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Clinical engineering

Y-C Huang, J Xiao, W Y Leung, W W Lu, Y Hu, K D Luk
Previous human study suggested that fresh-frozen intervertebral disc allograft transplantation can relieve neurological symptoms and restore segmental kinematics. Before wide clinical application, research into the pathophysiology of the postoperative disc allograft is needed. One important question that remains to be answered in disc allografting is the healing process of the host-graft interface and the subsequent change of the endplates. With the goat model for lumbar disc allografting, histology, micro-computed tomography analysis, scanning electron microscopy and energy-dispersive X-ray spectroscopy mapping were applied to evaluate the healing of the host-graft interfaces, the remodelling of subchondral bone, and the changes of the bony and cartilaginous endplates after transplantation...
October 19, 2016: European Cells & Materials
Grace Yim, Wenliang Wang, Maulik N Thaker, Stephanie Tan, Gerard D Wright
Modification of natural product backbones is a proven strategy for the development of clinically useful antibiotics. Such modifications have traditionally been achieved through medicinal chemistry strategies or via in vitro enzymatic activities. In an orthogonal approach, engineering of biosynthetic pathways using synthetic biology techniques can generate chemical diversity. Here we report the use of a minimal teicoplanin class glycopeptide antibiotic (GPA) scaffold expressed in a production-optimized Streptomyces coelicolor strain to expand GPA chemical diversity...
September 9, 2016: ACS Infectious Diseases
Alondra Escudero-Castellanos, Blanca E Ocampo-García, Ma Victoria Domínguez-García, Jaime Flores-Estrada, Miriam V Flores-Merino
Hydrogels are suitable materials to promote cell proliferation and tissue support because of their hydrophilic nature, porous structure and sticky properties. However, hydrogel synthesis involves the addition of additives that can increase the risk of inducing cytotoxicity. Sterilization is a critical process for hydrogel clinical use as a proper scaffold for tissue engineering. In this study, poly(ethylene glycol) (PEG), poly(ethylene glycol)-chitosan (PEG-CH) and multi-arm PEG hydrogels were synthesized by free radical polymerization and sterilized by gamma irradiation or disinfected using 70 % ethanol...
December 2016: Journal of Materials Science. Materials in Medicine
Alicia M Waters, Laura L Stafman, Evan F Garner, Smitha Mruthyunjayappa, Jerry E Stewart, Gregory K Friedman, Jennifer M Coleman, James M Markert, G Yancey Gillespie, Elizabeth A Beierle
Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV), are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ134...
October 2016: Translational Oncology
Gordon B Parker, Heather Brotchie, Rebecca K Graham
OBJECTIVE: To examine whether vitamin D deficiency or insufficiency is associated with depression and whether vitamin D supplementation is an effective treatment for depression. METHOD: Empirical papers published in recent years were identified using three search engines and online databases - PubMed, Google Scholar and Cochrane Database. Specific search terms used were 'vitamin D', 'depression' and 'treatment' and articles were selected that examined the association between vitamin D deficiency/insufficiency and depression, vitamin D supplementation and Vitamin D as a treatment for depression...
October 11, 2016: Journal of Affective Disorders
Bingjie Shi, Juan Li, Xuanling Shi, Wenxu Jia, Yi Wen, Xiongbing Hu, Fengfeng Zhuang, Jianzhong Xi, Linqi Zhang
Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity and low cytotoxicity. We report here systematic design and characterization of twenty eight novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity and lower cytotoxicity compared to zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials...
October 3, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Ken G Andersson, Maryam Oroujeni, Javad Garousi, Bogdan Mitran, Stefan Ståhl, Anna Orlova, John Löfblom, Vladimir Tolmachev
The epidermal growth factor receptor (EGFR) is overexpressed in a number of malignant tumors and is a molecular target for several specific anticancer antibodies and tyrosine kinase inhibitors. The overexpression of EGFR is a predictive biomarker for response to several therapy regimens. Radionuclide molecular imaging might enable detection of EGFR overexpression by a non-invasive procedure and could be used repeatedly. Affibody molecules are engineered scaffold proteins, which could be selected to have a high affinity and selectivity to predetermined targets...
October 5, 2016: International Journal of Oncology
Mark W Lowdell, Amy Thomas
Advanced therapy medicinal products (ATMPs) represent the current pinnacle of 'patient-specific medicines' and will change the nature of medicine in the near future. They fall into three categories; somatic cell-therapy products, gene therapy products and cells or tissues for regenerative medicine, which are termed 'tissue engineered' products. The term also incorporates 'combination products' where a human cell or tissue is combined with a medical device. Plainly, many of these new medicines share similarities with conventional haematological stem cell transplant products and donor lymphocyte infusions as well as solid organ grafts and yet ATMPs are regulated as medicines and their development has remained predominantly in academic settings and within specialist centres...
October 17, 2016: British Journal of Haematology
B Lucendo-Villarin, H Rashidi, K Cameron, D C Hay
Pluripotent stem cell derived liver cells (hepatocytes) represent a promising alternative to primary tissue for biological and clinical applications. To date, most hepatocyte maintenance and differentiation systems have relied upon the use of animal derived components. This serves as a significant barrier to large scale production and application of stem cell derived hepatocytes. Recently, the use of defined biologics has overcome those limitations in two-dimensional monolayer culture. In order to improve the cell phenotype further, three-dimensional culture systems have been employed to better mimic the in vivo situation, drawing upon materials chemistry, engineering and biology...
May 28, 2016: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Wing-Fu Lai, Zhen-Dan He
Hydrogels are swellable polymer networks which can imbibe a substantial amount of fluids while retaining their internal network structure. Compared to bulk hydrogels, hydrogel nanoparticles exhibit added values in drug delivery because they can be internalized into cells to deliver pharmaceutical agents into the cytosol. Their large surface area also allows for multivalent conjugations, making optimization of the nanoparticles towards in vivo and clinical applications possible. These features, together with the tunable properties and biocompatibility of hydrogels, account for the widespread use of hydrogel-based nanoparticulate systems in drug formulation...
October 13, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
B Vijayalakshmi Ayyar, Sushrut Arora, Richard O'Kennedy
Antibody-based therapies have garnered considerable success in recent years. This is due to the availability of strategies to successfully engineer antibodies into humanized forms, better understanding of the biological processes involved in cancer development, the availability of novel recombinant antibody formats, better antibody selection platforms, and improved antibody conjugation methodologies. Such achievements have led to an explosion in the generation of antibodies and antibody-associated constructs for the treatment of cancer and other diseases...
October 10, 2016: Trends in Pharmacological Sciences
Elizabeth Murray, Eric B Hekler, Gerhard Andersson, Linda M Collins, Aiden Doherty, Chris Hollis, Daniel E Rivera, Robert West, Jeremy C Wyatt
Digital health interventions have enormous potential as scalable tools to improve health and healthcare delivery by improving effectiveness, efficiency, accessibility, safety, and personalization. Achieving these improvements requires a cumulative knowledge base to inform development and deployment of digital health interventions. However, evaluations of digital health interventions present special challenges. This paper aims to examine these challenges and outline an evaluation strategy in terms of the research questions needed to appraise such interventions...
November 2016: American Journal of Preventive Medicine
Rebecca S Abraham, Duane A Mitchell
Dendritic cell (DC) vaccines are an immunotherapeutic approach to cancer treatment that use the antigen-presentation machinery of DCs to activate an endogenous anti-tumor response. In this treatment strategy, DCs are cultured ex vivo, exposed to tumor antigens and administered to the patient. The ex vivo culturing provides a unique and powerful opportunity to modify and enhance the DCs. As such, a variety of genetic engineering approaches have been employed to optimize DC vaccines, including the introduction of messenger RNA and small interfering RNA, viral gene transduction, and even fusion with whole tumor cells...
November 2016: Cytotherapy
Yury A Bochkov, Kelly Watters, Sarmila Basnet, Shakher Sijapati, Marchel Hill, Ann C Palmenberg, James E Gern
Viruses in the rhinovirus C species (RV-C) can cause severe respiratory illnesses in children including pneumonia and asthma exacerbations. A transduced cell line (HeLa-E8) stably expressing the CDHR3-Y529 receptor variant, supports propagation of RV-C after infection. C15 clinical or recombinant isolates replicate in HeLa-E8, however progeny yields are lower than those of related strains of RV-A and RV-B. Serial passaging of C15 in HeLa-E8 resulted in stronger cytopathic effects and increased (≥10-fold) virus binding to cells and progeny yields...
October 13, 2016: Virology
Lisa M Li, Titus Wong, Emily Rose, Graham Wickham, Elizabeth Bryce
BACKGROUND: A tabletop-type ultraviolet C (UVC) light-emitting disinfecting device was evaluated for microbiologic effectiveness, safety, usability, and end-user satisfaction. METHODS: Three different inoculums of methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter calcoaceticus-baumannii complex strains suspended in both saline and trypticase soy broth were applied onto stainless steel carriers and electronic device surfaces in triplicate and cultured for growth after UVC disinfection...
October 11, 2016: American Journal of Infection Control
Januario E Castro, Thomas J Kipps
Treatment of patients with chronic lymphocytic leukemia and other B cell malignancies is evolving very rapidly. We have observed the quick transition during the last couple of years, from chemo-immunotherapy based treatments to oral targeted therapies based on B cell receptor signaling and Bcl-2 inhibitors, as well as the increasing use of second generation glyco-engineered antibodies. The next wave of revolution in the treatment for this conditions is approaching and it will be based on strategies that harness the power of the immune system to fight cancer...
March 2016: Best Practice & Research. Clinical Haematology
Joanna D Nowacka, Christian Baumgartner, Cristiana Pelorosso, Mareike Roth, Johannes Zuber, Manuela Baccarini
The dual-specificity kinases MEK1 and MEK2 act downstream of RAS/RAF to induce ERK activation, which is generally considered protumorigenic. Activating MEK mutations have not been discovered in leukemia, in which pathway activation is caused by mutations in upstream components such as RAS or Flt3. The anti-leukemic potential of MEK inhibitors is being tested in clinical trials; however, downregulation of MEK1 promotes Eμ-Myc-driven lymphomagenesis and MEK1 ablation induces myeloproliferative disease in mice, raising the concern that MEK inhibitors may be inefficient or counterproductive in this context...
October 10, 2016: Oncotarget
Ayman Eid, Magdy M Mahfouz
Molecular scissors engineered for site-specific modification of the genome hold great promise for effective functional analyses of genes, genomes and epigenomes and could improve our understanding of the molecular underpinnings of disease states and facilitate novel therapeutic applications. Several platforms for molecular scissors that enable targeted genome engineering have been developed, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and, most recently, clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated-9 (Cas9)...
October 14, 2016: Experimental & Molecular Medicine
Fan Zhang, Peter Bohlen, Michael D Lewek, He Huang
This study investigated the feasibility of predicting intrinsically caused trips (ICTs) in individuals with stroke. Gait kinematics collected from twelve individuals with chronic stroke, who demonstrated ICTs in treadmill walking, were analyzed. A prediction algorithm based on the outlier principle was employed. Sequential forward selection (SFS) and minimum-redundancy- maximum-relevance (mRMR) were used separately to identify the precursors for accurate ICT prediction. The results showed that it was feasible to predict ICTs around 50- 260ms before ICTs occurred in the swing phase by monitoring lower limb kinematics during the preceding stance phase...
October 11, 2016: IEEE Transactions on Neural Systems and Rehabilitation Engineering
Rishi G Vaswani, Victor S Gehling, Les A Dakin, Andrew Cook, Christopher G Nasveschuk, Martin Duplessis, Priyadarshini Iyer, Srividya Balasubramanian, Feng Zhao, Andrew C Good, Robert Campbell, Christina Lee, Nico Cantone, Richard T Cummings, Emmanuel Normant, Steven F Bellon, Brian K Albrecht, Jean-Christophe P Harmange, Patrick Trojer, James E Audia, Ying Zhang, Neil Justin, Shuyang Chen, Jon Wilson, Steve Gamblin
Polycomb repressive complex 2 (PRC2) has been shown to play a major role in transcriptional silencing in part by installing methylation marks on lysine 27 of histone 3. Dysregulation of PRC2 function correlates with certain malignancies and poor prognosis. EZH2 is the catalytic engine of the PRC2 complex and thus represents a key candidate oncology target for pharmacological intervention. Here we report the optimization of our indole based EZH2 inhibitor series that led to the identification of CPI-1205, a highly potent (biochemical IC50 = 0...
October 14, 2016: Journal of Medicinal Chemistry
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