• Characterization of Schu S4 delta aroD as a putative vaccine candidate against pulmonary tularemia

      Cunningham, Aimee L.; Santiago, Araceli E.; Mann, Barbara J., Ph.D.; Qin, Aiping; Grassel, Christen; Vogel, Stefanie N.; Barry, Eileen M. (2015-03-09)
      Francisella tularensis is the etiological agent of the human disease tularemia and a Tier 1 Select Agent. There is a need for an efficacious vaccine against this pathogen due to its low infectious dose, high mortality rate, and ability to be spread by aerosol. To this end, we have engineered a defined live attenuated strain derived from the highly human virulent F. tularensis WT strain Schu S4, designated Schu S4ΔaroD; this strain lacks aroD, the 3rd enzyme in the chorismate biosynthesis pathway used for synthesis of aromatic amino acids. Schu S4ΔaroD is attenuated for growth in broth cultures and in both J774 and primary murine peritoneal macrophages, with a pulmonary LD50 > 105 CFU in C57BL/6 mice (compared to WT Schu S4 LD50 < 10 CFU). Intranasal immunization with Schu S4ΔaroD protects against high-dose WT pulmonary challenge in C57BL/6 mice. A single 50 CFU dose of Schu S4ΔaroD generated 80% protection against 100 CFU challenge, and addition of a 105 CFU booster to the initial 50 CFU vaccination is 80% and 40% protective against 500 or 1000 CFU challenge, respectively. Further studies revealed that a 103 or 105 CFU priming dose followed by a 108 CFU boost is 100% protective against 1000 CFU WT Schu S4 pulmonary challenge. This level of protection has not previously been demonstrated by any tularemia vaccine candidate. Bacterial burden following i.n. vaccination found that regardless of initial dose, immunized mice show identical bacterial loads (107 CFU/g tissue in the lung and 105 CFU/g tissue in the liver) at the peak of infection. However, time to peak burden was dose-dependent, as animals receiving a higher initial inoculum (at least 5600 CFU) reach this peak at day 3, as opposed to day 7 in lower initial inoculum groups. Peak bacterial burden correlates with maximal associated histopathology in the liver and peak pro-inflammatory cytokine and chemokine production in lungs, liver, and spleen (TNF-α, IL-1β, Cox-2, KC, iNOS, MCP-1). Our study shows Schu S4ΔaroD serves as an efficacious defined live attenuated vaccine against pulmonary tularemia. We have revealed a dose-dependent response to Schu S4ΔaroD, which may help determine the protective capacity of this vaccine and assist in development of vaccine-associated correlates of protection in the mouse model.
    • Risks Factors for Colorectal Precancerous and Cancerous Lesions in HIV-infected Patients

      Yimgang, Doris; Magder, Laurence S.; Stafford, Kristen Alyce; Fisher, Lydia H.; Cullen, Nicole R.; Riedel, David J.; Kang, Minji; Innis, Ellen K.; Wang, Elizabeth W.; Riner, Andrea N.; et al. (2015-03-09)
      Although data are conflicting, some studies suggest that HIV-infected patients may have a higher risk for colorectal cancer. The purpose of this study is to analyze the relationship between known and potential HIV specific risk factors on the incidence of precancerous and cancerous lesions found on colonoscopy in HIV-infected individuals. This is a retrospective analysis of clinical data collected on 263 HIV-infected patients.
    • Exome sequencing from extreme responders to aspirin identifies a novel variant associated with platelet aggregation

      Backman, Joshua David; Ning, B.; Lou, W.; Perry, James; Shi, L.; Lewis, J.; Shuldiner, Alan R.; Yerges-Armstrong, Laura M. (2015-03-09)
      Objective: To identify novel variants that may significantly impact platelet response to aspirin and DAPT (Dual Anti-Platelet Therapy).
    • Regulators of Hematopoietic Progenitor Differentiation

      Baldeosingh, Rajkumar; Gao, Hongjuan; Wu, Xiaorong; Fossett, Nancy (2015-03-09)
      Hematopoietic stem cells (HSCs) must be capable of both self-renewal and production of progenitor cells that give rise to all of the blood cell types, the two basic principles of stem cell biology. Investigations into gene networks controlling HSC response to stress have been conducted using model organisms such as Drosophila melanogaster. One of the factors controlling vertebrate HSC multipotency and differentiation is the GATA:FOG complex. GATA:FOG complexes regulate the development of a number of blood lineages. In Drosophila, the GATA:FOG complex blocks the differentiation of hematopoietic progenitors into the stress-responsive lamellocyte lineage. Drosophila hematopoietic progenitors are strikingly similar to HSCs and are used as a model for these vertebrate stem cells. We used fly genetics to identify GATA:FOG network members that block the stress-response of hematopoietic progenitors.
    • The Effects of reactive and voluntary step training on balance recovery during lateral perturbation in individuals with chronic stroke

      Yang, Chieh-ling; Gray, Vicki L.; McCombe-Waller, Sandra; Rogers, Mark William (2016-04)
      Falls have been reported as high as 73% in community dwelling individuals following a stroke. Many falls happen while transferring weight laterally. To guard against loss of balance with this lateral weight transfer a reactive, protective step is commonly used to recover balance. Current rehabilitation practices mainly focus on intentional voluntary actions to improve balance control which may not carry-over to the development of protective stepping strategies to avoid a fall. Objective: The purpose of this study is to determine the effects of six weeks of reactive versus voluntary step training on balance recovery during lateral perturbations in individuals with chronic stroke
    • Multi-Joint Somatosensory Assessment in Patients Post Stroke

      Zhang, Li-Qun; Xu, Dali; Kang, Sang Hoon; Roth, Elliot J.; Ren, Yupeng (2017-10-09)
      Introduction: Stroke survivors experience sensory impairment, which was reported as a main predictor for motor recovery post stroke. Understanding the characteristics of somatosensory deficits post stroke is helpful in motor relearning and recovery. Previous studies of touch and proprioception focused on characteristics of a single joint (Pumpa, Cahill, & Carey, 2015; Winward, Halligan, & Wade, 1999). There has been a lack of characterization of multi-joint proprioception and their changes post stroke. Considering that human functional activities almost always involve multiple joints simultaneously, examination and treatment of multiple joints are important. Objectives: To investigate the somatosensory perceptions at the shoulder, elbow and wrist joints and their changes post stroke, as compared to that of healthy subjects.
    • Comparison of a novel, endoscopic chest tube insertion technique versus the standard, open technique performed by novice users in a human cadaver model: A randomized, crossover, assessor-blinded study

      Drumheller, Byron C.; Basel, Anthony; Adnan, Sakib; Rabin, Joseph; Pasley, Jason D.; Brocker, Jason; Galvagno, Samuel M. (2018-12-27)
      Background: The technique of tube thoracostomy has been standardized for years without significant updates. Alternative procedural methods may be beneficial in certain prehospital and inpatient environments with limited resources. We sought to compare the efficacy of chest tube insertion using a novel, endoscopic device (The Reactor™) to standard, open tube thoracostomy. Methods: Novice users were randomly assigned to pre-specified sequences of six chest tube insertions performed on a human cadaver model in a crossover design, alternating between the Reactor™ and standard technique. All subjects received standardized training in both procedures prior to randomization. Insertion site, which was randomly assigned within each cadaver's hemithorax, was marked by the investigators; study techniques began with skin incision and ended with tube insertion. Adequacy of tube placement (intrapleural, unkinked, not in fissure) and incision length were recorded by investigators blinded to procedural technique. Insertion time and user-rated difficulty were documented in an unblinded fashion. After completing the study, participants rated various aspects of use of the Reactor™ compared to the standard technique in a survey evaluation. Results: Sixteen subjects were enrolled (7 medical students, 9 paramedics) and performed 92 chest tube insertions (n = 46 Reactor™, n = 46 standard). The Reactor™ was associated with less frequent appropriate tube positioning (41.3% vs. 73.9%, P = 0.0029), a faster median insertion time (47.3 s, interquartile range 38-63.1 vs. 76.9 s, interquartile range 55.3-106.9, P < 0.0001) and shorter median incision length (28 mm, interquartile range 23-30 vs. 32 mm, interquartile range 26-40, P = 0.0034) compared to the standard technique. Using a 10-point Likert scale (1-easiest, 10-hardest) participants rated the ease of use of the Reactor™ no different from the standard method (3.8 ± 1.9 vs. 4.7 ± 1.9, P = 0.024). The Reactor™ received generally favorable scores for all parameters on the post-participation survey. Conclusions: In this randomized, assessor-blinded, crossover human cadaver study, chest tube insertion using the Reactor™ device resulted in faster insertion time and shorter incision length, but less frequent appropriate tube placement compared with the standard technique. Additional studies are needed to evaluate the efficacy, safety and potential advantages of this novel device. © 2018 The Author(s).
    • PATIENTS Day 2019: Which Patients are Likely to Refuse to Participate in a Clinical Trial? A latent Class Analysis

      O'Hara, Nathan N.; Degani, Yasmin; Marvel, Debra; Wells, David; Mullins, C. Daniel; Wegener, Stephen; Frey, Katherine; Taylor, Tara; Castillo, Renan; O'Toole, Robert V. (2019-05-31)
    • PATIENTS Day 2019: Pathway to Diagnosis: Caregiver and Person with Dementia Experiences on Reaching a Diagnosis

      Hanna, Maya L.; Majid, Tabassum; Rosenthal, Ilene; Albrecht, Jennifer S.; Perfetto, Eleanor M. (2019-05-31)
    • PATIENTS Day 2019: What Motivates People with Substance Use Disorders to Pursue Treatment? A Patient-Centered Approach to Understanding Patient Experiences and Patient-Provider Interactions

      Gressler, Laura E.; Natafgi, Nabil; DeForge, Bruce R.; Robinson-Shaneman, Barbarajean; Welsh, Christopher; Shaya, Fadia T. (2019-05-31)
    • Respiratory protection safety culture beliefs among healthcare workers

      Hines, Stella E.; Oliver, Marc; Gucer, Patricia; Frisch, Melissa; Hogan, Regina; Roth, Tracy; Chang, James, C.I.H.; McDiarmid, Melissa (2019-10-30)
    • Evaluation of Surgical Site Infections after Change in Surgical Prophylaxis in Ventricular Assist Device Patients

      Min, Emily A.; Adediran, Timileyan; Thom, Kerri A.; Heil, Emily L. (2020)
      Background: Current guidelines for antimicrobial surgical prophylaxis in ventricular assist device (VAD) patients recommend single-agent cefazolin for either single dose or <24 hr continuation. In the clinical setting, prophylaxis choices for VAD patients historically included broader spectrum agents due to high morbidity and mortality associated with VAD infections. At the University of Maryland, antibiotic choice for surgical prophylaxis in VAD patients historically included broad gram-positive and gram-negative (including Pseudomonas) coverage, often vancomycin/piperacillin-tazobactam, for prolonged periods – increasing risk of antimicrobial resistance. In Oct. 2013, UMMC established standardized prophylaxis protocol for VAD patients: vancomycin + ceftriaxone for 72 hrs. Objective: To evaluate rate of surgical site infection (SSI) in VAD patients after implementation of this protocol
    • Designing Specific Inhibitors to Target S100B in Melanoma

      Vera-Rodriguez, Darex J.; Young, Brianna; Spriggs, Shardell; Yu, Wenbo; Wilder, Paul T.; MacKerell, Alexander D., Jr.; Weber, David J., Ph.D. (2020)
      Malignant melanoma (MM) is defined as the most dangerous form of skin cancer, causing a large majority of skin cancer deaths. Previous studies demonstrate S100B as a tumor marker in MM, a protein that interacts with the tumor suppressor p53, inhibiting p53 function. With the goal of blocking this interaction, three binding sites on S100B for small molecules have been identified. However, developing drugs specific for S100B over other S100-family members remains a challenge. This project aims to identify S100B-specific small molecule inhibitors and understand the basis of their specificity over other S100 family members, specifically S100A1. A 2D-[1H,15N] NMR HSQC of S100B bound to a non-specific fragment showed multiple chemical shifts perturbations (CSPs) including residues A9, L10, F43, L40, F73, and C84. Interestingly, fewer and less pronounced CSPs were observed for a S100B-specific fragment. Site-Identified Ligand Competitive Saturation (SILCS) molecular dynamics (MD) simulations were performed to determine potential S100B binding sites that could explain the CSPs. Results show a strong hydrophobic pocket at low Grid Free Energy (GFE) levels comprised by the residues that showed CSPs for compounds that bind S100B. FDA-approved compounds were tested using SILCS-Monte Carlo (MC) to determine ligand binding poses at this pocket. Specific compounds were targeted with strong hydrophobic interactions and hydrogen bonds at low Ligand GFE (GFE). These data provide important information relevant to developing S100B-specific drugs to treat MM.
    • Effective Collaboration Towards Positive Perioperative Outcomes for the Cardiac Surgery Patient: A Perioperative Services - Cardiac Surgery Performance Innovation Project

      Perry, Mary; Fortuno, Maridulce Belen (2020)
      Nurses in the University of Maryland Medical Center (UMMC) Procedure Readiness Evaluation and Preparation (PREP) Center care for complex patients and support multiple surgical specialties, including cardiac surgery. Workflows related to cardiac surgery, specifically identification of blood type and antibodies (“blood banding”), presented a particular challenge for the clinic, and cardiac surgery patients were not always ready for the operating room (OR) on the day of surgery. PROJECT AIMS: To provide an efficient outpatient pre-operative 30-day blood band process in the PREP Center for the outpatient adult Cardiac Surgery patient. To establish a mutually beneficial internal work flow between UMMC Perioperative Services and Cardiac Surgery staff to minimize downstream OR delays.
    • Red Herring

      Al-Hamad, Suzanne; Pietris, Nicholas; Falck, Alison (2020)
    • A Clinical Care Cascade for Hepatitis B Virus Vaccination in a Current Era HIV Clinic

      Deming, Meagan; Kottilil, Shyamasundaran (2020)
      Background: Hepatitis B virus (HBV) infections remain a global health issue with complications including liver cirrhosis and hepatocellular carcinoma. Individuals co-infected with Human Immunodeficiency Virus (HIV) and HBV have increased liver-related morbidity and mortality compared to those with HBV mono-infection. Vaccination is a potent intervention to prevent HBV infection, but certain critical populations including people living with HIV are less likely to achieve seroprotection after vaccination. Seroprotection (antibody to hepatitis B surface antigen [HBsAb] titer ≥10 IU/mL) was historically poor, with trial rates ranging from 34 to 88% and improving with immunologic reconstitution and viral suppression. We hypothesized that the seroprotection rates (SPR) in a clinic population of Veterans would reflect the improving immunologic status of the cohort.