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Jonathan Martens, Giel Berden, Herman Bentlage, Karlien L M Coene, Udo F Engelke, David Wishart, Monique van Scherpenzeel, Leo A J Kluijtmans, Ron A Wevers, Jos Oomens
The identification of molecular biomarkers is critical for diagnosing and treating patients and for establishing a fundamental understanding of the pathophysiology and underlying biochemistry of inborn errors of metabolism. Currently, liquid chromatography/high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy are the principle methods used for biomarker research and for structural elucidation of small molecules in patient body fluids. While both are powerful techniques, several limitations exist that often make the identification of unknown compounds challenging...
March 19, 2018: Journal of Inherited Metabolic Disease
Dharmendra K Yadav, Surendra Kumar, Saloni, Sanjeev Misra, Lalit Yadav, Mahesh Teli, Praveen Sharma, Sandeep Chaudhary, Naresh Kumar, Eun Ha Choi, Hyung Sik Kim, Mi-Hyun Kim
SIRT6 and COX-2 are oncogenes target that promote the expression of proinflammatory and pro-survival proteins through a signaling pathway, which leads to increased survival and proliferation of tumor cells. However, COX-2 also suppresses skin tumorigenesis and their relationship with SIRT6, making it an interesting target for the discovery of drugs with anti-inflammatory and anti-cancer properties. Herein, we studied the interaction of thieno[3,2-c]pyran analogs and RONS species with SIRT6 and COX-2 through the use of molecular docking and molecular dynamic simulations...
March 19, 2018: Scientific Reports
Soham Sengupta, Rachel Nechushtai, Patricia A Jennings, Jose' N Onuchic, Pamela A Padilla, Rajeev K Azad, Ron Mittler
The iron-sulfur (2Fe-2S) binding motif CDGSH appears in many important plant and animal proteins that regulate iron and reactive oxygen metabolism. In human it is found in CISD1-3 proteins involved in diabetes, obesity, cancer, aging, cardiovascular disease and neurodegeneration. Despite the important biological role of the CDGSH domain, its origin, evolution and diversification, are largely unknown. Here, we report that: (1) the CDGSH domain appeared early in evolution, perhaps linked to the heavy use of iron-sulfur driven metabolism by early organisms; (2) a CISD3-like protein with two CDGSH domains on the same polypeptide appears to represent the ancient archetype of CDGSH proteins; (3) the origin of the human CISD3 protein is linked to the mitochondrial endosymbiotic event; (4) the CISD1/2 type proteins that contain only one CDGSH domain, but function as homodimers, originated after the divergence of bacteria and archaea/eukaryotes from their common ancestor; and (5) the human CISD1 and CISD2 proteins diverged about 650-720 million years ago, and CISD3 and CISD1/2 share their descent from an ancestral CISD about 1-1...
March 19, 2018: Scientific Reports
Yair Fastman, Shany Assaraf, Miriam Rose, Elad Milrot, Katherine Basore, B Sivanandam Arasu, Sanjay A Desai, Michael Elbaum, Ron Dzikowski
Plasmodium falciparum, the causative agent of the deadliest form of human malaria, alternates expression of variable antigens, encoded by members of a multi-copy gene family named var. In var2csa, the var gene implicated in pregnancy-associated malaria, translational repression is regulated by a unique upstream open reading frame (uORF) found only in its 5' UTR. Here, we report that this translated uORF significantly alters both transcription and posttranslational protein trafficking. The parasite can alter a protein's destination without any modifications to the protein itself, but instead by an element within the 5' UTR of the transcript...
March 15, 2018: Nucleic Acids Research
Ron J Smith
BACKGROUND: Siege, a process of political domination aimed at isolating an entire population, is a unique threat to health-care provision. The aim of this study was to qualitatively examine the effects of the Israeli siege on the practices and systems that underlie health in the Gaza Strip. METHODS: Data were from participant observation between 2009 and 2017, including 20 interviews with doctors and health administrators in non-governmental organisations (NGO), government, and UN sectors...
February 21, 2018: Lancet
Yair Lahav, Yoram Epstein, Ron Kedem, Haggai Schermann
Anthropometric measures of body composition are often used for rapid and cost-effective estimation of percentage body fat (%BF) in field research, serial measurements and screening. Our aim was to develop a validated estimate of %BF for the general population, based on simple body circumferences measures. The study cohort consisted of two consecutive samples of health club members, designated as 'development' (n 476, 61 % men, 39 % women) and 'validation' (n 224, 50 % men, 50 % women) groups. All subjects underwent anthropometric measurements as part of their registration to a health club...
March 2018: British Journal of Nutrition
Ron Basuroy, Cathy Bouvier, John Ramage, Maia Sissons, Alexandra Kent, Raj Srirajaskanthan
<br>Introduction The gastrointestinal tract and pancreas are common primary sites for neuroendocrine tumours (NETs). Patients often report long duration of non-specific symptoms in the year prior to diagnosis. The aims of this study were to establish pre-diagnosis patterns of symptoms. Secondly, to determine the time from onset of symptoms to NET diagnosis and understand the interaction with primary and secondary healthcare providers. Method A survey was designed on a web-based survey platform with the focus on patient symptoms prior to diagnosis and a screen for functional diarrhoea (Rome III criteria (C4))...
March 18, 2018: Neuroendocrinology
Monika Raab, Mourad Sanhaji, Yves Matthess, Albrecht Hörlin, Ioana Lorenz, Christina Dötsch, Nils Habbe, Oliver Waidmann, Elisabeth Kurunci-Csacsko, Ron Firestein, Sven Becker, Klaus Strebhardt
The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities...
March 16, 2018: Nature Communications
Bryan W Heckman, K Michael Cummings, Georges J Nahas, Marc C Willemsen, Richard J O'Connor, Ron Borland, Alexander A Hirsch, Warren K Bickel, Matthew J Carpenter
Introduction: The demand for alternative nicotine/tobacco products is not well established. This paper uses a behavioral economic approach to test whether smokers have differential demand for conventional factory-made, electronic, and very low nicotine content cigarettes (FMCs/ECs/VLNCs) and uses the prospective cohort design to test the predictive validity of demand indices on subsequent use of commercially available FMCs and ECs. Methods: Daily smokers (>16 years) from the Netherlands completed an online survey in April 2014 (N=1215)...
March 14, 2018: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
Ron Stauder, Ralf Welsch, Maurizio Camagna, Wouter Kohlen, Gerd U Balcke, Alain Tissier, Michael H Walter
Strigolactones (SLs) are apocarotenoid phytohormones synthesized from carotenoid precursors. They are produced most abundantly in roots for exudation into the rhizosphere to cope with mineral nutrient starvation through support of root symbionts. Abscisic acid (ABA) is another apocarotenoid phytohormone synthesized in roots, which is involved in responses to abiotic stress. Typically low carotenoid levels in roots raise the issue of precursor supply for the biosynthesis of these two apocarotenoids in this organ...
2018: Frontiers in Plant Science
Rami Benbenishty, Ron Avi Astor, Ilan Roziner
OBJECTIVES: To assess the between-school variation in suicide ideation and to estimate the contribution of school-level attributes, student-level characteristics, and 2 cross-level interactions (school by student) to student suicide ideation. STUDY DESIGN: A secondary analysis of the California Healthy Kids Survey in 2 large and representative samples of California high schools and students: 2009-2011 and 2011-2013. This is a population sample of all public high school students (grades 9 and 11) in California...
March 7, 2018: Journal of Pediatrics
Ryan B Scott, Jason Samaha, Ron Chrisley, Zoltan Dienes
While theories of consciousness differ substantially, the 'conscious access hypothesis', which aligns consciousness with the global accessibility of information across cortical regions, is present in many of the prevailing frameworks. This account holds that consciousness is necessary to integrate information arising from independent functions such as the specialist processing required by different senses. We directly tested this account by evaluating the potential for associative learning between novel pairs of subliminal stimuli presented in different sensory modalities...
March 12, 2018: Cognition
Hiroshi Nakatani, Paul Gomes, Ron Bradford, Qiang Guo, Eleonora Safyan, David A Hollander
PURPOSE: To compare alcaftadine and olopatadine ophthalmic solutions, and vehicle for preventing allergen-mediated conjunctivitis in Japanese subjects. METHODS: Japanese cedar pollen-sensitive subjects were randomized to alcaftadine 0.25%, olopatadine 0.1%, or vehicle. Ocular itching was assessed at 3, 5 (primary outcome), 7, and 15 min post-conjunctival allergen challenge (CAC) and conjunctival hyperemia assessed at 7, 15 (secondary outcome), and 20 min post-CAC...
March 15, 2018: Ocular Immunology and Inflammation
Mario Novak, Vlasta Vyroubal, Željko Krnčević, Maja Petrinec, Rachel Howcroft, Ron Pinhasi, Mario Slaus
Childhood stress, using both subadult and adult remains from early mediaeval (8th -11th c. CE) sites on the eastern Adriatic coast is analysed in this report. A total of 242 individuals (83 subadults, 69 adult females, and 90 adult males) were assessed for the presence of linear enamel hypoplasia, cribra orbitalia, sub-periosteal new bone formation, and scurvy. In addition, the dietary profile of nine subadults was assessed by the analysis of carbon and nitrogen stable isotopes from bulk collagen. Over three quarters of individuals with preserved permanent dentition (44/56 or 78...
March 14, 2018: Anthropologischer Anzeiger; Bericht über die Biologisch-anthropologische Literatur
Ron A Wevers, Nenad Blau
No abstract text is available yet for this article.
March 14, 2018: Journal of Inherited Metabolic Disease
Jasveen J Kandhai-Ragunath, Carine J M Doggen, Liefke C van der Heijden, Marlies M Kok, Paolo Zocca, Bjorn de Wagenaar, Cees Doelman, Harald T Jørstad, Ron J G Peters, Clemens von Birgelen
Knowledge about the changes in endothelial function after ST-elevation myocardial infarction (STEMI) is of substantial interest, but serial data are scarce. The aim of the present study was to noninvasively evaluate whether endothelial function, as assessed shortly after primary percutaneous coronary intervention (PPCI) for STEMI, may improve until 12-month follow-up. This prospective observational cohort study was performed in patients in the RESPONSE randomized trial who participated in a substudy and underwent noninvasive assessment of endothelial function at 1 (baseline), 6, and 12-month follow-up after treatment of a STEMI by PPCI...
March 14, 2018: Heart and Vessels
Anand Rughani, Jason M Schwalb, Christos Sidiropoulos, Julie Pilitsis, Adolfo Ramirez-Zamora, Jennifer A Sweet, Sandeep Mittal, Alberto J Espay, Jorge Gonzalez Martinez, Aviva Abosch, Emad Eskandar, Robert Gross, Ron Alterman, Clement Hamani
QUESTION 1: Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson's disease, as measured by improvements in Unified Parkinson's Disease Rating Scale, part III (UPDRS-III) scores? RECOMMENDATION: Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson's disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms...
March 12, 2018: Neurosurgery
Claire E Kendall, Esther S Shoemaker, Janet Raboud, Amy E Mark, Ahmed M Bayoumi, Ann N Burchell, Mona Loutfy, Sean B Rourke, Clare E Liddy, Ron Rosenes, Timothy Rogers, Tony Antoniou
Timely presentation to care for people newly diagnosed with HIV is critical to optimize health outcomes and reduce onward HIV transmission. Studies describing presentation to care following diagnosis during a hospital admission are lacking. We sought to assess the timeliness of presentation to care and to identify factors associated with delayed presentation. We conducted a population-level study using health administrative databases. Participants were all individuals older than 16 and newly diagnosed with HIV during hospital admission in Ontario, Canada, between April 1, 2007 and March 31, 2015...
March 13, 2018: AIDS and Behavior
Anum Saeed, Vijay Nambi, Wensheng Sun, Salim S Virani, George Taffet, Anita Deswal, Elizabeth Selvin, Kunihiro Matsushita, Lynne E Wagenknecht, Ron Hoogeveen, Josef Coresh, James A de Lemos, Christie M Ballantyne
BACKGROUND: Current prevention guidelines recommend using the Pooled Cohort Equation (PCE) for 10-year atherosclerotic cardiovascular disease (CVD) risk assessment. However, the PCE has serious limitations in older adults: it excludes heart failure (HF) hospitalization, estimates 10-year risk which may not be the most relevant time frame, and is not indicated for individuals aged >79 years. OBJECTIVES: To determine whether adding biomarkers to PCE variables improves global CVD (coronary heart disease [CHD], stroke, and HF) risk prediction in older adults over a shorter time period...
March 3, 2018: Journal of the American College of Cardiology
Ersilia M DeFilippis, Avinainder Singh, Sanjay Divakaran, Ankur Gupta, Bradley L Collins, David Biery, Arman Qamar, Amber Fatima, Mattheus Ramsis, Daniel Pipilas, Roxanna Rajabi, Monica Eng, Jon Hainer, Josh Klein, James L Januzzi, Khurram Nasir, Marcelo F Di Carli, Deepak L Bhatt, Ron Blankstein
BACKGROUND: Substance abuse is increasingly prevalent among young adults but data on cardiovascular outcomes remain limited. OBJECTIVES: Our objective was to assess the prevalence of cocaine and marijuana use in adults with their first myocardial infarction (MI) at ≤50 years and determine its association with long-term outcomes. METHODS: We retrospectively analyzed records of patients presenting with a Type 1 MI at ≤50 years at two academic hospitals from 2000-2016...
March 5, 2018: Journal of the American College of Cardiology
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