Value Of Translational Research Research Articles

A New American University Model for Training the Future MCH Workforce Through a Translational Research Team

ObjectivesTo describe the process of developing and implementing experiential learning through translational research teams that engage diverse undergraduate and graduate students.MethodsAfter a college redesign, translational research teams were developed to foster multidisciplinary research and better integrate students with faculty research, community, and clinical activities. Three primary approaches were used to engage undergraduate and graduate students in the maternal and child health translational research team (MCH TrT). These included an undergraduate experiential learning course; participation in translational research team meetings and events; and mentorship activities including graduate student theses and supplementary projects.ResultsSince 2019, a total of 56 students have engaged with the MCH translational research team. The majority (64%) of students engaging in translational research were undergraduates. Racial and ethnic diversity was evident with 16% Latinx, 14% Black/African American, 12% Asian, 10% two or more races, and 4% Native American or Native Hawaiian. A large proportion (42%) of students indicated that they were first-generation college students, while 24% indicated they had a disability. Five themes emerged from student feedback about their involvement in the experiential learning course: the value of translational research, development of research skills, collaboration, practice development, and value for community partners.Conclusions for PracticeThrough an MCH translational research team, we have established a pathway to enhance diversity among the MCH workforce which will increase recruitment and retention of underrepresented groups, and ultimately improve MCH research and practice.

Preclinical models of endometriosis and interstitial cystitis/bladder pain syndrome: an Innovative Medicines Initiative-PainCare initiative to improve their value for translational research in pelvic pain.

Endometriosis (ENDO) and interstitial cystitis/bladder pain syndrome (IC/BPS) are chronic pain conditions for which better treatments are urgently needed. Development of new therapies with proven clinical benefit has been slow. We have conducted a review of existing preclinical in vivo models for ENDO and IC/BPS in rodents, discussed to what extent they replicate the phenotype and pain experience of patients, as well as their relevance for translational research. In 1009 publications detailing ENDO models, 41% used autologous, 26% syngeneic, 18% xenograft, and 11% allogeneic tissue in transplantation models. Intraperitoneal injection of endometrial tissue was the subcategory with the highest construct validity score for translational research. From 1055 IC/BPS publications, most interventions were bladder centric (85%), followed by complex mechanisms (8%) and stress-induced models (7%). Within these categories, the most frequently used models were instillation of irritants (92%), autoimmune (43%), and water avoidance stress (39%), respectively. Notably, although pelvic pain is a hallmark of both conditions and a key endpoint for development of novel therapies, only a small proportion of the studies (models of ENDO: 0.5%-12% and models of IC/BPS: 20%-44%) examined endpoints associated with pain. Moreover, only 2% and 3% of publications using models of ENDO and IC/BPS investigated nonevoked pain endpoints. This analysis highlights the wide variety of models used, limiting reproducibility and translation of results. We recommend refining models so that they better reflect clinical reality, sharing protocols, and using standardized endpoints to improve reproducibility. We are addressing this in our project Innovative Medicines Initiative-PainCare/Translational Research in Pelvic Pain.

Magnetic Resonance Imaging for Drug Development.

Given the merit of high-resolution cross-sectional imaging, magnetic resonance imaging (MRI) has been utilized in many preclinical and clinical research fields. In addition to T2-weighted imaging for assessing anatomic changes by disease and therapeutic agents, diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy can provide disease- and drug-specific functional information in both in vivo and ex vivo status. Another advantage of MRI is its ability to bridge the preclinical and clinical experiments as it allows similar study methods and environments between animals and humans. Therefore, MRI can be used as a useful tool for drug development. Investigators have discovered a variety of MRI biomarkers that can quantitatively measure the biological alteration led by disease and treatment. In this chapter, a number of commonly used preclinical MRI biomarkers for drug development will be introduced and discussed, particularly being focused on their value for translational research.

Indispensability of Clinical Bioinformatics for Effective Implementation of Genomic Medicine in Pathology Laboratories

AbstractPatient care is rapidly evolving toward the inclusion of precision genomic medicine when genomic tests are used by clinicians to determine disease predisposition, prognosis, diagnosis, and improve therapeutic decision-making. However, unlike other clinical pathology laboratory tests, the development, deployment, and delivery of genomic tests and results are an intricate process. Genomic technologies are diverse, fast changing, and generate massive data. Implementation of these technologies in a Clinical Laboratory Improvement Amendments-certified and College of American Pathologists-accredited pathology laboratory often require custom clinical grade computational data analysis and management workflows. Additionally, accurate classification and reporting of clinically actionable genetic mutation requires well-curated disease/application-specific knowledgebases and expertise. Moreover, lack of “out of the box” technical features in electronic health record systems necessitates custom solutions for communicating genetic information to clinicians and patients. Genomic data generated as part of clinical care easily adds great value for translational research. In this article, we discuss current and future innovative clinical bioinformatics solutions and workflows developed at our institution for effective implementation of precision genomic medicine across molecular pathology, patient care, and translational genomic research.

Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research.

In 1989 ILAR published a list and description of immunodeficient rodents used in research. Since then, advances in understanding of molecular mechanisms; recognition of genetic, epigenetic microbial, and other influences on immunity; and capabilities in manipulating genomes and microbiomes have increased options and opportunities for selecting mice and designing studies to answer important mechanistic and therapeutic questions. Despite numerous scientific breakthroughs that have benefitted from research in mice, there is debate about the relevance and predictive or translational value of research in mice. Reproducibility of results obtained from mice and other research models also is a well-publicized concern. This review summarizes resources to inform the selection and use of immune relevant mouse strains and stocks, aiming to improve the utility, validity, and reproducibility of research in mice. Immune sufficient genetic variations, immune relevant spontaneous mutations, immunodeficient and autoimmune phenotypes, and selected induced conditions are emphasized.

Clinical profi ling of patients with peripartum cardiomyopathy and its value for translational research

Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology and exposes women to high risk of mortality after delivery despite optimal medical therapy. Experimental data suggested that enhanced oxidative stress promotes the proteolytical processing of the lactation hormone prolactin into a biologically active derivative, the 16kDa prolactin, which appears to be a major cause for PPCM. We observed increased oxLDL levels in a subset of these PPCM patients, indicative of oxidative stress, enhanced Cathepsin D activity and substantial levels of the cleaved 16kDa form of prolactin. We therefore propose that the excessive generation of 16kDa prolactin mediates PPCM in humans and suggest that inhibition of prolactin release may represent a novel therapeutic strategy for PPCM.

Human umbilical endothelial cells (HUVECs) have a sex: characterisation of the phenotype of male and female cells.

BackgroundHuman umbilical endothelial cells (HUVECs) are widely used to study the endothelial physiology and pathology that might be involved in sex and gender differences detected at the cardiovascular level. This study evaluated whether HUVECs are sexually dimorphic in their morphological, proliferative and migratory properties and in the gene and protein expression of oestrogen and androgen receptors and nitric oxide synthase 3 (NOS3). Moreover, because autophagy is influenced by sex, its degree was analysed in male and female HUVECs (MHUVECs and FHUVECs).MethodsUmbilical cords from healthy, normal weight male and female neonates born to healthy non-obese and non-smoking women were studied. HUVEC morphology was analysed by electron microscopy, and their function was investigated by proliferation, viability, wound healing and chemotaxis assays. Gene and protein expression for oestrogen and androgen receptors and for NOS3 were evaluated by real-time PCR and Western blotting, respectively, and the expression of the primary molecules involved in autophagy regulation [protein kinase B (Akt), mammalian target of rapamycin (mTOR), beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)] were detected by Western blotting.ResultsCell proliferation, migration NOS3 mRNA and protein expression were significantly higher in FHUVECs than in MHUVECs. Conversely, beclin-1 and the LC3-II/LC3-I ratio were higher in MHUVECs than in FHUVECs, indicating that male cells are more autophagic than female cells. The expression of oestrogen and androgen receptor genes and proteins, the protein expression of Akt and mTOR and cellular size and shape were not influenced by sex. Body weights of male and female neonates were not significantly different, but the weight of male babies positively correlated with the weight of the mother, suggesting that the mother’s weight may exert a different influence on male and female babies.ConclusionsThe results indicate that sex differences exist in prenatal life and are parameter-specific, suggesting that HUVECs of both sexes should be used as an in vitro model to increase the quality and the translational value of research. The sex differences observed in HUVECs could be relevant in explaining the diseases of adulthood because endothelial dysfunction has a crucial role in the pathogenesis of cardiovascular diseases, diabetes mellitus, neurodegeneration and immune disease.

The translational research chain: is it delivering the goods?

Purpose: To address whether the translational research chain has influenced clinical practice in radiation oncology. Methods and Materials: Merits and limitations of the various steps of the translational chain, i.e., in vitro studies, animal experiments, biomathematical modeling, Phase I and II trials, and randomized Phase III trials are briefly reviewed. The process and value of translational research in radiation oncology are addressed using dose fractionation and the time factor in tumors as examples. Results: The examples show that translational research may indeed change clinical practice in radiation oncology. However, it takes several decades and considerable efforts to define and test new strategies. The “translational process” is by no means unidirectional but a continuing multiway dialog among basic scientists, applied scientists, clinical scientists, and clinical oncologists. Conclusion: Translational research works in radiation oncology, and it is difficult to conceive a better alternative for future improvement of therapy. The slow speed of the translational process indicates that there is a need for improving the various steps of the translational network and the interaction as a whole. Massive investments in one part of the network are likely to be at least partly wasted unless the other links are strengthened as well.