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Evidence generating medicine

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https://www.readbyqxmd.com/read/30110355/striatal-transcriptome-of-a-mouse-model-of-adhd-reveals-a-pattern-of-synaptic-remodeling
#1
Anastasia M Sorokina, Michael Saul, Tassia M Goncalves, Joseph V Gogola, Petra Majdak, Sandra L Rodriguez-Zas, Justin S Rhodes
Despite the prevalence and high heritability of Attention-Deficit/Hyperactivity Disorder (ADHD), genetic etiology remains elusive. Clinical evidence points in part to reduced function of the striatum, but which specific genes are differentially expressed and how they sculpt striatal physiology to predispose ADHD are not well understood. As an exploratory tool, a polygenic mouse model of ADHD was recently developed through selective breeding for high home cage activity. Relative to the Control line, the High-Active line displays hyperactivity and motor impulsivity which are ameliorated with amphetamine...
2018: PloS One
https://www.readbyqxmd.com/read/30097238/clinical-implication-of-changes-in-body-composition-and-weight-in-patients-with-early-stage-and-metastatic-breast-cancer
#2
REVIEW
Ilaria Trestini, Luisa Carbognin, Sara Monteverdi, Sara Zanelli, Alessandro De Toma, Clelia Bonaiuto, Rolando Nortilli, Elena Fiorio, Sara Pilotto, Massimo Di Maio, Antonio Gasbarrini, Giovanni Scambia, Giampaolo Tortora, Emilio Bria
Breast cancer represents the most frequent cancer among women in Western countries. Although physicians and patients have witnessed a significant evolution in both treatment strategies and personalized medicine (the identification of featured patients' subsets such as HER2-driven disease), the identification of additional prognostic clinical predictors referring to patients' dietary habits represents a research area aiming to further improve the overall management of this disease. In this regard, body composition (i...
September 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/30094075/multidisciplinary-molecular-tumour-board-a-tool-to-improve-clinical-practice-and-selection-accrual-for-clinical-trials-in-patients-with-cancer
#3
Christian Rolfo, Paolo Manca, Roberto Salgado, Peter Van Dam, Amelie Dendooven, Andreia Machado Coelho, Jose Ferri Gandia, Annemie Rutten, Willem Lybaert, Joanna Vermeij, Thomas Gevaert, Christine Weyn, Anneke Lefebure, Sofie Metsu, Steven Van Laere, Marc Peeters, Patrick Pauwels
Background: The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network. Materials and methods: Patients diagnosed with solid tumours progressing to standard treatments were referred to our Phase I unit...
2018: ESMO Open
https://www.readbyqxmd.com/read/30086079/klhl14-antisense-rna-is-a-target-of-key-skeletogenic-transcription-factors-in-the-developing-intervertebral-disc
#4
Petra Kraus, V Sivakamasundari, Victoria Olsen, Victoria Villeneuve, Abbey Hinds, Thomas Lufkin
STUDY DESIGN: RNA in situ hybridization (RISH) allows for validation and characterization of the long non-coding (lnc) natural antisense RNA (NAT) Klhl14as in the embryonic murine intervertebral disc (IVD) in the context of loss-of-function mutants for key transcription factors (TF) in axial skeleton development. OBJECTIVE: Validation of Klhl14as in the developing murine IVD. SUMMARY OF BACKGROUND DATA: The IVD is a focus of regenerative medicine, however processes and signaling cascades resulting in the different cell types in a mature IVD still require clarification in most animals including humans...
August 6, 2018: Spine
https://www.readbyqxmd.com/read/30083881/a-novel-germline-mutation-at-exon-10-of-men1-gene-a-clinical-survey-and-positive-genotype-phenotype-analysis-of-a-men1-italian-family-including-monozygotic-twins
#5
REVIEW
Andrea Palermo, Ettore Capoluongo, Rossella Del Toro, Silvia Manfrini, Paolo Pozzilli, Daria Maggi, Giuseppe Defeudis, Francesco Pantano, Roberto Coppola, Francesco Maria Di Matteo, Marco Raffaelli, Paola Concolino, Alberto Falchetti
CONTEXT: Clinical phenotype variability in MEN1 syndrome exists and evidence for an established genotype-phenotype is lacking. However, a higher aggressiveness of MEN1-associated gastro-entero-pancreatic (GEP) (neuro)endocrine tumours (NETs) tumours has been reported when MEN1 gene truncating mutations are detected. We found a novel germline truncating mutation of MEN1 gene at exon 10 in a subject with an aggressive clinical behavior of GEP-NETs. Successively, other two mutant-affected familial members have been identified...
August 6, 2018: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/30079101/gene-drives-in-our-future-challenges-of-and-opportunities-for-using-a-self-sustaining-technology-in-pest-and-vector-management
#6
REVIEW
James P Collins
Gene drives are systems of biased inheritance that enhance the likelihood a sequence of DNA passes between generations through sexual reproduction and potentially throughout a local population and ultimately all connected populations of a species. Gaps in our knowledge of gene drive systems prompted the US National Institutes of Health (NIH) and the Foundation for the NIH to ask the US National Academies of Sciences, Engineering, and Medicine (NASEM) to convene an expert panel to provide an independent, objective examination of what we know about gene drive systems...
2018: BMC Proceedings
https://www.readbyqxmd.com/read/30074590/evidence-based-recommendations-for-pediatric-orthopaedic-practice
#7
Kishore Mulpuri, Emily K Schaeffer, James Sanders, Ira Zaltz, Mininder S Kocher
BACKGROUND: The evidence-based approach to guide clinical practice has gained great importance in the medical field. High-quality evidence is of paramount importance to inform clinical decision-making and optimize patient outcomes. The generation of high-quality evidence relies on sound methodology and study design to facilitate appropriate interpretation and subsequent application of the clinical findings. The purpose of this review is to objectively critique the methodological design and clinical findings of 2 pediatric orthopaedic studies on children with cerebral palsy (CP) to assess their potential to impact clinical practice...
August 1, 2018: Journal of Pediatric Orthopedics
https://www.readbyqxmd.com/read/30073483/complementary-medicine-in-radiation-oncology-german-health-care-professionals-current-qualifications-and-therapeutic-methods
#8
Kerstin A Kessel, Evelyn Klein, Carolin C Hack, Stephanie E Combs
INTRODUCTION: Recently, complementary and alternative medicine (CAM) has moved more into the focus, and cancer societies such as the German Cancer Society (Deutsche Krebsgesellschaft, DKG) have established working groups to develop a guideline for CAM. The present work aims to evaluate the acceptance of CAM in the whole radiation oncology community. METHODS: We conducted an online survey on CAM and sent the modified questionnaire that was successfully distributed to all members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynakologische Onkologie, AGO) of the DKG in 2014 to the members of the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie und Strahlentherapie, DEGRO)...
August 2, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/30053872/emerging-roles-of-myc-in-stem-cell-biology-and-novel-tumor-therapies
#9
REVIEW
Go J Yoshida
The pathophysiological roles and the therapeutic potentials of Myc family are reviewed in this article. The physiological functions and molecular machineries in stem cells, including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, are clearly described. The c-Myc/Max complex inhibits the ectopic differentiation of both types of artificial stem cells. Whereas c-Myc plays a fundamental role as a "double-edged sword" promoting both iPS cells generation and malignant transformation, L-Myc contributes to the nuclear reprogramming with the significant down-regulation of differentiation-associated genetic expression...
July 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/30052961/recommendations-from-the-international-evidence-based-guideline-for-the-assessment-and-management-of-polycystic-ovary-syndrome
#10
Helena J Teede, Marie L Misso, Michael F Costello, Anuja Dokras, Joop Laven, Lisa Moran, Terhi Piltonen, Robert J Norman
STUDY QUESTION: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise and consumer preference? SUMMARY ANSWER: International evidence-based guidelines, including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated...
July 19, 2018: Human Reproduction
https://www.readbyqxmd.com/read/30050359/nodding-syndrome-recent-insights-into-etiology-pathophysiology-and-treatment
#11
REVIEW
Amos Deogratius Mwaka, Jerome Roy Semakula, Catherine Abbo, Richard Idro
Nodding syndrome is an enigmatic neuropsychiatric and epileptiform disorder associated with psychomotor, mental, and physical growth retardation. The disorder affects otherwise previously normal children aged 3-18 years, with a slight preponderance for the male child. Nodding syndrome has been described in rural regions of some low-income countries in sub-Saharan Africa including northern Uganda, South Sudan, and a mountainous region of southern Tanzania. The cause of the disorder has hitherto eluded scientists...
2018: Research and Reports in Tropical Medicine
https://www.readbyqxmd.com/read/30044800/cardiac-regenerative-capacity-is-age-and-disease-dependent-in-childhood-heart-disease
#12
Alexandra Traister, Rachana Patel, Anita Huang, Sarvatit Patel, Julia Plakhotnik, Jae Eun Lee, Maria Gonzalez Medina, Chris Welsh, Prutha Ruparel, Libo Zhang, Mark Friedberg, Jason Maynes, John Coles
OBJECTIVE: We sought to define the intrinsic stem cell capacity in pediatric heart lesions, and the effects of diagnosis and of age, in order to inform evidence-based use of potential autologous stem cell sources for regenerative medicine therapy. METHODS: Ventricular explants derived from patients with hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TF), dilated cardiomyopathy (DCM) and ventricular septal defect (VSD) were analyzed following standard in vitro culture conditions, which yielded cardiospheres (C-spheres), indicative of endogenous stem cell capacity...
2018: PloS One
https://www.readbyqxmd.com/read/30044011/building-a-total-bioartificial-heart-harnessing-nature-to-overcome-the-current-hurdles
#13
Doris A Taylor, O H Frazier, Abdelmotagaly Elgalad, Camila Hochman-Mendez, Luiz C Sampaio
Engineering a bio-artificial heart has become a possibility in part because of the regenerative medicine approaches to repairing or replacing damaged organs that have evolved over the past two decades. With the advent of inducible pluripotent stem cell technology, it is now possible to generate personalized cells that make the concept of autologous tissue engineering imaginable. Scaffolds, that provide form, function, and biological cues to cells likewise potentially enable the engineering of biocompatible vascularized solid organs...
July 25, 2018: Artificial Organs
https://www.readbyqxmd.com/read/30039249/sglt2-inhibitors-in-type-2-diabetes-management-key-evidence-and-implications-for-clinical-practice
#14
REVIEW
John Wilding, Kevin Fernando, Nicola Milne, Marc Evans, Amar Ali, Steve Bain, Debbie Hicks, June James, Philip Newland-Jones, Dipesh Patel, Adie Viljoen
Management of type 2 diabetes mellitus (T2DM) is complex and challenging, particularly for clinicians working in primary care who are faced with many competing clinical priorities. The range of available T2DM treatments has diversified significantly in recent years, generating a busy and data-rich environment in which evidence is rapidly evolving. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) agents are a relatively new class of oral glucose-lowering therapy that have been available in the UK for approximately 5 years...
July 23, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/30037107/understanding-the-role-of-dysfunctional-and-healthy-mitochondria-in-stroke-pathology-and-its-treatment
#15
REVIEW
Hung Nguyen, Sydney Zarriello, Mira Rajani, Julian Tuazon, Eleonora Napoli, Cesar V Borlongan
Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cell transplantation, may hold promise as a stroke therapy, because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery...
July 21, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30036600/generating-evidence-to-inform-an-update-of-asthma-clinical-practice-guidelines-perspectives-from-the-national-heart-lung-and-blood-institute
#16
George A Mensah, James P Kiley, Gary H Gibbons
Asthma is the most prevalent chronic respiratory disease worldwide. Its increasing prevalence and evidence of suboptimal control require renewed efforts in the development and widespread implementation of clinical practice guidelines for prevention, treatment, and control. Given the rapidly changing landscape and evolving best practices for guideline development, the National Heart, Lung, and Blood Institute made a commitment to support rigorous systematic evidence reviews that frontline health care providers and stakeholders could use to create new or update existing guidelines...
July 21, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/30033227/recommendations-from-the-international-evidence-based-guideline-for-the-assessment-and-management-of-polycystic-ovary-syndrome
#17
Helena J Teede, Marie L Misso, Michael F Costello, Anuja Dokras, Joop Laven, Lisa Moran, Terhi Piltonen, Robert J Norman
STUDY QUESTION: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER: International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated...
August 2018: Fertility and Sterility
https://www.readbyqxmd.com/read/30026923/real-world-evidence-rwe-a-disruptive-innovation-or-the-quiet-evolution-of-medical-evidence-generation
#18
Sajan Khosla, Robert White, Jesús Medina, Mario Ouwens, Cathy Emmas, Tim Koder, Gary Male, Sandra Leonard
Stakeholders in healthcare are increasingly turning to real world evidence (RWE) to inform their decisions, alongside evidence from randomized controlled trials. RWE is generated by analysing data gathered from routine clinical practice, and can be used across the product lifecycle, providing insights into areas including disease epidemiology, treatment effectiveness and safety, and health economic value and impact. Recently, the US Food and Drug Administration and the European Medicines Agency have stated their ambition for greater use of RWE to support applications for new indications, and are now consulting with their stakeholders to formalize standards and expected methods for generating RWE...
2018: F1000Research
https://www.readbyqxmd.com/read/30026469/embryonic-germ-cell-extracts-erase-imprinted-genes-and-improve-the-efficiency-of-induced-pluripotent-stem-cells
#19
Jing Hu, Qiaoshi Zhao, Yukuan Feng, Na Li, Yanli Gu, Ruizhen Sun, Lian Duan, Yanshuang Wu, Zhiyan Shan, Lei Lei
Patient-specific induced pluripotent stem cells (iPSCs) have the potential to be useful in the treatment of human diseases. While prior studies have reported multiple methods to generate iPSCs, DNA methylation continues to limit the totipotency and reprogramming efficiency of iPSCs. Here, we first show the competency of embryonic germ cells (EGCs) as a reprogramming catalyst capable of effectively promoting reprogramming induced by four defined factors, including Oct4, Sox2, Klf4 and c-Myc. Combining EGC extracts with these four factors resulted in formation of more embryonic stem cell-like colonies than did factors alone...
July 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30023769/x-ray-structure-based-identification-of-compounds-with-activity-against-targets-from-different-families-and-generation-of-templates-for-multitarget-ligand-design
#20
Erik Gilberg, Dagmar Stumpfe, Jürgen Bajorath
Compounds with multitarget activity (promiscuity) are increasingly sought in drug discovery. However, promiscuous compounds are often viewed controversially in light of potential assay artifacts that may give rise to false-positive activity annotations. We have reasoned that the strongest evidence for true multitarget activity of small molecules would be provided by experimentally determined structures of ligand-target complexes. Therefore, we have carried out a systematic search of currently available X-ray structures for compounds forming complexes with different targets...
January 31, 2018: ACS Omega
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