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Aging is a highly complicated, fundamental biological process that exists in all organisms, with few exceptions. Evolutionary evidence suggests that aging is plastic, given the vastly different lifespans of closely related species. Studies into simple model organisms such as the budding yeast S. cerevisiae and the nematode C. elegans have led to the identification of genes whose deletion extends lifespan, many of which are conserved in humans. In many cases, these gene deletions remove the brakes from lifespan-enhancing processes in the organism. Of interest here, deletions of genes belonging to large ribosomal subunits in yeast first unveiled the highly conserved, stress-responsive transcription factor Gcn4 (yeast) / ATF-4 (worms) / ATF4 (flies, mammals) as a mediator of lifespan. Since then, this transcription factor has been studied extensively and has been shown to be responsible for lifespan extension under conditions of lowered protein synthesis. In this dissertation, I take you through Gcn4 / ATF-4 / ATF4’s aging story.

Introduction: Neurodevelopmental disorders are a group of conditions that start in childhood and lead to impairments in functioning. HNRNPH2-related neurodevelopmental disorder is an ultra-rare disorder in which individuals present with cognitive, behavioral, language and motor function impairments that often leads to reliance on their caregivers. Existing conceptual models of neurodevelopment are not specific to this ultra rare disorder and do not highlight the caregiver impact of living with HNRNPH2-related neurodevelopmental disorder. Purpose: The purpose of this study is to understand the caregiver perspective on the everyday functioning of people living with HNRNPH2-related neurodevelopmental disorder to generate a person-centered conceptual model. Methods: Semi-structured interviews with twenty caregivers of individuals with HNRNPH2-related neurodevelopmental disorder were conducted. The interviews were transcribed verbatim and analyzed using thematic analysis. An initial conceptual model was developed using an adapted grounded theory framework. Results: Twenty primary caregivers including 14 female caregivers and 6 male caregivers of females with HNRNPH2-related neurodevelopmental disorder living in 9 countries: United Kingdom (35%); United States (30%); Netherlands (10%); Denmark, France, Norway, Portugal, and Switzerland (each 5%) were interviewed. The defining concepts of the condition include cognition, communication, neurological, behavioral, visual, musculoskeletal/orthopedics, gastrointestinal and others. Individuals with HNRNPH2-related neurodevelopmental disorder have impacts on daily functioning including proximal impacts (activities), distal impacts (participation), and modifiers including personal and external factors. In light of caregiver’s major role in supporting the everyday functioning of individuals with HNRNPH2 a conceptual disease model was developed from the study data diagraming the defining concepts or symptoms, impacts on people living with HNRNPH2-related neurodevelopmental disorder and caregiver impacts. Practical Implications: This study highlights the unique features of HNRNPH2-related neurodevelopmental disorder impacting the everyday functioning of those living with the condition and impact on their caregivers. The person-centered conceptual model can be implemented by families to describe key features of the condition and their child’s current level of function; by clinicians and advocates to develop practical care consideration guidelines and policies; and by researchers to develop person centered assessments and treatments specifically for relevant and meaningful functions of individuals with HNRNPH2-related neurodevelopmental disorder.

In the past 30 years, there have been major advancements on how to treat and diagnose disease because of the improvement and increase in accessibility of sequencing technology. Nucleic acid-based therapeutics can manipulate protein expression. Likewise, pathogens can be identified and detected with single nucleotide specificity. However, the underlying oligonucleotide technology requires protection against natural defense systems that have evolved to destroy foreign nucleic acids. Many chemical modifications that can protect nucleotides also have significant cytotoxic side effects and must be carefully designed into the strands. A novel way to protect against nuclease-mediated degradation is through the use of mirror-image, left-handed nucleotides which twist to the left, as opposed to the right-handed twist of natural DNA (D-DNA). This enantiomer of natural DNA (L-DNA) is thought to have low cytotoxicity and immunogenicity and have the same hybridization and thermodynamic properties of natural DNA. My thesis is that the combination of heterochiral DNA with dynamic, logic based DNA nanotechnology is a powerful tool for biomedical oligonucleotide development. In my work, I have developed an interface which can link an L-DNA bioorthogonal computing system to the natural, right-handed world of biology by using heterochiral DNA, DNA containing sections of left- and right-handed chirality in the same strand. My system can translate signals from one chiral domain to another and can be further improved by the addition of L-DNA domains that act as protective caps on D-DNA domains. I establish that the D-DNA components of strand displacement-based molecular circuits constructed using this technique resist degradation during extended incubations in serum-supplemented media and in a living human cell line.

Improving patient safety in anesthesia has proven to be an arduous and challenging task. Despite the many strategies and interventions to improve patient safety that have been employed, patient harm in anesthesia remains a problem. The struggle to reduce patient harm in anesthesia is both attributable to and representative of the complexity of the anesthesia system. In navigating this complex system, anesthesia providers have different approaches to how they accomplish their work, which results in variability in anesthesia practice. This variability provides an immense challenge to designing and implementing efforts to improve patient safety, as rigid interventions are often met with intransigence due to their inability to mesh with variable practice. Just as anesthesia providers must be flexible to adapt to the complexities each case presents, human factors engineers are faced with the challenge of developing interventions that boast the same level of flexibility to fit within these work systems. In order to do so, we must first further our knowledge of the existing variability in anesthesia so it can be appropriately considered in future designs. It is only through proper consideration of the existing variability in anesthesia that we will be able to determine avenues for improving patient safety that are flexible to the entire scope of medication administration, and therefore are not susceptible to the same pitfalls that have inhibited the success of prior efforts. Thus, the overall objective of this dissertation was to provide a scope of the variability that exists in the practice of anesthesia such that it can be utilized by engineers to create interventions which are flexible to the entire scope of medication administration. Three studies were completed in this dissertation. The first study investigated the scope of variability and inconsistency in patient safety-related terminology in anesthesia through a structured literature review. The main finding of this study is that the term “medication error” had widely variant definitions which represent fundamentally different concepts. This inconsistency in terminology can lead to problems with synthesizing, interpreting, and overall sensemaking in relation to anesthesia medication safety. The second study investigated the scope of variability in the use and dosing of anesthesia medications through several statistical analyses of a large anesthesia dataset. The main finding of this study is that there was significant variability in the use and dosing of medications between five different hospitals within the same health system. By examining variability between hospitals in the same health system, we can identify potential avenues for interventions that improve patient safety and foresee potential difficulties with implementing these interventions. The third study investigated the feasibility of designing a standardized medication set that accounts for variability in anesthesia medication use through the development and use of a greedy algorithm. The main finding of this study is that, depending on the available size for a standardized medication set, a single standard set may be able to effectively cover a vast majority of cases at all institutions. Improving patient safety through standardization is possible despite the large amount of variability identified, though the design and implementation of such systems must be done with careful consideration of the existing variability. This dissertation informs anesthesia patient safety ideology and provides guidance towards how we can make lasting, widespread improvements to anesthesia patient safety.

Background: The study aimed to investigate the factors influencing the intentions of Volunteer Firefighters in the USA to engage in physical activity. The Theory of Planned Behavior (TPB) constructs, including Attitudes, Perceived Behavioral Control, Actual Behavioral Control, and Subjective Norms, alongside three new constructs not linked to TPB—Habits, Environmental Factors, and lack of knowledge—as potential predictors of physical activity intentions. Purpose: The purpose of this study was to examine the relationship between TPB constructs and the newly emerged factors with the intentions of Volunteer Firefighters to be physically active. By understanding these factors, the study sought to shed light on potential barriers and facilitators that could influence their physical activity behaviors. Methods: The study used a basic qualitative design with purposeful, criterion and snowball sampling methods, analyzing data from Volunteer Firefighters across the USA. Participants' intentions to be physically active were assessed based on the TPB constructs. Data were collected through surveys and interviews. A twelve-item semi-structured interview protocol, developed from the TPB was used with probes to conduct approximately 30 minutes’ interviews with each participant. The interviews were conducted until no new codes emerged, recorded, and then transcribed verbatim. The transcripts were coded using open, in-vivo, and descriptive coding approaches. Inter-coder consensus was reached. Categories were developed from the codes for thematic analysis. The TPB constructs informed some of the themes and three newly identified themes—Habits, environmental factors, and lack of knowledge emerged. Results: The analysis revealed that TPB constructs, including Attitudes, Perceived Behavioral Control, Actual Behavioral Control, and Subjective Norms, were predictors of physical activity intentions among Volunteer Firefighters in the USA. Additionally, the study found that the newly emerged factors, Habits, environmental factors, and lack of knowledge, also contributed to predicting intentions to be physically active. Conclusion: The study's findings underscore the importance of considering both TPB constructs and the additional factors when developing interventions to promote physical activity among Volunteer Firefighters. Addressing barriers related to time constraints, weight concerns, harsh weather conditions, and lack of sleep may help improve their intentions to engage in regular physical activity. Moreover, recognizing the influence of family support and the significance of mental agility and awareness in firefighting situations can further enhance strategies aimed at promoting physical activity and overall well-being among Volunteer Firefighters. Overall, this research provides valuable insights into the complex interplay of factors that influence physical activity intentions among Volunteer Firefighters. It serves as a foundation for the development of targeted interventions and strategies to address the specific challenges faced by this population, promoting their health and fitness. Additionally, the application of theory in this study highlights its potential utility in understanding physical activity intentions among Volunteer Firefighters and offers valuable implications for future research and intervention development in this area.

Background: Athletic identity is the extent to which one identifies with the athlete role, but we do not know what that looks like in club sports and its effect on concussion reporting intention. The athletic identity of club sport athletes and their intention to report concussive injuries is limited and needs further research. Purpose: Describe athletic identity in club sport athletes and determine its influence on concussion reporting in club sport participants. Methods: A convenience sample of 149 (age 18-28 (M= 19.95±1.81) years old) club sport athletes at Georgia Southern University completed the Athletic Identity Measurement Scale (AIMS) and Intention to Report Subscale (Theory of Planned Behavior Scale) during the 2022-2023 calendar year. Scores from the AIMS and Intention to Report Subscale served as dependent variables. Correlation analyses utilizing Pearson and Spearman’s Rho correlations examined the relationship between age, sex, sport, level of involvement, previous history of concussions, previous history of concussion education, athletic identity, and intention to report. Results: Participants averaged 11.16 years (SD = 5.34) of sport involvement with lacrosse (20.1%), men’s volleyball (12.5%), dance (11.1%), women’s volleyball (9.0%), cheer (7.6%), and quidditch (6.9%) providing the most responses. The average AIMs score for the entire sample was relatively moderate (M= 35.24± 7.77). The total number of years that athletes participated in sports was significantly associated with athletic identity (r= .387, p < 0.001). Age was negatively associated with athletic identity (r= -0.23, p= 0.006). A moderate-high intent to report (M= 16.82±4.60) concussion was obtained. No correlations existed between athletic identity, age, sex, club sport, years in sport, and intention to report a concussion in club sport athletes. Conclusions: Club sport athletes do have an established athletic identity which could be impacted by years of participation in sport and age. No relationship existed between athletic identity and intention to report a concussion; however, the influence of identity playing a role in concussion reporting intention in club sport athletes should not be discounted because of the moderate-high intention to report found in this study.

Introduction: One of the goals of endodontic therapy is to debride infected pulps of teeth and return the tooth to a state of health in preparation of restorative care and return to function. Chemically cleansing of the canal system augments mechanical debridement by flushing out debris, dissolving tissue, and disinfecting the root canal system. The purpose of this research is to compare the efficacy of five irrigants: 0.008% HOCl acid (Endocyn®), 0.03% HOCl (Vashe®), 6% and 8.25% sodium hypochlorite (NaOCl), and Ozone against a typical bacterial species found in infected pulps, Enterococcus faecalis (E. faecalis). Methods: After 24 hours of growth of E. faecalis onto an Innovatech 96 well hydroxyapatite coated peg plate, the biofilms were introduced to five different irrigants for 30 seconds of exposure, then immersed into a Difco D/E Neutralizing broth solution for 30 minutes. Each hydroxyapatite peg was placed into 1.5mL centrifuge tubes and diluted by a factor of 10. Dilution samples were transferred into experimental 5mL bottom round test tubes and the Invitrogen’s Molecular Probes LIVE/DEAD BacLight Bacterial Viability Counting Kit was used to prepare the final samples for analysis at WVU’s Flow Cytometry and Single Cell Core Facility. Results: There was a significant difference in antibacterial effectiveness among the five irrigant groups (p Conclusions: All irrigants tested had antibacterial properties against E. faecalis. 6% NaOCl and 8.25% NaOCl demonstrated the greatest antibacterial effect against E. faecalis compared to other irrigants.

Spatially resolved transcriptomics technologies investigate gene expression in the context of a tissue. While imaging-based technologies enable gene expression quantification at a single-cell level, only two NGS-based technologies are currently capable of single-cell resolution. Both Stereo-seq and Seq-Scope involve two rounds of sequencing: one to sequence the location of spatial barcodes and the other to obtain sequence of cDNA. Thus, the objective of the research study is to develop a technology that can capture transcripts from every cell of a tissue without the need for two rounds of sequencing. To this end, a capture surface or barcoded array (similar to 10x Genomics’ Visium platform) with feature sizes of 2.0µm and 0.6µm was manufactured. Spatial transcriptomics was performed on a fresh-frozen and FFPE mouse brain tissue section. The research study demonstrates successful capture of transcripts from the tissue. Furthermore, spatial domains and spatially variable genes identified were consistent with published literature.

Tibial stress fractures are a common overuse injury accounting for 21.9 – 69% of stress fractures among runners and 24 – 51.2% of stress fractures in military cadets. Current treatment involves wearing a walking boot for 3 – 12 weeks, which limits ankle motion and causes lower limb muscle atrophy. A Dynamic Ankle Orthosis (DAO) provided a distractive force that offloaded the ankle and retained sagittal ankle excursion during walking. It remains unclear how tibial loading is affected by a walking boot or the DAO. This thesis presents a feasibility study confirming the offloading effects of the DAO on tibial loads and Achilles tendon forces during treadmill walking, and a cadaveric study evaluating the offloading effects of the DAO on distal tibia strain. The objective of study 1 was to determine the effects of the DAO and walking boot on tibial compressive force and ankle motion during treadmill walking. Twenty healthy young adults walked on a split-belt instrumented treadmill at 1.0 m/s in two brace conditions: DAO and walking boot. A 3D motion capture system recorded kinematic data, force treadmill recorded ground reaction forces, and vertical force insoles measured in-shoe vertical reaction force. Kinetic and kinematic variable calculations were used to determine the peak tibial compressive force. Target offloading of the DAO was 10% body weight. The DAO moderately reduced peak tibial compressive force (10.9%) and Achilles tendon force (12%) compared to the walking boot. Sagittal plane ankle motion during stance phase was largely reduced by 54.9% in the walking boot compared to the DAO. The objective of study 2 was to evaluate changes in strain magnitude due to the offloading effect of the DAO on tibial bone mechanics compared to standard-of-care walking boot using fresh frozen cadaver specimens. Three fresh frozen cadaver legs were placed in a robotic testing platform and dynamically loaded to 900N at a rate of 3.2mm/s in the DAO and walking boot. Linear strain gauges were attached to the distal tibia and midshaft tibia to measure the compressive strain at specific points along the longitudinal axis of the tibia. Vertical force sensing insoles measured in-shoe vertical reaction force. Target offloading of the DAO was 10% of the applied load. Peak strain was significantly reduced at the distal tibia (23.31%) wearing the DAO compared to the walking boot. Pearson correlations showed moderate to strong negative linear relationship between the compressive strain and vertical reaction force measurements within subjects at both the distal and midshaft tibia. These findings indicate the DAO moderately reduced tibial compression force and Achilles tendon force while providing greater sagittal ankle excursion compared to a walking boot. In addition to reproducing similar strain data to previous literature, the DAO strongly reduced the peak strain primarily at the distal tibia as well as reduced vertical reaction force. Moderate to strong linear correlations occurred between the external vertical reaction force and internal strain magnitude. This body of work provides evidence that the DAO could function as an alternative rehabilitation device for treating tibial stress fractures by reducing bone strain and tibial loading during walking.

Open-source laboratory equipment has become an increasingly popular alternative to commercially available options due to its simple implementation, capability of user-customized modifications, and cost-effectiveness. Presented here is the development of a programmable and open-source fluidic system comprised of three custom-built syringe pumps for cell culture applications. The fluidic system was directly integrated with a multiwell plate on an environmentally controlled microscope platform for live-cell imaging and time-lapse analyses of cellular responses as culture conditions are adjusted using the programmable fluidic system. Proof-of-concept of this system is obtained by controlling autophagic activity in A549 cells by adjustment of nutrient supply. The programmability of this fluidic system allows for straightforward, low-cost implementation of feedback control methods in cell culture systems. These results will enable future research on understanding cell responses to time-dependent modulation of culture conditions or dosing with multiple pharmaceutical reagents.

Traumatic brain injury (TBI) mechanism and severity are heterogenous clinically, resulting in a multitude of physical, cognitive, and behavioral deficits. However, approximately 80% suffer from milder injuries. Thus, examining pathophysiological changes associated with mild TBI is imperative for improving clinical translation and evaluating the efficacy of potential therapeutic strategies. Through this work, we developed models of TBI, ranging in both injury mechanism and severity, using an electromagnetic controlled cortical impact (CCI) device. First, we characterized and optimized a closed head, mild TBI model (DTBI) to determine the clinical translatability and practicality of producing repeated mild injuries. Interestingly, we determined that impact speed was highly dependent on both input velocity and depth. Indeed, impact conditions differed from input parameters, and we suggest researchers characterize closed head models using CCI devices to ensure data is interpreted based on the true impact conditions. Additionally, we investigated how impact speeds influenced pathophysiology, specifically autophagic flux. Our results show that autophagic flux was impaired acutely in the hippocampus, regardless of impact speed, providing rationale for evaluating autophagic flux following mild, diffuse impacts. Thus, we continued investigating pathophysiological changes associated with a spectrum of TBI, including severe CCI, modified mild TBI (MTBI), and previously characterized DTBI. Following impacts, we observed distinct differences in gross neuropathology, which corresponded with changes in the progression of cell death. Indeed, severe CCI resulted in dramatic increases in oncosis, while mild models differed regarding apoptotic response, suggesting injury mechanism and severity shift the progression of cell death. Interestingly, each of the three impact models resulted in impaired autophagic flux, which coincided with changes in both oncotic and apoptotic cell death. Thus, these results provide evidence that the pathophysiological mechanisms affiliated with TBI heterogeneity may be linked through common upstream events, namely impaired autophagic flux and lysosomal dysfunction. Therefore, therapeutic strategies designed to intervene in the amelioration of these consequences may alleviate molecular dysfunction, in addition to the cognitive and behavioral deficits observed following TBI. Advisor: Forrest M. Kievit

Statement of the Problem: The Masgutova Method® is a research emergent area with a growing yet limited research base. In order to facilitate a widespread and robust acceptance and integration of The Masgutova Method® as evidence-based practice, a significant increase in research is warranted. MNRI® Core Specialists are well-positioned to be scholars in The Masgutova Method®. At this time, there is no literature exploring MNRI® Core Specialists’ foundational research knowledge, attitude toward research, and research practice. Purpose of the Study: The purpose of this study is to establish a baseline understanding of MNRI® Core Specialists’ research knowledge, attitude, and practices. Methods: This study utilized a modified concurrent parallel mixed-methods methodology. The survey questionnaire included The Research Knowledge Assessment®, Attitudes Toward Research Scale®, the Wessex Research Network Spider®, and open-ended questions exploring barriers and facilitating factors to research. A sample of 69 United States-based and 33 International MNRI® Core Specialists participated in this study (n = 102). Results: Research Knowledge scores on the Research Knowledge Assessment® ranged from 24.00 to 96.00, with M = 54.71, SD = 15.08, and α = .82. Research Attitude scores on the Attitude Toward Research Scale© ranged from 2.73 to 6.50, with M = 4.64, SD = 0.74, and α = .89. Research Practice scores on the Wessex Research Network Spider ranged from 1.00 to 5.00, with M = 2.16, SD = 0.84, and α = .94. Using Spearman Correlation Coefficient, Educational Degree was related only to Research Practice rs(102) = .38, p < .001. The Spearman correlation between Years of Professional Experience and Research Knowledge, Research Attitude, and Research Practice was not statistically significant. The Spearman correlation between Research Knowledge and Research Attitudes was statistically significant, rs(102) = .35, p < .001. The Spearman correlation between Research Knowledge and Research Practice was statistically significant, rs(102) = .22, p = .030. The Spearman correlation between Research Attitudes and Research Practice was statistically significant, rs(102) = .48, p < .001. Barrier and Facilitating factors to research engagement included individual factors, methodological factors, organizational factors, recognition in the medical community- range of evidence, and emotions. Conclusions: A baseline understanding of MNRI® Core Specialists’ research knowledge, attitude, and practice can inform future research capacity-building initiatives in The Masgutova Method®. Successful research capacity-building initiatives can facilitate research engagement, expand the available empirical literature, and ultimately increase practitioners' potential for evidence-based practice when using The Masgutova Method®. Keywords and phrases: Masgutova Neurosensorimotor Reflex Integration (MNRI®), The Masgutova Method®, MNRI® Core Specialist, Knowledge Attitudes Practice Model (KAPM), Research Knowledge, Research Attitude, Research Practice, Research Knowledge Assessment© (RKA), Attitudes Toward Research Scale© (ATR-S), and Wessex Research Network Spider © (WReN).

Conjunctival hemangiomas and hemangiosarcomas are vascular tumors that affect the tissue in the eyes of canines. While relatively rare, these tumors can be costly to remove, and have a possibility of recurrence. Therefore, more understanding of the nature of these tumors and recurrence rates is of importance to the veterinary ophthalmologist. To date, there is limited data in the literature (2 retrospective studies) that examine the development, treatment, and recurrence of these vascular tumors; furthermore, the analyses do not examine the potential recurrence of tumors after treatment with therapies adjunctive to surgery (such as cryoablation, radiotherapy, and others). For this reason, additional information describing the characteristics and outcomes of patients diagnosed with these vascular neoplasms could help guide veterinary ophthalmologists to establish the best route of treatment for their patients. In this work, a retrospective analysis of canines treated at a specialty veterinary hospital in Albuquerque, New Mexico between 2011 to 2021 for conjunctival hemangiomas and hemangiosarcomas is presented. The recurrence rates between canines diagnosed histologically with conjunctival hemangioma versus hemangiosarcoma after surgical intervention with adjunctive cryotherapy were compared. In addition, analysis of the association between recurrence and location of the neoplasms and recurrence and completeness of surgical excision was done. It was found that there was no statistically significant association between: recurrence and diagnosis, recurrence and location, and recurrence and completeness of excision. Further study is needed to advocate for the role of adjunctive cryotherapy in lessening the chance of recurrence when incomplete or narrow surgical margins are obtained. However, from this study it is recommended that monitoring of both hemangiosarcomas and the more benign hemangiomas is warranted after surgical intervention, as there is no statistical evidence that diagnosis of one or the other favors or lessens the chance of recurrence.

Tissue engineering is an emerging field that came from the fields of medicine, materials science, and engineering. The foundation of tissue engineering uses a paradigm that incorporates cells, biomaterials, and exogenous factors to create living tissues for medical, pharmaceutical, and research purposes. Within the last 100 years, biomaterials have been developed to solve many medical and research problems. As biomaterials have developed throughout the years new materials have been developed to have specific properties appropriate for medical applications. Fumarate is a naturally derived molecule in the body and has been found useful for developing polyesters that can be crosslinked into degradable biomaterials. This work explores a new method for synthesizing oligo(poly(ethylene glycol) fumarate) (OPF) and poly(butylene fumarate) (PBF). OPF was used to create a positively charged hydrogel platform for aortic valve engineering and PBF was synthesized with different types of butanediol to modify material properties for bone engineering. Conclusions show that a new acid scavenger free synthesis method creates OPF and PBF with reduced hydrochloric acid and fewer post-processing steps. Oligo(poly(ethylene glycol) fumarate) can be photocrosslinked into hydrogels with positively charged functional groups for encapsulation of valvular cells. Finally, PBF material properties can be chemically controlled by the type of butanediol used and they can be crosslinked into hard plastic films. Overall, the contributions of this dissertation will aid in the development of a new application for currently used biomaterial (OPF) for soft tissue engineering as well as develop and characterize a new variation of PBF for bone tissue engineering.

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the BBB following LiFUS is correlated to microbubble and cavitation dose. We also observe a biphasic and size-dependent increase in BBB permeability. Next, we studied the application of the clinical LiFUS parameters to evaluate efficacy and survival of combinatorial chemotherapy in a preclinical model of breast cancer brain metastases. When LiFUS was combined with paclitaxel and Doxil, we saw an additive increase in therapeutic efficacy and slower tumor progression. Lastly we explored the time-dependent effect of LiFUS on brain physiology and identified inflammation-associated understudied areas for improving LiFUS assisted CNS therapy.

Hydrogen sulfide (H2S) is a gasotransmitter critical in maintaining microcirculation homeostasis. Impaired microcirculation occurs in multiple disease states such as peripheral vascular disease, diabetes mellitus (DM), and hypertension. Early detection and identification of patients with DM who are at risk for heart attack, stroke and amputation due to microvascular disease is crucial. Human skin is an accessible vascular bed that provides an opportunity to non-invasively measure H2S, which could be used as a biomarker to evaluate microvascular health. In this work, a novel H2S gas sensor, called the transdermal arterial gasotransmitter sensor (TAGSTM), was researched and developed to detect physiological levels of transdermal H2S in humans. Data was collected from 29 individuals (14 DM and 15 non-DM) between the ages of 30-60. 10 of the 29 subjects were used to evaluate the precision of the TAGSTM system by comparing measurements to a commercial H2S-selective Serinus 55 TRSTM analyzer (accurate to 0.5 ppb). Strong correlation was seen between the two devices (R2=0.876, p2S levels were measured using a monobromobimane (MBB) assay and cardiovascular risk markers were measured through blood and urine in order to evaluate correlations between transdermal H2S levels. No significant correlations were seen, although mean TAGSTM readings were lower in the DM group. Thus, the device precisely measures physiological levels of transdermal H2S and further testing is warranted to determine the usefulness of the device in medical applications such as monitoring microvascular disease changes and/or the efficacy of wound healing interventions.

Title:Strategies for the improvement of healthcare through simulation Background: Medical errors continue to plague the healthcare industry. The annual rates of morbidity are approximately 2.69 million (AHRQ, 2019), while mortality rates exceed 400,000 per annum (Makary & Daniel, 2016). There may be no panacea to combat these egregious rates. However, simulation of patient care events may better prepare healthcare professionals to prevent medical errors as it has been proven to be an effective learning strategy (Kirkham, 2018), enhancing skills while gaining experiential knowledge, without risk to actual patients. Purpose: The purpose of this qualitative study was to gain a better understanding of factors that impede or foster the frequent utilization of simulation as a modality to rehearse patient care activities for healthcare professionals, and to better identify processes that could reduce medical errors across the continuum. Aim 1: Describe the demographics of the study population: Current profession, area of specialty, time in profession, time in current role, education level, age of the participant, gender of the participant, and operational setting. Aim 2: Explore and identify barriers to the frequent practice of healthcare simulation. Aim 3: Identify processes that can lead to the reduction of errors in the healthcare industry. Methods: This was a hermeneutic phenomenological qualitative study that also used descriptive statistics to gain a better understanding of the subjects and their responses to the solicited survey. Findings: The barriers of time, space, access, and cost continue to pose impediments to iterative rehearsal. These factors were compounded by the paucity of qualified facilitators & support personnel in this modality; all exacerbated by the pandemic. A need for diversity in SBLE to reflect patient population was also identified. According to the participants, the value of simulation is realized through relevant and iterative SBLE. To enhance confidence and competence, participants overwhelmingly indicated the need for monthly rehearsal of patient care events. Leadership buy-in was identified as key to program success. Implications: By employing regular practice of simulated patient care events, positive patient outcomes can be realized, as the healthcare provider’s clinical acumen is exercised and further developed. Keywords: healthcare simulation, simulation-based education (SBE), simulation-based learning events (SBLE), iteration, simulationist

ABSTRACT Exploring Antibiotic Resistance and the Effect of Antimicrobial Stewardship on Physicians’ and Non-Physician Prescribing Clinicians through Knowledge, Attitudes, Practices and Beliefs (KAPB) Utilizing the Social Cognitive Theory (SCT) Tamika Carty Seton Hall University, 2021 Dissertation Chair: Genevieve Pinto Zipp, PT, EdD, FNAP Background: Antibiotics are one of the greatest medical discoveries, revolutionizing the field of medicine. However, antimicrobial and antibiotic over usage has become a prevalent issue among outpatients, leading to antibiotic resistance (AR) (Ventola, 2015). As a result of, its widespread usage and associated concerns, the World Health Organization (WHO) has cited AR as a growing concern for many nations (WHO, 2015). This in turn has led to the development of management programs such as stewardships which are often led by health professionals and clinicians to address this growing issue. One would argue that stewardship programs are only as effective if those leading them are adequately prepared. Therefore, it is imperative to identify physicians’ and prescribing non-physician practitioners’ knowledge, attitudes, practices, and beliefs regarding AR and the incorporation of Antimicrobial Stewardship Programs (ASPs) to combat AR. Purpose: The purpose of this study was threefold: first to create, validate and test the reliability of the novel instrument “Antibiotic Resistance & Antimicrobial Stewardship Assessment Tool (ABRASAT)”. The second purpose was to test the valid and reliable tool in physicians’ and non-physician prescribing practitioners. The final purpose was to use the valid and reliable tool in the population of interest to understand physicians’ and non-physician prescribing practitioners’ knowledge, attitudes, practices, and beliefs with regard to antibiotic resistance and ASPs as combative method for AR. Methods: This study employed a mixed methods research approach, utilizing specifically an explanatory mixed methods design. The study can also further be categorized as non-experimental, descriptive, cross sectional, correlational and explanatory. The study consisted of two practitioner groups (physicians’ and non-physician prescribing practitioners) in which their knowledge, attitudes, practices, and beliefs were explored utilizing the ABRASAT instrument which was rooted in the available “evidenced based” literature, KAPBs theory and the Social Cognitive Theory (SCT). The ABRASAT consisted of 10 demographic questions and 25 questions relating to KAPBs, expectations, suggestions and thoughts on AR and ASPs. Data Collection and Analysis: Data was collected from both practitioner groups. Participants were recruited via social media (Facebook, WhatsApp, Twitter, Reddit and LinkedIn) and research platform (Research Gate), in addition to convenience sampling. The PI utilized descriptive statistics in addition to statistical analysis tests (ANOVA, T-Test, MANOVA and Pearson’s Correlation) to analyze quantitative data. The PI employed an inductive approach utilizing descriptive and in vivo coding to analyze qualitative data. Both the quantitative and qualitative data helped to form an inclusive overview of KAPBs of physicians’ and non-physician prescribing practitioners. Results: A total of 234 participants completed the survey. The study results for both the quantitative and qualitative data for descriptive research questions (RQ) 1 -5 resulted in the following: for RQ1, the quantitative and the qualitative data shows overall both practitioner groups had high knowledge on AR. For RQ2, the quantitative and the qualitative data shows overall both practitioner groups had high knowledge on what ASPs were. For RQ3, the quantitative and the qualitative data shows overall both practitioner groups had favorable attitudes with regards to ASPs. For RQ4, the quantitative and the qualitative data shows overall both practitioner groups had good ASP practices. For RQ5, the quantitative and the qualitative data shows overall both practitioner groups had favorable beliefs with regards to ASPs. The study results for both the quantitative and qualitative data for relational research questions (RQ) and hypotheses 6 -13 resulted in the following: for RQs 6 & 7, there was no significant difference in practitioner groups on knowledge, resulting in failure to reject the null hypothesis. For RQs 8 - 11, there was a significant difference in practitioner groups on attitudes and beliefs resulting in rejection of the null hypothesis. Finally, for RQ 12 & 13, like RQs 6 & 7, there was no significant difference in practitioner groups on practices, resulting in failure to reject the null hypothesis. While the overall instrument had a high reliability of .843 and successfully measured attitudes, practices and beliefs, knowledge had a poor reliability. While knowledge had poor reliability, it did not affect the overall reliability of the tool. However, it will need to be reassessed for future use as an individual construct. Conclusion: Though knowledge scored poorer in reliability it does not dispute the fact that physicians’ and non-physician prescribing clinicians have knowledge of AR, and displayed positive attitudes and beliefs towards ASPs. As a result, practitioners are generally in favor of ASPs yet improvements should still be made to ensure maximum benefits, thus society must continue to implement and refine these programs.

Antimicrobial resistant Neisseria gonorrhoeae (N. gonorrhoeae) has become a major global public health concern in the 21st century. Surveillance activities are essential in identifying risk factors in priority populations. The purpose of this study was to identify risk factors associated with and trends in antimicrobial susceptibility patterns in N. gonorrhoeae strains identified through the Gonococcal Isolate Surveillance Project (GISP). A study sample of 37,157 men was evaluated to measure adherence to changes in CDC’s STD treatment guidelines in 2012 and 2015. Data were analyzed to measure associations between independent and dependent variables by conducting bivariate and logistic regression analyses. Overall, treatment of gonorrhea was prescribed as recommended. Risk factors that were statistically significant included both demographic and behavioral characteristics. Information on treatment regimens following implementation of STD treatment guidelines can be useful in assessing prescribing practices and adherence to guidelines in treating gonorrhea, particularly in populations at risk of antimicrobial resistant gonorrhea.

PURPOSE: Injuries to the hamstring complex are one of the most commonly seen lower extremity injuries in athletic populations. It is currently unknown how psychological or sociological factors affect an athlete after the recovery process has ended and if these factors play a role in re-injury rates relating to the hamstring. It is also unknown if athlete confidence level changes while in a fatigued state after an athlete returns to play from a hamstring injury. METHODS: Twenty-six physically active adults with and without a previous hamstring injury were recruited for this study. Participants completed a Qualtrics survey that included demographic questions for participant matching purposes, the Oslo Sport Trauma’s Hamstring Outcome Score (HaOS), the Injury Psychological Readiness to Return to Sport (I-PRRS), and the Athletic Fear Avoidance Questionnaire (AFAQ). DATA ANALYSIS: Descriptive statistics were run to report means and standard deviations of questionnaire scores for the Hamstring (HS) and Control (Con) groups. Multiple one-way ANOVAs were used to compare the HaOS subscales and total score, I-PRRS scores, and AFAQ scores between previously-injured hamstring individuals and their healthy, matched control after splitting the SPSS data file between competitive (HS_Comp and Con_Comp) and non-competitive athletes (HS_Non-Comp and Con_Non-Comp). A paired-samples t-test was also run to determine differences between the I-PRRS scores within each group. RESULTS: There was a statistically significant difference in Pain, Function, and Total HaOS scores for the HS_Non-Comp compared to the Con_Non-Comp (P=0.05) but not between the HS_Comp and Con_Comp groups (P=0.09). No other statistically significant differences were observed (P > 0.05). CONCLUSION: Non-competitive athletes with a previous hamstring injury reported a greater degree of disability due to pain and function when compared to non-competitive athletes with no history of hamstring injury, but this was not observed in the competitive hamstring group. The results also suggest that fear of re-injury may exist after returning to activity following a hamstring injury, but confidence in performance may not change after returning to play. Future research should focus on the fear avoidance that may remain after injury and why non-competitive athletes had long-term reports of disability whereas competitive athletes did not.

The Physician Assistant (PA) profession has grown at a rapid rate with an expected increase of 31% by 2028 (Bureau of Labor Statistics, 2019). PA educational programs are expanding to fill the demand. However, faculty shortages have persisted for years. During the 2017-2018 academic year, 75.5% of new faculty were recruited directly from the clinical environment with no prior experience in PA education, and for those who leave academia, 25.7% report a return to clinical practice (PAEA, 2018). New PA faculty are often not provided adequate mentorship or guidance which can influence perception of satisfaction in their academic positions. Job embeddedness (JE) is the theoretical framework containing three constructs of fit, links, and sacrifice which house job satisfaction variables that influence an employee’s retention in their role (Mitchell, et al., 2001). In this quantitative research study, job satisfaction variables including but not limited to clinical to academic support, institutional leadership, working clinically, clinical to academic stress, promotion potential, and fair treatment selected from the PAEA 2018 Faculty & Program Director Survey were utilized as independent variables in multiple regression models to determine how these factors influence faculty longevity and their predictive value of identifying if faculty were new or established. Satisfaction with institutional leadership, agreeing with being treated fairly, and stressful transition from clinical work had negative relationships with longevity but positive relationships with being new faculty. Being male was associated with a decrease in years of employment and women correlated strongly with being new faculty. Results revealed a counterintuitive inverse relationship between satisfaction with JE variables and longevity with all faculty, indicating that with increased satisfaction in JE variables, there was decreased longevity in PA faculty careers. When examining new or established faculty, a direct relationship between JE variables was identified, indicating that the greater the satisfaction in JE factors, the greater the likelihood that PA faculty were new. New faculty were also found to have a relationship with increased clinical to academic stress and decreased length of employment. Decreased longevity was associated with males, Hispanic, Latino, or Spanish participants and those who previously worked clinically. The explained variance in all models was consistently low, between 1%-4%. Future research is needed to examine and discover predictors of longevity, particularly in differentiating the experiences of new versus established PA faculty in relation to longevity. Additional recommendations involve securing detailed quantitative and qualitative information from new faculty at incremental benchmarks of employment to increase understanding of their job satisfaction experiences and trends toward retention and attrition. Future studies should investigate current trends of poor retention of males and minorities in PA education, as well as the influence of past employment in clinical roles, in efforts to promote greater diversity in the field. Lastly, PAEA surveys require investigation into significant structural and content modifications toward efforts of greater inclusivity. Distinguishing new faculty and established faculty experiences can aid in gaining clearer insight into job satisfaction factors to potentially enhance retention in PA education.

Abnormal functioning of small GTPases is implicated in a variety of diseases, ranging from neurological and developmental diseases to cancer. In fact, mutant GTPases are found in up to 30% of cancers. Thus, small GTPases are a highly relevant target in drug discovery and development. High-throughput targeted screening of small molecules is the most productive method of discovering compounds that can give insights into drug development. This thesis describes improvements made to a high-throughput GTPase-targeted screening method to minimize confounding systematic error. It also describes the follow-up characterization of a compound that was identified in a high-throughput screen. The compound under investigation, PR-619, was shown to be a pan-GTPase inhibitor that competitively inhibits guanine nucleotide binding in a panel of sixteen members of the Ras superfamily of small GTPases. Additionally, PR-619 was demonstrated to inhibit GTPase-effector interaction and to produce effects in cellular studies.

With advances in acute medical care, longevity has increased in persons with SCI; however, morbidity due to cardiovascular disease (CVD) occurs at an earlier age compared to the general population. Arterial stiffness (AS) is recognized as an independent risk factor for CVD and, specifically, pulse wave velocity (PWV) has been proven to be a valid tool to predict and track structural arterial changes that reflect arteriosclerosis. Evidence has shown that persons with SCI have increased AS compared to uninjured able-bodied controls; however, possible contributors to this increase are not yet fully understood. After a SCI, sympathetic control in the regions below the lesion level are severely disrupted; however, parasympathetic function is preserved. Due to the dissociation between the two systems, those with lesions above T6 experience low resting blood pressure (BP) and further decreases in BP when changing postures (orthostatic hypotension (OH)). As a consequence, individuals with high-level injuries have a heightened reliance on the renin-angiotensin-aldosterone system (RAAS) to maintain and stabilize BP. A mechanism for increased AS in the uninjured population is over activation of the RAAS. In this study, individuals with high-level SCI (injured above T1) and low-level SCI (injured between T6-T12) had increased AS compared to age-matched controls. The change in renin from supine rest to 60-degree head-up tilt (HUT) was a significant predictor to the change in systolic BP; however, the group predictor was not significant. Additionally, group and change in renin were significant predictors to AS. The data indicate that individuals with high-level injuries rely heavily on RAAS to maintain and normalize BP during OH, which is correlated to increased AS. A better way to treat asymptomatic OH in the SCI population is needed to decrease CVD.

Health information management is an engaging and dynamic occupational field that employs thousands of individuals throughout the United States across the spectrum of health care providing organizations. The ability to navigate these opportunities is influenced heavily by the location of available positions and the skillsets desired by employers. Through study of workforce development data and research in health information management one is able to determine the location and skillset of positions that will help distinguish oneself in a competitive marketplace that values not only education and experience, but the ability to lead in a field that is rapidly changing and growing as the health care industry responds to a consumer that is empowered in their own health and demands more of the industry as a whole.

Background and Purpose of the Study: Sport-related concussions are a major public health issue, particularly so in the setting of sports. Sports dominate American culture and with millions of athletes of all ages participating in these sports these athletes predispose themselves to the risks of sport-related concussions. High-school athletes are of particular interest because of the heightened risks of long-term consequences and of particular note second impact syndrome, which is a catastrophic injury primarily reported in the adolescent aged athlete. Appropriate concussion assessment and management is necessary for reducing the possibility of these long- term effects of concussions. Properly trained and educated medical personnel such as Certified Athletic Trainers (ATC) can help reduce these risks, however, there is a lack of these qualified healthcare professionals throughout high-school sports. With this limited number of high schools employing Certified Athletic Trainers and medical professionals, coaches become the primary decision makers in their absence. Methods: This study utilized a modified mixed methods methodology with a triangulation design to measure the knowledge and attitudes of high-school coaches. A sample of 183 high school coaches participated in this study. Results: High-school coaches had adequate knowledge of sport-related concussions (Mean: 18.96) and good attitudes (Mean: 66.67) as measured by the RoCKAS-HSCH instrument. Statistically significant differences were found between high-school coaches’ knowledge and coaching experience (p=.008) and gender coached (p=.017). This indicated that those coaches who had higher levels of coaching experience and coached both male and female athlete’s had significantly higher mean knowledge scores. Significant differences also existed between high school coaches’ attitudes and experience (p=.010) as well as level of sport coached (.001) indicating those coaches with higher levels of coaching experience who coached a combination of freshman, junior varsity and varsity level sports had significantly higher mean attitude scores. Conclusion: It is vital to understand the knowledge and attitudes that coaches have about concussion and to persist with educational efforts and the assessment of their efficacy in a systemic and organized manner. Through ensuring that coaches are educated about sport-related concussion, athletic trainers and coaches can work together to make sure that the best care is being provided to athletes and develop Initiatives to assist the coaches in helping them establish team cultures that are supportive of concussion safety. Together, coaches and athletic trainers can ensure that athletes and parents are educated about concussion recognition and can work collaboratively to develop and implement concussion safety policies at their schools.

Understanding the structure-function relationship of membrane receptors is essential to comprehend the crosstalk between key signaling pathways. Aberrant trans-activation between receptors can lead to tumorigenesis. Two of these receptors known to be involved in cancer development are receptor tyrosine kinases (RTKs), RON (Recepteur d'Origine Nantais) and EGFR (Epidermal Growth Factor Receptor). There has been evidence of heterodimerization and crosstalk between these two receptors based on co-immunoprecipitation, however the structural requirements behind these interactions remain unknown. Structural studies could provide insights into these RTKs’ modes of dimerization and structure-function relationship. However, structural studies of full-length membrane proteins are often difficult due to poor solubility of the hydrophobic transmembrane domains. This affects protein structure and functionality. The use of nanodiscs for protein structural studies helps provide a native-like environment for membrane proteins, helping to avoid denaturing and aggregation, as well as providing a homogeneous size which makes them ideal for imaging techniques. In this work, we focus on optimizing a nanodisc assembly protocol to incorporate full-length RON and EGFR receptors into nanodiscs, as well as developing techniques to detect protein incorporation into these nanodiscs, which would ultimately facilitate structural studies for RON and EGFR heterodimerization. These studies could provide a mechanistic justification for novel targeted therapies in cancer.

Preparing a successful small grant proposal involves research, planning, preparation, and determination, but obtaining funding for a creative project is not unrealistic. Practitioners are in the trenches on a daily basis, and many likely have novel ideas and relevant questions, especially when it comes to interventions. These intervention questions are important, with the American Occupational Therapy Association reporting that more studies are needed to investigate and support occupation-based intervention. By developing partnerships, educators, practitioners, and students can engage in small scale projects to further the knowledge base in the field of occupational therapy.

Sarcopenia, the age-related decline in skeletal muscle mass, results in a loss of strength and functional capacity, which subsequently increases the risk of disease, disability, frailty, and all-cause mortality. Exercise is known to be an efficacious paradigm for improving health and attenuating or preventing many chronic diseases. For the previous two decades, our laboratory has established an in vivo rodent dynamometer model to explore the effects of various skeletal muscle training paradigms following stretch-shortening contractions (SSCs).The responses tohigh-intensity resistance-type exercise training (RTET) using this physiological model ranges from adaptation, characterized by enhanced skeletal muscle performance along with increased muscle mass, to maladaptation, defined as an absence or diminishment of skeletal muscle performance and no improvements in muscle mass. Utilizing a non-injurious SSC protocol, training-induced adaptation occurs in young rodents; this response is altered with age in which old rodents undergo maladaptation when exposed to this same chronic loading protocol. Additionally, with respect to chronologically advancing age, our previous work indicates an altered adaptive phenotype following SSC RTET occurs prior to complete biological development of the rodent – six months of age in the adult rat, which we believe may indicate the onset of a loss in homeostatic control leading to an age-specific biological departure from the adaptive response. However, recently we have shown that modifying the frequency of RTET from three to two days per week in older rodents (e.g. 30-31 months of age) attenuates age-dependent maladaptation and restores muscle quality to a younger phenotype. Despite the therapeutic potential of RTET, a fundamental basis for evidence-based exercise prescription is still largely undetermined because the molecular, cellular and integrated physiological pathways involved in exercise-induced muscle adaptation are not fully understood. Aging in-and-of-itself is a biological process associated with an altered phenotype, and emerging evidence suggests these changes are possibly linked to epigenomic processes. Excitingly, recent research has shown that exercise can influence changes in DNA methylation in skeletal muscle. However, it is currently unknown how exactly DNA methylation may be influencing the adaptation of skeletal muscle to high-intensity SSC RTET, which could be an important mechanism underlying the responsivity of the muscle to training in the context of aging. Traditionally, the term muscle memory has been defined as describing the capability of skeletal muscle to respond more quickly to an applied stimulus that has been encountered previously in spite of periods of inactivity. Recently, emerging evidence has pointed to the existence of a cellular foundation of skeletal muscle memory. Because environmental stimuli and stressors lead to modifications in gene expression, epigenetics/epigenomics are highly likely to form the underlying basis for this cellular memory. However, despite this collective knowledge, to date no studies have determined whether or not changes via DNA methylation that occur as a result of exposure to an adaptive exercise stimulus has a lasting influence on the adaptability of skeletal muscle upon reintroduction to the same stimulus at a later life. In order to examine these unresolved issues, the purpose of this dissertation followed three specific aims: 1) To determine the effects of aging and a reduced training frequency on the activation of molecular signaling pathways associated with the adaptation of skeletal muscle following one month of high-intensity SSC RTET in old rats; 2) to investigate whether DNA methylation influences the molecular signaling activity and adaptability of skeletal muscle following one month of high-intensity SSC RTET, and whether reducing the training frequency modifies the methylation profile of skeletal muscle in response to the training stimulus; 3) to examine if introducing high-intensity SSC RTET at an earlier relative age promotes changes in molecular signaling and DNA methylation that positively influences the ability of skeletal muscle to adapt upon re-exposure to the same paradigm at a later agepreviously shown to have the inability to go through the full adaptive response . The hypotheses for this research were that the ability of aged muscle to adapt to high-intensity SSC RTET would be compromised when exposed to an inappropriate stimulus (i.e., maladaptive) as a consequence of a dysregulated molecular signaling response which would be observable in distinct pathways crucial in muscle homeostasis and remodeling; furthermore, these potential age-related dysregulated events in gene activity would occur as a consequence to altered DNA methylation. Moreover, older animals exposed to a reduced frequency of high-intensity SSC RTET would respond favorably to the training stimulus and in an appropriate manner (i.e., adaptation) and would have a resemblance more like young rats in terms of the molecular signaling pathway and DNA methylation responses compared to age-matched counterparts exposed to a higher frequency that induces maladaptation. Additionally, training rodents at a younger relative age compared to where age-dependent maladaptation occurs would attenuate DNA methylation and therefore positively augment the adaptability of muscle to respond favorably to chronic SSC RTET at a later age following detraining. The results from this study could be vital in understanding the underlying performance, physiological, molecular, and environmental factors influencing the capability of aged skeletal muscle to undergo adaptation in response to RTET; and, thus have important ramifications in the attenuation and/or reversal of sarcopenia. Additionally, we sought to determine the therapeutic efficacy of a training-retraining paradigm using our in vivo high-intensity RTET paradigm by investigating whether or not training at an earlier age is able to prevent functional and physiological decrements of skeletal muscle during the later stages of life.

Hypromellose, or hydroxypropyl methylcellulose (HPMC) - has been widely used for biomedical and pharmaceutical applications due to its advantages, including that it is modifiable in terms of viscosity, and it has the ability to form thermally reversible hydrogels. The thermal gelation temperature (TGel) of a given HPMC solution strongly depends on its characteristic grade and the solution concentration. Applying certain additives can modify the TGel even further; depending on their nature and concentration. With the addition of said additives, a lower or higher TGel can be obtained. For example, the addition of sodium chloride (NaCl) reduces the TGel, whilst sodium iodide (NaI) increases the TGel, for a given HPMC solution. Therefore, for a certain application, the gelation temperature of a solution could be modified by adding a selected additive at an appropriate concentration. The effects of various additives have been described in the literature. However, there has been no in-depth experimental reporting on the effect of sodium fluoride (NaF) on the TGel. Here, we investigate the impact of NaF in comparison to NaCl on the thermal gelation temperature of HPMC 2910 using rheological analyses. The sol-gel transition temperature was evaluated by examining the viscosity, the storage modulus, and the loss modulus of HPMC solutions as a function of concentration. The results indicated that both NaCl and NaF were able to reduce the TGel of HPMC 2910. However, the effect of NaF was found to be significantly greater in reducing the TGel compared to NaCl; the change in TGel as a function of additive composition was approximately 3.6 times higher for NaF compared to that of NaCl. In conclusion, these findings suggest that NaF is a suitable additive to combine with HPMC solutions for in-situ gelation at body temperature. Furthermore, the data indicated that only 1.6% NaF was needed to reduce the gelation temperature of HPMC from 60 ˚C to body temperature (approx. 37 ˚C). HPMC solutions containing NaF can form a viscoelastic solid gel at body temperature; this could potentially be used to prolong the release of fluoride for dental remineralization purposes.

Prenatal alcohol and early life stress exposure are associated with reduced levels of BDNF in the frontal cortex. Several studies have implicated (BDNF) in frontal cortex as important contributor of learning and memory. In the present study, we look to determine whether early housing conditions could mitigate the impact of prenatal alcohol exposure on learning as well as BDNF expression in sex-specific manner in frontal cortex of mice. Compared to control, prenatal alcohol mice expresses reduced total BDNF levels and displayed reduced freezing behavior response during contextual fear conditioning in both female and male mice. Female displayed increased BDNF levels compared to male in control group, thus displaying sex-specific expression of BDNF. Prenatal alcohol was associated with reduced levels of BDNF caused by reduced expression of variant 3 (exon IV) and variant 4 (exon VI) in the frontal cortex. While contextual fear condition was associated with decreased variant 4 and invalidation of BDNF. Mice from dams that were communally housed exhibited higher freezing behavior in prenatal alcohol mice even with reduced levels of variant 3, variant 4 and BDNF in male and female. These results indicate that prenatal alcohol exposure reduces BDNF levels and reduces fear learning behavior in mice and some of these deficits are mitigated by pre and early postnatal rearing environments. These results are discussed relative to the impact of prenatal ethanol and housing on stress and stress behavior responding.

This dissertation describes fabrication of devices and other tools for biomedical applications through the integration of acoustofluidic systems with bio separation assays, instrumentation components, and soft materials interfaces. For example, we engineer a new class of transparent acoustic flow chambers ideal for optical interrogation. We demonstrate efficacy of these devices by enhancing the signal for high throughput acoustic flow cytometry, capable of robust particle focusing across multiple parallel flowing streams. We also investigate an automated sampling system to determine the parameters of transient particle stream focusing in between sample boluses and air bubbles to model a high throughput, multi-sampling acoustic flow cytometry platform. As an extension of our acoustic separations work, we have created a proof of concept lab in a syringe assay to separate elastomeric biofunctionalized negative acoustic contrast particles (NACs) from red blood cells in dilute blood. Finally, we overcome the challenge of fabricating cell culture hydrogels in water/water emulsion systems by engineering an easily deployable microfluidic device that uses acoustic actuation from an audio speaker to create culture microgels that generate cancer cell spheroid-like assemblies. Across all these application spaces, we have illustrated the versatility of integrating acoustofluidic technologies and soft materials across multiple biomedical engineering platforms.

Background and Purpose of the Study: Healthcare costs in the United States has continued to increase annually, and new policy's attempt at protocol changes in healthcare practices does not ensure quality care delivery. An example of these policies include provisions and new guidelines under the 2010 healthcare legislation, - The Patient Protection and Affordable Care Act (ACA). The premise with the Affordable Care Act (ACA) is increased healthcare access for patients. However, not responsibly balancing the increased demand with the escalating cost of care creates an unsustainable system (Department of Health & Human Services, 2015). Healthcare organizations, including hospitals and medical practices, are challenged as they seek to balance between being a diagnostic, clinical entity, and one that can effectively and affordably resolve issues. The synopsis of care delivery in the US thus became one of high-cost pressure and high administrative burden, invariably leading to low-quality patient care. The purpose of this study is to understand the factors affecting healthcare organizational sustainability. Secondly, to determine if the varying perception of healthcare organizations among healthcare professionals (HCPs) affect how they support the implementation of programs in building sustainable organizations. The perception levels were broken into four dependent groups: Unsustainable, Somewhat Sustainable, Moderately Sustainable and Very Sustainable. Methods: This study utilized a quantitative methodology with a descriptive, exploratory, cross-sectional and correlational research design to measure the differences in perception levels of program implementation processes and determine the relationship between the factors of organizational sustainability. Eight (8) dependent variables were identified: Funding, Communication, Environmental, Partnerships, Evaluation, Adaptation, Strategic Planning, and Organization Capacity. A sample of 301 healthcare professionals participated in the study with a completion rate of 53%. Results: All variables had a positive relationship to organizational sustainability in the small (r=0.29, p to moderate rate (r=0.42, p correlation. As scores for each of the sustainability variable increases, so does perception of the program within healthcare organizations. The results of the Multivariate Analysis of Variance (MANOVA) across the 4 perception groups (IV) and 8 dependent variables were statistically significant at an alpha level of 0.01 but for the Environmental, Partnerships and Evaluation variables. Conclusion: Healthcare policies might continue to change in an attempt to resolve issues around quality care delivery, but organizational cultures and design have a greater impact on healthcare organizational sustainability. The eight sustainability factors proved essential further highlighting their inter-relatedness and mutually reinforcing attributes. There were subtle inconsistencies in the perception of these variables and how they manifest across organizations among HCPs. The implementation of programs requires engagement from all employee levels and multi-disciplinary teams within a healthcare organization. If healthcare programs are deliberately structured with the eight sustainability factors in mind, organizations – including physician offices, and multi-system hospitals can be more successful. Further research is needed to determine categorical predictors for perception levels of organizational sustainability in light of healthcare policy changes. With a holistic framework for sustainability, healthcare managers can implement strategies to respond to policy changes, fine-tune operations and successfully manage the quality delivery of care.

Background: Acute Coronary Syndrome (ACS) is a leading cause of morbidity and mortality. Metabolic syndrome and obesity are major risk factors for atherosclerosis and ACS. Dysbiosis plays an important role in metabolic syndrome and obesity. Studies show a markedly increased risk of heart attacks in patients with high levels of the pro-atherogenic metabolite trimethylamine-N-Oxide (TMAO). TMAO is produced by the intestinal microbial flora through metabolism of dietary phospholipids; Gram-negative bacteria (Phylum Proteobacteria) is the major source of TMAO metabolism. Patients with obesity and metabolic syndrome have a defective intestinal tight-junctional (TJ) barrier, which allows paracellular permeation of luminal antigens such as lipopolysaccharides (LPS; endotoxins); leading to endotoxemia. Endotoxins are also associated with increased risk of atherosclerosis and cardiovascular disease. We aim to study the hypothesis that patients with ACS have dysbiosis, including higher proportion of Gram-negative bacterial species capable of vi producing the pro-atherogenic metabolite TMAO, and test if dysbiosis in ACS patients is associated with increased intestinal permeability and endotoxemia. Methods: This is a prospective case-control study conducted at a single university hospital. We enrolled ACS patients (within 72 hours of acute cardiac events) and healthy controls. Relevant clinical and demographic data were collected. Stool microbiome composition was examined using the 16S ribosomal RNA (Illumina) method to identify microbiota taxonomic genera. LPS serum level was measured by an ELISA-based method. The intestinal TJ barrier function was evaluated using lactulose-to-mannitol urinary excretion ratio (L/M ratio). Serum TMAO was measured using a mass spectrometry. Results: We enrolled 19 patients and 19 controls. ACS patients had increased relative abundance of Gammaproteobacteria and Proteobacteria compared to healthy controls, with mean proportions of 1.8 ± 3.0 vs 0.2 ± 0.4 % (P = .04) and 4.1 ± 3.8 vs 2.1 ± 1.7% (P=.056), respectively. L/M-ratio was three times higher in ACS patients compared to healthy controls (.06 ± .07 vs .023 ± .02, P = .014). There was no difference in the mean serum LPS or TMAO levels. Conclusion: ACS patients have dysbiosis and increased intestinal permeability. Further studies are required to find the role of dysbiosis in acute cardiac events.

The increased prevalence of opioid use in society has led to an increase in surgical patients with a history of such use. Patients who use or are addicted to opioids have different tolerances and responses to anesthesia than non-opioid users, and will require different care than non-users both pre- and post-operatively. The means to identify this population prior to a surgical procedure is needed as a way to organize, plan and manage patient care during the perioperative period. An Opioid Risk Assessment Tool (ORAT) was used as a way to streamline the process of identifying these patients. This paper addresses the development, implementation and execution of this quality improvement project, along with the screening results from a population of 512 pre-surgical patients. As a result, the ORAT was installed as part of the computer screening tools in the Pre-Surgical Testing (PST) department at a leading academic cancer hospital.

Astounding success of Human genome project and accelerating success of sequencing technologies have enabled $ 1000 genome goals possible. But, this is still far-fetched from the reach of many resource refrained populations with high genetic variations causing lethal genetic diseases. Based on present technology principles, I have developed prototypes for affordable, scalable and customizable point-of-care genotyping and targeted sequencing. Ion-sensitive field effect transistors with novel read-out and signal amplification techniques are used for laying foundation of possible ISFET based allele-arrays. Sequencing-by-synthesis based full-fledge sequencer is made with novel immobilization, flow-cell and data acquisition methods for massive sequenciing.

Debriefing plays a critical role in the transfer of knowledge in simulation education. Various methods are used in the debriefing process based on a variety of factors; this presentation sheds light on the pathway to the use of a structured and supported approach as traversed in the Department of Occupational Therapy at the University of Tennessee Healthcare Center as well as reflections and lessons learned along the way. Engagement in this session will allow learners to further develop their debriefing skills through exposure to information about strategies to use in the debriefing process that can be used as part of simulation learning experiences to foster reflective thinking and facilitate transformative learning. Through listening to this account and the related research presented, learners will be able to list 5 steps involved in a holistic debriefing process, identify 3 ways to address the emotional charge resulting from SIM encounters, and discuss specific strategies to use to support students in connecting new learning to a larger clinical environment. Research supporting the use of the structured and supported model for debriefing will be shared along with observations of student and faculty responses that have come as a result of the implementation of these techniques in the experience of the presenters. Challenges in debriefing as well as plans for continued growth in this area will be discussed as part of this session as well.

Breast cancer treatment response varies by subtype, treatment regiment, and additionally by vasculature characteristics. For this reason, breast cancer is a model disease for the development of both targeted therapy and prognostic and predictive biomarkers. Mathematical modeling allows for personalized patient specific prediction of treatment outcome based on parameters found to be important to the cancer type. Mathematical modeling is beneficial in providing insight into why cancer treatment fails and in what cases, additionally determining what characteristics result in a successful treatment. Presented in Chapter 1 is a scientific introduction and discussion focusing on representative modeling works specified towards breast cancer which give quantitative insight into chemotherapy resistance and how drug resistance can be overcome or minimized to optimize chemotherapy treatment. Demonstrated in Chapter 2, a modeling tool was created to predict the likelihood of response to neoadjuvant chemotherapy using patient specific tumor vasculature biomarkers measured in a total of 48 patients. To perform accurate and rapid throughput, a semi-automated analysis was implemented, improving on previous methods requiring hand-made measurements. In effort to translate this model towards clinical practice, 48 patients undergoing neoadjuvant chemotherapy were evaluated, collecting clinically relevant data including pre- and post-treatment pathology specimens, and dynamic contrast-enhanced magnetic resonance imaging. Analysis of histology parameters, specifically radius of drug source divided by diffusion penetration distance (L/rb), a normalization penetration distance, and blood volume fraction (BVF), provides a separation of patients obtaining a pathologic complete response (pCR) and those that do not, with 80% accuracy (p= 0.0269), providing a personalized approach to breast cancer treatment. Nanoparticles are shown to improve on cancer treatment efficacy, demonstrating improved cell kill when compared to free drug. Due to drug resistance and patient heterogeneity, patient outcome can vary greatly, in order to explore this phenomenon mouse treatment outcome relative to tumor and organ nanoparticle deposition is analyzed. A mouse study is presented in Chapter 3 as a proof-of-concept demonstrating the heterogeneous distribution of nanoparticles, and the improved cancer cell kill efficacy in an exponential fashion relative to accumulation of nanoparticles in the tumor. The combination of using nanoparticles as improved drug delivery vehicles, analysis of tumor biomarkers, and mathematical modeling to understand the underlying phenomena of treatment efficacy can be used in the clinical setting to help improve cancer treatment, and identify patients likely to respond well to differing and improved cancer treatment. Lastly, future directions are discussed in Chapter 4 whereby the application of chemotherapy, nanotherapeutics, and mathematical modeling may greatly improve and connect the theoretical and clinical side of cancer science.

Parents and/or caregivers of premature infants provide the interaction needed to promote better outcomes for these challenged infants at risk for developmental delays. This descriptive, exploratory study utilized convenience sampling. Inclusion criteria consisted of parents/caregivers who were at least 18 years of age and older with infants born 35 weeks gestation or less and currently in the NICU. This study focused on the research question: What do parents perceive they need in the NICU to enjoy interacting with their infant in the home? To collect the data needed to capture the perceptions of parent’s needs of infants in the NICU, open-ended questions were developed by the Principal Investigator (PI), based upon the Parent Child Interaction (PCI) questionnaire. Devised by the PI in a pilot study, the PCI questionnaire is a reliable and valid tool to investigate what information and needs parents/caregivers have before discharge to gain confidence and enjoy interacting with their infant. A qualitative research approach using a phenomenological approach was taken with five open-ended questions in 21 semi-structured focus groups. Retrieval of the information utilized groups ranging from two to four parents totaling 50 participants. Utilizing a thematic analysis with the PI and an objective second reader to attain trustworthiness of data, seven themes emerged from these intimate focus groups exploring the parent’s needs. The emergent themes are: 1) Roles and Responsibilities, 2) Communication and Parenting, 3) Self-Help, 4) Face-to-Face Education, 5) Consistency of Care, 6) Interaction with Infant, and 7) Be Heard. More contact with the infant produces increased confidence. Based on these themes, this study suggests that parents/caregivers feel there is a need for the consistent communication of information by professionals to parents/caregivers as well as by professionals with each other. Additionally, parents/caregivers would like to be perceived as the best source of knowing their infant's needs and would like more contact with their infant to gain confidence in caring for and enjoying their infant after release from the NICU. Imparting information to gain knowledge of how to care for and interact with their infant is perceived to be most effective when done on a one-to-one basis instead of through classes, technology/media, or handouts. This information will promote programming to develop better-informed parents to influence the parent/infant dyad interaction for improvement of the child’s overall development.

Candida species are the cause of many bloodstream infections through contamination of indwelling medical devices. These infections account for a 40% mortality rate, posing a significant risk to immunocompromised patients. Traditional treatments against Candida infections include amphotericin B and various azole treatments. Unfortunately, these treatments are associated with high toxicity, and resistant strains have become more prevalent. As a new frontier, light-activated phenylene ethynylenes have shown promising biocidal activity against Gram-positive and -negative bacterial pathogens, as well as the environmental yeast, Saccharomyces cerevisiae. In this thesis, we monitored the viability of Candida species after treatment with a cationic conjugated polymer (PPE) or oligomer (OPE) by flow cytometry in order to explore the antifungal properties of these compounds. The oligomer was found to disrupt Candida albicans yeast membrane integrity independent of light-activation, while the PPE is only able to do so in the presence of light, allowing for some control as to the manner which cytotoxic effects are exhibited. Furthermore, treatment with PPE-DABCO unmasked Candida albicans β-glucan, and increased phagocytosis by Dectin-1-expressing HEK-293 cells.Additionally OPE exhibited potent antifungal activity against Candida albicans and Candida parapsilosis, two medically significant fungal pathogens. In contrast, another major Candida species pathogen, Candida glabrata, displayed intrinsically low susceptibility to OPE, relative to C. ablicans and C. parapsilosis. In C. glabrata, the primary mechanism of azole-resistance is attributed to alterations in the ERG11 gene and over-expression of the CgCDR1 efflux pump gene. We hypothesize that similar mechanisms may account for C. glabrata resistance to OPE. We monitored the susceptibility of C. glabrata to OPE by flow cytometry after treatment with clorgyline, a broad spectrum efflux pump inhibitor. Clorgyline showed synergy with OPE in type strain ATCC2001. In summary, cationic phenylene ethynylenes show promising biocidal activity against pathogenic Candida spp. alone and in combination with clorgyline.

Background and Purpose of the Study The rate of Autism continues to rise nationally. However, disparities in the age of diagnosis amongst underrepresented minority groups, still remains a major concern. Research supports that racial and ethnic disparities are key factors influencing noted age of diagnosis discrepancies. Traditionally, the medical community has used the biomedical or disability model, as revealed in the Diagnostic Statistical Manual of Mental Disorders, to explore diagnostic differences. However, these models limit the healthcare professional’s ability to examine elements outside of pathology. In attempt to address the issue with a broader perspective, this study explored the various factors impacting the noted disparity in the age of diagnoses of Autism Spectrum Disorder (ASD), in under-represented minority groups. The Biopsychosocial model provided a comprehensive view to examine and define the disparities in the diagnostic process. Methods For this study, the researcher employed a retrospective Cohort Design to conduct a secondary data analysis on the Survey of Pathways to Diagnosis and Services, 2011 survey data. The database houses past parental telephone interviews and self-administered surveys regarding personal recounts before and along the journey towards children receiving the ASD diagnosis. After obtaining data access, the principle investigator (PI) conducted data cleaning, and stratification. The PI implemented a random selection process to identify 150 subjects for the groups, Caucasian and Underrepresented Minorities (URM) groups for further review. Results The findings resulted in non-significant differences in age of diagnosis, age of concern, and child’s age at which parent consulted with a medical professional. However, an apparent discrepancy existed in the age of concern and age of diagnosis for both groups. Furthermore, parental educational level correlated to the child’s age for when the parent consulted a medical professional. Lastly, URM group parents reported more concerns regarding symptoms and behaviors of their child as compared with Caucasian children. Discussion/Conclusion The findings of this study highlight a key concern regarding a notable gap between the child’s age when parents sought out consultation with a medical professional, based upon their observed concerns, and the child’s age of diagnosis amongst all racial groups. Thus, healthcare professionals must expand their awareness of the multi-faceted influences that may reduce the gap between the child’s age when concerns are noted and their age when a diagnosis occurs. The findings offer two theoretical models to explore. The study observations provide insight that more personal factors, possessed by the parent and child, result in a higher age of concern, seeking of a medical professional, and age of diagnosis. Personal factors include the components of the theoretical model; Society and Medical Professionals, Culture, Community and Family, Primary Caregiver, and Symptomatology. Based upon the inferences gleaned from this work, future research should address the two-person factors and explore use of more qualitative methodology.

To answer the Clinical PICO question: For patients managing chronic disease, how does the implementation of the teach-back method compared to usual standard of care affect health outcomes? By implementing the teach-back method, we will improve the management of chronic disease in the primary care setting.

Supplementation with beetroot juice (BR) has been shown to reduce blood pressure (BP) at rest and improve several performance parameters during submaximal and maximal exercise. BR effects on BP during submaximal exercise have not been investigated. Furthermore, the effects of BR on VO2max are inconclusive. The purpose of this study was to investigate the effects of BR on VO2max and BP during submaximal exercise. 20 healthy, recreationally trained volunteers (age 21.8±2.35 years, weight 75.10±10.62 kg, height 177.4±6.39 cm) participated in this study, which had a double-blind placebo controlled randomized crossover design. Participants began supplementation with either 8 oz. servings of placebo (water with McCormick red food coloring FD&C reds 40 and 3) or 70 ml BR servings (Beet it, James White Drinks, Ipswich, UK, nitrate concentration of 6.4 mmol/day) for 7 days. Participants completed a modified ramp treadmill protocol for determination of VO2max. BP was taken at 70% of max heart rate calculated using the Karvonen method. There was no significant change in VO2max after BR supplementation (51.07±6.12 ml/kg/min) compared to placebo (50.46±6.06 ml/kg/min), t(19)=1.41, p=0.17. There was also no significant change in systolic blood pressure after beetroot juice supplementation (180.65±23.37 mm Hg) compared to placebo (177.65±22.07 mm Hg), t(19)=0.49, p=0.63, nor in diastolic blood pressure after beetroot juice supplementation (92.90±18.89 mm Hg) compared to placebo (90.75±17.73 mm Hg), t(19)=0.51, p=0.62. BR did not affect VO2max, nor did it affect blood pressure during submaximal exercise.

Mesoporous silica nanoparticle (MSNP) supported-lipid bilayers, termed ‘protocells,’ represent a potentially transformative class of therapeutic and theranostic delivery vehicles. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single ‘magic bullet’. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous silica core can have variable size and shape to direct biodistribution and controlled pore size and surface chemistry to accommodate diverse cargos. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. Many nanocarrier cancer therapeutics currently under development, as well as those used in the clinical setting, rely upon the enhanced permeability and retention (EPR) effect to passively accumulate in the tumor microenvironment and kill cancer cells. In leukemia, where leukemogenic stem cells and their progeny circulate within the peripheral blood or bone marrow, the EPR effect may not be operative. Thus, for leukemia therapeutics, it is essential to target and bind individual circulating cells. Here, we investigate protocells, an emerging class of nanocarriers, and establish the synthesis conditions and lipid bilayer composition needed to achieve highly monodisperse protocells that remain stable in complex media as assessed in vitro by dynamic light scattering and cryo-electron microscopy and ex ovo by direct imaging within a chick chorioallantoic membrane (CAM) model. We show that for vesicle fusion conditions where the lipid surface area exceeds the external surface area of the MSNP and the ionic strength exceeds 20 mM, we form monosized protocells (polydispersity index < 0.1) on MSNP cores with varying size, shape, and pore size, whose conformal zwitterionic supported lipid bilayer confers excellent stability as judged by circulation in the CAM and minimal opsonization in vivo in a mouse model. Having established protocell formulations that are stable colloids, we further modified them with anti-EGFR antibodies as targeting agents and re-verified their monodispersity and stability. Then using intravital imaging in the CAM we directly observed in real time the progression of selective targeting of individual leukemia cells (using the established REH leukemia cell line transduced with EGFR) and delivery of a model cargo. Overall we have established the effectiveness of the protocell platform for individual cell targeting and delivery needed for leukemia and other disseminated disease.

Head and neck cancers (HNCs) are common causes of cancer-related deaths worldwide. An increasing incidence of subsets of HNCs is due to human papillomavirus (HPV). Other subsets are associated with tobacco and alcohol use. Determination of differential biomarkers and molecular mechanisms distinguishing HPV-associated and unassociated HNCs should improve diagnostic and therapeutic strategies. This study was designed to identify potential biomarkers for HPV detection, and to evaluate viral and host genetic and epigenetic mechanisms involved in HPV-associated HNCs. Overexpression of a cellular protein, p16INK4a, which is widely used as a surrogate marker for HPV-positive HNC, is non-specific because some HPV-negative cancers can overexpress p16INK4a. I found “mitosoid cells” and “HPV E7 serology”, respectively, as histologic and serum biomarkers, which would improve diagnosis of HPV-positive head and neck (HN) tumors. Mitosoid cells were not only observed in HPV-positive benign epithelial hyperplasias but also abundantly present in subsets of pre-malignant tumors (high-grade oral epithelial dysplasia, hgOED). P16INK4a could be used as an HPV-surrogate marker only in Group 1 hgOED (containing diffuse mitosoid cells), but not in Group 2 (with focal mitosoid cells) and Group 3 (lacking these cells). My study revealed that E7 seropositivity complements p16INK4a overexpression in HNCs and a decrease in E7 serology potentially predicts patients’ response to treatment. To evaluate genetic and epigenetic changes in HPV-induced malignancy, I assessed viral DNA- integration and -methylation, and viral-induced methylation of host tumor vii suppressor genes (TSGs). Since viral DNA integration predicts malignancy, my data showing integrated HPV in Group 1 and malignant tumors, suggest greater malignant transforming potential of Group 1 than the other groups. Although viral methylation is another regulatory mechanism for malignancy, the HPV epigenome was mostly unmethylated in both premalignant and malignant HN tumors. Screening 38 host TSGs identified EREG as a candidate gene, which may be epigenetically regulated, specifically in HPV-positive HNC. Overall, the present study found that mitosoid cells and E7 serology in combination with p16INK4a overexpression are significant markers for HPV-associated head and neck malignancy. HPV DNA integration and host EREG gene methylation, but not viral DNA methylation, may play roles in HPV-associated head and neck carcinogenesis.

Processing dynamic tactile inputs is a key function of somatosensory systems. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of motor function following neurological insult. Little is known about tactile velocity encoding in trigeminal networks associated with mechanosensory inputs to the face, or the consequences of movement. High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile inputs to perioral hairy skin in 20 healthy adults. A custom multichannel, scalable pneumotactile array consisting of 7 TAC-Cells was used to present 5 stimulus conditions: 5 cm/s, 25 cm/s, 65 cm/s, ALL-ON synchronous activation, and ALL-OFF. The spatial organization of cerebral and cerebellar blood oxygen level-dependent (BOLD) response as a function of stimulus velocity was analyzed using general linear modeling (GLM) of pooled group fMRI signal data. The sequential saltatory inputs to the lower face produced localized, predominantly contralateral BOLD responses in primary somatosensory (SI), secondary somatosensory (SII), primary motor (MI), supplemental motor area (SMA), posterior parietal cortices (PPC), and insula, whose spatial organization and intensity were highly dependent on velocity. Additionally, ipsilateral sensorimotor, insular and cerebellar BOLD responses were prominent during the lowest velocity (5 cm/s). Advisor: Steven M. Barlow

The passing of the Health Information Technology for Economic and Clinical Health Act (HITECH) has created a growing push for healthcare organizations to no longer use paper based records and convert to an Electronic Health Record (EHR). Along with the adoption of an EHR comes a necessary change for ancillary services like nutrition and dietetic services because it affects patient care as well. In order to maintain a professional standard in patient healthcare as other health disciplines have done, the development of nutrition informatics model has become necessary. Nutrition informatics will prove to be a necessary addition to the developing field of healthcare informatics. The training of registered dieticians and nutrition technicians in using information technology along with their knowledge and expertise is what will improve data accuracy, patient care, and quality. The development of a standardized vocabulary will also attribute to the success of developing nutrition informatics along with the willingness to embrace and develop information technology skills necessary to navigate electronic applications and tools. Although skill levels and change obstacles will have to be accessed, the overall findings reveal that dieticians and nutritionist are not very knowledgeable in the area of nutrition informatics but are willing to embrace it through education and training.

Occupational therapy (OT) educators strive to prepare entry-level practitioners who have the expertise to meet the diverse health care needs of society. A variety of instructional methods are used in the University of Tennessee Health Science Center (UTHSC) MOT program, including traditional lecture-based instruction (LBI), problem-based learning (PBL), team-based learning (TBL), and game-based learning (GBL). Research suggests that active learning strategies develop the critical thinking and problem-solving skills that are necessary for effective clinical reasoning and decision-making abilities. PBL, TBL, GBL are being successfully implemented in the UTHSC MOT Program to enhance the learning process and improve student engagement.

Background and Purpose of the Study: With the rise in healthcare costs, partly due to an aging demographic (of whom these care-receivers and their informal family member/friend caregivers are experiencing high stress and anxiety levels resulting in an increase in nursing home placement), a need exists for a cost-effective alternative to the traditional medical approach. Specifically, Music Therapy, a form of Complementary and Alternative Medicine (CAM) has been shown to decrease the severity of the problem by alleviating symptoms of an illness and improving overall well-being. The purpose of this study was to create a valid tool entitled “The Global Complementary/Alternative and Music Therapy Assessment (GCAMTA)” and then implement this tool in the population in order to help identify and understand the differences between physicians’ (MD, DO) and non-physician practitioners’ (NP, NA, NM, CNS, PA) recommending practices, perceptions of knowledge, attitudes, beliefs and expectations regarding music as a cost-effective complementary and alternative medicine approach. Methods: This study utilized a quantitative methodology with a descriptive, exploratory, cross-sectional and correlational research design to measure recommending practices, perceptions of knowledge, attitudes, beliefs and expectations of physicians and non-physician practitioners. A sample of 544 healthcare practitioners across seven fields of medicine participated in this study. Results: Reliability for the GCAMTA on the whole with all five dependent variable factors combined was excellent (Cronbach’s alpha α = .94). Individually, for each factor of the GCAMTA, the reliability ranged from good to excellent: Recommending Practices (α = .81), Perceptions of Knowledge (α =.92), Attitudes (α = .81), Beliefs (α = .88), Expectations (α = .87). Physicians (MD, DO) were neutral in their recommending practices, perceptions of knowledge, attitudes, beliefs and expectations towards music as a CAM therapy. Non-physician practitioners (NP, NA, NM, CNS, PA) were less conservative than the physicians and, thus, more favorable towards music as a CAM therapy for their patients. As perceptions of knowledge increased for both groups, favorability towards music as a CAM therapy increased as well. Results of the Multivariate Analysis of Variance (MANOVA) across all five dependent variables were statistically significant (p = .0001) at an alpha level of 0.01. Conclusion: Educational curricula may be the root of the discrepancy in the views between physicians and non-physician practitioners. Teachings in allopathic approaches may need to include teachings in holistic medicine in order for awareness of CAM such as Music Therapy to be obtained. In addition, further evidence-based research and longitudinal studies are needed for increased acceptance and eventual recommendation of these types of complementary approaches by healthcare practitioners in their practice.

School based health clinics provide medical services and healthcare to students within the school setting. Research suggests that students who use school based health clinic services perform better academically in school by improving their attendance, health status, and addressing their medical needs. This retrospective study explored the relationship between school based health clinics and academic performance in elementary school-aged children. Academic performance was measured using students’ final grades, New Jersey Assessment of Skills and Knowledge (NJ ASK), and Language Arts Literacy (LAL) scores. Students were tracked longitudinally from grades 3-5 comparing students who used an onsite school based health clinic versus those who did not use an onsite school based health clinic. Results explore relationships between school based health clinic users versus school based health clinic non-users as well as differences between school based health clinic users and non-users. These findings suggest that having an onsite school based health clinic may improve academic performance in elementary school-aged children.

Cardiovascular disease is the leading cause of death in the United States, and conventional treatment often emphasizes pharmaceutical approaches. Research has recently started exploring non-pharmaceutical approaches, including nutritional interventions. This research study was conducted to test the effectiveness of a novel nutritional approach, curcumin, on the improvement of cardiovascular health in young, obese males (BMI≥30 kg/m2). This study included 22 men, matched based on BMI and randomly assigned to the intervention (n=11) or placebo group (n=11). The intervention consisted of 12 weeks of curcumin supplementation (1.0 g/day) with fenugreek added to enhance the curcumin bioavailability; the placebo consisted of 12 weeks of equal parts fenugreek to that found in the intervention. To determine cardiovascular improvements, arterial stiffness via gold-standard carotid-femoral pulse wave velocity (cfPWV), endothelial dysfunction via reactive hyperemia index (RHI), and inflammation via plasma cytokine concentrations were measured. There were no overall differences in cfPWV (p=0.428) or RHI (p=0.951) between groups following the 12 weeks of intervention. However, some individuals did respond to the curcumin treatment with reductions in cfPWV, while others did not. Subjects who did respond to the curcumin treatment (n=6) entered the study with higher baseline values of cfPWV than those that did not respond (n=5) (6.81 m/s v. 5.84 m/s, p = 0.045). This suggests a potential role for curcumin to improve arterial stiffness in individuals with stiffer arteries at baseline. A possible mechanism to explain the difference in responsiveness is a trending increase in IL-13 (p=0.052), an anti-inflammatory cytokine that has been associated with amelioration of collagen content in the arteries. Also, 12 weeks of curcumin intervention resulted in reductions in brachial pulse pressure (p