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https://www.readbyqxmd.com/read/28437792/phase-plate-cryo-em-structure-of-a-class-b-gpcr-g-protein-complex
#1
Yi-Lynn Liang, Maryam Khoshouei, Mazdak Radjainia, Yan Zhang, Alisa Glukhova, Jeffrey Tarrasch, David M Thal, Sebastian G B Furness, George Christopoulos, Thomas Coudrat, Radostin Danev, Wolfgang Baumeister, Laurence J Miller, Arthur Christopoulos, Brian K Kobilka, Denise Wootten, Georgios Skiniotis, Patrick M Sexton
Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B receptor, the calcitonin receptor, in complex with peptide ligand and heterotrimeric Gαsβγ protein determined by Volta phase-plate single-particle cryo-electron microscopy. The peptide agonist engages the receptor by binding to an extended hydrophobic pocket facilitated by the large outward movement of the extracellular ends of transmembrane helices 6 and 7...
April 24, 2017: Nature
https://www.readbyqxmd.com/read/28437065/a-macrocyclic-peptide-ligand-binds-the-oncogenic-microrna-21-precursor-and-suppresses-dicer-processing
#2
Matthew D Shortridge, Matthew J Walker, Tom Pavelitz, Yu Chen, Gabriele Varani
MicroRNAs (miRNAs) help orchestrate cellular growth and survival through post-transcriptional mechanisms. The dysregulation of miRNA biogenesis can lead to cellular growth defects, chemotherapeutic resistance and plays a direct role in the development of many chronic diseases. Among these RNAs, miR-21 is consistently overexpressed in most human cancers leading to the down regulation of key tumor suppressing and pro-apoptotic factors; suggesting that inhibition of miR-21 biogenesis could reverse these negative effects...
April 24, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28437021/optimal-outcome-achievement-in-partial-nephrectomy-for-t1-renal-masses-a-contemporary-analysis-of-open-and-robotic-cases
#3
Matthew J Maurice, Daniel Ramirez, Önder Kara, Ercan Malkoç, Ryan J Nelson, Khaled Fareed, Robert J Stein, Amr F Fergany, Jihad H Kaouk
OBJECTIVES: To compare optimal outcome achievement between open and robotic partial nephrectomy. PATIENTS AND METHODS: Using our institutional partial nephrectomy database, we reviewed 605 cases performed for unifocal clinical T1 renal masses in non-solitary kidneys from 2011-2015. Tetrafecta, which was defined as negative surgical margins, freedom from perioperative complications, ≥80% renal functional preservation, and no chronic kidney disease upstaging, was chosen as the composite optimal outcome...
April 24, 2017: BJU International
https://www.readbyqxmd.com/read/28436316/first-in-man-experience-of-self-expanding-nitinol-stents-combined-with-drug-coated-balloon-in-the-treatment-of-femoropopliteal-occlusive-disease
#4
Bibombe Patrice Mwipatayi, Kalpa Perera, Ali Daneshmand, Rhys Daniel, Jackie Wong, Shannon D Thomas, Sally A Burrows
Purpose The present study aimed to determine the safety and efficacy of a drug-coated balloon inflated within a thin-strut self-expanding bare-metal stent in patients with severe and complex femoropopliteal occlusive disease. Methods This prospective study used the Pulsar-self-expanding stent and Passeo-18 Lux drug-coated balloon in patients with severe and complex femoropopliteal occlusive disease. The primary endpoint was the 12-month primary patency, and the secondary endpoints included 24-month primary patency, assisted primary patency, secondary patency, and clinically associated target lesion revascularisation...
January 1, 2017: Vascular
https://www.readbyqxmd.com/read/28435157/the-systemic-nature-of-ckd
#5
REVIEW
Carmine Zoccali, Raymond Vanholder, Ziad A Massy, Alberto Ortiz, Pantelis Sarafidis, Friedo W Dekker, Danilo Fliser, Denis Fouque, Gunnar H Heine, Kitty J Jager, Mehmet Kanbay, Francesca Mallamaci, Gianfranco Parati, Patrick Rossignol, Andrzej Wiecek, Gerard London
The accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney...
April 24, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28434671/resveratrol-improves-mitochondrial-function-in-the-remnant-kidney-from-5-6-nephrectomized-rats
#6
Yan Hui, Miaomiao Lu, Yarong Han, Hongli Zhou, Wei Liu, Lijing Li, Ruixia Jin
Mitochondrial dysfunction is involved in the pathogenesis of chronic kidney disease (CKD). Resveratrol has been demonstrated to be beneficial for the recovery of kidney diseases. In this study, the 5/6 nephrectomized rat was used as a CKD model and the TGF-β1-exposed mouse mesangial cells were used as an in vitro model. Pathological examination showed that resveratrol treatment attenuated glomerular injury in the remnant kidney of 5/6 nephrectomized rat. Additionally, resveratrol improved mitochondrial function in vivo and in vitro, as evidenced by increasing mitochondrial membrane potential, increasing ATP, decreasing reactive oxygen species production and enhancing activities of complex I and III...
April 20, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28434551/neuromuscular-fatigue-during-exercise-methodological-considerations-etiology-and-potential-role-in-chronic-fatigue
#7
REVIEW
Rosie Twomey, Saied Jalal Aboodarda, Renata Kruger, Susan Nicole Culos-Reed, John Temesi, Guillaume Y Millet
The term fatigue is used to describe a distressing and persistent symptom of physical and/or mental tiredness in certain clinical populations, with distinct but ultimately complex, multifactorial and heterogenous pathophysiology. Chronic fatigue impacts on quality of life, reduces the capacity to perform activities of daily living, and is typically measured using subjective self-report tools. Fatigue also refers to an acute reduction in the ability to produce maximal force or power due to exercise. The classical measurement of exercise-induced fatigue involves neuromuscular assessments before and after a fatiguing task...
April 20, 2017: Neurophysiologie Clinique, Clinical Neurophysiology
https://www.readbyqxmd.com/read/28434143/the-mtor-signaling-pathway-in-myocardial-dysfunction-in-type-2-diabetes-mellitus
#8
REVIEW
Tomohiro Suhara, Yuichi Baba, Briana K Shimada, Jason K Higa, Takashi Matsui
PURPOSE OF REVIEW: T2DM (type 2 diabetes mellitus) is a risk factor for heart failure. The mTOR (mechanistic target of rapamycin) is a key mediator of the insulin signaling pathway. We will discuss the role of mTOR in myocardial dysfunction in T2DM. RECENT FINDINGS: In T2DM, chronically activated mTOR induces multiple pathological events, including a negative feedback loop that suppresses IRS (insulin receptor substrate)-1. While short-term treatment with rapamycin, an mTOR inhibitor, is a promising strategy for cardiac diseases such as acute myocardial infarction and cardiac hypertrophy in T2DM, there are many concerns about chronic usage of rapamycin...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28434089/pregnancy-and-kidney-disease-from-medicine-based-on-exceptions-to-exceptional-medicine
#9
EDITORIAL
Giorgina Barbara Piccoli, Gianfranca Cabiddu
The Webster dictionary defines exception as an anomaly, a person or thing that does not follow a rule, while the adjective exceptional has a different nuance, and means "above average". These two words may describe how obstetric nephrology has shifted from the description of very rare cases, to the development of a complex new and fascinating branch of medicine, that counterbalances obstetricians' usually optimistic outlook by focusing on subtle challenges posed by chronic diseases, and mitigate the frequently grim approach of nephrologists, with a message of hope: women with kidney disease can have the same basic life goals as healthy women their age...
April 22, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28433492/is-tavr-ready-for-the-global-aging-population
#10
REVIEW
Travis Bergmann, Partho P Sengupta, Jagat Narula
The emergence of the global pandemic of chronic diseases necessitates critical assessment of interventions that can be targeted at both the individual and population levels. Among cardiovascular diseases, the increasing prevalence of valvular heart diseases such as aortic stenosis parallels the rising burden of atherosclerotic cardiovascular diseases. As an alternative to surgical aortic valve replacement, technological innovation has allowed development of minimally invasive transcatheter aortic valve replacement (TAVR)...
April 19, 2017: Global Heart
https://www.readbyqxmd.com/read/28433350/open-repair-of-chronic-thoracic-and-thoracoabdominal-aortic-dissection-using-deep-hypothermia-and-circulatory-arrest
#11
Joel Corvera, Hannah Copeland, David Blitzer, Adam Hicks, Joshua Manghelli, Philip Hess, John Fehrenbacher
BACKGROUND: Chronic dissection of the thoracic and thoracoabdominal aorta as sequela of a prior type A or B dissection is a challenging problem that requires close radiographic surveillance and prompt operative intervention in the presence of symptoms or aneurysm formation. Open repair of chronic thoracic and thoracoabdominal aortic dissection using deep hypothermia has been our preferred method to treat this complex pathology. The advantages of this technique include organ and spinal cord protection, the flexibility to extend the repair proximally into the arch, and the ability to limit ischemia to all vascular beds...
March 18, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28432005/radial-ulnar-angioplasty-in-selected-patients-undergoing-elective-angiography-or-pci-using-complex-forearm-approach
#12
Santiago Jesús Camacho Freire, Antonio Enrique Gómez Menchero, Javier León Jiménez, Jessica Roa Garrido, Rosa Cardenal Piris, José Francisco Díaz Fernández
BACKGROUND: Angioplasty on the radial artery have been performed with good success rates in patients with critical hand ischemia. We sought to assess the feasibility and safety of radial angioplasty on complex radial access in patients undergoing coronary angiography. METHODS/MATERIAL: A prospective series of procedures with complex radial/ulnar access to which radial-ulnar angioplasty (RU-A) was performed. We set goals of efficacy and safety that included the success rate of the procedure (need for ¨Crossover femoral¨) and the existence of radial pulse at one month...
April 11, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28431796/lessons-learned-from-twins-in-autoimmune-and-chronic-inflammatory-diseases
#13
REVIEW
Elena Generali, Angela Ceribelli, Maria Antonietta Stazi, Carlo Selmi
Autoimmunity and chronic inflammation recognize numerous shared factors and, as a result, the resulting diseases frequently coexist in the same patients or respond to the same treatments. Among the convenient truths of autoimmune and chronic inflammatory diseases, there is now agreement that these are complex conditions in which the individual genetic predisposition provides a rate of heritability. The concordance rates in monozygotic and dizygotic twins allows to estimate the weight of the environment in determining disease susceptibility, despite recent data supporting that only a minority of immune markers depend on hereditary factors...
April 18, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28431138/cardiovascular-outcome-trials-in-patients-with-chronic-kidney-disease-challenges-associated-with-selection-of-patients-and-endpoints
#14
Patrick Rossignol, Rajiv Agarwal, Bernard Canaud, Alan Charney, Gilles Chatellier, Jonathan C Craig, William C Cushman, Ronald T Gansevoort, Bengt Fellström, Dahlia Garza, Nicolas Guzman, Frank A Holtkamp, Gerard M London, Ziad A Massy, Alexandre Mebazaa, Peter G M Mol, Marc A Pfeffer, Yves Rosenberg, Luis M Ruilope, Jonathan Seltzer, Amil M Shah, Salim Shah, Bhupinder Singh, Bergur V Stefánsson, Norman Stockbridge, Wendy Gattis Stough, Kristian Thygesen, Michael Walsh, Christoph Wanner, David G Warnock, Christopher S Wilcox, Janet Wittes, Bertram Pitt, Aliza Thompson, Faiez Zannad
Although cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28429555/management-of-mineral-and-bone-disorders-in-renal-transplant-recipients
#15
Matthew J Damasiewicz, Peter R Ebeling
The management of post-transplantation bone disease is a complex problem that remains under-appreciated in clinical practice. In these patients, pre-existing metabolic bone disorder is further impacted by the use of immunosuppressive medications (glucocorticoids and calcineurin-inhibitors), variable post-transplantation renal allograft function and post-transplantation diabetes mellitus. The treatment of post-transplantation bone loss should begin pre-transplantation. All patients active on transplant waiting lists should be screened for bone disease...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28429549/is-there-a-practical-role-for-a-virtual-bone-biopsy-using-high-resolution-imaging-of-bone-in-patients-with-chronic-kidney-disease
#16
Ashish K Sharma, Nigel D Toussaint
Renal osteodystrophy (ROD) refers to alterations in bone turnover, mineralisation, mass and microarchitecture in patients with chronic kidney disease (CKD) and represents the skeletal component of 'CKD-mineral and bone disorder'. Changes in bone structure lead to impaired bone quality, compromised bone strength and increased susceptibility to fractures with associated significant morbidity, mortality and financial cost. Diagnosis and management of ROD is hindered by the inadequacy of currently available diagnostic methods to interpret the complex pathophysiology...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28429548/is-serum-phosphate-a-useful-target-in-patients-with-chronic-kidney-disease-and-what-is-the-role-for-dietary-phosphate-restriction
#17
Nigel D Toussaint, Stephen G Holt
A complex system of endocrine and paracrine signals exists to control phosphate balance. Dysregulation of these systems in patients with chronic kidney disease has serious clinical consequences. Whilst observational studies have shown associations between higher serum phosphate levels and poor clinical outcomes, the direction of causality has not been demonstrated. Whether there is a target level of serum phosphate remains controversial and no randomized trials to date have proved that strategies to lower extracellular phosphate actually improve clinical outcomes...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28429546/should-nephrologists-consider-vascular-calcification-screening
#18
Rathika Krishnasamy, Eugenie Pedagogos
Vascular calcification (VC) has been widely discussed over the last few decades and is associated with significant morbidity and mortality among patients with chronic kidney disease. Importantly, these patients have premature and rapidly progressive calcification when compared with the general population. VC is an active and complex process that is closely regulated by a growing list of inducers and inhibitors. VC can be detected using several non-invasive modalities including plain radiography, echocardiogram and computed tomography scans...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28428115/p300-and-c-ebp%C3%AE-regulated-ikk%C3%AE-expression-are-involved-in-thrombin-induced-il-8-cxcl8-expression-in-human-lung-epithelial-cells
#19
Zheng-Wei Huang, Gi-Shih Lien, Chien-Huang Lin, Chun-Ping Jiang, Bing-Chang Chen
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic lung inflammatory diseases. Thrombin and interleukin (IL)-8/C-X-C chemokine ligand 8 (CXCL8) play critical roles in lung inflammation. Our previous study showed that c-Src-dependent IκB kinase (IKK)/IκBα/nuclear factor (NF)-κB and mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/ribosomal S6 protein kinase (RSK)-dependent CAAT/enhancer-binding protein β (C/EBPβ) activation are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells...
April 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28427431/from-inflammation-to-gastric-cancer-the-importance-of-hedgehog-gli-signaling-in-helicobacter-pylori-induced-chronic-inflammatory-and-neoplastic-diseases
#20
REVIEW
Silja Wessler, Linda M Krisch, Dominik P Elmer, Fritz Aberger
Infections with the human pathogen Helicobacter pylori (H. pylori) are closely associated with the development of inflammatory disorders and neoplastic transformation of the gastric epithelium. Drastic changes in the micromilieu involve a complex network of H. pylori-regulated signal transduction pathways leading to the release of proinflammatory cytokines, gut hormones and a wide range of signaling molecules. Besides controlling embryonic development, the Hedgehog/GLI signaling pathway also plays important roles in epithelial proliferation, differentiation, and regeneration of the gastric physiology, but also in the induction and progression of inflammation and neoplastic transformation in H...
April 20, 2017: Cell Communication and Signaling: CCS
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