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https://www.readbyqxmd.com/read/28735360/navigating-the-future-of-cardiovascular-drug-development-leveraging-novel-approaches-to-drive-innovation-and-drug-discovery-summary-of-findings-from-the-novel-cardiovascular-therapeutics-conference
#1
REVIEW
Thomas J Povsic, Rob Scott, Kenneth W Mahaffey, Robert Blaustein, Jay M Edelberg, Martin P Lefkowitz, Scott D Solomon, Jonathan C Fox, Kevin E Healy, Aarif Y Khakoo, Douglas W Losordo, Fady I Malik, Brett P Monia, Rusty L Montgomery, Jeffrey Riesmeyer, Gregory G Schwartz, Steven L Zelenkofske, Joseph C Wu, Scott M Wasserman, Matthew T Roe
PURPOSE: The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiovascular disease. METHODS: The Novel Cardiovascular Therapeutics Summit first reviewed recent examples of ongoing or recently completed programs translating basic science observations to targeted drug development, highlighting successes (protein convertase sutilisin/kexin type 9 [PCSK9] and neprilysin inhibition) and targets still under evaluation (cholesteryl ester transfer protein [CETP] inhibition), with the hope of gleaning key lessons to successful drug development in the current era...
July 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28735109/design-and-rationale-for-a-real-world-observational-cohort-of-patients-with-nonalcoholic-fatty-liver-disease-the-target-nash-study
#2
A Sidney Barritt, Norman Gitlin, Samuel Klein, Anna S Lok, Rohit Loomba, Laura Malahias, Margaret Powell, Miriam B Vos, L Michael Weiss, Kenneth Cusi, Brent A Neuschwander-Tetri, Arun Sanyal
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. NAFLD comprises the spectrum from simple steatosis (nonalcoholic fatty liver, NAFL), to steatosis with inflammation (nonalcoholic steatohepatitis, NASH). Current primary therapy recommended for NAFLD is weight loss induced by lifestyle modification. The difficulty in achieving this has led to robust pharmacological therapy development. While new drugs may show efficacy in selected phase II/III clinical trial populations, their real-world effectiveness is unknown...
July 19, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28735098/cholangiocytes-cell-transplantation
#3
REVIEW
Lorenzo Ridola, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, Domenico Alvaro
BACKGROUND: Due to significant limitations to the access to orthotropic liver transplantation, cell therapies for liver diseases have gained large interest worldwide. SCOPE OF REVIEW: To revise current literature dealing with cell therapy for liver diseases. We discussed the advantages and pitfalls of the different cell sources tested so far in clinical trials and the rationale underlying the potential benefits of transplantation of human biliary tree stem cells (hBTSCs)...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28735000/application-of-pharmacometrics-and-quantitative-systems-pharmacology-to-cancer-therapy-the-example-of-luminal-a-breast-cancer
#4
REVIEW
Brett Fleisher, Kayla Andrews, Ashley A Brown, Sihem Ait-Oudhia
Breast cancer (BC) is the most common cancer in women, and the second most frequent cause of cancer-related deaths in women worldwide. It is a heterogeneous disease composed of multiple subtypes with distinct morphologies and clinical implications. Quantitative systems pharmacology (QSP) is an emerging discipline bridging systems biology with pharmacokinetics (PK) and pharmacodynamics (PD) leveraging the systematic understanding of drugs' efficacy and toxicity. Despite numerous challenges in applying computational methodologies for QSP and mechanism-based PK/PD models to biological, physiological, and pharmacological data, bridging these disciplines has the potential to enhance our understanding of complex disease systems such as BC...
July 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28734944/triple-negative-breast-cancer-next-generation-sequencing-for-target-identification
#5
REVIEW
Jonathan D Marotti, Francine B de Abreu, Wendy A Wells, Gregory J Tsongalis
Our ability to now study disease at the most fundamental molecular level has led to a reclassification of human cancers into numerous subtypes that vary in disease progression and response to therapy. Like most solid tumors, breast cancer is a heterogeneous disease with considerable variation in histological and biological features. Triple negative breast cancer (TNBC) is a subtype of breast cancer in which estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor receptor 2 is not amplified or overexpressed...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28734880/dual-versus-single-antiplatelet-regimen-with-or-without-anticoagulation-in-transcatheter-aortic-valve-replacement-indirect-comparison-and-meta-analysis
#6
Monica Verdoia, Lucia Barbieri, Matteo Nardin, Harry Suryapranata, Giuseppe De Luca
INTRODUCTION AND OBJECTIVES: There is uncertainty on the correct management of antithrombotic therapies after transcatheter aortic valve replacement (TAVR), with dual antiplatelet therapy (DAPT) being currently recommended on an empirical basis. The aim of the present meta-analysis was to assess the safety and effectiveness of DAPT in patients undergoing TAVR. METHODS: Studies comparing different antithrombotic regimens after TAVR were included. The primary endpoint was 30-day overall mortality...
July 19, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28734860/the-expanding-field-of-biologics-in-the-management-of-chronic-urticaria
#7
Shyam Joshi, David A Khan
Chronic urticaria (CU) is the occurrence of urticaria with or without angioedema for at least 6 weeks. Management has traditionally involved antihistamines as first-line therapy with various alternative therapies for refractory cases. Largely based on the success of biologics for various diseases, this class of drugs has come to the forefront of medical research. The first and only Food and Drug Administration-approved biologic for the management of CU is omalizumab (humanized anti-IgE mAb). In the past decade, a substantial amount of research has been centered on the mechanism of action, efficacy, dosing, and safety of omalizumab...
July 19, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28734722/guidelines-for-the-understanding-and-management-of-pain-in-chronic-pancreatitis
#8
REVIEW
Asbjørn M Drewes, Stefan A W Bouwense, Claudia M Campbell, Güralp O Ceyhan, Myriam Delhaye, Ihsan Ekin Demir, Pramod K Garg, Harry van Goor, Christopher Halloran, Shuiji Isaji, John P Neoptolemos, Søren S Olesen, Tonya Palermo, Pankaj Jay Pasricha, Andrea Sheel, Tooru Shimosegawa, Eva Szigethy, David C Whitcomb, Dhiraj Yadav
Abdominal pain is the foremost complication of chronic pancreatitis (CP). Pain can be related to recurrent or chronic inflammation, local complications or neurogenic mechanisms with corresponding changes in the nervous systems. Both pain intensity and the frequency of pain attacks have been shown to reduce quality of life in patients with CP. Assessment of pain follows the guidelines for other types of chronic pain, where the multidimensional nature of symptom presentation is taken into consideration. Quantitative sensory testing may be used to characterize pain, but is currently used in a research setting in advanced laboratories...
July 13, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28734595/arrhythmias-after-left-ventricular-assist-device-implantation-incidence-and-management
#9
REVIEW
Anis J Kadado, Joseph G Akar, James P Hummel
The use of mechanical circulatory support has become an increasingly common practice in patients with heart failure, whether used as bridge to transplantation or as destination therapy. The last couple of decades has seen a drastic change in the functioning of the left ventricular assist devices (LVAD), changing from the first generation devices running on pulsatile flow to the current continuous flow devices. Atrial and ventricular arrhythmias are common among heart failure patients, and though the systematic circulation is well supported in patients on mechanical circulatory support, these arrhythmias can still be the cause of detrimental symptoms and lead to potentially fatal outcomes...
July 10, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28734548/ubiquitin-like-modifications-in-the-dna-damage-response
#10
REVIEW
Zhifeng Wang, Wei-Guo Zhu, Xingzhi Xu
Genomic DNA is damaged at an extremely high frequency by both endogenous and environmental factors. An improper response to DNA damage can lead to genome instability, accelerate the aging process and ultimately cause various human diseases, including cancers and neurodegenerative disorders. The mechanisms that underlie the cellular DNA damage response (DDR) are complex and are regulated at many levels, including at the level of post-translational modification (PTM). Since the discovery of ubiquitin in 1975 and ubiquitylation as a form of PTM in the early 1980s, a number of ubiquitin-like modifiers (UBLs) have been identified, including small ubiquitin-like modifiers (SUMOs), neural precursor cell expressed, developmentally down-regulated 8 (NEDD8), interferon-stimulated gene 15 (ISG15), human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10), ubiquitin-fold modifier 1 (UFRM1), URM1 ubiquitin-related modifier-1 (URM1), autophagy-related protein 12 (ATG12), autophagy-related protein 8 (ATG8), fan ubiquitin-like protein 1 (FUB1) and histone mono-ubiquitylation 1 (HUB1)...
July 11, 2017: Mutation Research
https://www.readbyqxmd.com/read/28734226/inhibition-of-prb-pathway-differentially-modulates-apoptosis-in-esophageal-cancer-cells
#11
Rossana C Soletti, Deborah Biasoli, Nathassya A L V Rodrigues, João M A Delou, Renata Maciel, Vera L A Chagas, Rodrigo A P Martins, Stevens K Rehen, Helena L Borges
Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Current chemotherapy regimens include a combination of 5-fluorouracil (5-FU) and cisplatin, but more efficient therapy strategies are needed to increase 5-year survival. Alterations in the signaling pathway of the tumor suppressor gene Rb-1, which encodes a phosphoprotein (pRB) that negatively regulates the G1/S transition of the cell cycle, are present in 70% of all tumors, but its role in esophageal cancer is still unclear...
July 19, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28734195/implementation-of-psychological-clinical-trials-in-epilepsy-review-and-guide
#12
REVIEW
Avani C Modi, Janelle Wagner, Aimee W Smith, Tanja S Kellermann, Rosa Michaelis
The International League Against Epilepsy (ILAE) Neuropsychiatry commission and United States Institute of Medicine report both identified cognitive and psychological comorbidities as a significant issue for individuals with epilepsy, with rates as high as 60%. However, there is a paucity of evidence-based treatments for many psychological conditions (e.g., learning disorders, cognitive disorders, behavioral disorders). Because of inherent challenges in the implementation of psychological therapy trials and specific considerations for the population with epilepsy, the focus of the current review was to provide guidance and recommendations to conduct psychological trials for individuals with epilepsy...
July 19, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28734176/cancer-immunotherapy-moving-forward-with-peptide-t-cell-vaccines
#13
REVIEW
Takumi Kumai, Aaron Fan, Yasuaki Harabuchi, Esteban Celis
Recent advances in cancer immunology, such as the discovery of immune checkpoint inhibitors, have validated immune cells as potential key players for effective cancer treatment. The efficacy of these therapies seems to be codependent on a tumor-reactive T lymphocyte response. For many years, numerous attempts and strategies in developing vaccines to generate tumor-reactive T cells have yielded poor results in the clinic due to suboptimal immunogenicity and the inability to overcome an immunosuppressive tumor microenvironment...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28733944/the-gastric-and-intestinal-microbiome-role-of-proton-pump-inhibitors
#14
REVIEW
Artem Minalyan, Lilit Gabrielyan, David Scott, Jonathan Jacobs, Joseph R Pisegna
PURPOSE OF REVIEW: The discovery of Helicobacter pylori and other organisms colonizing the stomach and the intestines has shed some light on the importance of microbiome in maintaining overall health and developing pathological conditions when alterations in biodiversity are present. The gastric acidity plays a crucial role in filtering out bacteria and preventing development of enteric infections. In this article, we discuss the physiology of gastric acid secretion and bacterial contribution to the composition of gastric and intestinal barriers and review the current literature on the role of proton pump inhibitors (PPIs) in the microbial biodiversity of the gastrointestinal tract...
August 2017: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/28733935/g3-gep-nens-category-are-basic-and-clinical-investigations-well-integrated
#15
Massimo Milione, Nicola Fazio
Gastroenteropancreatic neuroendocrine neoplasms grade 3, all of them with >20% Ki-67, can be heterogeneous on the basis of their morphological features, comprising well and poorly differentiated neoplasms; the former are named tumors and the latter carcinomas. Several papers about gastroenteropancreatic neuroendocrine neoplasms grade 3 heterogeneity have been reporting over the last years by clinicians and pathologists, indicating that the differential diagnosis between named tumors grade 3 and named carcinomas grade 3 may be relevant in defining a different approach in terms of characterization of disease, staging, and treatment...
July 21, 2017: Endocrine
https://www.readbyqxmd.com/read/28733933/immunohistochemical-analysis-of-h3k27me3-demonstrates-global-reduction-in-group-a-childhood-posterior-fossa-ependymoma-and-is-a-powerful-predictor-of-outcome
#16
Pooja Panwalkar, Jonathan Clark, Vijay Ramaswamy, Debra Hawes, Fusheng Yang, Christopher Dunham, Stephen Yip, Juliette Hukin, Yilun Sun, Matthew J Schipper, Lukas Chavez, Ashley Margol, Melike Pekmezci, Chan Chung, Adam Banda, Jill M Bayliss, Sarah J Curry, Mariarita Santi, Fausto J Rodriguez, Matija Snuderl, Matthias A Karajannis, Amanda M Saratsis, Craig M Horbinski, Anne-Sophie Carret, Beverly Wilson, Donna Johnston, Lucie Lafay-Cousin, Shayna Zelcer, David Eisenstat, Marianna Silva, Katrin Scheinemann, Nada Jabado, P Daniel McNeely, Marcel Kool, Stefan M Pfister, Michael D Taylor, Cynthia Hawkins, Andrey Korshunov, Alexander R Judkins, Sriram Venneti
Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available...
July 21, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28733926/perioperative-management-of-endocrine-insufficiency-after-total-pancreatectomy-for-neoplasia
#17
REVIEW
Ajay V Maker, Raashid Sheikh, Vinita Bhagia
PURPOSE: Indications for total pancreatectomy (TP) have increased, including for diffuse main duct intrapapillary mucinous neoplasms of the pancreas and malignancy; therefore, the need persists for surgeons to develop appropriate endocrine post-operative management strategies. The brittle diabetes after TP differs from type 1/2 diabetes in that patients have absolute deficiency of insulin and functional glucagon. This makes glucose management challenging, complicates recovery, and predisposes to hospital readmissions...
July 21, 2017: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/28733905/glp-1-glucagon-receptor-co-agonism-for-treatment-of-obesity
#18
REVIEW
Miguel A Sánchez-Garrido, Sara J Brandt, Christoffer Clemmensen, Timo D Müller, Richard D DiMarchi, Matthias H Tschöp
Over a relatively short period, obesity and type 2 diabetes have come to represent a large medical and economic burden to global societies. The epidemic rise in the prevalence of obesity has metabolic consequences and is paralleled by an increased occurrence of other diseases, such as diabetes, cancer and cardiovascular complications. Together, obesity and type 2 diabetes constitute one of the more preventable causes of premature death and the identification of novel, safe and effective anti-obesity drugs is of utmost importance...
July 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28733901/current-knowledge-on-exosome-biogenesis-and-release
#19
REVIEW
Nina Pettersen Hessvik, Alicia Llorente
Exosomes are nanosized membrane vesicles released by fusion of an organelle of the endocytic pathway, the multivesicular body, with the plasma membrane. This process was discovered more than 30 years ago, and during these years, exosomes have gone from being considered as cellular waste disposal to mediate a novel mechanism of cell-to-cell communication. The exponential interest in exosomes experienced during recent years is due to their important roles in health and disease and to their potential clinical application in therapy and diagnosis...
July 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28733851/autism-and-equine-assisted-interventions-a-systematic-mapping-review
#20
B Caitlin McDaniel Peters, Wendy Wood
This systematic mapping review mapped current knowledge of equine-assisted interventions for people with autism to help guide future practice and research. Thirty-three studies including children and adolescents with autism, 3 of which confirmed diagnoses, were reviewed. Five types of equine-assisted activities were identified across 25 studies, with reported improvements in behavior, social interaction, and communication. Four types of equine-assisted therapies were identified across 8 studies, with reported improvements in motor control and self-care...
July 21, 2017: Journal of Autism and Developmental Disorders
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