors have been found in many retinal neurons including melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), suggesting it could modulate the physiology of these inner retinal photoreceptors. Here, we investigated whether melatonin modulates the alpha-like M4-type ipRGCs, which are believed to mediate image-forming vision as well as non-image-forming photoresponses. Applying melatonin during daytime (when endogenous melatonin secretion is low) caused whole-cell-recorded M4 cells' rod/cone-driven depolarizing photoresponses to become broader and larger, whereas the associated elevation in spike rate was reduced. Melanopsin-based light responses were not affected significantly. Nighttime application of the melatonin receptor antagonist luzindole also altered M4 cells' rod/cone-driven light responses but in the opposite ways: the duration and amplitude of the graded depolarization were reduced, whereas the accompanying spiking increase was enhanced. These luzindole-induced changes confirmed that M4 cells are modulated by endogenous melatonin. Melatonin could induce the above effects by acting directly on M4 cells because immunohistochemistry detected MT1 receptors in these cells, although it could also act presynaptically. Interestingly, the daytime and nighttime recordings showed significant differences in resting membrane potential, spontaneous spike rate and rod/cone-driven light responses, suggesting that M4 cells are under circadian control. This is the first report of a circadian variation in ipRGCs' resting properties and synaptic input, and of melatoninergic modulation of ipRGCs.

Correlates of bone mineral density in men of African ancestry: the Tobago bone health study.

UNLABELLED: Correlates of BMD were examined in a cross-sectional analysis of men of West African ancestry. BMD, measured at the total hip and the femoral neck subregion, was associated with age, anthropometric, lifestyle, and medical factors in multiple linear regression models. These models explained 25-27% of the variability in total hip and femoral neck BMD, respectively, and 13% of the variability in estimated volumetric BMD. OBJECTIVE: To examine the correlates of bone mineral density (BMD) in men of West African ancestry. METHODS: Two thousand five hundred and one men aged 40 to 93 years were recruited from the Caribbean Island of Tobago. Participants completed a questionnaire and physical examination. We measured hip BMD and body composition, using DXA. Volumetric BMD was estimated as bone mineral apparent density (BMAD). RESULTS: BMD was 10% and 20% higher in African Caribbean males compared to U.S. non-Hispanic black and white males, respectively. In multiple linear regression models, greater lean mass, history of working on a fishing boat or on a farm, frequent walking, and self-reported diabetes were significantly associated with higher BMD. Fat mass, history of farming, and self-reported hypertension were also associated with higher BMAD. Older age, mixed African ancestry, and history of a fracture were associated with lower BMD and BMAD. Lean body mass explained 20%, 18% and 6% of the variance in BMD at the total hip, femoral neck and BMAD, respectively. CONCLUSIONS: African Caribbean males have the highest BMD on a population level ever reported. Lean mass was the single most important correlate. Variability in BMD/BMAD was also explained by age, mixed African ancestry, anthropometric, lifestyle, and medical factors.