The Translation Evidence Mechanism. The Compact between Researcher and Clinician.

Currently, best evidence is a concentrated effort by researchers. Researchers produce information and expect that clinicians will implement their advances in improving patient care. However, difficulties exist in maximizing cooperation and coordination between the producers, facilitators, and users (patients) of best evidence outcomes. The Translational Evidence Mechanism is introduced to overcome these difficulties by forming a compact between researcher, clinician and patient. With this compact, best evidence may become an integral part of private practice when uncertainties arise in patient health status, treatments, and therapies. The mechanism is composed of an organization, central database, and decision algorithm. Communication between the translational evidence organization, clinicians and patients is through the electronic chart. Through the chart, clinical inquiries are made, patient data from provider assessments and practice cost schedules are collected and encrypted (HIPAA standards), then inputted into the central database. Outputs are made within a timeframe suitable to private practice and patient flow. The output consists of a clinical practice guideline that responds to the clinical inquiry with decision, utility and cost data (based on the "average patient") for shared decision-making within informed consent. This shared decision-making allows for patients to "game" treatment scenarios using personal choice inputs. Accompanying the clinical practice guideline is a decision analysis that explains the optimized clinical decision. The resultant clinical decision is returned to the central database using the clinical practice guideline. The result is subsequently used to update current best evidence, indicate the need for new evidence, and analyze the changes made in best evidence implementation. When updates in knowledge occur, these are transmitted to the provider as alerts or flags through patient charts and other communication modalities

Dissemination of evidence-based standards of care.

Standards of care pertain to crafting and implementing patient-centered treatment interventions. Standards of care must take into consideration the patient's gender, ethnicity, medical and dental history, insurance coverage (or socioeconomic level, if a private patient), and the timeliness of the targeted scientific evidence. This resolves into a process by which clinical decision-making about the optimal patient-centered treatment relies on the best available research evidence, and all other necessary inputs and factors to provide the best possible treatment. Standards of care must be evidence-based, and not merely based on the evidence - the dichotomy being critical in contemporary health services research and practice. Evidence-based standards of care must rest on the best available evidence that emerges from a concerted hypothesis-driven process of research synthesis and meta-analysis. Health information technology needs to become an every-day reality in health services research and practice to ensure evidence-based standards of care. Current trends indicate that user-friendly methodologies, for the dissemination of evidence-based standards of care, must be developed, tested and distributed. They should include approaches for the quantification and analysis of the textual content of systematic reviews and of their summaries in the form of critical reviews and lay-language summaries

Salivary biomarkers in psychobiological medicine.

The value of salivary biomarkers for diagnostic and prognostic assessments has become increasingly well established in medicine, pharmacology, and dentistry. Certain salivary components mirror the neuro-endocrine status of the organism. Other saliva products are protein in nature, and can serve to reflect immune surveillance processes. The autonomic nervous system regulates the process of salivation, and the concentration of yet other salivary components, such as alpha-amylase, which provide a reliable outcome measure of the sympathetic response. Here, we discuss molecular technologies that have permitted giant steps in the utilization of salivary samples and micro-fluidics for the benefit of diagnostic medicine and dentistry, and their putative role in springing forward research in psychobiology

The Molecular Immunology of Mucositis: Implications for Evidence-Based Research in Alternative and Complementary Palliative Treatments

The terms ‘mucositis’ and ‘stomatitis’ are often used interchangeably. Mucositis, however, pertains to pharyngeal-esophago-gastrointestinal inflammation that manifests as red, burn-like sores or ulcerations throughout the mouth. Stomatitis is an inflammation of the oral tissues proper, which can present with or without sores, and is made worse by poor dental hygiene. Mucositis is observed in a variety of immunosuppressed patients, but is most often consequential to cancer therapy. It appears as early as the third day of intervention, and is usually established by Day 7 of treatment. Mucositis increases mortality and morbidity and contributes to rising health care costs. The precise immune components involved in the etiology of mucositis are unclear, but evidence-based research (EBR) data has shown that applications of granulocyte–macrophage-colony stimulating factor prevent the onset or the exacerbation of oropharyngeal mucositis. The molecular implications of this observation are discussed from the perspective of future developments of complementary and alternative treatments for this condition. It must be emphasized that this article is meant to be neither a review on mucositis and the various treatments for it, nor a discussion paper on its underlying molecular immunology. It is a statement of the implications of EBR for CAM-based interventions for mucositis. It explores and discusses the specific domain of molecular immunology in the context of mucositis and its direct implications for EBR research in CAM-based treatments for mucositis

Epigenetic regulation of osteogenesis: human embryonic palatal mesenchymal cells.

Mesenchymal stem cells (MSCs) provide an appropriate model to study epigenetic changes during osteogenesis and bone regeneration due to their differentiation potential. Since there are no unique markers for MSCs, methods of identification are limited. The complex morphology of human embryonic palatal mesenchyme stem cell (HEPM) requires analysis of fractal dimensions to provide an objective quantification of self-similarity, a statistical transformation of cellular shape and border complexity. We propose the hypothesis of a study to compare and contrast sequential steps of osteogenic differentiation in HEPMs both phenotypically using immunocytochemistry, and morphometrically using fractal analysis from undifferentiated passage 1 (P1) to passage 7 (P7) cells. The proof-of-concept is provided by results we present here that identify and compare the modulation of expression of certain epigenetic biomarkers (alkaline phosphatase, ALP; stromal interaction molecule-1, STRO-1; runt-related transcription factor-2, RUNX2), which are established markers of osteogenesis in bone marrow studies, of osteoblastic/skeletal morphogenesis, and of osteoblast maturation. We show that Osteoinductive medium (OIM) modulates the rate of differentiation of HEPM into Run-2+ cells, the most differentiated subpopulation, followed by ALP+ and STRO-1+ cells. Taken together, our phenotypical and morphometric data demonstrate the feasibility of using HEPM to assess osteogenic differentiation from an early undifferentiated to a differentiated stage. This research model may lay the foundation for future studies aimed at characterizing the epigenetic characteristics of osteoimmunological disorders and dysfunctions (e.g., osteoarthritis, temporomandibular joint disorders), so that proteomic profiling can aid the diagnosis and monitor the prognosis of these and other osteoimmunopathologies

Tunable Photonic Multilayers from Stimulus-Responsive, Photo-Crosslinkable Polymers

This dissertation describes the synthesis of photo-crosslinkable copolymers and their utilization for the fabrication and testing of tunable and responsive one-dimensional (1D) photonic multilayers. Photonic multilayers exhibit structural color due to the interference of incident light at layer interfaces, providing a convenient route towards optically responsive materials that do not rely on potentially light- or oxygen-sensitive chromophore-containing pigments and dyes. A fabrication technique based on sequential spin-coating and crosslinking of photo-crosslinkable polymers is used to assemble tunable and responsive photonic multilayers. Chapter One introduces the fundamental underlying principles of 1D photonic structures and explores their importance in a variety of areas, including sensors, responsive films, as well as the necessity of their optimization through routes such as the incorporation of nanocomposites for enhanced refractive index. This chapter also details the experimental approach used here for fabricating tunable and responsive 1D photonic multilayers utilizing sequential spin-coating and crosslinking of photo-crosslinkable polymers. Chapter Two describes the use of these multilayer photonic films as thermochromic materials using poly(N-isopropylacrylamide) (PNIPAM) as the low-refractive index, stimulus responsive layers and poly(p-methyl styrene) (PpMS) as the high-refractive index, hydrophobic layers. Temperature is utilized as an analyte to validate this platform as a feasible and flexible approach for the fabrication of a variety of tunable and responsive structures. Building upon the knowledge developed in Chapters 1 and 2, this photonic sensing platform is next expanded to detect additional analytes and further optimize sensor performance by improving reflectance efficiency, response and exploring various multilayer geometries and arrays. Chapter 3 describes the utilization of polymeric photonic multilayers for colorimetric sensing of ionizing radiation. Chapter 4 explores a method of enhancing the reflectance efficiency of multilayers through the incorporation of high refractive index zirconia nanoparticles. The utilization of nanoparticles also enables the fabrication of all-gel multilayers for flexible, potentially mechanochromatic, photonic materials by eliminating the necessity of the high refractive index, but brittle, PpMS. Chapter 5 explores in detail the kinetic response of photonic multilayers with a variety of responsive polymer materials during the swelling and de-swelling phases. Chapter 6 details how this approach can be expanded to create new multilayer geometries, including Bragg filters, as well as multifunctional sensors and arrays on a single substrate. Chapter 7 introduces preliminary work studying the electrochromic response of photonic multilayers. Applied voltage triggers the reversible de-swelling of the responsive layers and subsequently a blue-shift in the wavelength of reflected light. Finally, Chapter 8 provides a summary of this dissertation and proposes future directions for photonic polymer multilayers