HEALTH CARE RESOURCE USE, HEALTH CARE EXPENDITURES AND ABSENTEEISM COSTS ASSOCIATED WITH OSTEOARTHRITIS

Menon, Jyothi, Ph.D., Purdue University, December 2015. Health Care Resource Use, Health Care Expenditures and Absenteeism Costs Associated with Osteoarthritis. Major Professor: Joseph Thomas III

Current State of Breast Cancer Diagnosis, Treatment, and Theranostics

Breast cancer is one of the leading causes of cancer-related morbidity and mortality in women worldwide. Early diagnosis and effective treatment of all types of cancers are crucial for a positive prognosis. Patients with small tumor sizes at the time of their diagnosis have a significantly higher survival rate and a significantly reduced probability of the cancer being fatal. Therefore, many novel technologies are being developed for early detection of primary tumors, as well as distant metastases and recurrent disease, for effective breast cancer management. Theranostics has emerged as a new paradigm for the simultaneous diagnosis, imaging, and treatment of cancers. It has the potential to provide timely and improved patient care via personalized therapy. In nanotheranostics, cell-specific targeting moieties, imaging agents, and therapeutic agents can be embedded within a single formulation for effective treatment. In this review, we will highlight the different diagnosis techniques and treatment strategies for breast cancer management and explore recent advances in breast cancer theranostics. Our main focus will be to summarize recent trends and technologies in breast cancer diagnosis and treatment as reported in recent research papers and patents and discuss future perspectives for effective breast cancer therapy

Ultrasound-Enhanced Chemiluminescence for Bioimaging

Tissue imaging has emerged as an important aspect of theragnosis. It is essential not only to evaluate the degree of the disease and thus provide appropriate treatments, but also to monitor the delivery of administered drugs and the subsequent recovery of target tissues. Several techniques including magnetic resonance imaging (MRI), computational tomography (CT), acoustic tomography (AT), biofluorescence (BF) and chemiluminescence (CL), have been developed to reconstruct three-dimensional images of tissues. While imaging has been achieved with adequate spatial resolution for shallow depths, challenges still remain for imaging deep tissues. Energy loss is usually observed when using a magnetic field or traditional ultrasound (US), which leads to a need for more powerful energy input. This may subsequently result in tissue damage. CT requires exposure to radiation and a high dose of contrast agent to be administered for imaging. The BF technique, meanwhile, is affected by strong scattering of light and autofluorescence of tissues. The CL is a more selective and sensitive method as stable luminophores are produced from physiochemical reactions, e.g. with reactive oxygen species. Development of near infrared-emitting luminophores also bring potential for application of CL in deep tissues and whole animal studies. However, traditional CL imaging requires an enhancer to increase the intensity of low-level light emissions, while reducing the scattering of emitted light through turbid tissue environment. There has been interest in the use of focused ultrasound (FUS), which can allow acoustic waves to propagate within tissues and modulate chemiluminescence signals. While light scattering is decreased, the spatial resolution is increased with the assistance of US. In this review, chemiluminescence detection in deep tissues with assistance of FUS will be highlighted to discuss its potential in deep tissue imaging

Scaffold-based lung tumor culture on porous PLGA microparticle substrates

Scaffold-based cancer cell culture techniques have been gaining prominence especially in the last two decades. These techniques can potentially overcome some of the limitations of current three-dimensional cell culture methods, such as uneven cell distribution, inadequate nutrient diffusion, and uncontrollable size of cell aggregates. Porous scaffolds can provide a convenient support for cell attachment, proliferation and migration, and also allows diffusion of oxygen, nutrients and waste. In this paper, a comparative study was done on porous poly (lactic-co-glycolic acid) (PLGA) microparticles prepared using three porogens—gelatin, sodium bicarbonate (SBC) or novel poly N-isopropylacrylamide [PNIPAAm] particles, as substrates for lung cancer cell culture. These fibronectin-coated, stable particles (19–42 μm) supported A549 cell attachment at an optimal cell seeding density of 250,000 cells/ mg of particles. PLGA-SBC porous particles had comparatively larger, more interconnected pores, and favored greater cell proliferation up to 9 days than their counterparts. This indicates that pore diameters and interconnectivity have direct implications on scaffold-based cell culture compared to substrates with minimally interconnected pores (PLGA-gelatin) or pores of uniform sizes (PLGA-PMPs). Therefore, PLGA-SBC-based tumor models were chosen for preliminary drug screening studies. The greater drug resistance observed in the lung cancer cells grown on porous particles compared to conventional cell monolayers agrees with previous literature, and indicates that the PLGA-SBC porous microparticle substrates are promising for in vitro tumor or tissue development

Porous Polymeric Microspheres With Controllable Pore Diameters for Tissue Engineered Lung Tumor Model Development

Complex cell cultures are more representative of in vivo conditions than conventionally used monolayer cultures, and are hence being investigated for predictive screening of therapeutic agents. Poly lactide co-glycolide (PLGA) polymer is frequently used in the development of porous substrates for complex cell culture. Substrates or scaffolds with highly interconnected, micrometric pores have been shown to positively impact tissue model formation by enhancing cell attachment and infiltration. We report a novel alginate microsphere (AMS)-based controlled pore formation method for the development of porous, biodegradable PLGA microspheres (PPMS), for tissue engineered lung tumor model development. The AMS porogen, non-porous PLGA microspheres (PLGAMS) and PPMS had spherical morphology (mean diameters: 10.3 ± 4, 79 ± 21.8, and 103 ± 30 μm, respectively). The PPMS had relatively uniform pores and a porosity of 45.5%. Degradation studies show that PPMS effectively maintained their structural integrity with time whereas PLGAMS showed shrunken morphology. The optimized cell seeding density on PPMS was 25 × 103 cells/mg of particles/well. Collagen coating on PPMS significantly enhanced the attachment and proliferation of co-cultures of A549 lung adenocarcinoma and MRC-5 lung fibroblast cells. Preliminary proof-of-concept drug screening studies using mono- and combination anti-cancer therapies demonstrated that the tissue-engineered lung tumor model had a significantly higher resistance to the tested drugs than the monolayer co-cultures. These studies indicate that the PPMS with controllable pore diameters may be a suitable platform for the development of complex tumor cultures for early in vitro drug screening applications

Nursing management of adults with severe traumatic brain injury: A narrative review

Effective nursing management strategies for adults with severe traumatic brain injury (STBI) are still a remarkable issue and a difficult task for neurologists, neurosurgeons, and neuronurses. A list of justified indications and scientific rationale for nursing management of these patients are continuously evolving. The objectives of the study are to analyze the pertinently available research and clinical studies that demonstrate the nursing management strategies for adults with STBI and to synthesize the available evidence based on the review. A comprehensive literature search was made in following databases such as Google Scholar, Cochrane, J‑Gate, ProQuest, and ScienceDirect for retrieving the related studies. In the included studies, data were extracted and evaluated according to the objective. Narrative analysis was adopted to write this review. Patients with STBI have poor prognosis and require quality care for maximizing patients’ survival. With a thorough knowledge and discernment of care of such patients, nurses can improve these patients’ neurological outcomes

3D Bioprinted Implants for Cartilage Repair in Intervertebral Discs and Knee Menisci

Cartilage defects pose a significant clinical challenge as they can lead to joint pain, swelling and stiffness, which reduces mobility and function thereby significantly affecting the quality of life of patients. More than 250,000 cartilage repair surgeries are performed in the United States every year. The current gold standard is the treatment of focal cartilage defects and bone damage with nonflexible metal or plastic prosthetics. However, these prosthetics are often made from hard and stiff materials that limits mobility and flexibility, and results in leaching of metal particles into the body, degeneration of adjacent soft bone tissues and possible failure of the implant with time. As a result, the patients may require revision surgeries to replace the worn implants or adjacent vertebrae. More recently, autograft – and allograft-based repair strategies have been studied, however these too are limited by donor site morbidity and the limited availability of tissues for surgery. There has been increasing interest in the past two decades in the area of cartilage tissue engineering where methods like 3D bioprinting may be implemented to generate functional constructs using a combination of cells, growth factors (GF) and biocompatible materials. 3D bioprinting allows for the modulation of mechanical properties of the developed constructs to maintain the required flexibility following implantation while also providing the stiffness needed to support body weight. In this review, we will provide a comprehensive overview of current advances in 3D bioprinting for cartilage tissue engineering for knee menisci and intervertebral disc repair. We will also discuss promising medical-grade materials and techniques that can be used for printing, and the future outlook of this emerging field

Thermo-responsive Fluorescent Nanoparticles for Multimodal Imaging and Treatment of Cancers

Theranostic systems capable of delivering imaging and therapeutic agents at a specific target are the focus of intense research efforts in drug delivery. To overcome non-degradability and toxicity concerns of conventional theranostic systems, we formulated a novel thermo-responsive fluorescent polymer (TFP) and conjugated it on the surface of iron oxide magnetic nanoparticles (MNPs) for imaging and therapeutic applications in solid tumors. Methods: TFP-MNPs were synthesized by copolymerizing poly(N-isopropylacrylamide), allylamine and a biodegradable photoluminescent polymer, and conjugating it on MNPs via a free radical polymerization reaction. Physicochemical properties of the nanoparticles were characterized using Fourier transform infrared spectroscopy, dynamic light scattering, and vibrational sample magnetometry. Nanoparticle cytocompatibility, cellular uptake and cytotoxicity were evaluated using in vitro cell assays. Finally, in vivo imaging and therapeutic efficacy studies were performed in subcutaneous tumor xenograft mouse models. Results: TFP-MNPs of ~135 nm diameter and -31 mV ζ potential maintained colloidal stability and superparamagnetic properties. The TFP shell was thermo-responsive, fluorescent, degradable, and released doxorubicin in response to temperature changes. In vitro cell studies showed that TFP-MNPs were compatible to human dermal fibroblasts and prostate epithelial cells. These nanoparticles were also taken up by prostate and skin cancer cells in a dose-dependent manner and exhibited enhanced killing of tumor cells at 41°C. Preliminary in vivo studies showed theranostic capabilities of the nanoparticles with bright fluorescence, MRI signal, and therapeutic efficacy under magnetic targeting after systemic administration in tumor bearing mice. Conclusion: These results indicate the potential of TFP-MNPs as multifunctional theranostic nanoparticles for various biological applications, including solid cancer management

Developing virtual and augmented reality applications for science, technology, engineering and math education

The Rhode Island IDeA Network of Biomedical Research Excellence Molecular Informatics Core at the University of Rhode Island Information Technology Services Innovative Learning Technologies developed virtual and augmented reality applications to teach concepts in biomedical science, including pharmacology, medicinal chemistry, cell culture and nanotechnology. The apps were developed as full virtual reality/augmented reality and 3D gaming versions, which do not require virtual reality headsets. Development challenges included creating intuitive user interfaces, text-to-voice functionality, visualization of molecules and implementing complex science concepts. In-app quizzes are used to assess the user\u27s understanding of topics, and user feedback was collected for several apps to improve the experience. The apps were positively reviewed by users and are being implemented into the curriculum at the University of Rhode Island

Air pollution in Delhi: A review of past and current policy approaches

Delhi National Capital Region (Delhi NCR) is facing serious challenges linked to worrying levels of air pollution (mainly NO2, PM10 and PM2.5). The CADTIME prject (Clean Air in Delhi through Implementation, Mitigation and Engagement) aims to understand what is required to deliver significant reductions in levels of air pollution. This paper presents the results of the first stage of the project: it firstly contextualises the challenges of air quality management in Delhi within the broader evolution of environmental policies and governance in India, with particular consideration to the tensions between environmental protection and the country's development objectives. Secondly, it sets out how CADTIME will combine multiple source qualitative and quantitative data to develop an air quality action plan and an implementation strategy. In particular, through two workshops with local and national experts and stakeholders, and two rounds of focus groups with citizens of Delhi we will contrast stakeholders' priorities and preferences for existing and potential solutions to air pollution with citizens' lived experiences, thus assessing the political/technical feasibility and public acceptability of current and proposed measures. Furthermore, we will complement the primary qualitative data with a critical review examining the successes and failures of UK and European policies to draw lessons that can be relevant for Delhi and to avoid ineffective policies and achieve cost-effective solutions for the city in the shortest possible time