The application of molecular imaging to advance translational research in chronic inflammation.

Over the past several decades, molecular imaging techniques to assess cellular processes in vivo have been integral in advancing our understanding of disease pathogenesis. 18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) imaging in particular has shaped the field of atherosclerosis research by highlighting the importance of underlying inflammatory processes that are responsible for driving disease progression. The ability to assess physiology using molecular imaging, combining it with anatomic delineation using cardiac coronary angiography (CCTA) and magnetic resonance imaging (MRI) and lab-based techniques, provides a powerful combination to advance both research and ultimately clinical care. In this review, we demonstrate how molecular imaging studies, specifically using 18-FDG PET, have revealed that early vascular disease is a systemic process with multiple, concurrent biological mechanisms using inflammatory diseases as a basis to understand early atherosclerotic mechanisms in humans.

An Innovative Online Knowledge Translation Curriculum in Graduate Education.

BACKGROUND: There is increased acknowledgment of the importance of knowledge translation (KT) in the role of graduate-prepared healthcare practitioners, such as nurses, as change agents in the mobilization of evidence-based knowledge. The offering of flexible educational programming online and hybrid course delivery in higher education is a response to insufficient didactic methods for providing graduate students with the competencies to facilitate KT. AIMS: To describe the development, implementation, and evaluation of a cohort-based, online, innovative KT curriculum using a theoretical approach to KT called the Knowledge-As-Action Framework, which focuses on the knower, knowledge, and context as being inseparable. This process strategically engages with stakeholders to link practice concerns with existing realities, thus providing the best available knowledge to inform KT action in complex healthcare contexts. METHODS: The Model of Evidence-Informed, Context-Relevant, Unified Curriculum Development in Nursing Education guided the cohort-based online KT course process. The development, implementation, and evaluation involved (a) an environmental scan, (b) a literature review, (c) faculty development, (d) curriculum design of two 10-week courses, and (e) a summation of the concurrent participatory evaluation of the two courses, including faculty and student responses. The Knowledge-As-Action Framework is comprised of six interrelated dimensions as part of a "kite" metaphor, with the underlying premise that if any one of the dimensions results in an imbalance, the KT process may be grounded. RESULTS: Evaluation revealed (a) intentionality of the core processes of curriculum work; (b) effectiveness of indicators for evaluating the KT courses; (c) leadership should be added as a learning domain for KT; (d) the Knowledge-As-Action Framework provided an integrated, philosophical, and evidence-based approach to KT; (e) cohort model facilitated a community of inquiry; and (f) the formalized structured approach of the courses with ongoing supervision and mentoring allowed for timely completion. LINKING EVIDENCE TO ACTION: Teaching and learning in an online cohort model created a community of inquiry and facilitated experiential learning. The active engagement of students with their practice-based stakeholders promoted change in clinical settings and enhanced students' professional development to lead change.

The Liebau phenomenon: a translational approach to new paradigms of CSF circulation and related flow disturbances.

PURPOSE: The aim of the study is to provide a comparison between Liebau's effect, underlying the working principles of impedance pumps, and the cerebrospinal fluid (CSF) circulation. METHODS: Gerhard Liebau was a cardiologist with a specific interest in severe aortic regurgitation. Such interest drew his scientific attention to the flow-driven efficiency of valveless pumps. During one of his experiments, he assembled two rubber tubes of different sizes and documented how water could be aspirated against gravity when the tube of larger diameter underwent rhythmic compression. He subsequently tested an elastic tube connected to glass pipes of the same size on both ends, immersed in a water bucket. When the elastic tube was periodically pumped with a finger, a net flow could be observed in both directions; depending on the pumping site on the elastic tube, the flow was directed towards the most closely connected glass tube. The principles of a hydraulic system of different elasticity and compliance were also recently applied to the physiology and fluid dynamics of embryonic hearts. RESULTS: Impedance pumps and the CSF dynamics model are both valveless systems and can both be activated by the effects of the cardiac cycle. The novel hydraulic model of impedance pumps was the foundation for the development of modern valveless micropumps and contributes to explain how the embryonic valveless tubular heart is capable of generating blood flow. CONCLUSIONS: Liebau's effect and the mechanism of impedance pumps can enlighten some of the aspects of CSF dynamics and related flow disturbances.

BOLD fMRI in awake prairie voles: A platform for translational social and affective neuroscience.

The advancement of neuroscience depends on continued improvement in methods and models. Here, we present novel techniques for the use of awake functional magnetic resonance imaging (fMRI) in the prairie vole (Microtus ochrogaster) - an important step forward in minimally-invasive measurement of neural activity in a non-traditional animal model. Imaging neural responses in prairie voles, a species studied for its propensity to form strong and selective social bonds, is expected to greatly advance our mechanistic understanding of complex social and affective processes. The use of ultra-high-field fMRI allows for recording changes in region-specific activity throughout the entire brain simultaneously and with high temporal and spatial resolutions. By imaging neural responses in awake animals, with minimal invasiveness, we are able to avoid the confound of anesthesia, broaden the scope of possible stimuli, and potentially make use of repeated scans from the same animals. These methods are made possible by the development of an annotated and segmented 3D vole brain atlas and software for image analysis. The use of these methods in the prairie vole provides an opportunity to broaden neuroscientific investigation of behavior via a comparative approach, which highlights the ethological relevance of pro-social behaviors shared between voles and humans, such as communal breeding, selective social bonds, social buffering of stress, and caregiving behaviors. Results using these methods show that fMRI in the prairie vole is capable of yielding robust blood oxygen level dependent (BOLD) signal changes in response to hypercapnic challenge (inhaled 5% CO2), region-specific physical challenge (unilateral whisker stimulation), and presentation of a set of novel odors. Complementary analyses of repeated restraint sessions in the imaging hardware suggest that voles do not require acclimation to this procedure. Taken together, awake vole fMRI represents a new arena of neurobiological study outside the realm of traditional rodent models.

Pharmaco-EEG Studies in Animals: An Overview of Contemporary Translational Applications.

The contemporary value of animal pharmaco-electroencephalography (p-EEG)-based applications are strongly interlinked with progress in recording and neuroscience analysis methodology. While p-EEG in humans and animals has been shown to be closely related in terms of underlying neuronal substrates, both translational and back-translational approaches are being used to address extrapolation issues and optimize the translational validity of preclinical animal p-EEG paradigms and data. Present applications build further on animal p-EEG and pharmaco-sleep EEG findings, but also on stimulation protocols, more specifically pharmaco-event-related potentials. Pharmaceutical research into novel treatments for neurological and psychiatric diseases has employed an increasing number of pharmacological as well as transgenic models to assess the potential therapeutic involvement of different neurochemical systems and novel drug targets as well as underlying neuronal connectivity and synaptic function. Consequently, p-EEG studies, now also readily applied in modeled animals, continue to have an important role in drug discovery and development, with progressively more emphasis on its potential as a central readout for target engagement and as a (translational) functional marker of neuronal circuit processes underlying normal and pathological brain functioning. In a similar vein as was done for human p-EEG studies, the contribution of animal p-EEG studies can further benefit by adherence to guidelines for methodological standardization, which are presently under construction by the International Pharmaco-EEG Society (IPEG).

Advantages and challenges of small animal magnetic resonance imaging as a translational tool.

The utilization of magnetic resonance imaging (MRI) methods in rodent models of psychiatric disorders provides considerable benefits for the identification of disease-associated brain circuits and metabolic changes. In this review, we discuss advantages and challenges of animal MRI and provide an overview of the major structural (voxel-based morphometry and diffusion tensor imaging) and functional approaches [resting-state functional MRI (rs-fMRI), MR spectroscopy (MRS), regional cerebral blood volume measurement and arterial spin labelling] that are applied in animal MRI research. The review mainly focuses on rs-fMRI and MRS. Finally, we take a look at some recent developments and refinements in the field.

Translational applications of flow cytometry in clinical practice.

Flow cytometry has evolved over the past 30 y from a niche laboratory technique to a routine tool used by clinical pathologists and immunologists for diagnosis and monitoring of patients with cancer and immune deficiencies. Identification of novel patterns of expressed Ags has led to the recognition of cancers with unique pathophysiologies and treatment strategies. FACS had permitted the isolation of tumor-free populations of hematopoietic stem cells for cancer patients undergoing stem cell transplantation. Adaptation of flow cytometry to the analysis of multiplex arrays of fluorescent beads that selectively capture proteins and specific DNA sequences has produced highly sensitive and rapid methods for high through-put analysis of cytokines, Abs, and HLA genotypes. Automated data analysis has contributed to the development of a "cytomics" field that integrates cellular physiology, genomics, and proteomics. In this article, we review the impact of the flow cytometer in these areas of medical practice.

Minimally invasive imaging method based on second harmonic generation and multiphoton excitation fluorescence in translational respiratory research.

For translational respiratory research including in the development of clinical diagnostic tools, a minimally invasive imaging method, which can provide both cellular and extracellular structural details with sufficient specificity, sensitivity and spatial resolution, is particularly useful. Multiphoton microscopy causes excitation of endogenously fluorescent macromolecular systems and induces highly specific second harmonic generation signals from non-centrosymmetric macromolecules such as fibrillar collagens. Both these signals can be captured simultaneously to provide spatially resolved 3D structural organization of extracellular matrix as well as the cellular morphologies in their native states. Besides briefly discussing the fundamentals of multiphoton excitation fluorescence and harmonic generation signals and the instrumentation details, this review focuses on the specific applications of these imaging modalities in lung structural imaging, particularly morphological features of alveolar structures, visualizing and quantifying extracellular matrix remodelling accompanying emphysematous destructions as well as the IPF, detecting lung cancers and the potential use in the tissue engineering applications.

The ONCO-I2b2 project: integrating biobank information and clinical data to support translational research in oncology.

The University of Pavia and the IRCCS Fondazione Salvatore Maugeri of Pavia (FSM), has recently started an IT initiative to support clinical research in oncology, called ONCO-i2b2. ONCO-i2b2, funded by the Lombardia region, grounds on the software developed by the Informatics for Integrating Biology and the Bedside (i2b2) NIH project. Using i2b2 and new software modules purposely designed, data coming from multiple sources are integrated and jointly queried. The core of the integration process stands in retrieving and merging data from the biobank management software and from the FSM hospital information system. The integration process is based on a ontology of the problem domain and on open-source software integration modules. A Natural Language Processing module has been implemented, too. This module automatically extracts clinical information of oncology patients from unstructured medical records. The system currently manages more than two thousands patients and will be further implemented and improved in the next two years.

Good practices in harnessing social media for scholarly discourse, knowledge translation, and education.

INTRODUCTION: There still remains a gap between those who conduct science and those who engage in educating others about health sciences through various forms of social media. Few empirical studies have sought to define useful practices for engaging in social media for academic use in the health professions. Given the increasing importance of these platforms, we sought to define good practices and potential pitfalls with help of those respected for their work in this new field. METHODS: We conducted a qualitative study, guided by constructivist grounded theory principles, of 17 emerging experts in the field of academic social media. We engaged in a snowball sampling technique and conducted a series of semi-structured interviews. The analytic team consisted of a diverse group of researchers with a range of experience in social media. RESULTS: Understanding the strengths of various platforms was deemed to be of critical importance across all the participants. Key to building online engagement were the following: 1) Culture-building strategies; 2) Tailoring the message; 3) Responsiveness; and 4) Heeding rules of online engagement. Several points of caution were noted within our participants' interviews. These were grouped into caveat emptor and the need for critical appraisal, and common pitfalls when broadcasting one's self. DISCUSSION: Our participants were able to share a number of key practices that are central to developing and sharing educational content via social media. The findings from the study may guide future practitioners seeking to enter the space. These good practices support professionals for effective engagement and knowledge translation without being harmed.

MRI-Compatible and Conformal Electrocorticography Grids for Translational Research.

Intraoperative electrocorticography (ECoG) captures neural information from the surface of the cerebral cortex during surgeries such as resections for intractable epilepsy and tumors. Current clinical ECoG grids come in evenly spaced, millimeter-sized electrodes embedded in silicone rubber. Their mechanical rigidity and fixed electrode spatial resolution are common shortcomings reported by the surgical teams. Here, advances in soft neurotechnology are leveraged to manufacture conformable subdural, thin-film ECoG grids, and evaluate their suitability for translational research. Soft grids with 0.2 to 10 mm electrode pitch and diameter are embedded in 150 µm silicone membranes. The soft grids are compatible with surgical handling and can be folded to safely interface hidden cerebral surface such as the Sylvian fold in human cadaveric models. It is found that the thin-film conductor grids do not generate diagnostic-impeding imaging artefacts (<1 mm) nor adverse local heating within a standard 3T clinical magnetic resonance imaging scanner. Next, the ability of the soft grids to record subdural neural activity in minipigs acutely and two weeks postimplantation is validated. Taken together, these results suggest a promising future alternative to current stiff electrodes and may enable the future adoption of soft ECoG grids in translational research and ultimately in clinical settings.

Pharmacogenomics Biomarker Discovery and Validation for Translation in Clinical Practice.

Interindividual variability in drug efficacy and toxicity is a major challenge in clinical practice. Variations in drug pharmacokinetics (PKs) and pharmacodynamics (PDs) can be, in part, explained by polymorphic variants in genes encoding drug metabolizing enzymes and transporters (absorption, distribution, metabolism, and excretion) or in genes encoding drug receptors. Pharmacogenomics (PGx) has allowed the identification of predictive biomarkers of drug PKs and PDs and the current knowledge of genome-disease and genome-drug interactions offers the opportunity to optimize tailored drug therapy. High-throughput PGx genotyping, from targeted to more comprehensive strategies, allows the identification of PK/PD genotypes to be developed as clinical predictive biomarkers. However, a biomarker needs a robust process of validation followed by clinical-grade assay development and must comply to stringent regulatory guidelines. We here discuss the methodological challenges and the emerging technological tools in PGx biomarker discovery and validation, at the crossroad among molecular genetics, bioinformatics, and clinical medicine.

Social media in knowledge translation and education for physicians and trainees: a scoping review.

INTRODUCTION: The use of social media is rapidly changing how educational content is delivered and knowledge is translated for physicians and trainees. This scoping review aims to aggregate and report trends on how health professions educators harness the power of social media to engage physicians for the purposes of knowledge translation and education. METHODS: A scoping review was conducted by searching four databases (PubMed, Scopus, Embase, and ERIC) for publications emerging between 1990 to March 2018. Articles about social media usage for teaching physicians or their trainees for the purposes of knowledge translation or education were included. Relevant themes and trends were extracted and mapped for visualization and reporting, primarily using the Cook, Bordage, and Schmidt framework for types of educational studies (Description, Justification, and Clarification). RESULTS: There has been a steady increase in knowledge translation and education-related social media literature amongst physicians and their trainees since 1996. Prominent platforms include Twitter (n = 157), blogs (n = 104), Facebook (n = 103), and podcasts (n = 72). Dominant types of scholarship tended to be descriptive studies and innovation reports. Themes related to practice improvement, descriptions of the types of technology, and evidence-based practice were prominently featured. CONCLUSIONS: Social media is ubiquitously used for knowledge translation and education targeting physicians and physician trainees. Some best practices have emerged despite the transient nature of various social media platforms. Researchers and educators may engage with physicians and their trainees using these platforms to increase uptake of new knowledge and affect change in the clinical environment.