Exogenous oestrogen inhibits genital transmission of cell-associated HIV-1 in DMPA-treated humanized mice.

Introduction: HIV affects more women than any other life-threatening infectious agent, and most infections are sexually transmitted. HIV must breach the female genital tract mucosal barrier to establish systemic infection, and clinical studies indicate virus more easily evades this barrier in women using depot-medroxyprogesterone acetate (DMPA) and other injectable progestins for contraception. Identifying a potential mechanism for this association, we learned DMPA promotes susceptibility of wild-type mice to genital herpes simplex virus type 2 (HSV-2) infection by reducing genital tissue expression of the cell-cell adhesion molecule desmoglein-1 (DSG-1) and increasing genital mucosal permeability.

Improved influenza viral vector based Brucella abortus vaccine induces robust B and T-cell responses and protection against Brucella melitensis infection in pregnant sheep and goats.

We previously developed a potent candidate vaccine against bovine brucellosis caused by Brucella abortus using the influenza viral vector expressing Brucella Omp16 and L7/L12 proteins (Flu-BA). Our success in the Flu-BA vaccine trial in cattle and results of a pilot study in non-pregnant small ruminants prompted us in the current study to test its efficacy against B. melitensis infection in pregnant sheep and goats.

Exposure to human alveolar lining fluid enhances Mycobacterium bovis BCG vaccine efficacy against Mycobacterium tuberculosis infection in a CD8 T-cell-dependent manner.

Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.

NF-κB regulates GDF-15 to suppress macrophage surveillance during early tumor development.

Macrophages are attracted to developing tumors and can participate in immune surveillance to eliminate neoplastic cells. In response, neoplastic cells utilize NF-κB to suppress this killing activity, but the mechanisms underlying their self-protection remain unclear. Here, we report that this dynamic interaction between tumor cells and macrophages is integrally linked by a soluble factor identified as growth and differentiation factor 15 (GDF-15).

Bidirectional Retroviral Integration Site PCR Methodology and Quantitative Data Analysis Workflow.

Integration Site (IS) assays are a critical component of the study of retroviral integration sites and their biological significance. In recent retroviral gene therapy studies, IS assays, in combination with next-generation sequencing, have been used as a cell-tracking tool to characterize clonal stem cell populations sharing the same IS. For the accurate comparison of repopulating stem cell clones within and across different samples, the detection sensitivity, data reproducibility, and high-throughput capacity of the assay are among the most important assay qualities.

Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression.

Despite the development of combined modality treatments against liposarcoma in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking.

Successful treatment of donor-derived hepatitis C infection in a lung transplant recipient.

Data are limited regarding the use of direct-acting antivirals for treatment of hepatitis C infection post lung transplant, especially in a donor-derived infection. We present a case of a lung transplant recipient with donor-derived hepatitis C that was successfully treated with a 12-week regimen of simeprevir and sofosbuvir. This case reiterates the importance of screening recipients of increased-risk donor organs for disease transmission and the value of early therapy.

First evaluation of an influenza viral vector based Brucella abortus vaccine in sheep and goats: Assessment of safety, immunogenicity and protective efficacy against Brucella melitensis infection.

Previously we developed and evaluated a candidate influenza viral vector based Brucella abortus vaccine (Flu-BA) administered with a potent adjuvant Montanide Gel01 in cattle, which was found safe and highly effective. This study was aimed to establish a proof-of-concept of the efficacy of Flu-BA vaccine formulation in sheep and goats. We vaccinated sheep and goats with Flu-BA vaccine and as a positive control vaccinated a group of animals with a commercial B.

Simultaneous subcutaneous and conjunctival administration of the influenza viral vector based Brucella abortus vaccine to pregnant heifers provides better protection against B. abortus 544 infection than the commercial B. abortus S19 vaccine.

In this study, we explored possibility of increasing the protective efficacy of our novel influenza viral vector based B. abortus vaccine (Flu-BA) in pregnant heifers by adapting an innovative method of vaccine delivery. We administered the vaccine concurrently via the conjunctival and subcutaneous routes to pregnant heifers, and these routes were previously tested individually.

Inactivated porcine reproductive and respiratory syndrome virus vaccine adjuvanted with Montanide™ Gel 01 ST elicits virus-specific cross-protective inter-genotypic response in piglets.

The efficacy of a novel BEI-inactivated porcine reproductive and respiratory syndrome virus (PRRSV) candidate vaccine in pigs, developed at RIBSP Republic of Kazakhstan and delivered with an adjuvant Montanide™ Gel 01 ST (D/KV/ADJ) was compared with a commercial killed PRRSV vaccine (NVDC-JXA1, C/KV/ADJ) used widely in swine herds of the Republic of Kazakhstan. Clinical parameters (body temperature and respiratory disease scores), virological and immunological profiles [ELISA and virus neutralizing (VN) antibody titers], macroscopic lung lesions and viral load in the lungs (quantitative real-time PCR and cell culture assay) were assessed in vaccinated and both genotype 1 and 2 PRRSV challenged pigs. Our results showed that the commercial vaccine failed to protect pigs adequately against the clinical disease, viremia and lung lesions caused by the challenged field isolates, Kazakh strains of PRRSV type 1 and type 2 genotypes.

Reliability of measuring pectoralis minor muscle resting length in subjects with and without signs of shoulder impingement.

Background: Pectoralis minor adaptive shortening may change scapula resting position and scapular kinematics during arm elevation. A reliable and clinically feasible method for measuring pectoralis minor length will be useful for clinical decision making when evaluating and treating individuals with shoulder pain and dysfunction.

Objectives: To evaluate intrarater, interrater, and between-day reliability of a pectoralis minor (PM) muscle length measurement in subjects with and without signs of shoulder impingement.

Exercise-driven metabolic pathways in healthy cartilage.

Objective: Exercise is vital for maintaining cartilage integrity in healthy joints. Here we examined the exercise-driven transcriptional regulation of genes in healthy rat articular cartilage to dissect the metabolic pathways responsible for the potential benefits of exercise.

Methods: Transcriptome-wide gene expression in the articular cartilage of healthy Sprague-Dawley female rats exercised daily (low intensity treadmill walking) for 2, 5, or 15 days was compared to that of non-exercised rats, using Affymetrix GeneChip arrays.

Characterizing Community Health Workers on Research Teams: Results From the Centers for Population Health and Health Disparities.

Objectives: To quantify the characteristics of community health workers (CHWs) involved in community intervention research and, in particular, to characterize their job titles, roles, and responsibilities; recruitment and compensation; and training and supervision.

Methods: We developed and administered a structured questionnaire consisting of 25 closed- and open-ended questions to staff on National Institutes of Health-funded Centers for Population Health and Health Disparities projects between March and April 2014. We report frequency distributions for CHW roles, sought-after skills, education requirements, benefits and incentives offered, and supervision and training activities.

SAR405838: A Novel and Potent Inhibitor of the MDM2:p53 Axis for the Treatment of Dedifferentiated Liposarcoma.

Purpose: Dedifferentiated liposarcoma (DDLPS) is an aggressive malignancy that can recur locally or disseminate even after multidisciplinary care. Genetically amplified and expressed MDM2, often referred to as a "hallmark" of DDLPS, mostly sustains a wild-type p53 genotype, substantiating the MDM2:p53 axis as a potential therapeutic target for DDLPS. Here, we report on the preclinical effects of SAR405838, a novel and highly selective MDM2 small-molecule inhibitor, in both in vitro and in vivo DDLPS models.

The hepatocyte growth factor receptor as a potential therapeutic target for dedifferentiated liposarcoma.

Dedifferentiated liposarcomas (DDLPS) are highly resistant to conventional chemo- and radiotherapies, with surgical resection remaining the classic treatment strategy; therefore, there is a pressing need for novel anti-DDLPS-targeted chemotherapeutics. Hepatocyte growth factor receptor (Met) expression is elevated in DDLPS, but the functional role of Met signaling in this disease is not known. We found that the in vitro stimulation of DDLPS cells with hepatocyte growth factor (HGF) elevated the degree of PI3K/AKT and MAPK pathway signaling, and that pro-tumorigenic phenotypes such as cell proliferation, invasion, and migration were significantly enhanced.

Development of an inpatient operational pharmacy productivity model.

Purpose: An innovative model for measuring the operational productivity of medication order management in inpatient settings is described.

Methods: Order verification within a computerized prescriber order-entry system was chosen as the pharmacy workload driver. To account for inherent variability in the tasks involved in processing different types of orders, pharmaceutical products were grouped by class, and each class was assigned a time standard, or "medication complexity weight" reflecting the intensity of pharmacist and technician activities (verification of drug indication, verification of appropriate dosing, adverse-event prevention and monitoring, medication preparation, product checking, product delivery, returns processing, nurse/provider education, and problem-order resolution).

Evaluation of industrial dairy waste (milk dust powder) for acetone-butanol-ethanol production by solventogenic Clostridium species.

Readily available inexpensive substrate with high product yield is the key to restoring acetone-butanol-ethanol (ABE) fermentation to economic competitiveness. Lactose-replete cheese whey tends to favor the production of butanol over acetone. In the current study, we investigated the fermentability of milk dust powder with high lactose content, for ABE production by Clostridium acetobutylicum and Clostridium beijerinckii.

A collaborative approach to residency preparation programming for pharmacy students.

Purpose: An innovative program to help pharmacy students navigate the residency application and interview process is described, including results of a survey evaluating the program's impact.

Summary: The Ohio State University (OSU) chapter of the Student Society of Health-System Pharmacy (SSHP) collaborated with OSU College of Pharmacy faculty members, pharmacists from OSU Wexner Medical Center and surrounding areas, and current pharmacy residents to provide programming to equip pharmacy students with skills to succeed as residency candidates. The programming has four components: Curriculum Vitae (CV) Critique, Mock Residency Interviews, Residency 101, and Midyear to Match (M-M), a six-part series that provides guidance on the Residency Showcase at the American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting, Match day (the annual matching process coordinated by ASHP), and the post-Match "scramble," in which unmatched applicants compete for unfilled residency slots.

Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate therapeutic target in glioblastoma.

Glioblastoma is the most common and aggressive histologic subtype of brain cancer with poor outcomes and limited treatment options. Here, we report the selective overexpression of the protein arginine methyltransferase PRMT5 as a novel candidate theranostic target in this disease. PRMT5 silences the transcription of regulatory genes by catalyzing symmetric dimethylation of arginine residues on histone tails.

Idiopathic pulmonary fibrosis is strongly associated with productive infection by herpesvirus saimiri.

Idiopathic pulmonary fibrosis is a fatal disease without effective therapy or diagnostic test. To investigate a potential role for γ-herpesviruses in this disease, 21 paraffin-embedded lung biopsies from patients diagnosed with idiopathic pulmonary fibrosis and 21 lung biopsies from age-matched controls with pulmonary fibrosis of known etiology were examined for a series of γ-herpesviruses' DNA/RNA and related proteins using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods. We detected four proteins known to be in the genome of several γ-herpesviruses (cyclin D, thymidylate synthase, dihydrofolate reductase, and interleukin-17) that were strongly co-expressed in the regenerating epithelial cells of each of the 21 idiopathic pulmonary fibrosis cases and not in the benign epithelia of the controls.

ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.

Cyclin dependent kinase (CDK) inhibitors, such as flavopiridol, demonstrate significant single-agent activity in chronic lymphocytic leukemia (CLL), but the mechanism of action in these nonproliferating cells is unclear. Here we demonstrate that CLL cells undergo autophagy after treatment with therapeutic agents, including fludarabine, CAL-101, and flavopiridol as well as the endoplasmic reticulum (ER) stress-inducing agent thapsigargin. The addition of chloroquine or siRNA against autophagy components enhanced the cytotoxic effects of flavopiridol and thapsigargin, but not the other agents.

Differential anti-proliferative activities of poly(ADP-ribose) polymerase (PARP) inhibitors in triple-negative breast cancer cells.

Despite recent advances in the clinical evaluation of various poly(ADP-ribose) polymerase (PARP) inhibitors in triple-negative breast cancer (TNBC) patients, data defining potential anti-tumor mechanisms beyond PARP inhibition for these agents are lacking. To address this issue, we investigated the effects of four different PARP inhibitors (AG-014699, AZD-2281, ABT-888, and BSI-201) in three genetically distinct TNBC cell lines (MDA-MB-468, MDA-MB-231, and Cal-51). Assays of cell viability and colony formation and flow cytometric analysis were used to determine effects on cell growth and cell cycle progression.

Impact of United States Pharmacopeia chapter 797: results of a national survey.

Purpose: The initial response of the pharmacy profession to United States Pharmacopeia (USP) chapter 797 and the current state of hospital pharmacy practice as it relates to implementing this chapter were studied.

Methods: A stratified random sample of 600 hospital pharmacy directors across the nation were surveyed by mail.

Results: A total of 251 surveys (41.

Improving the safety of medication administration using an interactive CD-ROM program.

Purpose: The impact of an interactive CD-ROM program on the rate of medication administration errors made by nurses was studied.

Methods: This randomized, controlled, nonblinded study was conducted at three community hospitals. Study participants included 30 registered nurses who had at least one year of nursing experience in acute care and who worked on medical or medical-surgical units.