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Ankita Sharma, Monu, Sagarika Biswas
BACKGROUND: Transthyretin (TTR) is the transporter protein (55 kDA) that carries retinol binding protein and thyroxin (T4) in its functional tetramer form. Presence of mutation in this protein (TTR) may lead to the dissociation of tetramers to monomer which unfolds and self associates to form amyloid aggregates. Aggregation of this protein has been found to be associated with various life threatening disorders such as coronary artery disease (CAD) which is the major cause of mortality and morbidity worldwide...
March 20, 2018: Current Computer-aided Drug Design
Ni Zhang, Sheng Bi
Physical activity or exercise contributes to energy balance via affecting energy expenditure and food intake, but how exercise affects food intake and the neural mechanism of the feeding effect of exercise remain to be determined. Growing evidence indicates that physical exercise exerts a distinct action in the control of food intake and body weight. Studies of exercise in rodent models with voluntary access to running wheels reveal an inhibitory effect of voluntary exercise on food intake and body weight. Voluntary running activity decreases food intake and body weight, prevents obesity, and slows down body weight regain...
March 17, 2018: Physiology & Behavior
Yu Xia, Xianghua Wen, Bing Zhang, Yunfeng Yang
Understanding diversity and assembly patterns of microbial communities in activated sludge (AS) is pivotal for addressing fundamental ecological questions and wastewater treatment engineering. Recent applications of molecular methods especially next generation sequencing (NGS) have led to the explosion of information about AS community diversity, including the identification of uncultured taxa, and characterization of low-abundance but environmentally important populations such as antibiotic resistant bacteria and pathogens...
March 15, 2018: Biotechnology Advances
Hisao Otsuki, Junichi Yamaguchi, Kazuho Kamishima, Hiroyuki Arashi, Nobuhisa Hagiwara
Previous reports have focused on cardiovascular and bleeding events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, antithrombotic treatment strategies and clinical outcomes after second-generation drug-eluting stents (DES) implantation in AF patients remain to be determined. We enrolled 244 consecutive AF patients treated with second-generation DES. The study population was derived from multi-center AF registry (including 8 centers in Japan) from 2010 to 2012...
March 16, 2018: Heart and Vessels
Christoph Niemietz, Christoph Röcken, Matthias Schilling, Jörg Stypman, Constantin E Uhlig, Hartmut H-J Schmidt
Transthyretin-related Familial Amyloid Polyneuropathy (ATTR Amyloidosis, former FAP, here called TTR-FAP) is a rare, progressive autosomal dominant inherited amyloid disease ending fatal within 5 - 15 years after final diagnosis. TTR-FAP is caused by mutations of transthyretin (TTR), which forms amyloid fibrils affecting peripheral and autonomic nerves, the heart and other organs. Due to the phenotypic heterogeneity and partly not specific enough clinical symptoms, diagnosis of TTR-FAP can be complicated...
March 2018: Deutsche Medizinische Wochenschrift
Sylvie Perreault, Payman Shahabi, Robert Côté, Stéphanie Dumas, Étienne Rouleau-Mailloux, Yassamin Feroz Zada, Sylvie Provost, Ian Mongrain, Marc Dorais, Thao Huynh, Simon Kouz, Ariel Diaz, Mark Blostein, Simon de Denus, Jacques Turgeon, Jeffrey Ginsberg, Jacques Lelorier, Lyne Lalonde, Lambert Busque, Jeannine Kassis, Mario Talajic, Jean-Claude Tardif, Marie-Pierre Dubé
BACKGROUND: Over- and under-coagulation with warfarin is associated with hemorrhagic and thromboembolic events, respectively. Genetic and clinical factors affect warfarin response, and the causes of this variability remain unclear. We present descriptive statistics and test for predictors of poor anticoagulation control. METHODS: The Quebec Warfarin Cohort (QWC) comprises 1,059 new warfarin users, with prospective follow up using telephone questionnaires every 3 months for one year, and using healthcare administrative databases (RAMQ and Med-Echo) for 5-year prior to cohort entry and up to 10-years following active patient participation...
March 15, 2018: Clinical Cardiology
Miwa Isshiki, Satoshi Hirayama, Tsuyoshi Ueno, Masayuki Ito, Ayaka Furuta, Kouji Yano, Kotoko Yamatani, Masami Sugihara, Mayumi Idei, Takashi Miida
BACKGROUND: Rapid turnover proteins (RTPs), such as transthyretin (TTR), retinol binding protein (RBP), and transferrin (Tf), provide an accurate assessment of nutritional status but are susceptible to inflammation. Lipid-related markers, which have short half-lives in serum, may be better suited for nutritional assessment. We sought to identify sensitive nutritional markers unaffected by inflammation. METHODS: Fasting serum samples were collected from 30 malnourished inpatients and 25 healthy volunteers...
March 11, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Tatsuo Shimura, Masahiko Shibata, Yasuhide Kofunato, Ryo Okada, Teruhide Ishigame, Takashi Kimura, Akira Kenjo, Shigeru Marubashi
BACKGROUND: Although serum albumin has been reported to be useful as a prognostic biomarker for various malignancies, it is not suitable for prognosis of patients with hepatocellular carcinoma (HCC) due to impaired liver function. We aimed to determine whether serum transthyretin (TTR) level can be used as a novel prognostic biomarker. METHODS: Serum levels of TTR, as well as other nutritional and inflammatory parameters including angiogenic factors, were examined in 25 patients with HCC...
March 13, 2018: ANZ Journal of Surgery
Jasper H A van Miert, Sarah Bos, Nic J G M Veeger, Karina Meijer
BACKGROUND: Vitamin K antagonist (VKA) therapy is safer and more effective when patients have a high time within the therapeutic range and low international normalised ratio variability. The SAMe-TT2R2 score aims to identify those at risk for poor VKA control. OBJECTIVES: To evaluate the predictive value and clinical usefulness of the SAMe-TT2R2 score to identify those at risk for poor VKA control. METHODS: We performed a systematic review in MEDLINE and Embase for original research papers assessing the SAMe-TT2R2's relation to poor TTR...
2018: PloS One
Kok Haw Jonathan Lim, Lavinia Spain, Claire Barker, Alexandros Georgiou, Gerard Walls, Martin Gore, Samra Turajlic, Ruth Board, James M Larkin, Paul Lorigan
Background: Agreement on the utility of imaging follow-up in patients with high-risk melanoma is lacking. A UK consensus statement recommends a surveillance schedule of CT or positron-emission tomography-CT and MRI brain (every 6 months for 3 years, then annually in years 4 and 5) as well as clinical examination for high-risk resected Stages II and III cutaneous melanoma. Our aim was to assess patterns of relapse and whether imaging surveillance could be of clinical benefit. Patients and methods: A retrospective study of patients enrolled between July 2013 and June 2015 from three UK tertiary cancer centres followed-up according to this protocol was undertaken...
2018: ESMO Open
Wenke Cheng, Weijun Liu, Bin Li, Dongfang Li
BACKGROUND: Currently, it is considered that atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia, which is independent of stroke. However, the relationship between anticoagulant drugs and cognitive function in patients with atrial fibrillation is unknown. OBJECTIVES: This study aimed to complete a meta-analysis, and investigate the association between Anticoagulant therapy and cognitive impairment in patients undergoing AF. METHODS AND RESULTS: Two investigators systematically searched the Cochrane Library, PubMed, Embase databases and Web of Science for all studies showing associations...
March 2, 2018: Journal of Cardiovascular Pharmacology
João R Gomes, Inês Cabrito, Hugo R Soares, Susete Costelha, Anabela Teixeira, Angela Wittelsberger, Catelijne Stortelers, Peter Vanlandschoot, Maria J Saraiva
Transthyretin (TTR) is a transport protein of retinol and thyroxine in serum and cerebrospinal fluid (CSF), which is mainly secreted in liver and choroid plexus, and in smaller amounts in other cells throughout the body. The exact role of TTR and its specific expression in Central Nervous System (CNS) remains understudied. We investigated TTR expression and metabolism in CNS, through the intranasal and intracerebroventricular delivery of a specific anti-TTR Nanobody to the brain, unveiling Nanobody pharmacokinetics to the CNS...
March 12, 2018: Journal of Neurochemistry
Norman Junge, Qinggong Yuan, Thu Huong Vu, Simon Krooss, Christien Bednarski, Asha Balakrishnan, Toni Cathomen, Michael P Manns, Ulrich Baumann, Amar Deep Sharma, Michael Ott
AIM: To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout ( Fah -/-) mice by homologous-recombination-mediated targeted addition of the Fah gene. METHODS: C57BL/6 Fah∆exon5 mice served as an animal model for human tyrosinaemia type 1 in our study. The vector was created by amplifying human Fah cDNA including the TTR promoter from a lentivirus plasmid as described. The Fah expression cassette was flanked by homologous arms (620 bp and 749 bp long) of the Rosa26 gene locus...
February 27, 2018: World Journal of Hepatology
Li Yang, Qing-Hua Zou, Yan Zhang, Yin Shi, Chun-Rong Hu, Cai-Xia Hui, Xiao-Fei Liu, Yong-Fei Fang
Rheumatoid arthritis (RA) patients may suffer from comorbid neuropsychiatric symptoms including mild cognitive impairment (MCI). Although comorbidity of MCI is common, there are currently no validated plasma biomarkers to aid MCI diagnosis. This study screened plasma from patients with RA with and without comorbid MCI to identify potential biomarkers useful in the differential diagnosis of comorbid MCI. Plasma samples were collected from patients with RA without comorbid MCI, with comorbid MCI, and from healthy controls...
March 10, 2018: Clinical Rheumatology
Saeed Dabestani, Christian Beisland, Grant D Stewart, Karim Bensalah, Eirikur Gudmundsson, Thomas B Lam, William Gietzmann, Paimaun Zakikhani, Lorenzo Marconi, Sergio Fernandéz-Pello, Serenella Monagas, Samuel P Williams, Christian Torbrand, Thomas Powles, Erik Van Werkhoven, Richard Meijer, Alessandro Volpe, Michael Staehler, Börje Ljungberg, Axel Bex
BACKGROUND: Optimal follow-up (FU) strategy to detect potentially curable (PC) recurrences after treatment of localised clear cell renal cell carcinoma (ccRCC) is unclear. This study retrospectively analysed a large international database to determine recurrence patterns and overall survival (OS), as part of a wider project to issue recommendations on FU protocols. OBJECTIVE: To analyse associations between RCC recurrences in patients with ccRCC, their risk group stratifications, treatments, and subsequent outcomes...
March 7, 2018: European Urology Focus
Broes Martens, Michel De Pauw, Jan L De Bleecker
Familial amyloid polyneuropathy (FAP) is a most often length-dependent axonal neuropathy, often part of a multisystem disorder also affecting other organs, such as cardiac, gastrointestinal, genitourinary, renal, meningeal and eye tissue. It is most frequently the result of a mutation in the TTR gene, most commonly a p.Val50Met mutation. TTR-FAP is a rare autosomal dominant heritable disabling, heterogeneous disease in which early diagnosis is of pivotal importance when attempting treatment. This paper discusses the course of four Belgian FAP patients with different TTR mutations (p...
March 9, 2018: Acta Neurologica Belgica
Carolina Lavigne-Moreira, Vanessa Daccach Marques, Marcus V Magno Gonçalves, Mauricio Fernandes de Oliveira, Pedro J Tomaselli, José Nunez, Osvaldo J Moreira do Nascimento, Amilton Antunes Barreira, Wilson Marques
OBJECTIVE: To present the genetic heterogeneity of a sample of the Brazilian population with TTR mutations. METHODS: This cohort study was descriptive and retrospective, and enrolled patients with peripheral neuropathy of unknown cause that were found to have a mutation in the TTR gene during the process of etiological investigation, between July 1997 to January 2016. RESULTS: Over the study period, 129 point mutations were identified in 448 tested patients, of whom 128 were of Brazilian origin...
March 9, 2018: Journal of the Peripheral Nervous System: JPNS
Wengen Chen, Van-Khue Ton, Vasken Dilsizian
PURPOSE OF REVIEW: The two most common types of cardiac amyloidosis are caused by fibril deposits of immunoglobulin light chains (AL) and transthyretin (TTR), each with distinct prognosis and clinical management. Cardiac amyloidosis is under-recognized among heart failure patients with preserved ejection fraction (HFpEF). Bone-seeking tracers like99m Tc-PYP and99m Tc-DPD have long been used to identify cardiac amyloidosis, and more recently, to differentiate TTR from AL cardiac amyloidosis in symptomatic patients...
March 8, 2018: Current Cardiology Reports
Christopher R Ensor, Carlo J Iasella, Kate M Harrigan, Matthew R Morrell, Cody A Moore, Norihisa Shigemura, Adriana Zeevi, John F McDyer, Raman Venkataramanan
Calcineurin inhibitors (CNIs) are the backbone of traditional immunosuppressive regimens for lung transplant recipients (LTR). The CNIs are both narrow therapeutic index drugs with significant interpatient and intrapatient variability that require therapeutic drug monitoring to ensure safety and effectiveness. We hypothesized that tacrolimus time-in-therapeutic range (TTR) affects acute and chronic rejection rates in LTRs. This was a single-center, observational, cross-sectional study of 292 adult LTRs. Subjects who received tacrolimus post-transplant for the first year were included...
March 7, 2018: American Journal of Transplantation
Kayla M Pate, Brandon J Kim, Eric V Shusta, Regina M Murphy
β-amyloid (Aβ) aggregation is causally linked to neuronal pathology in Alzheimer's disease; therefore, several small molecules, antibodies, and peptides have been tested as anti-Aβ agents. We developed two compounds based on the Aβ-binding domain of transthyretin (TTR), a cyclic peptide cG8 and an engineered protein mTTR, and compared them for therapeutically relevant properties. Both mTTR and cG8 inhibit fibrillogenesis of Aβ, with mTTR inhibiting at a lower concentration than cG8. Both inhibit aggregation of amylin but not of α-synuclein...
March 7, 2018: ChemMedChem
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