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Translational medicine

Pavani Rangachari
In 1999, the Institute of Medicine reported that 98,000 people die each year due to medical errors. In the following years, the focus on hospital quality was intensified nationally, with policymakers providing evidence-based practice guidelines for improving health care quality. However, these innovations (evidence-based guidelines) that were being produced at policy levels were not translating to clinical practice at the hospital organizational level easily, and stark variations continued to persist, in the quality of health care...
2018: Innov Entrep Health
Alice Huertas, Christophe Guignabert
The European Respiratory Society (ERS) Research Seminar entitled " Pulmonary Vascular Endothelium: Orchestra Conductor in Respiratory Diseases - Highlights from Basic Research to Therapy " brought together international experts of dysfunctional pulmonary endothelium, from basic science to translational medicine, to discuss several important aspects in acute and chronic lung diseases. This review will briefly sum up the different topics of discussion of this meeting held in Paris (France) on October 27th and 28th, 2016...
March 15, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Brenda Si Elias, Ana Hanlon-Dearman, Betty Head, Geoffrey G Hicks
Translating to the Community (T2C) is a social bio-repository designed to advance new diagnostic tools and realign community-clinical processes, with the aim to mitigate the short-and-long term impacts of Fetal Alcohol Spectrum Disorder (FASD), prenatal alcohol exposure, and its co-morbidities and behaviors. In this paper, we describe the evolution of this repository as a new translational partnership to advance a precision medicine approach to FASD. Key to its evolution was a partnership between academic researchers, Indigenous communities, families and a regional diagnostic clinic...
March 15, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Alborz Karimzadeh, Vanessa M Scarfone, Erika Varady, Connie Chao, Karin Grathwohl, John W Fathman, David A Fruman, Thomas Serwold, Matthew A Inlay
Hematopoietic stem cells (HSCs) are the self-renewing multipotent progenitors to all blood cell types. Identification and isolation of HSCs for study has depended on the expression of combinations of surface markers on HSCs that reliably distinguish them from other cell types. However, the increasing number of markers required to isolate HSCs has made it tedious, expensive, and difficult for newcomers, suggesting the need for a simpler panel of HSC markers. We previously showed that phenotypic HSCs could be separated based on expression of CD11a and that only the CD11a negative fraction contained true HSCs...
March 15, 2018: Stem Cells Translational Medicine
Bingbo Zhang, Wei Yan, Yanjing Zhu, Weitao Yang, Wenjun Le, Bingdi Chen, Rongrong Zhu, Liming Cheng
Patients are increasingly being diagnosed with neuropathic diseases, but are rarely cured because of the loss of neurons in damaged tissues. This situation creates an urgent clinical need to develop alternative treatment strategies for effective repair and regeneration of injured or diseased tissues. Neural stem cells (NSCs), highly pluripotent cells with the ability of self-renewal and potential for multidirectional differentiation, provide a promising solution to meet this demand. However, some serious challenges remaining to be addressed are the regulation of implanted NSCs, tracking their fate, monitoring their interaction with and responsiveness to the tissue environment, and evaluating their treatment efficacy...
March 15, 2018: Advanced Materials
Matheus Roque, Sandro C Esteves
Varicocele, the leading cause of male infertility, can impair sperm quality and fertility via various oxidative stress mechanisms. An imbalance between excessive reactive oxygen species production and antioxidant protection causes alterations in nuclear and mitochondrial sperm DNA, thus rendering a subset of varicocele men less fertile. In particular, sperm DNA fragmentation is usually elevated in men with clinical varicocele in both abnormal and normal semen parameters by the current World Health Organization criteria...
March 14, 2018: International Urology and Nephrology
Carine Smith
The modern lifestyle is characterised by various factors that cause accelerating ageing by the upregulation of oxidative stress and inflammation-two processes that are inextricably linked in an endless circle of self-propagation. Inflammation in particular is commonly accepted as aetiological factor in many chronic disease states, such as obesity, diabetes and depression. In terms of disease prevention or treatment, interventions aimed at changing dietary and/or exercise habits have had limited success in practise, mostly due to poor long-term compliance...
March 14, 2018: Journal of Physiology and Biochemistry
Carolina Torres, Paul J Grippo
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cause of cancer-related deaths by 2020. Although it has traditionally been approached as one disease, accumulated evidences point to the clinical heterogeneity of this disease which translates into disparity in outcomes between patients. Much emphasis has been put into patient classification introducing a platform for more tailored therapies. In the last ten years, there have been important advances in the understanding of the molecular pathogenesis of PDAC, which has culminated with a comprehensive integrated genomic analysis from RNA expression profiles...
March 14, 2018: Annals of Medicine
Heng Xu, Yang Shu
Treatment outcomes for acute lymphoblastic leukemia (ALL), especially pediatric ALL, have greatly improved due to the risk-adapted therapy. Combination of drug development, clinical practice, as well as basic genetic researches has brought the survival rate of ALL from less than 10% to more than 90% today, not only increasing the treatment efficacy but also limiting adverse drug reactions (ADRs). In this review, we summarized the landscape identification of ALL genetic alterations, which provided the opportunity to increase the survival rate and especially minimize the relapse risk of ALL, and highlighted the importance of the development of new technologies of genomic investigation for translational medicine...
2018: Methods in Molecular Biology
Mehdi Trifa, Dmitry Tumin, Hina Walia, Kathleen L Lemanek, Joseph D Tobias, Tarun Bhalla
Background: The use of complementary and alternative medicine (CAM) therapies has increased in children, especially in those with chronic health conditions. However, this increase may not translate into acceptance of CAM in the perioperative setting. We surveyed caregivers of patients undergoing surgery to determine their knowledge and acceptance of hypnotherapy, acupuncture, and music therapy as alternatives to standard medication in the perioperative period. Materials and methods: An anonymous, 12-question survey was administered to caregivers of children undergoing procedures under general anesthesia...
2018: Journal of Pain Research
Olle Ringden, Arjang Baygan, Mats Remberger, Britt Gustafsson, Jacek Winiarski, Bita Khoein, Guido Moll, Lena Klingspor, Magnus Westgren, Behnam Sadeghi
Severe acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The placenta protects the fetus from the mother's immune system. We evaluated placenta-derived decidua stromal cells (DSCs), which differ from bone marrow mesenchymal stromal cells (BM-MSCs), as a treatment for severe acute GVHD. DSCs were obtained from term placentas. The DSCs were given to 38 patients with severe acute GVHD; 25 were steroid refractory (SR). DSCs were thawed and infused in buffer supplemented with either 10% AB plasma (group 1, n = 17), or 5% albumin (group 2, n = 21)...
March 13, 2018: Stem Cells Translational Medicine
Jinho Lee, Gary K Geiss, Gokhan Demirkan, Christopher P Vellano, Brian Filanoski, Yiling Lu, Zhenlin Ju, Shuangxing Yu, Huifang Guo, Lisa Y Bogatzki, Warren E Carter, Rhonda K Meredith, Savitri Krishnamurthy, Zhiyong Ding, Joseph M Beechem, Gordon Mills
Molecular analysis of tumors forms the basis for personalized cancer medicine and increasingly guides patient selection for targeted therapy.  Future opportunities for personalized medicine are highlighted by the measurement of protein expression levels via immunohistochemistry, protein arrays, and other approaches; however, sample type, sample quantity, batch effects, and "time to result" are limiting factors for clinical application.  Here, we present a development pipeline for a novel multiplexed DNA-labeled antibody platform which digitally quantifies protein expression from lysate samples...
March 12, 2018: Molecular & Cellular Proteomics: MCP
Virginia Neyro, Evelyne Jacqz-Aigrain, Tiphaine Adam de Beaumais
Identification of markers involved in drug disposition is crucial for drugs with a narrow therapeutic index. Individual genomic differences can affect the pharmacology of some drugs and participate to inter-individual variability in drug response. Pharmacogenetics is a useful tool in clinical practice for dosage adjustment and to limit drug toxicities. In pediatrics, physiological changes can also influence the disposition of drugs in infants, children and adolescents. The importance of ontogeny translates into different responses to the same drug in children and adults...
February 16, 2018: Thérapie
Vincenzo Mirabello, Fernando Cortezon-Tamarit, Sofia I Pascu
Hypoxia has been identified as one of the hallmarks of tumor environments and a prognosis factor in many cancers. The development of ideal chemical probes for imaging and sensing of hypoxia remains elusive. Crucial characteristics would include a measurable response to subtle variations of pO2 in living systems and an ability to accumulate only in the areas of interest (e.g., targeting hypoxia tissues) whilst exhibiting kinetic stabilities in vitro and in vivo . A sensitive probe would comprise platforms for applications in imaging and therapy for non-communicable diseases (NCDs) relying on sensitive detection of pO2 ...
2018: Frontiers in Chemistry
Anna Zuk, Paul M Palevsky, Linda Fried, Frank E Harrell, Samina Khan, Dianne B McKay, Luke Devey, Lakhmir Chawla, Mark de Caestecker, James S Kaufman, B Taylor Thompson, Anupam Agarwal, Tom Greene, Mark Douglas Okusa, Joseph V Bonventre, Laura M Dember, Kathleen D Liu, Benjamin D Humphreys, Daniel Gossett, Yining Xie, Jenna M Norton, Paul L Kimmel, Robert A Star
AKI is a complex clinical condition associated with high mortality, morbidity, and health care costs. Despite improvements in methodology and design of clinical trials, and advances in understanding the underlying pathophysiology of rodent AKI, no pharmacologic agent exists for the prevention or treatment of AKI in humans. To address the barriers that affect successful clinical translation of drug targets identified and validated in preclinical animal models of AKI in this patient population, the National Institute of Diabetes and Digestive and Kidney Diseases convened the "AKI Outcomes: Overcoming Barriers in AKI" workshop on February 10-12, 2015...
March 9, 2018: Clinical Journal of the American Society of Nephrology: CJASN
K Johanna R Hoyer, Sebastian Dittrich, Malte P Bartram, Markus M Rinschen
Renal diseases are driven by alterations in the entity of proteins within the kidney, at the level of single cells, nephron subunits (such as glomerulus and tubule), tissues and body fluids. Histologically, kidney diseases are extremely heterogeneous. Mass-spectrometry based proteomics provides a unique opportunity to interrogate heterogeneity and dynamics of various proteome layers within the kidney to better understand physiology and pathophysiology, and to translate signaling networks into therapies. Yet, the success of this endeavor will largely depend on improving proteomic data acquisition methods toward increased reproducibility...
March 6, 2018: Journal of Proteomics
Kran Suknuntha, Lihong Tao, Vera Brok-Volchanskaya, Saritha S D'Souza, Akhilesh Kumar, Igor Slukvin
Identification of transcription factors that directly convert pluripotent stem cells (PSCs) into endothelial and blood cells and advances in the chemical modifications of messenger RNA (mRNA) offer alternative nucleic acid-based transgene-free approach for scalable production of these cells for drug screening and therapeutic purposes. Here we evaluated the effect of 5' and 3' RNA untranslated regions (UTRs) on translational efficiency of chemically-modified synthetic mRNA (modRNA) in human PSCs and showed that an addition of 5'UTR indeed enhanced protein expression...
March 8, 2018: Stem Cell Reviews
Peter Balicza, Andras Terebessy, Zoltan Grosz, Noemi Agnes Varga, Aniko Gal, Balint Andras Fekete, Maria Judit Molnar
Objective: Next-generation sequencing is increasingly utilized worldwide as a research and diagnostic tool and is anticipated to be implemented into everyday clinical practice. Since Central-Eastern European attitude toward genetic testing, especially broad genetic testing, is not well known, we performed a survey on this issue among Hungarian participants. Methods: A self-administered questionnaire was distributed among patients and patient relatives at our neurogenetic outpatient clinic...
March 2018: EPMA Journal
Hao Zhang, Zhong-Li Li, Xiang-Zheng Su, Li Ding, Ji Li, Heng Zhu
Rabbit mesenchymal stem cells (MSCs) are important seed cells in regenerative medicine research, particularly in translational research. In the current study, we showed that rabbit subchondral bone is a reliable source of MSCs. First, we harvested subchondral bone (SCB) from the rabbit knee-joint and initiated the MSC culture by cultivating enzyme-treated SCB. Adherent fibroblast-like cells that outgrew from SCB fulfill the common immuno-phenotypic criteria for defining MSCs, but with low contamination of CD45+ hematopoietic cells...
March 8, 2018: Experimental Animals
Juergen Dukart, Štefan Holiga, Christopher Chatham, Peter Hawkins, Anna Forsyth, Rebecca McMillan, Jim Myers, Anne R Lingford-Hughes, David J Nutt, Emilio Merlo-Pich, Celine Risterucci, Lauren Boak, Daniel Umbricht, Scott Schobel, Thomas Liu, Mitul A Mehta, Fernando O Zelaya, Steve C Williams, Gregory Brown, Martin Paulus, Garry D Honey, Suresh Muthukumaraswamy, Joerg Hipp, Alessandro Bertolino, Fabio Sambataro
Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action...
March 6, 2018: Scientific Reports
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