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Ajit Dash, Robert A Figler, Arun J Sanyal, B R Wamhoff
Drug induced steatohepatitis (DISH), a form of drug induced liver injury (DILI) is characterized by intracellular accumulation of lipids in hepatocytes and subsequent inflammatory events, in some ways similar to the pathology seen with other metabolic, viral and genetic causes of non alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH). Areas covered: This paper provides a comprehensive review of the main underlying mechanisms by which various drugs cause DISH, and outlines existing preclinical tools to predict it and study underlying pathways involved...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Jinwoo Ma, Jaehun Lee, Sang Sub Han, Kyu Hwan Oh, Ki Tae Nam, Jeong-Yun Sun
Protein-based hydrogels have received attention for biomedical applications and tissue engineering because they are biocompatible and abundant. However, the poor mechanical properties of these hydrogels remain a hurdle for practical use. We have developed a highly stretchable and notch-insensitive hydrogel by integrating casein micelles into polyacrylamide (PAAm) networks. In the casein-PAAm hybrid gels, casein micelles and polyacrylamide chains synergistically enhance the mechanical properties. Casein-PAAm hybrid gels are highly stretchable, stretching to more than 35 times their initial length under uniaxial tension...
October 17, 2016: ACS Applied Materials & Interfaces
Jonathan C Niclis, Carlos W Gantner, Walaa F Alsanie, Stuart J McDougall, Chris R Bye, Andrew G Elefanty, Edouard G Stanley, John M Haynes, Colin W Pouton, Lachlan H Thompson, Clare L Parish
: : Recent studies have shown evidence for the functional integration of human pluripotent stem cell (hPSC)-derived ventral midbrain dopamine (vmDA) neurons in animal models of Parkinson's disease. Although these cells present a sustainable alternative to fetal mesencephalic grafts, a number of hurdles require attention prior to clinical translation. These include the persistent use of xenogeneic reagents and challenges associated with scalability and storage of differentiated cells. In this study, we describe the first fully defined feeder- and xenogeneic-free protocol for the generation of vmDA neurons from hPSCs and utilize two novel reporter knock-in lines (LMX1A-eGFP and PITX3-eGFP) for in-depth in vitro and in vivo tracking...
October 14, 2016: Stem Cells Translational Medicine
Jun-Hyung Tak, Murray B Isman
Although screening for new and reliable sources of botanical insecticides remains important, finding ways to improve the efficacy of those already in use through better understanding of their modes-of-action or metabolic pathways, or by improving formulations, deserves greater attention as the latter may present lesser regulation hurdles. Metabolic processing of citral (a combination of the stereoisomers geranial and neral), a main constituent of lemongrass (Cymbopogon citratus) essential oil has not been previously examined in insects...
October 2016: Pesticide Biochemistry and Physiology
Annette R Waznonis
AIM: A study was conducted to describe simulation debriefing practices of faculty in accredited, traditional, baccalaureate nursing programs in the United States. BACKGROUND: Best debriefing practices include debriefing by a competent facilitator in a safe environment using a structured framework. Yet, structured frameworks and evaluation of debriefing are lacking in nursing education. METHOD: This article reports the interview findings from the qualitative component of a large-scale mixed-methods study...
September 2016: Nursing Education Perspectives
Marcus D Darabbie, Emmanuel C Opara
The promise of pancreatic islet transplantation is hindered by organ shortage, and the need for immunosuppression of transplant recipient in order to prevent rejection. Alginate microencapsulation can overcome these hurdles; however further optimization of this technique is required. Among the critical factors to be optimized is the durability of alginate microcapsules, which can be determined by their mechanical strength tests. Here we describe several simple and reliable methods to assist in assessing the mechanical strength of alginate beads...
2017: Methods in Molecular Biology
Nayan Lamba, Daniel Holsgrove, Marike L Broekman
BACKGROUND: Since the turn of the last century, the prospect of head transplantation has captured the imagination of scientists and the general public. Recently, head transplant has regained attention in popular media, as neurosurgeons have proposed performing this procedure in 2017. Given the potential impact of such a procedure, we were interested in learning the history of the technical hurdles that need to be overcome, and determine if it is even technically possible to perform such a procedure on humans today...
October 14, 2016: Acta Neurochirurgica
Prahlad V Raninga, Giovanna Di Trapani, Slavica Vuckovic, Kathryn F Tonissen
Multiple myeloma (MM) is an incurable plasma B cell malignancy. Despite recent advancements in anti-MM therapies, development of drug resistance remains a major clinical hurdle. DJ-1, a Parkinson's disease-associated protein, is upregulated in many cancers and its knockdown suppresses tumor growth and overcomes chemoresistance. However, the role of DJ-1 in MM remains unknown. Using gene expression databases we found increased DJ-1 expression in MM patient cells, which correlated with shorter overall survival and poor prognosis in MM patients...
October 12, 2016: Apoptosis: An International Journal on Programmed Cell Death
Xintao Hu, Antonio Valentin, Frances Dayton, Viraj Kulkarni, Candido Alicea, Margherita Rosati, Bhabadeb Chowdhury, Rajeev Gautam, Kate E Broderick, Niranjan Y Sardesai, Malcolm A Martin, James I Mullins, George N Pavlakis, Barbara K Felber
HIV sequence diversity and the propensity of eliciting immunodominant responses targeting variable regions of the HIV proteome are hurdles in the development of an effective AIDS vaccine. An HIV-derived conserved element (CE) p24(gag) plasmid DNA (pDNA) vaccine is able to redirect immunodominant responses to otherwise subdominant and often more vulnerable viral targets. By homology to the HIV immunogen, seven CE were identified in SIV p27(Gag) Analysis of 31 rhesus macaques vaccinated with full-length SIV gag pDNA showed inefficient induction (58% response rate) of cellular responses targeting these CE...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Oh Young Bang, Eun Hee Kim, Jae Min Cha, Gyeong Joon Moon
Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation...
September 2016: Journal of Stroke
Brenna N Burkett, John M Thomason, Holly M Hurdle, Robert W Wills, Robin L Fontenot
OBJECTIVE: Determine the effects of nonsteroidal anti-inflammatory drugs (NSAID) on platelet function and thromboxane synthesis immediately after drug administration and following 5 days of NSAID administration in healthy horses. STUDY DESIGN: Randomized cross-over study. ANIMALS: Healthy adult horses (n=9; 6 geldings and 3 mares). METHODS: Horses received either flunixin meglumine (1.1 mg/kg IV every 12 hours), phenylbutazone (2...
October 12, 2016: Veterinary Surgery: VS
Nargis Khan, Susanta Pahari, Aurobind Vidyarthi, Mohammad Aqdas, Javed N Agrewala
Tuberculosis (TB) is the leading cause of morbidity and mortality among all infectious diseases. Failure of Bacillus Calmette Guerin as a vaccine and serious side-effects and toxicity due to long-term TB drug regime are the major hurdles associated with TB control. The problem is further compounded by the emergence of drug-resistance strains of Mycobacterium tuberculosis (Mtb). Consequently, it demands a serious attempt to explore safer and superior treatment approaches. Recently, an improved understanding of host-pathogen interaction has opened up new avenues for immunotherapy for treating TB...
2016: Frontiers in Immunology
Tanaka Kenta, Jessica E M Edwards, Roger K Butlin, Terry Burke, W Paul Quick, Peter Urwin, Matthew P Davey
Whilst genotype-environment interaction is increasingly receiving attention by ecologists and evolutionary biologists, such studies need genetically homogeneous replicates-a challenging hurdle in outcrossing plants. This could potentially be overcome by using tissue culture techniques. However, plants regenerated from tissue culture may show aberrant phenotypes and "somaclonal" variation. Here we examined the somaclonal variation due to tissue culturing using the response to cold treatment of the photosynthetic efficiency (chlorophyll fluorescence measurements for Fv/Fm, Fv'/Fm' and ΦPSII, representing maximum efficiency of photosynthesis for dark- and light-adapted leaves, and the actual electron transport operating efficiency, respectively, which are reliable indicators of photoinhibition and damage to the photosynthetic electron transport system)...
October 11, 2016: G3: Genes—Genomes—Genetics
Edward L Squires
Most equine embryos are collected from the donor mare and transferred immediately as fresh embryos or shipped cooled to a recipient station for transfer within 24 hours. Very few equine embryos are frozen despite the numerous advantages of embryo cryopreservation. There are 2 major hurdles: Only the small embryos (<300 μm) provide good pregnancy rates after freezing/thawing and transfer. Also there is no good procedure for superovulating mares; thus, extra embryos for freezing are not readily available...
October 8, 2016: Veterinary Clinics of North America. Equine Practice
J B Matthews, P Geldhof, T Tzelos, E Claerebout
The global increase in anthelmintic resistant nematodes of ruminants, together with consumer concerns about chemicals in food, necessitates the development of alternative methods of control for these pathogens. Sub-unit recombinant vaccines are ideally placed to fill this gap. Indeed, they are probably the only valid option for the long term control of ruminant parasitic nematodes given the increasing ubiquity of multi-drug resistance in a range of worm species across the world. The development of a sub-unit multicellular parasite vaccine to the point of practical application would be a ground-breaking step in the control of these important endemic infections of livestock...
October 11, 2016: Parasite Immunology
Justin D Radolf, Ranjit K Deka, Arvind Anand, David Šmajs, Michael V Norgard, X Frank Yang
The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation 'the stealth pathogen'. Despite the many hurdles to studying syphilis pathogenesis, most notably the inability to culture and to genetically manipulate T. pallidum, in recent years, considerable progress has been made in elucidating the structural, physiological, and regulatory facets of T...
October 10, 2016: Nature Reviews. Microbiology
Mildred C Embree, Mo Chen, Serhiy Pylawka, Danielle Kong, George M Iwaoka, Ivo Kalajzic, Hai Yao, Chancheng Shi, Dongming Sun, Tzong-Jen Sheu, David A Koslovsky, Alia Koch, Jeremy J Mao
Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment...
October 10, 2016: Nature Communications
Angira Patel, Gregory Webster, Kendra Ward, John Lantos
: Aim The aim of the present study was to determine general paediatrician knowledge, practices, and attitudes towards electrocardiogram (ECG) screening in school athletes during pre-participation screening exam (PPSE). METHODS: Paediatricians affiliated with a tertiary children's hospital completed a survey about ECGs for PPSE. RESULTS: In total, 205/498 (41%) responded; 92% of the paediatricians did not include an ECG as part of PPSE; 56% were aware of a case in which a student athlete in their own community had died of sudden unexplained death; 4% had an athlete in their practice die...
October 10, 2016: Cardiology in the Young
Raffaele Pugliese, Fabrizio Gelain
Peptidic biomaterials represent a particularly exciting topic in regenerative medicine. Peptidic scaffolds can be specifically designed for biomimetic customization for targeted therapy. The field is at a pivotal point where preclinical research is being translated into clinics, so it is crucial to understand the theory and describe the status of this rapidly developing technology. In this review, we highlight major advantages and current limitations of self-assembling peptide-based biomaterials, and we discuss the most widely used classes of assembling peptides, describing recent and promising approaches in tissue engineering, drug delivery, and clinics...
October 4, 2016: Trends in Biotechnology
Pranab Chatterjee, Manish Kakkar, Sanjay Chaturvedi
BACKGROUND: Globally, the threat of infectious diseases, particularly emerging infectious diseases, originating at the human-animal-environment interface, has caught health systems off guard. With forecasts that future pathogen emergence will be centred in hotspots in Asia, Africa, and Latin America, the need to prepare policy frameworks that can combat this threat is urgent. DISCUSSION: Emergence of diseases such as avian influenza and Ebola virus disease, which threatened social disruption, have established the need for intersectoral coordination/collaboration...
October 3, 2016: Infectious Diseases of Poverty
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