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Clinical actionability

Pawel Kuklik, Benjamin Schäffer, Boris A Hoffmann, Anand N Ganesan, Doreen Schreiber, Julia M Moser, Ruken Ö Akbulak, Arian Sultan, Daniel Steven, Bart Maesen, Ulrich Schotten, Christian Meyer, Stephan Willems
BACKGROUND: Electrogram-based identification of the regions maintaining persistent Atrial Fibrillation (AF) is a subject of ongoing debate. Here, we explore the concept of local electrical dyssynchrony to identify AF drivers. METHODS AND RESULTS: Local electrical dyssynchrony was calculated using mean phase coherence. High-density epicardial mapping along with mathematical model were used to explore the link between local dyssynchrony and properties of wave conduction...
2016: PloS One
Meijun Song, Hongcheng Wu, Shibo Wu, Ting Ge, Guoan Wang, Yingyan Zhou, Shimo Sheng, Jingbo Jiang
Lung cancer is the leading cause of cancer death worldwide and its clinical management remains challenge. Here, we repurposed antibiotic levofloxacin for lung cancer treatment. We show that levofloxacin is effectively against a panel of lung cancer cell lines via inhibiting proliferation and inducing apoptosis, regardless of cellular origin and genetic pattern, in in vitro cell culture system and in vivo xenograft lung tumor model. Mechanistically, levofloxacin inhibits activities of mitochondrial electron transport chain complex I and III, leading to inhibition of mitochondrial respiration and reduction of ATP production...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Wen-Lei Shi, Ting Zhang, Jiang-Rui Zhou, Yong-Hua Huang, Chun-Lei Jiang
Glucocorticoids (GCs) play a vital role in the regulation of blood pressure by their permissive effects in potentiating vasoactive responses to catecholamines through glucocorticoid receptors. GCs achieve this function by controlling vascular smooth muscle tone. Clinically, low to moderate doses of GCs are generally used in the treatment of septic shock in recent years. GCs are now known to have both genomic and non-genomic effects. While genomic effects of GCs were well studied, few non-genomic effects were reported, much less the non-genomic mechanisms...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ryan A Devenyi, Francis A Ortega, Willemijn Groenendaal, Trine Krogh-Madsen, David J Christini, Eric A Sobie
Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. Here we combined mathematical modeling with information-rich dynamic-clamp experiments to elucidate regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell...
October 24, 2016: Journal of Physiology
Xinmin Zhao, Xianghua Wu, Wen Yu, Xuwei Cai, Qi Liu, Xiaolong Fu, Zhebin Liu, Dali Hu, Shiyun Pan, Qiling Huang
The present study examined the potential of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) to inhibit proliferation and induce apoptosis in non‑small‑cell lung cancer (NSCLC) cell lines. It also investigated its mechanisms of action in different genotypes of human NSCLC. A total of three NSCLC cell lines, PC‑9, A549, and NCI‑H1975, were treated with PA‑MSHA at different concentrations. The anti‑proliferative effect of PA‑MSHA was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay...
October 20, 2016: Molecular Medicine Reports
N Szentandrassy, B Horvath, K Vaczi, K Kistamas, L Masuda, J Magyar, T Banyasz, Z Papp, P P Nanasi
Omecamtiv mecarbil (OM) is a myosin activator agent recently developed for treatment of heart failure. Although its action on extending systolic ejection time and increasing left ventricular ejection fraction is well documented, no data is available regarding its possible side-effects on cardiac ion channels. Therefore, the present study was designed to investigate the effects of OM on action potential morphology and the underlying ion currents in isolated canine ventricular myocytes using sharp microelectrodes, conventional patch clamp, and action potential voltage clamp techniques...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Jia-Ze Tan, Yuan Man, Fei Xiao
BACKGROUND: Congenital myasthenic syndromes are a group of rare disorders that are clinically and genetically heterogeneous and caused by mutations in the genes encoding proteins of the neuromuscular junction. Here, we described a Chinese family that presented with phenotypes of classic slow-channel congenital myasthenic syndrome (SCCMS). METHODS: Clinical characteristics and electrophysiological features of three patients from a Chinese family were examined, and next-generation sequencing followed by direct sequencing was carried out...
2016: Chinese Medical Journal
Marie Eliade, Jeremy Skrzypski, Amandine Baurand, Caroline Jacquot, Geoffrey Bertolone, Catherine Loustalot, Charles Coutant, France Guy, Pierre Fumoleau, Yannis Duffourd, Laurent Arnould, Alexandra Delignette, Marie-Martine Padéano, Côme Lepage, Géraldine Raichon-Patru, Axelle Boudrant, Marie-Christine Bône-Lépinoy, Anne-Laure Villing, Aurélie Charpin, Karine Peignaux, Sandy Chevrier, Frédérique Vegran, François Ghiringhelli, Romain Boidot, Nicolas Sevenet, Sarab Lizard, Laurence Faivre
Until recently, the molecular diagnosis of hereditary breast and ovarian cancer (HBOC) was mostly based on BRCA1/2 testing. Next generation sequencing and the recent discovery of new genes involved in HBOC now permit the transfer of genomic capture targeting multiple candidate genes from research to clinical use. However, the implications for the management of patients and their families have not been extensively studied, in particular since some of these genes are not well-established cancer predisposing genes...
October 15, 2016: Oncotarget
R B Raffa, G Burdge, J Gambrah, H E Kinecki, F Lin, B Lu, J T Nguyen, V Phan, A Ruan, M A Sesay, T N Watkins
WHAT IS KNOWN AND OBJECTIVE: Chronic pain presents a difficult clinical challenge because of the limited efficacy, the limiting adverse-effect profile or the abuse potential of current analgesic options. Cebranopadol is a novel new agent in clinical trials that combines dual agonist action at opioid and nociceptin/orphanin FQ peptide (NOP) receptors. It is the first truly unique, centrally acting analgesic in several years. We here review the basic and clinical pharmacology of cebranopadol...
October 24, 2016: Journal of Clinical Pharmacy and Therapeutics
Arshag D Mooradian
The availability of effective drugs targeting the major risk factors of cardiovascular disease (CVD) has reduced morbidity and mortality. Cumulative relative risk of CVD events can be reduced by 75 % with a combination of aspirin, a β-adrenoceptor antagonist (β-blocker), an HMG-CoA reductase inhibitor (statin), and an angiotensin-converting enzyme inhibitor. The principal pharmacodynamics of these drugs cannot explain the entirety of their cardioprotective action, as other drugs with similar pharmacologic targets have not been associated with favorable clinical effects...
October 24, 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Federica Agosta, Roberto Gatti, Elisabetta Sarasso, Maria Antonietta Volonté, Elisa Canu, Alessandro Meani, Lidia Sarro, Massimiliano Copetti, Erik Cattrysse, Eric Kerckhofs, Giancarlo Comi, Andrea Falini, Massimo Filippi
Gait disorders represent a therapeutic challenge in Parkinson's disease (PD). This study investigated the efficacy of 4-week action observation training (AOT) on disease severity, freezing of gait and motor abilities in PD, and evaluated treatment-related brain functional changes. 25 PD patients with freezing of gait were randomized into two groups: AOT (action observation combined with practicing the observed actions) and "Landscape" (same physical training combined with landscape-videos observation). At baseline and 4-week, patients underwent clinical evaluation and fMRI...
October 24, 2016: Journal of Neurology
Reena Gupta, Kathleen Barnes, Thomas Bodenheimer
No abstract text is available yet for this article.
October 2016: Journal of Graduate Medical Education
E Longo, M Masellis, G Fondi, C Cedri, C Debbia, A Pitidis
Accidents and burns are a major problem in Italy and in industrialized countries, due to the consequences they have on health, especially in children aged 0-4 years. In Italy, about 400 people die each year from burns, with over 70% of these occurring in the home. In the European Union, burns are one of the top five causes of death from accidents, accounting for 3% of all deaths from accidents and violence in those age groups. One percent of all deaths in children are due to burns. In this paper, we illustrate the results of qualitative analysis, conducted according to the methodology of content analysis, on narratives included in the anamnesis of clinical papers at the ED in 738 cases of burns in children (0-14 years) observed in a sample of Emergency Departments in the years 2005-2009...
December 31, 2015: Annals of Burns and Fire Disasters
Satoshi Tanaka
Zoledronic acid hydrate(zoledronic acid)is an osteoporosis therapeutic agent which shows the fracture suppression effect with once-yearly intravenous infusion. Although zoledronic acid is quickly disappeared from the blood after intravenous infusion, it is taken into the bone immediately and incorporated into the bone tissue. In addition, zoledronic acid shows the potent suppression effect on bone resorption by inhibiting farnesyl diphosphate synthase of the mevalonate pathway(FPPS)strongly. In vivo study, the single intravenous administration of zoledronic acid to the mature ovariectomized(OVX)rats demonstrated to suppress the decreasing bone strength dose-dependently in 32 weeks, corresponding to more than one year in human...
2016: Clinical Calcium
James A McCubrey, Kvin Lertpiriyapong, Timothy L Fitzgerald, Alberto M Martelli, Lucio Cocco, Dariusz Rakus, Agnieszka Gizak, Massimo Libra, Melchiorre Cervello, Guiseppe Montalto, Li V Yang, Stephen L Abrams, Linda S Steelman
TP53 is a critical tumor suppressor gene that regulates cell cycle progression, apoptosis, cellular senescence and many other properties critical for control of normal cellular growth and death. Due to the pleiotropic effects that TP53 has on gene expression and cellular physiology, mutations at this tumor suppressor gene result in diverse physiological effects. T53 mutations are frequently detected in numerous cancers. The expression of TP53 can be induced by various agents used to treat cancer patients such as chemotherapeutic drugs and ionizing radiation...
October 6, 2016: Advances in Biological Regulation
M Luconi, L Raimondi, A Di Franco, E Mannucci
BACKGROUND: The results of the EMPA-REG-OUTCOME trial on type 2 diabetic patients at high risk for prior cardiovascular events showed that empagliflozin produces a remarkable reduction in the rates of hospitalization for heart failure (35%), cardiovascular death (38%), and all-cause death (32%). This unexpected cardio-protective action cannot be accounted for by the improvement of "classical" cardiovascular risk factors. AIMS: This review aims at summarizing current knowledge on the cardiovascular action of SGLT2 inhibitors and discuss the different hypotheses formulated to explain the results of the EMPA-REG-OUTCOME-study...
September 10, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Rhodri L Williams, Wayne N Ayre, Wasim S Khan, Amisha Mehta, Rhidian Morgan-Jones
BACKGROUND: Thorough debridement is mandatory in revision for infected total knee arthroplasties (TKA). We investigated a novel adjuvant chemical debridement strategy using acetic acid (AA) that seeks to create a hostile environment for microorganisms. We report the first orthopedic in vivo series using an AA soak in infected TKAs. We also investigated the in vitro efficacy of AA against bacteria isolated from these knees. METHODS: Twenty-three patients with infected TKA were treated with a standard debridement protocol and chemical debridement with a 20-minute AA soak...
September 28, 2016: Journal of Arthroplasty
Vera Lucia Rasera Zotelli, Cássia Maria Grillo, Maria da Luz Rosário de Sousa
When nausea, an extremely unpleasant symptom, is experienced during dental treatment, it generates disorders and obstacles for both the patient and the professional, compromising the good quality of dental care. Clinical studies have confirmed the antiemetic action of acupuncture and shown its use for the treatment of nausea and vomiting. In the scientific literature there are several recent studies that address the placebo effect of acupuncture. The aim of this manuscript is to present a case report of a 46-year-old Caucasian male patient, who had severe symptoms of nausea while undergoing dental care...
October 2016: Journal of Acupuncture and Meridian Studies
Sven Jarius, Marius Ringelstein, Jürgen Haas, Irina I Serysheva, Lars Komorowski, Kai Fechner, Klaus-Peter Wandinger, Philipp Albrecht, Harald Hefter, Andreas Moser, Eva Neuen-Jacob, Hans-Peter Hartung, Brigitte Wildemann, Orhan Aktas
BACKGROUND: Recently, we described a novel autoantibody, anti-Sj/ITPR1-IgG, that targets the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in patients with cerebellar ataxia. However, ITPR1 is expressed not only by Purkinje cells but also in the anterior horn of the spinal cord, in the substantia gelatinosa and in the motor, sensory (including the dorsal root ganglia) and autonomic peripheral nervous system, suggesting that the clinical spectrum associated with autoimmunity to ITPR1 may be broader than initially thought...
October 24, 2016: Journal of Neuroinflammation
Markolf Hanefeld, Denis Raccah, Louis Monnier
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with hyperglycemia, which can lead to serious vascular complications. Current treatment guidelines place particular emphasis on personalization of therapy. Within this guidance, the use of various second-line therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is recommended under certain circumstances. Areas covered: Factors influencing glucose homeostasis, including gastric emptying and the associated cardiovascular (CV) risk when homeostasis is not maintained, are reviewed...
October 25, 2016: Expert Opinion on Drug Metabolism & Toxicology
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