Emotional Memory Moderates the Relationship Between Sigma Activity and Sleep-Related Improvement in Affect

Sleep is essential for regulating mood and affect, and it also consolidates emotional memories. The mechanisms underlying these effects may overlap. Here, we investigated whether the influence of sleep on affect may be moderated by emotional memory consolidation. Young adults viewed 45 negative and 45 neutral pictures before taking an afternoon nap measured with polysomnography. Following the nap period, participants viewed the same pictures intermixed with novel ones and indicated whether they remembered each picture. Affect was measured with the Positive and Negative Affect Schedule (PANAS) at baseline before the initial picture viewing task, immediately following the initial picture viewing task, and following the nap. The ratio of positive to negative affect declined over the task period and recovered over the nap period. When controlling for pre-nap affect, NREM sigma activity significantly predicted post-nap affect. Memory for negative pictures moderated this relationship such that a positive association between sigma activity and affect occurred when memory was low but not when memory was high. These results indicate that emotional memory consolidation influences the relationship between nap physiology and mood

Detecting explosive-device emplacement at multiple granularities

This paper appeared in the Proceedings of the Military Sensing Society (MSS) National Symposium, Las Vegas, Nevada, U.S., July 2010.We report on experiments with a nonimaging sensor network for detection of suspicious behavior related to pedestrian emplacement of IEDs. Emplacement is the time when detection is the most feasible for IEDs since it almost necessarily must involve some unusual behaviors. Sensors at particularly dangerous locations such as bridges, culverts, road narrowings, and road intersections could provide early warning of such activity. Imaging for surveillance has weaknesses in its susceptibility to occlusion, problems operating at night, sensitivity to angle of view, high processing requirements, and need to invade privacy. Our approach is to use a variety of nonimaging sensors with different modalities to track people. We particularly look for clues as to accelerations since these are often associated with suspicious behavior. Our approach involves preanalyzing terrain for the probability of emplacement of an IED, then combining this with real-time assessment of suspicious behavior obtained from probabilities of location derived from sensor data. We describe some experiments with a prototype sensor network and the promising results obtained.supported by the U.S. National Science Foundation under grant 0729696 of the EXP ProgramApproved for public release; distribution is unlimited

Setup and performance of RHIC for the 2008 run with deuteron-gold collisions.

This year (2008) deuterons and gold ions were collided in the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory (BNL) for the first time since 2003. The setup and performance of the collider for the 2008 run is reviewed with a focus on improvements that have led to an order of magnitude increase in luminosity over that achieved in the 2003 run

Inhibition of Dipeptidyl Peptidase-4 by Vildagliptin During Glucagon-Like Peptide 1 Infusion Increases Liver Glucose Uptake in the Conscious Dog

OBJECTIVE—This study investigated the acute effects of treatment with vildagliptin on dipeptidyl peptidase-4 (DPP-4) activity, glucagon-like peptide 1 (GLP-1) concentration, pancreatic hormone levels, and glucose metabolism. The primary aims were to determine the effects of DPP-4 inhibition on GLP-1 clearance and on hepatic glucose uptake

Resveratrol has antiinflammatory and antifibrotic effects in the peptidoglycan‐polysaccharide rat model of Crohn's disease

Background: Resveratrol has antiinflammatory and antifibrotic effects. Resveratrol decreases proliferation and collagen synthesis by intestinal smooth muscle cells. We hypothesized that resveratrol would decrease inflammation and fibrosis in an animal model of Crohn's disease. Methods: Peptidoglycan‐polysaccharide (PG‐PS) or human serum albumin (HSA) was injected into the bowel wall of Lewis rats at laparotomy. Resveratrol or vehicle was administered daily by gavage 1–27 days postinjection. On day 28, gross abdominal and histologic findings were scored. Cecal collagen content was measured by colorimetric analysis of digital images of trichrome‐stained sections. Cecal levels of procollagen, cytokine, and growth factor mRNAs were determined. Results: PG‐PS‐injected rats (vehicle‐treated) developed more fibrosis than HSA‐injected rats by all measurements: gross abdominal score ( P < 0.001), cecal collagen content ( P = 0.04), and procollagen I and III mRNAs ( P ≤ 0.0007). PG‐PS‐injected rats treated with 40 mg/kg resveratrol showed a trend toward decreased gross abdominal score, inflammatory cytokine mRNAs, and procollagen mRNAs. PG‐PS‐injected rats treated with 100 mg/kg resveratrol had lower inflammatory cytokine mRNAs (IL‐1β [3.50 ± 1.08 vs. 10.79 ± 1.88, P = 0.005], IL‐6 [17.11 ± 9.22 vs. 45.64 ± 8.83, P = 0.03], tumor necrosis factor alpha (TNF‐α) [0.80 ± 0.14 vs. 1.89 ± 0.22, P = 0.002]), transforming growth factor beta 1 (TGF‐β1) mRNA (2.24 ± 0.37 vs. 4.06 ± 0.58, P = 0.01), and histologic fibrosis score (6.4 ± 1.1 vs. 9.8 ± 1.0; P = 0.035) than those treated with vehicle. There were trends toward decreased gross abdominal score and decreased cecal collagen content. Procollagen I, procollagen III, and IGF‐I mRNAs also trended downward. Conclusions: Resveratrol decreases inflammatory cytokines and TGF‐β1 in the PG‐PS model of Crohn's disease and demonstrates a promising trend in decreasing tissue fibrosis. These findings may have therapeutic applications in inflammatory bowel disease. (Inflamm Bowel Dis 2011;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90530/1/21843_ftp.pd

Accelerating Drug Development Using Biomarkers: A Case Study with Sitagliptin, A Novel DPP4 Inhibitor for Type 2 Diabetes

The leveraged use of biomarkers presents an opportunity in understanding target engagement and disease impact while accelerating drug development. For effective integration in drug development, it is essential for biomarkers to aid in the elucidation of mechanisms of action and disease progression. The recent years have witnessed significant progress in biomarker selection, validation, and qualification, while enabling surrogate and clinical endpoint qualification and application. Biomarkers play a central role in target validation for novel mechanisms. They also play a central role in the learning/confirming paradigm, particularly when utilized in concert with pharmacokinetic/pharmacodynamic modeling. Clearly, these attributes make biomarker integration attractive for scientific and regulatory applications to new drug development. In this review, applications of proximal, or target engagement, and distal, or disease-related, biomarkers are highlighted using the example of the recent development of sitagliptin for type 2 diabetes, wherein elucidation of target engagement and disease-related biomarkers significantly accelerated sitagliptin drug development. Importantly, use of biomarkers as tools facilitated design of clinical efficacy trials while streamlining dose focus and optimization, the net impact of which reduced overall cycle time to filing as compared to the industry average

Dipeptidyl Peptidase-4 Inhibition by Vildagliptin and the Effect on Insulin Secretion and Action in Response to Meal Ingestion in Type 2 Diabetes

OBJECTIVE—The purpose of this study was to determine the mechanism by which dipeptidyl peptidase-4 inhibitors lower postprandial glucose concentrations

Closed-Loop Insulin Delivery Using a Subcutaneous Glucose Sensor and Intraperitoneal Insulin Delivery: Feasibility study testing a new model for the artificial pancreas

International audienceOBJECTIVE: Attempts to build an artificial pancreas by using subcutaneous insulin delivery from a portable pump guided by an subcutaneous glucose sensor have encountered delays and variability of insulin absorption. We tested closed-loop intraperitoneal insulin infusion from an implanted pump driven by an subcutaneous glucose sensor via a proportional-integral-derivative (PID) algorithm. RESEARCH DESIGN AND METHODS: Two-day closed-loop therapy (except for a 15-min pre-meal manual bolus) was compared with a 1-day control phase with intraperitoneal open-loop insulin delivery, according to randomized order, in a hospital setting in eight type 1 diabetic patients treated by implanted pumps. The percentage of time spent with blood glucose in the 4.4-6.6 mmol/l range was the primary end point. RESULTS During the closed-loop phases, the mean +/- SEM percentage of time spent with blood glucose in the 4.4-6.6 mmol/l range was significantly higher (39.1 +/- 4.5 vs. 27.7 +/- 6.2%, P = 0.05), and overall dispersion of blood glucose values was reduced among patients. Better closed-loop glucose control came from the time periods excluding the two early postprandial hours with a higher percentage of time in the 4.4-6.6 mmol/l range (46.3 +/- 5.3 vs. 28.6 +/- 7.4, P = 0.025) and lower mean blood glucose levels (6.9 +/- 0.3 vs. 7.9 +/- 0.6 mmol/l, P = 0.036). Time spent with blood glucose <3.3 mmol/l was low and similar for both investigational phases. CONCLUSIONS: Our results demonstrate the feasibility of intraperitoneal insulin delivery for an artificial beta-cell and support the need for further study. Moreover, according to a semiautomated mode, the features of the pre-meal bolus in terms of timing and amount warrant further research

Is There Evidence That Oral Hypoglycemic Agents Reduce Cardiovascular Morbidity/Mortality? Yes

Athough type 2 diabetes is a heterogeneous condition encompassing multiple metabolic and vascular alterations, it can be easily described as a disease characterized by chronic hyperglycemia and increased cardiovascular (CV) risk. Hyperglycemia is the diagnostic criterion for diabetes, the target for antidiabetic therapy, and, together with A1C, the marker of glycemic control. Progressive worsening of glycemic control has been described in type 2 diabetic patients irrespective of initial form of treatment, leading the U.K. Prospective Diabetes Study (UKPDS) investigators to describe such changes as the “natural history” of the disease ( 1). Still, maintaining good glycemic control is crucial, since it is associated with marked reduction in the risk of developing retinopathy, nephropathy, and neuropathy in both type 1 ( 2) and type 2 diabetic patients ( 1). But it is CV disease that worsens long-term prognosis in type 2 diabetes ( 3), to the point that diabetes has been proposed as a CV risk equivalent owed to the observation that 10-year risk for major coronary events approximates the risk in CHD in patients without diabetes with previous CV events ( 4), increased case fatality rate after myocardial infarction, and worse overall prognosis after CHD ( 5). In diabetic patients, even after correction for known CV risk factors, the incidence of myocardial infarction or stroke is two- to threefold higher than in the nondiabetic population, with a twofold increase in risk of death ( 6), suggesting that some feature of diabetes must confer excessive propensity toward CV disease. Can this feature be hyperglycemia? No better issue can be chosen for debate. From an epidemiological point of view, there is evidence that the risk of CV mortality increases with the increase of plasma glucose concentrations ( 7) and A1C values ( 8). Moreover, multiple atherogenic mechanisms have been identified that can be activated by hyperglycemia ( 9)