Limited proteolysis of neutrophil granule proteins by the bacterial protease RgpB depletes neutrophil antimicrobial capacity.

Neutrophils are highly abundant in the gingival tissues where they play an essential role in immune homeostasis by preventing microbial invasion. Here, we show that the oral periodontal pathogen Porphyromonas gingivalis utilizes its cysteine proteases (gingipains) to disengage phagosomal antimicrobial capacity. Arginine gingipains are a sub-family of trypsin-like proteases produced by P.

Comparison of hyperpolarized He-MRI, CT based parametric response mapping, and mucus scores in asthmatics.

The purpose of this study was to anatomically correlate ventilation defects with regions of air trapping by whole lung, lung lobe, and airway segment in the context of airway mucus plugging in asthma. A total of 34 asthmatics [13M:21F, 13 mild/moderate, median age (range) of 49.5 (36.

Cystic fibrosis macrophage function and clinical outcomes after elexacaftor/tezacaftor/ivacaftor.

Background: Abnormal macrophage function caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) is a critical contributor to chronic airway infections and inflammation in people with cystic fibrosis (PWCF). Elexacaftor/tezacaftor/ivacaftor (ETI) is a new CFTR modulator therapy for PWCF. Host-pathogen and clinical responses to CFTR modulators are poorly described.

Ventilation defects on hyperpolarized helium-3 MRI in asthma are predictive of 2-year exacerbation frequency.

Background: There is an unmet need for an objective biomarker to predict asthma exacerbations.

Objective: Our aim was to assess the ventilation defect percent (VDP) on hyperpolarized helium-3 magnetic resonance imaging as a predictor of exacerbation frequency following imaging.

Methods: Subjects underwent hyperpolarized helium-3 and conventional clinical measurements, including pulmonary function tests, during a period of disease stability, and exacerbations were recorded prospectively over the following 2 years.

Vitamin D Supplementation to Treat Statin-Associated Muscle Symptoms: A Review.

For the past 15 years, cardiovascular disease (CVD) has been the leading cause of death for both men and women in the United States and worldwide. With an aging population, there has been increasing use of statin therapy to reduce the risk of CVD. However, statin-associated muscle symptoms (SAMS) remain an obstacle to this treatment, leading to discontinuation and nonadherence to statin therapy.

Intraperitoneal nanotherapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin.

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites.

Detecting aberrant opioid behavior in the emergency department: a prospective study using the screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R), Current Opioid Misuse Measure (COMM)™, and provider gestalt.

Emergency department (ED) providers have limited time to evaluate patients at risk for opioid misuse. A validated tool to assess the risk for aberrant opioid behavior may mitigate adverse sequelae associated with prescription opioid misuse. We sought to determine if SOAPP-R, COMM, and provider gestalt were able to identify patients at risk for prescription opioid misuse as determined by pharmacy records at 12 months.

Adaptation and Validation of the Fresno Test of Competence in Evidence-Based Medicine in Doctor of Pharmacy Students.

To adapt and validate an instrument assessing competence in evidence-based medicine (EBM) in Doctor of Pharmacy students. The Fresno test was validated in medical residents. We adapted it for use in pharmacy students.

Emergency medicine providers' opioid prescribing practices stratified by gender, age, and years in practice.

Background: Emergency medicine providers (EMPs) prescribe about 25% of opioids, but the effect of EMP risk perception on decisions to prescribe opioids is unknown. This study was undertaken to identify factors that influence EMP risk and opioid prescribing practices.

Methods: We distributed an anonymous questionnaire to EMPs at a military trauma and referral center.

Alzheimer's disease and type 2 diabetes: what is the connection?

Alzheimer's disease (AD) is a progressive neurodegenerative condition primarily affecting individuals 65 years of age and older. There are few therapies available, and the disease is eventually fatal. Although the molecular mechanisms responsible for the development of AD remain unknown, a strong correlation between insulin dysfunction in type 2 diabetes mellitus and AD has recently been established.

Impact of pharmacy student and resident-led discharge counseling on heart failure patients.

Purpose: Many health systems have implemented interventions to reduce the rate of heart failure readmissions. Pharmacists have the training and expertise to provide effective medication-related education. However, few studies have examined the impact of discharge education provided by pharmacy students and residents on patients hospitalized with heart failure exacerbations.

A polypill for all? Critical review of the polypill literature for primary prevention of cardiovascular disease and stroke.

Objective: To evaluate the efficacy and safety of the polypill for prevention of cardiovascular disease (CVD) and stroke and to present literature related to the polypill components (statin, aspirin, antihypertensive) for primary prevention of CVD and stroke.

Data Sources: A literature search was conducted in MEDLINE (1948-January 2011) and EMBASE (1974-January 2011) using the terms polypill and Polycap. When limited to clinical trials, systematic reviews, or meta-analyses, 7 studies were identified.

Pharmacy student impact on inappropriate prescribing of acid suppressive therapy.

Objective: To examine the impact that having pharmacy students on internal medicine patient care teams had on inappropriate prescribing of acid suppressive therapy (AST).

Methods: In this observational cohort study, internal medicine patients who received care from teams with a pharmacy student were compared to patients who received care from teams without a pharmacy student. The primary endpoint was proportion of patients on inappropriate AST.

Food-entrained rhythmic expression of apolipoprotein E expression in the hypothalamus of rats.

Apolipoprotein E (apoE) is a protein mainly synthesized in the liver and brain. To further understand the role of brain apoE in the management of daily food intake, we have examined the circadian pattern of hypothalamic apoE gene and protein expression in freely-fed (FF) and food-restricted (RF, food provided 4 h daily between 1000 h and 1400 h) rats sacrificed at 3-h intervals throughout the light-dark cycle. In FF rats, hypothalamic apoE mRNA and protein levels fluctuated with peaks occuring during the dark phase and the nadirs occuring during the light phase.

Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration.

CCK and apolipoprotein AIV (apo AIV) are gastrointestinal satiety signals whose synthesis and secretion by the gut are stimulated by fat absorption. Intraperitoneally administered CCK-8 is more potent in suppressing food intake than a similar dose administered intravenously, but the reason for this disparity is unclear. In contrast, both intravenous and intraperitoneally administered apo AIV are equally as potent in inhibiting food intake.

Brain apolipoprotein E: an important regulator of food intake in rats.

Objective: The worldwide prevalence of obesity is increasing at an alarming rate, along with the associated increased rates of type 2 diabetes, heart disease, and some cancers. While efforts to address environmental factors responsible for the recent epidemic must continue, investigation into the anorectic functions of potential molecules we present here, such as apolipoprotein (apo)E, offers exciting possibilities for future development of successful anti-obesity therapies.

Research Design And Methods: Changes in feeding behavior after intracerebroventricular injection of apoE, the regulation of hypothalamic apoE gene expression by energy status, and the interaction of hypothalamic apoE with other neuropeptides were studied.