Background: Dietary magnesium intake has been favorably associated with reduced risk of metabolic outcomes in observational studies; however, few randomized trials have introduced a systemsbiology approach to explore molecular mechanisms of pleiotropic metabolic actions of magnesium supplementation. Objective: We examined the effects of oral magnesium supplementation on metabolic biomarkers and global genomic and proteomic profiling in overweight individuals. Design: We undertook this randomized, crossover, pilot trial in 14 healthy, overweight volunteers [body mass index (in kg/m 2 ) 25] who were randomly assigned to receive magnesium citrate (500 mg elemental Mg/d) or a placebo for 4 wk with a 1-mo washout period. Fasting blood and urine specimens were collected according to standardized protocols. Biochemical assays were conducted on blood specimens. RNA was extracted and subsequently hybridized with the Human Gene ST 1.0 array (Affymetrix, Santa Clara, CA). Urine proteomic profiling was analyzed with the CM10 ProteinChip array (Bio-Rad Laboratories, Hercules, CA). Results: We observed that magnesium treatment significantly decreased fasting C-peptide concentrations (change: 20.4 ng/mL after magnesium treatment compared with +0.05 ng/mL after placebo treatment; P = 0.004) and appeared to decrease fasting insulin concentrations (change: 22.2 lU/mL after magnesium treatment compared with 0.0 lU/mL after placebo treatment; P = 0.25). No consistent patterns were observed across inflammatory biomarkers. Gene expression profiling revealed up-regulation of 24 genes and down-regulation of 36 genes including genes related to metabolic and inflammatory pathways such as C1q and tumor necrosis factorrelated protein 9 (C1QTNF9) and pro-platelet basic protein (PPBP). Urine proteomic profiling showed significant differences in the expression amounts of several peptides and proteins after treatment. Conclusion: Magnesium supplementation for 4 wk in overweight individuals led to distinct changes in gene expression and proteomic profiling consistent with favorable effects on several metabolic pathways. This trial was registered at clinicaltrials.gov as NCT00737815.

The patient had multiple sclerosis while receiving ocrelizumab monotherapy. EXPOSURES Ocrelizumab monotherapy.RESULTS A 78-year-old man with progressive multiple sclerosis treated with ocrelizumab monotherapy for 2 years presented with 2 weeks of progressive visual disturbance and confusion. Examination demonstrated a right homonymous hemianopia, and magnetic resonance imaging revealed an enlarging nonenhancing left parietal lesion without mass effect. Cerebrospinal fluid revealed 1000 copies/mL of JC virus, confirming the diagnosis of PML. Blood work on diagnosis revealed grade 2 lymphopenia, with absolute lymphocyte count of 710/μL, CD4 of 294/μL (reference range, 325-1251/μL), CD8 of 85/μL (reference range, 90-775/μL), CD19 of 1/μL, preserved CD4/CD8 ratio (3.45), and negative HIV serology. Retrospective absolute lymphocyte count revealed intermittent grade 1 lymphopenia that preceded ocrelizumab (absolute lymphocyte count range, 800-1200/μL). The patient's symptoms progressed over weeks to involve bilateral visual loss, right-sided facial droop, and dysphasia. Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated. The patient nevertheless declined rapidly and ultimately died. PML was confirmed at autopsy. CONCLUSIONS AND RELEVANCEIn this case report, PML occurrence was likely a result of the immunomodulatory function of ocrelizumab as well as age-related immunosenescence. This case report emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections such as elderly patients.

Few studies have been conducted in low-selenium areas of China to assess the relationships between dietary intake of selenium and zinc and the risk of squamous cell carcinoma of the esophagus (SCCE). We studied dietary mineral and trace element intake and risk of SCCE in a population- based, case-control study in Taixing, China, in 2000. A total of 218 SCCE patients and 415 population healthy controls were interviewed using a standard dietary and health questionnaire. The median and quartiles were calculated to represent the average level and distribution of selected dietary minerals and trace elements estimated by the Chinese Standard Tables of Food Composition. The adjusted odds ratios (ORs) comparing the highest with the lowest quartiles were 0.30 (95% confidence intervals, CIs = 0.13-0.67) for selenium intake and 0.28 (95% CI = 0.11-0.70) for zinc intake with obvious dose-dependent patterns (P values for trend = 0.01). The adjusted OR for the combined effect of selenium and zinc intake was 0.53 (95% CI = 0.29-0.96) after controlling for potential confounding factors, including age, gender, educational level, body mass index, and total energy intake. Our results suggested that the potential joint effect of zinc and selenium might contribute to SCCE risk. Increased dietary intake of selenium and zinc may decrease the risk of SCCE in a low-selenium area of China.

A multicenter, prospective, randomized comparison of a novel signal transmission capsule endoscope to an existing capsule endoscope. Eric H ChoiRiverside Medical Clinic, Riverside, California, ericchoimd@gmail.com Klaus Mergener