• Drug Delivery Through Intact And Ablated Skin

      Ganti, Sindhu Sunkara
      While transdermal drug delivery offers numerous advantages, the morphology of skin limits its scope to a narrow range of drugs (potent, log P between 1-3, with a molecular weight <500 Da) that can be delivered at therapeutically relevant flux. Cosmetic techniques such as non-ablative fractional lasers, microdermabrasion and microneedle treatment can intervene to reversibly compromise the integrity of the skin making skin more permeable to hydrophilic compounds that have otherwise limited dermal diffusion. The first half of our aims focus on the novel use of these cosmetic techniques to enhance the transdermal permeation of small molecular drugs. All in vitro permeation studies were performed using vertical Franz diffusion cell which essentially consists of donor compartment where the drug formulation is added, a receptor compartment that holds phosphate buffer saline, and human dermatomed skin clamped between the two compartments. High Performance Liquid Chromatography was used to quantitate all drugs analyzes in our work. The average cumulative amount of drug that permeated through untreated skin (control/passive) resulted in transdermal delivery of 72.61 ± 50.35 μg/cm2 and 22.80 ± 0.64 μg/cm2 of diclofenac sodium and sumatriptan succinate, respectively. Laser pre-treatment of skin significantly increased (p<0.005) delivery of diclofenac sodium to 575.66 ± 207.18 μg/cm2 and sumatriptan succinate to 498.32 ± 97.54 μg/cm2. In case of microdermabrasion and microneedle pretreatment studies, the transdermal delivery of sumatriptan succinate increased from 6.45 ± 0.17 μg/sq.cm and 21.16 ± 2.90 μg/sq.cm to 116.08 ± 70.88 μg/sq.cm and 512.07 ± 89.76μg/sq.cm in 24 hours, respectively. Results of our studies demonstrate significant enhancement of in vitro transdermal permeation of small molecular weight drugs over human dermatomed skin when pre-treated with the cosmetic technique (non-ablative fractional laser, microdermabrasion and microneedle) in comparison to passive (without application of any cosmetic technique) permeation. Visual characterization studies (histological staining, dye binding studies, proscope imaging, scanning electron microscopy) of skin validate the mechanisms underlying the techniques. The second half of our studies focused on the development of transdermal gel formulation and drug-in-adhesive matrix type patch of 4-benzylpiperidine for cocaine use disorder and attention deficit hyperactivity disorder. 4-benzylpiperidine is a substitute agonist for cocaine use disorder with a short duration of action and hence can benefit from sustaining its duration of action and this can be achieved by a transdermal formulation. Our studies incorporated the drug into a transdermal hydroxy propyl cellulose based gel formulation and provided sustained release of the drug over 24 hours. Gels were formulated with varying amount of gelling agent and subjected to rheological analysis. Franz cells were used to investigate the in vitro permeation and high performance liquid chromatography was used to quantitate the drug. Transdermal permeation of 4-benzylpiperidine from propylene glycol solution (1, 10, 20 and 50 mg/ml) corresponded to 16% to 31% delivery (49.45  11.60, 258.47  48.50, 600.26  74.18, 1945.20  405.59 �?�g/cm2). The average cumulative amount of drug delivered from gel formulation was 1824.90 ± 425.12 µg/cm2. Thixotropic test demonstrated 2% hydroxyl propyl cellulose based gel to have the highest structure recovery ratio. The calculated theoretical permeability coefficient and theoretical flux value (32.637 ug/cm2/h) predicted high percutaneous absorption. This was further validated by the experimentally determined permeability coefficients and flux values (62.73 ± 12.14 ug/cm2/h), demonstrating proficient transdermal delivery of 4-benzylpiperidine. Literature demonstrates correlation between cocaine use disorder treatment and pharmacotherapy of attention deficit hyperactivity disorder. While gels can provide sustained release of the drug, drug release from a patch can be controlled better and it is harder to extract drug from a patch for abuse. Hence, further studies aimed at developing a drug-in-adhesive matrix type patch of 4-benzylpiperdine to treat attention deficit hyperactivity disorder. Several common adhesives, backing membranes and release liner were analyzed to develop patches. Among the patches developed, polyisobutylene adhesive based patch with higher drug concentration exhibited superior transdermal permeation (1608.5 53.4 µg/cm2 over 48 hrs). In the last aim, we evaluated the deactivation efficiency of an activated carbon based drug disposal system. Food and Drug Administration has protocols in place for drug disposal but these protocols do not deactivate the drug and therefore the drug can pose a risk to contaminate water systems or can be abused by extraction. The deactivation efficiency of a disposal system was analyzed by employing an immediate release (meperidine HCl) and controlled release (oxycodone HCl) opioid drug dosage forms of high abuse potential. The deactivation efficiency of the system was tested by collecting samples at different time points up to 28 days. High performance liquid chromatography was used to quantitate the drugs. At the end of the 28-day study, 100 % of both the drugs were deactivated. In the desorption study, no drug leached out from the activated carbon in larger volume of water and less than 1.4 % leached out on extraction with ethanol.
    • Dual Modulator Of The Akt And Jnk Pathways Targets Mtor In Human Adenocarcinoma Cells / By Blair P. Curless.

      Curless, Blair P.
      Chaetoglobosin K (ChK) is a natural product that has been shown to promote F-actin capping, inhibit growth, arrest cell cycle G2 phase, and induce apoptosis. ChK has been shown to downregulate two important kinases involved in oncogenic pathways, Akt and JNK. This report investigates how ChK is involved in the receptor tyrosine kinase (RTK) pathway (RTK/PI3K/mTORC2/Akt) to the centrally located protein kinase, Akt. Akt’s two activation sites, T308 and S473, are known to be affected by ChK treatment. Studies have reported that ChK does not inhibit PI3K, unlike wortmannin, and does not affect PDK1 activation. PDK1 is responsible for phosphorylation on Akt T308, while mTORC2 phosphorylates Akt S473. It was my hypothesis that ChK acts on the mTORC2 complex to inhibit the phosphorylation seen at Akt S473. Inhibition of the mTORC2 complex would be expected to decrease phosphorylation of both Akt and mTOR in the mTORC2 complex, as observed by the known mTOR specific inhibitor, Torin1. Human lung adenocarcinoma H1299 cells were treated with IGF-1 or calyculin A to increase phosphorylation at complex mTORC2 and Akt. Pretreatment with ChK was able to significantly decrease phosphorylation at Akt S473 similarly to Torin1, with either IGF-1 or calyculin A treatment. Moreover, the autophosphorylation site on complex mTORC2, S2481, was also significantly reduced with ChK pretreatment, similar to Torin1. This is the first report to illustrate that ChK has a significant effect at mTORC2 S2481 and Akt S473 comparable to Torin1, indicating that it may be a mTOR inhibitor.
    • Educated Beyond Adversity: Understanding Resilience And Attachment In Homeless Young Adults Pursuing Higher Education

      Tillman, Felicia
      Researchers have studied resilience and attachment to determine the significance in the lives of homeless young adults in the United States. However, little research has determined the potential link between resilience and attachment of these young adults who choose to persevere beyond their adversity. This study examined the interactions between homelessness and educational goals with resilience and attachment for homeless young adults pursuing post-secondary education. The researcher administered both the Revised Adult Attachment Scale- Close Relationships Version and the Resilience Scale-14 to 84 participants who have experienced homelessness as young adults and pursued higher education. Administration of a qualitative question added narrative thickness to the two-way MANOVA statistics garnered from the administered instruments. The testing of the research hypotheses were to prove whether a significant interaction effect exists between length of homelessness and educational goals on resilience and attachment for the selected population. Potential implications could help counselors and educators better assist homeless young adults to be successful in their educational endeavors.
    • Effects Of Q-angle On Lower Extremity Biomechanics And Injuries In Female Collegiate Track And Field Athletes

      Ham, Myranda Hope
      The purpose of this study is to investigate the effect that quadriceps angle, or Q-angle, has on lower extremity biomechanics in female collegiate track and field athletes, and in turn, investigate the effect that Q-angle has on the incidence of sports-related injury. Twenty members of the Mercer University Women’s Track and Field team were asked to participate in this study. Each subject’s limb length and Q-angle were measured and 2D gait analysis was performed in the Mercer Biomechanics and Gait Lab. Then, electromyographic (EMG) analysis was performed on eleven of the subjects on one of the university’s intramural fields. Each subject was also asked to provide a full history of sports injuries they had previously sustained. For data analysis, the subjects were divided into three groups based on Q-angle (group 1: 10�?�-14�?�, group 2: 15�?�-17�?�, and group 3: 18�?�+). Statistical analysis was performed using t-tests and Mood’s median tests to compare the three groups. Subjects from group 1 were found to have a lower angle hip adduction (p=0.002 compared to group 2 and p=0.05 compared to group 3) in the left frontal plane at initial contact and high incidence of shin splints (66.67%) and ankle sprains (33.33%). Subjects from group 2 were found to have larger range of motion of the knee in the sagittal plane (p=0.021 compared to group 1) and higher incidence of hamstring strains (50%). Subjects from group 3 were found to have high incidence of shin splints (50%) and injuries to the knee (26.67%). Although no statistical significance was found in the EMG data, meaningful trends were observed. Muscle activity in the vastus lateralis, rectus femoris, and lateral gastrocnemius was found to increase as Q-angle decreased. In the future, this study could be done with a higher sample size so more firm conclusions could be drawn.
    • Effects Of T2r Activation On Different Lung Sensory Signaling

      Emamifar, Nick
      Pharmaceuticals are commonly bitter tasting and therefore may activate bitter taste receptors (T2Rs), which are canonically expressed in the taste buds of the tongue. An accumulation of recent evidence has suggested T2Rs carrying out a diverse set of non-tasting functions that are critical to the maintenance of homeostasis in extraoral locations throughout the body which give rise to the possibility of new medications to target these receptors. Using whole-cell patch-clamp recordings, the present study aims to illustrate how the bitter tasting pharmaceuticals, through the activation of T2Rs, modulate the neuroplasticity and therefore the function of lung sensory neurons. Three different airway irritants were used to activate pulmonary sensory receptors: zinc, an agonist for TRPA1; low pH or acid, an activator for both acid-sensing ion channels (ASICs) and TRPV1; and ATP, an agonist for P2X purinoceptors. Our results show that pretreatment with T2Rs activator chloroquine (0.01, 0.1 and 1 mM, 90 s) concentration-dependently potentiates zinc (30 µM, 3−16 s)-evoked TRPA1 currents and markedly inhibits ATP (0.3 or 1 µM, 4−6 s)-evoked P2X currents, whereas affects acid (pH 5.5 and pH 6.5, 4−16 s)-evoked inward currents differently: an inhibition for the slow inactivation ASIC-like current and a potentiation for the TRPV1-like current as well as the fast-inactivation ASIC current. Our results demonstrate that T2R activation in lung afferents has distinct modulatory effects on various ion channels that are sensitive to different airway irritants.
    • Effects of Weathering Cycles on the Mechanical Properties of Thermoplastic Polyurethane

      Pickren, Darren Brantley; School of Engineering
      In the present work, a method for synthesizing pure thermoplastic polyurethane (TPU) and TPU composite test specimens was developed to show stress-stretch dependency, to observe the effects of weathering on samples, and to show the potential of TPU as a superior coating agent over traditional polyurethane in aerospace applications. The TPU specimens were tensile tested using ASTM standards to extremely high deformations: stretch values of 5 times original length in tensile testing. During testing, TPU specimens exhibited typical behavior of nonlinear viscoelastic materials with extensive energy dissipation during stretch-release cycles. A portion of the tested samples were exposed to 168 hours of UV radiation, moisture, and temperature fluctuation to simulate accelerated weathering and exposure to harsh environments. When comparing weathered TPU samples to non-weathered TPU samples, there was no appreciable difference in the mechanical properties or the amount of energy absorbed during deformation; the stretch-stress curves were nearly identical before and after weathering. When returned to a zero-stress state, considerable residual strain remained in all specimens. It is conjectured that strain-induced crystallization is responsible for the unique shape-memory effect that the TPU specimens experience. Slower loading rates with the same peak stretch values showed higher peak stresses in samples from the same batch, showing that the rate of crystallization is dependent upon the rate at which TPU samples are deformed. The same tests were performed with TPU composites, filled with molybdenum disulfide. While TPU composites have slightly different overall mechanical properties from pure TPU, the exposure to weathering also had minimal effect on mechanical properties of composite specimens. Fracture tests were also performed on pure TPU and composite TPU samples. The effect of UV weathering on fracture toughness of pure TPU and TPU composites is more prevalent, as specimens were hardened and their abilities to absorb energy during crack growth was greatly reduced.
    • Elementary Teachers' Perception Of Professional Capital Within Their Community Of Practice / By Allison Walker

      Walker, Allison
      Many teachers, after having worked in isolation for so long and a business capital model of education reform, do not understand the concept of professional capital and its impact for transforming education. The purpose of this study was to examine elementary teachers’ perception of professional capital within their community of practice. The data were collected two ways: completion of the self-assessed Teacher Professional Capital Survey (Hargreaves & Fullan, 2012) and semi-structured interviews. The Teacher Professional Capital Survey (Hargreaves & Fullan, 2012) was administered to glean teachers’ understanding of the concept of professional capital within their community of practice. The survey item data analysis revealed that on thirty-one of the thirty-six self-assessed items the teacher participants had an understanding of the precepts of professional capital within their community of practice. The semi-structured interview data analysis revealed two a priori codes and eight emergent codes. In the process of a priori coding two codes were presented: 1) sharing, and 2) joint work. In the process of emergent coding the interview data eight codes presented: 1) relevant professional development; 2) self-directed learning; 3) trust; 4) freedom of expression; 5) professional to personal relationships; 6) dictated/scripted autonomy; 7) commitment and 8) triadic capital connections. Overall, the results of the study revealed that most elementary teachers, within this community of practice, are aware of the precepts of professional capital as represented by the survey analysis results and the ten coded themes presented from the semi-structured interview data.
    • Emergence Of Informal Clinical Leadership Among Bedside Nurses In The Acute Care Clinical Setting: A Mixed Methods Study

      Rogers, Darlene
      Quality and safety initiatives direct all nurses to lead practice change. Existing nurse leadership research predominantly focuses on formal nursing leaders and overlooks a critical resource pool: informal leaders at the point of care. This study explored influences on the emergence of informal clinical leadership among bedside nurses in the acute care hospital setting. Nurse personal attributes (demographic characteristics, professional experience, and psychological capital) and situational context in the acute care workplace setting were examined as predictors of clinical leadership behavior. The study used a convergent parallel mixed methods design with an exploratory correlational quantitative strand and a descriptive qualitative strand. A convenience sample of 134 nurses (mean age = 35.62 years, 94% female, 81% white, 85% BSN-prepared) were recruited from eight acute care hospitals in three different geographic areas in the United States. The data collection instrument included a researcher-developed personal attributes questionnaire, the Clinical Leadership Behaviors Questionnaire (CLB-Q), the Psychological Capital Questionnaire 12-Item (PCQ-12), and three open-ended questions. Data collection occurred through an online survey. The findings supported nurses are interconnected in practice, and informal clinical leaders can emerge from this network. Nurses described preferring to seek clinical guidance from peers with a positive attitude about providing help or work in general or from experienced peers. Psychological capital was the only significant predictor in the regression model accounting for 42% of the variance in clinical leadership behavior scores. Whereas, the professional experience variables were not supported statistically as predictors of clinical leadership behavior. Additional research is needed to further explore the complexities of the interpersonal relationships among nurses and the resulting influences on informal leadership at the point of care. However, given the strength of the association between psychological capital and informal clinical leadership and the other positive nursing practice outcomes associated with psychological capital, nurse professional development in the clinical setting, in academia, or informally among nurse peers should afford opportunities for nurses to increase their psychological capital. Given the emphasis on positive attitude, nurses with specialized knowledge and skills should be afforded opportunities to develop interpersonal skills to promote their emergence as informal clinical leaders.
    • Empathy and Compassion as Predictors or Counselor Burnout and Resilience

      Elder, Carrie L.; College of Professional Advancement
      Empathy is frequently taught as a core disposition and helping skill in counselor education programs. Recent studies have found empathy to activate the pain network within the brain and compassion to activate non-overlapping brain regions. These findings have led neuroscientists to hypothesize that empathy leads to burnout and compassion leads to resilience. These findings have implications for the field of counseling since burnout has the potential to lead to impaired client treatment. The purpose of this study is to use a quantitative, multiple regression analysis to determine if empathy is predictive of counselor burnout and compassion predictive of counselor resilience. Results indicate that increases in empathy, and decreases in self-compassion, are predictive of counselor burnout. Results also indicate that self-compassion, compassion towards others, and a decrease in empathy is predictive of counselor resilience. Furthermore, results indicate that the model that best predicts counselor burnout is empathy (fantasy, personal distress, and less ability to take the perspective of others), working outside of private practice, one to five years of experience, and lower scores on self-compassion and compassion towards others. The model that best predicts counselor resilience is compassion towards self and others, empathic perspective taking, less empathic personal distress, less empathic fantasy, working in private practice, and Republican affiliation. Results from this study indicate that compassion plays a significant role in predicting both high resilience and low levels of burnout. These findings support counselor educators in teaching compassion skills equal to empathy skills to counselors in training as a measure of self and client care.
    • End-of-life Education Experiences Of Respiratory Therapists : Implications For University Leadership / By Ralph David Zimmerman.

      Zimmerman, Ralph David
      Abstract Ralph David Zimmerman, Jr. End-of-life education experiences of respiratory therapists : implications for university leadership Under the direction of Elaine Artman, Ed.D. The study addressed the problem of the implications surrounding a lack of end-of- life education in the respiratory therapy curriculum. Respiratory Therapy programs need to integrate therapists’ lived experiences with palliative care into their educational programs in an effort to facilitate an improved level of end-of-life care and teach future therapists how to better deal with the stress associated with witnessing death in the clinical setting (Giordano, 2000). Using the qualitative approach of interpretive phenomenological analysis, the research was conducted at a large public university. Subjects who had graduated within the past three to 5 years were recruited by email and recorded interviews were transcribed, analyzed, and coded. Superordinate, sub-superordinate, and emergent themes were defined and used to analyze the transcribed interviews. The researcher identified three superordinate themes that addressed the research question: (a) Needs for the Patient (b) Needs for the Family (c) Needs for the Care Provider. Sub-superordinate themes included Suffering, Time, and Honesty (under needs for the patient); Support, Compassion, and Engagement (under needs for the family); Memorable Experiences, Coping, Stress, and Education (under needs for the care xi provider). Results of the study show that a lack of end-of-life education in the respiratory therapy curriculum can impact therapists, patients, and family members. Practicing respiratory therapists desire more education on how to care for dying patients in order for this impact to be lessened. Recommendations for further study include expanding the size of the study to include other regions of the country and surveying programs to ascertain the amount of end-of-life education students are receiving during their education.