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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
Dagmar Schmitz
Since cell-free DNA (cfDNA) fragments of placental origin can be isolated and analyzed from the blood of pregnant women. Applications of this finding have been developed and implemented in clinical care pathways worldwide at an unprecedented pace and manner. Implementation patterns, however, exhibit considerable insufficiencies. Different "motors" of implementation processes, like the market or various regulatory institutions, can be identified at a national level. Each "motor" entails characteristic ethical challenges which are exemplified impressively by a rising number of case reports...
2016: Advances in Experimental Medicine and Biology
Abel Jacobus Bronkhorst, Johannes F Wentzel, Janine Aucamp, Etresia van Dyk, Lissinda H du Plessis, Piet J Pretorius
Non-invasive screening that utilizes cell-free DNA (cfDNA) offers remarkable potential as a method for the early detection of genetic disorders and a wide variety of cancers. Unfortunately, one of the most prominent elements delaying the translation of cfDNA analyses to clinical practice is the lack of knowledge regarding its origin and composition. The elucidation of the origin of cfDNA is complicated by the apparently arbitrary variability of quantitative and qualitative characteristics of cfDNA in the blood of healthy as well as diseased individuals...
2016: Advances in Experimental Medicine and Biology
Vincent Matthias Brandenburg, Nadine Kaesler, Rafael Kramann, Jürgen Floege, Nikolaus Marx
Disturbances in magnesium homeostasis are frequent clinical conditions, particularly the prevalence of hypomagnesaemia is high. However, it remains an open question which laboratory method is optimal to assess the magnesium level in the body. Most frequently physicians measure total magnesium in serum. Many associative data from observational studies point towards an association between low magnesium levels and increased cardiovascular risk as well as increased mortality. Vice versa, normal-to-high magnesium levels in patients with advanced renal failure translate to a better outcome...
October 2016: Deutsche Medizinische Wochenschrift
Anne Vuadens, Simone Ackermann, Fabio Levi, Jean-Luc Bulliard
Switzerland, particularly its western region, has the highest incidence of melanoma in Europe. Although the risk of melanoma increases with sun overexposure during childhood, sun-related knowledge and attitudes of Swiss children are scarcely documented. We report the first investigation of the knowledge of the danger of ultraviolet radiation, attitudes towards a suntan and parental influence of schoolchildren in western Switzerland. All fifth, eighth and eleventh graders (average ages of 9, 12 and 15, respectively) in the 18 primary (fifth grade, n=431) and secondary (eighth and eleventh grades, n=837) public schools of La Chaux-de-Fonds were surveyed during regular school classes...
October 5, 2016: European Journal of Cancer Prevention
Nicholas W Gilpin, Jeff L Weiner
Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly co-morbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of co-morbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on co-morbid PTSD and AUD: we summarize epidemiological data documenting the prevalence of this co-morbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD, and discuss successes and failures of past and current treatment strategies...
October 17, 2016: Genes, Brain, and Behavior
Hong Zhang, Peng He, Rongzhong Huang, Lin Sun, Siwen Liu, Jingjing Zhou, Yujie Guo, Deyu Yang, Peng Xie
MicroRNAs (miRNAs) are recognized as important regulators of gene expression via translational depression or mRNA degradation. Previously, dysregulated miRNAs have been found in neurodegenerative and neuropsychiatric disorders. Borna disease virus (BDV) is a neurotropic, negative single‑stranded RNA virus, which may be a cause of human neuropsychiatric disease. BDV is regarded as an ideal model to analyze the molecular mechanisms of mental disorders caused by viral infection. In the present study, 10 miRNAs were dysregulated in human oligodendrocytes (OL cells) infected with the BDV strain, Hu‑H1 (OL/BDV)...
October 13, 2016: Molecular Medicine Reports
Sairam Parthasarathy, Mary A Carskadon, Girardin Jean-Louis, Judith Owens, Adam Bramoweth, Daniel Combs, Lauren Hale, Elizabeth Harrison, Chantelle N Hart, Brant P Hasler, Sarah M Honaker, Elisabeth Hertenstein, Samuel Kuna, Clete Kushida, Jessica C Levenson, Caitlin Murray, Allan I Pack, Vivek Pillai, Kristi Pruiksma, Azizi Seixas, Patrick Strollo, Saurabh S Thosar, Natasha Williams, Daniel Buysse
A wealth of scientific knowledge is being generated in sleep and circadian science. In order for us to realize the return on investment for such scientific knowledge and to improve the health of the nation, we need to disseminate and implement research findings into practice. An implementation gap - termed a "quality chasm" by the Institutes of Medicine - separates the scientific knowledge we possess and the implementation of such knowledge into preventative interventions or healthcare treatments. It is frequently reported that a time lag of 17 years transpires before medical research reaches clinical practice...
October 10, 2016: Sleep
Clizia Chinello, Vincenzo L'Imperio, Martina Stella, Andrew James Smith, Giorgio Bovo, Angelica Grasso, Marco Grasso, Francesca Raimondo, Marina Pitto, Fabio Pagni, Fulvio Magni
Renal cell carcinoma (RCC) is the most fatal of the common urologic cancers, with approximately 35% of patients dying within 5 years following diagnosis. Therefore, there is a need for non-invasive markers that are capable of detecting and determining the severity of small renal masses at an early stage in order to tailor treatment and follow-up. Proteomic studies have proved to be very useful in the study of tumors. Areas covered: In this review, we will detail the current knowledge obtained by the different proteomic approaches, focusing on MS-based strategies, used to investigate RCC biology in order to identify diagnostic, prognostic and predictive biomarkers on tissue, cultured cells and biological fluids...
October 17, 2016: Expert Review of Proteomics
Steven W Barger
Ask any neuroscientist to name the most profound discoveries in the field in the past 60 years, and at or near the top of the list will be a phenomenon or technique related to genes and their expression. Indeed, our understanding of genetics and gene regulation has ushered in whole new systems of knowledge and new empirical approaches, many of which could not have even been imagined prior to the molecular biology boon of recent decades. Neurochemistry, in the classic sense, intersects with these concepts in the manifestation of neuropeptides, obviously dependent upon the central dogma (the established rules by which DNA sequence is eventually converted into protein primary structure) not only for their conformation but also for their levels and locales of expression...
October 17, 2016: Journal of Neurochemistry
Egidio Iorio, Maria José Caramujo, Serena Cecchetti, Francesca Spadaro, Giulia Carpinelli, Rossella Canese, Franca Podo
Triple-negative breast cancer (TNBC), defined as lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2, is still a clinical challenge despite progress in breast cancer care. (1)H magnetic resonance spectroscopy allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improve in vivo diagnosis and follow-up and also to identify new targets for treatment...
2016: Frontiers in Oncology
Julius T Kamwesiga, Lena von Koch, Anders Kottorp, Susanne Guidetti
BACKGROUND: Knowledge is scarce about the impact of stroke in Uganda, and culturally adapted, psychometrically tested patient-reported outcome measures are lacking. The Stroke Impact Scale 3.0 is recommended, but it has not been culturally adapted and validated in Uganda. OBJECTIVE: To culturally adapt and determine the psychometric properties of the Stroke Impact Scale 3.0 in the Ugandan context on a small scale. METHOD: The Stroke Impact Scale 3...
2016: SAGE Open Medicine
Sriram Neelamegham, Lara K Mahal
Glycosylation is a ubiquitous mammalian post-translational modification that both decorates a majority of expressed proteins and regulates their function. Cellular glycan biosynthesis is facilitated by a few hundred enzymes that are collectively termed 'glycoenzymes'. The expression and activity of these enzymes is controlled at the transcription, translation and post-translation levels. New wet-lab advances are providing analytical methods to collect large-scale data at these multiple levels, relational databases are starting to collate these results, and computer models are beginning to integrate this information across scales in order to gain new knowledge...
October 13, 2016: Current Opinion in Structural Biology
Pietro Maggi, Pascal Sati, Luca Massacesi
Magnetic resonance imaging (MRI) is an invaluable tool for the diagnosis and monitoring of patients with multiple sclerosis (MS) as well as for the study of the disease pathophysiology. Because of its strong clinical, radiological and histopathological similarities with the human disease, experimental autoimmune encephalomyelitis (EAE) in the common marmoset has been studied more intensively over the past several years. Here, we review the current knowledge on MRI in the marmoset EAE, and we outline the physiopathological significance and translational values of these studies with respect to MS...
October 8, 2016: Journal of Neuroimmunology
Chris McGlory, Michaela C Devries, Stuart M Phillips
Exercise results in the rapid remodelling of skeletal muscle imparting a positive impact on human health. This process is underpinned by acute and chronic changes in both gene and protein synthesis. In this short review we provide a brief summary of our current understanding regarding how exercise influences these processes as well as the subsequent impact on muscle protein turnover and resultant shift in muscle phenotype. We explore concepts of ribosomal biogenesis and the potential role of increased translational capacity versus translational efficiency in contributing to muscular hypertrophy...
October 14, 2016: Journal of Applied Physiology
Priyakshi Kalita-de Croft, Fares Al-Ejeh, Amy E McCart Reed, Jodi M Saunus, Sunil R Lakhani
Our understanding of the natural history of breast cancer has evolved alongside technologies to study its genomic, transcriptomic, proteomic, and metabolomics landscapes. These technologies have helped decipher multiple molecular pathways dysregulated in breast cancer. First-generation 'omics analyses considered each of these dimensions individually, but it is becoming increasingly clear that more holistic, integrative approaches are required to fully understand complex biological systems. The 'omics represent an exciting era of discovery in breast cancer research, although important issues need to be addressed to realize the clinical utility of these data through precision cancer care...
November 2016: Advances in Anatomic Pathology
Hongjiu Yu, Yonggui Ge, Lianying Guo, Lin Huang
Ewing's sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise...
October 11, 2016: Oncotarget
Adelaide R Murray, Rosemary M Caron
BACKGROUND: The American College Health Association's, National College Health Assessment (ACHA's NCHA) estimates 46.1% of college students reported being vaccinated in the last year. OBJECTIVE: 1) To understand the college student's knowledge, attitude, and beliefs in regards to influenza vaccination; 2) To establish recommendations in a population where high risk transmission does not consistently translate into high vaccination rates. METHODS: Utilizing the health belief model (HBM), a cross-sectional study of college student perspectives of influenza vaccination was conducted...
October 14, 2016: International Journal of Adolescent Medicine and Health
Rahul Krishnan, David Ko, Clarence E Foster, Wendy Liu, A M Smink, Bart de Haan, Paul De Vos, Jonathan R T Lakey
Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves...
2017: Methods in Molecular Biology
Tanes I Lima, Hygor N Araujo, Eveline S Menezes, Carlos H Sponton, Michel B Araújo, Lucas H M Bomfim, André L Queiroz, Madla A Passos, Thais Amaral E Sousa, Sandro M Hirabara, Amanda R Martins, Helena C L B Sampaio, Alice Rodrigues, Rui Curi, Everardo M Carneiro, Antônio C Boschero, Leonardo R Silveira
Mitochondria play a critical role in several cellular processes and cellular homeostasis. Mitochondrion dysfunction has been correlated with numerous metabolic diseases such as obesity and type 2 diabetes. MicroRNAs are non-coding RNAs that have emerged as key regulators of cell metabolism. The microRNAs act as central regulators of metabolic gene networks by leading to the degradation of their target messenger RNA or repression of protein translation. In addition, vesicular and non-vesicular circulating miRNAs exhibit a potential role as mediators of the cross-talk between the skeletal muscle and other tissues/organs...
October 13, 2016: Journal of Cellular Physiology
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