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https://www.readbyqxmd.com/read/28538136/genetic-and-pharmacologic-inactivation-of-angptl3-and-cardiovascular-disease
#1
Frederick E Dewey, Viktoria Gusarova, Richard L Dunbar, Colm O'Dushlaine, Claudia Schurmann, Omri Gottesman, Shane McCarthy, Cristopher V Van Hout, Shannon Bruse, Hayes M Dansky, Joseph B Leader, Michael F Murray, Marylyn D Ritchie, H Lester Kirchner, Lukas Habegger, Alex Lopez, John Penn, An Zhao, Weiping Shao, Neil Stahl, Andrew J Murphy, Sara Hamon, Aurelie Bouzelmat, Rick Zhang, Brad Shumel, Robert Pordy, Daniel Gipe, Gary A Herman, Wayne H H Sheu, I-Te Lee, Kae-Woei Liang, Xiuqing Guo, Jerome I Rotter, Yii-Der I Chen, William E Kraus, Svati H Shah, Scott Damrauer, Aeron Small, Daniel J Rader, Anders Berg Wulff, Børge G Nordestgaard, Anne Tybjærg-Hansen, Anita M van den Hoek, Hans M G Princen, David H Ledbetter, David J Carey, John D Overton, Jeffrey G Reid, William J Sasiela, Poulabi Banerjee, Alan R Shuldiner, Ingrid B Borecki, Tanya M Teslovich, George D Yancopoulos, Scott J Mellis, Jesper Gromada, Aris Baras
Background Loss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease. Methods We sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study. We performed tests of association for loss-of-function variants in ANGPTL3 with lipid levels and with coronary artery disease in 13,102 case patients and 40,430 controls from the DiscovEHR study, with follow-up studies involving 23,317 case patients and 107,166 controls from four population studies...
May 24, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28531214/suspected-lynch-syndrome-associated-msh6-variants-a-functional-assay-to-determine-their-pathogenicity
#2
Hellen Houlleberghs, Anne Goverde, Jarnick Lusseveld, Marleen Dekker, Marco J Bruno, Fred H Menko, Arjen R Mensenkamp, Manon C W Spaander, Anja Wagner, Robert M W Hofstra, Hein Te Riele
Lynch syndrome (LS) is a hereditary cancer predisposition caused by inactivating mutations in DNA mismatch repair (MMR) genes. Mutations in the MSH6 DNA MMR gene account for approximately 18% of LS cases. Many LS-associated sequence variants are nonsense and frameshift mutations that clearly abrogate MMR activity. However, missense mutations whose functional implications are unclear are also frequently seen in suspected-LS patients. To conclusively diagnose LS and enroll patients in appropriate surveillance programs to reduce morbidity as well as mortality, the functional consequences of these variants of uncertain clinical significance (VUS) must be defined...
May 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28530674/fifteen-new-risk-loci-for-coronary-artery-disease-highlight-arterial-wall-specific-mechanisms
#3
Joanna M M Howson, Wei Zhao, Daniel R Barnes, Weang-Kee Ho, Robin Young, Dirk S Paul, Lindsay L Waite, Daniel F Freitag, Eric B Fauman, Elias L Salfati, Benjamin B Sun, John D Eicher, Andrew D Johnson, Wayne H H Sheu, Sune F Nielsen, Wei-Yu Lin, Praveen Surendran, Anders Malarstig, Jemma B Wilk, Anne Tybjærg-Hansen, Katrine L Rasmussen, Pia R Kamstrup, Panos Deloukas, Jeanette Erdmann, Sekar Kathiresan, Nilesh J Samani, Heribert Schunkert, Hugh Watkins, Ron Do, Daniel J Rader, Julie A Johnson, Stanley L Hazen, Arshed A Quyyumi, John A Spertus, Carl J Pepine, Nora Franceschini, Anne Justice, Alex P Reiner, Steven Buyske, Lucia A Hindorff, Cara L Carty, Kari E North, Charles Kooperberg, Eric Boerwinkle, Kristin Young, Mariaelisa Graff, Ulrike Peters, Devin Absher, Chao A Hsiung, Wen-Jane Lee, Kent D Taylor, Ying-Hsiang Chen, I-Te Lee, Xiuqing Guo, Ren-Hua Chung, Yi-Jen Hung, Jerome I Rotter, Jyh-Ming J Juang, Thomas Quertermous, Tzung-Dau Wang, Asif Rasheed, Philippe Frossard, Dewan S Alam, Abdulla Al Shafi Majumder, Emanuele Di Angelantonio, Rajiv Chowdhury, Yii-Der Ida Chen, Børge G Nordestgaard, Themistocles L Assimes, John Danesh, Adam S Butterworth, Danish Saleheen
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls...
May 22, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28528013/congenital-h-type-tracheoesophageal-fistula-a-multicenter-review-of-outcomes-in-a-rare-disease
#4
Sara C Fallon, Jacob C Langer, Shawn D St Peter, KuoJen Tsao, Caroline M Kellagher, Dave R Lal, Jill S Whitehouse, Diana L Diesen, Michael D Rollins, Elizabeth Pontarelli, Marcus M Malek, Corey W Iqbal, Jeffrey S Upperman, Charles M Leys, Mark L Wulkan, Sarah J Hill, Martin L Blakely, Timothy D Kane, David E Wesson
OBJECTIVE: To perform a multicenter review of outcomes in patients with H-type tracheoesophageal fistula (TEF) in order to better understand the incidence and causes of post-operative complications. BACKGROUND: H-type TEF without esophageal atresia (EA) is a rare anomaly with a fundamentally different management algorithm than the more common types of EA/TEF. Outcomes after surgical treatment of H-type TEF are largely unknown, but many authoritative textbooks describe a high incidence of respiratory complications...
May 11, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28518003/caffeine-consumption-among-naval-aviation-candidates
#5
Thomas E Sather, Ronald D Williams, Donald R Delorey, Conrad L Woolsey
INTRODUCTION: Education frequently dictates students need to study for prolonged periods of time to adequately prepare for examinations. This is especially true with aviation preflight indoctrination (API) candidates who have to assimilate large volumes of information in a limited amount of time during API training. The purpose of this study was to assess caffeine consumption patterns (frequency, type, and volume) among naval aviation candidates attending API to determine the most frequently consumed caffeinated beverage and to examine if the consumption of a nonenergy drink caffeinated beverage was related to energy drink consumption...
April 1, 2017: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28511193/a-validation-study-of-the-fitbit-one-in-daily-life-using-different-time-intervals
#6
Anouk Middelweerd, Hidde P VAN DER Ploeg, Aart VAN Halteren, Jos W R Twisk, Johannes Brug, Saskia J Te Velde
PURPOSE: Accelerometer-based wearables can provide the user with real-time feedback through the device's interface and the mobile platforms. Few studies have focused on the minute-by-minute validity of wearables, which is essential for high-quality real-time feedback. This study aims to assess the validity of the Fitbit One compared with the ActiGraph GT3x + for assessing physical activity (i.e., steps, time spent in moderate, vigorous, and moderate-vigorous physical activity) in young adults using traditional time intervals (i...
June 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28507165/reliability-and-validity-of-an-agility-like-incremental-exercise-test-with-multidirectional-change-of-direction-movements-in-response-to-a-visual-stimulus
#7
Dennis-Peter Born, Philipp Kunz, Billy Sperlich
The aim of the study was to evaluate the reliability and validity of cardiorespiratory and metabolic variables, that is, peak oxygen uptake (V'O2peak) and heart rate (HRpeak), obtained from an agility-like incremental exercise test for team sport athletes. To investigate the test-retest reliability, 25 team sport athletes (age: 22 ± 3 years, body mass: 75 ± 7 kg, height: 182 ± 6 cm) performed an agility-like incremental exercise test on the SpeedCourt (SC) system incorporating multidirectional change-of-direction (COD) movements twice...
May 2017: Physiological Reports
https://www.readbyqxmd.com/read/28504677/%C3%AE-lactone-formation-during-product-release-from-a-nonribosomal-peptide-synthetase
#8
Jason E Schaffer, Margaret R Reck, Neha K Prasad, Timothy A Wencewicz
Nonribosomal peptide synthetases (NRPSs) are multidomain modular biosynthetic assembly lines that polymerize amino acids into a myriad of biologically active nonribosomal peptides (NRPs). NRPS thioesterase (TE) domains employ diverse release strategies for off-loading thioester-tethered polymeric peptides from termination modules typically via hydrolysis, aminolysis, or cyclization to provide mature antibiotics as carboxylic acids/esters, amides, and lactams/lactones, respectively. Here we report the enzyme-catalyzed formation of a highly strained β-lactone ring during TE-mediated cyclization of a β-hydroxythioester to release the antibiotic obafluorin (Obi) from an NRPS assembly line...
May 15, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28501538/biopsies-from-allograft-liver-contain-histologic-features-of-hepatitis-c-virus-infection-following-virus-eradication
#9
Emma Whitcomb, Won-Tak Choi, Keith R Jerome, Linda Cook, Charles Landis, Joseph Ahn, Helen S Te, Jamak Esfeh, Ibrahim A Hanouneh, Stephen C Rayhill, William Gibson, Thomas Plesec, Jamie Koo, Hanlin L Wang, John Hart, Rish K Pai, Maria Westerhoff
BACKGROUND & AIMS: Most patients, even those who have received liver transplants, achieve a sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection. Little is known about the histologic features of liver biopsies collected following SVR, particularly in patients who have received liver transplants. We aimed to better characterize the histologic features of allograft liver biopsies from patients who achieved a SVR to anti-HCV therapy following liver transplantation...
May 10, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28500333/novel-algorithms-for-improved-sensitivity-in-non-invasive-prenatal-testing
#10
L F Johansson, E N de Boer, H A de Weerd, F van Dijk, M G Elferink, G H Schuring-Blom, R F Suijkerbuijk, R J Sinke, G J Te Meerman, R H Sijmons, M A Swertz, B Sikkema-Raddatz
Non-invasive prenatal testing (NIPT) of cell-free DNA in maternal plasma, which is a mixture of maternal DNA and a low percentage of fetal DNA, can detect fetal aneuploidies using massively parallel sequencing. Because of the low percentage of fetal DNA, methods with high sensitivity and precision are required. However, sequencing variation lowers sensitivity and hampers detection of trisomy samples. Therefore, we have developed three algorithms to improve sensitivity and specificity: the chi-squared-based variation reduction (χ(2)VR), the regression-based Z-score (RBZ) and the Match QC score...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28498852/ultra-high-field-7tesla-magnetic-resonance-spectroscopy-in-amyotrophic-lateral-sclerosis
#11
Nazem Atassi, Maosheng Xu, Christina Triantafyllou, Boris Keil, Robert Lawson, Paul Cernasov, Elena Ratti, Christopher J Long, Sabrina Paganoni, Alyssa Murphy, Nouha Salibi, Ravi Seethamraju, Bruce Rosen, Eva-Maria Ratai
The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence...
2017: PloS One
https://www.readbyqxmd.com/read/28497464/in-vivo-proton-observed-carbon-edited-poce-13-c-magnetic-resonance-spectroscopy-of-the-rat-brain-using-a-volumetric-transmitter-and-receive-only-surface-coil-on-the-proton-channel
#12
Chathura Kumaragamage, Dan Madularu, Axel P Mathieu, Henk De Feyter, M Natasha Rajah, Jamie Near
PURPOSE: In vivo carbon-13 ((13) C) MR spectroscopy (MRS) is capable of measuring energy metabolism and neuroenergetics, noninvasively in the brain. Indirect ((1) H-[(13) C]) MRS provides sensitivity benefits compared with direct (13) C methods, and normally includes a (1) H surface coil for both localization and signal reception. The aim was to develop a coil platform with homogenous B1+ and use short conventional pulses for short echo time proton observed carbon edited (POCE) MRS. METHODS: A (1) H-[(13) C] MRS coil platform was designed with a volumetric resonator for (1) H transmit, and surface coils for (1) H reception and (13) C transmission...
May 12, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28484398/detection-of-glutamate-alterations-in-the-human-brain-using-1-h-mrs-comparison-of-steam-and-slaser-at-7-t
#13
Anouk Marsman, Vincent O Boer, Peter R Luijten, Hilleke E Hulshoff Pol, Dennis W J Klomp, René C W Mandl
PURPOSE: To assess reproducibility of glutamate measurement in the human brain by two short echo time (TE) (1)H-MRS sequences [stimulated echo acquisition mode (STEAM) and semi-localized by adiabatic selective refocusing (sLASER)] at 7 T. Reliable assessment of glutamate is important when studying a variety of neurological and neuropsychiatric disorders. At 7 T, the glutamate signal can be separated from the glutamine signal and hence more accurately measured as compared to lower field strengths...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28483579/comparison-of-2-d-shear-wave-elastography-and-transient-elastography-for-assessing-liver-fibrosis-in-chronic-hepatitis-b
#14
Jie Zeng, Jian Zheng, Zeping Huang, Shigao Chen, Jing Liu, Tao Wu, Rongqin Zheng, Mingde Lu
This study compared 2-D shear wave elastography (SWE) and transient elastography (TE) for liver fibrosis staging in patients with chronic hepatitis B (CHB) infection using liver biopsy as the reference standard. Patients with CHB infection who underwent liver biopsy were consecutively included. After exclusions, 257 patients were analyzed. Two-dimensional SWE resulted in a significantly higher rate of reliable measurements (98.1%, 252/257) than TE (93.0%, 239/257) (p = 0.011). Liver stiffness measurements of the two examinations exhibited a strong correlation (r = 0...
May 5, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28476688/ltr-retrotransposons-in-plants-engines-of-evolution
#15
REVIEW
Leonardo Galindo-González, Corinne Mhiri, Michael K Deyholos, Marie-Angèle Grandbastien
LTR retrotransposons are the most abundant group of transposable elements (TEs) in plants. Among them, Ty1-copia elements can fall close to genes, and therefore influence their expression and evolution. This review aims to examine how LTR retrotransposons, especially Ty1-copia elements, mediate gene evolution. Various stimuli, including polyploidization and biotic and abiotic elicitors, result in the transcription and movement of these retrotransposons, and can facilitate adaptation. The presence of cis-regulatory motifs in the LTRs are central to their stress-mediated responses and are shared with host stress-responsive genes, showing a complex evolutionary history in which TEs provide new regulatory units to genes...
May 2, 2017: Gene
https://www.readbyqxmd.com/read/28474657/tracheal-stenting-under-flexible-bronchoscopy-for-large-tracheoesophageal-malignant-lymphadenopathy
#16
Irfan Ismail Ayub, Kalaichelvi Kannan, R Dhenesh, Anand Thiagarajan
A 67-year-old man with poorly controlled chronic obstructive pulmonary disease presented with progressive dysphagia and was diagnosed with locally advanced carcinoma of the esophagus. Positron emission tomography-computed tomography staging showed mediastinal lymphadenopathy including a large lymph node in the tracheoesophageal groove with moderate tracheal compression. He was advised chemoradiotherapy but was reluctant to proceed with the same. He developed stridor 2 months later and repeat imaging showed increased size of the tracheoesophageal lymph node with critical airway narrowing...
May 2017: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/28459864/tyrosinase-inhibitory-activity-molecular-docking-studies-and-antioxidant-potential-of-chemotypes-of-lippia-origanoides-verbenaceae-essential-oils
#17
Alessandra P da Silva, Natália de F Silva, Eloísa Helena A Andrade, Tais Gratieri, William N Setzer, José Guilherme S Maia, Joyce Kelly R da Silva
The essential oils (EOs) of the aerial parts of Lippia origanoides (LiOr), collected in different localities of the Amazon region, were obtained by hydrodistillation and analyzed by GC and CG-MS. Principle component analysis (PCA) based on chemical composition grouped the oils in four chemotypes rich in mono- and sesquiterpenoids. Group I was characterized by 1,8-cineole and α-terpineol (LiOr-1 and LiOr-4) and group II by thymol (LiOr-2). The oil LiOr-3 showed β-caryophyllene, α-phellandrene and β-phellandrene as predominant and LiOr-5 was rich in (E)-nerolidol and β-caryophyllene...
2017: PloS One
https://www.readbyqxmd.com/read/28449006/a-meta-analysis-comparing-the-risk-of-metastases-in-patients-with-rectal-cancer-and-mri-detected-extramural-vascular-invasion-mremvi-vs-mremvi-negative-cases
#18
Muhammed R S Siddiqui, Constantinos Simillis, Chris Hunter, Manish Chand, Jemma Bhoday, Aurelie Garant, Te Vuong, Giovanni Artho, Shahnawaz Rasheed, Paris Tekkis, Al-Mutaz Abulafi, Gina Brown
BACKGROUND: Pathological extramural vascular invasion (EMVI) is an independent prognostic factor in rectal cancer, but can also be identified on MRI-detected extramural vascular invasion (mrEMVI). We perform a meta-analysis to determine the risk of metastatic disease at presentation and after surgery in mrEMVI-positive patients compared with negative tumours. METHODS: Electronic databases were searched from January 1980 to March 2016. Conventional meta-analytical techniques were used to provide a summative outcome...
April 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28448516/natural-variation-of-pirna-expression-affects-immunity-to-transposable-elements
#19
Sergei Ryazansky, Elizaveta Radion, Anastasia Mironova, Natalia Akulenko, Yuri Abramov, Valeriya Morgunova, Maria Y Kordyukova, Ivan Olovnikov, Alla Kalmykova
In the Drosophila germline, transposable elements (TEs) are silenced by PIWI-interacting RNA (piRNA) that originate from distinct genomic regions termed piRNA clusters and are processed by PIWI-subfamily Argonaute proteins. Here, we explore the variation in the ability to restrain an alien TE in different Drosophila strains. The I-element is a retrotransposon involved in the phenomenon of I-R hybrid dysgenesis in Drosophila melanogaster. Genomes of R strains do not contain active I-elements, but harbour remnants of ancestral I-related elements...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28440347/performance-of-2d-swe-ge-for-predicting-different-stages-of-liver-fibrosis-using-transient-elastography-as-the-reference-method
#20
Felix Bende, Ioan Sporea, Roxana Sirli, Alina Popescu, Ruxandra Mare, Bogdan Miutescu, Raluca Lupusoru, Tudor Moga, Corina Pienar
AIM: To evaluate the performance of 2D shear-wave elastography from General Electric (2D-SWE.GE) for the noninvasiveassessment of liver fibrosis and to identify liver stiffness (LS) cut-off values for predicting different stages of fibrosisusing Transient Elastography (TE) as the reference method. MATERIAL AND METHOD: We included 331 consecutive subjectswith or without chronic hepatopathies in whom LS was evaluated in the same session by means of 2 elastographic techniques:TE and 2D-SWE...
April 22, 2017: Medical Ultrasonography
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