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

P53 codon 72 polymorphisms have been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the interaction of select risk factors and p53 codon 72 polymorphisms in gastric cancer susceptibility. 155 gastric cancer cases and 134 cancer-free controls were enrolled at the Memorial Sloan Kettering Cancer Center (MSKCC) from November 1992 to November 1994. The crude odds ratio (OR1) associated with the (Pro/Pro) polymorphism and the risk of gastric cancer was 1.27 (0.70-2.33). Adjusting for age, sex, race and education (OR2) and further adjusting for BMI, calories, sodium, smoking, vitamin C, fiber, alcohol, fat, and H. pylori status (OR3) did not yield significant results. Significant joint effects were associated with high fat consumption (OR1 = 2.61 (95% CI:1.13-6.06); OR2 = 2.85 (95% CI:1.14-7.15) for total cancers and for proximal tumors (OR1 = 2.56 (95%CI:1.00-6.54)). The low vitamin C intake/high-risk polymorphism group (Pro/Pro) had an OR1 of 4.82 (95% CI: 1.

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sensitivity in detecting lesions on capsule endoscopy. A group of novice readers can pre-screen recordings to thumbnail potential areas of small bowel lesions for further review. These thumbnails must be reviewed to determine the clinical relevance. Further studies are ongoing to assess other cohorts. INTRODUCTIONCapsule endoscopy is a new diagnostic procedure developed for the complete examination of the small intestine through video images transmitted from an ingestible camera [1][2][3] . Briefly, the PillCam TM capsule endoscopy and diagnostic imaging system (GIVEN Imaging, Yoqneam, Israel) is a commercially available system consisting of three major components: PillCam TM capsule which captures images and transmits digital pictures (at 2 frames/s) over an 8-h period, sensor array and data recorder, which receives and records the data transmitted from the PillCam TM capsule and RAPID TM Workstation, which is used to initialize the data recorder and to download and process the raw data from the data recorder [4,5] . The processed information, composed of approximately 50 000 still images collected over an 8-h period, can be reviewed as a continuous video stream. The reported time range typically needed for a complete review of a single capsule endoscopy recording case is anywhere from 50 [6,7] to 120 min [8] . Numerous studies have now demonstrated that the sensitivity and specificity of capsule endoscopy are advantageous over the traditional diagnostic methods of small bowel lesions [5][6][7][9][10][11] . Capsule endoscopy may also reduce total medical utilization and costs as well as improve patient's quality of life in certain circumstances [12] . RAPID COMMUNICATION Sensitivity and inter METHODS:Ten capsule endoscopy cases of small bowel lesions were administered to the readers. Gold standard findings were pre-defined by gastroenterologists. Ten gold standard "targets" were identified among the 10 cases. Readers were given a 30-min overview of Rapid Reader software and instructed to mark any potential areas of abnormalities. A software program was developed using SAS to analyze the thumbnailed findings. RESULTS:The overall sensitivity for detecting the gold standard findings was 80%. As a group, at least 5 out of 10 readers detected each gold standard finding per recording. All the gold standard targets were identified when the readers' results were combined. Incidental finding/false positive rate ranged between 8.2-59.8 per reader. CONCLUSION:A panel of medical students with minimal endoscopic experience can achieve high