A monitoring effort that spanned across one and a half years was conducted to examine three types of produce-associated microbiota. Produce type was determined to be the predominant factor affecting the microbial communities. Other significant factors that resulted in differences in the microbial populations were the origin and sampling date. Specifically, produce-associated microbiota among lettuce and tomatoes clustered based on the sampling period. Through molecular and cultivation-based approaches, sporadic presence of extended spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae and Acinetobacter baumannii was detected on lettuce and cucumbers during certain periods of sampling. Quantitative microbial risk assessment denoted varying levels of ingestion risks associated with different types of produce. In particular, the risks arising from ESBL-positive K. pneumoniae in the lettuce were higher than the acceptable annual risk of 10-4. Commonly used approaches to clean and wash the produce were insufficient in removing majority of the produce-associated microbiota. More invasive cleaning approaches or thorough cooking of the produce would be required to mitigate the associated risks. Most of the current reports of ESBL-positive bacterial isolates were identified in nosocomial environment. However, the carriage of such drug-resistant bacteria in food that is consumed daily

For III-nitride wide-bandgap materials, the lack of efficient p-type wide bandgap semiconductors limits the full potential of group-III nitride-based optoelectronic devices. Conventional wide bandgap p-type materials consisting of magnesium-doped gallium nitride (GaN:Mg) and magnesium-doped aluminum gallium nitride (AlGaN:Mg) typically exhibit low hole carrier concentrations of <1018 cm-3 . Hence, I used different wide bandgap inorganic p-type materials as a promising solution, e.g., copper thiocyanate (CuSCN). CuSCN has multiple attractive properties that hold potential for applications in III-nitride materials. For example, its energy band gap is up to 3.9 e.V and its electron effective mass is higher than its hole effective mass. These two key features make CuSCN a potential wide bandgap p-type material for III-nitride systems. By exposing CuSCN to chlorine, Cl2-infused CuSCN thin film achieves a hole concentration up to 3 × 1018 cm-3 and maintains its visible-light-blind optical properties. Based on these desirable features, p CuSCN/n-GaN heterojunction ultraviolet photodetectors, as well as the p-CuSCN and n GaN interface, were fabricated to investigate the potential applications of p-CuSCN in III nitride devices. Moreover, p-CuSCN also benefits the corresponding organic solar cells; p CuSCN-based organic solar cells perform better in power conversion efficiency and stability tests under various conditions than intrinsic CuSCN-based organic solar cells. This work on p-CuSCN not only paves the way for new III-nitride semiconductor devices, but may also potentially enable the development of organic devices with better performance and longer lifetime. To explore the potential of transition metal oxides in UV photodetectors, NiO was selected to proceed with device fabrication because of its wider energy bandgap and lower hole effective mass than other transition metal oxides. Since single crystal quality is required to maintain its visible-light-blind optical property, brand-new templates were invented to grow single-crystal NiO thin films, TiN/MgO, and TiN/Si. Use of TiN thin film between NiO and the substrates provides a good back-side metal contact for NiO-based semiconductor devices. Several tools were employed to ascertain the single-crystal quality of as-grown NiO thin films on TiN/MgO and TiN/Si. I demonstrate NiO/TiN/MgO and NiO/TiN/Si bilayer structures may pave the way towards better NiO-based ultraviolet optoelectronic devices.

La prévalence croissante du diabète de type II et les risques cardiovasculaires associés, sont maintenant considérés comme un enjeu majeur de santé publique. L'agrégation du polypeptide amyloïde humain des îlots (hIAPP) est liée à une dégénérescence des cel-lules β pancréatiques et à la pathogénèse du diabète de type II. Le mécanisme de la toxi-cité de hIAPP et la nature des espèces concernées (oligomères et/ou fibres) sont loin d'être élucidés, bien que de récentes études ont montré que les oligomères formés lors des étapes précoces du processus pourraient être les plus toxiques. Très peu de tech-niques permettent à l’heure actuelle de suivre cette oligomérisation en temps réel et d’évaluer des inhibiteurs de ce processus pathologique. Au cours de cette thèse, nous avons exploré la CE et l’IMS-MS comme techniques permettant de suivre l’oligomérisation de hIAPP in vitro en temps réel. Une méthode de CE a été développée, permettant d’évaluer de nouveaux inhibiteurs envers cette oligomérisation. Une méthode d’IMS-MS a également été développée pour décrire les interactions formées entre hIAPP et un inhibiteur.Des inhibiteurs peptidomimétiques ont été rationnellement conçus et syn-thétisés afin de déstabiliser les structures β formées lors de l’oligomérisation de hIAPP. L’évaluation de ces composés a permis de mettre en évidence la relation entre leurs structures et leurs activités inhibitrices. Des études de viabilité cellulaire sont en cours afin d’améliorer la compréhension de l’activité de ces molécules. / The rising prevalence of type II diabetes, and associated adverse cardiovascular risks, is now considered as a major public health challenge. The aggregation of human islet amyloid polypeptide (hIAPP) is linked to beta-cell degeneration and to the pathogenesis of type II diabetes. The mechanism of hIAPP toxicity and the species involved (oligomers and/or fibrils) are far to be elucidated, although recent studies have shown that early formed species could be the most toxic species. Very few techniques are currently available to monitor in real time this oligomerization and to evaluate inhibitors of this pathological process. During this PhD project, we investigated CE and IMS-MS as potential techniques to monitor in vitro and in real time the oligomerization of hIAPP. A CE-UV method has been developed, which allows the activity evaluation of new inhibitors. An IMS-MS method has also been developed to investigate the interactions formed between hIAPP and the inhibitors. Peptidomimetics inhibitors have been rationally designed and synthesized in order to destabilize beta-sheets structures formed during the oligomerization process of hIAPP. The evaluation of those compounds revealed a relation between their structures and their inhibitory activities. Cellular viability tests are on-going to get more insights on those molecules activity.

Type 1 diabetes is an autoimmune disease that involves destruction of pancreatic cells that produce insulin. The disease typically presents in children and adolescents. The burden of disease management, fear of complications, and disruption of normal childhood that the disease causes place youth with type 1 diabetes at increased risk for developing depression compared to peers without the disease. The presence and severity of depression correlates with disease outcomes. Use of continuous subcutaneous insulin infusion pumps has been shown to improve youth’s quality of life compared to use of multiple daily insulin injections. Although quality of life measures are associated with the risk of developing depression, no studies have compared depression symptomatology in youth using insulin pumps to those using multiple daily insulin injections. The proposed project will assess relative depression symptomatology in youth ages 10-17 using insulin pumps and multiple daily insulin injections. The results of this proposed project could help inform clinicians’ decisions about whether to initiate type 1 diabetes therapy in youth with either insulin pumps or insulin injections. Given the financial burden of depression, it could also potentially encourage insurance companies to increase coverage of insulin pumps.

Type 1 diabetes mellitus is a metabolic disorder characterized by an autoimmune attack against the insulin producing Beta-cells of the pancreas. Also known as insulin-dependent diabetes, patients must receive exogenous injections of insulin in order to maintain glycemic homeostasis. The necessity of monitoring one’s own blood glucose levels and self-administering insulin is a tedious routine for type 1 diabetics, and this standard treatment option fails to treat any of the underlying causes of the disease. According to van Belle et al, the prevalence of diabetes is rising worldwide amongst all age-groups, from 2.8% in 2000 to an estimated 4.4% by 2030, thus the need to find a more curative treatment approach is eminent. In the emerging field of regenerative medicine, mesenchymal stem cells have been identified as a possible therapeutic tool to replace damaged parenchymal tissue. Along with their ability to modulate the local microenvironment, the introduction of properly differentiated mesenchymal stem cells into patients with Type 1 diabetes may provide a treatment option that helps supplement the lost islet cells without provoking an immune response. Preliminary clinical trials have shown that stem cell therapy decreases the amount of exogenous insulin required daily, decreases fasting glucose levels, decreases amount of glycated hemoglobin and increases C-peptide levels. These four indicators of diabetic control suggest that mesenchymal stem cells are an effective means of helping manage Type 1 diabetes. Still, much research needs to be done to fully understand the biomechanics behind the cells’ actions in order to expand human clinical trials. Although complete insulin independence is rarely achieved in patients receiving mesenchymal stem cell treatment, the promising results shown so far suggest more studies be undertaken in hopes of finding a corrective approach to treat Type 1 diabetes.

A series of heteroleptic and homoleptic platinum(II) complexes has been synthesized and characterized towards their use in thin film devices such as organic light-emitting diodes (OLEDs) and organic thin film transistors (OTFTs). Pyridylpyrazolate- and pyridyltetrazolate-containing ligands were selected due to their structural rigidity and ease of functionalization. Single-crystal x-ray diffraction studies of two selected heteroleptic complexes show strong aggregation with preferential stacking into vertical columns with a varying degree of overlap of the neighboring square planar molecular units. It is shown that the close proximity of the molecules to one another in the stack increases semiconducting character, phosphorescence quantum yields, and shorter radiative lifetimes. The potential for these materials towards incorporation into high-efficiency doping free white OLEDs (DFW-OLEDs) for solid-state lighting and display applications has been realized and will be expanded upon by present and future embodiments of materials in this thesis.

Type 2 diabetes mellitus (T2DM) is a widespread metabolic disorder that continues to grow in prevalence both in the United States and worldwide. T2DM is an immense public health crisis and has been declared an epidemic by the United States Centers for Disease Control and Prevention. T2DM is a heterogeneous disease that is characterized by chronic hyperglycemia that is caused by dysfunction of the insulin transduction pathway. Particularly in T2DM, individuals with the disease experience a progressive loss of insulin production by pancreatic β cells in the setting of peripheral insulin resistance. Due to the dysfunction of insulin’s actions, glucose in circulation is unable to enter insulin’s target cells and remains in the bloodstream. Formerly known as adult-onset diabetes, T2DM has recently become more commonplace in youthful populations, particularly in adolescents during puberty. Several risk factors have been identified for T2DM, which defines a population of study to determine the underlying pathogenesis of T2DM and possible therapeutic interventions. While extensive research on T2DM has been performed, the heterogeneous nature of the disease makes it difficult to understand the relationship between genetic susceptibility and environmental triggers. The trend of reaching younger populations is extremely worrying as the loss of glycemic control in T2DM is associated with various medical complications. The most commonly seen complications in T2DM include neuropathy, nephropathy, retinopathy, and cardiovascular disease. These complications come with a significant burden that greatly increases mortality and reduces one’s quality of life. One of the underlying causes of the growing prevalence of youth-onset T2DM is the growing pediatric obese population. The increasing prevalence of pediatric obesity, in turn, is likely tied to adolescents getting less sleep, having diets high in carbohydrates, and having insufficient physical activity. Compared to T2DM that precipitates later in life, youth-onset T2DM appears to have a more aggressive nature, where glycemic control is quickly lost, and complications arise sooner in the disease course than adults. Unfortunately, compared to the various drug classes available to adults, options for youths with T2DM are limited. Currently, the only pharmacologic therapies available to youths are metformin and insulin and given that youths quickly lose metabolic control, new therapies are desperately needed to combat this epidemic. Lifestyle interventions are also widely used in pediatric populations, but success with lifestyle monotherapy is limited. Adherence to treatment plans is a barrier to positive outcomes in youthful populations, which may be improved by having patients and their families attend diabetes education programs. The aggressive nature of youth-onset T2DM and the limited amount of available therapies make it difficult to maintain control diabetes in this youthful population, which is concerning given the huge costs associated with diabetes for both individuals and health care systems. To combat this epidemic of youth-onset T2DM, aggressive monitoring is needed to identify high-risk populations and to prevent and delay T2DM in these populations. Reducing the prevalence of youth-onset T2DM will require efforts to increase the physical activity of youths and to reduce the consumption of foods that greatly increase blood sugar. Additionally, efforts should be made to ensure that youths are getting adequate amounts of sleep. Bariatric surgery has been demonstrated positive results in remission of T2DM in youths, but such an invasive procedure may be an extreme solution in a vulnerable population.

The use of telehealth in healthcare has grown in recent years; however, little is known about the effectiveness of this delivery method in the management of Type 2 diabetes mellitus (T2DM). Guided by the chronic care model and telehealth in chronic disease model, the purpose of this systematic literature review was to explore evidence related to lowering hemoglobin A1c levels and managing T2DM using telehealth in the outpatient setting. The practice-focused questions explored telehealth interventions used in T2DM management and their effectiveness. The Joanna Briggs Institute (JBI) method for conducting systematic literature reviews was the process, and data were compiled using the PRISMA evidence-based minimum set for reporting. Eighteen studies met the inclusion criteria for this project. Data were extracted, analyzed, and synthesized using JBI tools for data extraction and critical appraisal. Article appraisals revealed numerous telehealth interventions for management of T2DM including telephone, Internet-based, clinical video, remote monitoring, and smart phones/applications. Overall, telehealth interventions showed statistically significant improvement in the hemoglobin A1c levels of participants compared to traditional outpatient care. Success of the interventions is associated with components of evidenced-based diabetes management such as education, self-management, support, and feedback loop. The implications of this project for positive social change include the integration of telehealth interventions in the outpatient setting to manage T2DM with enhanced access to care, reduction in health disparities, and improved health outcomes for society.

No description available.

Type II diabetes mellitus (TIIDM) causes multiple complications under chronic hyperglycemia. Long term persistent exposure to elevated glucose conditions is considered one of the major factors for diabetic complications. Pathologically, mechanical and biochemical stimuli will induce a signaling cascade in cardiac fibroblasts, which causes myocardial fibrosis and leading to ventricular stiffness. Non-enzymatically, high levels of glucose can react with long-lived proteins, such as collagen to form advanced glycation end-products (AGEs). AGEs have been shown to be associated with many of the diabetic cardiovascular complications due to their interaction with the receptor for AGE (RAGE). AGE/RAGE activation stimulates the secretion of growth factors, promotes increased collagen production that leads to tissue fibrosis, and increased RAGE expression. The purpose of this study is to identify the role for Rap1a in regulating fibrosis under TIIDM conditions, as well as to offer insight into the AGE-RAGE signaling cascade definition for cardiovascular extracellular matrix remodeling under TIIDM condition. To test our hypothesis, both loss-ofunction and gain-ofunction based experiments were performed to manipulate Rap1a protein expression in AGE-RAGE mediated fibrosis. Also, we down-regulated the activity of downstream molecules in the AGE-RAGE signaling cascade, such as protein kinase C-ζ (PKC-ζ) and ERK1/2 by specific inhibitor treatments, to test their positions in AGE-RAGE mediated fibrosis pathway. To perform our experiment in vivo, we used high fat diet to feed Rap1a heterozygous mice in order to build a Rap1a heterozygous diabetic animal model. Our results showed that Rap1a protein plays a key role in AGE-RAGE signaling pathway under TIIDM, and changes in Rap1a activity altered the signaling pathway. Also, we found that PKC-ζ is the upstream player relatively to ERK1/2, and Rap1a is the upstream player for both PKC-ζ and ERK1/2. By understanding the role Rap1a played in AGE-RAGE signaling cascade, a new molecular mechanism is found possibly to reduce the cardiac fibrosis in TIIDM patients.