Advanced Surgical Skills for Exposure in Trauma (ASSET) course improves military surgeon confidence.

Objective: Active duty military surgeons often have limited trauma surgery experience prior to deployment. Consequently, military-civilian training programs have been developed at high-volume trauma centers to evaluate and maintain proficiencies. Advanced Surgical Skills for Exposure in Trauma (ASSET) was incorporated into the predeployment curriculum at the Army Trauma Training Detachment in 2011.

Novel inhibitors that target bacterial virulence identified via HTS against intra-macrophage survival of .

is a facultative intracellular pathogen that causes shigellosis, a human diarrheal disease characterized by the destruction of the colonic epithelium. Novel antimicrobial compounds to treat infections are urgently needed due to the proliferation of bacterial antibiotic resistance and lack of new effective antimicrobials in the market. Our approach to find compounds that block the virulence pathway has three potential advantages: (i) resistance development should be minimized due to the lack of growth selection pressure, (ii) no resistance due to environmental antibiotic exposure should be developed since the virulence pathways are not activated outside of host infection, and (iii) the normal intestinal microbiota, which do not have the targeted virulence pathways, should be unharmed.

Elucidation of the DNA-Binding Activity of VirF from Shigella flexneri for the and Promoters and Characterization of the N-Terminal Domain To Identify Residues Crucial for Dimerization.

A novel approach to treat the highly virulent and infectious enteric pathogen Shigella flexneri, with the potential for reduced resistance development, is to target virulence pathways. One promising such target is the AraC-family transcription factor VirF, which activates downstream virulence factors. VirF harbors a conserved C-terminal DNA-binding domain (DBD) and an N-terminal dimerization domain (NTD).

Simulated redistricting plans for the analysis and evaluation of redistricting in the United States.

This article introduces the 50STATESIMULATIONS, a collection of simulated congressional districting plans and underlying code developed by the Algorithm-Assisted Redistricting Methodology (ALARM) Project. The 50STATESIMULATIONS allow for the evaluation of enacted and other congressional redistricting plans in the United States. While the use of redistricting simulation algorithms has become standard in academic research and court cases, any simulation analysis requires non-trivial efforts to combine multiple data sets, identify state-specific redistricting criteria, implement complex simulation algorithms, and summarize and visualize simulation outputs.

Elucidation of Key Interactions between VirF and the Promoter in Shigella flexneri Using E. coli MarA- and GadX-Based Homology Models and Analysis of the DNA-Binding Domains of VirF and MarA.

Infection with , the organism responsible for the diarrheal disease shigellosis, leads to approximately 200,000 deaths globally annually. Virulence of this pathogen is primarily controlled by the DNA-binding transcriptional activator VirF. This AraC family protein activates transcription of two major virulence genes, and , which lead to the pathogen's ability to invade and spread within colonic epithelial cells.

Optimization of Benzoxazinorifamycins to Improve RNA Polymerase Inhibition and Treatment of Tuberculosis.

Rifampin (RMP), a very potent inhibitor of the (MTB) RNA polymerase (RNAP), remains a keystone in the treatment of tuberculosis since its introduction in 1965. However, rifamycins suffer from serious drawbacks, including 3- to 9-month treatment times, Cyp450 induction (particularly problematic for HIV-MTB coinfection), and resistant mutations within RNAP that yield RIF-resistant (RIF) MTB strains. There is a clear and pressing need for improved TB therapies.

Optimization of Benzoxazinorifamycins to Minimize hPXR Activation for the Treatment of Tuberculosis and HIV Coinfection.

Tuberculosis (TB) is one of the most significant world health problems, responsible for 1.5 M deaths in 2020, and yet, current treatments rely largely on 40 year old paradigms. Although the rifamycins (RIFs), best exemplified by the drug rifampin (RMP), represent a well-studied and therapeutically effective chemotype that targets the bacterial RNA polymerase (RNAP), these agents still suffer from serious drawbacks including the following: 3-9 month treatment times; cytochrome P450 (Cyp450) induction [particularly problematic for human immunodeficiency virus- (MTB) co-infection]; and the existence of RIF-resistant (RIF) MTB strains.

Metal-HisTag coordination for remote loading of very small quantities of biomacromolecules into PLGA microspheres.

Challenges to discovery and preclinical development of long-acting release systems for protein therapeutics include protein instability, use of organic solvents during encapsulation, specialized equipment and personnel, and high costs of proteins. We sought to overcome these issues by combining remote-loading self-healing encapsulation with binding HisTag protein to transition metal ions. Porous, drug-free self-healing microspheres of copolymers of lactic and glycolic acids with high molecular weight dextran sulfate and immobilized divalent transition metal (M) ions were placed in the presence of proteins with or without HisTags to bind the protein in the pores of the polymer before healing the surface pores with modest temperature.

(Re)defining their place at the table: Frank discussions by adults with disabilities on contemporary self-advocacy.

Adults with disabilities have long been at the forefront of disability advocacy in the United States. Grounded in the tenets of radical disability studies and principles of disability justice, this study explored the lived experiences of 12 adults with disabilities, including intellectual disability and developmental disabilities, with a particular focus on self-advocacy. Two focus groups were primary data sources.

Cardiopulmonary Mortality and Fine Particulate Air Pollution by Species and Source in a National U.S. Cohort.

The purpose of this study was to estimate cardiopulmonary mortality associations for long-term exposure to PM species and sources (i.e., components) within the U.

Designing health impact functions to assess marginal changes in outdoor fine particulate matter.

Estimating health benefits from improvements in ambient air quality requires the characterization of the magnitude and shape of the association between marginal changes in exposure and marginal changes in risk, and its uncertainty. Several attempts have been made to do this, each requiring different assumptions. These include the Log-Linear(LL), IntegratedExposure-Response(IER), and GlobalExposureMortalityModel(GEMM).

Greenness, air pollution, and mortality risk: A U.S. cohort study of cancer patients and survivors.

Background: Several studies suggest that living in areas of high surrounding greenness may be associated with a lower cardiopulmonary mortality risk. However, associations of greenness with specific causes of death in cancer patients and survivors has not been examined and it is unknown whether this relationship is affected by area levels of fine particulate matter air pollution (PM). This study evaluated associations between greenness and PM on causes of death in a large, U.

Shape of BMI-Mortality Risk Associations: Reverse Causality and Heterogeneity in a Representative Cohort of US Adults.

Objective: This study examines BMI-mortality associations and evaluates strategies intended to limit reverse causality. Heterogeneity in BMI-mortality risk associations across subgroups and causes of death is explored.

Methods: A cohort of 654,382 adults from the US National Health Interview Survey was constructed.

The Key to Combat Readiness Is a Strong Military-Civilian Partnership.

Introduction: In peacetime, it is challenging for Army Forward Resuscitative Surgical Teams (FRST) to maintain combat readiness as trauma represents <0.5% of military hospital admissions and not all team members have daily clinical responsibilities. Military surgeon clinical experience has been described, but no data exist for other members of the FRST.

High-throughput screening to discover inhibitors of the CarD·RNA polymerase protein-protein interaction in Mycobacterium tuberculosis.

Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) accounts for 3.7% of new cases of TB annually worldwide and is a major threat to global public health. Due to the prevalence of the MDR-TB and extensively drug resistant tuberculosis (XDR-TB) cases, there is an urgent need for new drugs with novel mechanisms of action.

Registered Report: Transcriptional Analysis of Savings Memory Suggests Forgetting is Due to Retrieval Failure.

There is fundamental debate about the nature of forgetting: some have argued that it represents the decay of the memory trace, others that the memory trace persists but becomes inaccessible because of retrieval failure. These different accounts of forgetting lead to different predictions about savings memory, the rapid re-learning of seemingly forgotten information. If forgetting is because of decay, then savings requires re-encoding and should thus involve the same mechanisms as initial learning.

Source of the Fitness Defect in Rifamycin-Resistant Mycobacterium tuberculosis RNA Polymerase and the Mechanism of Compensation by Mutations in the β' Subunit.

is a critical threat to human health due to the increased prevalence of rifampin resistance (RMP). Fitness defects have been observed in RMP mutants with amino acid substitutions in the β subunit of RNA polymerase (RNAP). In clinical isolates, this fitness defect can be ameliorated by the presence of secondary mutations in the double-psi β-barrel (DPBB) domain of the β' subunit of RNAP.

Academic Freedom Should Be Redefined: Point and Counterpoint.

As part of the 2014-15 Academic Leadership Fellows Program, the cohort teams presented debates on topics relevant to academic pharmacy at a public forum during the 2015 American Association of Colleges of Pharmacy Interim Meeting. The topic of one of the debates was "Academic Freedom Should Be Redefined." The "point" of the debate focused on important issues such as the fundamental definition of academic freedom as it was written in the 1940 American Association of University Professors' Statement and the need for redefinition as a consequence of many misunderstandings and misinterpretations that have arisen over time.

Novel Chemical Scaffolds for Inhibition of Rifamycin-Resistant RNA Polymerase Discovered from High-Throughput Screening.

Rifampin has been a cornerstone of tuberculosis (TB) treatment since its introduction. The rise of multidrug-resistant and extensively drug-resistant TB makes the development of novel therapeutics effective against these strains an urgent need. Site-specific mutations in the target enzyme of rifampin, RNA polymerase (RNAP) comprises the majority (~97%) of rifamycin-resistant (Rif) strains of Mycobacterium tuberculosis (MTB).

Structural basis for rifamycin resistance of bacterial RNA polymerase by the three most clinically important RpoB mutations found in Mycobacterium tuberculosis.

Since 1967, Rifampin (RMP, a Rifamycin) has been used as a first line antibiotic treatment for tuberculosis (TB), and it remains the cornerstone of current short-term TB treatment. Increased occurrence of Rifamycin-resistant (RIF ) TB, ∼41% of which results from the RpoB S531L mutation in RNA polymerase (RNAP), has become a growing problem worldwide. In this study, we determined the X-ray crystal structures of the Escherichia coli RNAPs containing the most clinically important S531L mutation and two other frequently observed RIF mutants, RpoB D516V and RpoB H526Y.

Using simulation for disaster preparedness.

Background: As it addresses both technical and nontechnical skills, simulation-based training is playing an increasingly important role in surgery. In addition to the focus on skill acquisition, it is also important to ensure that surgeons are able to perform a variety of tasks in unique and challenging situations. These situations include responding to mass casualties, dealing with disease outbreaks, and preparing for wartime missions.

Mechanism of Action and Initial, In Vitro SAR of an Inhibitor of the Shigella flexneri Virulence Regulator VirF.

Shigella spp. are among the main causative agents of acute diarrheal illness and claim more than 1 million lives per year worldwide. There are multiple bacterial genes that control the pathogenesis of Shigella, but the virF gene may be the most important.

Integrating a new medicinal chemistry and pharmacology course sequence into the PharmD curriculum.

Objective: To evaluate the implementation of an integrated medicinal chemistry/pharmacology course sequence and its alignment with a therapeutics series.

Design: Each topic was divided into modules consisting of 2-hour blocks, and the content was integrated and aligned with the therapeutics series. Recitation sessions emphasizing application skills in an interactive environment followed each of three 2-hour blocks.

Potential novel antibiotics from HTS targeting the virulence-regulating transcription factor, VirF, from Shigella flexneri.

VirF is an AraC-type transcriptional regulator responsible for activating the transcription of virulence genes required for the intracellular invasion and cell-to-cell spread of Shigella flexneri. Gene disruption studies have validated VirF as a potential target for an anti-virulence therapy to treat shigellosis by determining that VirF is necessary for virulence, but not required for bacterial viability. Using a bacteria-based, β-galactosidase reporter assay we completed a high-throughput screening (HTS) campaign monitoring VirF activity in the presence of over 140,000 small molecules.