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https://www.readbyqxmd.com/read/28647083/the-production-of-3d-tumor-spheroids-for-cancer-drug-discovery
#1
REVIEW
Shilpa Sant, Paul A Johnston
New cancer drug approval rates are ≤5% despite significant investments in cancer research, drug discovery and development. One strategy to improve the rate of success of new cancer drugs transitioning into the clinic would be to more closely align the cellular models used in the early lead discovery with pre-clinical animal models and patient tumors. For solid tumors, this would mandate the development and implementation of three dimensional (3D) in vitro tumor models that more accurately recapitulate human solid tumor architecture and biology...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28643030/hospital-electronic-prescribing-system-implementation-impact-on-discharge-information-communication-and-prescribing-errors-a-before-and-after-study
#2
Pamela Ruth Mills, Anita Elaine Weidmann, Derek Stewart
PURPOSE: The study aimed to test the hypothesis that hospital electronic prescribing and medicine administration system (HEPMA) implementation impacted patient discharge letter quality, nature and frequency of prescribing errors. METHOD: A quasi experimental before and after retrospective case note review was conducted in one United Kingdom district general hospital. The total sample size was 318 (random samples of 159 before and after implementation), calculated to achieve a 10% error reduction with a power of 80% and p < 0...
June 22, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28643003/recent-developments-in-solution-nuclear-magnetic-resonance-nmr-based-molecular-biology
#3
REVIEW
Joshua J Ziarek, Diego Baptista, Gerhard Wagner
Visualizing post-translational modifications, conformations, and interaction surfaces of protein structures at atomic resolution underpins the development of novel therapeutics to combat disease. As computational resources expand, in silico calculations coupled with experimentally derived structures and functional assays have led to an explosion in structure-based drug design (SBDD) with several compounds in clinical trials. It is increasingly clear that "hidden" transition-state structures along activation trajectories can be harnessed to develop novel classes of allosteric inhibitors...
June 23, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28638433/shenqiwan-ameliorates-renal-fibrosis-in-rats-by-inhibiting-tgf-%C3%AE-1-smads-signaling-pathway
#4
Hongshu Chen, Yiqing Xu, Yuanxiao Yang, Xiaojie Zhou, Shijie Dai, Changyu Li
Epithelial-mesenchymal transition (EMT) refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF). Traditional Chinese Medicine Shenqiwan (SQW) is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-β1/Smads signaling pathway. A rat model of adenine (150 mg/kg) was established and intragastrically treated with various concentrations of SQW at dose of 1...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28637360/who-or-what-has-agency-in-the-discussion-of-antimicrobial-resistance-in-uk-news-media-2010-2015-a-transitivity-analysis
#5
Luke Curtis Collins, Rusi Jaspal, Brigitte Nerlich
The increase in infections resistant to the existing antimicrobial medicines has become a topic of concern for health professionals, policy makers and publics across the globe; however, among the public there is a sense that this is an issue beyond their control. Research has shown that the news media can have a significant role to play in the public's understanding of science and medicine. In this article, we respond to a call by research councils in the United Kingdom to study antibiotic or antimicrobial resistance as a social phenomenon by providing a linguistic analysis of reporting on this issue in the UK press...
June 1, 2017: Health (London)
https://www.readbyqxmd.com/read/28636347/the-structure-and-dynamics-of-alginate-gels-crosslinked-by-polyvalent-ions-probed-via-solid-state-nmr-spectroscopy
#6
Jiří Brus, Martina Urbanová, Jiri Czernek, Miroslava Pavelkova, Katerina Kubova, Jakub Vyslouzil, Sabina Abbrent, Rafal Konefal, Jiri Horsky, David Vetchy, Jan Vysloužil, Pavel Kulich
Alginate gels are an outstanding biomaterial widely applicable in tissue engineering, medicine, and pharmacy for cell transplantation, wound healing and efficient bioactive agent delivery, respectively. This contribution provides new and comprehensive insight into the atomic-resolution structure and dynamics of polyvalent ion-crosslinked alginate gels in microbead formulations. By applying various advanced solid-state NMR (ssNMR) spectroscopy techniques, we verified the homogenous distribution of the crosslinking ions in the alginate gels and the high degree of ion exchange...
June 21, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28634908/an-entrustable-professional-activity-epa-based-framework-to-prepare-fourth-year-medical-students-for-internal-medicine-careers
#7
D Michael Elnicki, Meenakshy K Aiyer, Maria L Cannarozzi, Alexander Carbo, Paul R Chelminski, Shobhina G Chheda, Saumil M Chudgar, Heather E Harrell, L Chad Hood, Michelle Horn, Karnjit Johl, Gregory C Kane, Diana B McNeill, Marty D Muntz, Anne G Pereira, Emily Stewart, Heather Tarantino, T Robert Vu
The purpose of the fourth year of medical school remains controversial. Competing demands during this transitional phase cause confusion for students and educators. In 2014, the Association of American Medical Colleges (AAMC) released 13 Core Entrustable Professional Activities for Entering Residency (CEPAERs). A committee comprising members of the Clerkship Directors in Internal Medicine and the Association of Program Directors in Internal Medicine applied these principles to preparing students for internal medicine residencies...
June 20, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/28632338/difluoromethylation-reactions-of-organic-compounds
#8
Damian E Yerien, Sebastian Barata-Vallejo, Al Postigo
The relevance of the -CF2H moiety has attracted considerable attention from organic synthetic and medicinal chemistry communities, because this group can act as a more lipophilic isostere of the carbinol, thiol, hydroxamic acid or amide groups. Being weakly acidic, the CF2H moiety can establish hydrogen bonding interactions to improve the binding selectivity of biologically active compounds. Therefore, the hydroxyl, amino, and thio substituents of lead structures are routinely replaced by a CF2H motif in drug discovery, with great benefits in the pharmacological activity of drugs and drug candidates and agrochemicals...
June 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28631853/high-sensitivity-mr-acoustic-radiation-force-imaging-using-transition-band-balanced-steady-state-free-precession
#9
Yuan Zheng, Michael Marx, G Wilson Miller, Kim Butts Pauly
PURPOSE: MR acoustic radiation force imaging (MR-ARFI) provides a method to visualize the focal spot of a focused ultrasound (FUS) beam without introducing a significant temperature rise. With conventional spoiled MR-ARFI pulse sequences, the ARFI phase always equals the motion-encoded phase. In this work, MR-ARFI using transition band balanced steady-state free precession (bSSFP) is presented, which improves the sensitivity of MR-ARFI with high acquisition speed. THEORY AND METHODS: Motion-encoding gradients (MEG) are inserted into bSSFP sequences for MR-ARFI...
June 20, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28630157/pore-formation-by-dimeric-bak-and-bax-an-unusual-pore
#10
REVIEW
Rachel T Uren, Sweta Iyer, Ruth M Kluck
Apoptotic cell death via the mitochondrial pathway occurs in all vertebrate cells and requires the formation of pores in the mitochondrial outer membrane. Two Bcl-2 protein family members, Bak and Bax, form these pores during apoptosis, and how they do so has been investigated for the last two decades. Many of the conformation changes that occur during their transition to pore-forming proteins have now been delineated. Notably, biochemical, biophysical and structural studies indicate that symmetric homodimers are the basic unit of pore formation...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630151/assembly-mechanism-of-the-%C3%AE-pore-forming-toxin-cytolysin-a-from-escherichia-coli
#11
REVIEW
Daniel Roderer, Rudi Glockshuber
The cytolytic toxin cytolysin A (ClyA) from Escherichia coli is probably one of the best-characterized examples of bacterial, α-pore-forming toxins (α-PFTs). Like other PFTs, ClyA exists in a soluble, monomeric form that assembles to an annular, homo-oligomeric pore complex upon contact with detergent or target membranes. Comparison of the three-dimensional structures of the 34 kDa monomer and the protomer in the context of the dodecameric pore complex revealed that ClyA undergoes one of the largest conformational transitions described for proteins so far, in which 55% of the residues change their position and 16% of the residues adopt a different secondary structure in the protomer...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28626570/riboflavin-as-a-bioorthogonal-photocatalyst-for-the-activation-of-a-pt-iv-prodrug
#12
Silvia Alonso-de Castro, Emmanuel Ruggiero, Ane Ruiz-de-Angulo, Elixabete Rezabal, Juan C Mareque-Rivas, Xabier Lopez, Fernando López-Gallego, Luca Salassa
Encouraging developments demonstrate that few transition metal and organometallic catalysts can operate in a bioorthogonal fashion and promote non-natural chemistry in living systems by minimizing undesired side reactions with cellular components. These catalytic processes have potential for applications in medicinal chemistry and chemical biology. However, the stringent conditions of the cell environment severely limit the number of accessible metal catalysts and exogenous reactions. Herein, we report an unorthodox approach and a new type of bioorthogonal catalytic reaction, in which a metal complex is an unconventional substrate and an exogenous biological molecule acts as a catalyst...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28623784/antihypertensive-and-vasodilator-effects-of-methanolic-extract-of-inula-viscosa-biological-evaluation-and-pom-analysis-of-cynarin-chlorogenic-acid-as-potential-hypertensive
#13
Zineb Hakkou, Alexandre Maciuk, Veronique Leblais, Nour Elhouda Bouanani, Hassane Mekhfi, Mohammed Bnouham, Mohammed Aziz, Abderrahime Ziyyat, Abdur Rauf, Taibi Ben Hadda, Usama Shaheen, Seema Patel, Rodolphe Fischmeister, Abdelkhaleq Legssyer
BACKGROUND: Inula viscosa L. (Asteraceae) is a medicinal plant widely used as a folk medicine in oriental Morocco, to treat hypertension. The antihypertensive effect of the methanolic extract obtained from I. viscosa leaves was evaluated in hypertensive L-NAME rats. Systolic blood pressure (SBP) was measured using a non-invasive indirect tail-cuff plethysmographic method. Four groups of rats were used: a control group; a hypertensive group treated with L-NAME (32mg/kg/day); a positive control group treated with L-NAME plus enalapril (15mg/kg/day) as a reference antihypertensive agent; and a group treated with L-NAME plus MeOH-extract (40mg/kg/day)...
June 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28621834/from-intricate-to-integrated-biofabrication-of-articulating-joints
#14
Wilhelmina Margaretha Groen, Paweena Diloksumpan, Paul René van Weeren, Riccardo Levato, Jos Malda
Articulating joints owe their function to the specialized architecture and the complex interplay between multiple tissues including cartilage, bone and synovium. Especially the cartilage component has limited self-healing capacity and damage often leads to the onset of osteoarthritis, eventually resulting in failure of the joint as an organ. Although in its infancy, biofabrication has emerged as a promising technology to reproduce the intricate organization of the joint, thus enabling the introduction of novel surgical treatments, regenerative therapies, and new sets of tools to enhance our understanding of joint physiology and pathology...
June 16, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#15
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28617022/reducing-hospital-readmission-through-team-based-primary-care-a-7-week-pilot-study-integrating-behavioral-health-and-pharmacy
#16
Lauren N DeCaporale-Ryan, Nabila Ahmed-Sarwar, Robbyn Upham, Karen Mahler, Katie Lashway
INTRODUCTION: A team-based service delivery model was applied to provide patients with biopsychosocial care following hospital discharge to reduce hospital readmission. Most previous interventions focused on transitions of care occurred in the inpatient setting with attention to predischarge strategies. These interventions have not considered psychosocial stressors, and few have explored management in primary care settings. METHOD: A 7-week team-based service delivery model was implemented in a family medicine practice emphasizing a biopsychosocial approach...
June 2017: Families, Systems & Health: the Journal of Collaborative Family Healthcare
https://www.readbyqxmd.com/read/28607235/meeting-the-current-and-future-health-care-needs-of-sri-lanka-s-ageing-population
#17
Dilhar Samaraweera, Shiromi Maduwage
Sri Lanka is one of the fastest-ageing countries in the world. This rapid demographic transition is expected to result in one quarter of the population being elderly by the year 2041. Profound challenges face the country as a result, especially with respect to planning adequate elderly-oriented services in the social-care and health-care sectors. In response to this need, many initiatives have been put in place to promote and protect the welfare of older people, and these rights have been inscribed in law. Within the health sector, despite the wealth of policies and initiatives in recent years, it is clear that the existing health infrastructure and systems still require strengthening, reorientation and coordination, to meet the needs of the growing population of elderly individuals...
September 2016: WHO South-East Asia Journal of Public Health
https://www.readbyqxmd.com/read/28605555/operationalizing-multidisciplinary-assessment-and-treatment-as-a-quality-metric-for-interventional-pain-practices
#18
Edward K Heres, David Itskevich, Ajay D Wasan
Objective.:  Quality improvement (QI) is an underutilized approach among pain medicine specialists to improve comprehensive pain assessment and the delivery of multimodal pain care. We report the results of a QI program that utilized peer review and financial incentives to improve these processes in interventional pain clinics. Design.:  Retrospective chart review. Setting.:  Eight academic and community-based practices that included separate hospital-based and non-hospital-based interventional pain clinics...
June 12, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28604245/state-of-the-art-or-the-art-of-medicine-transnational-mobility-and-perceptions-of-multiple-biomedicines-among-nigerian-physicians-in-the-u-s
#19
Judith Schühle
Over the last 40 years, several thousand Nigerian-trained doctors have migrated to the U.S. to practice in what they regard as the state-of-the-art of global biomedicine. Based on interviews with Nigerian physicians, this article shows how their professional mobility, and their transition to the new professional environment of U.S. biomedicine, makes them aware of local differences in practicing medicine. Adapting to local ways of practicing in the U.S. creates a new sense of belonging and professional identity...
June 12, 2017: Global Public Health
https://www.readbyqxmd.com/read/28603416/successful-in-vivo-hyperthermal-therapy-toward-breast-cancer-by-chinese-medicine-shikonin-loaded-thermosensitive-micelle
#20
Yonghua Su, Nian Huang, Di Chen, Li Zhang, Xia Dong, Yun Sun, Xiandi Zhu, Fulei Zhang, Jie Gao, Ying Wang, Kexing Fan, Puichi Lo, Wei Li, Changquan Ling
The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide) and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN) with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT), high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly...
2017: International Journal of Nanomedicine
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