Harnessing T-cell activity against prostate cancer: A therapeutic microparticulate oral cancer vaccine.

Prostate Cancer specific immunotherapy in combination with immune stimulating adjuvants may serve as a viable strategy for facilitating tumor regression and preventing recurrence. In this study, an oral microparticulate vaccine encapsulating tumor associated antigens (TAA) extracted from a murine prostate cancer cell line, TRAMP-C2, was formulated with the help of a spray dryer. Microparticles were characterized in vitro to determine their physicochemical properties and antigenicity.

Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury.

Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epithelial-mesenchymal transition (EMT), are thought to play a significant role in the etiology of DN. Microparticles (MPs), the small membrane vesicles containing bioactive signals shed by cells upon activation or during apoptosis, are elevated in diabetes and were identified as biomarkers in DN.

Activation of 6-Alkoxy-Substituted Methylenecyclopropane Nucleoside Analogs Requires Enzymatic Modification by Adenosine Deaminase-Like Protein 1.

To determine the mechanism of action of third-generation methylenecyclopropane nucleoside analogs (MCPNAs), DNA sequencing of herpes simplex virus 1 (HSV-1) isolates resistant to third-generation MCPNAs resulted in the discovery of G841S and N815S mutations in HSV-1 UL30. Purified HSV-1 UL30 or human cytomegalovirus (HCMV) UL54 was then subjected to increasing concentrations of MBX-2168-triphosphate (TP), with results demonstrating a 50% inhibitory concentration (IC) of ∼200 μM, indicating that MBX-2168-TP does not inhibit the viral DNA polymerase. Further metabolic studies showed the removal of a moiety on the guanine ring of MBX-2168.

Placenta growth factor and sFlt-1 as biomarkers in ischemic heart disease and heart failure: a review.

Coronary heart disease (CHD) and heart failure (HF) produce significant morbidity/mortality but identifying new biomarkers could help in the management of each. In this article, we summarize the molecular regulation and biomarker potential of PIGF and sFlt-1 in CHD and HF. PlGF is elevated during ischemia and some studies have shown PlGF, sFlt-1 or PlGF:sFlt-1 ratio, when used in combination with standard biomarkers, strengthens predictions of outcomes.

Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly.

Synthetic HDLs (sHDLs), small nanodiscs of apolipoprotein mimetic peptides surrounding lipid bilayers, were developed clinically for atheroma regression in cardiovascular patients. Formation of HDL involves interaction of apolipoprotein A-I (ApoA-I) with phospholipid bilayers and assembly into lipid-protein nanodiscs. The objective of this study is to improve understanding of physico-chemical aspects of HDL biogenesis such as the thermodynamics of ApoA-I-peptide membrane insertion, lipid binding, and HDL self-assembly to improve our ability to form homogeneous sHDL nanodiscs that are suitable for clinical administration.

Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea.

Background: The National Health Service in England advises hospitals collect data on hospital-onset diarrhoea (HOD). Contemporaneous data on HOD are lacking.

Aim: To investigate prevalence, aetiology and management of HOD on medical, surgical and elderly-care wards.

Molecular Mechanisms Underpinning Microparticle-Mediated Cellular Injury in Cardiovascular Complications Associated with Diabetes.

Microparticles (MPs) are small vesicles shed from the cytoplasmic membrane of healthy, activated, or apoptotic cells. MPs are very heterogeneous in size (100-1,000 nm), and they harbor proteins and surface antigens specific to cells they originate from. Virtually, all cells can shed MPs, and therefore, they can be found in all body fluids, but also entrapped in tissues.

Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines.

Clear cell renal cell carcinoma (ccRCC) is the most common and lethal form of urological cancer diagnosed globally. Mutations of the von Hippel-Lindau tumor-suppressor gene and the resultant overexpression of hypoxia-inducible factor (HIF)-1α protein are considered hallmarks of ccRCC. Persistently activated HIF-1α is associated with increased cell proliferation, angiogenesis, and epithelial⁻mesenchymal transition (EMT), consequently leading to ccRCC progression and metastasis to other organs.

Crosstalk Between Oxidative Stress and Endoplasmic Reticulum (ER) Stress in Endothelial Dysfunction and Aberrant Angiogenesis Associated With Diabetes: A Focus on the Protective Roles of Heme Oxygenase (HO)-1.

Type-2 diabetes prevalence is continuing to rise worldwide due to physical inactivity and obesity epidemic. Diabetes and fluctuations of blood sugar are related to multiple micro- and macrovascular complications, that are attributed to oxidative stress, endoplasmic reticulum (ER) activation and inflammatory processes, which lead to endothelial dysfunction characterized, among other features, by reduced availability of nitric oxide (NO) and aberrant angiogenic capacity. Several enzymatic anti-oxidant and anti-inflammatory agents have been found to play protective roles against oxidative stress and its downstream signaling pathways.

Macrophage-Derived Slit3 Controls Cell Migration and Axon Pathfinding in the Peripheral Nerve Bridge.

Slit-Robo signaling has been characterized as a repulsive signal for precise axon pathfinding and cell migration during embryonic development. Here, we describe a role for Sox2 in the regulation of Robo1 in Schwann cells and for Slit3-Robo1 signaling in controlling axon guidance within the newly formed nerve bridge following peripheral nerve transection injury. In particular, we show that macrophages form the outermost layer of the nerve bridge and secrete high levels of Slit3, while migratory Schwann cells and fibroblasts inside the nerve bridge express the Robo1 receptor.

The use of Socrative and Yammer online tools to promote interactive learning in pharmacy education.

Background And Purpose: Engagement of students in the didactic classroom setting restricts students' time spent towards active learning, which in turn, adversely affects the retention of concepts taught through traditional teaching methods. Thus, interactive learning is used as an alternative to engage students in the classroom and to enrich their learning experience. Integrating interactive learning activities has been shown to facilitate student learning and improve the learning outcomes.

Quality of stepped-wedge trial reporting can be reliably assessed using an updated CONSORT: crowd-sourcing systematic review.

Objectives: The Consolidated Standards of Reporting Trials extension for the stepped-wedge cluster randomized trial (SW-CRT) is a recently published reporting guideline for SW-CRTs. We assess the quality of reporting of a recent sample of SW-CRTs.

Study Design And Setting: Quality of reporting was asssessed according to the 26 items in the new guideline using a novel crowd sourcing methodology conducted independently and in duplicate, with random assignment, by 50 reviewers.

Suggested pharmacy practice laboratory activities to align with pre-APPE domains in the Doctor of Pharmacy curriculum.

Our Situation: The Accreditation Council for Pharmacy Education outlines ability statements that pharmacy students should be able to demonstrate prior to beginning their Advanced Pharmacy Practice Experiences (APPEs). Practice laboratory courses offer extensive opportunities for students to participate in activities and assessments that enable them to meet the objectives outlined in the Pre-APPE Core Domains in Standards 2016. This review identifies selected published literature, activities, and assessment methods that can be adapted and implemented in practice laboratory courses to help achieve the abilities outlined within the Pre-APPE Core Domains.

Targeting the terminase: An important step forward in the treatment and prophylaxis of human cytomegalovirus infections.

A key step in the replication of human cytomegalovirus (HCMV) in the host cell is the generation and packaging of unit-length genomes into preformed capsids. Enzymes required for this process are so-called terminases, first described for double-stranded DNA bacteriophages. The HCMV terminase consists of the two subunits, the ATPase pUL56 and the nuclease pUL89, and a potential third component pUL51.

A Journey to Understand Enjoyment in Academic Writing.

To assist academic writers in finding enjoyment in writing, this paper draws a distinction between enjoying the process of writing and enjoying the nature of writing. Based on an examination of academic writing literature, analysis of personal experiences, and a review of the positive psychology literature, conditions that support writing enjoyment are posited. Readers are invited to examine their personal experience with writing enjoyment relative to these levers.

The benefit of minocycline on negative symptoms of schizophrenia in patients with recent-onset psychosis (BeneMin): a randomised, double-blind, placebo-controlled trial.

Background: The antibiotic minocycline has neuroprotective and anti-inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study, we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved.

Methods: In this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts.

Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.

Background: Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk.

Methods: From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability.

Effect of Aspirin on Disability-free Survival in the Healthy Elderly.

Background: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.

Methods: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability.

Effect of Aspirin on All-Cause Mortality in the Healthy Elderly.

Background: In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo.

Methods: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability.

Changing student attitudes and perceptions toward opioid use disorder.

Introduction: With the opioid epidemic creating a group of patients with unique health care needs, pharmacists have an opportunity to be a good resource for patients recovering from opioid use disorder (OUD). To accomplish this, it is essential that pharmacists are knowledgeable and unbiased toward this patient population.

Methods: Because the curriculum in place to obtain a PharmD at Drake University does not include in-depth information on substance use disorders, study investigators offered students an opportunity to receive more intensive education.

Role of Methylglyoxal in Diabetic Cardiovascular and Kidney Diseases: Insights from Basic Science for Application into Clinical Practice.

Background: The incidence and prevalence of diabetes mellitus are increasing globally at alarming rates. Cardiovascular and renal complications are the major cause of morbidity and mortality in patients with diabetes. Methylglyoxal (MG) - a highly reactive dicarbonyl compound - is increased in patients with diabetes and has been implicated to play a detrimental role in the etiology of cardiovascular and renal complications.

Not all head injured patients on antiplatelet drugs need platelets: Integrating platelet reactivity testing into platelet transfusion guidelines.

Introduction: Antiplatelet medication use continues to rise in an aging population, and these agents can have a deleterious effect for patients with traumatic intracranial hemorrhage (tICH). The purpose of the current investigation is to assess the safety and efficacy of using platelet reactivity testing (PRT) to direct platelet transfusion for tICH patients.

Patients And Methods: A Level I trauma center adopted a targeted platelet transfusion guideline using PRT to determine whether platelets were inhibited by an antiplatelet medication (aspirin or P2Y12 inhibitors).

A prospective, multi-center cohort study: investigating the ability of warfarin-treated patients to predict their INR.

Background: In practice, warfarin-treated patients may share insight regarding their international normalized ratio (INR) value before it is measured. The accuracy and potential utility of these predictions have not been evaluated.

Objective: To (1) test how accurately patients can predict their INR; (2) identify demographic factors associated with their ability to predict their INR accurately; and (3) identify demographic factors associated with the patient's INR being in the therapeutic range.

Nanoparticle formulations that allow for sustained delivery and brain targeting of the neuropeptide oxytocin.

Oxytocin is a promising candidate for the treatment of social-deficit disorders such as Autism Spectrum Disorder, but oxytocin cannot readily pass the blood-brain barrier. Moreover, oxytocin requires frequent dosing as it is rapidly metabolized in blood. We fabricated four polymeric nanoparticle formulations using poly(lactic-co-glycolic acid) (PLGA) or bovine serum albumin (BSA) as the base material.