The Interplay between α-Synuclein and Microglia in α-Synucleinopathies.

Synucleinopathies are a set of devastating neurodegenerative diseases that share a pathologic accumulation of the protein α-synuclein (α-syn). This accumulation causes neuronal death resulting in irreversible dementia, deteriorating motor symptoms, and devastating cognitive decline. While the etiology of these conditions remains largely unknown, microglia, the resident immune cells of the central nervous system (CNS), have been consistently implicated in the pathogenesis of synucleinopathies. Microglia are generally believed to be neuroprotective in the early stages of α-syn accumulation and contribute to further neurodegeneration in chronic disease states. While the molecular mechanisms by which microglia achieve this role are still being investigated, here we highlight the major findings to date. In this review, we describe how structural varieties of inherently disordered α-syn result in varied microglial receptor-mediated interactions. We also summarize which microglial receptors enable cellular recognition and uptake of α-syn. Lastly, we review the downstream effects of α-syn processing within microglia, including spread to other brain regions resulting in neuroinflammation and neurodegeneration in chronic disease states. Understanding the mechanism of microglial interactions with α-syn is vital to conceptualizing molecular targets for novel therapeutic interventions. In addition, given the significant diversity in the pathophysiology of synucleinopathies, such molecular interactions are vital in gauging all potential pathways of neurodegeneration in the disease state.

A single institution pre-/post-comparison after introduction of an external urinary collection device for female medical patients.

Background: External urinary collection devices (EUCDs) may serve as an alternative to indwelling urinary catheters (IUCs) and decrease the rate of catheter associated urinary tract infections (CAUTIs). PureWick® is a novel female EUCD; however, no study has definitively proven benefit regarding reduction of CAUTIs. Aim: We sought to compare the CAUTI rate and IUC days before and after availability of the PureWick® EUCD at a single institution. We provide a descriptive analysis of female medical patients receiving an EUCD. Methods: A retrospective review of adult female patients admitted to a single institution on a medical service who received an IUC and/or an EUCD was performed. Patients who received an IUC in the 3 months before EUCD availability (PRE) were compared to patients who received an IUC and/or EUCD in the 12 months after (POST). Results: Out of 848 female patients, 292 received an EUCD in the POST cohort and overall, 656 received an IUC (259 (100%) PRE vs. 397 (67.4%) POST). Compared to the PRE cohort, the POST cohort had a higher number of IUC days (median, 3 vs 2 days, p = 0.001) and a higher rate of CAUTI (infections per 1000 catheter days, 9.3 vs 2.3, p = 0.001). The rate of UTI associated with EUCD use was 9.8 infections per 1000 device days. Discussion: While EUCDs might appear to be a promising alternative to IUCs for female patients, this single center pre-/post-analysis found that both the number of IUC days and the CAUTI rate increased after introduction of a female EUCD.

Role of and Recent Evidence for Antiplatelet Therapy in Prevention of Cardiovascular Disease in Diabetes.

PURPOSE OF REVIEW: When treating patients with diabetes mellitus (DM), the benefits of antiplatelet therapy in preventing cardiovascular disease must be weighed against an increased risk of bleeding. Recent trials have sought to determine both the optimal anti-platelet regimen for patients with DM, and who specifically requires medication among the DM population. This paper will review recent trials and evidence recommending the use of antiplatelet therapy in the prevention of cardiovascular disease in patients with diabetes. RECENT FINDINGS: Seven notable trials assessed the effectiveness of antiplatelet therapy in the DM population. The ASCEND trial concluded 100 mg aspirin/day reduced rates of serious vascular events (OR 0.88, p < 0.01) but also increased rates of major bleeding events (OR 1.29, p < 0.01). The DAPT study revealed a longer dual antiplatelet regimen (30 months vs. 18 months) after coronary stent placement was more effective in reducing rates of stent thrombosis (0.5% vs. 1.1%, p = 0.06) and rates of myocardial infarction (3.5% vs. 4.8%, p = 0.06). DECLARE DIABETES showed that adding cilostazol to dual antiplatelet therapy after a coronary stent procedure reduced rates of in-stent and in-segment late loss and increased rates of revascularization (p < 0.04). In PEGASUS-TIMI, daily ticagrelor demonstrated reduced rates of major adverse cardiovascular and cerebrovascular events (OR 0.84, p < 0.04). The DAVID trial compared daily picotamide with daily aspirin therapy, finding reduced mortality rates in the picotamide group (OR 0.55, p < 0.05). Lastly, ACUITY found bivalirudin monotherapy resulted in lower rates of major bleeding events when compared to a glycoprotein IIb/IIa inhibitor and heparin or bivalirudin combination regimen (p < 0.01). Dual antiplatelet therapy guidelines still typically revolve around aspirin, but an increasing number of studies have demonstrated other drugs that may have a role in preventing atherosclerotic cardiovascular disease while decreasing the risk of major bleeding. Overall, it is wise to weigh the cardiovascular risk of a DM patient before prescribing antiplatelet medication. More research is necessary to determine a universal drug or combination of drugs that is safe and effective for DM patients.