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Purpose of Review: After decades of hype, cell-based therapies are emerging into the clinical arena for the purposes of promoting recovery after stroke. In this review, we discuss the most recent science behind the role of cell-based therapies in ischemic stroke and the efforts to translate these therapies into human clinical trials., Recent Findings: Preclinical data support numerous beneficial effects of cell-based therapies in both small and large animal models of ischemic stroke. These benefits are driven by multifaceted mechanisms promoting brain repair through immunomodulation, trophic support, circuit reorganization, and cell replacement. Cell-based therapies offer tremendous potential for improving outcomes after stroke through multimodal support of brain repair. Based on recent clinical trials, cell-based therapies appear both feasible and safe in all phases of stroke. Ongoing translational research and clinical trials will further refine these therapies and have the potential to transform the approach to stroke recovery and rehabilitation.

Fifteen years after the completion of first human genome sequencing, the technique is almost a commodity but there is still little evidence of its usefulness as a diagnostic, prognostic or therapeutic tool. In France, the France genomics plan 2025 was launched in 2015 with the goal of integrating genomic tests into clinical practice and developing a National genomics network including industrial partnerships. Reflection on scientific applications and operational or societal issues is needed to make recommendations to help better associate Genomics and the medicine of tomorrow. In the perspective of personalized Evidence-based Medicine, studies with an appropriate methodological level to improve the definition of evidence should be promoted. The many operational challenges require the implementation of organisations and means to streamline the process of results reporting, and regulatory adaptations concerning the status of professions involved, the management of data generated, and the consent of patients. In parallel, genetic training for healthcare professionals and raising awareness on genetic tests for the public should be considered. The ethical stake should also be taken into account, especially on the participation of the patient in decisions concerning them and integrating the notion of uncertainty into the information given. The sociological effects on the experience and expectations of patients and the general population towards genomic medicine should also be evaluated to improve information, prevention and support for people. Finally, medico-economic studies must be conducted to inform policy-makers on the cost-effectiveness of complete genome sequencing for population health., (Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Placental pathology is a key modality for determining placental health during pregnancy, especially in the event of adverse pregnancy outcomes. However, issues with standardization in placental diagnosis, reporting practices and clinical translation prevent this modality from being used to its full potential. This article will highlight these standardization issues and summarize ongoing work in this field to overcome them. Additionally, we propose a synoptic reporting framework for placental pathology based on current consensus guidelines, aimed at enhancing the comprehensiveness and quality of reporting placental findings. We believe this approach will improve our understanding of the placenta in adverse pregnancy outcomes and, importantly, offer the opportunity to increase knowledge translation to key stakeholder groups including patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Electrophysiology is a direct measure of neuronal processes, and it is uniquely sensitive to canonical neural operations that underlie emergent psychological operations. These qualities make it well suited for discovery of aberrant neural mechanisms that underlie complicated disease states. This technique is routinely utilized in vitro, in vivo, and in outpatient neurological clinics, offering a translatable bridge between animal models and human patients. The bench-to-bedside potential of this approach is unparalleled, yet it also remains undeveloped due to the slow inertia of legacy techniques and interpretations. In this review, I discuss these strengths of the method, and I detail compelling reasons why future advancements can have a direct and tangible influence over clinical practice. I hope to motivate a blurring of traditional boundaries between preclinical, computational, imaging, and clinical fields by advancing electrophysiology as a common hub for methodological integration and theoretical advancement., (© 2018 Society for Psychophysiological Research.)

The diagnosis, prognosis and treatment of cancer has had a great improvement due to the "omics" technologies such as genomics, proteomics, epigenomics, pharmacogenomics, and metabolomics. The technological progress of these technologies has allowed precision medicine to become a clinical reality. The study of different biomolecules such as DNA, RNA and proteins has helped to detect alterations in genes, changes in gene expression profiles and loss or gain of protein function, which allows us to make associations and better understand the cancer biology. Data obtained from different "omics" technologies gives a complementary spectrum of information that helps us to understand and unveil new information for a better diagnosis, prognosis, prediction of new molecular targets of anticancer therapies, etc. This chapter presents a general landscape of the interaction between the Pharmaco-Geno-Proteo-Metabolomic and translational medicine research in cancer.

Epigenomics refers to the study of genome-wide changes in epigenetic mechanisms including DNA methylation, histone modifications and non-coding RNAs expression. The alterations in normal DNA methylation and histone acetylation/deacetylation patterns lead to deregulated transcription and chromatin organization resulting in altered gene expression profiles that facilitates tumor development and progression. In consequence, novel therapeutic strategies aimed at reversing aberrant epigenetic marks in cancer cells have been developed and used in recent molecular studies and clinical trials. Pharmaco-epigenomics is a research area, which refers to the study of epigenome changes in cancer development and how chemotherapeutic agents can reverse these aberrant epigenetic marks by targeting the epigenetic machinery. Besides, the effects of genome-wide polymorphisms in populations leading to variations in drug response are also study subject of pharmaco-epigenomics and are being studied extensively in cancer. Recent findings showed that drug response could be largely influenced by the presence of aberrant epigenetic marks of the whole genome. This implies that biological pathways and cellular processes are under the impact of epigenome status. However, data about the relationship between drug response and the epigenomic variations is still scarce mainly because the epigenome is highly variable between individuals. The present chapter reviewed the advances on the epigenetics changes mainly DNA methylation and histones modifications on cervical and breast human cancers. A special emphasis in how they could be used as targets for the development and use of novel drugs in cancer therapy is delineated.

High-quality biobanking within routine health services, through the use of existing health-care practices and infrastructure, with respect to safety and integrity of patients in line with the Swedish Biobank Act, enables large-scale collection of biological material at reasonable costs. Complementing the extensive information on myocardial infarction patients from a national registry gives unique opportunities for research focusing on better understanding of cardiovascular disease occurrence and prognosis, developing of new diagnostic methods, and personalized treatments with greater efficacy and fewer side effects.

From the time it was conceptualized in 1998 to the present, RNAS + has largely concentrated on research that will generate results to facilitate control, prevention and elimination of its target diseases. Diagnostics has remained an active field of research in order to develop tools that are appropriate for each stage from the first efforts until attempts to block transmission. For example, with regard to schistosomiasis, chemotherapy has excellent impact on morbidity, while better diagnostics and vaccine research have been promoted to complement the other components of the control programme. The need for surveillance in areas where the prevalence has been brought down to very low levels necessitated development of spatio-temporal tools and ecological models based on geographical information systems (GIS) to produce risk and distribution maps for monitoring and evaluation of programme success. New knowledge and experiences in management of the diseases contribute to the formulation of new schemes in management and treatment. Ways of drawing attention to the disease, such as determining disability weights for use in computation of burden of disease, updating epidemiological profile and unravelling new aspects of the disease provide bases for modifying the operation of control programmes as we move forward. Programme evaluation based on reports of actual implementation of activities brought to the fore problems related to the distribution of chemotherapy as well as social, cultural and behavioural aspects of endemic communities. Importantly, this highlighted the necessity of adapting control activities to specific situations of the endemic areas. New models evolving from reviews of this kind and success stories, such us the elimination of lymphatic filariasis (LF) in PR China and Cambodia are presented., (© 2019 Elsevier Ltd All rights reserved.)

A growing body of literature has shown that stem cells are very effective for the treatment of degenerative diseases in rodents but these exciting results have not translated to clinical practice. The difference results from the divergence in genetic, metabolic, and physiological phenotypes between rodents and humans. The high degree of similarity between non-human primates (NHPs) and humans provides the most accurate models for preclinical studies of stem cell therapy. Using a NHP model to understand the following key issues, which cannot be addressed in humans or rodents, will be helpful for extending stem cell applications in the basic science and the clinic. These issues include pluripotency of primate stem cells, the safety and efficiency of stem cell therapy, and transplantation procedures of stem cells suitable for clinical translation. Here we review studies of the above issues in NHPs and current challenges of stem cell applications in both basic science and clinical therapies. We propose that the use of NHP models, in particular combining the serial production and transplantation procedures of stem cells is the most useful for preclinical studies designed to overcome these challenges.

Uppsala Clinical Research Center (UCR) is a non-profit organization that provides service for clinical research aiming for development and improvement of health care in Sweden and worldwide. UCR was started in 2001 with the ambition to shift the focus of clinical research from new medications or devices launched by the industry to problem-based research on issues identified in clinical reality, for example through the national quality registries. In order to accomplish these goals, UCR has established services in: 1) clinical trials of new and old methods in health care; 2) quality development of the health care system supported by internet-based national quality registries; 3) biostatistics, epidemiology, and data management; 4) biobanking of biological materials (Uppsala Biobank); 5) high-throughput biochemical analyses (UCR laboratory); and 6) academic leadership by the members of the UCR research faculty. The UCR clinical trials group provides services for investigator-driven projects in all areas of health care, for global mega-trials on new pharmaceutical treatments and devices, for biobanking including biomarker and genetics analyses, and for clinical events adjudication in national as well as global mega-trials. During the last few years, UCR has been a pioneer in establishing the registry-based randomized clinical trial (R-RCT), which today is an international model on how to perform cost-effective pragmatic randomized trials in the real-world environment. In 2002, UCR started the first national competence center for national quality registries, which pioneered the development of the current internet-based technologies for registering, reporting, and supporting continuous systematic improvement of health care. UCR is currently harboring around 20 national quality registries in all areas of health care. Today, UCR is the leading European center for registry-based quality development and evaluation of new medical treatments in cardiovascular care and has started to support other European countries in implementing the UCR registry platform in order to improve quality of care in the European Union.

Purpose: This article introduces the importance and nature of the role of the nurse scientist as a knowledge broker., Design: A systematic literature review was completed using a modified version of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) appraisal tool to trace the emergence and characteristics of the knowledge broker role across disciplines internationally and in the United States., Methods: Salient publications were identified using PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Sociological Abstracts, and ProQuest Dissertations & Theses, as well as hand searches and searches of the grey literature. Authors used these resources to define the knowledge broker role and with their role-related experiences developed the Thompson Knowledge Brokering Model., Findings: A knowledge broker is one who connects science and society by building networks and facilitating opportunities among knowledge producers and knowledge users. The knowledge broker role includes three components: forming and sustaining partnerships; facilitating knowledge application; and creating new knowledge. There are five major strategies central to each role component: establish, engage, educate, empower, and evaluate., Conclusions: The knowledge broker role has been increasingly recognized worldwide as key to translating science into practice and policy. The nurse scientist is ideally suited for this role and should be promoted worldwide. The Thompson Knowledge Brokering Model can be used as a guide for nurse scientists., Clinical Relevance: The role of the knowledge broker is to facilitate translation of useful research to practice and policy by connecting stakeholders through meaningful engagement., (© 2018 Sigma Theta Tau International.)

Pharmacogenomics (PGx) can be seen as a model for biomedical studies: it includes all disease areas of interest and spans in vitro studies to clinical trials, while focusing on the relationships between genes and drugs and the resulting phenotypes. This review will examine different characteristics of PGx study publications and provide examples of excellence in framing PGx questions and reporting their resulting data in a way that maximizes the knowledge that can be built on them., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)

From the mid-20th century, accumulating evidence has supported the introduction of screening for cancers of the cervix, breast, colon and rectum, prostate (via shared decisions), and lung. The opportunity to detect and treat precursor lesions and invasive disease at a more favorable stage has contributed substantially to reduced incidence, morbidity, and mortality. However, as new discoveries portend advancements in technology and risk-based screening, we fail to fulfill the greatest potential of the existing technology, in terms of both full access among the target population and the delivery of state-of-the art care at each crucial step in the cascade of events that characterize successful cancer screening. There also is insufficient commitment to invest in the development of new technologies, incentivize the development of new ideas, and rapidly evaluate promising new technology. In this report, the authors summarize the status of cancer screening and propose a blueprint for the nation to further advance the contribution of screening to cancer control., (© 2019 American Cancer Society.)

Scientific prizes confer credibility to persons, ideas, and disciplines, provide financial incentives, and promote community-building celebrations. We examine the growth dynamics and interlocking relationships found in the worldwide scientific prize network. We focus on understanding how the knowledge linkages among prizes and scientists' propensities for prizewinning relate to knowledge pathways between disciplines and stratification within disciplines. Our data cover more than 3,000 different scientific prizes in diverse disciplines and the career histories of 10,455 prizewinners worldwide for over 100 years. We find several key links between prizes and scientific advances. First, despite an explosive proliferation of prizes over time and across the globe, prizes are more concentrated within a relatively small group of scientific elites, and ties among elites are highly clustered, suggesting that a relatively constrained number of ideas and scholars push the boundaries of science. For example, 64.1% of prizewinners have won two prizes and 13.7% have won five or more prizes. Second, certain prizes strongly interlock disciplines and subdisciplines, creating key pathways by which knowledge spreads and is recognized across science. Third, genealogical and coauthorship networks predict who wins multiple prizes, which helps to explain the interconnectedness among celebrated scientists and their pathbreaking ideas., Competing Interests: The authors declare no conflict of interest.

The analysis of the state of innovation activity of NRCRM was carried out. The main types of innovation activity of the institution are highlighted, namely: creation and implementation of innovative product, innovative consulting. The perspective directions of its development were substantiated: increase of the level of implementation with the use of modern informational and publishing mechanisms, in particular digital object identification, and develop- ment of academic entrepreneurship., (L. Lyashenko, L.Yanovych, N. Chuprovska, A. Saienko.)

Chronic lymphocytic leukemia (CLL) has been 1 of the most dynamic fields of clinical research over the last 2 decades. Important advances in understanding the biology of CLL have led to the development of new prognostic and diagnostic tools. Concurrently, several recently approved new agents hold the potential to fundamentally change the management of this leukemia and have started to improve clinical outcomes for patients. This conceptual review summarizes the major recent insights regarding the biology of CLL, the technological advances that have allowed refinement of the prognostication of the clinical course, and the new therapeutic strategies that are currently under investigation to further ameliorate the outcome for patients with CLL., Competing Interests: Conflict-of-interest disclosure: M.H. has received research funding and honoraria from Roche, Gilead, Mundipharma, Janssen, Celgene, Pharmacyclics, and AbbVie., (© 2018 by The American Society of Hematology. All rights reserved.)

Heart failure is a major cause of global morbidity and mortality. Acute myocardial infarction (AMI) is a primary cause of heart failure due in large part to residual myocardial damage despite timely reperfusion therapy. Since the 1970's, multiple preclinical laboratories have tested whether reducing myocardial oxygen demand with a mechanical support pump can reduce infarct size in AMI. In the past decade, this hypothesis has been studied using contemporary circulatory support pumps. We will review the most recent series of preclinical studies in the field which led to the recently completed Door to Unload ST-segment Elevation Myocardial Infarction (DTU-STEMI) safety and feasibility pilot trial., Competing Interests: Competing interests: Navin Kapur has received research funding from Abiomed Inc., Abbott (Santa Clara, CA, USA), Boston Scientific (Minneapolis, MN, USA), MD Start (Paris, France), CardiacAssist Inc. (Pittsburgh, PA, USA), and Maquet Cardiovascular Inc. (Rastatt, Germany). Kiyotake Ishikawa has received research funding from Abiomed Inc. The other authors declare that they have no competing interests.No competing interests were disclosed.No competing interests were disclosed.

From the beginning, induced pluripotent stem cell (iPSC) technology was touted as a path to improve our understanding of disease biology and enable drug discovery. Advances in iPSC culture, genome engineering, and differentiation protocols have rapidly expanded the use of iPSC-derived disease models from the specialized work of stem cell biology into the mainstream toolkit of cellular neuroscience. Here we provide guidance for using iPSC-derived neurons for disease modeling with a focus on enabling screening platforms amenable to therapeutic drug discovery. We also highlight the potential for incorporating three-dimensional systems that may create more translational in vitro models., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Overcoming the widening "Valley of Death" between stem cell laboratory discoveries and clinical translation is imperative to develop the next generation of effective therapies. We asked 9 clinical experts to share their perspectives on how to bridge this gap and increase the clinical impact of basic research., (Copyright © 2018. Published by Elsevier Inc.)

Objective - To briefly describe the history of and available data on anti-calcitonin gene-related peptide (CGRP) therapies for headache. Background - CGRP was proposed as a target for primary headache therapies. Translational research involved moving from delineating the relationships between CGRP and primary headaches and the clinical development of anti-CGRP treatments. The first anti-CGRP treatment, an intravenous CGRP-receptor antagonist or gepant, olcegepant, was described as effective in terminating migraines in humans in 2004. Methods - The author briefly reviews some of the pathophysiology and translational research that led to the development of the gepants initially and then subsequently to the anti-CGRP and anti-CGRP receptor monoclonal antibodies. All accessible randomized controlled trials, abstracts, platform presentations, and press releases on the monoclonal antibody trials are summarized. The trajectory from bench research to the approval of the first anti-CGRP receptor monoclonal antibody for clinical use in migraine prevention, erenumab, is discussed, as well as potential clinical uses of the anti-CGRP treatments. Results - The US Food and Drug Administration (FDA) approved erenumab, an anti-CGRP receptor monoclonal antibody, for prevention of migraine May 17, 2018. At the time of this writing (May 2018), 2 other anti-CGRP monoclonal antibodies have been submitted to the FDA for the indication of prevention of migraine, galcanezumab and fremanezumab. Galcanezumab has reportedly shown effectiveness in preventing episodic cluster headache as well, although has not yet been submitted to the FDA for this indication. Eptinezumab will likely be submitted to the FDA for prevention of migraine later in 2018. Two gepants, ubrogepant and rimegepant, have completed positive pivotal trials for acute treatment of migraine, but have not yet been submitted to the FDA for this indication. Conclusions - The development of anti-CGRP therapies opens a new era in the acute and preventive treatment of primary headache disorders., (© 2018 American Headache Society.)

Objectives: Pediatric gastroenterology is a clinical and research discipline principally developed over the past 50 years. Bibliometric methods provide quantitative analysis and identify research trends. Study aims were to characterize the growth and trends in pediatric gastroenterology clinical and translational research using citation analysis., Methods: Using citations analysis software, a search strategy specific for pediatric gastroenterology was implemented for the years 1970 to 2017. The 50 most-cited research articles per decade were identified. These 250 articles were coded for topic and study attribute. Analysis included authors, affiliations, journals, countries, and funding sources., Results: Overall average annual growth rate for pediatric gastroenterology publications was significantly higher than that for general pediatrics (51.7% vs 6.2%; P < 0.05). Among the top 250 cited articles, the distribution of study focus was epidemiology (43%), pathophysiology (18%), treatment (16%), diagnosis (8%), prevention (8%), and comorbidities of gastrointestinal diseases (7%).There were 38 different topics represented and there was a notable shift in topic focus over time. Cholestasis, biliary atresia, and total parenteral nutrition were common topics from 1970 to 1989 and obesity, nonalcoholic fatty liver disease, and eosinophilic esophagitis were common topics after 1990. Notably, 2.3% of the authors accounted for 30% of the top 250 articles., Conclusions: Pediatric gastroenterology research has undergone rapid growth yielding advancements in the management of gastrointestinal conditions in children. The emergence of new diseases in need of better diagnostics and therapeutics led to a temporal shift in research focus. Further advancements will require multidisciplinary collaborations and continued funding for pediatric gastroenterology research.

Remarkable advances in quantitative mass spectrometry have shifted the focus of proteomics from the characterization of protein expression profiles to detailed investigations on the spatial and temporal organization of the proteome. Demands for precision therapy and personalized medicine are challenged by heterogeneity in the larger population, which have led to drawbacks in biomarker performance and therapeutic efficacy. The consistent adaptation of the cellular proteome in response to distinctive signals defines a phenotype. Acquisition of quantitative multi-layered omics data on multiple individuals over defined time scales has made it possible to establish means to probe the extent to which the genome, transcriptome and environment influence the variability of the proteome in given conditions, over time. Comprehensive, reproducible datasets generated with contemporary quantitative, massively parallel, targeted proteomic approaches offer as yet untapped benefits for biomarker discovery, development, and validation. The objective of this review is to recapitulate on advances in targeted proteomics approaches for quantifying the cellular proteome and to address ways to incorporate these data towards improving present day methodologies for biomarker evaluation and precision medicine. SIGNIFICANCE: Advances in quantitative mass spectrometry have shifted the focus of proteomics from the characterization of protein expression profiles to detailed investigations on the spatial and temporal organization of the proteome. This review expounds on avenues through which targeted proteomic methodologies can be constructively implemented in translational research and precision medicine to overcome existing challenges that hinder the success of protein biomarkers in clinics, and to develop precise therapeutics for future applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are a heterogeneous group of small lipid-enclosed structures with myriad roles in physiology and disease. The recent surge of interest in EVs has led to greater understanding of their biology and appreciation of how they might be utilised as diagnostic and therapeutic tools. There remain, however, a number of challenges that must be overcome before EVs may be used routinely in the clinic. In this review we will discuss the translational potential of EVs and the current technologies available to isolate, purify and analyse EVs and their contents., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Translational cancer research has benefitted significantly from the generation of preclinical models that recapitulate the native tumour environment. While conventional cell models have contributed substantially to the current understanding of cancer biology and therapeutic development, a missing link between cell culture and their clinical applications is evident. Patient derived xenograft (PDX) models represent this missing link as they enable the examination of patient tumour tissue in a native environment without significantly affecting the cellular complexity, genomics, and stromal architecture of the neoplasms. The use of PDXs to model head and neck cancer (HNC) begets the development of novel therapeutics, increased understanding of tumorigenesis and the advent of personalised treatments cancer patients. There has been an increase in attempts to generate viable PDXs for HNCs in recent years. This concise review summarizes the current developments in the field of PDXs for HNCs., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Qualitative research should strive for knowledge translation toward the goal of closing the gap between knowledge and practice. However, it is often a challenge in nursing to identify knowledge translation strategies able to illustrate the usefulness of qualitative results in any given context. This article defines storytelling and uses pragmatism to examine storytelling as a strategy to promote the knowledge translation of qualitative results. Pragmatism posits that usefulness is defined by the people affected by the problem and that usefulness is promoted by modalities, like storytelling, that increase sensitivity to an experience. Indeed, stories have the power to give meaning to human behaviors and to trigger emotions, and in doing so bring many advantages. For example, by contextualizing research results and appealing to both the reason and the emotions of audiences, storytelling can help us grasp the usefulness of these research results. Various strategies exist to create stories that will produce an emotional experience capable of influencing readers' or listeners' actions. To illustrate the potential of storytelling as a knowledge translation strategy in health care, we will use our story of discovering this strategy during a qualitative study in a nursing home as an example., (© 2018 John Wiley & Sons Ltd.)

The 2013 Breast Cancer Campaign gap analysis established breast cancer research priorities without a specific focus on surgical research or the role of surgeons on breast cancer research. This Review aims to identify opportunities and priorities for research in breast surgery to complement the 2013 gap analysis. To identify these goals, research-active breast surgeons met and identified areas for breast surgery research that mapped to the patient pathway. Areas included diagnosis, neoadjuvant treatment, surgery, adjuvant therapy, and attention to special groups (eg, those receiving risk-reducing surgery). Section leads were identified based on research interests, with invited input from experts in specific areas, supported by consultation with members of the Association of Breast Surgery and Independent Cancer Patients' Voice groups. The document was iteratively modified until participants were satisfied that key priorities for surgical research were clear. Key research gaps included issues surrounding overdiagnosis and treatment; optimising treatment options and their selection for neoadjuvant therapies and subsequent surgery; reducing rates of re-operations for breast-conserving surgery; generating evidence for clinical effectiveness and cost-effectiveness of breast reconstruction, and mechanisms for assessing novel interventions; establishing optimal axillary management, especially post-neoadjuvant treatment; and defining and standardising indications for risk-reducing surgery. We propose strategies for resolving these knowledge gaps. Surgeons are ideally placed for a central role in breast cancer research and should foster a culture of engagement and participation in research to benefit patients and health-care systems. Development of infrastructure and surgical research capacity, together with appropriate allocation of research funding, is needed to successfully address the key clinical and translational research gaps that are highlighted in this Review within the next two decades., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

IL-5 is an important cytokine for priming and survival of mature eosinophils and for proliferation and maturation of their progenitors. Hence, IL-5(Rα) targeting will be increasingly used in diseases where eosinophils are the key immune effector cells such as eosinophilic asthma (EA), hypereosinophilic syndrome (HES), eosinophilic esophagitis (EE), and eosinophilic granulomatosis with polyangiitis (EGPA). Therefore, several neutralizing monoclonal antibodies directed against IL-5 (mepolizumab and reslizumab) and its receptor IL-5Rα (benralizumab) have found or will find their way to the clinic. While the clinical effect of these drugs has been extensively investigated and reviewed, the understanding of the underlying immunological and hematological mechanisms remains less clear. This review will discuss the translational outcomes of treatment with these monoclonal antibodies in humans to shed light on the mechanisms underlying the main immunological and hematological findings from these clinical trials in humans., (© 2018 The Authors. Allergy published by John Wiley & Sons Ltd.)

We provide an overview of groundbreaking studies that laid the foundation for our current understanding of exercise-induced mitochondrial biogenesis and its contribution to human skeletal muscle fitness. We highlight the mechanisms by which skeletal muscle responds to the acute perturbations in cellular energy homeostasis evoked by a single bout of endurance-based exercise and the adaptations resulting from the repeated demands of exercise training that ultimately promote mitochondrial biogenesis through hormetic feedback loops. Despite intense research efforts to elucidate the cellular mechanisms underpinning mitochondrial biogenesis in skeletal muscle, translating this basic knowledge into improved metabolic health at the population level remains a future challenge., (Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.)

Medicine is at the crossroads of expanding disciplines. Prompt adaptation of medicine to each rapidly advancing research field, bridging bench to bedside, is a key step toward health improvement. Cardiovascular disease still ranks first among the mortality causes in the Western world, indicating a poor adaptation rate of cardiovascular medicine, albeit the gigantic scientific breakthroughs of this century. This urges the cardiovascular research field to explore novel concepts with promising prognostic and therapeutic potential. This review attempts to introduce the newly emerging field of epitranscriptome (or else known as RNA epigenetics) to cardiovascular researchers and clinicians summarizing its applications on health and disease. The traditionally perceived, intermediate carrier of genetic information or as contemporary revised as, occasionally, even the final product of gene expression, RNA, is dynamically subjected to >140 different kinds of chemical modifications determining its fate, which may profoundly impact the cellular responses and thus both health and disease course. Which are the most prevalent types of these RNA modifications, how are they catalyzed, how are they regulated, which role may they play in health and disease, and which are the implications for the cardiovascular medicine are few important questions that are discussed in the present review.