Translation from research to applications

The article summarizes the collective views expressed at the fourth session of the workshop Tissue Engineering-the Next Generation, which was devoted to the translation of results of tissue engineering research into applications. Ernst Hunziker described the paradigm of a dual translational approach, and argued that tissue engineering should be guided by the dimensions and physiological setting of the bodily compartment to be repaired. Myron Spector discussed collagen-glycosaminoglycan (GAG) scaffolds for musculoskeletal tissue engineering. Jeanette Libera focused on the biological and clinical aspects of cartilage tissue engineering, and described a completely autologous procedure for engineering cartilage using the patient's own chondrocytes and blood serum. Arthur Gertzman reviewed the applications of allograft tissues in orthopedic surgery, and outlined the potential of allograft tissues as models for biological and medical studies. Savio Woo discussed a list of functional tissue engineering approaches designed to restore the biochemical and biomechanical properties of injured ligaments and tendons to be closer to that of the normal tissues. Specific examples of using biological scaffolds that have chemoattractants as well as growth factors with unique contact guidance properties to improve their healing process were shown. Anthony Ratcliffe discussed the translation of the results of research into products that are profitable and meet regulatory requirements. Michael Lysaght challenged the proposition that commercial and clinical failures of early tissue engineering products demonstrate a need for more focus on basic research. Arthur Coury described the evolution of tissue engineering products based on the example of Genzyme, and how various definitions of success and failure can affect perceptions and policies relative to the status and advancement of the field of tissue engineering.

Cardiovascular proteomics: implications for clinical applications

Proteomics is fulfilling its potential and beginning to impact the diagnosis and therapy of cardiovascular disease. As de novo proteomics analysis gets more streamlined, and robust high-throughput methods are developed, more and more attention is being directed toward the field of cardiovascular serum and plasma biomarker discovery. To take cardiovascular proteomics from bench to bedside, great care must be taken to achieve reproducible results. Despite technical advances, however, the absolute number of clinical biomarkers thus far discovered by a proteomics approach is small. Although several factors contribute to this lack, one step is to build "translation teams" involving a close collaboration between researchers and clinicians.

The role of post-translation regulation of Twist expression in the tumor progression of squamous cell carcinoma of head and neck

Squamous cell carcinoma of head and neck (SCCHN) is the tenth most common cancer in the world. Unfortunately, the survival of patients with SCCHN has not improved in the last 40 years. Therefore new targets for therapy are needed, and to this end we are studying signaling pathways activated by IL-6 which we have found stimulates cell migration and soft agar growth in SCCHN. Our data show that IL-6 increases TWIST expression in a transcription-independent mechanism in many SCCHN cell lines. Further investigation reveals TWIST can be phosphorylated upon IL-6 treatment. By computation prediction (http://scansite.mit.edu/motifscan_seq.phtml ), we found that TWIST has a putative phosphorylation site for casein kinase 2 (CK2) suggesting that this kinase could serve as a link between IL-6 stimulation and Twist stability. To test this hypothesis, we used a CK2 inhibitor and shRNA to CK2 and found that these interventions inhibited IL-6 stimulation of TWIST stability. In addition, mutation of the putative CK2 phosphorylation site (S18/S20A) in TWIST decreased the amount of phospho-ATP incorporated by TWIST in an in vitro kinase assay, and altered TWIST stability. In Boyd chamber migration assay and wound-healing assay, the CK2 inhibitor, DMAT, was found to decrease the motility of IL-6 stimulated SCCHN cells and over expression of either a wild-type or the hyperphosphorylated mimicking mutant S18/20D –Twist rather than the hypo-phosphorylated mimicking mutant S18/20A-Twist can promote SCCHN cell motility.To our knowledge, this is the first report to identify the importance of IL-6 stimulated CK2 phosphorylation of TWIST in SCCHN. As CK2 inhibitors are currently under phase I clinical trials, our findings indicate that CK2 may be a viable therapeutic target in SCCHN. Therefore, further pre-clinical studies of this inhibitor are underway.

Attitudes and other barriers to the utilization of clinical research findings by American physicians: A systematic review

Background: The Institute of Medicine estimates that only a maximum of 25% of clinical research findings are incorporated into practice by physicians. To improve clinical practice, efforts have been made to promote evidence-based medicine and the use of clinical guidelines. Despite these efforts, the gap between research and clinical practice remains wide.^ Objective: To systematically review the literature describing the factors which influence the use of clinical research recommendations by American physicians.^ Hypothesis: Barriers exist in the application of clinical research into clinical practice, and are multifactorial. The establishment of the Clinical and Translational Awards (CTSA; special federal grants awarded to selected institutions to support clinical and translational research) has reduced the effect of these barriers and improved the process of clinical research translation into practice among American physicians.^ Aims: Identify barriers and facilitators of the use of research findings in clinical practice by American physicians. Contrast studies published six years before and after the creation of the CTSA.^ Methods: The sources of data include published literature from Medline, PubMed and PsycINFO. Selected studies must be qualitative, a survey of American clinicians, based on evidence-based medicine practice, clinical guidelines or treatment pathways. Systematic reviews and reports were excluded, as well as studies with less than 100 respondents.^ Results: In total, 1036 abstracts were reviewed; 115 full text potential articles were identified and reviewed, and a total of 31 studies met all criteria for inclusion in the final review.^ Conclusions: The barriers against the application of clinical research findings, in the forms of clinical guidelines, evidence-based medicine guides and clinical pathways, can be divided broadly into physician barriers, practice/system barriers and patient barriers. Physician barriers are the most common barriers, especially the lack of familiarity with guidelines and the lack of time. Of the factors which improve the use of research based guidelines, physician factors such as younger age, lower duration of clinical practice, specialty training, and practice in large group Health Maintenance Organization (HMO) settings with fewer patients seen were the most commonly cited.^

A machine learning approach to identify clinical trials involving nanodrugs and nanodevices from ClinicalTrials.gov

BACKGROUND: Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano), and CTs that do not involve nanotechnology (non-nano). Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs-even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results. METHODS: We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i) extraction and manual annotation of CTs as nano vs. non-nano, ii) pre-processing and automatic classification, and iii) performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset. RESULTS AND CONCLUSIONS: The performance of the best automated classifier closely matches that of experts (AUC over 0.95), suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a particular nanoparticle or nanodevice, which is essential to discover any precedents for nanotoxicity events or advantages for targeted drug therapy.

Development and psychometric testing of the clinical learning environment, supervision and nurse teacher evaluation scale (CLES+T): The Spanish version

Background: The Clinical Learning Environment, Supervision and Nurse Teacher scale is a reliable and valid instrument to evaluate the quality of the clinical learning process in international nursing education contexts. Objectives: This paper reports the development and psychometric testing of the Spanish version of the Clinical Learning Environment, Supervision and Nurse Teacher scale. Design: Cross-sectional validation study of the scale. Setting: 10 public and private hospitals in the Alicante area, and the Faculty of Health Sciences (University of Alicante, Spain). Participants: 370 student nurses on clinical placement (January 2011–March 2012). Methods: The Clinical Learning Environment, Supervision and Nurse Teacher scale was translated using the modified direct translation method. Statistical analyses were performed using PASW Statistics 18 and AMOS 18.0.0 software. A multivariate analysis was conducted in order to assess construct validity. Cronbach’s alpha coefficient was used to evaluate instrument reliability. Results: An exploratory factorial analysis identified the five dimensions from the original version, and explained 66.4% of the variance. Confirmatory factor analysis supported the factor structure of the Spanish version of the instrument. Cronbach’s alpha coefficient for the scale was .95, ranging from .80 to .97 for the subscales. Conclusion: This version of the Clinical Learning Environment, Supervision and Nurse Teacher scale instrument showed acceptable psychometric properties for use as an assessment scale in Spanish-speaking countries.

Precision medicine in patients with allergic diseases: Airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology

In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine.

Text-book of insanity, based on clinical observations for practitioners and students of medicine.

Translation of Lehrbuch der Psychiatrie auf klinischer Grundlage für practische Aerzte und Studierende.

Lectures on clinical medicine, delivered in the Hospital Saint-Jacques, of Paris.

Translation of Leçons de clinique médical from notes taken by Jousset's students.

Clinical lectures on surgery : delivered at Hotel Dieu, in 1832 /

Translation of: Leçons orales de clinique chirurgicale.

Elements of clinical bacteriology for physicians and students,

Translation of Grundriss der klinischen Bakteriologie.

Translation and validation of the Chinese version of the Charing Cross Venous Ulcer Questionnaire

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Concise review:bone marrow for the treatment of spinal cord injury: mechanisms and clinical applications

Transplantation of bone marrow stem cells into spinal cord lesions enhances axonal regeneration and promotes functional recovery in animal studies. There are two types of adult bone marrow stem cell; hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might promote spinal cord repair following transplantation have been extensively investigated. The objective of this review is to discuss these mechanisms; we briefly consider the controversial topic of HSC and MSC transdifferentiation into central nervous system cells but focus on the neurotrophic, tissue sparing, and reparative action of MSC grafts in the context of the spinal cord injury (SCI) milieu. We then discuss some of the specific issues related to the translation of HSC and MSC therapies for patients with SCI and present a comprehensive critique of the current bone marrow cell clinical trials for the treatment of SCI to date.

Roadmap to clinical use of gold nanoparticles for radiation sensitization

The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.