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RANDOMIZED CONTROLLED TRIAL
Randy G Mungwira, Matthew B Laurens, Wongani Nyangulu, Titus H Divala, Nginache Nampota-Nkomba, Andrea G Buchwald, Osward M Nyirenda, Edson Mwinjiwa, Maxwell Kanjala, Lufina Tsirizani Galileya, Dominique E Earland, Matthew Adams, Christopher V Plowe, Terrie E Taylor, Jane Mallewa, Joep J van Oosterhout, Miriam K Laufer
OBJECTIVE: Many individuals living with the human immunodeficiency virus (HIV) infection and receiving antiretroviral therapy (ART) reside in areas at high risk for malaria but how malaria affects clinical outcomes is not well described in this population. We evaluated the burden of malaria infection and clinical malaria, and impact on HIV viral load and CD4 + cell count among adults on ART. DESIGN: We recruited Malawian adults on ART who had an undetectable viral load and ≥250 CD4 + cells/μl to participate in this randomized trial to continue daily trimethoprim-sulfamethoxazole (TS), discontinue daily co-trimoxazole, or switch to weekly chloroquine (CQ)...
October 1, 2022: AIDS
#42
JOURNAL ARTICLE
Aleksandra Gasecka, Michał Walczewski, Adam Witkowski, Maciej Dabrowski, Zenon Huczek, Radosław Wilimski, Andrzej Ochała, Radosław Parma, Piotr Scisło, Bartosz Rymuza, Karol Zbroński, Piotr Szwed, Marek Grygier, Anna Olasińska-Wiśniewska, Dariusz Jagielak, Radosław Targoński, Grzegorz Opolski, Janusz Kochman
Objectives: Patients with bicuspid aortic valve (BAV) stenosis were excluded from the pivotal trials of transcatheter aortic valve implantation (TAVI). We compared the in-hospital and long-term outcomes between patients undergoing TAVI for bicuspid and tricuspid aortic valve (TAV) stenosis. Methods: We performed a retrospective registry-based analysis on patients who underwent TAVI for BAV and TAV at five different centers between January 2009 and August 2017. The primary outcome was long-term all-cause mortality...
2022: Frontiers in Cardiovascular Medicine
#43
Muhammad Hamza Saad Shaukat, Julia Stys, Adam Stys, Tomasz Stys
Background: Tricuspid stenosis (native and prosthetic) is rare. Redo-sternotomy for isolated tricuspid replacement is associated with a higher risk. The efficacy and durability of transcatheter valve implantation for severe tricuspid stenosis are unclear. Case summary: Successful tricuspid valve-in-valve implantation (Edwards 26 mm Ultra) was performed to exteriorize a retained, unextractable pacemaker lead causing very early surgical bioprosthetic valve dysfunction in a 66-year-old Caucasian woman...
July 2022: European Heart Journal. Case Reports
#44
JOURNAL ARTICLE
Fuyang Li, Kathryn M Bondra, Samson Ghilu, Adam Studebaker, Qianqian Liu, Joel E Michalek, Mari Kogiso, Xiao-Nan Li, John A Kalapurakal, C David James, Sandeep Burma, Raushan T Kurmasheva, Peter J Houghton
PURPOSE: We investigated why three patient-derived xenograft (PDX) childhood BRAFV600E-mutant brain tumor models are highly sensitive to trametinib. Mechanisms of acquired resistance selected in situ, and approaches to prevent resistance were also examined, which may translate to both low-grade glioma (LGG) molecular subtypes. EXPERIMENTAL DESIGN: Sensitivity to trametinib [MEK inhibitor (MEKi)] alone or in combination with rapamycin (TORC1 inhibitor), was evaluated in pediatric PDX models...
September 1, 2022: Clinical Cancer Research
#45
JOURNAL ARTICLE
Adam Pietrobon, Julien Yockell-Lelièvre, Trevor A Flood, William L Stanford
Tuberous sclerosis complex (TSC) is a multisystem tumor-forming disorder caused by loss of TSC1 or TSC2. Renal manifestations predominately include cysts and angiomyolipomas. Despite a well-described monogenic etiology, the cellular pathogenesis remains elusive. We report a genetically engineered human renal organoid model that recapitulates pleiotropic features of TSC kidney disease in vitro and upon orthotopic xenotransplantation. Time course single-cell RNA sequencing demonstrates that loss of TSC1 or TSC2 affects multiple developmental processes in the renal epithelial, stromal, and glial compartments...
July 5, 2022: Cell Reports
#46
JOURNAL ARTICLE
Andrew D Grotzinger, Travis T Mallard, Wonuola A Akingbuwa, Hill F Ip, Mark J Adams, Cathryn M Lewis, Andrew M McIntosh, Jakob Grove, Søren Dalsgaard, Klaus-Peter Lesch, Nora Strom, Sandra M Meier, Manuel Mattheisen, Anders D Børglum, Ole Mors, Gerome Breen, Phil H Lee, Kenneth S Kendler, Jordan W Smoller, Elliot M Tucker-Drob, Michel G Nivard
We interrogate the joint genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis. We identify four broad factors (neurodevelopmental, compulsive, psychotic and internalizing) that underlie genetic correlations among the disorders and test whether these factors adequately explain their genetic correlations with biobehavioral traits. We introduce stratified genomic structural equation modeling, which we use to identify gene sets that disproportionately contribute to genetic risk sharing...
May 2022: Nature Genetics
#47
JOURNAL ARTICLE
Mirjam G Wild, Felix Kreidel, Michaela M Hell, Fabien Praz, Markus Mach, Matti Adam, David Reineke, Hendrik Ruge, Sebastian Ludwig, Lenard Conradi, Tanja K Rudolph, Sabine Bleiziffer, Jörg Kellermair, Andreas Zierer, Georg Nickenig, Marcel Weber, Anna Sonia Petronio, Cristina Giannini, Gry Dahle, Kjell A Rein, Augustin Coisne, André Vincentelli, Christophe Dubois, Alison Duncan, Cesare Quarto, Axel Unbehaun, Ignacio Amat-Santos, Javier Cobiella, Nicolas Dumonteil, Rodrigo Estevez-Loureiro, Andrea Fumero, Tobias Geisler, Philipp Lurz, Antonio Mangieri, Vanessa Monivas, Thilo Noack, Luis Nombela Franco, Miguel A Pinon, Lukas Stolz, Didier Tchétché, Thomas Walter, Bernhard Unsöld, Stephan Baldus, Martin Andreas, Jörg Hausleiter, Ralph S von Bardeleben
AIMS: Transcatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real-world data have not yet been reported. This study aimed to assess procedural and 30-day outcomes of TMVI in a real-world patient cohort. METHOD AND RESULTS: All consecutive patients undergoing implantation of a transapically delivered self-expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry...
January 22, 2022: European Journal of Heart Failure
#48
JOURNAL ARTICLE
Cynthia K Kahl, Rose Swansburg, Adam Kirton, Tamara Pringsheim, Gabrielle Wilcox, Ephrem Zewdie, Ashley Harris, Paul E Croarkin, Alberto Nettel-Aguirre, Sneha Chenji, Frank P MacMaster
INTRODUCTION: Tourette's syndrome (TS) affects approximately 1% of children. This study will determine the efficacy and safety of paired comprehensive behavioural intervention for tics (CBIT) plus repetitive transcranial magnetic stimulation (rTMS) treatment in children with Tourette's syndrome. We hypothesise that CBIT and active rTMS to the supplementary motor area (SMA) will (1) decrease tic severity, and (2) be associated with changes indicative of enhanced neuroplasticity (eg, changes in in vivo metabolite concentrations and TMS neurophysiology measures)...
December 24, 2021: BMJ Open
#49
JOURNAL ARTICLE
Nico Adelhöfer, Theresa Paulus, Moritz Mückschel, Tobias Bäumer, Annet Bluschke, Adam Takacs, Eszter Tóth-Fáber, Zsanett Tárnok, Veit Roessner, Anne Weissbach, Alexander Münchau, Christian Beste
Tourette syndrome is a common neurodevelopmental disorder defined by multiple motor and phonic tics. Tics in Tourette syndrome resemble spontaneously occurring movements in healthy controls and are therefore sometimes difficult to distinguish from these. Tics may in fact be mis-interpreted as a meaningful action, i.e. a signal with social content, whereas they lack such information and could be conceived a surplus of action or 'motor noise'. These and other considerations have led to a 'neural noise account' of Tourette syndrome suggesting that the processing of neural noise and adaptation of the signal-to-noise ratio during information processing is relevant for the understanding of Tourette syndrome...
2021: Brain communications
#50
JOURNAL ARTICLE
Jennifer Vermilion, Erika F Augustine, Heather R Adams, Amy Vierhile, Alyssa T Collins, Michael P McDermott, Thomas G O'Connor, Roger Kurlan, Edwin van Wijngaarden, Jonathan W Mink
BACKGROUND: Specific health-risk behaviors are present in older adolescents and young adults wtih Tourette syndrome (TS), but little is known about health-risk behaviors in youth with TS. METHODS: We compared responses on the Youth Risk Behavior Surveillance System (YRBS) in youth with TS with those in a concurrent community control group. The YRBS evaluates risk behaviors most closely associated with morbidity and mortality in young people. Tic severity, presence of comorbid attention-deficit/hyperactivity disorder (ADHD), measures of ADHD symptom severity, and whether or not the individual had been bullied in school were also compared between the groups...
January 2022: Pediatric Neurology
#51
Adam Borzęcki, Katarzyna Chyl-Surdacka, Monika Turska
Introduction: Tuberous sclerosis complex (TSC) is a rare, genetic disease which leads to neurological, cardiological, nephrological, ophthalmic, pulmonary and skin disorders. Case Presentation: Here, we describe a case of a 64-year-old man with the presence of giant angiofibromas located on his chin and nasolabial folds which caused inconvenience and unaesthetic appearance. All angiofibromas were removed with the use of a CO2 laser. The patient was extremely satisfied with the obtained result. No side effects were observed after a 6-month follow-up...
2021: Journal of Lasers in Medical Sciences
#52
JOURNAL ARTICLE
Natalia Szejko, Kamila Saramak, Adam Lombroso, Kirsten Müller-Vahl
INTRODUCTION: Gilles de la Tourette syndrome (GTS) is a childhood onset disorder characterised by the presence of motor and vocal tics. The guidelines of both the American Academy of Neurology (AAN) as well as the European Society for the Study of Tourette Syndrome (ESSTS) recommend behavioural therapy and pharmacotherapy, mainly with antipsychotics, as first line treatments for tics. In spite of these well-established therapeutic approaches, a significant number of patients are dissatisfied because of insufficient tic reduction or intolerable side effects...
October 28, 2021: Neurologia i Neurochirurgia Polska
#53
JOURNAL ARTICLE
Laurent M Willems, Susanne Schubert-Bast, Janina Grau, Christoph Hertzberg, Gerhard Kurlemann, Adelheid Wiemer-Kruel, Thomas Bast, Astrid Bertsche, Ulrich Bettendorf, Barbara Fiedler, Andreas Hahn, Hans Hartmann, Frauke Hornemann, Ilka Immisch, Julia Jacobs, Matthias Kieslich, Karl Martin Klein, Kerstin A Klotz, Gerhard Kluger, Markus Knuf, Thomas Mayer, Klaus Marquard, Sascha Meyer, Hiltrud Muhle, Karen Müller-Schlüter, Anna H Noda, Susanne Ruf, Matthias Sauter, Jan-Ulrich Schlump, Steffen Syrbe, Charlotte Thiels, Regina Trollmann, Bernd Wilken, Johann Philipp Zöllner, Felix Rosenow, Adam Strzelczyk
OBJECTIVE: This study aimed to measure health-related quality of life (HRQOL) in children and adolescents with tuberous sclerosis complex (TSC) and quality of life (QOL) and depressive symptoms among caregivers. METHODS: Adequate metrics were used to assess HRQOL in children and adolescents with TSC (4-18 years, KINDLR ) as well as QOL (EQ-5D) and symptoms of depression (BDI-II) among caregivers. Predictors for reduced HRQOL and depressive symptoms were identified by variance analysis, ordinal regression, and bivariate correlation...
October 7, 2021: European Journal of Paediatric Neurology: EJPN
#54
JOURNAL ARTICLE
Małgorzata Nieznańska, Karina Zatorska, Patrycjusz Stokłosa, Karolina Marzec, Małgorzata Misztal-Ogonowska, Ilona Kowalik, Maciej Dąbrowski, Zbigniew Chmielak, Adam Witkowski, Tomasz Hryniewiecki, Ilona Michałowska
INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an effective treatment of significant aortic stenosis. The occurrence of the paravalvular leak (PVL) is one of the most common complications of the procedure. OBJECTIVE: The aim of this study was to assess whether the aortic root morphology affects the occurrence of PVL after TAVI. PATIENTS AND METHODS: 50 patients with bicuspid and 50 patients with tricuspid aortic valve who underwent multislice computed tomography (MSCT) and transthoracic echocardiography (TTE) prior to TAVI were enrolled in the study...
September 27, 2021: Polish Archives of Internal Medicine
#55
JOURNAL ARTICLE
Joonho Yoon, Zhenan Liu, Eunyoung Lee, Liping Liu, Silvia Ferre, Johanne Pastor, Jianning Zhang, Orson W Moe, Audrey N Chang, R Tyler Miller
BACKGROUND: The kidney is the source of sKlotho and kidney-specific loss of Klotho leads to a phenotype resembling the premature multiorgan failure phenotype in Klotho-hypomorphic mice ( kl/kl mice). Klotho and the Ca-sensing receptor (CaSR) are highly expressed in the distal convoluted tubule (DCT). The physiologic mechanisms that regulate sKlotho levels are unknown. METHODS: We measured sKlotho in WT and tubule-specific CaSR -/- (TS-CaSR -/- ) mice treated with calcimimetics, alkali, or acid, and Klotho shed from minced mouse kidneys, and from HEK-293 cells expressing the CaSR and Klotho, in response to calcimimetics, calcilytics, alkalotic and acidic pH, and ADAM protease inhibitors...
December 1, 2021: Journal of the American Society of Nephrology: JASN
#56
JOURNAL ARTICLE
Eszter Tóth-Fáber, Zsanett Tárnok, Ádám Takács, Karolina Janacsek, Dezső Németh
Tourette syndrome is a childhood-onset neurodevelopmental disorder characterized by motor and vocal tics. On the neural level, tics are thought to be related to the disturbances of the cortico-basal ganglia-thalamo-cortical loops, which also play an important role in procedural learning. Several studies have investigated the acquisition of procedural information and the access to established procedural information in TS. Based on these, the notion of procedural hyperfunctioning, i.e., enhanced procedural learning, has been proposed...
2021: Frontiers in Human Neuroscience
#57
JOURNAL ARTICLE
Anna Antoniak, Iga Biskupek, Krzysztof K Bojarski, Cezary Czaplewski, Artur Giełdoń, Mateusz Kogut, Małgorzata M Kogut, Paweł Krupa, Agnieszka G Lipska, Adam Liwo, Emilia A Lubecka, Mateusz Marcisz, Martyna Maszota-Zieleniak, Sergey A Samsonov, Adam K Sieradzan, Magdalena J Ślusarz, Rafał Ślusarz, Patryk A Wesołowski, Karolina Ziȩba
The UNited RESidue (UNRES) force field was tested in the 14th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP14), in which larger oligomeric and multimeric targets were present compared to previous editions. Three prediction modes were tested (i) ab initio (the UNRES group), (ii) contact-assisted (the UNRES-contact group), and (iii) template-assisted (the UNRES-template group). For most of the targets, the contact restraints were derived from the server models top-ranked by the DeepQA method, while the DNCON2 method was used for 11 targets...
August 17, 2021: Journal of Molecular Graphics & Modelling
#58
REVIEW
Susanne Schubert-Bast, Adam Strzelczyk
Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by mutations in the TSC1 or TSC2 genes, which encode proteins that antagonise the mammalian isoform of the target of rapamycin complex 1 (mTORC1) - a key mediator of cell growth and metabolism. TSC is characterised by the development of benign tumours in multiple organs, together with neurological manifestations including epilepsy and TSC-associated neuropsychiatric disorders (TAND). Epilepsy occurs frequently and is associated with significant morbidity and mortality; however, the management is challenging due to the intractable nature of the seizures...
2021: Therapeutic Advances in Neurological Disorders
#59
JOURNAL ARTICLE
Dong Jiang, Yonggang Yao, Tangyuan Li, Gang Wan, Xavier Isidro Pereira-Hernández, Yubing Lu, Jinshu Tian, Konstantin Khivantsev, Mark H Engelhard, Chengjun Sun, Carlos E García-Vargas, Adam S Hoffman, Simon R Bare, Abhaya K Datye, Liangbing Hu, Yong Wang
Single-atom Pt 1 /CeO 2 catalyst by atom trapping (AT, 800 o C in air) shows excellent thermal stability, however, it is inactive for CO oxidation at low temperatures due to over-stabilization of Pt 2+ in a highly symmetric square-planar Pt 1 O 4 coordination. Reductive activation forming Pt nanoparticles (NPs) results in enhanced activity, however, NPs are easily oxidized leading to drastic activity loss. Here we show that tailoring the local environment of isolated Pt 2+ via thermal-shock (TS) synthesis leads to a highly active and thermally stable Pt 1 /CeO 2 catalyst...
August 3, 2021: Angewandte Chemie
#60
JOURNAL ARTICLE
Laurent M Willems, Felix Rosenow, Susanne Schubert-Bast, Gerhard Kurlemann, Johann Philipp Zöllner, Thomas Bast, Astrid Bertsche, Ulrich Bettendorf, Daniel Ebrahimi-Fakhari, Janina Grau, Andreas Hahn, Hans Hartmann, Christoph Hertzberg, Frauke Hornemann, Ilka Immisch, Julia Jacobs, Karl Martin Klein, Kerstin A Klotz, Gerhard Kluger, Susanne Knake, Markus Knuf, Klaus Marquard, Thomas Mayer, Sascha Meyer, Hiltrud Muhle, Karen Müller-Schlüter, Felix von Podewils, Susanne Ruf, Matthias Sauter, Hannah Schäfer, Jan-Ulrich Schlump, Steffen Syrbe, Charlotte Thiels, Regina Trollmann, Adelheid Wiemer-Kruel, Bernd Wilken, Bianca Zukunft, Adam Strzelczyk
BACKGROUND: The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder. OBJECTIVE: The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient's perspective...
October 2021: CNS Drugs
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