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https://www.readbyqxmd.com/read/28102470/neuronal-ryanodine-receptors-in-development-and-aging
#1
REVIEW
Nawaf Abu-Omar, Jogita Das, Vivian Szeto, Zhong-Ping Feng
Ryanodine receptors (RyRs) are intracellular calcium-release channels found on the endoplasmic reticulum of all cells. All three RyR isoforms, RyR1-3, are expressed in the brain, with RyR2 predominating. RyRs are localized within the soma, axons, dendritic spines, and presynaptic terminals of neurons. RyRs are highly expressed in the cerebellum, hippocampus, olfactory region, basal ganglia, and cerebral cortex. During the physiological processes of development and aging, the intracellular calcium homeostasis is largely regulated by RyRs...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28102082/characterization-of-the-molecular-mechanisms-underlying-the-chronic-phase-of-stroke-in-a-cynomolgus-monkey-model-of-induced-cerebral-ischemia
#2
Henry C H Law, Samuel S W Szeto, Quan Quan, Yun Zhao, Zaijun Zhang, Olga Krakovska, Leong Ting Lui, Chengyou Zheng, Simon Ming Yuen Lee, K W Michael Siu, Yuqiang Wang, Ivan K Chu
Stroke is one of the main causes of mortality and long-term disability worldwide. The pathophysiological mechanisms underlying this disease are not well understood, particularly in the chronic phase after the initial ischemic episode. In this study, a Macaca fascicularis stroke model consisting of two sample groups, as determined by MRI-quantified infarct volumes as a measure of the stroke severity 28 days after the ischemic episode, was evaluated using qualitative and quantitative proteomics analyses. By using multiple online multidimensional liquid chromatography platforms, 8790 non-redundant proteins that condensed to 5223 protein groups at 1% global false discovery rate (FDR)...
January 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28063595/the-mitochondrial-targeted-peptide-ss-31-improves-glomerular-architecture-in-mice-of-advanced-age
#3
Mariya T Sweetwyne, Jeffrey W Pippin, Diana G Eng, Kelly L Hudkins, Ying Ann Chiao, Matthew D Campbell, David J Marcinek, Charles E Alpers, Hazel H Szeto, Peter S Rabinovitch, Stuart J Shankland
Although age-associated changes in kidney glomerular architecture have been described in mice and man, the mechanisms are unknown. It is unclear if these changes can be prevented or even reversed by systemic therapies administered at advanced age. Using light microscopy and transmission electron microscopy, our results showed glomerulosclerosis with injury to mitochondria in glomerular epithelial cells in mice aged 26 months (equivalent to a 79-year-old human). To test the hypothesis that reducing mitochondrial damage in late age would result in lowered glomerulosclerosis, we administered the mitochondrial targeted peptide, SS-31, to aged mice...
January 4, 2017: Kidney International
https://www.readbyqxmd.com/read/28049625/regulation-of-the-macrophage-oxytocin-receptor-in-response-to-inflammation
#4
Angela Szeto, Ni Sun-Suslow, Armando J Mendez, Rosa I Hernandez, Klaus V Wagner, Philip M McCabe
It has been demonstrated that the neuropeptide oxytocin (OT) attenuates oxidative stress and inflammation in macrophages. In the current study, we examined the role of inflammation on the expression of the oxytocin receptor (OXTR). We hypothesized that OXTR expression is increased during the inflammation though a nuclear factor kappa B (NF-κB) mediated pathway, thus responding as an acute phase protein. Inflammation was induced by treating macrophages (human primary, THP-1, and murine) with lipopolysaccharide (LPS) and monitored by expression of IL-6...
January 3, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28035745/one-amino-acid-in-mouse-factor-viia-defines-its-endothelial-protein-c-receptor-binding-and-modulates-its%C3%A2-epcr-dependent-hemostatic-activity-in-vivo
#5
G Pavani, S M Zintner, L Ivanciu, J C Small, K A Stafford, J H Szeto, P Margaritis
BACKGROUND: Human activated Factor VII (hFVIIa), used in hemophilia treatment, binds to the endothelial Protein C (PC) receptor (EPCR) with unclear hemostatic consequences. Interestingly, mice lack the Factor VIIa (FVIIa)-EPCR interaction. Therefore, to investigate the hemostatic consequences of this interaction in hemophilia, we previously engineered a mouse FVIIa (mFVIIa) molecule that bound mouse EPCR (mEPCR) using 3 substitutions from mouse Protein C (mPC, Leu4→Phe, Leu8→Met and Trp9→Arg)...
December 30, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28017714/long-term-valve-performance-of-tavr-and-savr-a-report-from-the-partner-i-trial
#6
Melissa A Daubert, Neil J Weissman, Rebecca T Hahn, Philippe Pibarot, Rupa Parvataneni, Michael J Mack, Lars G Svensson, Deepika Gopal, Samir Kapadia, Robert J Siegel, Susheel K Kodali, Wilson Y Szeto, Raj Makkar, Martin B Leon, Pamela S Douglas
OBJECTIVES: The aim of this study was to evaluate the long-term performance of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) through longitudinal echocardiographic analysis. BACKGROUND: The long-term performance of the SAPIEN TAVR is not well-described. Therefore, we examined the hemodynamic and valvular profile of the SAPIEN TAVR over 5 years. METHODS: All patients receiving TAVR or SAVR with first post-implant (FPI) and 5-year echoes were analyzed for aortic valve (AV) peak velocity, AV mean gradient, AV area, peak left ventricular (LV) outflow tract and in-stent velocities, Doppler velocity index, aortic regurgitation (AR), LV mass index, stroke volume index, and cardiac index...
December 8, 2016: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/27970206/tct-80-characterizing-the-incidence-and-predictors-of-paravalvular-regurgitation-after-transcatheter-aortic-valve-replacement-tavr-and-its-impact-on-outcomes-a-study-of-the-society-of-thoracic-surgeons-american-college-of-cardiology-transcatheter-valve-therapies
#7
Saif Anwaruddin, Ajay Kirtane, Vinod Thourani, Sreekanth Vemulapalli, Pratik Manandhar, Howard Herrmann, Joseph Bavaria, Jay Giri, Prashanth Vallabhajosyula, Birgitte Krogsgaard Andersen, Wilson Szeto
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27970068/tct-691-sex-specific-differences-after-transcatheter-or-surgical-aortic-valve-replacement-in-intermediate-risk-patients-an-analysis-from-the-partner-2-randomized-trial
#8
Jonathan White, Darshan Doshi, Mathew Williams, Molly Szerlip, John Squiers, John Webb, Rebecca Hahn, Ajay Kirtane, Claire Litherland, David Cohen, E Murat Tuzcu, Wilson Szeto, Alan Zajarias, S Chris Malaisrie, Maria Alu, Craig Smith, Martin Leon, Michael Mack, Susheel Kodali
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27970048/tct-672-outcomes-in-the-commercial-use-of-self-expanding-prostheses-in-transcatheter-aortic-valve-replacement-a-comparison-of-the-medtronic-corevalve-and-evolut-r-platforms-in-the-society-of-thoracic-surgeons-american-college-of-cardiology-transcatheter-valve
#9
Paul Sorajja, Susheel Kodali, Michael Reardon, Wilson Szeto, Stanley Chetcuti, James Hermiller, David Adams, Jeffrey Popma
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27970038/tct-661-the-clinical-impact-of-diabetes-mellitus-on-outcomes-after-transcatheter-aortic-valve-replacement-insights-from-the-partner-ii-sapien-3-cohort
#10
Yigal Abramowitz, Brian Lindman, Tarun Chakravarty, Hasanian Jilaihawi, Samir Kapadia, Wilson Szeto, Philippe Pibarot, Vasilis Babaliaros, Howard Herrmann, Richard Smalling, Lars Svensson, Torsten Vahl, Vinod Thourani, Susheel Kodali, Craig Smith, Yiran Zhang, Maria Alu, Michael Mack, Martin Leon, Raj Makkar
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27969714/tct-36-frailty-in-intermediate-risk-patients-undergoing-transcatheter-or-surgical-aortic-valve-replacement-cut-points-and-relationship-with-outcomes-an-analysis-of-the-placement-of-aortic-transcatheter-valves-partner-2-cohort-a-randomized-trial
#11
Philip Green, Mark Russo, Suzanne Arnold, Darshan Doshi, Augusto Pichard, Wilson Szeto, Raj Makkar, Vasilis Babaliaros, William Fearon, Lars Svensson, John Webb, Tamim Nazif, Alan Zajarias, Nishath Quader, Rupa Parvataneni, Ajay Kirtane, David Cohen, Michael Mack, Martin Leon
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27969473/ps01-05-early-and-persistent-oligoclonal-t-cell-expansion-correlates-with-durable-response-to-anti-pd1-therapy-in-nsclc-topic-medical-oncology
#12
Sope Olugbile, Kazuma Kiyotani, Jae-Hyun Park, Philip Hoffman, Livia Szeto, Jyoti Patel, Everett Vokes, Yusuke Nakamura
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27926855/temporally-programmed-cd8%C3%AE-dc-activation-enhances-combination-cancer-immunotherapy
#13
Alice Tzeng, Monique J Kauke, Eric F Zhu, Kelly D Moynihan, Cary F Opel, Nicole J Yang, Naveen Mehta, Ryan L Kelly, Gregory L Szeto, Willem W Overwijk, Darrell J Irvine, K Dane Wittrup
Numerous synergistic cancer immunotherapy combinations have been identified, but the effects of relative dose timing are rarely considered. In established syngeneic mouse tumor models, we found that staggering interferon-α (IFNα) administration after, rather than before or simultaneously with, serum-persistent interleukin-2 (IL-2) and tumor-specific antibody significantly increased long-term survival. Successful combination therapy required IFNα-induced activation of cross-presenting CD8α(+) dendritic cells (DCs) following the release of antigenic tumor debris by the IL-2- and antibody-mediated immune response...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27920129/chronic-inhibition-of-renal-outer-medullary-potassium-channel-not-only-prevented-but-also-reversed-development-of-hypertension-and-end-organ-damage-in-dahl-salt-sensitive-rats
#14
Xiaoyan Zhou, Michael J Forrest, Wanda Sharif-Rodriguez, Gail Forrest, Daphne Szeto, Olga Urosevic-Price, Yonghua Zhu, Andra S Stevenson, Yuchen Zhou, Sloan Stribling, Maya Dajee, Shawn P Walsh, Alexander Pasternak, Kathleen A Sullivan
The renal outer medullary potassium (ROMK) channel mediates potassium recycling and facilitates sodium reabsorption through the Na(+)/K(+)/2Cl(-) cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Evidence from the phenotype of humans and rodents with functional ROMK deficiency supports the contention that selective ROMK inhibitors (ROMKi) will represent a novel diuretic with potential of therapeutic benefit for hypertension. ROMKi have recently been synthesized by Merck & Co, Inc...
December 5, 2016: Hypertension
https://www.readbyqxmd.com/read/27890121/prevalence-and-risk-factors-associated-with-musculoskeletal-complaints-among-users-of-mobile-handheld-devices-a-systematic-review
#15
REVIEW
Yanfei Xie, Grace Szeto, Jie Dai
This systematic review aimed at evaluating the prevalence and risk factors for musculoskeletal complaints associated with mobile handheld device use. Pubmed, Medline, Web of Science, CINAHL and Embase were searched. The methodological quality of included studies was assessed. Strength of evidence for risk factors was determined based on study designs, methodological quality and consistency of results. Five high-quality, eight acceptable-quality and two low-quality peer-reviewed articles were included. This review demonstrates that the prevalence of musculoskeletal complaints among mobile device users ranges from 1...
March 2017: Applied Ergonomics
https://www.readbyqxmd.com/read/27881606/mitochondria-protection-after-acute-ischemia-prevents-prolonged-upregulation-of-il-1%C3%AE-and-il-18-and-arrests-ckd
#16
Hazel H Szeto, Shaoyi Liu, Yi Soong, Surya V Seshan, Leona Cohen-Gould, Viacheslav Manichev, Leonard C Feldman, Torgny Gustafsson
The innate immune system has been implicated in both AKI and CKD. Damaged mitochondria release danger molecules, such as reactive oxygen species, DNA, and cardiolipin, which can cause NLRP3 inflammasome activation and upregulation of IL-18 and IL-1β It is not known if mitochondrial damage persists long after ischemia to sustain chronic inflammasome activation. We conducted a 9-month study in Sprague-Dawley rats after 45 minutes of bilateral renal ischemia. We detected glomerular and peritubular capillary rarefaction, macrophage infiltration, and fibrosis at 1 month...
November 23, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27870228/dialysate-bacterial-endotoxin-as-a-prognostic-indicator-of-peritoneal-dialysis-related-peritonitis
#17
Cheuk-Chun Szeto, Ka-Bik Lai, Kai-Ming Chow, Bonnie Ching-Ha Kwan, Man-Ching Law, Wing-Fai Pang, Terry King-Wing Ma, Chi-Bon Leung, Philip Kam-Tao Li
Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our present study is to explore the prognostic value of endotoxin level in PD effluent for the prediction of treatment failure in PD-related peritonitis. We studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected every 5 days for endotoxin level and leukocyte count. Patients were followed for relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary treatment failure; 41 (12.6%) developed relapsing, 19 (5...
December 2016: Nephrology
https://www.readbyqxmd.com/read/27867039/peritoneal-dialysis-effluent-mir-21-and-mir-589-levels-correlate-with-longitudinal-change-in-peritoneal-transport-characteristics
#18
Cheuk-Chun Szeto, Kai-Ming Chow, Bonnie Ching-Ha Kwan, Phyllis Mei-Shan Cheng, Cathy Choi-Wan Luk, Jack Kit-Chung Ng, Man-Ching Law, Chi-Bon Leung, Philip Kam-Tao Li
BACKGROUND: The role of microRNA (miRNA) in peritoneal fibrosis and longitudinal change in transport is uncertain. METHODS: We studied 80 new peritoneal dialysis (PD) patients. Peritoneal transport was determined by standard peritoneal equilibration test (PET) of creatinine at baseline. Based on published literature, PD effluent levels of 10 miRNA targets were quantified. PET and miRNA quantification were repeated one year later in 46 patients. RESULTS: Baseline PD effluent levels of all targets tested had modest but significant correlation with peritoneal transport parameters...
January 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27818807/successful-use-of-tocilizumab-in-a-patient-with-coexisting-rheumatoid-arthritis-and-ulcerative-colitis
#19
Matthew Chak Hin Szeto, Metin Devrim Yalçın, Abdul Khan, Andrzej Piotrowicz
Tocilizumab is an interleukin-6 receptor inhibitor licensed for moderate to severe rheumatoid arthritis (RA). We report a case of Tocilizumab monotherapy for severe active RA in a patient with coexisting ulcerative colitis (UC). The patient was intolerant to multiple disease-modifying drugs, so Tocilizumab monotherapy was commenced. We found clinical improvement in both RA and UC. There was no major adverse event after 2 years. Manufacturer advised caution in using Tocilizumab in patient with gastrointestinal ulceration due to an increased risk of bowel perforation...
2016: Case Reports in Immunology
https://www.readbyqxmd.com/read/27816631/imi-oral-biopharmaceutics-tools-project-evaluation-of-bottom-up-pbpk-prediction-success-part-2-an-introduction-to-the-simulation-exercise-and-overview-of-results
#20
Alison Margolskee, Adam S Darwich, Xavier Pepin, Leon Aarons, Aleksandra Galetin, Amin Rostami-Hodjegan, Sara Carlert, Maria Hammarberg, Constanze Hilgendorf, Pernilla Johansson, Eva Karlsson, Dónal Murphy, Christer Tannergren, Helena Thörn, Mohammed Yasin, Florent Mazuir, Olivier Nicolas, Sergej Ramusovic, Christine Xu, Shriram M Pathak, Timo Korjamo, Johanna Laru, Jussi Malkki, Sari Pappinen, Johanna Tuunainen, Jennifer Dressman, Simone Hansmann, Edmund Kostewicz, Handan He, Tycho Heimbach, Fan Wu, Carolin Hoft, Loic Laplanche, Yan Pang, Michael B Bolger, Eva Huehn, Viera Lukacova, James M Mullin, Ke X Szeto, Chester Costales, Jian Lin, Mark McAllister, Sweta Modi, Charles Rotter, Manthena Varma, Mei Wong, Amitava Mitra, Jan Bevernage, Jeike Biewenga, Achiel Van Peer, Richard Lloyd, Carole Shardlow, Peter Langguth, Irina Mishenzon, Mai Anh Nguyen, Jonathan Brown, Hans Lennernäs, Bertil Abrahamsson
Orally administered drugs are subject to a number of barriers impacting bioavailability (Foral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp®, and GastroPlus™) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters. Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise...
January 1, 2017: European Journal of Pharmaceutical Sciences
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