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Kevin Isgrig, Wade W Chien
Inner ear gene therapy offers great promise as a potential treatment for hearing loss and dizziness. One of the critical determinants of the success of inner ear gene therapy is to find a delivery method which results in consistent transduction efficiency of targeted cell types while minimizing hearing loss. In this study, we describe the posterior semicircular canal approach as a viable method for inner ear gene delivery in neonatal mice. We show that gene delivery through the posterior semicircular canal is able to perfuse the entire inner ear...
March 2, 2018: Journal of Visualized Experiments: JoVE
Hao-Hsiang Hsu, John-Kevin Kracht, Laura Elisabeth Harder, Kerstin Rudnik, Gerd Lindner, Katharina Schimek, Uwe Marx, Ralf Pörtner
In vitro cultivated skin models have become increasingly relevant for pharmaceutical and cosmetic applications, and are also used in drug development as well as substance testing. These models are mostly cultivated in membrane-insert systems, their permeability toward different substances being an essential factor. Typically, applied methods for determination of these parameters usually require large sample sizes (e.g., Franz diffusion cell) or laborious equipment (e.g., fluorescence recovery after photobleaching (FRAP))...
February 23, 2018: Journal of Visualized Experiments: JoVE
Koren Hanson, Kevin P Haggerty, Charles B Fleming, Martie L Skinner, Mary Casey-Goldstein, W Alex Mason, Ronald W Thompson, Cleve Redmond
OBJECTIVE: As legalization of nonmedical retail marijuana increases, states are implementing public health campaigns designed to prevent increases in youth marijuana use. This study investigated which types of marijuana-related messages were rated most highly by parents and their teens and whether these preferences differed by age and marijuana use. METHOD: Nine marijuana-focused messages were developed as potential radio, newspaper, or television announcements...
March 2018: Journal of Studies on Alcohol and Drugs
Kevin A Hallgren, Adam D Wilson, Katie Witkiewitz
OBJECTIVE: Interest in studying mechanisms of behavior change (MOBCs) in substance use disorder (SUD) treatments has grown considerably in the past two decades. Much of this work has focused on identifying which variables statistically mediate the effect of SUD treatments on clinical outcomes. However, a fuller conceptualization of MOBCs will require greater understanding of questions that extend beyond traditional mediation analysis, including better understanding of when MOBCs change during treatment, when they are most critical to aiding the initiation or maintenance of change, and how MOBCs themselves arise as a function of treatment processes...
March 2018: Journal of Studies on Alcohol and Drugs
Meredith B Rosenthal, Carrie H Colla, Nancy E Morden, Thomas D Sequist, Alexander J Mainor, Zhonghe Li, Kevin H Nguyen
OBJECTIVES: A substantial portion of healthcare spending is wasted on services that do not directly improve patient health and that cause harm in some cases. Features of health insurance coverage, including enrollment in high-deductible health plans (HDHPs) or health maintenance organizations (HMOs), may provide financial and nonfinancial mechanisms to potentially reduce overuse of low-value healthcare services. STUDY DESIGN: Using 2009 to 2013 administrative data from 3 large commercial insurers, we examined patient characteristics and health insurance plan types associated with overuse of 6 healthcare services identified by the Choosing Wisely campaign...
March 2018: American Journal of Managed Care
Zirui Song, Amol S Navathe, Ezekiel J Emanuel, Kevin G Volpp
The United States is simultaneously moving toward value-based payments for populations and precision medicine for individuals. During this evolution, innovations in payment and delivery that enhance tailoring of treatments to individuals while improving the value of care are needed. We propose one such innovation that would allow physician payment and patient cost sharing to better reflect the value of care by allowing the appropriateness of a service for a given patient in a given clinical situation to play a more meaningful role in the design of such incentives...
March 2018: American Journal of Managed Care
Jeanine F Amacher, Fangfang Zhong, George P Lisi, Michael Q Zhu, Stephanie L Alden, Kevin R Hoke, Dean R Madden, Ekaterina V Pletneva
No abstract text is available yet for this article.
March 19, 2018: Journal of the American Chemical Society
Nobuhisa Morimoto, Chikako Kasuga, Airi Tanaka, Keiko Kamachi, Masumi Ai, Kevin Y Urayama, Akira Tanaka
An easily understandable index that measures the quality of carbohydrate may aid people in adopting dietary habits that improve their glucose tolerance. We aimed to evaluate the relationship between a ratio of dietary fibre to carbohydrate intakes (fibre:carbohydrate ratio (F:C-R)) and glucose tolerance cross-sectionally and longitudinally. Subjects were 190 Japanese men and women without type 2 diabetes (mean age 55·4 years) who participated in a 5-month diet and exercise programme. We compared baseline anthropometric, dietary and metabolic profiles between those with higher F:C-R and those with lower ratios...
March 2018: British Journal of Nutrition
Scott A Goldberg, Jeremy Maggin, Michael S Molloy, Olesya Baker, Ritu Sarin, Michael Kelleher, Kevin Mont, Adedeji Fajana, Eric Goralnick
OBJECTIVE: Mass gathering events can substantially impact public safety. Analyzing patient presentation and transport rates at various mass gathering events can help inform staffing models and improve preparedness. METHODS: A retrospective review of all patients seeking medical attention across a variety of event types at a single venue with a capacity of 68,756 from January 2010 through September 2015. RESULTS: We examined 232 events with a total of 8,260,349 attendees generating 8157 medical contacts...
March 19, 2018: Disaster Medicine and Public Health Preparedness
Roland Thuenauer, Simon Nicklaus, Marco Frensch, Kevin Troendle, Josef Madl, Winfried Römer
A key factor determining the fate of individual cells within an epithelium is the unique microenvironment that surrounds each cell. It regulates location-dependent differentiation into specific cellular sub-types, but, on the other hand, a disturbed microenvironment can promote malignant transformation of epithelial cells leading to cancer formation. Here, we present a tool based on a microfluidic biochip that enables novel research approaches by providing a means to control the basolateral microenvironment of a confined number of neighbouring cells within an epithelial monolayer...
February 19, 2018: RSC Advances
John R Hurst, Maria Dilleen, Kevin Morris, Siân Hills, Birol Emir, Rupert Jones
Purpose: Inappropriate use of an inhaled corticosteroid (ICS) for COPD has clinical and economic disadvantages. This retrospective analysis of The UK Health Improvement Network (THIN) database identified factors influencing treatment escalation (step-up) from a long-acting muscarinic antagonist (LAMA) to triple therapy (LAMA + long-acting β-agonist-ICS). Secondary objectives included time to step up from first LAMA prescription, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grouping (2011/2013, 2017), and Medical Research Council (MRC) grade prior to treatment escalation...
2018: International Journal of Chronic Obstructive Pulmonary Disease
Alexander Lam, Kevin Bui, Eduardo Hernandez Rangel, Michael Nguyentat, Dayantha Fernando, Kari Nelson, Nadine Abi-Jaoudeh
Radiogenomics involves the integration of mineable data from imaging phenotypes with genomic and clinical data to establish predictive models using machine learning. As a noninvasive surrogate for a tumor's in vivo genetic profile, radiogenomics may potentially provide data for patient treatment stratification. Radiogenomics may also supersede the shortcomings associated with genomic research, such as the limited availability of high-quality tissue and restricted sampling of tumoral subpopulations. Interventional radiologists are well suited to circumvent these obstacles through advancements in image-guided tissue biopsies and intraprocedural imaging...
March 15, 2018: Journal of Vascular and Interventional Radiology: JVIR
Nishant Saran, Chaim Locker, Sameh M Said, Richard C Daly, Simon Maltais, John M Stulak, Kevin L Greason, Alberto Pochettino, Hartzell V Schaff, Joseph A Dearani, Lyle D Joyce, Brian D Lahr, David L Joyce
BACKGROUND: We sought to identify the trends in bilateral internal thoracic artery use and determine the degree to which the survival advantage of bilateral internal thoracic artery revascularization persists among perceived "high-risk" patients, compared with the use of left internal thoracic artery alone. METHODS: A retrospective review was conducted of patients who underwent isolated coronary artery bypass grafting for multivessel coronary artery disease at the Mayo Clinic between January 2000 and December 2015...
February 23, 2018: Journal of Thoracic and Cardiovascular Surgery
Anthony M Mustoe, Steven Busan, Greggory M Rice, Christine E Hajdin, Brant K Peterson, Vera M Ruda, Neil Kubica, Razvan Nutiu, Jeremy L Baryza, Kevin M Weeks
mRNAs can fold into complex structures that regulate gene expression. Resolving such structures de novo has remained challenging and has limited our understanding of the prevalence and functions of mRNA structure. We use SHAPE-MaP experiments in living E. coli cells to derive quantitative, nucleotide-resolution structure models for 194 endogenous transcripts encompassing approximately 400 genes. Individual mRNAs have exceptionally diverse architectures, and most contain well-defined structures. Active translation destabilizes mRNA structure in cells...
March 13, 2018: Cell
Ketan K Mane, Kevin B Rubenstein, Najlla Nassery, Adam L Sharp, Ejaz A Shamim, Navdeep S Sangha, Ahmed Hassoon, Mehdi Fanai, Zheyu Wang, David E Newman-Toker
No abstract text is available yet for this article.
March 17, 2018: BMJ Quality & Safety
Wei Chen, Suhong Pan, Hao Cheng, Andrew J Sweetman, Hao Zhang, Kevin C Jones
A passive water sampler based on the diffusive gradients in thin-films (DGT) technique was developed and tested for 3 groups of endocrine disrupting chemicals (EDCs, including oestrogens, alkyl-phenols and bisphenols). Three different resins (hydrophilic-lipophilic-balanced (HLB), XAD18 and Strata-XL-A (SXLA)) were investigated for their suitability as the binding phase for DGT devices. Laboratory tests across a range of pH (3.5-9.5), ionic strength (0.001-0.5 M) and dissolved organic matter concentration (0-20 mg L-1 ) showed HLB and XAD18-DGT devices were more stable compared to SXLA-DGT...
March 12, 2018: Water Research
Kevin Linka, Markus Hillgärtner, Mikhail Itskov
In recent experimental studies a possible damage mechanism of collagenous tissues mainly caused by fatigue was disclosed. In this contribution, a multi-scale constitutive model ranging from the tropocollagen (TC) molecule level up to bundles of collagen fibers is proposed and utilized to predict the elastic and inelastic long-term tissue response. Material failure of collagen fibrils is elucidated by a permanent opening of the triple helical collagen molecule conformation, triggered either by overstretching or reaction kinetics of non-covalent bonds...
March 14, 2018: Acta Biomaterialia
Susan E Maloney, Catherine Creeley, Richard E Hartman, Carla M Yuede, Charles F Zorumski, Vesna Jevtovic-Todorovic, Krikor Dikranian, Kevin K Noguchi, Nuri B Farber, David F Wozniak
Fifteen years ago Olney and colleagues began using animal models to evaluate the effects of anesthetic and sedative agents (ASAs) on neurodevelopment. The results from ongoing studies indicate that, under certain conditions, exposure to these drugs during development induces an acute elevated apoptotic neurodegenerative response in the brain and long-term functional impairments. These animal models have played a significant role in bringing attention to the possible adverse effects of exposing the developing brain to ASAs when few concerns had been raised previously in the medical community...
March 14, 2018: Neurobiology of Learning and Memory
Nitika Paudel, Kevin P Bethke, Lilian C Wang, Jonathan B Strauss, John P Hayes, Eric D Donnelly
PURPOSE: The current standard of care for women diagnosed with early stage breast cancer is breast-conserving surgery (BCS) followed by external beam radiation therapy, commonly delivered over 3-6 weeks. As an alternative, select patients can undergo intra-operative radiation therapy (IORT) at the time of BCT. This technique delivers a single fraction of radiation at the time of surgery, enabling patients to undergo both surgery and radiation in a single session. Our current study analyzed the value of incorporating breast MRI into the routine work-up of patients deemed eligible for IORT, to quantify the impact on patient eligibility and requirement for additional work-up...
March 2018: Surgical Oncology
Buyun Chen, Pingping Lu, Dugan Freeman, Yang Gao, Edna Choo, Kevin DeMent, Scott Savage, Kelly Zhang, Dennis Milanwoski, Lichuan Liu, Brian Dean, Yuzhong Deng
The pH labile metabolite, hydrophobicity, high oral dose and systematic exposure of GDC-0810 posed tremendous challenges to develop a LC-MS method for a stable isotope labeled aBA study. In this study, we explored practical solutions to balance stability and sensitivity and to cope with the impact of high Cp.o. to Ci.v. ratio on the labeling selection and assay dynamic range. A [13 C9 ] GDC-0810 was synthesized to minimize the isotopic interference between PO dose, internal standard and I.V. microtracer. A highly sensitive LC-MS assay was validated for quantitation of [13 C9 ] GDC-0810 from 5 to 1250 pg/mL...
February 23, 2018: Journal of Pharmaceutical and Biomedical Analysis
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