and immune responses against vaccines are comparable among Fischer 344 rat substrains.

Identifying suitable animal models and standardizing preclinical methods are important for the generation, characterization, and development of new vaccines, including those against . Non-human primates represent an important animal model to evaluate tularemia vaccine efficacy, and the use of correlates of vaccine-induced protection may facilitate bridging immune responses from non-human primates to people. However, among small animals, Fischer 344 rats represent a valuable resource for initial studies to evaluate immune responses, to identify correlates of protection, and to screen novel vaccines.

Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis.

Francisella tularensis, the causative agent of tularemia, is classified as Tier 1 Select Agent with bioterrorism potential. The efficacy of the only available vaccine, LVS, is uncertain and it is not licensed in the U.S.

Identification of an Attenuated Substrain of SCHU S4 by Phenotypic and Genotypic Analyses.

Pneumonic tularemia is a highly debilitating and potentially fatal disease caused by inhalation of Most of our current understanding of its pathogenesis is based on the highly virulent subsp. strain SCHU S4. However, multiple sources of SCHU S4 have been maintained and propagated independently over the years, potentially generating genetic variants with altered virulence.

COVID-19 global pandemic planning: Decontamination and reuse processes for N95 respirators.

There is a critical shortage of personal protective equipment (PPE) around the globe. This article describes the safe collection, storage, and decontamination of N95 respirators using hydrogen peroxide vapor (HPV). This article is unique because it describes the HPV process in an operating room, and is therefore, a deployable method for many healthcare settings.

Vaccine-Mediated Mechanisms Controlling SCHU S4 Growth in a Rat Co-Culture System.

causes the severe disease tularemia. In the present study, the aim was to identify correlates of protection in the rat co-culture model by investigating the immune responses using two vaccine candidates conferring distinct degrees of protection in rat and mouse models. The immune responses were characterized by use of splenocytes from naïve or Live vaccine strain- (LVS) or ∆∆-immunized Fischer 344 rats as effectors and bone marrow-derived macrophages infected with the highly virulent strain SCHU S4.

Increased Mortality in Mice following Immunoprophylaxis Therapy with High Dosage of Nicotinamide in Persistent Infections.

Bacterial persistence, known as noninherited antibacterial resistance, is a factor contributing to the establishment of long-lasting chronic bacterial infections. In this study, we examined the ability of nicotinamide (NA) to potentiate the activity of different classes of antibiotics against persister cells. Here we demonstrate that addition of NA in models of infection resulted in a significant depletion of the persister population in response to various classes of antibiotics.

A panel of correlates predicts vaccine-induced protection of rats against respiratory challenge with virulent Francisella tularensis.

There are no defined correlates of protection for any intracellular pathogen, including the bacterium Francisella tularensis, which causes tularemia. Evaluating vaccine efficacy against sporadic diseases like tularemia using field trials is problematic, and therefore alternative strategies to test vaccine candidates like the Francisella Live Vaccine Strain (LVS), such as testing in animals and applying correlate measurements, are needed. Recently, we described a promising correlate strategy that predicted the degree of vaccine-induced protection in mice given parenteral challenges, primarily when using an attenuated Francisella strain.

High-Throughput Flow Cytometry Screening of Multidrug Efflux Systems.

The resistance nodulation cell division (RND) family of proteins are inner membrane transporters that associate with periplasmic adaptor proteins and outer membrane porins to affect substrate transport from the cytosol and periplasm in Gram-negative bacteria. Various structurally diverse compounds are substrates of RND transporters. Along with their notable role in antibiotic resistance, these transporters are essential for niche colonization, quorum sensing, and virulence as well as for the removal of fatty acids and bile salts.

PKC-η-MARCKS Signaling Promotes Intracellular Survival of Unopsonized .

Pathogenic rely on host factors for efficient intracellular replication and are highly refractory to antibiotic treatment. To identify host genes that are required by spp. during infection, we performed a RNA interference (RNAi) screen of the human kinome and identified 35 host kinases that facilitated intracellular survival in human monocytic THP-1 cells.

The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4.

A stable live bacterial vaccine.

Formulating vaccines into a dry form enhances its thermal stability. This is critical to prevent administering damaged and ineffective vaccines, and to reduce its final cost. A number of vaccines in the market as well as those being evaluated in the clinical setting are in a dry solid state; yet none of these vaccines have achieved long-term stability at high temperatures.

Stereotactic radiotherapy using tomotherapy for early-stage non-small cell lung carcinoma: analysis of intrafraction tumour motion.

Introduction: Intrafraction tumour motion in helical tomotherapy was investigated by comparing pre- and mid-fraction CT scans in patients with early non-small cell lung carcinoma (NSCLC) to assess the efficacy of a 7-mm margin around gross tumour volumes (GTVs) in stereotactic body radiation therapy (SBRT).

Methods: Thirty patients with early-stage NSCLC received SBRT in four or five fractions for a total of 141 treatments. A slow positron emission tomography/CT scan was fused with the simulation CT to determine the GTV.

Medical Physics Residency Consortium: collaborative endeavors to meet the ABR 2014 certification requirements.

In 2009, Mary Bird Perkins Cancer Center (MBPCC) established a Radiation Oncology Physics Residency Program to provide opportunities for medical physics residency training to MS and PhD graduates of the CAMPEP-accredited Louisiana State University (LSU)-MBPCC Medical Physics Graduate Program. The LSU-MBPCC Program graduates approximately six students yearly, which equates to a need for up to twelve residency positions in a two-year program. To address this need for residency positions, MBPCC has expanded its Program by developing a Consortium consisting of partnerships with medical physics groups located at other nearby clinical institutions.

Impact of the global economic crisis on the health of unemployed autoworkers.

A phenomenological investigation was undertaken to examine the effects of the 2008-09 global economic recession on the health of unemployed blue-collar autoworkers in the Canadian province of Ontario between September and November 2009. A total of 22 men and 12 women took part. Participants completed a quantitative demographic and financial questionnaire.

Determining between chyle leak and anastomotic leak after esophageal reconstruction: the utility of methylene blue dye.

Objectives/hypothesis: Two common complications of esophagectomy and immediate reconstruction comprise thoracic duct injury leading to chyle leak and anastomotic leakage. These can delay optimized nutrition, speech, and swallowing rehabilitation, and thus are important to identify and treat accordingly. When either chyle leak or anastomotic leak are clinically suspected, differentiation between the two can be very difficult clinically.

Identification of circulating bacterial antigens by in vivo microbial antigen discovery.

Unlabelled: Detection of microbial antigens in clinical samples can lead to rapid diagnosis of an infection and administration of appropriate therapeutics. A major barrier in diagnostics development is determining which of the potentially hundreds or thousands of antigens produced by a microbe are actually present in patient samples in detectable amounts against a background of innumerable host proteins. In this report, we describe a strategy, termed in vivo microbial antigen discovery (InMAD), that we used to identify circulating bacterial antigens.

Progression of cancer from indolent to aggressive despite antigen retention and increased expression of interferon-gamma inducible genes.

Many cancers escape host immunity without losing tumor-specific rejection antigens or MHC class I expression. This study tracks the evolution of one such cancer that developed in a mouse following exposure to ultraviolet light. The primary autochthonous tumor was not highly malignant and was rejected when transplanted into naïve immunocompetent mice.

Antibodies contribute to effective vaccination against respiratory infection by type A Francisella tularensis strains.

Pneumonic tularemia is a life-threatening disease caused by inhalation of the highly infectious intracellular bacterium Francisella tularensis. The most serious form of the disease associated with the type A strains can be prevented in experimental animals through vaccination with the attenuated live vaccine strain (LVS). The protection is largely cell mediated, but the contribution of antibodies remains controversial.

The Fischer 344 rat reflects human susceptibility to francisella pulmonary challenge and provides a new platform for virulence and protection studies.

Background: The pathogenesis of Francisella tularensis, the causative agent of tularemia, has been primarily characterized in mice. However, the high degree of sensitivity of mice to bacterial challenge, especially with the human virulent strains of F. tularensis, limits this animal model for screening of defined attenuated vaccine candidates for protection studies.

The pathogenesis of acute pulmonary viral and bacterial infections: investigations in animal models.

Acute viral and bacterial infections in the lower respiratory tract are major causes of morbidity and mortality worldwide. The proper study of pulmonary infections requires interdisciplinary collaboration among physicians and biomedical scientists to develop rational hypotheses based on clinical studies and to test these hypotheses in relevant animal models. Animal models for common lung infections are essential to understand pathogenic mechanisms and to clarify general mechanisms for host protection in pulmonary infections, as well as to develop vaccines and therapeutics.

Vaccination of Fischer 344 rats against pulmonary infections by Francisella tularensis type A strains.

Pneumonic tularemia caused by inhalation of the type A strains of Francisella tularensis is associated with high morbidity and mortality in humans. The only vaccine known to protect humans against this disease is the attenuated live vaccine strain (LVS), but it is not currently registered for human use. To develop a new generation of vaccines, multiple animal models are needed that reproduce the human response to F.

T cells from lungs and livers of Francisella tularensis-immune mice control the growth of intracellular bacteria.

Parenteral and respiratory vaccinations with the intracellular bacterium Francisella tularensis have been studied using the live vaccine strain (LVS) in a mouse model, and spleen cells from immune mice are often used for immunological studies. However, mechanisms of host immunological responses may be different in nonlymphoid organs that are important sites of infection, such as lung and liver. Using parenteral (intradermal) or respiratory (cloud aerosol) vaccination, here we examine the functions of resulting LVS-immune liver or lung cells, respectively.

In vitro activity of telavancin against resistant gram-positive bacteria.

The in vitro activity of telavancin was tested against 743 predominantly antimicrobial-resistant, gram-positive isolates. Telavancin was highly active against methicillin-resistant staphylococci (MIC(90), 0.5 to 1 microg/ml), streptococci (all MICs, < or =0.