BackgroundMost previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups.MethodsDNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS.ResultsA total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001).ConclusionsComprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.

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The study suggests that pharmacist-provided HBMR is effective in reducing readmissions and ED visits in the elderly. More studies in the Asian population are needed to determine its long term benefits and patient's acceptability.

The present study investigates whether producing gestures would facilitate route learning in a navigation task and whether its facilitation effect is comparable to that of hand movements that leave physical visible traces. In two experiments, we focused on gestures produced without accompanying speech, i.e., co-thought gestures (e.g., an index finger traces the spatial sequence of a route in the air). Adult participants were asked to study routes shown in four diagrams, one at a time. Participants reproduced the routes (verbally in Experiment 1 and non-verbally in Experiment 2) without rehearsal or after rehearsal by mentally simulating the route, by drawing it, or by gesturing (either in the air or on paper). Participants who moved their hands (either in the form of gestures or drawing) recalled better than those who mentally simulated the routes and those who did not rehearse, suggesting that hand movements produced during rehearsal facilitate route learning. Interestingly, participants who gestured the routes in the air or on paper recalled better than those who drew them on paper in both experiments, suggesting that the facilitation effect of co-thought gesture holds for both verbal and nonverbal recall modalities. It is possibly because, co-thought gesture, as a kind of representational action, consolidates spatial sequence better than drawing and thus exerting more powerful influence on spatial representation.

Highlights• Medication utilization trends for type 2 diabetes have changed significantly over the years with a shift towards newer agents, and in line with prevailing treatment guidelines. • Metformin is currently the most commonly prescribed glucose-lowering agent, while the use of insulin has increased tremendously in our institution. Use of sulfonylureas decreased, but to a lesser extent than other studies. • Glycemic control has remained largely stable throughout the 11-year study period, but the rate of severe hypoglycemia has increased. AbstractBackground: Use of glucose-lowering agents is a cornerstone in combating type 2 diabetes (T2DM). Treatment guidelines have changed significantly over the past decade. We report temporal trends in medication utilization, glycemic control and rate of severe hypoglycemia in T2DM patients at a tertiary referral center in Singapore. Methods: We analyzed data of 36 924 T2DM patients seen at Singapore General Hospital from 2007 to 2017. Annual age-, sex-and racially-standardized proportions of patients (a) prescribed with each class of glucose-lowering agent, (b) on various glucose-lowering regimens, and (c) had an HbA 1c of less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, or 9% or more were estimated using logistic regression. Poisson regression was used to estimate standardized rate of severe hypoglycemia. Results: From 2007 to 2017, use of metformin (45.9% to 59.6%) and insulin (24.4% to 57.9%) increased, while utilization of sulfonylureas (52.0% to 44.9%) decreased (all P < 0.001). Utilization of dipeptidyl peptidase-4 inhibitors (1.2% to 31.2%) and sodium-glucose cotransporter-2 inhibitors (0.5% to 7.4%) increased from 2008 to 2017 and 2012 to 2017, respectively (all P < 0.001). More patients were prescribed a combination of insulin and oral agents (17.3% to 46.0%, P < 0.001). The proportion of patients with HbA 1c of 8% or more increased (33.7% to 36.0%, P < 0.001). Rates of severe hypoglycemia (5.0 to 8.4 per 100 patient-years, P < 0.001) also rose. Conclusion: Medication utilization patterns have changed significantly over the past 11 years with a shift towards newer agents. Glycemic control has remained *Co-first author