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https://www.readbyqxmd.com/read/28431145/long-term-effects-of-a-lifestyle-intervention-and-oral-glucosamine-sulphate-in-primary-care-on-incident-knee-oa-in-overweight-women
#1
Bastiaan C de Vos, Marieke L A Landsmeer, Marienke van Middelkoop, Edwin H G Oei, Marjolein Krul, Sita M A Bierma-Zeinstra, Jos Runhaar
Objectives.: The present study was designed to evaluate the effect of a lifestyle intervention aimed to reduce body weight and of oral glucosamine sulphate on the incidence of knee osteoarthritis (OA) after 6-7 years in a population of middle-aged, overweight women, without knee OA at baseline. Methods.: The Prevention of knee Osteoarthritis in Overweight Females study, ISRCTN42823086, was a randomized controlled trial with a 2 × 2 factorial design. Four hundred and seven women aged 50-60 years with a BMI of ⩾27 kg/m 2 and free of knee OA were randomized...
April 20, 2017: Rheumatology
https://www.readbyqxmd.com/read/28430851/accuracy-of-offspring-reported-parental-hip-fractures-a-novel-population-based-parent-offspring-record-linkage-study
#2
Lisa M Lix, William D Leslie, Shuman Yang, Lin Yan, Randy Walld, Suzanne N Morin, Sumit R Majumdar, Leslie L Roos
The objective of this study was to test the validity of offspring-reported parental hip fracture in a unique bone mineral density (BMD) registry linked to administrative databases spanning 4 decades. Population-based data were from Manitoba, Canada, and included hospital abstracts, health insurance registrations, and the provincewide BMD registry. The cohort included individuals aged ≥40 years with BMD tests and self-reports of parental hip fracture between 2006 and 2014. Population registry data for 1966-2014 were used to link offspring with their parents, and hospital records were used to ascertain parental fractures...
April 20, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28429068/nicotine-deprivation-elevates-neural-representation-of-smoking-related-cues-in-object-sensitive-visual-cortex-a-proof-of-concept-study
#3
Anne Havermans, Onno C P van Schayck, Eric F P M Vuurman, Wim J Riedel, Job van den Hurk
OBJECTIVE: In the current study, we use functional magnetic resonance imaging (fMRI) and multi-voxel pattern analysis (MVPA) to investigate whether tobacco addiction biases basic visual processing in favour of smoking-related images. We hypothesize that the neural representation of smoking-related stimuli in the lateral occipital complex (LOC) is elevated after a period of nicotine deprivation compared to a satiated state, but that this is not the case for object categories unrelated to smoking...
April 21, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28428272/hur-small-molecule-inhibitor-elicits-differential-effects-in-adenomatosis-polyposis-and-colorectal-carcinogenesis
#4
Michaela Lang, David Berry, Katharina Passecker, Ildiko Mesteri, Sabin Bhuju, Florian Ebner, Vitaly Sedlyarov, Rayko Evstatiev, Kyle Dammann, Alexander Loy, Orest Kuzyk, Pavel Kovarik, Vineeta Khare, Martin Beibel, Guglielmo Roma, Nicole Meisner-Kober, Christoph Gasche
HuR is an RNA-binding protein implicated in immune homeostasis and various cancers, including colorectal cancer. HuR binding to AU-rich elements within the 3' untranslated region of mRNAs encoding oncogenes, growth factors, and various cytokines leads message stability and translation. In this study, we evaluated HuR as a small-molecule target for preventing colorectal cancer in high-risk groups such as those with familial adenomatosis polyposis (FAP) or inflammatory bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and colorectal cancer, but not in patients with IBD-dysplasia...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427903/atrial-fibrillation-is-associated-with-hypermethylation-in-human-left-atrium-and-treatment-with-decitabine-reduces-atrial-tachyarrhythmias-in-spontaneously-hypertensive-rats
#5
R Doñate Puertas, E Meugnier, C Romestaing, C Rey, E Morel, J Lachuer, N Gadot, A Scridon, C Julien, F Tronc, B Chapuis, C Valla, A Janin, L Pirola, A Méjat, S Rome, P Chevalier
Atrial fibrillation (AF) is the most common cardiac arrhythmia. As the molecular mechanisms underlying the pathology are largely unknown, this cardiac arrhythmia remains difficult to treat. To identify specific molecular actors involved in AF, we have performed a transcriptomic analysis on left atrium (LA) from patients with valvular heart disease with or without AF. We showed that 1627 genes had altered basal expression level in LA tissue of AF patients compared with the control group. The significantly enriched gene ontology biological process "anatomical structure morphogenesis" contained the highest number of genes in line with changes in structure that occur when the human heart remodels following AF development (ie, LA dilatation and interstitial fibrosis)...
March 30, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28427316/a-multiscale-modelling-approach-to-understand-atherosclerosis-formation-a-patient-specific-case-study-in-the-aortic-bifurcation
#6
Mona Alimohammadi, Cesar Pichardo-Almarza, Obiekezie Agu, Vanessa Díaz-Zuccarini
Atherogenesis, the formation of plaques in the wall of blood vessels, starts as a result of lipid accumulation (low-density lipoprotein cholesterol) in the vessel wall. Such accumulation is related to the site of endothelial mechanotransduction, the endothelial response to mechanical stimuli and haemodynamics, which determines biochemical processes regulating the vessel wall permeability. This interaction between biomechanical and biochemical phenomena is complex, spanning different biological scales and is patient-specific, requiring tools able to capture such mathematical and biological complexity in a unified framework...
May 2017: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
https://www.readbyqxmd.com/read/28427193/targeting-high-aurora-kinases-expression-as-an-innovative-therapy-for-hepatocellular-carcinoma
#7
Fuchen Liu, Guangyong Wang, Xiaoqiang Wang, Zhihui Che, Wei Dong, Xinggang Guo, Zhenguang Wang, Ping Chen, Daisen Hou, Qi Zhang, Wenli Zhang, Yida Pan, Dongqin Yang, Hui Liu
The Aurora kinases A and B control tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, however, it remains unknown whether Aurora A and B overexpressed concomitantly and its clinical significance in hepatocellular carcinoma (HCC). Here, we obsearved Aurora A and B tended to overexpress parallelly on protein level (r = 0.8679, P < 0.0001) and their co-overexpression (Aurora AHBH), associated with the worst prognosis, was an independent predictor for the survival. Importantly, with the lower IC50 and stronger anti-tumor effect than selective inhibitors, SNS-314, the pan-inhibitor of Aurora kinases, which induced YAP (Yes-associated protein) reduction and resulted in P21 accumulation, significantly promoted the polyploidy (> 4N) formation and apoptosis in HCC...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426554/barking-up-the-right-tree-advancing-our-understanding-and-treatment-of-lymphoma-with-a-spontaneous-canine-model
#8
Dania Villarnovo, Angela L McCleary-Wheeler, Kristy L Richards
PURPOSE OF REVIEW: Spontaneous lymphoma in pet dogs is increasingly recognized as an ideal model for studying the disease in humans and for developing new targeted therapeutics for patients. Increasing interest by funding agencies, the private sector, and multidisciplinary academic collaborations between different disciplines and sectors now enables large knowledge gaps to be addressed and provides additional proof-of-concept examples to showcase the significance of the canine model. RECENT FINDINGS: The current review addresses the rationale for a canine lymphoma model including the valuable role it can play in drug development, serving as a link between mouse xenograft models and human clinical trials and the infrastructure that is now in place to facilitate these studies...
April 19, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#9
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425073/molecular-therapy-of-primary-hyperoxaluria
#10
Cristina Martin-Higueras, Armando Torres, Eduardo Salido
During the last few decades, the molecular understanding of the mechanisms involved in primary hyperoxalurias (PHs) has set the stage for novel therapeutic approaches. The availability of PH mouse models has facilitated preclinical studies testing innovative treatments. PHs are autosomal recessive diseases where the enzymatic deficit plays a central pathogenic role. Thus, molecular therapies aimed at restoring such deficit or limiting the consequences of the metabolic derangement could be envisioned, keeping in mind the specific challenges posed by the cell-autonomous nature of the deficiency...
April 19, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28424996/-quality-assurance-of-pain-care-in-austria-classification-of-management-facilities
#11
REVIEW
Wolfgang Jaksch, Rudolf Likar, Erika Folkes, Klaus Machold, Friedrich Herbst, Katharina Pils, Peter Stippl, Sandra Lettner, Mildred Alfons, Richard Crevenna, Christian Wiederer, Janina Dieber, Reinhold Glehr
In Austria there is no nationwide coverage of pain management, which meets even approximately international criteria. At present there are about 30 interdisciplinary pain management offices and clinics providing care according to a concept of the Austrian Pain Society (ÖSG), about 10 other outpatient pain clinics are located in district and country hospitals. A few years ago, there still were about 50 pain clinics. Yet closure of outpatient clinics and cost-cutting measures in the health sector jeopardize adequate pain relief for patients with chronic pain conditions...
April 19, 2017: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28424597/working-memory-after-traumatic-brain-injury-the-neural-basis-of-improved-performance-with-methylphenidate
#12
Anne E Manktelow, David K Menon, Barbara J Sahakian, Emmanuel A Stamatakis
Traumatic brain injury (TBI) often results in cognitive impairments for patients. The aim of this proof of concept study was to establish the nature of abnormalities, in terms of activity and connectivity, in the working memory network of TBI patients and how these relate to compromised behavioral outcomes. Further, this study examined the neural correlates of working memory improvement following the administration of methylphenidate. We report behavioral, functional and structural MRI data from a group of 15 Healthy Controls (HC) and a group of 15 TBI patients, acquired during the execution of the N-back task...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28424071/imatinib-treatment-of-poor-prognosis-mesenchymal-type-primary-colon-cancer-a-proof-of-concept-study-in-the-preoperative-window-period-impacct
#13
I Ubink, H J Bloemendal, S G Elias, M A Brink, M P Schwartz, Y C W Holierhoek, P M Verheijen, A W Boerman, R H J Mathijssen, W W J de Leng, R A de Weger, W M U van Grevenstein, M Koopman, M P Lolkema, O Kranenburg, I H M Borel Rinkes
BACKGROUND: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cancer...
April 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28423600/systematic-screening-of-isogenic-cancer-cells-identifies-dusp6-as-context-specific-synthetic-lethal-target-in-melanoma
#14
Stephanie Wittig-Blaich, Rainer Wittig, Steffen Schmidt, Stefan Lyer, Melanie Bewerunge-Hudler, Sabine Gronert-Sum, Olga Strobel-Freidekind, Carolin Müller, Markus List, Aleksandra Jaskot, Helle Christiansen, Mathias Hafner, Dirk Schadendorf, Ines Block, Jan Mollenhauer
Next-generation sequencing has dramatically increased genome-wide profiling options and conceptually initiates the possibility for personalized cancer therapy. State-of-the-art sequencing studies yield large candidate gene sets comprising dozens or hundreds of mutated genes. However, few technologies are available for the systematic downstream evaluation of these results to identify novel starting points of future cancer therapies.We improved and extended a site-specific recombination-based system for systematic analysis of the individual functions of a large number of candidate genes...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423546/tetraspanin-8-tspan-8-as-a-potential-target-for-radio-immunotherapy-of-colorectal-cancer
#15
Aurelie Maisonial-Besset, Tiffany Witkowski, Isabelle Navarro-Teulon, Odile Berthier-Vergnes, Giovanna Fois, Yingying Zhu, Sophie Besse, Olivia Bawa, Arnaud Briat, Mercedes Quintana, Alexandre Pichard, Mathilde Bonnet, Eric Rubinstein, Jean-Pierre Pouget, Paule Opolon, Lydia Maigne, Elisabeth Miot-Noirault, Jean-Michel Chezal, Claude Boucheix, Françoise Degoul
Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided significant efficiency for immunotherapy in CRC pre-clinical models. We therefore evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2. Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with 111In or 177Lu with radiochemical purities >95%, specific activity ranging from 300 to 600 MBq/mg, and radioimmunoreactive fractions >80%...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422786/antibody-mediated-immune-exclusion-of-hiv
#16
Ruth M Ruprecht, Samir K Lakhashe
PURPOSE OF REVIEW: Although approximately 90% of all HIV transmissions in humans occur through mucosal contact, the induction of mucosal anti-HIV immune responses has remained understudied. Here we summarize data demonstrating the powerful protection that is achievable at mucosal frontlines through virus-specific mucosal IgA alone or combined with IgG. RECENT FINDINGS: Passive immunization with different monoclonal antibody subclasses but identical epitope specificity (the conserved V3-loop crown of HIV gp120) has revealed that the dimeric IgA1 (dIgA1) form with its open hinge can prevent simian-human immunodeficiency virus (SHIV) acquisition in rhesus macaques at a higher rate than dIgA2...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422654/novel-mri-technique-enables-non-invasive-measurement-of-atrial-wall-thickness
#17
Marta Varela, Ross Morgan, Adeline Theron, Desmond Dillon-Murphy, Henry Chubb, John Whitaker, Markus Henningsson, Paul Aljabar, Tobias Schaeffter, Christoph Kolbitsch, Oleg V Aslanidi
Knowledge of atrial wall thickness (AWT) has the potential to provide important information for patient stratification and the planning of interventions in atrial arrhythmias. To date, information about AWT has only been acquired in post-mortem or poor-contrast CT studies, providing limited coverage and highly variable estimates of AWT. We present a novel contrast agent-free MRI sequence for imaging AWT and use it to create personalized AWT maps and a biatrial atlas. A novel black-blood phase-sensitive inversion recovery protocol was used to image 10 volunteers and 2 atrial fibrillation patients, as proof of concept...
April 13, 2017: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/28422122/infant-milk-fat-droplet-size-and-coating-affect-postprandial-responses-in-healthy-adult-men-a-proof-of-concept-study
#18
S Baumgartner, B J M van de Heijning, D Acton, R P Mensink
BACKGROUND/OBJECTIVES: Fat droplets in human milk (HM) are larger and surrounded by a phospholipid membrane compared with infant milk formulas (IMF). Since the physical structure of fat droplets might affect digestion and postprandial metabolism, an IMF was developed more mimicking HM lipid structure than current IMF. SUBJECTS/METHODS: A randomised, double-blind, crossover study was performed in 29 fasted healthy men (aged 18-25 years, BMI: 18-25 kg/m(2)) to compare 5-hour postprandial responses after consumption of an experimental IMF (Concept, Nuturis) with a current IMF (Control)...
April 19, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28421831/a-novel-automated-slide-based-technology-for-visualization-counting-and-characterization-of-the-formed-elements-of-blood-a-proof-of-concept-study
#19
James W Winkelman, Milenko J Tanasijevic, David J Zahniser
CONTEXT: - A novel automated slide-based approach to the complete blood count and white blood cell differential count is introduced. OBJECTIVE: - To present proof of concept for an image-based approach to complete blood count, based on a new slide preparation technique. A preliminary data comparison with the current flow-based technology is shown. DESIGN: - A prototype instrument uses a proprietary method and technology to deposit a precise volume of undiluted peripheral whole blood in a monolayer onto a glass microscope slide so that every cell can be distinguished, counted, and imaged...
April 19, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28420725/monitoring-daily-dynamics-of-early-tumor-response-to-targeted-therapy-by-detecting-circulating-tumor-dna-in-urine
#20
Hatim Husain, Vladislava O Melnikova, Karena Kosco, Brian Woodward, Soham More, Sandeep C Pingle, Elizabeth Weihe, Ben Ho Park, Muneesh Tewari, Mark G Erlander, Ezra E W Cohen, Scott M Lippman, Razelle Kurzrock
Purpose: Non-invasive drug biomarkers for the early assessment of tumor response can enable adaptive therapeutic decision-making and proof-of-concept studies for investigational drugs. Circulating tumor DNA (ctDNA) is released into the circulation by tumor cell turnover and has been shown to be detectable in urine. Experimental Design : We tested the hypothesis that dynamic changes in epidermal growth factor receptor (EGFR) activating (exon 19del and L858R) and resistance (T790M) mutation levels detected in urine could inform tumor response within days of therapy for advanced non-small cell lung cancer (NSCLC) patients receiving osimertinib, a second line third generation anti-EGFR tyrosine kinase inhibitor...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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