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Alessandro Mantovani, Stefano Bonapace, Gianluigi Lunardi, Matteo Salgarello, Clementina Dugo, Guido Canali, Christopher D Byrne, Stefania Gori, Enrico Barbieri, Giovanni Targher
BACKGROUND: Recent studies have suggested that specific plasma ceramides are independently associated with major adverse cardiovascular events in patients with coronary artery disease (CAD), but it is currently unknown whether plasma ceramide levels are associated with stress-induced reversible myocardial ischemia. METHODS: We measured six previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1)] in 167 consecutive patients with established or suspected CAD who underwent either exercise or dypiridamole myocardial perfusion scintigraphy (MPS) for various clinical indications...
May 16, 2018: Metabolism: Clinical and Experimental
E Laboute, E James-Belin, P L Puig, P Trouve, E Verhaeghe
PURPOSE: The risk of graft failure after anterior cruciate ligament (ACL) reconstructions with hamstring or patellar tendon was evaluated in a French population of athletes. METHODS: Athletes who had undergone ACL autograft reconstruction and who received rehabilitation care at the European Center for Sports Rehabilitation (CERS; Capbreton, France) were screened for this prospective cohort study. Eligibility criteria included a simple hamstring autograft or patellar tendon autograft surgical technique...
May 16, 2018: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
Olga N Raguimova, Nikolai Smolin, Elisa Bovo, Siddharth Bhayani, Joseph M Autry, Aleksey V Zima, Seth L Robia
The conformational changes of a calcium transport A TPase were investigated with molecular dynamics (MD) simulations as well as fluorescence resonance energy transfer (FRET) measurements to determine the significance of a discrete structural element for regulation of the conformational dynamics of the transport cycle. Previous MD simulations indicated that a loop in the cytosolic domain of the SERCA calcium transporter facilitates an open-to-closed structural transition. To investigate the significance of this structural element, we performed additional MD simulations and new biophysical measurements of SERCA structure and function...
May 15, 2018: Journal of Biological Chemistry
Laura Sonea, Mihail Buse, Diana Gulei, Anca Onaciu, Ioan Simon, Cornelia Braicu, Ioana Berindan-Neagoe
Lung cancer continues to be the leading topic concerning global mortality rate caused by can-cer; it needs to be further investigated to reduce these dramatic unfavorable statistic data. Non-coding RNAs (ncRNAs) have been shown to be important cellular regulatory factors and the alteration of their expression levels has become correlated to extensive number of pathologies. Specifically, their expres-sion profiles are correlated with development and progression of lung cancer, generating great interest for further investigation...
May 2018: Current Genomics
Pierluigi Tricoci, L Kristin Newby, Robert M Clare, Sergio Leonardi, C Michael Gibson, Robert P Giugliano, Paul W Armstrong, Frans Van de Werf, Gilles Montalescot, David J Moliterno, Claes Held, Philip E Aylward, Lars Wallentin, Robert A Harrington, Eugene Braunwald, Kenneth W Mahaffey, Harvey D White
OBJECTIVES: In 13,038 patients with non-ST-segment elevation acute coronary syndrome undergoing index percutaneous coronary intervention (PCI) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome) and TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trials, the relationship between PCI-related myocardial infarction (MI) and 1-year mortality was assessed. BACKGROUND: The definition of PCI-related MI is controversial...
May 14, 2018: JACC. Cardiovascular Interventions
Suzanne P Stam, Maryse Cj Osté, Michele F Eisenga, Hans Blokzijl, Aad P van den Berg, Stephan Jl Bakker, Vincent E de Meijer
Long-term survival in orthotopic liver transplant (OLT) recipients remains impaired due to many contributing factors, among which a low pre-transplant muscle mass (or sarcopenia). However, influence of post-transplant muscle mass on survival is currently unknown. We hypothesized that post-transplant urinary creatinine excretion rate (CER), an established non-invasive marker of total body muscle mass, is associated with long-term survival after OLT. In a single-center cohort study of 382 adult OLT recipients, mean±standard deviation CER at 1 year post-transplantation was 13...
May 9, 2018: American Journal of Transplantation
Piotr Zabielski, Hady Razak Hady, Marta Chacinska, Kamila Roszczyc, Jan Gorski, Agnieszka U Blachnio-Zabielska
We sought to determine whether metformin treatment reverses a high-fat diet (HFD)-induced hepatic insulin resistance (IRes) and to identify lipid intermediates involved in induction of liver IRes. The experiments were conducted on male Wistar rats divided into three groups: 1. Control, 2. fed HFD and 3. fed HFD and treated with metformin. The animals were infused with a [U-13 C]palmitate to measure fractional lipid synthesis rate. This allowed for the calculation of fractional synthesis rate of signaling lipids (FSR) through the estimation of their isotopic enrichment...
May 8, 2018: Scientific Reports
Frode Norheim, Thomas Bjellaas, Simon T Hui, Karthickeyan Chella Krishnan, Jakleen Lee, Sonul Gupta, Calvin Pan, Yehudit Hasin-Brumshtein, Brian W Parks, Daniel Li, Hai Bui, Marian Mosier, Yuping Wu, Adriana Huertas-Vazquez, Stanley W Hazen, Thomas E Gundersen, Margarete Mehrabian, Wilson Tang, Andrea L Hevener, Christian A Drevon, Aldons Jake Lusis
Elevated hepatic ceramides levels have been implicated in both insulin resistance (IR) and hepatic steatosis. To understand the factors contributing to hepatic ceramide levels in mice of both sexes, we have quantitated ceramides in a reference population of mice, the Hybrid Mouse Diversity Panel (HMDP) that has been previously characterized for a variety of metabolic syndrome traits. We observed significant positive correlations between Cer(d18:1/16:0) and IR/hepatic steatosis, consistent with previous findings, although the relationship broke down between sexes, as females were less insulin resistant but had higher Cer(d18:1/16:0) levels than males...
May 8, 2018: Journal of Lipid Research
Hongbo Yuan, M Sanni Ali, Emily S Brouwer, Cynthia J Girman, Jeff J Guo, Jennifer L Lund, Elisabetta Patorno, Jonathan L Slaughter, Xuerong Wen, Dimitri Bennett
On December 8, 2016, the New England Journal of Medicine published a sounding board on Real World Evidence (RWE)1 by the US Food and Drug Administration (FDA) leadership. While the value of RWE based on nonrandomized observational studies was appreciated, such as for hypothesis generating, safety, and measuring quality in healthcare delivery, the authors expressed concerns on the quality of data sources and the ability of methodologies to control for confounding. In response, we offer a few considerations regarding these concerns...
May 7, 2018: Clinical Pharmacology and Therapeutics
Huang Zheng, Xinli Xing, Tianpeng Hu, Yuan Zhang, Jiaquan Zhang, Gehao Zhu, Ying Li, Shihua Qi
The purpose of this study was to assess the human cancer risk due to the exposure to the soil-bound polycyclic aromatic hydrocarbons (PAHs) from Chengdu Economic Region (CER), western China with the main concern on cancer risk source apportionment. The total concentrations of sixteen PAHs ranged from 12.5 to 75431 ng g-1 , with a mean value of 3106 ng g-1 , which suggested that the most areas of CER were contaminated. Source apportionment of PAHs was conducted by the positive matrix factorization (PMF) model and the biomass burning contributed most (63...
May 3, 2018: Ecotoxicology and Environmental Safety
Kyeonga Jang, Jeeyeon Lee, Heeyoung Lee, Sejeong Kim, Jimyeong Ha, Yukyung Choi, Hyemin Oh, Yohan Yoon, Soomin Lee
The objective of this study was to investigate the pathogenicity and antimicrobial resistance of foodborne pathogens isolated from farmstead cheeses. Twenty-seven isolates, including 18 Bacillus cereus , two Escherichia coli , and seven Staphylococcus aureus , were subjected to polymerase chain reaction (PCR) to detect virulence genes and toxin genes, and the antibiotic resistances of the isolates were determined. All E. coli isolates were determined by PCR to be non-pathogenic. Among the 18 B . cereus isolates, 17 isolates (94...
February 2018: Korean Journal for Food Science of Animal Resources
Anjaneyulu Kowluru, Renu A Kowluru
The International Diabetes Federation predicts that by 2045 the number of individuals afflicted with diabetes will increase to 629 million. Furthermore, ∼352 million individuals with impaired glucose tolerance are at increased risk for developing diabetes. Several mechanisms have been proposed for the onset of metabolic dysfunction and demise of the islet β-cell leading to the pathogenesis of diabetes. It is widely accepted that the onset of type 2 diabetes is due to an intricate interplay between genetic expression of the disease and a multitude of factors including increased oxidative and endoplasmic reticulum stress consequential to glucolipotoxicity and inflammation...
April 28, 2018: Biochemical Pharmacology
Wei Li, Aiyin Li, Bin Wang, Xiuyuan Niu, Xin Cao, Xinyi Wang, Hao Shi
OBJECTIVES: To evaluate the effect of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASiR) technique in the reduction of radiation and contrast medium dose in typical hepatic hemangioma (HH) dual-energy spectral CT (DEsCT). METHODS: 62 patients with suspected HH were randomly divided into two groups equally: group A, conventional 120-kVp CT with standard iodine load; group B, DEsCT with ASIS technique and reduced iodine load, two sets of monochromatic spectral images were reconstructed: 69keV level with 30% ASiR (group B1 ) and 52keV level with 50%ASiR (group B2 )...
May 1, 2018: British Journal of Radiology
Yoshiaki Yao, Kota Toshimoto, Soo-Jin Kim, Takashi Yoshikado, Yuichi Sugiyama
Cerivastatin (CER) was withdrawn from the world market because of lethal rhabdomyolysis. Coadministrations of CER and cyclosporine A (CsA) or gemfibrozil (GEM) have been reported to increase the CER blood concentration. CsA is an inhibitor of OATP1B1 and CYP3A4, and GEM and its glucuronide (GEM-glu) inhibit OATP1B1 and CYP2C8. The purpose of this study was to describe the transporter-/enzymemediated drug-drug interactions (DDIs) of CER with CsA or GEM based on unified physiologically based pharmacokinetic (PBPK) models and to investigate whether the DDIs can be quantitatively analyzed by a bottom-up approach...
April 30, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Rakesh Gupta, Beena Rai
Skin electroporation has been used significantly to increase the drug permeation. However, molecular mechanism, which resulted in enhancement of flux through skin, is still not known. In this study, extensive atomistic molecular dynamics simulation of skin lipids (made up of ceramide (CER), cholesterol (CHOL) and free fatty acid (FFA)) have been performed at various external electric field. We show for the first time the pore formation in the skin lipid bilayer during the electroporation. We show the effect of applied external electrical field on the pore formation dynamics in lipid bilayer of different size and composition...
April 30, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Douglas P Landsittel, Larry Kessler, Christopher H Schmid, Paul Marantz, Maria E Suarez-Almazor
A number of publications have discussed approaches to training the scientific workforce in comparative effectiveness research (CER) and patient-centered outcomes research (PCOR). To meet this need, funders have offered resources for developing educational materials and establishing training programs. To extend these efforts into specific researcher communities, the Agency for Healthcare Research and Quality developed an R25 Funding Opportunity Announcement that called for basic, advanced, and experiential training for a specific researcher community in collaboration with associated program partners...
October 2017: Journal of Clinical and Translational Science
Katalin Sandor, Shibu Krishnan, Nilesh Mohan Agalave, Emerson Krock, Jaira Villarreal Salcido, Teresa Fernandez-Zafra, Payam Emami Khoonsari, Camilla I Svensson, Kim Kultima
By screening for neuropeptides in the mouse spinal cord using mass spectrometry (MS), we have previously demonstrated that one of the 78 peptides that is expressed predominantly (> 6-fold) in the dorsal horn compared to the ventral spinal cord is the atypical peptide desCER [des-Ser1]-cerebellin, which originates from the precursor protein cerebellin 1 (CBLN1). Furthermore, we found that intrathecal injection of desCER induces mechanical hypersensitivity in a dose dependent manner. The current study was designed to further investigate the relative expression of other CBLN derived peptides in the spinal cord and to examine whether they share similar nociceptive properties...
April 14, 2018: Neuropeptides
F Wang, W-H Tan, W Liu, Y-X Jin, D-D Dong, X-J Zhao, Q Liu
OBJECTIVE: PI3K/AKT/mTOR pathway plays important roles in tumor pathogenesis. mTOR is up-regulated and miR-214 is down-regulated in cervical can-*cers. This study investigated whether miR-214 regulated mTOR expression and affected cervical cancer cell proliferation, apoptosis or invasion. PATIENTS AND METHODS: Cervical cancer tissues were collected in parallel with normal epithelium for measuring the expression of miR-214 and mTOR. Dual luciferase expression assay was performed to evaluate the targeted relationship between miR-214 and mTOR...
April 2018: European Review for Medical and Pharmacological Sciences
Wang Haochen, Wang Jian, Song Li, Lv Tianshi, Tong Xiaoqiang, Zou Yinghua
Objective This study was performed to determine whether transarterial chemoembolization (TACE) plus multi-imaging-guided radiofrequency ablation (MIG-RFA) can completely eliminate 3.1- to 5.0-cm hepatocellular carcinoma (HCC) nodules and identify factors that may influence the complete elimination rate (CER) of this therapy. Methods Patients who underwent TACE+MIG-RFA for initial treatment of HCC from January 2008 to January 2016 were retrospectively reviewed. In total, 162 patients with 216 HCC nodules (3...
January 1, 2018: Journal of International Medical Research
Violeta García-Hernández, Carmen Sánchez-Bernal, Domitille Schvartz, José J Calvo, Jean-Charles Sanchez, Jesús Sánchez-Yagüe
Changes in the protein expression occurring within the initiation phase of acute pancreatitis (AP) might be vital in the development of this complex disease. However, the exact mechanisms involved in the onset of AP remains elusive and most of our knowledge about the pathobiology of AP comes from animal models. We performed in a rat pancreatitic model a high-throughput shotgun proteomic profiling of the soluble and whole membrane fractions from the pancreas during the early phase of cerulein (Cer)-induced AP...
April 17, 2018: Journal of Proteomics
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