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https://www.readbyqxmd.com/read/28431247/the-ubiquitin-ligase-chip-integrates-proteostasis-and-aging-by-regulation-of-insulin-receptor-turnover
#1
Riga Tawo, Wojciech Pokrzywa, Éva Kevei, Melek E Akyuz, Vishnu Balaji, Svenja Adrian, Jörg Höhfeld, Thorsten Hoppe
Aging is attended by a progressive decline in protein homeostasis (proteostasis), aggravating the risk for protein aggregation diseases. To understand the coordination between proteome imbalance and longevity, we addressed the mechanistic role of the quality-control ubiquitin ligase CHIP, which is a key regulator of proteostasis. We observed that CHIP deficiency leads to increased levels of the insulin receptor (INSR) and reduced lifespan of worms and flies. The membrane-bound INSR regulates the insulin and IGF1 signaling (IIS) pathway and thereby defines metabolism and aging...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431065/cha2ds2-vasc-score-and-blood-biomarkers-to-identify-patients-with-atrial-high-rate-episodes-and-paroxysmal-atrial-fibrillation
#2
Paulina Wakula, Benjamin Neumann, Jens Kienemund, Eva Thon-Gutschi, Tatjana Stojakovic, Martin Manninger, Daniel Scherr, Hubert Scharnagl, Martin Kapl, Burkert Pieske, Frank R Heinzel
Aims: Paroxysmal atrial fibrillation (PAF) is often asymptomatic but nonetheless harmful. We evaluated the performance of disease-related blood biomarkers and CHA2DS2-VASc score to discriminate for PAF in patients with continuous rhythm monitoring. Methods and Results: Clinical data and blood samples were obtained from patients with dual-chamber pacemakers selected according to the absence (no_AHRE) or presence of Atrial High-Rate Episodes (AHRE) >6 min in recent device history (case-control approach)...
April 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28431053/occurrence-of-simultaneous-cathodal-anodal-capture-with-left-ventricular-quadripolar-leads-for-cardiac-resynchronization-therapy-an-electrocardiogram-evaluation
#3
Eraldo Occhetta, Gabriele Dell'Era, Ailia Giubertoni, Andrea Magnani, Francesco Rametta, Alessandro Blandino, Vincenzo Magnano, Maurizio Malacrida, Paolo Marino
Aims: The occurrence of left ventricular (LV) anodal activation during pacing with modern multipolar cardiac resynchronization therapy (CRT) systems has never been reported. The aim of our study was to demonstrate, by means of electrocardiogram (ECG) analysis, the occurrence of simultaneous cathodal-anodal LV capture with quadripolar LV leads. Methods and Results: We studied 10 first-time recipients of a CRT device equipped with a quadripolar LV lead. During follow-up, standard supine 12-lead ECGs were obtained in available cathode-to-anode LV pacing configurations with a pulse amplitude equal to twice the pacing threshold...
April 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28430920/rates-and-predictors-of-hospital-readmission-after-transcatheter-aortic-valve-implantation
#4
Anna Franzone, Thomas Pilgrim, Nicolas Arnold, Dik Heg, Bettina Langhammer, Raffaele Piccolo, Eva Roost, Fabien Praz, Lorenz Räber, Marco Valgimigli, Peter Wenaweser, Peter Jüni, Thierry Carrel, Stephan Windecker, Stefan Stortecky
Aims: To analyse reasons, timing and predictors of hospital readmissions after transcatheter aortic valve implantation (TAVI). Methods and Results: Patients included in the Bern TAVI Registry between August 2007 and June 2014 were analysed. Fine and Gray competing risk regression was used to identify factors predictive of hospital readmission within 1 year after TAVI with bootstrap analysis for internal validation. Of 868 patients alive at discharge, 221 (25.4%) were readmitted within 1 year...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28430790/whole-genome-sequencing-suggests-mechanisms-for-22q11-2-deletion-associated-parkinson-s-disease
#5
Nancy J Butcher, Daniele Merico, Mehdi Zarrei, Lucas Ogura, Christian R Marshall, Eva W C Chow, Anthony E Lang, Stephen W Scherer, Anne S Bassett
OBJECTIVES: To investigate disease risk mechanisms of early-onset Parkinson's disease (PD) associated with the recurrent 22q11.2 deletion, a genetic risk factor for early-onset PD. METHODS: In a proof-of-principle study, we used whole-genome sequencing (WGS) to investigate sequence variants in nine adults with 22q11.2DS, three with neuropathologically confirmed early-onset PD and six without PD. Adopting an approach used recently to study schizophrenia in 22q11...
2017: PloS One
https://www.readbyqxmd.com/read/28430196/organocatalytic-stereoselective-8-2-and-6-4-cycloadditions
#6
Rasmus Mose, Gert Preegel, Jesper Larsen, Sofie Jakobsen, Eva Høgh Iversen, Karl Anker Jørgensen
Cycloadditions that involve more than six π electrons are termed higher-order cycloadditions and are an excellent tool for solving complex synthetic challenges, as they provide direct access to polycyclic scaffolds that contain medium-sized rings. They have interesting synthetic potential for the discovery of new bioactive molecules and in natural product synthesis. It is peculiar that stereocontrolled [8+2] and [6+4] cycloadditions have been largely neglected for the past 50 years. Here we demonstrate a cross-dienamine activation of 2-cyclopentenone and the unprecedented endocyclic linear-dienamine activation of 2-cyclohexenones and 2-cycloheptenones...
May 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28430016/the-use-of-intravenous-lidocaine-for-the-management-of-acute-pain-secondary-to-traumatic-ankle-injury
#7
Billy Sin, Diana Gritsenko, Grace Tam, Kimberly Koop, Eva Mok
Sports-related injuries are a frequent cause of visits to the emergency department (ED) across the United States. A majority of these injuries affect the lower extremities with the ankle as the most frequently reported site. Most sports-related injuries are not severe enough to require inpatient hospitalization; however, they often lead to acute distress and pain which require prompt treatment with analgesics. Approximately 22% of patients who presented to the ED required pharmacotherapy for acute pain management...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28429943/on-the-size-and-origins-of-long-range-orientational-water-correlations-in-dilute-aqueous-salt-solutions
#8
Eva Pluharova, Damien Laage, Pavel Jungwirth
Long-range ordering of water around solutes has been invoked repeatedly in the literature as the key to understanding its biological function. Recently, it has been shown that in a dilute 8 mM aqueous NaCl solution the orientational correlation between water molecules extends beyond 8 nanometers. This was interpreted as arising from a long-range effect induced by the ions on the water collective hydrogen-bond interactions. Within this interpretation, each ion was supposed to affect tens of thousands or more water molecules in its surroundings, invoking a picture of ordered domains extending to several nanometers...
April 21, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28428749/deep-brain-stimulation-improves-the-symptoms-and-sensory-signs-of-persistent-central-neuropathic-pain-from-spinal-cord-injury-a-case-report
#9
Walter J Jermakowicz, Ian D Hentall, Jonathan R Jagid, Corneliu C Luca, James Adcock, Alberto Martinez-Arizala, Eva Widerström-Noga
Central neuropathic pain (CNP) is a significant problem after spinal cord injury (SCI). Pharmacological and non-pharmacological approaches may reduce the severity, but relief is rarely substantial. While deep brain stimulation (DBS) has been used to treat various chronic pain types, the technique has rarely been used to attenuate CNP after SCI. Here we present the case of a 54-year-old female with incomplete paraplegia who had severe CNP in the lower limbs and buttock areas since her injury 30 years prior. She was treated with bilateral DBS of the midbrain periaqueductal gray (PAG)...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28428441/selective-glucocorticoid-receptor-modulators-sgrms-delay-castrate-resistant-prostate-cancer-growth
#10
Jacob Kach, Tiha M Long, Phillip Selman, Eva Y Tonsing-Carter, Maria A Bacalao, Ricardo R Lastra, Larischa de Wet, Shane Comiskey, Marc Gillard, Calvin VanOpstall, Diana C West, Wen-Ching Chan, Donald Vander Griend, Suzanne D Conzen, Russell Z Szmulewitz
Increased glucocorticoid receptor (GR) expression and activity following androgen blockade can contribute to castration-resistant prostate cancer (CRPC) progression. Therefore, we hypothesized that GR antagonism will have therapeutic benefit in CRPC. However, the FDA-approved nonselective, steroidal GR antagonist, mifepristone, lacks GR specificity, reducing its therapeutic potential. Here we report that two novel non-steroidal and highly selective GR modulators (SGRMs), CORT118335 and CORT108297, have the ability to block GR activity in prostate cancer (PC) and slow CRPC progression...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28428264/cb1-cannabinoid-receptor-drives-oocyte-maturation-and-embryo-development-via-pi3k-akt-and-mapk-pathways
#11
Angela Patricia López-Cardona, Serafín Pérez-Cerezales, Raúl Fernández-González, Ricardo Laguna-Barraza, Eva Pericuesta, Naiara Agirregoitia, Alfonso Gutiérrez-Adán, Ekaitz Agirregoitia
Endocannabinoids have been recognized as mediators of practically all reproductive events in mammals. However, little is known about the role of this system in oocyte maturation. In a mouse model, we observed that activation of the cannabinoid receptor (CB)1 during in vitro oocyte maturation modulated the phosphorylation status of Akt and ERK1/2 and enhanced the subsequent embryo production. In the absence of the CB1 receptor, in vivo oocyte maturation was impaired and embryo development delayed. The CB2 receptor was unable to rescue these effects...
April 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28428119/timing-of-high-efficacy-therapy-in-relapsing-remitting-multiple-sclerosis-a-systematic-review
#12
REVIEW
Bernd Merkel, Helmut Butzkueven, Anthony L Traboulsee, Eva Havrdova, Tomas Kalincik
BACKGROUND: Immunotherapy initiated early after first presentation of relapsing-remitting multiple sclerosis is associated with improved long-term outcomes. One can therefore speculate that early initiation of highly effective immunotherapies, with an average efficacy that is superior to the typical first-line therapies, could further improve relapse and disability outcomes. However, the most common treatment strategy is to commence first-line therapies, followed by treatment escalation in patients who continue to experience on-treatment disease activity...
April 17, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28427840/aav-id-a-rapid-and-robust-assay-for-batch-to-batch-consistency-evaluation-of-aav-preparations
#13
Simon Pacouret, Mohammed Bouzelha, Rajani Shelke, Eva Andres-Mateos, Ru Xiao, Anna Maurer, Mathieu Mevel, Heikki Turunen, Trisha Barungi, Magalie Penaud-Budloo, Frédéric Broucque, Véronique Blouin, Philippe Moullier, Eduard Ayuso, Luk H Vandenberghe
Adeno-associated virus (AAV) vectors are promising clinical candidates for therapeutic gene transfer, and a number of AAV-based drugs may emerge on the market over the coming years. To insure the consistency in efficacy and safety of any drug vial that reaches the patient, regulatory agencies require extensive characterization of the final product. Identity is a key characteristic of a therapeutic product, as it ensures its proper labeling and batch-to-batch consistency. Currently, there is no facile, fast, and robust characterization assay enabling to probe the identity of AAV products at the protein level...
April 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28427696/genetic-burden-of-ms-risk-variants-distinguish-patients-from-healthy-individuals-but-are-not-associated-with-disease-activity
#14
Helle Bach Søndergaard, Eva Rosa Petersen, Melinda Magyari, Finn Sellebjerg, Annette Bang Oturai
Weighted genetic risk score (wGRS) was analysed for association with disease activity in more than 500 MS patients before and during interferon-beta treatment. The wGRS was higher in MS patients than in healthy controls when analysing eight HLA - and 109 non-HLA MS risk gene variants. No significant associations were observed between number of relapses prior to or during treatment with interferon-beta, both with and without HLA risk alleles included in the wGRS. In conclusion, among Danes the wGRS was higher in MS patients than controls but was not associated with the overall disease activity or response to treatment with interferon-beta...
April 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28427503/oesophageal-cancer-which-treatment-is-the-easiest-to-swallow-a-review-of-combined-modality-treatments-for-resectable-carcinomas
#15
REVIEW
Bianca So, Loredana Marcu, Ian Olver, Raghu Gowda, Eva Bezak
Oesophageal cancer is a relatively uncommon malignancy, but with poor prognosis. Despite several treatment options that are available, the 5-year survival rates rarely exceed 40%. This review discusses the main challenges of oesophageal cancer, the available treatment options, and the most effective treatment in terms of overall survival. The outcomes of clinical trials show that neo-adjuvant chemo-radiotherapy using cisplatin and 5-fluorouracil followed by oesophagectomy results in the greatest survival. However, the optimal chemotherapy and radiotherapy schedule remains unclear...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427446/respiratory-chain-complex-iii-deficiency-due-to-mutated-bcs1l-a-novel-phenotype-with-encephalomyopathy-partially-phenocopied-in-a-bcs1l-mutant-mouse-model
#16
Saara Tegelberg, Nikica Tomašić, Jukka Kallijärvi, Janne Purhonen, Eskil Elmér, Eva Lindberg, David Gisselsson Nord, Maria Soller, Nicole Lesko, Anna Wedell, Helene Bruhn, Christoph Freyer, Henrik Stranneheim, Rolf Wibom, Inger Nennesmo, Anna Wredenberg, Erik A Eklund, Vineta Fellman
BACKGROUND: Mitochondrial diseases due to defective respiratory chain complex III (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is completed by the insertion of the Rieske iron-sulfur protein, a process for which BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising from mutations in this gene is wide. RESULTS: A case of CIII deficiency was investigated in depth to assess respiratory chain function and assembly, and brain, skeletal muscle and liver histology...
April 20, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28427179/comprehensive-mapping-of-the-effects-of-azacitidine-on-dna-methylation-repressive-permissive-histone-marks-and-gene-expression-in-primary-cells-from-patients-with-mds-and-mds-related-disease
#17
Magnus Tobiasson, Hani Abdulkadir, Andreas Lennartsson, Shintaro Katayama, Francesco Marabita, Ayla De Paepe, Mohsen Karimi, Kaarel Krjutskov, Elisabet Einarsdottir, Michael Grövdal, Monika Jansson, Asmaa Ben Azenkoud, Lina Corddedu, Sören Lehmann, Karl Ekwall, Juha Kere, Eva Hellström-Lindberg, Johanna Ungerstedt
Azacitidine (Aza) is first-line treatment for patients with high-risk myelodysplastic syndromes (MDS), although its precise mechanism of action is unknown. We performed the first study to globally evaluate the epigenetic effects of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq), DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3 (ChIP seq). Aza induced a general increase in gene expression with 924 significantly upregulated genes but this increase showed no correlation with changes in DNA methylation or H3K18ac, and only a weak association with changes in H3K9me3...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427050/expression-of-high-mobility-group-protein-b1-in-cardiac-tissue-of-elderly-patients-with-coronary-artery-disease-with-or-without-inflammatory-rheumatic-disease
#18
Mei Bruton, Ivana Hollan, Julie Xiao, Eva Lindroos, Knut Mikkelsen, Stein E Rynning, Kjell Saatvedt, Sven M Almdahl, Helena E Harris, Ingrid E Lundberg, Cecilia Wick
BACKGROUND: It is known from clinical practice and observational studies that elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a significantly increased risk for cardiovascular diseases such as coronary artery disease (CAD) and heart failure. The molecular mechanism, however, is still not known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly conserved single polypeptide expressed in all mammal eukaryotic cells, has been identified to mediate myocardial dysfunction in vitro once released from the nuclei of cardiomyocytes...
April 21, 2017: Gerontology
https://www.readbyqxmd.com/read/28426891/experiences-of-nurses-with-the-care-of-patients-with-dementia-in-acute-hospitals-a-secondary-analysis
#19
Christiane Pinkert, Eva Faul, Susi Saxer, Melanie Burgstaller, Doris Kamleitner, Hanna Mayer
AIM AND OBJECTIVES: The aim was to describe nurses' experiences in caring for people with dementia (PwD) in acute hospital settings. BACKGROUND: Recent research suggests that nurses' experience in caring for PwD in acute hospitals is characterized by frustration, overall job dissatisfaction and feelings of powerlessness and guilt. Despite a growing body of knowledge concerning the care of PwD in acute care settings, it remains unclear how nurses in acute hospitals provide care for PwD and what general conditions characterize the nursing care provided to these patients...
April 20, 2017: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/28426797/is-bilingualism-losing-its-advantage-a-bibliometric-approach
#20
Victor A Sanchez-Azanza, Raúl López-Penadés, Lucía Buil-Legaz, Eva Aguilar-Mediavilla, Daniel Adrover-Roig
This study uses several bibliometric indices to explore the temporal course of publication trends regarding the bilingual advantage in executive control over a ten-year window. These indices include the number of published papers, numbers of citations, and the journal impact factor. According to the information available in their abstracts, studies were classified into one of four categories: supporting, ambiguous towards, not mentioning, or challenging the bilingual advantage. Results show that the number of papers challenging the bilingual advantage increased notably in 2014 and 2015...
2017: PloS One
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