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.

Prostatitis: Updates on diagnostic evaluation

Prostatitis accounts for almost 2 million office visits to urologists and primary care physicians. The label “prostatitis” refers to a diverse constellation of symptoms and disease processes. The diagnosis and treatment of this disorder present numerous challenges for the physician, including a lack of abnormal findings on physical examination, laboratory tests, and radiographic images. In this article, we offer a review of the current literature and recommendations for the evaluation and diagnosis of the patient presenting with prostatitis.     

Catastrophic failure of modular Zirconia—Ceramic femoral head components after total hip arthroplasty

Catastrophic failure of two zirconia—ceramic modular femoral heads occurred, despite the theoretical improved toughness of zirconia—ceramic relative to alumina—ceramic. This experience led the authors to return to cobalt—chromium as the metal of choice for articulation against polyethylene in total hip arthroplasty.     

Localized 1H NMR spectra of glutamate in the human brain.

Localized 1H NMR spectra at TE = 12 ms were obtained from cerebral cortex of human subjects using ISIS with surface suppression. The 2.29-ppm resonance was assigned to C4 glutamate with contributions from C4 glutamine and GABA using in vivo spectral editing and comparison of chemical shift with pure compounds. The measured intensity ratio between the 2.29 resonance and the creatine resonance at 3.03 ppm was in good agreement with the ratio predicted from previously reported measurements of glutamate, glutamine, and GABA concentrations in biopsied human brain tissue.     

Longitudinal predictors of continued tobacco use among patients diagnosed with cancer

Even though continued smoking by cancer patients adversely affects survival and quality of life, about one third of patients who smoked prior to their diagnosis continue to smoke after their diagnosis. The implementation of smoking cessation treatments for cancer patients has been slowed by the lack of data on correlates of tobacco use in this population. Thus, this longitudinal study assessed demographic, medical, addiction, and psychological predictors of tobacco use among 74 head, neck, and lung cancer patients. Multivariable binary logistic regression analyses, with outcome categorized as smoker or nonsmoker, indicated that the likelihoodthat patients would be a smoker was associated with lower levels of perceived risk and a higher level of quitting cons. Multivariable nominal logistic regression, with outcome classified as continuous smoker, continuous quitter, relapser, or follow-up quitter, indicated that: (a) patients categorized as continuous smokers reported significantly lower quitting self-efficacy than follow-up quitters and continuous quitters, (b) relapsers reported a significantly lower level of quitting self-efficacy than either follow-up quitters or continuous quitters, and (c) continuous smokers exhibited a significantly lower level of risk perceptions than continuous abstainers. These findings can be useful for the development and evaluation of treatments to promote smoking cessation among cancer patients. Support for this study was provided by National Institutes of Health Grants CA57708, CA06927, CA88610, CA95678, and CA76644.