No description available.

No description available.

No description available.

No description available.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in adults over the age of 60. Currently, at least 11 million patients in the United States have some form of macular degeneration and this number is projected to grow as the population ages. The more severe form of the disease – neovascular (wet) AMD, is characterized by intraocular neovascularization, inflammation, and retinal damage; however, the disease progression can be deterred through intraocular injections of anti-angiogenic agents. The complications and burden that arise from repetitive injections as well as the difficulty posed by targeting the posterior segment of the eye make this an interesting territory for the development of novel drug delivery systems. New methods for drug delivery are being investigated exploring the use of nanoparticles and other polymeric materials. The goal of this project is to study the potential use of poly(lactide-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles in thermoreversible gels as localized sustained intraocular drug delivery. We prepared stable and reproducible corticosteroid-encapsulated nanoparticles in thermoreversible gels to inhibit vascular endothelial growth factor (VEGF) overexpression characteristic of neovascular AMD. We characterized the drug delivery system by obtaining size, shape, and drug encapsulation data. We also demonstrated that the polymer could be injected into the vitreous as a solution and transition to a gel phase based on the temperature difference between regular indoor environment and the vitreous body. The drug delivery system was tested on human retinal pigment epithelial cells (ARPE-19), for cytotoxicity, uptake and VEGF expression. We also examined the drug delivery system's ability to mitigate the disease progression in a mouse model of choroidal neovascularization (CNV). The effect on blood vessel area was shown and the changes in the mRNA expression of angiogenesis mediators were analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). These results indicate that the proposed drug delivery systems has the promise to be developed for retinal diseases, involving CNV, including neovascular AMD. Further studies are warranted in developing this promising intraocular drug delivery system for wet AMD and similar ophthalmic diseases. / Ph. D.

No / The present work explores inner structuration of in situ gelling system consisting of glyceryl monooleate (GMO) and oleic acid (OA). The system under study involves investigation of microstructural changes which are believed to govern the pharmaceutical performance of final formulation. The changes which are often termed mesophasic transformation were analysed by small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), rheology and plane polarised light (PPL) microscopy. The current work revealed transformation of blank system from W/O emulsion to reverse hexagonal structure upon addition of structural analogues of ibuprofen. Such transformations are believed to occur due to increased hydrophobic volume within system as probed by SAXS analysis. The findings of SAXS studies were well supported by DSC, rheology and PPL microscopy. The study established inverse relationship between log P value of structural analogues of ibuprofen and the degree of binding of water molecules to surfactant chains. Such relationship had pronounced effect on sol-gel transformation process. The prepared in situ gelling system showed sustained drug release which followed Higuchi model.

Stress research has recently gained attention in the importance of adapting to life stressors as well as to temporary stressors created in a laboratory. Much attention has recently been paid to the influence of individual differences in their contribution to performance and adaptation to stressful situations. The contribution of individual differences ranges from personality characteristics such as extraversion and introversion, optimism or pessimism and even in some cases, clinical diagnoses. On the other hand, coping with traumatic stress and its potential long-term implication sparks much controversy in various fields of psychology. Certain views predict higher resilience to stress with the ability to rise above the occasion and triumph in spite of stress while other theories indicate a decline in productivity and an inability to cope with stress. The goal of the present study was to empirically examine the effect of long-term traumatic exposure on adaptation to stress. This project was designed to detect trauma and traumatic symptomology in a nonclinical sample. This was done in order to determine the effect of traumatic stress in an operational context. The premise for the research involves the complex interplay of encoding traumatic memories. It involves main theories of the traumatic memory argument and the trauma equivalency argument which subsequently argue for varying levels of prevalence for traumatic occurrences. The main implications investigated include the functionality of traumatized individuals under the stress of sustained attention in the maximal adaptability model in stress and performance research. In order to conduct the investigation of trauma and human adaptability in performance, there were considered 3 main groupings for traumatized individuals in accordance to their range of stressful experiences. All participants were asked to perform a sustained attention task. Seventy-five participants in the age range of 18-41 enrolled in the study through the Sona System website for class participation in their respective psychology classes. The investigation used measures of demographics, the Dissociative Experiences Scale, the Traumatic Events Questionnaire, the Posttraumatic Stress Disorder Checklist, the Dundee Stress State Questionnaire, Conner's Continuous Performance Task II, and the NASA Task Load Index to assess traumatic stress, subjective distress and workload as well as to impose stress through sustained attention. Results indicated that significant differences in measures of impulsiveness in traumatized individuals suggest a heightened awareness and hypervigilance in their reactivity to performance measures. Meanwhile, interactions in performance and gender suggest differences attributed to biological influence to the stress reaction. Gender differences, when isolated by male and female groups showed differences in omission, the absence of a correctly hit target, and hit rate for females while males exhibited more impact on attentional capacity. The pertinence of these findings maintain significant differences in the subjects included in this sample. However, the limitations of the research propose design and measurement strategy differences to further explore trauma's full and versatile impact in stress performance. Implications for this research extend to military optimization and selection as well as training methods. The findings of the project contribute to clinical intervention and understanding of trauma while expanding the literature and knowledge in the field of psychology.

Increasing surface pressure buildup levels and surface venting flow rates on intermediate wellbore casing strings provided an opportunity to analyze wellbore field data to determine a distribution of leakage path permeability values. The gas leakage source in the leaky wellbore originated at depth, and formation gas/fluid traveled along defects in the cement to accumulate at the surface wellhead. The most likely pathway is the cement interface with casing or formation. Due to uncertainty about the location of the leak, and the different methods that were used for calculating leakage parameter values, a range of leakage path permeability values was produced. Most leakage pathway permeability values were greater than intact cement permeability (few microdarcies). This finding supports the practice of using cement filled annuli to provide a safe protective barrier against leakage and to prevent gas flow to surface. Proper cementing techniques are presented in order to identify possible reasons for cracks to form. It is hypothesized that the higher permeability values are a result of cracks in the cement interface with the casing or formation. These types of defects could also be found in wellbores that are in communication with CO2 sequestration reservoirs. The risk of leakage along such existing wellbores associated with CO2 sequestration projects is quantified by the distribution of leakage path permeability. The gas migration path through existing leaky wellbores is an analog for wellbores that are in contact with migrating CO2 plumes. Cracks in the leaky wellbores provide a highly permeable conduit for CO2 to migrate out of the injection zone to the surface. By quantifying leakage path permeability, proper leakage risk assessment can be further developed. / text

<p>Neuroinflammation associated with lumbar radiculopathy and peripheral nerve injury is characterized by locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF&alpha;). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in local delivery of anti-inflammatory drugs to treat this pathology, as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNF&alpha; in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. </p><p>ELPs are biopolymers capable of thermally-triggered in situ depot formation and have been successfully employed as drug carriers and biomaterials in several applications. A library of ELP-curcumin conjugates were synthesized and characterized. One lead conjugate was shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNF&alpha; and NF-&kappa;B with near-equivalent potency compared to free curcumin. When injected into the perineural space via intramuscular (i.m.) injection proximal to the sciatic nerve in mice, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4 days post-injection and decreased systemic exposure of curcumin 3-fold. </p><p>The results of this dissertation support the use of ELP as a drug carrier for local perineural drug delivery, and the strategy presented here for drug conjugate development and use of depot-forming ELP-curcumin conjugates represents a novel means of providing sustained treatment of neuroinflammation and pain associated with radiculopathy and peripheral nerve injury.</p> / Dissertation

The purpose of this study was to describe the behaviors of kindergarten students during Sustained Silent Reading sessions modified to be developmentally appropriate.