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    The Effects of an Occupational Therapy Program on the Overall Well-Being of Older Adults with Intellectual and Developmental Disorders in a Nontraditional Residential Setting

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    Background: Life expectancy for older adults with intellectual and developmental disorders (IDD) has increased significantly over the years. As longevity increases for adults with IDD, the number of Americans needing long-term services and support, such as residential facilities, is projected to increase as well. This shift has led to an increased need for external services in residential facilities, such as occupational therapy (OT), to address the psychosocial needs of older adults with IDD. Methods: A non-experimental, pre and post-test one-group design was used to assess the effects of a four-week OT program on the overall well-being and QOL of residents (n=8) over 65 with a diagnosis of IDD at a selected community site. Participants engaged in a four-week OT program every week, focusing on social participation, emotional regulation, and volition with activities of daily living (ADLs) and instrumental activities of daily living (IADLs). The Model of Human Occupational Screening Tool (MOHOST) and the Volitional Questionnaire (VQ) were used to assess changes in self-perception of occupational performance and volition with occupational performance. Results: The data collected via the MOHOST showed that participant’s MOHOST scores increased from the pretest (M = 55.50, SD = 6.39) to the post-test (M = 69.00, SD = 11.03) t (7) = -5.26, p <.001). A significant difference (Z = -2.395, p <.05) was noted between scores given for the pre- and post-MOHOST scores. Analysis of the VQ demonstrated mean scores related to volition differed significantly across three time points (F (1, 7) = 23.6, p < .05). Conclusion: These results indicate that OT can have a positive impact on the overall well-being and quality of Life (QOL) of older adults with IDD living in a residential facility. The positive results highlight the importance of expanding OT services on the overall well-being and QOL of the community, especially for underserved populations

    Planting Seeds: A Naturalistic Inquiry Into the Perceptions and Experiences of WIC Peer Counselors as they Interact with Mothers Making their Infant Feeding Decisions

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    Breastfeeding rates in the United States lag behind other developed and developing nations resulting in poorer outcomes for both the mother and infant (Dieterich, Felice, O’Sullivan, & Rasmussen, 2013). Breastfeeding confers health benefits for the infant by providing immunities against otitis media, gastrointestinal illnesses, necrotizing enterocolitis, childhood obesity and diabetes (AAP, 2012; Rasmussen, Latulippe, and Yaktine, 2016). Breastfeeding benefits the mother by providing decreased risk of developing breast and ovarian cancers, hypertension, obesity, and myocardial infarction (Schwarz & Nothnagle, 2015). Despite these and other benefits, Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participants are less likely to breastfeed compared to non-WIC participants (Tenefelde, Finnegan, & Hill, 2011) and have not met any Healthy People 2020 breastfeeding goals (Rasmussen, Latulippe, & Yaktine, 2016). There is a paucity of research pertaining to what happens in WIC offices as (WIC) Peer Counselors (WPCs) interact with mothers making their infant feeding decisions and there is a gap in the literature examining the perceptions and experiences of WPCs as they deal with their WIC clients. This study utilized Naturalistic Inquiry (Lincoln & Guba, 1985; Erlandson et al., 1993) to explore and describe the perceptions and experiences of WPCs as they interact with mothers as they are making their infant feeding decisions. Participants were recruited via purposive and snowball sampling resulting in nine WPCs who dealt with WIC mothers making their infant feeding decisions. Data collection and analysis was informed by semi-structured face-to-face interviews. Trustworthiness was assured using Lincoln and Guba’s criteria. Findings from the study highlighted the role of WIC peer counselors and how they get their breastfeeding messages across by using innovative strategies to help their WIC clients initiate and sustain breastfeeding. WIC’s utilizations of WPCs to support and promote breastfeeding has enhanced their breastfeeding rates (WIC Data Tables, USDA, 2020)

    The Differential Effects of Progressive Resistance Exercise Training on Measures of Sarcopenia and Acute Nutrient Response in Older Adults with and without Type 2 Diabetes Mellitus

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    Population-level studies have shown that sarcopenia is accelerated in older adults with Type 2 Diabetes Mellitus (T2DM), and that this acceleration is compounded by increasing disease severity. However, the reasons underlying this acceleration remain unknown. In a similar vein, the effect of T2DM on sarcopenia treatment outcomes, in addition to the moderating or mediating nature of potential mechanisms underlying such an effect, remains unknown. Therefore, this study is designed to ascertain how T2DM impacts physiological responses to the current “gold standard” for sarcopenia therapy – progressive resistance exercise training (PRET). To test the hypothesis that T2DM stymies physiological responses to PRET, 15 healthy older adults and 15 older adults with T2DM participated in various physiological testing and stable-isotope infusion studies with muscle biopsies before and after undergoing a supervised 13-week PRET program. The relationship between sarcopenia treatment outcomes, namely muscle mass and strength, and physiological adaptations in the blood and muscle, were then determined. This study confirmed the hypothesis that T2DM hinders sarcopenia treatment outcomes. Although the PRET intervention was still somewhat effective for increasing muscle mass, strength, and quality, individuals with T2DM were initially disadvantaged and did not respond as strongly to the intervention. Moderation of sarcopenia outcomes by T2DM was evident at the organismal level. However, mechanistic studies lacked the statistical power to determine T2DM’s status as a mediator and/or moderator of sarcopenia at the cellular level. Overall, available data suggest that treatment of sarcopenia in T2DM simply necessitates a more intensive addressal of common senescent mechanisms. However further research may indicate that additional treatment modalities are necessar

    Preserved extracellular matrix in non-enzymatically detached cultured keratinocyte sheets bolsters the healing effects on grafted burn wounds

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    After escharotomy, full thickness large burn wounds are temporarily covered with cadaver skin because of the limited availability of autologous skin. However, cadaver skin is eventually rejected still requiring autologous skin grafting. To overcome this obstacle, cultured autologous keratinocyte sheets (KS) have been proposed to substitute the autologous skin; however, this technology has not been translated to clinical practice because of the poor quality of KS. Although the exact reason remains unknown, it is suggested that the use of enzyme for the KS detachment may have negatively impacted the overall quality of KSs. The current work is designed to address this pitfall, offering novel technology for detachment of cultured KS. Our studies demonstrate that non-enzymatic detachment of cultured KS, using temperature responsive dishes preserves extracellular matrix (ECM) (such as collagen IV and laminin 5) in KS by activating the MAPK pathway which plays an important role in cells survival and proliferation. We have shown that the cytoskeleton of keratinocytes in cultured sheets was disrupted with Dispase treatment resulting in sheet shrinkage. Importantly, we did not observe the same shrinkage if the cells were cultured in temperature-responsive dishes and detached by culture temperature reduction (T-KS). It also appears that integrity of T-KS is preserved after shear stress. Additionally, we have determined proliferation rates of KS in novel in vitro wound healing models that mimic burn wound harsh environments; the T-KS proliferation capacity was significantly higher in T-KS than the KS detached using Dispase treatment (D-KS) with or without coincubation with burn wound exudates collected from ovine third degree burn wounds. Our major finding is that T-KS overlaid onto third degree burns grafted with cadaver skin (which is rejected) resulted in better burn wound healing than D-KS. The advanced wound healing was evidenced with a greater epithelialization rate and well defined dermal-epidermal junction with continuous and better-defined lamina densa and significantly higher numbers of hemi-desmosomes. Additionally, the wounds were more mature with T-KS treatment which was evidenced by reversed keratinocyte growth factors to normal ranges after its transient increase. Furthermore, vascularization percentage was higher in wounds treated with T-KS compared to wounds covered with D-KS. Taken together, our findings point out the critical importance of non-enzymatic detachment of cultured KS and demonstrate that the effects of non-enzymatically detached KSs are superior to those of enzymatically detached sheets on ovine grafted burn wounds healing. We believe that the results of our present study will potentially enable the successful translation of KS to clinical practice for treating burn wounds

    Impulsivity: Psychometrics of impulsivity in adolescents and links to adolescent risk behaviors

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    The purpose of this dissertation was to extend the theory of impulsivity and adolescent risk behaviors. Impulsivity is commonly measured with the Barratt Impulsivity Scale (Fossati, Barratt, Acquarini, & Di Ceglie, 2002; Patton, Stanford, & Barratt, 1995). However, the psychometrics and performance of the measure is understudied in adolescent populations in the U.S. The studies in this dissertation used data from Dating It Safe, an ongoing, longitudinal study of adolescent behaviors of a large, high school-based sample of 894 ethnically and socioeconomically diverse adolescents (mean age of 17 years in 2012, Wave 3). The psychometrics of the BIS-11-A (Fossati et al., 2002) is assessed in the current sample of high school adolescents. Then, an adapted 28-item BIS-11-A was used to determine the association of impulsivity with two understudied adolescent risk behaviors, prescription medication misuse and reproductive coercion. The purpose of examining impulsivity with these risk behaviors was to test the performance of impulsivity measures in this sample of adolescents, as well as determine whether impulsivity is a related factor in prescription medication misuse and reproductive coercion. In Aim 1, a two factor, 28-item BIS-11-A was the best fitting factor structure for the current study sample. Aim 2 determined patterns of a risk behavior, prescription medication misuse from adolescence to early adulthood, and examined the association between prescription medication misuse and impulsivity. Aim 3 examined the relationship between impulsivity and reproductive coercion perpetration and victimization and found no significant relationship. Reproductive coercion behaviors may require more planning and forethought. Exploring the performance of the BIS-11-A provides more psychometrics for the measure in adolescents in the U.S. and provides insight on impulsive behaviors as a risk factor for substance use and intimate partner violence

    Small Molecule Allosteric Modulation of G Protein-Coupled Receptors and Applications in the Pharmacological Targeting of 5-HT2 Receptors

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    The discovery of G protein-coupled receptors (GPCRs) and the extensive second messenger systems associated with their activation has ushered in an enormously productive period in drug discovery. The extent to which around one-third of FDA-approved medications target GPCRs. Predictably, small molecule allosteric modulation has emerged in recent years as a new means to control GPCR function with numerous examples nearing FDA approval. This body of work begins with a substantive review of drug discovery efforts in the development of Class A GPCR allosteric modulators as a means to compile successful strategies and take note of the distinct challenges in the field as our group approaches allosteric modulator discovery for the serotonin 5-HT2C receptor (5-HT2CR). From the time of its characterization, the 5-HT2CR has been marked by unique, untapped potential as a drug discovery target for numerous diseases and disorders of the central nervous system. Thus, the second chapter in this work provides a clear rationale for 5-HT2CR allosteric modulator discovery in context of the neurobiological framework wherein the 5-HT2CR plays an integral role in reward-related behaviors and cortical executive functions. With the rationale established, the following sections report our efforts in the discovery of novel 5-HT2CR positive allosteric modulators (PAMs) from their design and chemical synthesis to the in vitro and in vivo characterization of these molecules. Additionally, further work describing 5-HT2CR PAM pharmacokinetic properties as suitable for rodent behavioral assays and the structural determinants of 5-HT2CR PAM binding via molecular modeling are discussed. Having discovered allosteric modulators with functionality across the 5-HT2R subfamily and benefiting from the wealth of available structural data for these targets, the final chapter delves into a theoretical mechanism underpinning allosteric modulation of 5-HT2Rs. The enhanced activation state (EAS) is thus coined for the first time herein to describe 5-HT2R PAM functionality and is treated with a rigorous theoretical framing comprised of the observed pharmacological, structural, and computational studies that shape our understanding of GPCR dynamics, specifically the activation dynamics of 5-HT2Rs. The resultant body of work provides the reader a comprehensive understanding of allosteric modulation and its pharmacological utility in targeting 5-HT2Rs

    Opioid Prescribing and Opioid-Related Health Outcomes Among Cancer Survivors

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    The US population of older long-term cancer survivors—Americans who are free of cancer 5-years post-cancer diagnosis and not receiving cancer treatment—is growing. The prevalence of pain among cancer survivors after curative treatment is approximately 40% and opioids are frequently prescribed to manage the pain. The purpose of this dissertation is to explore long-term opioid therapy and opioid-related harms in cancer survivors using Surveillance Epidemiology and End Results – Medicare linked datasets. First, we explored the temporal and geographical variation in long-term opioid therapy among cancer survivors in the United States. We found that long-term opioid therapy rates were highest in the south and lowest in the northeast and that long-term opioid therapy rates peaked in 2012 but declined until 2016. Second, we assessed if patient level pain conditions and provider specialties seen at outpatient visits by cancer were associated with long-term opioid therapy. We found that cancer survivors who had been diagnosed with chronic pain or noncancer pain conditions and who were treated by noncancer specialists were more likely to receive long-term opioid therapy. Third, we assessed if cancer survivors were more likely than noncancer controls—matched on age, gender, race, pain conditions, previous opioid use—to experience an opioid-related emergency department visit or hospitalization. We found that the incidence of opioid-related adverse events were five times higher among cancer survivors who used opioids previously than opioid naïve cancer survivors. We found cancer survivors were as likely as persons without cancer to experience an opioid-related emergency department visit or hospitalization. In conclusion, we found high prevalence rates of long-term opioid therapy that differed by time and US geographical region and the risk of an opioid-related emergency department visit and hospitalization is comparable between cancer survivors and persons without a history of cancer. Our findings support the idea that policies and guidelines should continue to promote and incentivize the use of nonpharmacological and nonopioid interventions for managing pain among older adults

    Establishment and Improvement of Preclinical Murine Models of Severe Scrub Typhus to Define Immune Signatures and Pathogenic Mechanisms

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    Scrub typhus is a leading source of febrile illness in endemic countries due to infection with Orientia tsutsugamushi (Ot), a seriously understudied intracellular bacterium. Scrub typhus causes 150,000 deaths per year, with an estimated 1 million cases, and a further 1 billion people at risk. No vaccine is available for this reemerging and severely neglected infection. Frustratingly, scrub typhus can result from infection due to a variety of Ot strains with limited cross protection. However, little is understood about strain-specific virulence factors or host immune response. While there are many established murine models of scrub typhus, differences in route of infection, host resistance, and clinically unrelated pathologic outcomes diminish the usefulness of model studies. Therefore, there is a great need for the development of small animal models that reproducibly mimic human diseases for immunologic investigation and future vaccine studies. Our recent studies have established a new inbred murine model of hematogenous spread. To expand these models, we have established an outbred murine model of hematogenous transmission that mimics tissue tropism and pathologic lesions of scrub typhus patients. Interestingly, we find this outbred model exhibits the same pro-inflammatory/Th1 skewed immune response as seen in our previously established inbred model. We further developed our outbred and inbred models by using two clinically prevalent O. tsutsugamushi strains, Karp and Gilliam, and reveal cellular immune responses in inflamed lungs and potential biomarkers of disease severity. We find that outbred CD-1 mice are highly susceptible to both Karp and Gilliam strains; however, C57BL/6 (B6) mice are susceptible to Karp, but resistant to Gilliam (with self-limiting infection). Our outbred preclinical model is particularly useful for future translational and vaccine studies for severe scrub typhus. This body of work provides the first evidence of differential tissue cellular responses in an inbred model against Karp vs. Gilliam infection, thus offering a framework for future investigation of Ot strain-related mechanisms of disease pathogenesis

    An Exploration of School Nurses' Perspectives in Caring for Homeless Children

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    Naturalistic inquiry methodology was incorporated into a qualitative study designed to explore the experiences and perceptions of school nurses working with homeless, elementary school-aged children. The researcher employed purposive sampling to recruit participants from members of the National Association of School Nurses. Recruiting was supplemented by snowball sampling. Eligibility criteria were nurses with a minimum of one school year prior experience and current employment as school nurses providing direct care to elementary, school-aged children. Thirteen school nurses participated in semi-structured telephone interviews. Data were collected from demographic questionnaires and interview guides. Interview data were analyzed using Lincoln and Guba’s (1985) processes of unitizing data, emergent category designation, negative case analysis; and bridging, extending, and surfacing the data. Analysis of study findings resulted in the identification of three categories describing school nurses encounters with the health and social needs of homeless, elementary school-aged children: (a) school nurse education; (b) school nurse practice; and (c) policy impacts. Additional insights into school nurses’ practice issues related to nursing care of homeless, elementary school-aged children were discovered. Implications of the study findings provided a basis to recommend further research into this important but understudied aspect of school nurse practice

    Evaluating the use of Dermoscopy in the Primary Care Setting in Improving Clinical Outcomes in the Treatment of Melanoma: A Systematic Review

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    Melanoma is a significant public health problem and is the most lethal type of skin cancer. Rural and underserved populations have disproportionately worse melanoma-related health outcomes and mortality rates. In these populations, primary care providers are usually the first evaluate, make diagnoses, and initiate referrals/treatments. Dermoscopy, which is a magnification technique using visible light, is increasingly being used in the primary care setting as a tool to improve diagnostic accuracy. Dermoscopy training and the use of teledermoscopy in primary care settings are potential solutions for improving melanoma-related clinical outcomes. The objective of this systematic review was to determine if the use of dermoscopy in a primary care setting can improve clinical outcomes in the treatment of melanoma. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to search for and evaluate relevant studies in four electronic databases (Pubmed, Ovid, CINAHL, and Web of Science) from January 1, 1993 to December 31, 2018. Studies utilizing dermoscopy/teledermoscopy and reporting clinical outcomes associated with melanoma treatment were included. Studies not performed in a primary care/telemedicine setting, and those not concerning melanomas/pigmented skin lesions were excluded. Twenty studies met review criteria, but the heterogeneity of the outcomes measured precluded performance of a meta-analysis, thus data were synthesized in a narrative review. The use of dermoscopy/teledermoscopy in the setting of an adequately trained primary care provider was associated with improved diagnostic accuracy for detecting melanomas, decreased morbidity due to unnecessary removals of benign lesions, and reduced number of dermatology referrals. Cost effectiveness was explored in three of the studies, with two of three finding a significant cost advantage to dermoscopy. Patient acceptability and satisfaction was addressed in one of the studies and was positive. None of the included studies directly addressed the stage of diagnosis, time to diagnosis, or mortality measurements. Thus, widespread implementation of dermoscopy/teledermoscopy in the primary care setting has the potential to improve diagnostic accuracy of suspicious lesions for melanoma and reduce melanoma-related patient morbidity. However, reliable information regarding the amount and type of dermoscopy training needed, the cost effects, patient acceptability/satisfaction and mortality benefits need further exploration

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