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Elpida K Karadimou, Athanasios S Kallimanis, Ioannis Tsiripidis, Panayotis Dimopoulos
The relationship between species richness and area is one of the few well-established laws in ecology, and one might expect a similar relationship with functional diversity (FD). However, only a few studies investigate the relationship between trait-based FD and area, the Functional Diversity - Area Relationship (FDAR). To examine FDAR, we constructed the species accumulation curve and the corresponding FD curve. We used plant diversity data from nested plots (1-128 m(2)), recorded on the Volcanic islands of Santorini Archipelagos, Greece...
October 18, 2016: Scientific Reports
Katherine J Hahn, Shannon J Morales, James H Lewis
Anticoagulants are a well known cause of drug-induced liver injury (DILI). We recently encountered a 45-year-old male who developed DILI during treatment with enoxaparin, a low-molecular-weight heparin (LMWH), for dural venous thrombosis. The man received enoxaparin 80 mg subcutaneously, twice daily. After 4 days, the patient was asymptomatic but he developed liver aminotransferase elevations: AST 340 U/L and ALT 579 U/L. Investigation revealed an R ratio of 19.9 by day 5 and a Roussel Uclaf Causality Assessment Method score of 10, giving a high probable likelihood that enoxaparin was the cause of hepatic injury...
December 2015: Drug Saf Case Rep
Rachel Mourot-Cottet, Frédéric Maloisel, François Séverac, Olivier Keller, Thomas Vogel, Martine Tebacher, Jean-Christophe Weber, Georges Kaltenbach, Jacques-Eric Gottenberg, Bernard Goichot, Jean Sibilia, Anne-Sophie Korganow, Raoul Herbrecht, Emmanuel Andrès
BACKGROUND: Little data is currently available in the literature on neutropenia and agranulocytosis in the elderly, and, to our knowledge, idiosyncratic drug-induced agranulocytosis is particularly poorly covered, or not at all. OBJECTIVE: We herein describe the clinical picture and outcome of patients aged ≥75 years with established idiosyncratic drug-induced agranulocytosis. PATIENTS AND METHODS: Data from 61 patients over 75 years old with idiosyncratic drug-induced agranulocytosis were retrospectively reviewed...
September 5, 2016: Drugs—Real World Outcomes
Anton M Kolomeyer, Ken K Nischal, Ellen Mitchell
PURPOSE: To report a case of bilateral cavernous sinus thrombosis (CST) in a patient with tacrolimus-associated posttransplant thrombotic microangiopathy. METHODS: Case report. RESULTS: An 8-year-old boy with a medical history of orthotopic heart transplant, posttransplant lymphoproliferative disease, and recurrent infections was hospitalized for nausea, vomiting, and diarrhea. His ocular history included accommodative esotropia, hyperopia with astigmatism, Molluscum contagiosum lid lesions, and idiopathic intracranial hypertension...
October 13, 2016: European Journal of Ophthalmology
Christine Lin, Salman R Khetani
Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions...
2016: BioMed Research International
Elena Cabb, Shanna Baltar, David Wes Powers, Karthik Mohan, Antonio Martinez, Eric Pitts
Drug-induced liver injury (DILI) presents as a broad spectrum of adverse drug reactions which can range from a mild elevation in liver enzymes to fulminant liver failure. The primary goal is to identify DILI early when the patient's liver enzymes are elevated and to discontinue the offending agent as soon as possible to prevent further injury. Herbal, dietary supplements and anabolic steroids represent a significant component of the drugs thought to cause DILI in the United States. Unlike all other drugs known to cause DILI, these drugs fall into a category of injury that is neither intrinsic nor idiosyncratic due to overlapping characteristics between the two...
May 2016: Case Reports in Gastroenterology
Gabriel Aldaz, Sunil Puria, Larry J Leifer
BACKGROUND: Previous research has shown that hearing aid wearers can successfully self-train their instruments' gain-frequency response and compression parameters in everyday situations. Combining hearing aids with a smartphone introduces additional computing power, memory, and a graphical user interface that may enable greater setting personalization. To explore the benefits of self-training with a smartphone-based hearing system, a parameter space was chosen with four possible combinations of microphone mode (omnidirectional and directional) and noise reduction state (active and off)...
October 2016: Journal of the American Academy of Audiology
Yongjie Zhang, Nico P E Vermeulen, Jan N M Commandeur
AIMS: Oxidative bioactivation of amodiaquine (AQ) by cytochrome P450s to a reactive quinoneimine is considered as an important mechanism underlying its idiosyncratic hepatotoxicity. However, because internal exposure to its major metabolite N-desethylamodiaquine (DEAQ) is up to 240 fold higher than AQ, bioactivation of DEAQ might significant contribute to covalent binding. The aim of the present study was to compare the kinetics of bioactivation of AQ and DEAQ by human liver microsomes and to characterize the CYPs involved in bioactivation of AQ and DEAQ...
October 8, 2016: British Journal of Clinical Pharmacology
Marlena L Itz, Stefan R Schweinberger, Jürgen M Kaufmann
Recent findings show benefits for learning and subsequent recognition of faces caricatured in shape or texture, but there is little evidence on whether this caricature learning advantage generalizes to recognition of veridical counterparts at test. Moreover, it has been reported that there is a relatively higher contribution of texture information, at the expense of shape information, for familiar compared to unfamiliar face recognition. The aim of this study was to examine whether veridical faces are recognized better when they were learned as caricatures compared to when they were learned as veridicals-what we call a caricature generalization benefit...
October 7, 2016: Cognitive, Affective & Behavioral Neuroscience
Delphine Kapps, Marta Cela, Anne Théobald-Dietrich, Tamara Hendrickson, Magali Frugier
In this Review, we examine the so-called 'OB-fold', a tRNA-binding domain homologous to the bacterial tRNA-binding protein Trbp111. We highlight the ability of OB-fold homologs to bind tRNAs and summarize their distribution in evolution. Nature has capitalized on the advantageous effects acquired when an OB-fold domain binds to tRNA by evolutionarily selecting this domain for fusion to different enzymes. Here, we review our current understanding of how the complexity of OB-fold containing proteins and enzymes developed to expand their functions, especially in unicellular, pathogenic eukaryotes...
October 7, 2016: FEBS Letters
Beate Steinfeld, Anika Bauer, Manuel Waldorf, Nicole Engel, Karsten Braks, Thomas J Huber, Silja Vocks
Body-related checking behavior, as a behavioral manifestation of a disturbed body image, fosters the development and maintenance of eating disorders. The Body Checking Questionnaire (BCQ) is the most commonly used questionnaire for measuring body-related checking behavior internationally. To date, validation studies are only available for adult populations. Therefore, the aim of this study was to statistically test the German-language version of the BCQ in adolescents. A total of N=129 female adolescents were examined, comprising n=57 with Anorexia Nervosa, n=24 with Bulimia Nervosa, and n=48 healthy female adolescents...
October 6, 2016: Psychotherapie, Psychosomatik, Medizinische Psychologie
Lawrence E Armstrong, Elaine C Lee, Douglas Casa, Evan C Johnson, Matthew S Ganio, Brendon McDermott, Jakob Vingren, Hymn M Oh, Keith H Williamson
Although case reports of exertional hyponatremia (EH) during prolonged exercise implicate retention of excess fluid, athletes with EH experience either loss, gain, or no change of body weight. Thus, the etiology and predisposing factors of EH may not be the same in all athletes. The present field investigation evaluated two unacquainted recreational cyclists (LC, 31y and AM, 39y) who began exercise with normal serum electrolytes but finished a summer 164-km ride (ambient, 34±5°C) with a serum [Na+] of 130 mmol/L...
October 6, 2016: International Journal of Sport Nutrition and Exercise Metabolism
Patrick Davey, Siobhan Gee, Sukhi S Shergill
SUMMARY: A case is presented of a 25-year-old man with treatment-resistant paranoid schizophrenia whose only previous trial of clozapine had been stopped following a suspected clozapine-induced myocarditis. Due to the failure of his psychosis to respond to a number of antipsychotic treatments and augmentation strategies, clozapine was restarted on admission. His rechallenge was marked by intermittent pyrexia, tachycardia and elevated C-reactive protein (CRP), but eosinophilia was absent...
May 2016: BJPsych Open
Xiaoli Meng, Adriana Ariza, James Waddington, Kevin Park, Dean Naisbitt
Drug hypersensitivity reactions (DHRs) are adverse drug reactions that may be divided into several categories; namely pharmacologic intolerance, idiosyncratic reactions, pseudo-allergic reactions and allergic reactions. Drug allergic reactions are those DHRs that are mediated by either antibodies or drug-specific T cells. They vary in terms of severity, time-to-onset of clinical manifestations and target organ. Skin is most commonly implicated in drug hypersensitivity reactions; however, it is now apparent that reactions targeting internal organs fall under the definition of drug hypersensitivity...
October 3, 2016: Current Pharmaceutical Design
Saeideh Ghahghaei, Laura Walker
Crowding increases with eccentricity and is most readily observed in the periphery. During natural, active vision, however, central vision plays an important role. Measures of critical distance to estimate crowding are difficult in central vision, as these distances are small. Any overlap of flankers with the target may create an overlay masking confound. The crowding factor method avoids this issue by simultaneously modulating target size and flanker distance and using a ratio to compare crowded to uncrowded conditions...
September 1, 2016: Journal of Vision
Arun Tailor, James C Waddington, Xiaoli Meng, B Kevin Park
The covalent binding of drugs (metabolites) to proteins to form drug-protein adducts can have an adverse effect on the body. These adducts are thought to be responsible for idiosyncratic drug reactions including severe drug hypersensitivity reactions. Major advances in proteomics technology have allowed for the identification and quantification of target proteins for certain drugs. Human serum albumin (HSA) and Hb have been identified as accessible targets and potential biomarkers for drug-protein adducts formation, for numerous drugs (metabolites) including β-lactam antibiotics, reactive drug metabolites such as quinone imines (acetaminophen) and acyl glucuronides (diclofenac), and covalent inhibitors (neratinib)...
September 30, 2016: Chemical Research in Toxicology
Franck A Atienzar, Eric A Blomme, Minjun Chen, Philip Hewitt, J Gerry Kenna, Gilles Labbe, Frederic Moulin, Francois Pognan, Adrian B Roth, Laura Suter-Dick, Okechukwu Ukairo, Richard J Weaver, Yvonne Will, Donna M Dambach
Drug-induced liver injury (DILI) is a major cause of late-stage clinical drug attrition, market withdrawal, black-box warnings, and acute liver failure. Consequently, it has been an area of focus for toxicologists and clinicians for several decades. In spite of considerable efforts, limited improvements in DILI prediction have been made and efforts to improve existing preclinical models or develop new test systems remain a high priority. While prediction of intrinsic DILI has improved, identifying compounds with a risk for idiosyncratic DILI (iDILI) remains extremely challenging because of the lack of a clear mechanistic understanding and the multifactorial pathogenesis of idiosyncratic drug reactions...
2016: BioMed Research International
Robin Paudel, Prerna Dogra, Saurav Suman, Saurav Acharya, Jyoti Matta
Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80...
2016: Case Reports in Critical Care
Corina G Heidrich, Sanya Mitova, Andreas Schedlbauer, Sean R Connell, Paola Fucini, Judith N Steenbergen, Christian Berens
Omadacycline is an aminomethylcycline antibiotic with potent activity against many Gram-positive and Gram-negative pathogens, including strains carrying the major efflux and ribosome protection resistance determinants. This makes it a promising candidate for therapy of severe infectious diseases. Omadacycline inhibits bacterial protein biosynthesis and competes with tetracycline for binding to the ribosome. Its interactions with the 70S ribosome were, therefore, analyzed in great detail and compared with tigecycline and tetracycline...
2016: Antibiotics
Keisuke Goda, Tadakazu Takahashi, Akio Kobayashi, Toshiyuki Shoda, Hideyuki Kuno, Shoichiro Sugai
Drug-induced liver injury (DILI) is one of the serious and frequent drug-related adverse events. This adverse event is a main reason for regulatory action pertaining to drugs, including restrictions in clinical indications and withdrawal from clinical trials or the marketplace. Idiosyncratic DILI especially has become a major clinical concern because of its unpredictable nature, frequent hospitalization, need for liver transplantation and high mortality. The estimation of the potential for compounds to induce idiosyncratic DILI is very difficult in non-clinical studies because the precise mechanism of idiosyncratic DILI is still unknown...
2016: Journal of Toxicological Sciences
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