Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease models

Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer’s disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE₂) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE₂ receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE₂/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD.     

Clinical outcomes of bypass-first versus endovascular-first strategy in patients with chronic limb-threatening ischemia due to infrageniculate arterial disease

Background

Chronic limb-threatening ischemia (CLTI), defined as ischemic rest pain or tissue loss secondary to arterial insufficiency, is caused by multilevel arterial disease with frequent, severe infrageniculate disease. The rise in CLTI is in part the result of increasing worldwide prevalence of diabetes, renal insufficiency, and advanced aging of the population. The aim of this study was to compare a bypass-first with an endovascular-first revascularization strategy in patients with CLTI due to infrageniculate arterial disease.

Patients with prosthetic joints: Are they at risk when receiving invasive dental procedures?

Most prosthetic joint infections (PJI) are due to wound contamination at the time of surgery. Some infections occur due to the hematogenous spread of bacteria from distant sites of infection. A review of the literature fails to associate PJI with transient bacteremias from invasive dental procedures. Several authors have described conditions which, they believe, render patients with prosthetic joints more at risk for infection. Prosthetic joint patients with these "high risk" conditions have the same types of infecting organisms as other patients with PJI. This indicates that the infecting bacteria are from wound contamination or distant sites of infection and not related to dental procedure bacteremias. Based on this review, antibiotic prophylaxis is not indicated for patients with prosthetic joints when receiving invasive dental procedures, since there is no proven benefit and there are known risks involved with the use of antibiotics. However, the American Dental Association (ADA) and the American Academy of Orthopaedic Surgeons (AAOS), in an advisory statement, suggest prophylaxis for "high risk" patients. The ADA and AAOS recommend a single dose of amoxicillin, cephradine, or clindamycin when prophylaxis is selected. The dentist is ultimately responsible for making treatment recommendations for his or her patients.     

Pharmaceutical Marketing: Implications for Medical Residency Training

An educational intervention was developed to improve family practice residents' ability to obtain useful information from pharmaceutical representatives. The curriculum is based on the traditional one-on-one drug detail. The objectives are to develop residents' skills in controlling the interview, promote skills for critically analyzing drug-promotional material, and discuss ethical issues. The contents include an assessment tool, suggested readings, and interview questions with rationale. After 5 years, residents' confidence in all areas of the curriculum improved significantly.     

Body size, fatness, and leanness of Mexican American children in Brownsville, Texas: changes between 1972 and 1983.

Changes in the height, weight, body mass index, triceps skinfold, and arm and estimated midarm muscle circumferences in lower socioeconomic Mexican American children, 6 through 17 years of age, from Brownsville, Texas, were documented on the basis of surveys done in 1972 and 1983. With the exception of height in youths ages 14-17, all parameters show gains at most ages, and in particular an increase in fatness. Brownsville Mexican American youth are similar in height, weight, and the body mass index to Mexican American youth in other areas of Texas. These trends confirm the large proportion of relatively short but heavy children among Mexican Americans.