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Peter Stacey, Anne Mai Wassermann, Laura Kammonen, Emma Impey, Anna Wilbrey, Darren Cawkill
Screening against a disease-relevant phenotype to identify compounds that change the outcome of biological pathways, rather than just the activity of specific targets, offers an alternative approach to find modulators of disease characteristics. However, in pain research, use of in vitro phenotypic screens has been impeded by the challenge of sourcing relevant neuronal cell types in sufficient quantity and developing functional end-point measurements with a direct disease link. To overcome these hurdles, we have generated human induced pluripotent stem cell (hiPSC)-derived sensory neurons at a robust production scale using the concept of cryopreserved "near-assay-ready" cells to decouple complex cell production from assay development and screening...
March 1, 2018: SLAS Discovery
Andras Inotai, Marcell Csanadi, Guenka Petrova, Maria Dimitrova, Tomasz Bochenek, Tomas Tesar, Kristina York, Leos Fuksa, Alexander Kostyuk, Laszlo Lorenzovici, Vitaly Omelyanovskiy, Katalin Egyed, Zoltan Kalo
This policy research aims to map patient access barriers to biologic treatments, to explore how increased uptake of biosimilars may lower these hurdles and to identify factors limiting the increased utilisation of biosimilars. A policy survey was developed to review these questions in 10 Central and Eastern European (CEE) and Commonwealth of Independent States (CIS) countries. Two experts (one public and one private sector representative) from each country completed the survey. Questions were related to patient access, purchasing, clinical practice, and real-world data collection on both original biologics and biosimilars...
2018: BioMed Research International
Sophie Poty, Lynn C Francesconi, Michael R McDevitt, Michael J Morris, Jason S Lewis
With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous radionuclides that decay by α-particle emission, only a few of these can reasonably be exploited for therapeutic purposes. Factors including radioisotope availability and physical characteristics (e.g., half-life) can limit their wide-spread dissemination. The first part of this review will explore the diversity, basic radiochemistry, restrictions, and hurdles of α-emitters...
March 15, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Marnie J Meylor de Mooij, Rachael L Hodny, Daniel A O'Neil, Matthew R Gardner, Mekayla Beaver, Andrea T Brown, Barbara A Barry, Lorna M Ross, Amy J Jasik, Katharine M Nesbitt, Susan M Sobolewski, Susan M Skinner, Rajeev Chaudhry, Brian C Brost, Bobbie S Gostout, Roger W Harms
Using a human-centered design method, our team sought to envision a new model of care for women experiencing low-risk pregnancy. This model, called OB Nest, aimed to demedicalize the experience of pregnancy by providing a supportive and empowering experience that fits within patients' daily lives. To explore this topic, we invited women to use self-monitoring tools, a text-based smartphone application to communicate with their care team, and moderated online communities to connect with other pregnant women...
March 9, 2018: Mayo Clinic Proceedings
Thomas A Haugen, Paul A Solberg, Carl Foster, Ricardo Morán-Navarro, Felix Breitschädel, Will G Hopkins
The aim of this study was to quantify peak age and improvements over the preceding years to peak age in elite athletic contestants according to athlete performance level, sex and discipline. Individual season bests for world-ranked top 100 athletes from 2002 to 2016 (14937 athletes and 57049 individual results) were downloaded from the International Association of Athletics Federations' web site. Individual performance trends were generated by fitting a quadratic curve separately to each athlete's performance and age data using a linear modeling procedure...
March 15, 2018: International Journal of Sports Physiology and Performance
Akhil Kumar, Ashish Tiwari, Ashok Sharma
Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target...
March 15, 2018: Current Neuropharmacology
S C Thust, S Heiland, A Falini, H R Jäger, A D Waldman, P C Sundgren, C Godi, V K Katsaros, A Ramos, N Bargallo, M W Vernooij, T Yousry, M Bendszus, M Smits
OBJECTIVES: At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. METHODS: Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists' societies and distributed via social media...
March 13, 2018: European Radiology
Carla Ribeiro, João Borges, Ana M S Costa, Vítor M Gaspar, Verónica de Zea Bermudez, João F Mano
Hollow multilayered capsules have shown massive potential for being used in the biomedical and biotechnology fields, in applications such as cellular internalization, intracellular trafficking, drug delivery, or tissue engineering. In particular, hollow microcapsules, developed by resorting to porous calcium carbonate sacrificial templates, natural-origin building blocks and the prominent Layer-by-Layer (LbL) technology, have attracted increasing attention owing to their key features. However, these microcapsules revealed a great tendency to aggregate, which represents a major hurdle when aiming for cellular internalization and intracellular therapeutics delivery...
March 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Andrew J Kossow, Tyler G DeChiara, Steve M Neahous, William P Ebben
Plyometric exercises are frequently performed as part of a strength and conditioning program. Most studies assessed the kinetics of plyometric exercises primarily performed in the vertical plane. The purpose of this study was to evaluate the multi-planar kinetic characteristics of a variety of plyometric exercises, which have a significant horizontal component. This study also sought to assess sex differences in the intensity progression of these exercises. Ten men and ten women served as subjects. The subjects performed a variety of plyometric exercises including the double leg hop, standing long jump, single leg standing long jump, bounding, skipping, power skipping, cone hops, and 45...
March 12, 2018: Journal of Strength and Conditioning Research
Eleonora Vighi, Dragana Trifunović, Patricia Veiga-Crespo, Andreas Rentsch, Dorit Hoffmann, Ayse Sahaboglu, Torsten Strasser, Manoj Kulkarni, Evelina Bertolotti, Angelique van den Heuvel, Tobias Peters, Arie Reijerkerk, Thomas Euler, Marius Ueffing, Frank Schwede, Hans-Gottfried Genieser, Pieter Gaillard, Valeria Marigo, Per Ekström, François Paquet-Durand
Inherited retinal degeneration (RD) is a devastating and currently untreatable neurodegenerative condition that leads to loss of photoreceptor cells and blindness. The vast genetic heterogeneity of RD, the lack of "druggable" targets, and the access-limiting blood-retinal barrier (BRB) present major hurdles toward effective therapy development. Here, we address these challenges ( i ) by targeting cGMP (cyclic guanosine- 3',5'-monophosphate) signaling, a disease driver common to different types of RD, and ( ii ) by combining inhibitory cGMP analogs with a nanosized liposomal drug delivery system designed to facilitate transport across the BRB...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Mitchell A Rees, Nikhil B Amesur, Ruy J Cruz, Amir A Borhani, Kareem M Abu-Elmagd, Guilherme Costa, Anil K Dasyam
Intestinal transplantation has evolved from its experimental origins in the mid-20th century to its status today as an established treatment option for patients with end-stage intestinal failure who cannot be sustained with total parenteral nutrition. The most common source of intestinal failure in both adults and children is short-bowel syndrome, but a host of other disease processes can lead to this common end-point. The development of intestinal transplantation has presented multiple hurdles for the transplant community, including technical challenges, immunologic pitfalls, and infectious complications...
March 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Anthony A Peguero, Egbert Zavala, Zahra Shekarkhar, Moneque Walker-Pickett
The children of immigrants face a number of educational hurdles, such as disparate rates of victimization and increased risk of dropping out of high school. Few studies have explored how school victimization can explain the relationship between immigrant generation status and the likelihood of dropping out. The current study explores if, and how, the associations between school victimization, feeling unsafe at school, and dropping out vary across immigration generations andgender. Data are drawn from the Educational Longitudinal Study of 2002...
March 1, 2018: Journal of Interpersonal Violence
S Mathoulin-Pélissier, K Pritchard-Jones
Rare cancers are not so rare, their incidence is increasing and, as a group, they have worse survival than the common cancers. These factors emphasise the societal need to ensure sufficient focus on research into their biological basis, aetiological factors, new more effective therapies and organisation of healthcare to improve access to best practice and innovation. Accuracy of diagnosis is one of the first hurdles to be overcome, with around one third of tumours being reclassified - by type or risk group - when subject to a centralised pathology review process...
March 2, 2018: European Journal of Surgical Oncology
Sandra C Buttigieg, Joost van Hoof
Lehoux et al provide a highly valid contribution in conceptualizing value in value propositions for new health technologies and developing an analytic framework that illustrates the interplay between health innovation supply-side logic (the logic of emergence) and demand-side logic (embedding in the healthcare system). This commentary brings forth several considerations on this article. First, a detailed stakeholder analysis provides the necessary premonition of potential hurdles in the development, implementation and dissemination of a new technology...
July 3, 2017: International Journal of Health Policy and Management
Jessica Stevenson, Allison Tong, Katrina L Campbell, Jonathan C Craig, Vincent W Lee
OBJECTIVE: To describe the perspectives of healthcare providers on the nutritional management of patients on haemodialysis, which may inform strategies for improving patient-centred nutritional care. DESIGN: Face-to-face semistructured interviews were conducted until data saturation, and thematic analysis based on principles of grounded theory. SETTING: 21 haemodialysis centres across Australia. PARTICIPANTS: 42 haemodialysis clinicians (nephrologists and nephrology trainees (15), nurses (12) and dietitians (15)) were purposively sampled to obtain a range of demographic characteristics and clinical experiences...
March 8, 2018: BMJ Open
Amika K Sood, Matthew J Kesic, Michelle L Hernandez
Electronic cigarettes (EC) have been rapidly growing in popularity among youth and adults in the US over the last decade. This increasing prevalence is partially driven by the ability to customize devices, flavors, and nicotine content and the general notion that EC are harmless, particularly in comparison to conventional cigarettes (CC). In vitro and in vivo murine models have demonstrated a number of harmful biological effects of e-liquids (EL) and their aerosols. However, limited clinical data exists on whether these effects translate into detrimental long-term outcomes in humans...
March 6, 2018: Journal of Allergy and Clinical Immunology
Trisha L Andrew, Lushuai Zhang, Nongyi Cheng, Morgan Baima, Jae Joon Kim, Linden Allison, Steven Hoxie
Body-mountable electronics and electronically active garments are the future of portable, interactive devices. However, wearable devices and electronic garments are demanding technology platforms because of the large, varied mechanical stresses to which they are routinely subjected, which can easily abrade or damage microelectronic components and electronic interconnects. Furthermore, aesthetics and tactile perception (or feel) can make or break a nascent wearable technology, irrespective of device metrics...
March 9, 2018: Accounts of Chemical Research
Saumya S Gurbani, Eduard Schreibmann, Andrew A Maudsley, James Scott Cordova, Brian J Soher, Harish Poptani, Gaurav Verma, Peter B Barker, Hyunsuk Shim, Lee A D Cooper
PURPOSE: Proton MRSI is a noninvasive modality capable of generating volumetric maps of in vivo tissue metabolism without the need for ionizing radiation or injected contrast agent. Magnetic resonance spectroscopic imaging has been shown to be a viable imaging modality for studying several neuropathologies. However, a key hurdle in the routine clinical adoption of MRSI is the presence of spectral artifacts that can arise from a number of sources, possibly leading to false information...
March 9, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Françoise Debart, Christelle Dupouy, Jean-Jacques Vasseur
Oligonucleotides (ONs) have been envisaged for therapeutic applications for more than thirty years. However, their broad use requires overcoming several hurdles such as instability in biological fluids, low cell penetration, limited tissue distribution, and off-target effects. With this aim, many chemical modifications have been introduced into ONs definitively as a means of modifying and better improving their properties as gene silencing agents and some of them have been successful. Moreover, in the search for an alternative way to make efficient ON-based drugs, the general concept of prodrugs was applied to the oligonucleotide field...
2018: Beilstein Journal of Organic Chemistry
Alex Root, Peter Allen, Paul Tempst, Kenneth Yu
Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community...
March 7, 2018: Cancers
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