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https://www.readbyqxmd.com/read/28441034/thrombus-formation-at-high-shear-rate
#1
Lauren D C Casa, David N Ku
The final common pathway in myocardial infarction and ischemic stroke is occlusion of blood flow from a thrombus forming under high shear rates in arteries. A high-shear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood. Thrombosis at high shear rates depends primarily on the long protein von Willebrand factor (vWF) and platelets, with hemodynamics playing an important role in each stage of thrombus formation, including vWF binding, platelet adhesion, platelet activation, and rapid thrombus growth...
April 24, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/28440798/improved-gene-delivery-to-adult-mouse-spinal-cord-through-the-use-of-engineered-hybrid-adeno-associated-viral-serotypes
#2
J J Siu, N J Queen, W Huang, F Q Yin, X Liu, C Wang, D M McTigue, L Cao
Adeno-associated viral (AAV) vectors are often used in gene therapy for neurological disorders because of its safety profile and promising results in clinical trials. One challenge to AAV gene therapy is effective transduction of large numbers of the appropriate cell type, which can be overcome by modulating the viral capsid through DNA shuffling. Our previous study demonstrates that Rec2, among a family of novel engineered hybrid capsid serotypes (Rec1~4) transduces adipose tissue with far superior efficiency than naturally occurring AAV serotypes...
April 25, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28439866/mapping-protein-protein-interaction-using-high-throughput-yeast-2-hybrid
#3
Jessica Lopez, M Shahid Mukhtar
A tremendous asset to the analysis of protein-protein interactions is the yeast-2-hybrid (Y2H) method. The Y2H assay is a heterologous system that is expanding network biology knowledge via in vivo investigations of binary protein-protein interactions. Traditionally, the Y2H protocol entails the mating or co-transformation of yeast in solid agar media followed by visual analysis for diploid selection. Having played a key role in identifying protein-protein interactions for nearly three decades in a wide range of biological systems, the Y2H system assays the interaction between two proteins of interest which results in a reconstituted and/or activation of transcription factor allowing a reporter gene to be transcribed...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28439751/development-of-a-streamlined-work-flow-for-handling-patients-genetic-testing-insurance-authorizations
#4
Wendy R Uhlmann, Katie Schwalm, Victoria M Raymond
Obtaining genetic testing insurance authorizations for patients is a complex, time-involved process often requiring genetic counselor (GC) and physician involvement. In an effort to mitigate this complexity and meet the increasing number of genetic testing insurance authorization requests, GCs formed a novel partnership with an industrial engineer (IE) and a patient services associate (PSA) to develop a streamlined work flow. Eight genetics clinics and five specialty clinics at the University of Michigan were surveyed to obtain benchmarking data...
April 24, 2017: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/28439535/a-murine-preclinical-syngeneic-transplantation-model-for-breast-cancer-precision-medicine
#5
Lorenzo Federico, Zechen Chong, Dong Zhang, Daniel J McGrail, Wei Zhao, Kang Jin Jeong, Christopher P Vellano, Zhenlin Ju, Mihai Gagea, Shuying Liu, Shreya Mitra, Jennifer B Dennison, Philip L Lorenzi, Robert Cardnell, Lixia Diao, Jing Wang, Yiling Lu, Lauren A Byers, Charles M Perou, Shiaw-Yih Lin, Gordon B Mills
We previously demonstrated that altered activity of lysophosphatidic acid in murine mammary glands promotes tumorigenesis. We have now established and characterized a heterogeneous collection of mouse-derived syngeneic transplants (MDSTs) as preclinical platforms for the assessment of personalized pharmacological therapies. Detailed molecular and phenotypic analyses revealed that MDSTs are the most heterogeneous group of genetically engineered mouse models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor, correlated with RAS/MAPK signaling activity, as expected from studies in xenografts and clinical trials providing validation of the utility of the model...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28439079/translation-but-not-transfection-limits-clinically-relevant-exogenous-mrna-based-induction-of-alpha-4-integrin-expression-on-human-mesenchymal-stem-cells
#6
Adam Nowakowski, Anna Andrzejewska, Johannes Boltze, Franziska Nitzsche, Li-Li Cui, Jukka Jolkkonen, Piotr Walczak, Barbara Lukomska, Miroslaw Janowski
Mesenchymal stem cells (MSCs) represent promising resource of cells for regenerative medicine in neurological disorders. However, efficient and minimally invasive methods of MSCs delivery to the brain still have to be developed. Intra-arterial route is very promising, but MSCs are missing machinery for diapedesis through blood-brain barrier. Thus, here we have tested a mRNA-based method to induce transient expression of ITGA4, an adhesion molecule actively involved in cell extravasation. We observed that transfection with an ITGA4-mRNA construct bearing a conventional cap analogue (7-methylguanosine) failed to produce ITGA4 protein, but exogenous ITGA4-mRNA was detected in transfected MSCs...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28438144/development-and-effectiveness-of-a-mobile-phone-application-conducting-health-behavioral-intervention-among-men-who-have-sex-with-men-a-randomized-controlled-trial-study-protocol
#7
Jin Yan, Aidi Zhang, Liang Zhou, Zhulin Huang, Pan Zhang, Guoli Yang
BACKGROUND: Behavioral intervention is a key approach to HIV prevention among men who have sex with men (MSM). Widespread use of mobile phones provide us with novel opportunities to decrease HIV infection and transmission of MSM. The objective of the study was to design and develop a mobile phone application (app) aims to conduct behavioral intervention to MSM and to evaluate the efficacy of the app-based intervention compared to usual care, to analyze cost-effectiveness and mechanism of the intervention...
April 24, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28437235/breast-augmentation-and-reconstruction-from-a-regenerative-medicine-point-of-view-state-of-the-art-and-future-perspectives
#8
Luke Evan Visscher, Matthew Cheng, Mohit Chhaya, Madeline Louise Hintz, Jan-Thorsten Schantz, Phong Tran, Owen Ung, Clement Wong, Dietmar Werner Hutmacher
Breast reconstruction and augmentation are very common procedures, yet the prevailing current methods utilize silicone implants that may have significant local complications requiring reoperation. Lipofillling is increasingly used to contour and is considered safe, however its utility is limited by significant volume loss. A new approach could offer an alternative and increase the scope of patient choice. A small number of teams around the world are investigating a breast tissue-engineering paradigm. Conventional breast tissue engineering concepts are based on seeding a scaffold with the patients' own stem cells...
February 24, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28437178/a-novel-injectable-recombinant-collagen-i-peptide-based-macroporous-microcarrier-allows-superior-expansion-of-c2c12-and-human-bone-marrow-derived-mesenchymal-stromal-cells-and-supports-deposition-of-mineralized-matrix
#9
Davide Confalonieri, Margherita La Marca, Elisabeth Marianna Wilhelmina Maria van Dongen, Heike Walles, Franziska Ehlicke
The development of scaffold formulations based on extracellular matrix-inspired synthetic materials constitutes an important resource for the advance of cell-based therapies in bone tissue engineering approaches, where both cell and scaffold implantation are often needed. Culturing cells on porous microcarriers (MCs) allows cell expansion in a three-dimensional microenvironment and constitutes a possible solution for minimally invasive cell and scaffold simultaneous delivery, but the reduced pore dimension and pore interconnection diameter of several commercially available microcarriers limits de facto cell ingrowth, and ultimately their suitability for in vivo cell delivery...
March 3, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28436377/analysis-of-therapeutic-effectiveness-of-selected-types-of-collagen-in-prevention-and-treatment-of-degenerative-joint-disease
#10
Wiesław Tomaszewski, Anna Paradowska
Loss of collagen is a natural development accompanying aging of the body. It may be additionally accelerated by various conditions, including osteoarthritis (OA). Within the last two decades numerous and diverse studies have been conducted worldwide with the aim of identifying substances containing collagen, producing therapeutic preparations of expected effectiveness in the prevention and therapy of OA that would be safe to use and developing methods of delivering the final product into the body. The authors reviewed and analysed the latest available literature by selecting papers presenting the findings of studies conducted in line with the principles of Evidence-Based Medicine (EBM)...
January 26, 2017: Ortopedia, Traumatologia, Rehabilitacja
https://www.readbyqxmd.com/read/28434124/comparative-outcome-of-pfna-gamma-nails-pccp-medoff-plate-liss-and-dynamic-hip-screws-for-fixation-in-elderly-trochanteric-fractures-a-systematic-review-and-network-meta-analysis-of-randomized-controlled-trials
#11
Alisara Arirachakaran, Tanawat Amphansap, Pichaya Thanindratarn, Peerapong Piyapittayanun, Phutsapong Srisawat, Jatupon Kongtharvonskul
The ideal implant for the treatment of an unstable intertrochanteric femoral fracture is still a matter of discussion. The aim of this systematic review is to conduct a network meta-analysis of randomized controlled trials (RCTs) comparing clinical outcomes between dynamic hip screws (DHS), Medoff sliding plating, percutaneous compression plating (PCCP), proximal femoral nails (PFN), Gamma nails and less invasive stabilization system fixation in femoral trochanteric fractures in the elderly. These clinical outcomes consist of total intra-operative time, intra-operative fluoroscopy time, intra-operative blood loss, blood component transfusion, length of hospital stay, postoperative general complications, wound complications, late complications and reoperation rates...
April 22, 2017: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
https://www.readbyqxmd.com/read/28432853/an-evidence-based-approach-to-reducing-cardiac-telemetry-alarm-fatigue
#12
Ekta Srinivasa, Jaspreet Mankoo, Charles Kerr
BACKGROUND: It is estimated that between 80% and 99% of alarms in the clinical areas are in actionable alarms (Gross, Dahl, & Nielson). Alarm management is one of the Joint Commission's National Patient Safety Goals (2014) because sentinel events have directly been linked to the devices generating these alarms. PURPOSE: At an acute care facility in Boston, a multidisciplinary team consisting of Nursing, Biomedical Engineers, Patient Safety and Providers was formed to conduct a pilot study on the state of telemetry alarms on a surgical floor...
April 22, 2017: Worldviews on Evidence-based Nursing
https://www.readbyqxmd.com/read/28432815/immunoassays-for-the-quantification-of-alk-and-phosphorylated-alk-support-the-evaluation-of-on-target-alk-inhibitors-in-neuroblastoma
#13
Elizabeth R Tucker, Jennifer R Tall, Laura S Danielson, Sharon Gowan, Yann Jamin, Simon P Robinson, Udai Banerji, Louis Chesler
Targeted inhibition of Anaplastic Lymphoma Kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies, however the presence of resistant mutations necessitates both the development of more potent compounds and pharmacodynamic methods with which to determine their efficacy. We describe immunoassays designed to quantitate phosphorylation of ALK, and their use in preclinical models of neuroblastoma, a pediatric malignancy in which gain-of-function ALK mutations predict a poor overall outcome to conventional treatment...
April 22, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28432642/emerging-use-of-early-health-technology-assessment-in-medical-product-development-a-scoping-review-of-the-literature
#14
REVIEW
Maarten J IJzerman, Hendrik Koffijberg, Elisabeth Fenwick, Murray Krahn
Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products...
April 21, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28432439/characterization-of-a-functional-recombinant-human-creatine-kinase-mb-isoenzyme-prepared-by-tandem-affinity-purification-from-escherichia-coli
#15
Lihui Zou, Wen Su, Meng Wang, Wei Huang, Haijian Zhao, Enyi Zhang, Junhua Jin, Hongtao Xu, Fei Xiao
Creatine kinase isoform CK-MB has been widely applied as a biomarker of myocardial injury. While a variety of methods have been used to measure CK-MB activity or mass in clinical laboratories, a CK-MB standard is needed to eliminate between-method bias. Because the in vitro expression of human creatine kinase generates three isoenzymes, CK-MM, CK-MB, and CK-BB, it is important to establish an effective method to purify the isoform CK-MB from the mixture. In this study, we aimed at using tandem affinity purification (TAP) to purify recombinant CK-MB protein and evaluate its value in clinical laboratories...
April 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28432329/affinity-biosensors-using-recombinant-native-membrane-proteins-displayed-on-exosomes-application-to-botulinum-neurotoxin-b-receptor
#16
Richard Desplantes, Christian Lévêque, Benjamin Muller, Manuela Lotierzo, Géraldine Ferracci, Michel Popoff, Michael Seagar, Robert Mamoun, Oussama El Far
The development of simple molecular assays with membrane protein receptors in a native conformation still represents a challenging task. Exosomes are extracellular vesicles which, due to their stability and small size, are suited for analysis in various assay formats. Here, we describe a novel approach to sort recombinant fully native and functional membrane proteins to exosomes using a targeting peptide. Specific binding of high affinity ligands to the potassium channel Kv1.2, the G-protein coupled receptor CXCR4, and the botulinum neurotoxin type B (BoNT/B) receptor, indicated their correct assembly and outside out orientation in exosomes...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432128/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-issues-of-sovereignty-federalism-and-points-testing-in-the-prokaryotic-and-eukaryotic-spaces-of-the-host-microbial-superorganism
#17
Andrew J Macpherson
In contrast to live attenuated vaccines, which are designed to induce immunity through a time-limited bloom in systemic tissues, the microbiota is a persistent feature of body surfaces, especially the intestine. The immune responses to the microbiota are idiosyncratic depending on the niche intimacy of different taxa and generally adapt the host to avoid overgrowth and maintain mutualism rather than to eliminate the organisms of that taxon. Both the microbiota and the host have so much molecular cross talk controlling each other, that the prokaryotic and the eukaryotic spaces of the host-microbial superorganism are federal rather than sovereign...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28431470/engineering-and-characterization-of-an-enzyme-replacement-therapy-for-classical-homocystinuria
#18
Tomas Majtan, Insun Park, Jan P Kraus
Homocystinuria due to loss of cystathionine beta-synthase (CBS) causes accumulation of homocysteine and depletion of cysteine. Current treatments are suboptimal and thus the development of an enzyme replacement therapy based on PEGylated human truncated CBS (PEG-CBS) has been initiated. Attenuation of potency was observed, necessitating a screen of several PEG-CBS conjugates for their efficacy to correct and maintain the plasma metabolite profile of murine homocystinuria after repeated administrations interrupted with washouts...
April 21, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28431161/engineering-a-high-affinity-peptide-binding-site-into-the-anti-cea-mab-m5a
#19
Cindy Zer, Kendra N Avery, Kassondra Meyer, Leah Goodstein, Krzysztof P Bzymek, Gagandeep Singh, John C Williams
We have previously identified a cyclic peptide called meditope which binds to the central cavity of the Fab portion of cetuximab and shown that this peptide binding site can be grafted, or 'meditope-enabled', onto trastuzumab. This peptide has been shown to act as a hitch for the non-covalent attachment of imaging agents to meditope-enabled antibodies. Herein, we explore the process of grafting this peptide binding site onto M5A, an anti-CEA antibody in clinical trials for cancer diagnostics. In order to explore the contributions of the amino acids, we sequentially introduced pairs of amino acid substitutions into the Fab and then we reverse-substituted key residues in the presence of the other substitutions...
April 19, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28430399/targeting-conformational-activation-of-cdk2-kinase
#20
Morgan Pellerano, Sergey Tcherniuk, Corine Perals, Thi Nhu Ngoc Van, Elsa Garcin, Florence Mahuteau-Betzer, Marie-Paule Teulade-Fichou, May C Morris
Cyclin-dependent kinases constitute attractive pharmacological targets for cancer therapeutics, yet inhibitors in clinical trials target the ATP-binding pocket of the CDK and therefore suffer from limited selectivity and emergence of resistance. The more recent development of allosteric inhibitors targeting conformational plasticity of protein kinases offers promising perspectives for therapeutics. In particular tampering with T-loop dynamics of CDK2 kinase would provide a selective means of inhibiting this kinase, by preventing its conformational activation...
April 21, 2017: Biotechnology Journal
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