Translational Research Strategies Research Articles

Why Increased Focus on Aging With Disability Matters to Gerontology Research, Policy, and Practice

This symposium elaborates on the theme of the 2020 conference, “Why Age Matters”, to include aging with disability. We ask: “can an increased focus on aging with disability within gerontological research, policy, and practice advance our knowledge of disablement across the life cycle and improve our design and implementation of health and social service interventions’? Five experts will address this from differing perspectives (including gerontology and rehabilitation). One presentation draws on national/ regional data to illustrate the changing demographics of aging and disability and highlights the health consequences of aging with- and aging into, long-term physical disabilities. A second uses data from a mixed methods study to demonstrate the unique challenges experienced by adults aging with spinal cord injury with a focus on the impact of specific environmental barriers and facilitators to maintain health and participation in social roles. A third covers three reports on data from a scoping review to document the exclusion of middle-aged and older adults with disabilities from behavioral clinical trials and describes how translational research strategies can be used to help close this gap. A fourth presents examples of how technologies, such as videoconferencing and voice activation, are being used to deliver and enhance existing EB interventions to improve health, physical activity, and participation for individuals aging with mobility impairments. The last one draws on research and scholarly work from both gerontology and rehabilitation to highlight the co-occurring issues of ageism and ableism and describes how reducing ableism is central to successfully reframing aging. Lifelong Disabilities Interest Group Sponsored Symposium.

Underrepresentation of Adults and Older Adults With Disabilities in Behavioral Clinical Trials: A Scoping Review

A lack of evidence-based interventions for people aging with long-term physical disabilities exists. To examine the exclusion of people with disabilities in behavioral clinical trials, a scoping review was conducted. ClinicalTrials.gov was searched for interventional behavioral studies from the United States completed from 2008–2018, with results focused on adults (18–64) and older adults (65+). In total, 158 clinical trials were included. In 129 articles, health conditions were excluded 697 times. Seventy-one clinical trials excluded at least one health condition with strong justification, 11 with poor justification, and 115 without justification. There is strong evidence that people with disabilities are excluded from behavioral clinical trials, often without justification. To help close this gap, our presentation will discuss how translational research strategies, focused on adapting existing EB behavioral trials, can be used to increase the availability of interventions that address the needs of individuals aging with and into long-term disabilities. Part of a symposium sponsored by the Lifelong Disabilities Interest Group.

Exploring the role of RALYL in Alzheimer\u2019s disease reserve by network-based approaches

BackgroundAlzheimer’s disease (AD) reserve theory is based on specific individual characteristics that are associated with a higher resilience against neurodegeneration and its symptoms. A given degree of AD pathology may contribute to varying cognitive decline levels in different individuals. Although this phenomenon is attributed to reserve, the biological mechanisms that underpin it remain elusive, which restricts translational medicine research and treatment strategy development.MethodsNetwork-based approaches were integrated to identify AD reserve related genes. Then, AD brain transcriptomics data were clustered into co-expression modules, and a Bayesian network was developed using these modules plus AD reserve related phenotypes. The directed acyclic graph suggested that the module was strongly associated with AD reserve. The hub gene of the module of interest was filtered using the topological method. Validation was performed in the multi-AD brain transcriptomic dataset.ResultsWe revealed that the RALYL (RALY RNA Binding Protein-like) is the hub gene of the module which was highly associated with AD reserve related phenotypes. Pseudo-time projections of RALYL revealed the changes in relative expression drivers in the AD and control subjects over pseudo-time had distinct transcriptional states. Notably, the expression of RALYL decreased with the gradual progression of AD, and this corresponded to MMSE decline. Subjects with AD reserve exhibited significantly higher RALYL expression than those without AD reserve.ConclusionThe present study suggests that RALYL may be associated with AD reserve, and it provides novel insights into the mechanisms of AD reserve and highlights the potential role of RALYL in this process.

Overcoming Barriers in Clinical Acupuncture Research: Translating Clinical Practice into Fundamental Science.

Background: The translation of clinical practice into research presents unique challenges. This is especially the case in evaluating the effect of interventions in the management of chronic conditions such as pain, mental health, substance misuse, and oncology care. Chronic complex conditions might respond to different strategies at different points in time and may require an interdisciplinary approach to treatment. Objectives: To define the key barriers to the design, implementation, and evaluation of clinical trials of acupuncture that derive from a unidirectional translational research strategy. Results: Critical challenges to the design, implementation, and evaluation of clinical trials of acupuncture center around four areas: (1) insufficient early phase research, (2) suboptimal treatment protocols, (3) inadequate research questions, and 4) a narrowed assessment of outcomes. Conclusions: By promoting research priorities that reflect the complex nature of chronic illness, we can more clearly articulate research questions that better reflect clinical practice, while evaluating the impact of acupuncture in patient care. Key priorities include phase I research funding opportunities, pragmatic trials that evaluate acupuncture embedded in interprofessional teams, and the inclusion of hypothesis-driven secondary outcomes.

50th anniversary of the first clinical trial with ICI 46,474 (tamoxifen): then what happened?

Following the discovery and approval of the oral contraceptive, the pharmaceutical industry sought new opportunities for the regulation of reproduction. The discovery of the first non-steroidal anti-oestrogen MER25, with antifertility properties in laboratory animals, started a search for 'morning-after pills'. There were multiple options in the 1960s, however, one compound ICI 46,474 was investigated, but found to induce ovulation in subfertile women. A second option was to treat stage IV breast cancer. Although the patent for ICI 46,474 was awarded in the early 1960s in the UK and around the world, a patent in the USA was denied on the basis that the claims for breast cancer treatment were not supported by evidence. A trial at the Christie Hospital and Holt Radium Institute in Manchester, published in 1971, showed activity compared with alternatives: high-dose oestrogen or androgen treatment, but the US Patent Office was unswayed until 1985! The future of tamoxifen to be, was in the balance in 1972 but the project went forward as an orphan drug looking for applications and a translational research strategy was needed. Today, tamoxifen is known as the first targeted therapy in cancer with successful applications to treat all stages of breast cancer, male breast cancer, and the first medicine for the reduction of breast cancer incidence in high-risk pre- and post-menopausal women. This is the unlikely story of how an orphan medicine changed medical practice around the world, with millions of women's lives extended.

Translational research to support early childhood education in crisis settings: a case study of collaborative working with Rohingya refugees in Cox’s Bazar

ABSTRACT This case study used a co-creation approach to evaluate the effectiveness of a translational research strategy in supporting early childhood education. How Mapping Educational Specialist Knowhow (MESH) and Voluntary Service Overseas (VSO) collaborated to enhance the training of volunteers and learning provision for 1,500 refugee children is explored. The findings highlight that: training empowered a marginalised community to enhance children’s learning; language variation was a challenge; common values enabled effective partnership working between MESH and VSO; maintaining the relationship is vital for developing socio-culturally relevant resources; MESHGuides have great potential although features could be redesigned to increase impact. The strategy addressed United Nations Sustainable Development Goal (SGG) 4, to improve the quality of education for all and SDG 5, to enhance gender opportunities for girls and women.

How practitioners between bench and bedside evaluate biomedical translation?

AbstractWhile translational research (TR) aims at changing regulatory and organizational practices in the biomedical field, surprisingly little is known about how practitioners in the lab or the clinic think about translation. Addressing this gap, we present results from a Q-methodological study on the meanings and values associated with translation held by researchers, clinicians, and clinician scientists at two major German biomedical research institutions implementing TR strategies. We identify eight different collective understandings of translation, with respect to both where primary translational problems are located and what the most immediate and effective measures should be. Our findings suggest that there may not be a one-fits-all solution for improving translation and that general regulatory and organizational measures may be less effective than measures addressing specific audiences and their specific viewpoints. TR does, however, work well as an umbrella term in stimulating and orchestrating a productive interaction between various viewpoints, practices, and contexts.

In Vitro Blood-Brain Barrier-Integrated Neurological Disorder Models Using a Microfluidic Device.

The blood–brain barrier (BBB) plays critical role in the human physiological system such as protection of the central nervous system (CNS) from external materials in the blood vessel, including toxicants and drugs for several neurological disorders, a critical type of human disease. Therefore, suitable in vitro BBB models with fluidic flow to mimic the shear stress and supply of nutrients have been developed. Neurological disorder has also been investigated for developing realistic models that allow advance fundamental and translational research and effective therapeutic strategy design. Here, we discuss introduction of the blood–brain barrier in neurological disorder models by leveraging a recently developed microfluidic system and human organ-on-a-chip system. Such models could provide an effective drug screening platform and facilitate personalized therapy of several neurological diseases.

Oral Mucosal Injury Caused by Targeted Cancer Therapies.

Targeted cancer therapies have fundamentally transformed the treatment of many types of cancers over the past decade, including breast, colorectal, lung, and pancreatic cancers, as well as lymphoma, leukemia, and multiple myeloma. The unique mechanisms of action of these agents have resulted in many patients experiencing enhanced tumor response together with a reduced adverse event profile as well. Toxicities do continue to occur, however, and in selected cases can be clinically challenging to manage. Of particular importance in the context of this monograph is that the pathobiology for oral mucosal lesions caused by targeted cancer therapies has only been preliminarily investigated. There is distinct need for novel basic, translational, and clinical research strategies to enhance design of preventive and therapeutic approaches for patients at risk for development of these lesions. The research modeling can be conceptually enhanced by extrapolating "lessons learned" from selected oral mucosal conditions in patients without cancer as well. This approach may permit determination of the extent to which pathobiology and clinical management are either similar to or uniquely distinct from oral mucosal lesions caused by targeted cancer therapies. Modeling associated with oral mucosal disease in non-oncology patients is thus presented in this context as well. This article addresses this emerging paradigm, with emphasis on current mechanistic modeling and clinical treatment. This approach is in turn designed to foster delineation of new research strategies, with the goal of enhancing cancer patient treatment in the future.

Research Recommendations From the National Institutes of Health Workshop on Predicting, Preventing, and Treating Preeclampsia

Preeclampsia (PE) is a pregnancy-specific, multisystemic disorder that occurs in roughly 5% of pregnancies in the United States.1,2 The rates of PE in the United States have been steadily rising over the past 30 years with PE being a leading cause of maternal and fetal/neonatal morbidity and mortality.3 Women with PE, as well as their offspring, are at greater risk for chronic diseases, including cardiovascular disease (CVD) later in life.4,5 Despite being the leading cause of maternal death and a major contributor to maternal and perinatal morbidity, drug treatment to prevent PE is at best minimally effective, and current management therapies have significant limitations. In fact, at present, delivery is considered the only effective intervention for treating PE6 and even then PE may continue in the postpartum period or present de novo.7 The lack of progress in identifying new therapeutic targets for the treatment of PE is due in part to a paucity of animal models that address the heterogeneity of human PE as well as lack of understanding of basic disease mechanisms. There are no models of spontaneously developing PE in animals. Developing novel animal models to mimic human PE, identifying biomarkers to predict PE, conducting basic studies to better understand disease mechanisms, and ultimately, developing novel therapeutic strategies are clearly needed. The National Heart, Lung, and Blood Institute (NHLBI), in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), held a workshop to examine the topic of Predicting, Preventing and Treating Preeclampsia on May 21–22, 2018, in Bethesda, MD. Speakers were chosen for expertise in general areas identified as important and cutting edge by the organizers. Specific topics discussed during the workshop were: i) pathophysiology of PE; ii) immunological origins of PE; iii) how to define subsets of PE; iv) biomarkers; v) nutritional factors; vi) genetics and epigenetics; vii) animal models; viii) collaboration, harmonization, sharing large data and samples sets in the study of PE; ix) periconceptional contributors to pathophysiology; x) clinical risk factors for PE; xi) novel therapies for the prevention and treatment of PE; xii) long-term cardiovascular consequences of PE and xiii) patient perspectives. Based on these discussions, recommendations for future research were developed in the following general areas: 1) Pathophysiology of PE; 2) Impact of PE on long-term health outcomes; 3) Biomarkers and diagnostic tools; 4) Translational research and novel treatment strategies. The purpose of this report is to summarize the scientific research recommendations arising from deliberations of the invited speakers and meeting attendees. These research recommendations are summarized in Table 1 (which is keyed to the manuscript text) and are presented in no particular order of priority. The goal of the recommendations is to provide guidance regarding future research on PE and its short- and long-term consequences. Table1: Summary of recommendations from the NIH workshop on “Predicting, Preventing and Treating Preeclampsia”

Biobanking: Objectives, Requirements, and Future Challenges-Experiences from the Munich Vascular Biobank.

Collecting biological tissue samples in a biobank grants a unique opportunity to validate diagnostic and therapeutic strategies for translational and clinical research. In the present work, we provide our long-standing experience in establishing and maintaining a biobank of vascular tissue samples, including the evaluation of tissue quality, especially in formalin-fixed paraffin-embedded specimens (FFPE). Our Munich Vascular Biobank includes, thus far, vascular biomaterial from patients with high-grade carotid artery stenosis (n = 1567), peripheral arterial disease (n = 703), and abdominal aortic aneurysm (n = 481) from our Department of Vascular and Endovascular Surgery (January 2004–December 2018). Vascular tissue samples are continuously processed and characterized to assess tissue morphology, histological quality, cellular composition, inflammation, calcification, neovascularization, and the content of elastin and collagen fibers. Atherosclerotic plaques are further classified in accordance with the American Heart Association (AHA), and plaque stability is determined. In order to assess the quality of RNA from FFPE tissue samples over time (2009–2018), RNA integrity number (RIN) and the extent of RNA fragmentation were evaluated. Expression analysis was performed with two housekeeping genes—glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB)—using TaqMan-based quantitative reverse-transcription polymerase chain reaction (qRT)-PCR. FFPE biospecimens demonstrated unaltered RNA stability over time for up to 10 years. Furthermore, we provide a protocol for processing tissue samples in our Munich Vascular Biobank. In this work, we demonstrate that biobanking is an important tool not only for scientific research but also for clinical usage and personalized medicine.

New insights into acquired endocrine resistance of breast cancer.

The translational research strategy of targeting estrogen receptor α (ERα) positive breast cancer and then using long term anti-hormone adjuvant therapy (5-10 years) has reduced recurrences and mortality. However, resistance continues to occur and improvements are required to build on the success of tamoxifen and aromatase inhibitors (AIs) established over the past 40 years. Further translational research has described the evolution of acquired resistance of breast cancer cell lines to long term estrogen deprivation that parallels clinical experience over years. Additionally, recent reports have identified mutations in the ERα obtained from the recurrences of AI treated patients. These mutations allow the ERα to activate without ligands and auto stimulate metastatic tumor growth. Furthermore, the new biology of estrogen-induced apoptosis in acquired resistant models in vitro and in vivo has been interrogated and applied to clinical trials. Inflammation and stress are emerging concepts occurring in the process of acquired resistance and estrogen-induced apoptosis with different mechanisms. In this review, we will present progress in the understanding of acquired resistance, focus on stress and inflammatory responses in the development of acquired resistance, and consider approaches to create new treatments to improve the treatment of breast cancer with endocrine resistance.

Translational Molecular Approaches in Substance Abuse Research.

Excessive abuse of psychoactive substances is one of the leading contributors to morbidity and mortality worldwide. In this book chapter, we review translational research strategies that are applied in the pursuit of new and more effective therapeutics for substance use disorder (SUD). The complex, multidimensional nature of psychiatric disorders like SUD presents difficult challenges to investigators. While animal models are critical for outlining the mechanistic relationships between defined behaviors and genetic and/or molecular changes, the heterogeneous pathophysiology of brain diseases is uniquely human, necessitating the use of human studies and translational research schemes. Translational research describes a cross-species approach in which findings from human patient-based data can be used to guide molecular genetic investigations in preclinical animal models in order to delineate the mechanisms of reward circuitry changes in the addicted state. Results from animal studies can then inform clinical investigations toward the development of novel treatments for SUD. Here we describe the strategies that are used to identify and functionally validate genetic variants in the human genome which may contribute to increased risk for SUD, starting from early candidate gene approaches to more recent genome-wide association studies. We will next examine studies aimed at understanding how transcriptional and epigenetic dysregulation in SUD can persistently alter cellular function in the disease state. In our discussion, we then focus on examples from the literature illustrating molecular genetic methodologies that have been applied to studies of different substances of abuse - from alcohol and nicotine to stimulants and opioids - in order to exemplify how these approaches can both delineate the underlying molecular systems driving drug addiction and provide insights into the genetic basis of SUD.

Methods for High-Resolution Electrical Mapping in the Gastrointestinal Tract.

Over the last two decades, high-resolution (HR) mapping has emerged as a powerful technique to study normal and abnormal bioelectrical events in the gastrointestinal (GI) tract. This technique, adapted from cardiology, involves the use of dense arrays of electrodes to track bioelectrical sequences in fine spatiotemporal detail. HR mapping has now been applied in many significant GI experimental studies informing and clarifying both normal physiology and arrhythmic behaviors in disease states. This review provides a comprehensive and critical analysis of current methodologies for HR electrical mapping in the GI tract, including extracellular measurement principles, electrode design and mapping devices, signal processing and visualization techniques, and translational research strategies. The scope of the review encompasses the broad application of GI HR methods from in vitro tissue studies to in vivo experimental studies, including in humans. Controversies and future directions for GI mapping methodologies are addressed, including emerging opportunities to better inform diagnostics and care in patients with functional gut disorders of diverse etiologies.

Transdisciplinary Assistance and Translational Research Strategies to Improve the Quality of Life of Older Adults at Early Stages of Alzheimer Disease

Transdisciplinary Assistance and Translational Research Strategies to Improve the Quality of Life of Older Adults at Early Stages of Alzheimer Disease

Phylogenetic relationships, stage-specific expression and localisation of a unique family of inactive cysteine proteases in Sarcoptes scabiei

BackgroundScabies is worldwide one of the most common, yet neglected, parasitic skin infections, affecting a wide range of mammals including humans. Limited treatment options and evidence of emerging mite resistance against the currently used drugs drive our research to explore new therapeutic candidates. Previously, we discovered a multicopy family of genes encoding cysteine proteases with their catalytic sites inactivated by mutation (SMIPP-Cs). This protein family is unique in parasitic scabies mites and is absent in related non-burrowing mites. We postulated that the SMIPP-Cs have evolved as an adaptation to the parasitic lifestyle of the scabies mite. To formulate testable hypotheses for their functions and to propose possible strategies for translational research we investigated whether the SMIPP-Cs are common to all scabies mite varieties and where within the mite body as well as when throughout the parasitic life-cycle they are expressed.ResultsSMIPP-C sequences from human, pig and dog mites were analysed bioinformatically and the phylogenetic relationships between the SMIPP-C multi-copy gene families of human, pig and dog mites were established. Results suggest that amplification of the SMIPP-C genes occurred in a common ancestor and individual genes evolved independently in the different mite varieties. Recombinant human mite SMIPP-C proteins were produced and used for murine polyclonal antibody production. Immunohistology on skin sections from human patients localised the SMIPP-Cs in the mite gut and in mite faeces within in the epidermal skin burrows. SMIPP-C transcription into mRNA in different life stages was assessed in human and pig mites by reverse transcription followed by droplet digital PCR (ddPCR). High transcription levels of SMIPP-C genes were detected in the adult female life stage in comparison to all other life stages.ConclusionsThe fact that the SMIPP-Cs are unique to three Sarcoptes varieties, present in all burrowing life stages and highly expressed in the digestive system of the infective adult female life stage may highlight an essential role in parasitism. As they are excreted from the gut in scybala they presumably are able to interact or interfere with host proteins present in the epidermis.

Highlights of This Issue

Prospective prediction and mechanistic understanding of drug penetration across human blood-brain barrier (BBB) are critical to rational drug development and therapy for brain cancer. By using a translational research strategy that leverages preclinical studies, pharmacokinetic modeling, and clinical trials, Li and colleagues developed an IVIVE-PBPK modeling approach for quantitatively and mechanistically understanding tumor penetration of AZD1775 in glioblastoma patients. The knowledge and tool generated are of enormous value to the field of quantitative pharmacology and also to the development of more effective therapies for brain cancer, where sufficient drug brain penetration is the prerequisite for efficacy.Mutation signatures of homologous recombination deficiency (HRD) have recently been shown to be prevalent in many cancer types. To examine their clinical implications, Zhao and colleagues performed whole-genome sequencing of 93 breast cancers, 33 of which were treated with platinum-based chemotherapy. They quantified 6 HRD-associated mutation signatures shown to robustly predict BRCA1/2 status. Their observational analysis found that these HRD signatures also were associated with improved outcomes and treatment durations on platinum-based chemotherapy. They demonstrate an approach for computing HRD signatures, which may aid in the clinical translation of this potential predictive biomarker.Philadelphia chromosome positive acute lymphoblastic leukemia (BCR-ABL+ B-ALL) has poor prognosis in both pediatric and adult patients with the disease-free survival of 25%–30% in children and less than 20% in adults. Antiapoptotic MCL-1 is essential for the survival of BCR-ABL+ leukemic cells and they are resistant to BH3-mimetic navitoclax. Budhraja and colleagues identified that dihydroartemisinin (DHA), an antimalarial drug, represses MCL-1 expression and sensitizes BCR-ABL+ B-ALL cells to synergistic killing by navitoclax in vitro in patient-derived xenografts and in mouse models. The data suggested that combination of DHA and navitoclax could have implications to improve therapeutic response in BCR-ABL+ B-ALL.The high prevalence of AR in ER+ breast cancer along with the preclinical and clinical efficacy of classic androgens provide rationale for developing a new generation of selective AR agonist for this indication. Yu and colleagues report that RAD140, an oral, tissue-selective androgen receptor modulator (SARM), significantly inhibits the growth of AR/ER+ breast cancer models, an effect further enhanced by the coadministration of CDK4/6 inhibitor. Importantly, RAD140 treatment led to substantial decrease in ESR1 mRNA, suggesting a distinct AR-mediated mechanism of action compared with the agents targeting ER protein. RAD140 is now being evaluated in recurrent ER+ breast cancer.

Immunity and stroke, the hurdles of stroke research translation.

Immunomodulatory therapies after stroke have the potential to provide clinical benefit to a subset of patients, but risk subverting the protective, healing aspects of the innate immune response. Neutrophils clear necrotic cerebral tissue and are important in immunomodulation, but can also contribute to tissue injury. Human trials for immunomodulatory stroke treatments in the sub-acute time frame have attempted to prevent peripheral neutrophil infiltration, but none have been successful and one trial demonstrated harm. These unselected trials had broad inclusion criteria and appear to not have had a specific treatment target. Unfortunately, due to the heterogeneous nature of brain ischemia in humans resulting in variation in clinical severity, the negative effect of thrombolytic drugs on the blood-brain barrier, and the heterogeneity of immune response, it may only be a subset of stroke patients who can realistically benefit from immunomodulation therapies. Translational research strategies require both an understanding of lab practices which create highly controlled environments in contrast to clinical practice where the diagnosis of stroke does not require the identification of a vessel occlusion. These differences between lab and clinical practices can be resolved through the integration of appropriate patient selection criteria and use of advanced imaging and ridged patient selection practices in clinical trials which will be an important part to the success of any future trials of translational research such as immunomodulation.

Group II mGluRs suppress hyperexcitability in mouse and human nociceptors.

We introduce a strategy for preclinical research wherein promising targets for analgesia are tested in rodent and subsequently validated in human sensory neurons. We evaluate group II metabotropic glutamate receptors, the activation of which is efficacious in rodent models of pain. Immunohistochemical analysis showed positive immunoreactivity for mGlu2 in rodent dorsal root ganglia (DRG), peripheral fibers in skin, and central labeling in the spinal dorsal horn. We also found mGlu2-positive immunoreactivity in human neonatal and adult DRG. RNA-seq analysis of mouse and human DRG revealed a comparative expression profile between species for group II mGluRs and for opioid receptors. In rodent sensory neurons under basal conditions, activation of group II mGluRs with a selective group II agonist produced no changes to membrane excitability. However, membrane hyperexcitability in sensory neurons exposed to the inflammatory mediator prostaglandin E2 (PGE2) was prevented by (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC). In human sensory neurons from donors without a history of chronic pain, we show that PGE2 produced hyperexcitability that was similarly blocked by group II mGluR activation. These results reveal a mechanism for peripheral analgesia likely shared by mice and humans and demonstrate a translational research strategy to improve preclinical validation of novel analgesics using cultured human sensory neurons.

Translational research at NASA: From earth to space and back again

The Space Environment provides many challenges to the human physiology and therefore to extended habitation and exploration. Translational research and medical strategies are meeting these challenges by combining Earth based medical solutions with innovative and developmental engineering approaches. Translational methodologies are currently applied to spaceflight related dysregulations in the areas of: (1) cardiovascular fluid shifts, intracranial hypertension and neuro-ocular impairment 2) immune insufficiency and suppression/viral re-expression, 3) bone loss and fragility (osteopenia/osteoporosis) and muscle wasting, and finally 4) radiation sensitivity and advanced ageing. Over 40 years of research into these areas have met with limited success due to lack of tools and basic understanding of central issues that cause physiologic maladaptation and disrupt homeostasis. We will discuss the effects of living in space (reduced gravity, bone and muscle loss, increased radiation and varying atmospheric conditions [EVA]) during long-duration, exploration-class missions and how translational research has benefited not only space exploration but also Earth based medicine. Modern tools such as telemedicine advances in genomics, proteomics, and metabolomics (Omics-sciences) has helped address syndromes, at the systemic level by enlisting a global approach to assessing spaceflight physiology and to develop countermeasures thereby permitting our experience in space to be translated to the Earth’s medical community.Abstracts included in the manuscript are selected by the editors. The manuscript does not contain all the conference abstracts.