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P4 medicine

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https://www.readbyqxmd.com/read/28919180/development-of-a-cyclosporin-a-derivative-with-excellent-anti-hepatitis-c-virus-potency
#1
Jiping Fu, Christopher Becker, Li Cao, Michael Capparelli, Regis Denay, Roger Fujimoto, Yu Gai, Zhaobo Gao, Christian Guenat, Subramanian Karur, Hongyong Kim, Weikuan Li, Xiaolin Li, Wei Li, Thomas Lochmann, Amy Lu, Peichao Lu, Alexandre Luneau, Nicole Meier, Wosenu Mergo, Simon Ng, David Parker, Yunshan Peng, Bernard Riss, Alexey Rivkin, Silvio Roggo, Harald Schroeder, Friedrich Schuerch, Robert L Simmons, Feng Sun, Zachary K Sweeney, Meiliana Tjandra, Michael Wang, Ruidong Wang, Andrew H Weiss, Nicolas Wenger, Quanbing Wu, Xin Xiong, Su Xu, Wenjian Xu, Aregahegn Yifru, Jibin Zhao, Jianguang Zhou, Christian Zürcher, Fabrice Gallou
Synthetic modification of cyclosporin A at P3-P4 positions led to the discovery of NIM258, a next generation cyclophilin inhibitor with excellent anti-hepatitis C virus potency, with decreased transporter inhibition, and pharmacokinetics suitable for coadministration with other drugs. Herein is disclosed the evolution of the synthetic strategy to from the original medicinal chemistry route, designed for late diversification, to a convergent and robust development synthesis. The chiral centers in the P4 fragment were constructed by an asymmetric chelated Claisen rearrangement in the presence of quinidine as the chiral ligand...
September 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28845852/-rare-diseases-in-post-genomic-era
#2
Simonetta Pulciani, Andrea Vittozzi, Stefano Diemoz, Emanuele Nutile, Domenica Taruscio
The Human Genome Project and the "-omics" technologies will in future provide genetic maps and biosynthetic pathways permitting personalized medical interventions directed at maintaining or restoring wellbeing. This is reflected in the strategy aims of 4P medicine in being: predictive, preventive, personalized, and participatory. The results obtained in the field of cystic fibrosis, with the cloning of CFTR gene, and use of Kalydeco®, have demonstrated how using the mentioned strategies could also have success in rare disease management...
July 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28805797/human-genomics-projects-and-precision-medicine
#3
REVIEW
F Carrasco-Ramiro, R Peiró-Pastor, B Aguado
The completion of the Human Genome Project (HGP) in 2001 opened the floodgates to a deeper understanding of medicine. There are dozens of HGP-like projects which involve from a few tens to several million genomes currently in progress, which vary from having specialised goals or a more general approach. However, data generation, storage, management and analysis in public and private cloud computing platforms have raised concerns about privacy and security. The knowledge gained from further research has changed the field of genomics and is now slowly permeating into clinical medicine...
August 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28772093/metabolic-state-can-define-the-ovarian-response-to-environmental-contaminants-and-medicinal-plants
#4
Alexander V Sirotkin, Dušan Fabian, Janka Babeľová Kubandová, Radoslava Vlčková, Saleh Alwasel, Abdel Halim Harrath
Environmental contaminants and medicinal plants can affect reproductive processes. The aim of this study was to investigate the effect of maternal metabolic status on the response of mouse ovaries to the environmental contaminants benzene and xylene, as well as to extracts of the medicinal yucca plant. Ovaries isolated from normal-lean and slightly obese mice were cultured with or without 0.1% benzene or xylene for 24 h. Similarly, ovaries isolated from normal-lean, slightly obese, and significantly obese mice were cultured for 24 h with or without an extract of Yucca shildegera (YS, 10 µg/mL)...
August 3, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28698893/cytotoxicity-against-tumor-cell-lines-and-anti-inflammatory-properties-of-chitinases-from-calotropis-procera-latex
#5
Carolina Araújo Viana, Márcio V Ramos, José Delano Barreto Marinho Filho, Letícia Veras Costa Lotufo, Ingrid Samantha Tavares Figueiredo, Jefferson Soares de Oliveira, Pietro Mastroeni, José Vitor Lima-Filho, Nylane Maria Nunes Alencar
The role of chitinases from the latex of medicinal shrub Calotropis procera on viability of tumor cell lines and inflammation was investigated. Soluble latex proteins were fractionated in a CM Sepharose Fast-Flow Column and the major peak (LPp1) subjected to ion exchange chromatography using a Mono-Q column coupled to an FPLC system. In a first series of experiments, immortalized macrophages were cultured with LPp1 for 24 h. Then, cytotoxicity of chitinase isoforms (LPp1-P1 to P6) was evaluated against HCT-116 (colon carcinoma), OVCAR-8 (ovarian carcinoma), and SF-295 (glioblastoma) tumor cell lines in 96-well plates...
July 11, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28693305/comparison-the-characteristics-of-canine-adipose-tissue-derived-mesenchymal-stem-cells-extracted-from-different-sites-and-at-different-passage-numbers
#6
Kevin M Yaneselli, Cristiana Palma Kuhl, Paula Barros Terraciano, Fernanda dos Santos de Oliveira, Sabrina Beal Pizzato, Kamila Pazza, Alessandra Bileski Magrisso, Vanessa Torman, Analía Rial, María Moreno, Silvia Llambí, Elizabeth Cirne Lima, Jacqueline Maisonnave
Mesenchymal Stem Cells (MSCs) have attractive characteristics for therapy in animal models and veterinary medicine, due to the capacity of inducing tissue regeneration and immunomodulation. The objective of this study was to evaluate the differences between canine adipose tissue-derived MSCs (AD-MSCs) extracted from subcutaneous (Sc) and visceral (Vs) sites. Surface antigenic markers, in vitro differentiation and mineralized matrix quantification of AD-MSCs in different passages (P4, P6 and P8) were studied...
July 10, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28575140/optimizing-drug-development-in-oncology-by-clinical-trial-simulation-why-and-how
#7
Jocelyn Gal, Gérard Milano, Jean-Marc Ferrero, Esma Saâda-Bouzid, Julien Viotti, Sylvie Chabaud, Paul Gougis, Christophe Le Tourneau, Renaud Schiappa, Agnes Paquet, Emmanuel Chamorey
In therapeutic research, the safety and efficacy of pharmaceutical products are necessarily tested on humans via clinical trials after an extensive and expensive preclinical development period. Methodologies such as computer modeling and clinical trial simulation (CTS) might represent a valuable option to reduce animal and human assays. The relevance of these methods is well recognized in pharmacokinetics and pharmacodynamics from the preclinical phase to postmarketing. However, they are barely used and are poorly regarded for drug approval, despite Food and Drug Administration and European Medicines Agency recommendations...
May 29, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28549701/patient-centered-p4-medicine-and-the-older-person
#8
EDITORIAL
John E Morley, Bruno Vellas
No abstract text is available yet for this article.
June 1, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28535315/early-career-outcomes-of-family-medicine-residency-graduates-exposed-to-innovative-flexible-longitudinal-tracks
#9
Richard A Young, Dan Casey, Diana Singer, Elaine Waller, Patricia A Carney
BACKGROUND AND OBJECTIVES: The Preparing the Personal Physician for Practice (P4) project used a case series design to study innovations in the content, length, structure, and location of residency training in 14 geographically diverse family medicine programs between 2007 and 2012. We aimed to explore how offering flexible longitudinal tracks (FLT) affected graduates' scope of practice, particularly in maternal child health (MCH), which included at least 17 months of focused training that increased each year over 4 years...
May 2017: Family Medicine
https://www.readbyqxmd.com/read/28535314/team-training-in-family-medicine-residency-programs-and-its-impact-on-team-based-practice-post-graduation
#10
Patricia A Carney, Elaine Waller, Eve Dexter, Miguel Marino, Kelly Morton, Larry Green, Colleen T Fogarty, Samuel Jones, M Patrice Eiff
OBJECTIVE: Our objective was to examine perceptions of adequacy in team-based care training during residency and whether this influences practice choice post- residency training. METHODS: We analyzed self-administered survey data from recent residency graduates collected as part of the Preparing Personal Physicians for Practice (P4) Project to characterize residents' perceptions of adequacy of training they received on team-based care. Multivariable logistic regression was used to assess the association between adequacy of team-based care training and joining practices that use team-based care after residency graduation, adjusting for differences in demographics...
May 2017: Family Medicine
https://www.readbyqxmd.com/read/28529704/towards-a-systems-approach-for-chronic-diseases-based-on-health-state-modeling
#11
Michael Rebhan
Rising pressure from chronic diseases means that we need to learn how to deal with challenges at a different level, including the use of systems approaches that better connect across fragments, such as disciplines, stakeholders, institutions, and technologies. By learning from progress in leading areas of health innovation (including oncology and AIDS), as well as complementary indications (Alzheimer's disease), I try to extract the most enabling innovation paradigms, and discuss their extension to additional areas of application within a systems approach...
2017: F1000Research
https://www.readbyqxmd.com/read/28477347/p4-medicine-approach-to-obstructive-sleep-apnoea
#12
REVIEW
Diane C Lim, Kate Sutherland, Peter A Cistulli, Allan I Pack
P4 medicine is an evolving approach to personalized medicine. The four Ps offer a means to: Predict who will develop disease and co-morbidities; Prevent rather than react to disease; Personalize diagnosis and treatment; have patients Participate in their own care. P4 medicine is very applicable to obstructive sleep apnoea (OSA) because each OSA patient has a different pathway to disease and its consequences. OSA has both structural and physiological mechanisms with different clinical subgroups, different molecular profiles and different consequences...
July 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28467059/discovery-of-heteropolytantalate-synthesis-and-structure-of-two-6-peroxotantalo-4-phosphate-clusters
#13
Dongdi Zhang, Zhijie Liang, Suyi Liu, Longsheng Li, Pengtao Ma, Shufang Zhao, Haiying Wang, Jingping Wang, Jingyang Niu
Polyoxometalates (POMs) of Nb and Ta are greatly different from those of Mo, W, and V that have been studied extensively and developed well. The latter can be formed simply by acidification of their aqueous monomeric oxoanions and has found application areas from catalysis to magnetism, materials science, medicine, and nanotechnology. Even now the polyoxoniobate (PONb) chemistry has accelerated dramatically over the last 15 years, and a vast expansion of available PONbs has been reported. However, after nearly 200 years of POM research, Ta-based POM chemistry is still at its infant stage and only dominated by the isopolyoxotantalate ions (Ta6 and Ta10) and transition-metal-capped Ta6 species, along with two Ti-substituted polyoxotantalates [Ti2Ta8O28](8-) and [Ti12Ta6O44](10-) reported very recently...
May 3, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28443607/novel-approaches-for-the-promotion-of-physical-activity-and-exercise-for-prevention-and-management-of-type-2-diabetes
#14
REVIEW
R Arena, M Sagner, N M Byrne, A D Williams, A McNeil, S J Street, A P Hills
Despite increased evidence for the importance of lifestyle modification, physical activity and diet in diabetes prevention and management, habitual physical activity levels have declined in recent decades in China and India. Further, other risk factors for type 2 diabetes, including overweight, obesity and physical inactivity, have also worsened. Here we present evidence for the importance of physical activity and exercise in the amelioration of type 2 diabetes and propose a novel approach to address the challenge of improving lifestyle behaviors in China and India-Movement is Medicine and a P4 (predictive, preventive, personalized and participatory) approach...
July 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28430854/dynamic-modeling-and-network-approaches-for-omics-time-course-data-overview-of-computational-approaches-and-applications
#15
Yulan Liang, Arpad Kelemen
Inferring networks and dynamics of genes, proteins, cells and other biological entities from high-throughput biological omics data is a central and challenging issue in computational and systems biology. This is essential for understanding the complexity of human health, disease susceptibility and pathogenesis for Predictive, Preventive, Personalized and Participatory (P4) system and precision medicine. The delineation of the possible interactions of all genes/proteins in a genome/proteome is a task for which conventional experimental techniques are ill suited...
April 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28346620/varied-rates-of-implementation-of-patient-centered-medical-home-features-and-residents-perceptions-of-their-importance-based-on-practice-experience
#16
M Patrice Eiff, Larry A Green, Geoff Jones, Alex Verdieck Devlaeminck, Elaine Waller, Eve Dexter, Miguel Marino, Patricia A Carney
BACKGROUND AND OBJECTIVES: Little is known about how the patient-centered medical home (PCMH) is being implemented in residency practices. We describe both the trends in implementation of PCMH features and the influence that working with PCMH features has on resident attitudes toward their importance in 14 family medicine residencies associated with the P4 Project. METHODS: We assessed 24 residency continuity clinics annually between 2007-2011 on presence or absence of PCMH features...
March 2017: Family Medicine
https://www.readbyqxmd.com/read/28287417/the-effect-of-chinese-herbal-medicine-formula-mkg-on-allergic-asthma-by-regulating-lung-and-plasma-metabolic-alternations
#17
Meng Yu, Hong-Mei Jia, Feng-Xia Cui, Yong Yang, Yang Zhao, Mao-Hua Yang, Zhong-Mei Zou
Asthma is a chronic inflammatory disorder of the airway and is characterized by airway remodeling, hyperresponsiveness, and shortness of breath. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicines (TCM), has been demonstrated to have good therapeutic effects on experimental allergic asthma. However, its anti-asthma mechanism remains currently unknown. In the present work, metabolomics studies of biochemical changes in the lung tissue and plasma of ovalbumin (OVA)-induced allergic asthma mice with mKG treatment were performed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)...
March 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28286989/a-precision-medicine-initiative-for-alzheimer-s-disease-the-road-ahead-to-biomarker-guided-integrative-disease-modeling
#18
REVIEW
H Hampel, S E O'Bryant, S Durrleman, E Younesi, K Rojkova, V Escott-Price, J-C Corvol, K Broich, B Dubois, S Lista
After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine...
April 2017: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/28270929/changing-paradigms-in-the-management-of-rejection-in-kidney-transplantation-evolving-from-protocol-based-care-to-the-era-of-p4-medicine
#19
Mirela Maier, Tomoko Takano, Ruth Sapir-Pichhadze
PURPOSE OF REVIEW: P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine's relevance to the various stages of the kidney transplant cycle. SOURCES OF INFORMATION: A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016) using a combination of subject headings (MeSH) and free text in titles, abstracts, and author keywords for the concepts kidney transplantation and P4 medicine...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28222613/phytochemical-investigations-and-antiproliferative-secondary-metabolites-from-thymus-alternans-growing-in-slovakia
#20
COMPARATIVE STUDY
Stefano Dall'Acqua, Gregorio Peron, Sara Ferrari, Valentina Gandin, Massimo Bramucci, Luana Quassinti, Pavol Mártonfi, Filippo Maggi
CONTEXT: Thymus alternans Klokov (Lamiaceae) is a neglected species of the genus Thymus (Sect. Serpyllum) endemic to Carpathian area, where it is used as a flavouring agent and for medicinal purposes. OBJECTIVE: The aim of the work was to identify antiproliferative constituents from the flowering aerial parts of this plant. MATERIALS AND METHODS: Thymus alternans extracts were analyzed by HPLC-MS(n) and subjected to extensive chromatographic separations...
December 2017: Pharmaceutical Biology
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