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Florian Blachutzik, Niklas Boeder, Jens Wiebe, Alessio Mattesini, Oliver Dörr, Astrid Most, Timm Bauer, Jens Röther, Monique Tröbs, Christian Schlundt, Stephan Achenbach, Christian W Hamm, Holger M Nef
OBJECTIVES: The objective was to investigate the acute mechanical effects of post-dilatation on bioresorbable scaffolds (BRS) as determined by optical coherence tomography (OCT). BACKGROUND: Post-dilatation with high-pressure balloons is regarded as a key component of BRS implantation for treatment of coronary artery stenoses. However, the impact of post-dilatation on BRS in vivo has not been thoroughly investigated. METHODS: OCT was performed after the implantation procedure of 51 everolimus-eluting or novolimus-eluting polylactic acid-based BRS with (n = 27) or without non-compliant balloon post-dilatation (n = 24)...
October 18, 2016: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
T Hertz, M G Logan, M Rolland, C A Magaret, C Rademeyer, A Fiore-Gartland, P T Edlefsen, A DeCamp, H Ahmed, N Ngandu, B B Larsen, N Frahm, J Marais, R Thebus, D Geraghty, J Hural, L Corey, J Kublin, G Gray, M J McElrath, J I Mullins, P B Gilbert, C Williamson
INTRODUCTION: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. MATERIALS AND METHODS: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients...
October 15, 2016: Vaccine
Niklas F Boeder, Holger M Nef, Timm Bauer
A 64-year old woman was referred to the division of cardiology due to recurrent angina pectoris (CCS III). The patient's symptoms and high cardiovascular risk profile were an indication for coronary angiography. Relevant coronary heart disease was hereby ruled out; however, angiography showed a direct drainage of coronary vessels into the chambers. These Thebesian veins are of venoluminal nature in most cases and have a clinical implication in selected cases only.
September 30, 2016: Cardiovascular Revascularization Medicine: Including Molecular Interventions
Tim Vanbellingen, Beatrice Ottiger, Tobias Pflugshaupt, Jan Mehrholz, Stephan Bohlhalter, Tobias Nef, Thomas Nyffeler
BACKGROUND: Good responsive functional outcome measures are important to measure change in stroke patients. The aim of study was to compare the internal and external responsiveness, floor and ceiling effects of the motor, cognition, and communication subscales of the Lucerne ICF-based Multidisciplinary Observation Scale (LIMOS) with the motor and cognition subscales of the Functional Independence Measure (FIM), and the Barthel Index (BI), in a large cohort of stroke patients. METHODS: One hundred eighteen stroke patients participated in this study...
2016: Frontiers in Neurology
Mark W Kennedy, Enrico Fabris, Alexander J Ijsselmuiden, Holger Nef, Sebastian Reith, Javier Escaned, Fernando Alfonso, Niels van Royen, Wojtek Wojakowski, Adam Witkowski, Ciro Indolfi, Jan Paul Ottervanger, Harry Suryapranata, Elvin Kedhi
BACKGROUND: Fractional flow reserve (FFR) is a widely used tool for the identification of ischaemia-generating stenoses and to guide decisions on coronary revascularisation. However, the safety of FFR-based decisions in high-risk subsets, such as patients with Diabetes Mellitus (DM) or vulnerable stenoses presenting thin-cap fibro-atheroma (TCFA), is unknown. This study will examine the impact of optical coherence tomography (OCT) plaque morphological assessment and the identification of TCFA, in combination with FFR to better predict clinical outcomes in DM patients...
October 10, 2016: Cardiovascular Diabetology
Somayeh Kadkhodayan, Azam Bolhassani, Seyed Mehdi Sadat, Shiva Irani, Fatemeh Fotouhi
Cell penetrating peptides (CPPs) or protein transduction domains (PTDs) have been known as a new field in cargo delivery. These peptides such as Tat, Pep-1 and Cady-2 are able to deliver genes and biologically active proteins to cytoplasmic compartments via the plasma membrane. In current study, the efficiency of pEGFP-N1 eukaryotic vector for expression of HIV-1 Tat-Nef fusion was evaluated in HEK-293T cells using TurboFect transfection reagent. In addition, the recombinant GST-Tat-Nef protein was generated in E...
October 6, 2016: Current Drug Delivery
H M Nef, O Dörr, H Möllmann, A Elsässer
Bifurcation lesions are a therapeutic challenge in the interventional treatment of coronary artery disease. Thus, consideration of anatomical aspects and selection of the most appropriate strategy for an individual bifurcation have an impact on the interventional outcome. Accordingly, assessment of the type of bifurcation stenosis, including the relevance of the side branches, vessel diameter and the angle between the two branches are critical for the optimal choice of interventional strategy. The fractional flow reserve (FFR) is a parameter that provides a measure of the severity of coronary stenosis and despite some limitations, FFR can be applied to bifurcation lesions...
October 7, 2016: Herz
Shengxian Tu, Jelmer Westra, Junqing Yang, Clemens von Birgelen, Angela Ferrara, Mariano Pellicano, Holger Nef, Matteo Tebaldi, Yoshinobu Murasato, Alexandra Lansky, Emanuele Barbato, Liefke C van der Heijden, Johan H C Reiber, Niels R Holm, William Wijns
OBJECTIVES: The aim of this prospective multicenter study was to identify the optimal approach for simple and fast fractional flow reserve (FFR) computation from radiographic coronary angiography, called quantitative flow ratio (QFR). BACKGROUND: A novel, rapid computation of QFR pullbacks from 3-dimensional quantitative coronary angiography was developed recently. METHODS: QFR was derived from 3 flow models with: 1) fixed empiric hyperemic flow velocity (fixed-flow QFR [fQFR]); 2) modeled hyperemic flow velocity derived from angiography without drug-induced hyperemia (contrast-flow QFR [cQFR]); and 3) measured hyperemic flow velocity derived from angiography during adenosine-induced hyperemia (adenosine-flow QFR [aQFR])...
October 10, 2016: JACC. Cardiovascular Interventions
Amirhossein Manzourolajdad, Mileidy Gonzalez, John L Spouge
Because of a high mutation rate, HIV exists as a viral swarm of many sequence variants evolving under various selective pressures from the human immune system. Although the Nef gene codes for the most immunogenic of HIV accessory proteins, which alone makes it of great interest to HIV research, it also encodes an RNA structure, whose contribution to HIV virulence has been largely unexplored. Nef RNA helps HIV escape RNA interference (RNAi) through nucleotide changes and alternative folding. This study examines Historic and Modern Datasets of patient HIV-1 Nef sequences during the evolution of the North American epidemic for local changes in RNA plasticity...
2016: PloS One
Birthe Trautz, Virginia Pierini, Rebecka Wombacher, Bettina Stolp, Amanda J Chase, Massimo Pizzato, Oliver T Fackler
: SERINC 3 and 5 are recently identified host cell inhibitors of HIV-1 particle infectivity that are counteracted by the viral pathogenesis factor Nef. Here we confirm that HIV-1 Nef, but not HIV-1 Vpu, antagonizes the particle infectivity restriction of SERINC5. SERINC5 antagonism occurred in parallel to other Nef activities including cell surface receptor downregulation, trans-Golgi-network targeting of Lck and inhibition of host cell actin dynamics. Interaction motifs with host cell endocytic machinery, Nef-associated kinase complex as well as CD4 cytoplasmic tail/HIV-1 protease were identified as essential Nef determinants for SERINC5 antagonism...
September 28, 2016: Journal of Virology
Alberto C Guardo, Patrick Tjok Joe, L Miralles, M E Bargalló, B Mothe, A Krasniqi, C Heirman, F García, Kris Thielemans, Christian Brander, Joeri L Aerts, Montserrat Plana
BACKGROUND: The development of a prophylactic vaccine against HIV-1 has so far not been successful. Therefore, attention has shifted more and more towards the development of novel therapeutic vaccines. Here, we evaluated a new mRNA based therapeutic vaccine against HIV-1 encoding activation signals (TriMix: CD40L+CD70+caTLRA4) combined with rationally selected antigenic sequences (HTI sequence: comprised of 16 joined fragments from Gag, Pol, Vif and Nef). METHODS: For this purpose, PBMC from HIV-1-infected individuals on cART, lymph node explants from non-infected humans and splenocytes from immunized mice were collected and several immune functions were measured...
September 24, 2016: AIDS
Giesje Nefs, François Pouwer, Richard I G Holt, Søren Skovlund, Norbert Hermanns, Antonio Nicolucci, Mark Peyrot
OBJECTIVE: We examined (a) the demographic and clinical correlates of worries about hypoglycemia in adult family members of adults with diabetes, and (b) the association of these worries with measures of diabetes support. METHODS: The second multinational Diabetes Attitudes, Wishes and Needs (DAWN2) study cross-sectionally surveyed 2057 family members from 17 countries. Participants completed questions about demographics, diabetes, and psychosocial functioning, including worry about overall and nocturnal hypoglycemia...
October 2016: Journal of Psychosomatic Research
Tim Vanbellingen, Thomas Nyffeler, Tobias Nef, Gert Kwakkel, Stephan Bohlhalter, Erwin E H van Wegen
BACKGROUND: Patients with Parkinson's disease exhibit disturbed dexterity. Validated self-reported outcomes for dexterity in Parkinson's disease are lacking. The aim of this study was to investigate the reliability, content and construct validity of a new Dexterity Questionnaire 24. METHODS: One hundred and three patients with Parkinson's disease completed the Dexterity Questionnaire 24 (score range 24-96), at baseline and four weeks later. The internal consistency was determined...
September 15, 2016: Parkinsonism & related Disorders
Tatiana Pushkarsky, Evgeny Shilov, Natalya Kruglova, Ronald Naumann, Beda Brichacek, Lucas Jennelle, Dmitri Sviridov, Andrey Kruglov, Sergei Nedospasov, Michael I Bukrinsky
HIV-infected individuals are at high risk of developing atherosclerosis and cardiovascular disease, in part due to HIV-induced impairment of cholesterol metabolism. In vitro studies demonstrated that HIV-1 protein Nef inhibits activity of ABCA1, the main cellular cholesterol transporter, leading to cholesterol accumulation in macrophages and conversion of these cells into foam cells, characteristic for atherosclerosis. However, the mechanisms of Nef-mediated effects on cholesterol metabolism in vivo are not well characterized...
September 21, 2016: AIDS Research and Human Retroviruses
Xugang Qiao, Bing He, April Chiu, Daniel M Knowles, Amy Chadburn, Andrea Cerutti
No abstract text is available yet for this article.
September 20, 2016: Nature Immunology
Anke Heigele, Dorota Kmiec, Kerstin Regensburger, Simon Langer, Lukas Peiffer, Christina M Stürzel, Daniel Sauter, Martine Peeters, Massimo Pizzato, Gerald H Learn, Beatrice H Hahn, Frank Kirchhoff
The cellular factor serine incorporator 5 (SERINC5) impairs HIV-1 infectivity but is antagonized by the viral Nef protein. We analyzed the anti-SERINC5 activity of Nef proteins across primate lentiviruses and examined whether SERINC5 represents a barrier to cross-species transmissions and/or within-species viral spread. HIV-1, HIV-2, and SIV Nefs counteract human, ape, monkey, and murine SERINC5 orthologs with similar potency. However, HIV-1 Nefs are more active against SERINC5 than HIV-2 Nefs, and chimpanzee SIV (SIVcpz) Nefs are more potent than those of their monkey precursors...
September 14, 2016: Cell Host & Microbe
Sophie Melikishvili, Alexandra Poturnayova, Maksim Ionov, Maria Bryszewska, Tomáš Vary, Julius Cirak, María Ángeles Muñoz-Fernández, Rafael Gomez-Ramirez, Francisco Javier de la Mata, Tibor Hianik
In this study, dendrimers have been purposed as an alternative approach for delivery of HIV peptides to dendritic cells. We have investigated the interaction of dendriplexes formed from polyanionic HIV peptide Nef and cationic carbosilane dendrimer (CBD) with model lipid membranes - large unilamellar vesicles (LUVs), Langmuir monolayers and supported lipid membranes (sBLMs) containing various molar ratio of zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG2000)...
September 9, 2016: Biochimica et Biophysica Acta
Tim Vanbellingen, Manuela Wapp, Katharina Stegmayer, Manuel Bertschi, Eugenio Abela, Stefanie Kübel, Thomas Nyffeler, René Müri, Sebastian Walther, Tobias Nef, Mark Hallett, Stephan Bohlhalter
Dorsal pre-motor cortex (PMd) is thought to play a role in fine motor control. The aim of the present study was to investigate whether inhibitory or excitatory stimulation of PMd would have an impact on manual dexterity in Parkinson's disease (PD). Fifteen patients with PD participated in this study. High resolution structural MRI was used for neuro-navigated TBS. Participants were targeted with one train of TBS in three experimental sessions: sham stimulation over vertex, continuous TBS (cTBS) over PMd and intermittent TBS (iTBS) over PMd, respectively...
September 12, 2016: Journal of Neural Transmission
Sebastian Ewen, Christian Ukena, Thomas Felix Lüscher, Martin Bergmann, Peter J Blankestijn, Erwin Blessing, Bodo Cremers, Oliver Dörr, Dagmara Hering, Lukas Kaiser, Holger Nef, Elias Noory, Markus Schlaich, Faisal Sharif, Isabella Sudano, Britta Vogel, Michiel Voskuil, Thomas Zeller, Abraham R Tzafriri, Elazer R Edelman, Lucas Lauder, Bruno Scheller, Michael Böhm, Felix Mahfoud
BACKGROUND/PURPOSE: Catheter-based renal sympathetic denervation (RDN) can reduce blood pressure (BP) and sympathetic activity in certain patients with uncontrolled hypertension. Less is known about the impact of renal anatomy and procedural parameters on subsequent BP response. METHODS/MATERIALS: A total of 564 patients with resistant hypertension underwent bilateral RDN in 9 centers in Europe and Australia using a mono-electrode radiofrequency catheter (Symplicity Flex, Medtronic)...
October 2016: Cardiovascular Revascularization Medicine: Including Molecular Interventions
Christoph Lipps, Jenine H Nguyen, Lukas Pyttel, Thomas L Lynch, Christoph Liebetrau, Ganna Aleshcheva, Sandra Voss, Oliver Dörr, Holger M Nef, Helge Möllmann, Christian W Hamm, Sakthivel Sadayappan, Christian Troidl
Myocardial infarction (MI) leads to loss and degradation of contractile cardiac tissue followed by sterile inflammation of the myocardium through activation and recruitment of innate and adaptive cells of the immune system. Recently, it was shown that cardiac myosin binding protein-C (cMyBP-C), a protein of the cardiac sarcomere, is degraded following MI, releasing a predominant N-terminal 40-kDa fragment (C0C1f) into myocardial tissue and the systemic circulation. We hypothesized that early release of C0C1f contributes to the initiation of inflammation and plays a key role in recruitment and activation of immune cells...
September 8, 2016: Journal of Molecular and Cellular Cardiology
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