The Effect of Preoperative Chlorhexidine Gluconate Cleanse on Lower Extremity Surgical Site Infections: A Retrospective Cohort Study.

BACKGROUND: Lower extremity surgical sites are at an increased risk of wound infection following Mohs micrographic surgery. OBJECTIVE: To evaluate the rate of lower extremity surgical site infections following a 14-day regimen of preoperative 4% chlorhexidine gluconate (CHG) rinses and postoperative wound occlusion for 14 days. MATERIALS AND METHODS: Retrospective data were collected from procedures performed by the senior author from January 2022 through June 2023. To meet inclusion, patients must have completed waist-down CHG soak and rinse for 14 days before surgery, including the day before surgery. In addition, the patient must have kept the dressing clean, dry, and intact until the postoperative appointment at 14 days. RESULTS: A total of 100 Mohs cases met inclusion criteria. Zero patients developed a surgical site infection. CONCLUSION: Chlorhexidine gluconate preoperative rinsing and postoperative occlusion for 14 days may minimize the risk of wound infection. Although further research is indicated, an opportunity exists for the adoption of CHG into routine clinical practice in the outpatient dermatology setting.

Facility-based approach for the management of acute ST segment elevation myocardial infarction with cardiogenic shock in a rural medical centre: the Durango model.

INTRODUCTION: Cardiogenic shock (CS) complicates 5%-15% of cases of acute myocardial infarction (AMI) with inpatient mortality greater than 40%. The implementation of standardised protocols may improve clinical outcomes in patients with AMI-CS. METHODS AND ANALYSIS: The Durango model is a prospective single-centre registry designed to enable early identification of patients with STEMI-CS to facilitate primary reperfusion therapy with a shock team management algorithm in a rural level II heart attack centre. This prospective registry includes all patients >18 years of age presenting with STEMI with or without CS beginning on 1 February 2023. The primary outcome measures are adherence to model-based documentation of SCAI shock Classification prehospital and in the ED with appropriate STEMI shock alert for AMI and stages C, D, E shock; use of mechanical circulatory support Pre-PCI and door to support time <90 min. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board with a waiver of informed consent. The findings will be submitted for publication in a peer-review open access journal on completion of the study. CONCLUSIONS: The Durango model will demonstrate that the implementation of a STEMI shock team can be feasible in a rural medical centre through comprehensive education of a diverse group providers with different levels of experience, continuous model/device proficiency training and performance feedback.

The Host-Pathogen Interplay: A Tale of Two Stories within the Cornea and Posterior Segment.

Ocular infectious diseases are an important cause of potentially preventable vision loss and blindness. In the following manuscript, we will review ocular immunology and the pathogenesis of herpesviruses and Pseudomonas aeruginosa infections of the cornea and posterior segment. We will highlight areas of future research and what is currently known to promote bench-to-bedside discoveries to improve clinical outcomes of these debilitating ocular diseases.

Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide.

Epithelial adenocarcinoma of the ovary and colon are associated with the highest rates of cancer-related deaths in women in the U.S. The literature supports the role of HDL-associated apolipoproteins in the treatment of cancer and other pro-inflammatory diseases. Previously, we developed a novel 20-amino acid mimetic peptide, HM-10/10, which potently inhibits tumor development and growth in colon and ovarian cancer. Here, we report the properties of HM-10/10 relative to its stability in vitro. The results demonstrated that HM-10/10 had the highest half-life in human plasma compared to plasma from other species tested. HM-10/10 demonstrated stability in human plasma and simulated gastric environment, increasing its promise as an oral pharmaceutical. However, under conditions modeling the small intestine, HM-10/10 demonstrated significant degradation, likely due to the peptidases encountered therein. Furthermore, HM-10/10 demonstrated no evidence of time-dependent drug-drug interactions, although it demonstrated CYP450 induction slightly above cutoff. As proteolytic degradation is a common limitation of peptide-based therapeutics, we are pursuing strategies to improve the stability properties of HM-10/10 by extending its bioavailability while retaining its low toxicity profile. HM-10/10 holds promise as a new agent to address the international women's health crisis of epithelial carcinomas of the ovary and colon.

The Role of Lewis Acid Sites in γ-Al2 O3 Oligomerization.

Olefin oligomerization by γ-Al2 O3 has recently been reported, and it was suggested that Lewis acid sites are catalytic. The goal of this study is to determine the number of active sites per gram of alumina to confirm that Lewis acid sites are indeed catalytic. Addition of an inorganic Sr oxide base resulted in a linear decrease in the propylene oligomerization conversion at loadings up to 0.3 wt %; while, there is a >95 % loss in conversion above 1 wt % Sr. Additionally, there was a linear decrease in the intensity of the Lewis acid peaks of absorbed pyridine in the IR spectra with an increase in Sr loading, which correlates with the loss in propylene conversion, suggesting that Lewis acid sites are catalytic. Characterization of the Sr structure by XAS and STEM indicates that single Sr2+ ions are bound to the γ-Al2 O3 surface and poison one catalytic site per Sr ion. The maximum loading needed to poison all catalytic sites, assuming uniform surface coverage, was ∼0.4 wt % Sr, giving an acid site density of ∼0.2 sites per nm2 of γ-Al2 O3 , or approximately 3 % of the alumina surface.

The RADx Tech Deep Dive and Work Package 1 Process.

The RADxSM Tech program was a unique funding and support mechanism to accelerate the market introduction of diagnostic tests for SARS-CoV-2, the virus that causes COVID-19. In addition to providing funding, the RADx Tech program provided unprecedented levels of non- monetary support. Applications were evaluated using a deep dive process which involved a 1- to 2-week intensive collaboration between the applicant and a team of experts from RADx Tech. The result of this deep dive was a very comprehensive understanding of the potential and risks associated with the proposed work, which was far beyond what can typically be understood in a written grant application. This detail allowed the deep dive team to provide a better-informed recommendation on how to proceed. In some instances, the recommendation was made to not fund the project; in other cases, the recommendation was made to provide the applicant with more funding or support to help maximize their probability of success. After the deep dive, the project moved to a Work Package 1 (WP1) phase that focused on further de-risking. The same RADx Tech team that conducted the deep dive also worked with the applicant through the WP1 phase of the program. This allowed for joint responsibility of the work with the common goal of rapid, successful product introduction.

RADx Tech Viability and Steering Panels: A Model for MedTech Translational Grant Review.

RADxSM Tech's mission is to rapidly accelerate deployment of SARS-CoV-2 tests and could not utilize typical grant application and review processes that can run 4 to 6 months. Instead, RADx Tech leveraged methodologies developed by CIMIT and utilized by POCTRN as described further in this special issue. RADx Tech uses a multi-stage review with two review panels, a Viability Panel and a Steering Panel, that are supported by subject matter experts and a Deep Dive team. Members of the panels have extensive commercialization and business experience in addition to scientific and technical knowledge. The Viability Panel is responsible for assessing whether the proposal is a good fit with the RADx Tech Program and whether it should be recommended to move into a Deep Dive. Less detailed information is requested in the application than a typical SBIR application since the application is refined and details added during the Deep Dive. The Steering Panel reviews the results from the Deep Dive and decides whether to recommend further funding. Everyone on the Viability Panel and Steering Panel reviews every application, thereby providing consistency and context for the reviewers. Utilization of an "assess, improve, and then select" process with review panels comprised of highly experienced review panel members has resulted in improved timing, efficiency, and effectiveness of reviews and has the potential to be extensible beyond RADx Tech.

Differentiation of Francisella tularensis Subspecies and Subtypes.

The highly infectious and zoonotic pathogen Francisella tularensis is the etiologic agent of tularemia, a potentially fatal disease if untreated. Despite the high average nucleotide identity, which is >99.2% for the virulent subspecies and >98% for all four subspecies, including the opportunistic microbe Francisella tularensis subsp. novicida, there are considerable differences in genetic organization. These chromosomal disparities contribute to the substantial differences in virulence observed between the various F. tularensis subspecies and subtypes. The methods currently available to genotype F. tularensis cannot conclusively identify the associated subpopulation without using time-consuming testing or complex scoring matrices. To address this need, we developed both single and multiplex quantitative real-time PCR (qPCR) assays that can accurately detect and identify the hypervirulent F. tularensis subsp. tularensis subtype A.I, the virulent F. tularensis subsp. tularensis subtype A.II, F. tularensis subsp. holarctica (also referred to as type B), and F. tularensis subsp. mediasiatica, as well as opportunistic F. tularensis subsp. novicida from each other and near neighbors, such as Francisella philomiragia, Francisella persica, and Francisella-like endosymbionts found in ticks. These fluorescence-based singleplex and non-matrix scoring multiplex qPCR assays utilize a hydrolysis probe, providing sensitive and specific F. tularensis subspecies and subtype identification in a rapid manner. Furthermore, sequencing of the amplified F. tularensis targets provides clade confirmation and informative strain-specific details. Application of these qPCR- and sequencing-based detection assays will provide an improved capability for molecular typing and clinical diagnostics, as well as facilitate the accurate identification and differentiation of F. tularensis subpopulations during epidemiological investigations of tularemia source outbreaks.

rs11670527 Upstream of ZNF264 Associated with Body Mass Index in the Coriell Personalized Medicine Collaborative.

INTRODUCTION: the effects of obesity on health are a concern for the military as they affect the fitness to serve of active service members, increase costs to the Military Health System, and reduce quality of life for veterans and beneficiaries. Although obesity can be influenced by behavioral and environmental factors, it has also been shown to be associated with genetic risk factors that are not fully understood. MATERIALS AND METHODS: we performed a genome-wide association study of 5,251 participants in the Coriell Personalized Medicine Collaborative, which includes 2,111 Air Force participants. We applied a generalized linear model, using principal component analysis to account for population structure, and analyzed single-variant associations with body mass index (BMI) as a continuous variable, using a Bonferroni-corrected P-value threshold to account for multiplicity. RESULTS: we identified one genome-wide significant locus, rs11670527, upstream of the ZNF264 gene on chromosome 19, associated with BMI. CONCLUSIONS: the finding of an association between rs11670527 and BMI adds to the growing body of literature characterizing the complex genetics of obesity. These efforts may eventually inform personalized interventions aimed at achieving and maintaining healthy weight.

The Yale Center for Biomedical Innovation and Technology (CBIT): One Model to Accelerate Impact From Academic Health Care Innovation.

The process of translating academic biomedical advances into clinical care improvements is difficult, risky, expensive, and poorly understood. Notably, many clinicians who identify health care problems do not have the time or expertise to solve the problems, and many academic researchers are unaware of important gaps in clinical care to which their expertise may apply.Recognizing an opportunity to connect people who can identify health care problems with those who can solve them, the Yale Center for Biomedical Innovation and Technology (CBIT) was established in 2014 to educate and enhance the impact of health care innovators. The authors review other health care innovation centers and describe best practices borrowed by Yale CBIT, which tailored its activities and approach to its unique ecosystem.In four years, Yale CBIT has affected over 3,000 people and established a health care innovation cycle as an efficient strategy to guide translational research. Yale CBIT has created or supported graduate and undergraduate courses, clinical immersion programs for industry partners, and large health care hackathon events. Over 200 projects have been submitted to CBIT for mentorship, and some of those projects have been commercialized and raised millions of dollars of follow-on funding.The authors present Yale CBIT as one model of accelerating the impact of academic medicine on clinical practice and outcomes. The project advising strategy is intended to be a template to maximize the efficiency of biomedical innovation and ultimately improve the outcomes and experiences of future patients.

Individuals with CYP2C8 and CYP2C9 reduced metabolism haplotypes self-adjusted ibuprofen dose in the Coriell Personalized Medicine Collaborative.

OBJECTIVES: The objectives of this study were to determine whether differences in CYP2C8 and CYP2C9 haplotype influence the dose of ibuprofen self-administered by individuals, and to examine the potential relationship between CYP2C8 and CYP2C9 reduced metabolism haplotypes and adverse events. PARTICIPANTS AND METHODS: We investigated relationships between genetic variations in CYP2C8 and CYP2C9 and ibuprofen use, dose, and side effects (reported by questionnaire) in 445 participants from the Coriell Personalized Medicine Collaborative. RESULTS: Carriers of reduced metabolism haplotypes for CYP2C8 (*2, *3, *4) and CYP2C9 (*2, *3) were significantly (P=0.0171) more likely than those lacking these variants to take less than the recommended dose of ibuprofen, after controlling for sex, age, race, and cohort. In contrast to ibuprofen dose, there were no differences in ibuprofen use frequency or reported side effects based on haplotype. However, there are often no early signs of acute kidney injury, the most serious side effect of elevated ibuprofen exposure. CONCLUSION: These results suggest a subset of individuals with genetic variation in CYP2C8 and CYP2C9 recognize that they obtain adequate drug efficacy with lower ibuprofen doses, or take lower doses due to prior side effects. However, most (82.6%) individuals with reduced metabolism haplotypes nonetheless took recommended or higher doses, potentially putting them at increased risk for side effects.

Ideglira is Associated With Improved Short-Term Clinical Outcomes and Cost Savings Compared with Insulin Glargine U100 Plus Insulin Aspart in the U.S.

OBJECTIVE: In the DUAL (Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) VII trial, IDegLira (a combination of insulin degludec and liraglutide) was compared with insulin glargine U100 plus insulin aspart. Both treatment approaches achieved similar glycemic control, but there were differences in hypoglycemia, changes in body weight, and injection frequency. The aim of the present analysis was to assess the short-term cost effectiveness of IDegLira versus insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin in the U.S. METHODS: A cost-utility model was developed to evaluate the clinical and economic outcomes associated with the 2 treatments over a 1-year time horizon, capturing the impact on quality of life of hypoglycemic events, body mass index, and injection frequency. Costs were captured from a healthcare payer perspective in 2017 U.S. dollars ($). RESULTS: IDegLira was associated with improved quality of life by 0.12 quality-adjusted life years compared with insulin glargine U100 plus insulin aspart. The key drivers of this difference were reduced injection frequency and hypoglycemic events avoided. IDegLira was associated with increased annual drug costs, but this was entirely offset by reduced needle costs and reduced costs of self-monitoring of blood glucose testing. IDegLira was associated with total annual cost savings of $743 per patient. CONCLUSION: IDegLira was found to improve quality-adjusted life expectancy and reduce costs when compared with insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes not achieving glycemic control on basal insulin in the U.S. ABBREVIATIONS: ADA = American Diabetes Association; BMI = body mass index; CI = confidence interval; DUAL = Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes; GLP-1 = glucagon-like peptide-1; HbA1c = glycated hemoglobin; ICER = incremental cost-effectiveness ratio; IU = international units; QALY = quality-adjusted life year; SMBG = self-monitoring of blood glucose.

Long-term cost-effectiveness analysis shows that IDegLira is associated with improved outcomes and lower costs compared with insulin glargine U100 plus insulin aspart in the US.

AIMS: The clinical and economic impact of diabetes is growing in the US. Choosing therapies that are both effective and cost-effective is becoming increasingly important. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin, vs insulin glargine U100 plus insulin aspart, in the US setting. MATERIALS AND METHODS: Long-term projections of cost-effectiveness outcomes were made using the IQVIA CORE Diabetes Model. Clinical inputs were based on the DUAL VII trial, with costs (accounted from a healthcare payer perspective) and utilities based on published sources. Future costs and clinical benefits were discounted at 3% annually. RESULTS: IDegLira was associated with increased discounted life expectancy by 0.02 years and increased discounted quality-adjusted life expectancy by 0.22 quality-adjusted life years compared with insulin glargine U100 plus insulin aspart. Evaluation of direct medical costs suggested that the mean cost per patient with IDegLira was $3,571 lower than with insulin glargine U100 plus insulin aspart. The cost saving was driven predominantly by the lower acquisition cost of IDegLira compared with insulin glargine U100 plus insulin aspart, with further cost savings identified as a result of avoided treatment of diabetes-related complications. IDegLira was associated with improved clinical outcomes at a reduced cost compared with insulin glargine U100 plus insulin aspart. CONCLUSIONS: Based on clinical trial data, the present analysis suggests that IDegLira is associated with improved clinical outcomes and cost savings compared with treatment with insulin glargine U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US. Therefore, IDegLira is likely to be considered dominant (cost saving and more effective) and, consequently, highly cost-effective in the US setting.

The Intersection of Gender and Resuscitation Leadership Experience in Emergency Medicine Residents: A Qualitative Study.

OBJECTIVES: The objective was to examine emergency medicine (EM) residents' perceptions of gender as it intersects with resuscitation team dynamics and the experience of acquiring resuscitation leadership skills. METHODS: This was an exploratory, qualitative study using grounded theory and a purposive sample of postgraduate year (PGY) 2-4 EM residents who function as resuscitation team leaders in two urban EM programs. One-on-one interviews were conducted by a single experienced researcher. Audiotaped interviews were transcribed and deidentified by two research assistants. A research team composed of a PhD educational researcher, a research nurse, an MPH research assistant, and an EM resident reviewed the transcripts and coded and analyzed data using MAXQDA v12. Themes and coding schema were discussed until consensus was reached. We used member checking to assess the accuracy of our report and to confirm that the interpretations were fair and representative. RESULTS: Theme saturation was reached after interviewing 16 participants: 10 males and 6 females. The three major themes related to gender that emerged included leadership style, gender inequality, and relationship building. Both male and female residents reported that a directive style was more effective when functioning in the resuscitation leadership role. Female residents more often expressed discomfort with a directive style of leadership, preferring a more communicative and collaborative style. Both female and male residents identified several challenges as disproportionately affecting female residents, including negotiating interactions with nurses more and "earning the respect" of the team members. CONCLUSIONS: Residents acknowledged that additional challenges exist for female residents in becoming resuscitation team leaders. Increasing awareness in residency program leadership is key to affecting change to ensure all residents are trained in a similar manner, while also addressing gender-specific needs of residents where appropriate. We present suggestions for addressing these barriers and incorporating discussion of leadership styles into residency training.

Precision Military Medicine: Conducting a multi-site clinical utility study of genomic and lifestyle risk factors in the United States Air Force.

Following several years enrolling disease-specific and otherwise healthy cohorts into the Coriell Personalized Medicine Collaborative, a prospective study aimed at evaluating the clinical utility of personal genomic information for common complex disease and pharmacogenomics, the Coriell Personalized Medicine Collaborative expanded to create a military cohort, specifically, the United States Air Force. Initial recruitment focused on Air Force Medical Service personnel and later expanded to include all Active Duty Air Force members and beneficiaries. Now in its 6th year, the study has produced a wide variety of insights, including optimal study design for military-sponsored genomic research, and discussion on genetic information sharing between and amongst Air Force study participants, civilian and military researchers, and the United States Department of Defense. Over the longer term, analyses will further contribute to the development of policies and processes relevant to clinical decision support and data sharing within the US military, and on-going work with the Air Force Medical Service sub-cohort will generate critical insights into how best to deploy useful genomic information in clinical care. Here we discuss challenges faced and critical success factors for military-civilian collaborations around genomic research.

Secondary Students' Writing Achievement Goals: Assessing the Mediating Effects of Mastery and Performance Goals on Writing Self-Efficacy, Affect, and Writing Achievement.

The two studies reported here explored the factor structure of the newly constructed Writing Achievement Goal Scale (WAGS), and examined relationships among secondary students' writing achievement goals, writing self-efficacy, affect for writing, and writing achievement. In the first study, 697 middle school students completed the WAGS. A confirmatory factor analysis revealed a good fit for this data with a three-factor model that corresponds with mastery, performance approach, and performance avoidance goals. The results of Study 1 were an indication for the researchers to move forward with Study 2, which included 563 high school students. The secondary students completed the WAGS, as well as the Self-efficacy for Writing Scale, and the Liking Writing Scale. Students also self-reported grades for writing and for language arts courses. Approximately 6 weeks later, students completed a statewide writing assessment. We tested a theoretical model representing relationships among Study 2 variables using structural equation modeling including students' responses to the study scales and students' scores on the statewide assessment. Results from Study 2 revealed a good fit between a model depicting proposed relationships among the constructs and the data. Findings are discussed relative to achievement goal theory and writing.

Supporting Third Year Medical Students' Skill Acquisition and Self-Efficacy with Coping Models and Process Feedback during Laparoscopic Knot Tying Simulation.

Background: During the third year general surgery clerkship, medical students are required to develop laparoscopic knot-tying skills. Knot-tying skills studies often rely on objective variables (e.g., time, materials used, number of iterations) that lend themselves to correlational analysis of pre- and post-intervention skill level. This study differs by examining how instructional interventions-role modeling and feedback-affect medical students' skill acquisition and self-efficacy during a laparoscopic surgical simulation training session. Methods: Seventy-eight surgical clerkship students were assigned randomly to one cell of a 2X2 factorial design. Participants observed one of two types of role modeling (expert vs. coping) and received either process-oriented or outcome-oriented feedback during a 30-min laparoscopic training session. Participants also completed several surveys that assessed their interest in surgery and their self-efficacy for laparoscopic knot tying. Results: Coping model groups tended to perform better on the knot tying task, though this was less the case in the presence of outcome feedback. Expert model groups slightly outperformed the coping model group on the peg transfer task, but in the presence of outcome feedback they reported the lowest satisfaction with their performance and the lowest self-efficacy for the knot tying task. The coping model combined with process feedback had a positive influence on students' efficiency in learning the task, on their satisfaction with their performance, and on their self-efficacy for laparoscopic knot typing. Conclusions: Results are discussed relative to self-regulated learning theory.

Healthcare Commercialization Programs: Improving the Efficiency of Translating Healthcare Innovations From Academia Into Practice.

Academic investigators are generating a plethora of insights and technologies that have the potential to significantly improve patient care. However, to address the imperative to improve the quality, cost and access to care with ever more constrained funding, the efficiency and the consistency with which they are translated into cost effective products and/or services need to improve. Healthcare commercialization programs (HCPs) are described and proposed as an option that institutions can add to their portfolio to improve translational research. In helping teams translate specific healthcare innovations into practice, HCPs expand the skillset of investigators and enhance an institution's innovation capacity. Lessons learned are shared from configuring and delivering HCPs, which build on the fundamentals of the National Science Foundation's Innovation Corps program, to address the unique challenges in supporting healthcare innovations and innovators.

Disseminated vaccine-strain varicella as initial presentation of the acquired immunodeficiency syndrome: a case report and review of the literature.

Varicella-zoster virus (VZV) infections have declined in many industrialized countries due to vaccination with the attenuated Oka strain virus. Rare cases of severe, disseminated vaccine-strain VZV infection have occurred in the immunocompromised, although rarely in HIV-infected persons. We describe a man with previously-undiagnosed human immunodeficiency virus (HIV) infection who received VZV vaccination and subsequently presented to a combat hospital in Afghanistan with disseminated varicella, respiratory failure, and sepsis. The patient recovered with ventilator and hemodynamic support, intravenous acyclovir, and empiric antibiotic therapy. DNA sequencing detected Oka strain virus from patient blood specimens. Although safe in most populations, the VZV vaccine may cause life-threatening disease in immunocompromised patients. Improved detection of HIV infection may be useful in preventing such cases.

Francisella tularensis Subtype A.II Genomic Plasticity in Comparison with Subtype A.I.

Although Francisella tularensis is considered a monomorphic intracellular pathogen, molecular genotyping and virulence studies have demonstrated important differences within the tularensis subspecies (type A). To evaluate genetic variation within type A strains, sequencing and assembly of a new subtype A.II genome was achieved for comparison to other completed F. tularensis type A genomes. In contrast with the F. tularensis A.I strains (SCHU S4, FSC198, NE061598, and TI0902), substantial genomic variation was observed between the newly sequenced F. tularensis A.II strain (WY-00W4114) and the only other publically available A.II strain (WY96-3418). Genome differences between WY-00W4114 and WY96-3418 included three major chromosomal translocations, 1580 indels, and 286 nucleotide substitutions of which 159 were observed in predicted open reading frames and 127 were located in intergenic regions. The majority of WY-00W4114 nucleotide deletions occurred in intergenic regions, whereas most of the insertions and substitutions occurred in predicted genes. Of the nucleotide substitutions, 48 (30%) were synonymous and 111 (70%) were nonsynonymous. WY-00W4114 and WY96-3418 nucleotide polymorphisms were predominantly G/C to A/T allelic mutations, with WY-00W4114 having more A+T enrichment. In addition, the A.II genomes contained a considerably higher number of intact genes and longer repetitive sequences, including transposon remnants than the A.I genomes. Together these findings support the premise that F. tularensis A.II may have a fitness advantage compared to the A.I subtype due to the higher abundance of functional genes and repeated chromosomal sequences. A better understanding of the selective forces driving F. tularensis genetic diversity and plasticity is needed.