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.     

Effect of Preexposure to Triazoles on Susceptibility and Virulence of Rhizopus oryzae

Triazole prophylaxis has become the norm in patients with hematological malignancies. Breakthrough infections caused by Mucorales during triazole prophylaxis remain a challenging problem. We found that preexposure of Rhizopus oryzae to antifungal triazoles (fluconazole, voriconazole, posaconazole, and itraconazole) did not modify the in vitro susceptibility of Rhizopus oryzae to posaconazole. In contrast, preexposure of Rhizopus to triazoles was associated with the enhanced in vitro susceptibility of R. oryzae to amphotericin B. Preexposure to posaconazole did not alter the virulence of R. oryzae in the fly model of mucormycosis.     

Fluoroscopy: An essential diagnostic modality in the age of high-resolution cross-sectional imaging

The importance of fluoroscopy as an imaging modality has been minimized relative to other cross-sectional modalities, including high-resolution computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Fluoroscopy examinations have decreased in clinical practice due to reduced appreciation of its usefulness, insufficient training of residents, fewer staff with adequate expertise, and poor reimbursements relative to other modalities. We revisit and build upon the prior literature and history of this decreased utilization. We then seek to prove continued value, through categorized examples and within multiple subspecialties, wherein fluoroscopy plays an integral part toward clinical diagnoses as well as optimizing patient outcomes. This is particularly true for motility and esophageal disorders, where structure and function with real-time evaluation is essential.  We additionally show several post-operative cases where the synergy of fluoroscopy with CT and endoscopy is apparent.  The fluoroscopic radiologist also has the unique ability to vary patient positioning, as opposed to traditional CT or MRI, where orthogonal views are employed without positional or temporal changes. We turn attention to the modern era, with synergistic and novel cases demonstrating that fluoroscopy remains instrumental toward achieving a diagnosis alongside other modalities. Our cases stress the need to maintain expertise in fluoroscopy skill, and underline its continued importance in residency training programs.  We conclude that fluoroscopy is a relatively inexpensive modality that is often under-appreciated in diagnostic radiology. We suggest that competency in fluoroscopy is crucial for future generations of radiologists to both work with their peers, as well as to aid clinicians in the optimal treatment of patients.