Antagonism of group III metabotropic glutamate receptors results in impairment of LTD but not LTP in the hippocampal CA1 region, and prevents long-term spatial memory

Recently it has emerged that hippocampal long-term depression (LTD) may play an important role in the acquisition and storage of spatial memories. This form of synaptic plasticity is tightly regulated by metabotropic glutamate receptors (mGluRs) that negatively couple to adenylyl cyclase. Activation of group III mGluRs is necessary for persistent hippocampal LTD, but is not required for depotentiation or long-term potentiation (LTP) in the dentate gyrus in vivo. In the CA1 region antagonism of group III mGluRs prevents LTD in vivo. Effects on LTP in vivo are as yet unknown. We investigated the effects of group III mGluR antagonism on LTP and LTD at Schaffer collateral-CA1 synapses, and on spatial learning in the eight-arm radial maze. Daily application of the group III mGluR antagonist (R,S)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG) resulted in impairment of long-term (reference) memory, with effects becoming apparent 4 days after training and drug treatment began. Short-term (working) memory was unaffected throughout the 10-day study. Application of CPPG prevented LTD, but not LTP, in the CA1 region. These data suggest that activation of group III mGluRs is required for the establishment of spatial long-term memory. Their exclusive role in mediating hippocampal LTD provides correlational evidence for a role for LTD in the type of spatial learning studied.     

Effect of non‐steroidal anti‐inflammatory drugs on non‐melanoma skin cancer incidence in the SKICAP‐AK trial

Recent studies link the prostaglandin metabolic pathway to skin carcinogenesis expanding possibilities that cyclooxygenase (COX) inhibitors may be utilized in non‐melanoma skin cancer (NMSC) chemoprevention. Using data from a study of the efficacy of retinol supplementation on incidence of NMSC, we sought to determine the role of non‐steroidal anti‐inflammatory drugs (NSAIDs) in NMSC development. Cox proportional hazards models describe the relationship between NSAID use and time to first squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) among participants categorized by use pattern: continuous users (use for length of study duration), new users (use for less than study duration), and non‐users. For SCC and BCC, there was a statistically significant protective effect for participants who reported use for less than the study duration (HR = 0.49, 95%CI 0.28–0.87 and HR = 0.43, 95%CI 0.25–0.73, respectively). Categorical examination of NSAIDs (aspirin (ASA) vs. non‐ASA NSAIDs) showed significant effects for BCC among those using non‐ASA NSAIDs for less than the study duration (HR = 0.33, 95%CI 0.13–0.80). For SCC and BCC, NSAID use of shorter duration and potentially more recent, was more protective than longer duration of use. These results are counter to the idea that longer duration of NSAID use is more protective. Additional investigations are needed into the role NSAIDs play in the chemoprevention of NMSC. Copyright © 2009 John Wiley & Sons, Ltd.     

Residual effects of hypnotic drugs in aging drivers submitted to simulated accident scenarios: an exploratory study

Rationale  

The effects of hypnotic drugs on driving performance are most often evaluated on young healthy subjects by using a monotonous motorway driving test. The effects of drugs in urban driving situations have not yet been evaluated in any age group. Our objectives were to assess residual effects of the most prescribed hypnotics, zolpidem and zopiclone, on older middle-age drivers' capacities in an urban situation.     

The way forward

Good public-health decisionmaking is dependent on reliable and timely statistics on births and deaths (including the medical causes of death). All high-income countries, without exception, have national civil registration systems that record these events and generate regular, frequent, and timely vital statistics. By contrast, these statistics are not available in many low-income and lower-middle-income countries, even though it is in such settings that premature mortality is most severe and the need for robust evidence to back decisionmaking most critical. Civil registration also has a range of benefits for individuals in terms of legal status, and the protection of economic, social, and human rights. However, over the past 30 years, the global health and development community has failed to provide the needed technical and financial support to countries to develop civil registration systems. There is no single blueprint for establishing and maintaining such systems and ensuring the availability of sound vital statistics. Each country faces a different set of challenges, and strategies must be tailored accordingly. There are steps that can be taken, however, and we propose an approach that couples the application of methods to generate better vital statistics in the short term with capacity-building for comprehensive civil registration systems in the long run.     

The Diabetes Self-management Assessment Report Tool (D-SMART): process evaluation and patient satisfaction

PURPOSE: The purpose of this article is to present the results of the process evaluation and patient experience in completing the Diabetes Self-management Assessment Report Tool (D-SMART), an instrument within the AADE Outcome System to assist diabetes educators to assess, facilitate, and track behavior change in the provision of diabetes self-management education (DSME). METHODS: The D-SMART was integrated into computer and telephonic systems at 5 sites within the Pittsburgh Regional Initiative for Diabetes Education (PRIDE) network. Data were obtained from 290 patients with diabetes using the system at these programs via paper-and-pencil questionnaires following baseline D-SMART assessments and electronic system measurement of system performance. Process evaluation included time of completion, understanding content, usability of technology, and satisfaction with the system. Patients were 58% female and 85% Caucasian and had a mean age of 58 years. Fifty-six percent of patients had no more than a high school education, and 78% had Internet access at home. RESULTS: Most patients reported completing the D-SMART at home (78%), in 1 attempt (86%) via the Internet (55%), and in less than 30 minutes. Seventy-six percent believed the questions were easy to understand, and 80% did not need assistance. Age was negatively associated with ease of use. Moreover, 76% of patients believed the D-SMART helped them think about their diabetes, with 67% indicating that it gave the diabetes educator good information about themselves and their diabetes. Most (94%) were satisfied with the D-SMART. Level of satisfaction was independent of the system being used. CONCLUSIONS: The D-SMART was easily completed at home in 1 attempt, content was understandable, and patients were generally satisfied with the wording of questions and selection of answers. The D-SMART is easy to use and enhanced communication between the patient and clinician; however, elderly patients may need more assistance. Computer-based and telephonic D-SMARTs appear to be feasible and useful assessment methods for diabetes educators.     

Glucocorticoids in the control of neuroinflammation

Glucocorticoids are a class of steroid hormones that are endowed with profound anti-inflammatory and immunosuppressive activities. Endogenous glucocorticoids are key players in the modulation of the immune system and establish an endocrine basis of many inflammatory diseases. In addition, synthetic glucocorticoids are amongst the most commonly prescribed drugs worldwide for the treatment of autoimmune disorders. In this review we summarize our present knowledge on the mechanisms by which glucocorticoids impact on multiple sclerosis (MS), a highly prevalent neuroinflammatory disease, and its animal model experimental autoimmune encephalomyelitis (EAE). In spite of the new methodologies that have become available during recent years, we are still far from a comprehensive picture of the mechanism by which glucocorticoids control neuroinflammation.     

Three new alpha-globin variants: Hb Itapira [alpha30(B11)Glu-->Val (alpha1)], Hb Bom Jesus Da Lapa [alpha30(B11)Glu-->Ala (alpha1)] and Hb Boa Esperança [alpha16(A14)Lys-->Thr (alpha2)

Three novel alpha-globin variants were found during a screening program for hemoglobinopathies in blood donors at the UNICAMP Hematology and Hemotherapy Center, Campinas, State of S?o Paulo, Southeastern Brazil. They were named for the town of origin of the carrier as Hb Itapira [alpha30(B11)Glu-->Val], Hb Bom Jesus da Lapa [alpha30(B11)Glu-->Ala] and Hb Boa Esperan?a [alpha16(A14)Lys-->Thr]. Hb Itapira, like Hb Bom Jesus da Lapa, shows an electrophoretic mobility similar to that of Hb S [beta6(A3)GluVal, GAG-->GTG] at alkaline pH; it is associated with a triplicate alpha-globin allele (alphaalphaalpha(anti 3.7)) and corresponds to only 5.5% of the total hemoglobin (Hb). Hb Boa Esperan?a, found in two different individuals, moves faster than Hb A and exhibits an abnormal functional performance.