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J Czerwinska, M C Parkin, P I Dargan, C George, A T Kicman, V Abbate
Mephedrone is a new psychoactive substance known to be unstable in biological matrices stored at room temperature or refrigerated. While the instability of mephedrone has been investigated before, there is currently no data regarding the stability of mephedrone metabolites. In this study, a liquid chromatography tandem mass spectrometry method for the simultaneous quantification of mephedrone and five of its phase I metabolites (dihydro-mephedrone, nor-mephedrone, hydroxytolyl-mephedrone, 4-carboxy-mephedrone and dihydro-nor-mephedrone) in human whole blood has been developed and validated...
October 20, 2018: Drug Testing and Analysis
Zhaoke Pi, Yongpeng Huang, Yuanyuan Shen, Xiaojun Zeng, Yaxin Hu, Tie Chen, Chenyang Li, Hao Yu, Siping Chen, Xin Chen
Sonodynamic therapy (SDT) is a promising noninvasive method for cancer treatment. The anti-tumor effect of sinoporphyrin sodium (DVDMS)-mediated SDT on nude mice bearing intracranial U87 MG-Red-FLuc human glioblastoma was investigated. Focused ultrasound (FUS) with microbubbles (MBs) was utilized to open the blood-brain barrier for enhancing the delivery of the sonosensitizer DVDMS to the brain tumor first, and then the SDT treatment was performed. The in vitro study showed obvious cytotoxicity of DVDMS-mediated SDT (center frequency: 0...
October 12, 2018: Annals of Biomedical Engineering
Hooman Yadollahi-Farsani, Marcus Herrmann, David Frakes, Brian Chong
PURPOSE: To gain insight into the influence of coils on aneurysmal hemodynamics, computational fluid dynamics (CFD) can be used. Conventional methods of modeling coils consider the explicit geometry of the deployed devices within the aneurysm and discretize the fluid domain. However, the complex geometry of a coil mass leads to cumbersome domain discretization along with a significant number of mesh elements. These problems have motivated a homogeneous porous medium coil model, whereby the explicit geometry of the coils is greatly simplified, and relevant homogeneous porous medium parameters are approximated...
October 18, 2018: Cardiovascular Engineering and Technology
Osamu Wada, Noriaki Kurita, Tsukasa Kamitani, Naoki Nakano, Kiyonori Mizuno
Quadriceps strength is important for maintaining functional movement in patients with knee osteoarthritis (OA). We aimed to examine whether knee OA severity weakened the magnitude of the associations between leg muscle mass, quadriceps strength, and functional movement. Screening for People Suffering Sarcopenia in Orthopedic cohort of Kobe study (SPSS-OK) was a single-center cross-sectional study. We recruited 611 patients with knee OA. Leg muscle mass was determined by bioimpedance and used as a proxy for quadriceps muscle mass...
October 19, 2018: Clinical Rheumatology
Emma D Deeks
Doravirine is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Merck & Co for the treatment of HIV-1 infection. The drug is approved in the USA both as a single-agent tablet (Pifeltro™) and as a fixed-dose combination tablet with the nucleos(t)ide reverse transcriptase inhibitors lamivudine and tenofovir disoproxil fumarate (Delstrigo™). Each formulation is indicated in the USA for treating HIV-1 infection in adults with no prior antiretroviral treatment, has received a positive opinion in the EU for treating HIV-1 infection in adults without resistance to NNRTIs or (in the case of the fixed-dose combination tablet) lamivudine or tenofovir, and is also under regulatory review for the treatment of HIV-1 infection in Canada...
October 19, 2018: Drugs
Yuehong Chen, Jinlong Jian, Aubryanna Hettinghouse, Xueheng Zhao, Kenneth D R Setchell, Ying Sun, Chuan-Ju Liu
Tay-Sachs disease (TSD) is a lethal lysosomal storage disease (LSD) caused by mutations in the HexA gene, which can lead to deficiency of β-hexosaminidase A (HexA) activity and consequent accumulation of its substrate, GM2 ganglioside. Recent reports that progranulin (PGRN) functions as a chaperone of lysosomal enzymes and its deficiency is associated with LSDs, including Gaucher disease and neuronal ceroid lipofuscinosis, prompted us to screen the effects of recombinant PGRN on lysosomal storage in fibroblasts from 11 patients affected by various LSDs, which led to the isolation of TSD in which PGRN demonstrated the best effects in reducing lysosomal storage...
October 20, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Ning Zhang, Wen-Ying Wei, Hai-Han Liao, Zheng Yang, Can Hu, Sha-Sha Wang, Wei Deng, Qi-Zhu Tang
AdipoRon, a small-molecule adiponectin receptor (AdipoR) agonist, has been reported to be implicated in cardiovascular diseases. However, its role in pressure-overload-induced cardiac remodeling is still elusive. To elucidate the role of AdipoRon in the pathogenesis of cardiac remodeling in vivo and vitro, in the left ventricle of human end-stage heart failure, the expression of AdipoR2 is upregulated. Meanwhile, increased expression of AdipoR2 was also observed in mice failing hearts. Oral administration of AdipoRon alleviated cardiac hypertrophy and fibrosis induced by pressure overload, as evidenced by the beneficial change of cross-sectional area of cardiomyocytes, heart weight-to-body weight ratio, gene expression of hypertrophic markers, ventricle collagen ratio, and cardiac function...
October 19, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Christopher S Sundby, Geoffrey F Woodman, Keisuke Fukuda
Visual long-term memory allows us to store a virtually infinite amount of visual information (Brady, Konkle, Alvarez, & Oliva in Proceedings of the National Academy of Sciences of the United States of America, 105(38), 14325-14329, 2008; Standing in Quarterly Journal of Experimental Psychology, 25(2), 207-222, 1973). However, our ability to encode new visual information fluctuates from moment to moment. In Experiment 1, we tested the hypothesis that we have voluntary control over these periodic fluctuations in our ability to encode representations into visual long-term memory using a precueing paradigm combined with behavioral and electrophysiological indices of memory encoding...
October 19, 2018: Memory & Cognition
Wanlong Li, Qijun Zhang, Shuwen Wang, Marie A Langham, Dilkaran Singh, Robert L Bowden, Steven S Xu
Development of a complete wheat-Thinopyrum junceiforme amphiploid facilitated identification of resistance to multiple pests and abiotic stress derived from the wild species and shed new light on its genome composition. Wheat production is facing numerous challenges from biotic and abiotic stresses. Alien gene transfer has been an effective approach for wheat germplasm enhancement. Thinopyrum junceiforme, also known as sea wheatgrass (SWG), is a distant relative of wheat and a relatively untapped source for wheat improvement...
October 19, 2018: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
Surya Sapkota, Li-Ling Chen, Shanshan Yang, Katie E Hyma, Lance Cadle-Davidson, Chin-Feng Hwang
A major QTL for downy mildew resistance was detected on chromosome 18 (Rpv27) in Vitis aestivalis-derived 'Norton' based on a high-resolution linkage map with SNP and SSR markers as well as 2 years of field and laboratory phenotyping data. Grapevine downy mildew caused by the oomycete Plasmopara viticola is one of the most widespread and destructive diseases, particularly in humid viticultural areas where it damages green tissues and defoliates vines. Traditional Vitis vinifera wine grape cultivars are susceptible to downy mildew whereas several North American and a few Asian cultivars possess various levels of resistance to this disease...
October 19, 2018: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
S Oebel, G Hindricks
Syncope is a common problem in clinical practice, which affects approximately 1% of patients admitted to European emergency departments. The clinical practice guidelines for the diagnosis and management of syncope published by the European Society of Cardiology (ESC) are based on the newest scientific data in the field and have provided clinical cardiologists with a structured therapeutic approach for affected patients over many years. The previous ESC guidelines on syncope were published in 2009 and are compared to the most recent edition, which was published in 2018...
October 19, 2018: Herz
Oliver Strobel, John Neoptolemos, Dirk Jäger, Markus W Büchler
Pancreatic cancer is likely to become the second most frequent cause of cancer-associated mortality within the next decade. Surgical resection with adjuvant systemic chemotherapy currently provides the only chance of long-term survival. However, only 10-20% of patients with pancreatic cancer are diagnosed with localized, surgically resectable disease. The majority of patients present with metastatic disease and are not candidates for surgery, while surgery remains underused even in those with resectable disease owing to historical concerns regarding safety and efficacy...
October 19, 2018: Nature Reviews. Clinical Oncology
Mariateresa Di Stazio, Chiara Collesi, Diego Vozzi, Wei Liu, Mike Myers, Anna Morgan, Pio Adamo D Adamo, Giorgia Girotto, Elisa Rubinato, Mauro Giacca, Paolo Gasparini
Hereditary hearing loss (HHL) is an extremely heterogeneous disorder with autosomal dominant, recessive, and X-linked forms. Here, we described an Italian pedigree affected by HHL but also prostate hyperplasia and increased ratio of the free/total PSA levels, with the unusual and extremely rare Y-linked pattern of inheritance. Using exome sequencing we found a missense variant (r.206A>T leading to p.Asp69Val) in the TBL1Y gene. TBL1Y is homologous of TBL1X, whose partial deletion has described to be involved in X-linked hearing loss...
October 19, 2018: European Journal of Human Genetics: EJHG
Roberta Mancini, Tobias van der Bijl, Quentin Bourgeois-Jaarsma, Rizky Lasabuda, Alexander J Groffen
Recent advances in live Ca2+ imaging with increasing spatial and temporal resolution offer unprecedented opportunities, but also generate an unmet need for data processing. Here we developed SICT, a MATLAB program that automatically identifies rapid Ca2+ rises in time-lapse movies with low signal-to-noise ratios, using fluorescent indicators. A graphical user interface allows visual inspection of automatically detected events, reducing manual labour to less than 10% while maintaining quality control. The detection performance was tested using synthetic data with various signal-to-noise ratios...
October 19, 2018: Scientific Reports
Soundararajan Ashwinbalaji, Srinivasan Senthilkumari, Chidambaranathan Gowripriya, Subbaiah Krishnadas, B' Ann T Gabelt, Paul L Kaufman, Veerappan Muthukkaruppan
We investigated the effect of a new Rho kinase inhibitor, SB772077B (SB77) on aqueous outflow facility (OF) in human eyes using human organ-cultured anterior segment (HOCAS). IOP was monitored for 24 h post-treatment with either SB77 (0.1/10/50 µM) or vehicle after a stable baseline pressure. The hydrodynamic pattern of aqueous outflow was analysed by labelling outflow pathway with red fluorescent microspheres. The effect of SB77 on cell morphology, actin stress fibers, focal adhesions, ECM, status of RhoA activation and myosin light chain phosphorylation (p-MLC) were evaluated and compared with Y27632, by immunostaining using primary human trabecular meshwork (HTM) cells...
October 19, 2018: Scientific Reports
Antonio Bustamante, Maria Carmen Marques, Alejandro Sanz-Carbonell, Jose Miguel Mulet, Gustavo Gomez
miRNAs are fundamental endogenous regulators of gene expression in higher organisms. miRNAs modulate multiple biological processes in plants. Consequently, miRNA accumulation is strictly controlled through miRNA precursor accumulation and processing. Members of the miRNA319 family are ancient ribo-regulators that are essential for plant development and stress responses and exhibit an unusual biogenesis that is characterized by multiple processing of their precursors. The significance of the high conservation of these non-canonical biogenesis pathways remains unknown...
October 19, 2018: Scientific Reports
Katsuya Matsuda, Tatsuhiko Kawasaki, Yuko Akazawa, Yuhmi Hasegawa, Hisayoshi Kondo, Keiji Suzuki, Masachika Iseki, Masahiro Nakashima
Copy number alterations and loss of heterozygosity are associated with increasing tumor grade and bladder cancer stage. Our previous study suggested that co-expression of Ki-67 and p53-binding protein 1 (53BP1) could provide an indicator of an abnormal DNA damage response (DDR) pathway. The present study investigated 53BP1 expression as a novel molecular marker in urothelial carcinoma (UC) using bladder tissues with in total of 40 cases including a normal urothelium, urothelial papilloma, low-grade UC, or high-grade UC...
October 19, 2018: Scientific Reports
Pannathee Prangtaworn, Urai Chaisri, Watee Seesuay, Kodchakorn Mahasongkram, Nattawat Onlamoon, Onrapak Reamtong, Anchalee Tungtrongchitr, Nitaya Indrawattana, Wanpen Chaicumpa, Nitat Sookrung
Allergen-specific immunotherapy (AIT) facilitates long-term resolution of allergic morbidity resulting in reduced drug use and increased refractoriness to new sensitization. AIT effectiveness has been demonstrated in seasonal and perennial allergies, and insect stings. However, data and studies in AIT relative to cockroach (CR) allergy are relatively scarce. In this study, mice allergic to American CR (Periplaneta americana) were treated with a liposome (L)-entrapped vaccine made of mouse Tregitope289-Per a 9 of the CR, Tregitope167-Per a 9, or Per a 9 alone - or placebo...
October 19, 2018: Scientific Reports
Milena Rizzo, Pascale Beffy, Renata Del Carratore, Alessandra Falleni, Virginia Pretini, Romina D'Aurizio, Annalisa Botta, Monica Evangelista, Andrea Stoccoro, Fabio Coppedè, Denis Furling, Marcella Simili
Congenital myotonic dystrophy type 1 (CDM1) is characterized by severe symptoms that affect patients from birth, with 40% mortality in the neonatal period and impaired skeletal muscle development. In this paper, we examined the relationship between autophagy and abnormal myogenic differentiation of CDM1 myoblasts. We investigated these pathological features at both ultrastructural and molecular levels, utilizing two CDM1 foetal myoblasts, CDM13 and CDM15, with 1800 and 3200 repeats, respectively. The congenital nature of these CDM1 myoblasts was confirmed by the high methylation level at the DMPK locus...
October 19, 2018: Cell Death & Disease
Stephen Andrew Deppen, Pierre P Massion, Jeffrey Blume, Ronald C Walker, Sanja Antic, Heidi Chen, Michelle M Durkin, L Joseph Wheat, Eric L Grogan
BACKGROUND: Granulomas caused by infectious lung diseases present as indeterminate pulmonary nodules (IPNs) on radiography. Newly available serum enzyme immunoassay (EIA) for histoplasmosis has not been studied for the evaluation of IPNs. We investigated serum biomarkers of histoplasmosis antibodies as an indication of benign disease in IPNs from a highly endemic region. METHODS: 152 serum samples from patients presenting with pulmonary nodules ≤30mm in maximum diameter were analyzed for histoplasmosis antibodies by immunodiffusion and EIA IgG and IgM tests...
October 19, 2018: Cancer Epidemiology, Biomarkers & Prevention
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