Nano- and Micro- Technology Approaches to Enhance Drug Delivery

Small molecules and protein therapeutics are constantly being developed due to their high potency and biological function, but there are many barriers that reduce the therapeutic efficacy of these compounds such as short half-life leading to high clearance, and biological degradation. As a result, to overcome these challenges typically higher doses have to be administered with increased frequency to reach a therapeutically relevant concentration. To address these issues nano- and micro- technology has been utilized to increase drug absorption. This dissertation presents various approaches to drug delivery based on the disease target, application, and therapeutic compound. We showed with hydrogel microdevices a reversible increase in intestinal efflux transporters P-glycoprotein and Breast Cancer Resistance Protein, resulting in an increase in drug absorption. We demonstrate in a Caco-2 model that this decrease in efflux transporter function was due to a decreased amount of transporter present on the cell surface in the presence of microdevices. Also, presented are two polymer nanoparticle-based system designed for different disease targets. First, for cancer immunotherapy we designed a nanoparticle loaded with an adjuvant cocktail with a tumor specific peptide to promote antigen presenting cell activation and downstream lead to tumor specific T cell activation. Therapeutically, these drug-loaded nanoparticles were able to decrease tumor volume in a subcutaneous melanoma model and melanoma foci in a metastasis model. Second, in atherosclerosis where arteries were damaged, we showed that tissue factor peptide targeted nanoparticles loaded with an anti-inflammatory agent were able to target desired damaged arteries where tissue factor is typically exposed. The strategies presented here expand the application of nano- and micro- technology to be designed and implemented in a variety of different disease and targets to increase drug absorption and efficacy not only by increase drug half-life but by targeting the therapeutics to desired regions to increase local concentrations

Rolling smoothly along : the stories of eleven clinicians\u27 spiritual self-care as a vital aspect of avoiding burnout, compassion fatigue and vicarious traumatization

This study was designed to examine whether clinicians who identified themselves as maintaining a religious or spiritual practice as part of self-care routines found these practices helpful in continuing to practice effectively. To collect information regarding this question, eleven clinicians doing direct service work were interviewed; each clinician was asked the same set of questions. The study was qualitative in nature. Each clinician had a unique way of expressing, carrying out, and maintaining his or her religious and/or spiritual practices. As a whole, however, the eleven stories created a surprisingly cohesive narrative. All eleven clinicians reported maintaining religious and/or spiritual practices as part of their self-care helped them continue to do difficult work, avoiding burnout, compassion fatigue and vicarious traumatization

Pregnancy, prison and perinatal outcomes in New South Wales, Australia: a retrospective cohort study using linked health data

BACKGROUND Studies from the United States and the United Kingdom have found that imprisoned women are less likely to experience poorer maternal and perinatal outcomes than other disadvantaged women. This population-based study used both community controls and women with a history of incarceration as a control group, to investigate whether imprisoned pregnant women in New South Wales, Australia, have improved maternal and perinatal outcomes. METHODS Retrospective cohort study using probabilistic record linkage of routinely collected data from health and corrective services in New South Wales, Australia. Comparison of the maternal and perinatal outcomes of imprisoned pregnant women aged 18-44 years who gave birth between 2000-2006 with women who were (i) imprisoned at a time other than pregnancy, and (ii) community controls. OUTCOMES OF INTEREST onset of labour, method of birth, pre-term birth, low birthweight, Apgar score, resuscitation, neonatal hospital admission, perinatal death. RESULTS Babies born to women who were imprisoned during pregnancy were significantly more likely to be born pre-term, have low birthweight, and be admitted to hospital, compared with community controls. Pregnant prisoners did not have significantly better outcomes than other similarly disadvantaged women (those with a history of imprisonment who were not imprisoned during pregnancy). CONCLUSIONS In contrast to the published literature, we found no evidence that contact with prison health services during pregnancy was a "therapunitive" intervention. We found no association between imprisonment during pregnancy and improved perinatal outcomes for imprisoned women or their neonates. A history of imprisonment remained the strongest predictor of poor perinatal outcomes, reflecting the relative health disadvantage experienced by this population of women.This work was undertaken with funding from the National Health and Medical Research Council of Australia. Project Grant ID 457515

Voluntary Facility-Level Sustainability Performance Reporting: Current Status, Relationship to Organization-Level Reporting, and Principles for Progress

Dr. Mark Stoughton and his research assistant Elizabeth Levy provide a status report on voluntary facility-level sustainability performance reporting and explain what this system may provide for environmental sustainability

A comparison of cognitive restructuring and thought listing for excessive acquiring in hoarding disorder

Excessive acquiring is a common symptom of hoarding disorder (HD). Little is known about subjective distress associated with acquiring in HD. The present study examined acquiring- related distress and reactions to cognitive restructuring (CR) in 92 individuals with HD and 66 community control (CC) participants. All participants identified an item of interest at a high-risk acquiring location and then decided whether or not to acquire the item. HD participants completed the acquiring task while receiving a CR-based intervention or a thought-listing (TL) control condition. Results showed that HD participants reported more severe distress and greater urges to acquire the item of interest than did CC participants. Nevertheless, subjective distress decreased in both groups following the acquiring task. There were no differences in acquiring- related distress between the CR and TL conditions. The findings indicate that subjective distress may decrease after relatively short periods of time in individuals with HD, but that a single session of CR may not alleviate acquiring-related distress in HD participants.R01 MH068007 - NIMH NIH HHS; R01 MH068008 - NIMH NIH HHSAccepted manuscrip