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https://www.readbyqxmd.com/read/29758065/the-genetic-component-of-preeclampsia-a-whole-exome-sequencing-study
#1
Anette Tarp Hansen, Jens Magnus Bernth Jensen, Anne-Mette Hvas, Mette Christiansen
Preeclampsia is a major cause of maternal and perinatal deaths. The aetiology of preeclampsia is largely unknown but a polygenetic component is assumed. To explore this hypothesis, we performed an in-depth whole-exome sequencing study in women with (cases, N = 50) and without (controls, N = 50) preeclampsia. The women were identified in an unselected cohort of 2,545 pregnant women based on data from the Danish National Patient Registry and the Medical Birth Registry. Matching DNA was obtained from a biobank containing excess blood from routine antenatal care visits...
2018: PloS One
https://www.readbyqxmd.com/read/29739385/long-term-follow-up-on-biological-risk-factors-adiposity-and-cardiorespiratory-fitness-development-in-a-physical-education-intervention-a-natural-experiment-champs-study-dk
#2
Jakob Tarp, Eva Jespersen, Niels Christian Møller, Heidi Klakk, Barbara Wessner, Niels Wedderkopp, Anna Bugge
BACKGROUND: Schools are a key setting for large-scale primordial non-communicable disease prevention in young people, but little data on sustainability of impacts on cardiometabolic risk markers is available. METHODS: Six and a half year follow-up of a natural experiment. In 2008, six public schools in the municipality of Svendborg (Denmark) augmented their curricular physical education (intervention) and four matched schools served as controls. At long term follow up in 2015 n = 312 participants aged 5-11 years had complete data (33% of children providing necessary baseline data)...
May 9, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29717136/ancient-dna-study-reveals-hla-susceptibility-locus-for-leprosy-in-medieval-europeans
#3
Ben Krause-Kyora, Marcel Nutsua, Lisa Boehme, Federica Pierini, Dorthe Dangvard Pedersen, Sabin-Christin Kornell, Dmitriy Drichel, Marion Bonazzi, Lena Möbus, Peter Tarp, Julian Susat, Esther Bosse, Beatrix Willburger, Alexander H Schmidt, Jürgen Sauter, Andre Franke, Michael Wittig, Amke Caliebe, Michael Nothnagel, Stefan Schreiber, Jesper L Boldsen, Tobias L Lenz, Almut Nebel
Leprosy, a chronic infectious disease caused by Mycobacterium leprae (M. leprae), was very common in Europe till the 16th century. Here, we perform an ancient DNA study on medieval skeletons from Denmark that show lesions specific for lepromatous leprosy (LL). First, we test the remains for M. leprae DNA to confirm the infection status of the individuals and to assess the bacterial diversity. We assemble 10 complete M. leprae genomes that all differ from each other. Second, we evaluate whether the human leukocyte antigen allele DRB1*15:01, a strong LL susceptibility factor in modern populations, also predisposed medieval Europeans to the disease...
May 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29701884/retinal-vascular-diameters-in-relation-to-physical-activity-in-danish-children-the-champs-eye-study
#4
Kristian Lundberg, Jakob Tarp, Anders Højslet Vestergaard, Nina Jacobsen, Anne Suhr Thykjaer, Maria Sode Rønne, Anna Bugge, Ernst Goldschmidt, Tunde Peto, Niels Wedderkopp, Jakob Grauslund
Our objective was to determine associations between retinal vascular caliber and physical activity (PA) in a school-based child cohort. In a prospective study we created a childhood cumulative average PA-index using objectively measured PA (accelerometry) assessed at four periods between 2009 and 2015. Cumulative exposure to PA intensities was estimated. Cross-sectional examinations on biomarkers, anthropometry and ophthalmological data including retinal fundus photographs were performed in 2015. Semi-automated measurements of retinal vascular diameters were performed and summarized into central retinal arteriolar and venular equivalents (CRAE, CRVE)...
April 27, 2018: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/29660331/biophysical-characterization-of-actin-bundles-generated-by-the-chlamydia-trachomatis-tarp-effector
#5
Susmita Ghosh, Jinho Park, Mitchell Thomas, Edgar Cruz, Omar Cardona, Hyeran Kang, Travis Jewett
Chlamydia trachomatis entry into host cells is mediated by pathogen-directed remodeling of the actin cytoskeleton. The chlamydial type III secreted effector, translocated actin recruiting phosphoprotein (Tarp), has been implicated in the recruitment of actin to the site of internalization. Tarp harbors G-actin binding and proline rich domains required for Tarp-mediated actin nucleation as well as unique F-actin binding domains implicated in the formation of actin bundles. Little is known about the mechanical properties of actin bundles generated by Tarp or the mechanism by which Tarp mediates actin bundle formation...
April 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29649569/the-use-of-molecular-descriptors-in-the-development-of-co-amorphous-formulations
#6
Helena Meng-Lund, Georgia Kasten, Katrine Tarp Jensen, Antti Poso, Tatu Pantsar, Thomas Rades, Jukka Rantanen, Holger Grohganz
Co-amorphous systems consisting of a drug and an amino acid have been investigated extensively for the enhancement of drug solubility and amorphous stability. The purpose of this study is to investigate which molecular descriptors are important for predicting the likelihood of a successful co-amorphisation between amino acid and drug. The predictions are thought to be used in an early screening phase to identify potential drug-amino acid combinations for further studies. A large variety of molecular descriptors was calculated for six drugs (carvedilol, mebendazole, carbamazepine, furosemide, indomethacin and simvastatin) and the twenty naturally occurring amino acids...
April 9, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29581259/ltp-requires-postsynaptic-pdz-domain-interactions-with-glutamate-receptor-auxiliary-protein-complexes
#7
Nengyin Sheng, Michael A Bemben, Javier Díaz-Alonso, Wucheng Tao, Yun Stone Shi, Roger A Nicoll
Long-term potentiation (LTP) is a persistent strengthening of synaptic transmission in the brain and is arguably the most compelling cellular and molecular model for learning and memory. Previous work found that both AMPA receptors and exogenously expressed kainate receptors are equally capable of expressing LTP, despite their limited homology and their association with distinct auxiliary subunits, indicating that LTP is far more promiscuous than previously thought. What might these two subtypes of glutamate receptor have in common? Using a single-cell molecular replacement strategy, we demonstrate that the AMPA receptor auxiliary subunit TARP γ-8, via its PDZ-binding motif, is indispensable for both basal synaptic transmission and LTP...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29482619/population-based-analysis-of-ocular-chlamydia-trachomatis-in-trachoma-endemic-west-african-communities-identifies-genomic-markers-of-disease-severity
#8
A R Last, H Pickering, C H Roberts, F Coll, J Phelan, S E Burr, E Cassama, M Nabicassa, H M B Seth-Smith, J Hadfield, L T Cutcliffe, I N Clarke, D C W Mabey, R L Bailey, T G Clark, N R Thomson, M J Holland
BACKGROUND: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease. METHODS: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa...
February 26, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29386631/the-intrinsically-disordered-tarp-protein-from-chlamydia-binds-actin-with-a-partially-preformed-helix
#9
James Tolchard, Samuel J Walpole, Andrew J Miles, Robin Maytum, Lawrence A Eaglen, Ted Hackstadt, B A Wallace, Tharin M A Blumenschein
Tarp (translocated actin recruiting phosphoprotein) is an effector protein common to all chlamydial species that functions to remodel the host-actin cytoskeleton during the initial stage of infection. In C. trachomatis, direct binding to actin monomers has been broadly mapped to a 100-residue region (726-825) which is predicted to be predominantly disordered, with the exception of a ~10-residue α-helical patch homologous to other WH2 actin-binding motifs. Biophysical investigations demonstrate that a Tarp726-825 construct behaves as a typical intrinsically disordered protein; within it, NMR relaxation measurements and chemical shift analysis identify the ten residue WH2-homologous region to exhibit partial α-helix formation...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330067/protein-complexes-as-psychiatric-and-neurological-drug-targets
#10
REVIEW
Akihiko S Kato, Jeffrey M Witkin
The need for improved medications for psychiatric and neurological disorders is clear. Difficulties in finding such drugs demands that all strategic means be utilized for their invention. The discovery of forebrain specific AMPA receptor antagonists, which selectively block the specific combinations of principal and auxiliary subunits present in forebrain regions but spare targets in the cerebellum, was recently disclosed. This discovery raised the possibility that other auxiliary protein systems could be utilized to help identify new medicines...
January 9, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29296852/pregnancy-related-venous-thromboembolism-and-risk-of-occult-cancer
#11
Anette Tarp Hansen, Katalin Veres, Erzsébet Horváth-Puhó, Vera Ehrenstein, Paolo Prandoni, Henrik Toft Sørensen
The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected.An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29274279/rbm10-harmful-or-helpful-many-factors-to-consider
#12
Julie J Loiselle, Leslie C Sutherland
RBM10 is an RNA binding motif (RBM) protein expressed in most, if not all, human and animal cells. Interest in RBM10 is rapidly increasing and its clinical importance is highlighted by its identification as the causative agent of TARP syndrome, a developmental condition that significantly impacts affected children. RBM10's cellular functions are beginning to be explored, with initial studies demonstrating a tumor suppressor role. Very recently, however, contradictory results have emerged, suggesting a tumor promoter role for RBM10...
May 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29216460/getting-a-handle-on-neuropharmacology-by-targeting-receptor-associated-proteins
#13
REVIEW
Michael P Maher, Jose A Matta, Shenyan Gu, Mark Seierstad, David S Bredt
Targeted therapy for neuropsychiatric disorders requires selective modulation of dysfunctional neuronal pathways. Receptors relevant to CNS disorders typically have associated proteins discretely expressed in specific neuronal pathways; these accessory proteins provide a new dimension for drug discovery. Recent studies show that targeting a TARP auxiliary subunit of AMPA receptors selectively modulates neuronal excitability in specific forebrain pathways relevant to epilepsy. Other medicinally important ion channels, gated by glutamate, γ-aminobutyric acid (GABA), and acetylcholine, also have associated proteins, which may be druggable...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29202156/informed-consent-and-the-limited-english-patient-a-pilot-project-with-dental-hygiene-students-to-assess-student-knowledge-perceptions-and-attitudes
#14
Helen C Tarp, Tammy Sanderson, M Elizabeth Fore, Mary A Nies
Informed consent is the process by which a patient agrees to or rejects a proposed plan of treatment after a discussion with the provider about the benefits, risks, and alternative treatments available. In the United States, a signed informed consent form is required before any treatment plan may be implemented. However, there is no literature addressing how students in health professions understand informed consent in the context of encounters with limited English proficient (LEP) patients. The purpose of this interprofessional, interdisciplinary pilot project was to explore and assess Idaho State University's dental hygiene students' knowledge, perceptions, and attitudes associated with the process of informed consent when working with LEP patients in a dental hygiene setting...
2017: Journal of Allied Health
https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#15
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29123424/liver-related-morbidity-and-mortality-in-patients-with-chronic-hepatitis-c-and-cirrhosis-with-and-without-sustained-virologic-response
#16
Sofie Hallager, Steen Ladelund, Peer Brehm Christensen, Mette Kjær, Birgit Thorup Roege, Karin Elmegaard Grønbæk, Erika Belard, Toke S Barfod, Lone Galmstrup Madsen, Jan Gerstoft, Britta Tarp, Henrik Bygum Krarup, Nina Weis
Background: Chronic hepatitis C (CHC) causes liver cirrhosis in 5%-20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained virologic response (SVR). Furthermore we aimed to estimate the rate of hepatocellular carcinoma (HCC) and decompensation associated with certain prognostic factors. Materials and methods: Patients with CHC and cirrhosis registered in the Danish Database for Hepatitis B and C were eligible...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/29090671/targeted-blockade-of-tarp-g8-associated-ampa-receptors-anticonvulsant-activity-with-the-selective-antagonist-ly3130481-cerc-611
#17
Jeffrey M Witkin, Douglas A Schober, Scott D Gleason, John T Catlow, Warren J Porter, Jon Reel, X Jin, J Hobbs, Donald Gehlert, Douglas L Gernert, Kevin M Gardinier, Akihiko S Kato, X Ping, J L Smith
6-[(1S)-1-[1-[5-(2-hydroxyethoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one (LY3130481 or CERC-611) is a selective antagonist of AMPA receptors containing transmembrane AMPA receptor regulatory protein (TARP) g-8 that is under development for epilepsy. The present study provided a broad inquiry into its anticonvulsant properties. LY3130481 was anticonvulsant in multiple acute seizure provocation models in mice and rats. In addition, LY3130481 was effective against absence seizures in the GAERS genetic model and in the Frings mouse model...
November 1, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29073353/trial-characteristics-as-contextual-factors-when-evaluating-targeted-therapies-in-patients-with-psoriatic-disease-a-meta-epidemiological-study
#18
Christine Ballegaard, Tanja S Jørgensen, Marie Skougaard, Vibeke Strand, Philip J Mease, Lars E Kristensen, Lene Dreyer, Alice Gottlieb, Maarten de Wit, Robin Christensen, Simon Tarp
OBJECTIVES: To assess the importance of trial characteristics as contextual factors when evaluating treatment effect of targeted therapies for patients with psoriatic disease. METHODS: We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the two psoriatic conditions combined by using drug retention as common outcome, and separately by using ACR20 for PsA and PASI75 for psoriasis...
October 26, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/29028824/the-association-between-serum-brain-derived-neurotrophic-factor-and-a-cluster-of-cardiovascular-risk-factors-in-adolescents-the-champs-study-dk
#19
Natascha Holbæk Pedersen, Jakob Tarp, Lars Bo Andersen, Anne Kær Gejl, Tao Huang, Lone Peijs, Anna Bugge
BACKGROUND AND OBJECTIVE: Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain-derived neurotrophic factor (BDNF) probably due to diverse methodological approaches when analysing peripheral BDNF levels. Moreover, only a few studies have been performed in youth populations. Consequently, the main objective of this study was to examine the association between serum BDNF and a composite z-score consisting of six cardiovascular risk factors...
2017: PloS One
https://www.readbyqxmd.com/read/29020699/the-first-homemade-colonoscopy-trainer
#20
Dominik Andrzej Walczak, Maciej Grajek, Paulina Agnieszka Walczak, Magdalena Tuliszka-Gołowkin, Roman Massopust, Dariusz Pawełczak, Zbigniew Pasieka, Łukasz Krakowczyk, Adam Maciejewski
Introduction Colonoscopy trainers have gained recognition for improving endoscopy skills and preparing for real procedures on humans. Unfortunately, due to their high price, commercial simulators are hard to obtain, especially for small medical centers. However, a solution might be to construct a device for themselves. Aim Our goal was to build a relatively cheap and easy-to-construct simulator for residents who want to start learning colonoscopy. Materials and methods The box model colonoscopy trainer was designed and constructed...
October 2017: Zeitschrift Für Gastroenterologie
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