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https://www.readbyqxmd.com/read/28934680/a-phase-1-study-of-the-janus-kinase-2-jak2-v617f-inhibitor-gandotinib-ly2784544-in-patients-with-primary-myelofibrosis-polycythemia-vera-and-essential-thrombocythemia
#1
Srdan Verstovsek, Ruben A Mesa, Mohamed E Salama, Li Li, Celine Pitou, Fabio P Nunes, Gregory L Price, Jennifer L Giles, Deborah N D'Souza, Richard A Walgren, Josef T Prchal
Mutations in Janus kinase 2 (JAK2) are implicated in the pathogenesis of Philadelphia-chromosome negative myeloproliferative neoplasms, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Gandotinib (LY2784544), a potent inhibitor of JAK2 activity, shows increased potency for the JAK2(V617F) mutation. The study had a standard 3+3 dose-escalation design to define the maximum-tolerated dose. Primary objectives were to determine safety, tolerability, and recommended oral daily dose of gandotinib for patients with JAK2(V617F)-positive myelofibrosis, essential thrombocythemia, or polycythemia vera...
August 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28934615/working-memory-and-prefrontal-temporal-hemodynamic-responses-during-post-task-period-in-patients-with-schizophrenia-a%C3%A2-multi-channel-near-infrared-spectroscopy-study
#2
Takamasa Noda, Kazuyuki Nakagome, Shiori Setoyama, Eisuke Matsushima
The relationship between cognitive impairments and social dysfunction in schizophrenia is widely accepted. Neuroimaging studies in patients with schizophrenia have demonstrated abnormal function in the prefrontal region during various neurocognitive tasks. However, studies exploring the neural basis of these cognitive impairments are still limited. Multi-channel near-infrared spectroscopy (NIRS) is a non-invasive functional neuroimaging technique used to detect the spatiotemporal characteristics of brain activity...
September 4, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28934404/organizational-and-managerial-factors-associated-with-clinical-practice-guideline-adherence-a-simulation-based-study-in-36-french-hospital-wards
#3
Florence Saillour-Glénisson, Marion Kret, Sandrine Domecq, Matthieu Sibé, Valentin Daucourt, Virginie Migeot, David Veillard, Philippe Michel
Objectives: To identify managerial and organizational characteristics of multi-specialty medicine wards and individual characteristics of health professionals that are most strongly associated with clinical practice guidelines (CPG) adherence. Design: Cross-sectional stratified cluster sample design. Setting: Data were gathered from 36 randomly selected multi-specialty medicine wards. Participants: The study population included all health professionals involved in patient care working in the participating wards...
August 1, 2017: International Journal for Quality in Health Care
https://www.readbyqxmd.com/read/28934241/hla-dr7-and-hla-dq2-transgenic-mouse-strains-tested-as-a-model-system-for-ximelagatran-hepatotoxicity
#4
Hanna Lundgren, Klara Martinsson, Karin Cederbrant, Johan Jirholt, Daniel Mucs, Katja Madeyski-Bengtson, Said Havarinasab, Per Hultman
The oral thrombin inhibitor ximelagatran was withdrawn in the late clinical trial phase because it adversely affected the liver. In approximately 8% of treated patients, drug-induced liver injury (DILI) was expressed as transient alanine transaminase (ALT) elevations. No evidence of DILI had been revealed in the pre-clinical in vivo studies. A whole genome scan study performed on the clinical study material identified a strong genetic association between the major histocompatibility complex alleles for human leucocyte antigens (HLA) (HLA-DR7 and HLA-DQ2) and elevated ALT levels in treated patients...
2017: PloS One
https://www.readbyqxmd.com/read/28934202/platelet-dysfunction-contributes-to-bleeding-complications-in-patients-with-probable-leptospirosis
#5
Rahajeng N Tunjungputri, Muhammad Hussein Gasem, Willemijn van der Does, Pandu H Sasongko, Bambang Isbandrio, Rolf T Urbanus, Philip G de Groot, Andre van der Ven, Quirijn de Mast
BACKGROUND: Severe leptospirosis is frequently complicated by a hemorrhagic diathesis, of which the pathogenesis is still largely unknown. Thrombocytopenia is common, but often not to the degree that spontaneous bleeding is expected. We hypothesized that the hemorrhagic complications are not only related to thrombocytopenia, but also to platelet dysfunction, and that increased binding of von Willebrand factor (VWF) to platelets is involved in both platelet dysfunction and increased platelet clearance...
September 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28933798/pharmacokinetics-of-tecarfarin-and-warfarin-in-patients-with-severe-chronic-kidney-disease
#6
Mark Midei, Detlef Albrecht, Mintu P Turakhia, Daniel Ries, Thomas Marbury, William Smith, Debbie Dillon, Peter G Milner, Mark G Midei
Chronic kidney disease (CKD) complicates warfarin anticoagulation partially through its effect on CYP2C9 activity. Tecarfarin, a novel vitamin K antagonist, is not metabolized by CYP2C9. To evaluate the effect of CKD on their metabolism, we measured PK parameters of warfarin and tecarfarin in subjects with and without CKD. CKD subjects with estimated glomerular filtration rate < 30 mL/min not on dialysis (n = 13) were matched to healthy volunteers (HVs) (n = 10). Each subject was randomized to either warfarin 10 mg or tecarfarin 30 mg and was later crossed over to the other drug...
September 21, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28933605/early-active-rehabilitation-after-arthroscopic-rotator-cuff-repair-a-prospective-randomized-pilot-study
#7
Rudolf Raschhofer, Nikos Poulios, Wolfgang Schimetta, Rüdiger Kisling, Christian Mittermaier
OBJECTIVE: To compare two different rehabilitation strategies, primary passive motion versus early isometric loading of the rotator cuff. DESIGN: Prospective randomized controlled observer-blinded pilot study. SETTING: Institute of Physical Medicine and Rehabilitation. SUBJECTS: Thirty patients after rotator cuff surgery. INTERVENTION: All participants were randomly assigned to one of the two outpatient treatment groups: primary passive motion versus early isometric loading of the rotator cuff...
October 2017: Clinical Rehabilitation
https://www.readbyqxmd.com/read/28933604/the-nottingham-fatigue-after-stroke-notfast-study-factors-associated-with-severity-of-fatigue-in-stroke-patients-without-depression
#8
Avril Drummond, Louise Hawkins, Nikola Sprigg, Nick S Ward, Amit Mistri, Pippa Tyrrell, Gillian E Mead, Esme Worthington, Nadina B Lincoln
OBJECTIVE: To identify factors associated with post-stroke fatigue in a sample of stroke survivors without depression. DESIGN: Cross-sectional cohort study. SETTING: Recruitment was from four stroke units in the UK. SUBJECTS: Participants were assessed within four to six weeks of first stroke; those with high levels of depressive symptoms (score ⩾7 Brief Assessment Schedule Depression Cards) were excluded. MAIN MEASURES: Participants were assessed after stroke on the Fatigue Severity Scale of the Fatigue Assessment Inventory, the Rivermead Mobility Index, Nottingham Extended Activities of Daily Living scale, Beck Anxiety Index, Sleep Hygiene Index, 6m walk test, and measures of cognitive ability...
October 2017: Clinical Rehabilitation
https://www.readbyqxmd.com/read/28933516/anti-il5-therapies-for-asthma
#9
REVIEW
Hugo A Farne, Amanda Wilson, Colin Powell, Lynne Bax, Stephen J Milan
BACKGROUND: This review is the first update of a previously published review in The Cochrane Library (Issue 7, 2015). Interleukin-5 (IL-5) is the main cytokine involved in the activation of eosinophils, which cause airway inflammation and are a classic feature of asthma. Monoclonal antibodies targeting IL-5 or its receptor (IL-5R) have been developed, with recent studies suggesting that they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function...
September 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28933330/-short-term-results-of-surgical-treatment-of-patients-with-hallux-rigidus
#10
M Dygrýnová, M Uvízl, J Gallo
PURPOSE OF THE STUDY Hallux rigidus is common and degenerative arthritis of the first metatarsophalangeal joint. The aim of this study was to assess the results of cheilectomy and total joint replacement (TJR) in patients with hallux rigidus. Minimum duration of followup was 18 months. MATERIAL AND METHODS The study included fifty-nine patients who underwent surgery at our Department due to hallux rigidus between January 2013 and December 2014. Thirty-seven patients underwent cheilectomy and twenty-two patients had total joint arthroplasty using METIS®...
2017: Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca
https://www.readbyqxmd.com/read/28932647/immunotherapy-with-listeria-reduces-metastatic-breast-cancer-in-young-and-old-mice-through-different-mechanisms
#11
Arthee Jahangir, Dinesh Chandra, Wilber Quispe-Tintaya, Manisha Singh, Benson Chellakkan Selvanesan, Claudia Gravekamp
Cancer immunotherapy is one of the most promising and benign therapies against metastatic cancer. However, most cancer patients are old and elderly react less efficient to cancer vaccines than young adults, due to T cell unresponsiveness. Here we present data of cancer vaccination in young and old mice with metastatic breast cancer (4T1 model). We tested adaptive and innate immune responses to foreign antigens (Listeria-derived) and self-antigens (tumor-associated antigens (TAA)) and their contribution to elimination of metastases at young and old age...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#12
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932627/addition-of-anti-estrogen-therapy-to-anti-her2-dendritic-cell-vaccination-improves-regional-nodal-immune-response-and-pathologic-complete-response-rate-in-patients-with-er-pos-her2-pos-early-breast-cancer
#13
Lea Lowenfeld, Salman Zaheer, Crystal Oechsle, Megan Fracol, Jashodeep Datta, Shuwen Xu, Elizabeth Fitzpatrick, Robert E Roses, Carla S Fisher, Elizabeth S McDonald, Paul J Zhang, Angela DeMichele, Rosemarie Mick, Gary K Koski, Brian J Czerniecki
HER2-directed therapies are less effective in patients with ER(pos) compared to ER(neg) breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2(pos)/ER(pos) early breast cancer patients. In pre-clinical studies of HER2(pos) breast cancer cell lines, ER(pos) cells were partially resistant to CD4(+) Th1 cytokine-induced metabolic suppression compared with ER(neg) cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932574/lung-allocation
#14
REVIEW
Jens Gottlieb
Shortage of donor lungs in most western countries and broadening of indications for lung transplantation (LTx) has led increased waiting list mortality in the past. Usually donor lungs and recipients are matched by size as measured by total lung capacity and blood type in first order. In some countries regional allocation comes first, in other countries a national wait list exists and some nations are organized in supranational allocation systems. Organ distribution should respect the ethical principles of equity, justice, beneficence and utility...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28932369/diagnostic-accuracy-of-fecal-calprotectin-in-assessing-the-severity-of-inflammatory-bowel-disease-from-laboratory-to-clinic
#15
Soheila Moein, Durdi Qujeq, Mostafa Vaghari Tabari, Mehrdad Kashifard, Karimollah Hajian-Tilaki
BACKGROUND: Inflammatory bowel disease (IBD) involves chronic inflammation of the digestive tract. In the past decades, fecal calprotectin has been proposed as a useful biomarker for the differential diagnosis between IBD patients and healthy controls. We designed this study to evaluate the diagnostic ability of fecal calprotectin (FC) and conventional inflammatory markers in IBD patients. METHODS: Thirty patients who underwent colonoscopy were cases and thirty healthy subjects undergoing colonoscopy as part of a medical check-up were the controls...
2017: Caspian Journal of Internal Medicine
https://www.readbyqxmd.com/read/28932306/prevalence-of-asymptomatic-arterial-hypertension-and-its-correlation-with-inflammatory-activity-in-early-rheumatoid-arthritis
#16
Ismet H Bajraktari, Sylejman Rexhepi, Idriz Berisha, Ali Lahu, Avni Kryeziu, Bastri Durmishi, Halit Bajraktari, Elton Bahtiri
BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that worsens during the course of the disease and can cause disability. Early RA refers to the onset of symptoms within the past 3 months. In RA, increased levels of mediators of inflammation may cause arterial stiffness consequently leading to arterial hypertension. AIM: The aim of this cross-sectional study was to assess the prevalence of asymptomatic arterial hypertension in early RA patients as well as the correlation with parameters of inflammation...
August 15, 2017: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28932292/methotrexate-blood-pressure-and-markers-of-arterial-function-in-patients-with-rheumatoid-arthritis-a-repeated-cross-sectional-study
#17
Arduino A Mangoni, Leena R Baghdadi, E Michael Shanahan, Michael D Wiese, Sara Tommasi, David Elliot, Richard J Woodman
BACKGROUND: Methotrexate (MTX) treatment in rheumatoid arthritis (RA) has been associated with lower cardiovascular risk compared to other disease-modifying antirheumatic drugs (DMARDs). We sought to identify whether the MTX-associated cardioprotection involves changes in blood pressure (BP) and/or arterial function. METHODS: Clinic and 24-hour peripheral and central systolic and diastolic BP (SBP and DBP), augmentation index (AIx), pulse wave velocity (PWV) and plasma asymmetric dimethylarginine (ADMA) were assessed in RA patients on stable treatment with either MTX ± other DMARDs (MTX group, n = 56, age 61 ± 13 years, 70% females) or other DMARDs (non-MTX group, n = 30, age 63 ± 12 years, 76% females)...
September 2017: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/28932229/association-between-a-single-donor-tarc-ccl17-promotor-polymorphism-and-obstructive-chronic-lung-allograft-dysfunction-after-lung-transplantation
#18
Kevin Budding, Jessica van Setten, Eduard A van de Graaf, Oliver A van Rossum, Tineke Kardol-Hoefnagel, Erik-Jan D Oudijk, C Erik Hack, Henderikus G Otten
Lung transplantation (LTx) outcome is hampered by development of chronic rejection, often manifested as the bronchiolitis obliterans syndrome (BOS). Low serum levels of thymus and activation-regulated chemokine (TARC/CCL17), a chemoattractant, measured during the first month post-LTx are predictive for BOS development. Since TARC/CCL17 promotor polymorphisms correlate with serum TARC/CCL17 levels, we investigated seven single-nucleotide polymorphisms (SNPs) within this region and their potential association with LTx outcome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28932141/comparison-of-the-pendulum-appliance-and-the-jones-jig-a-prospective-comparative-study
#19
Sushruth Shetty, Rajkumar Maurya, H V Pruthvi Raj, Anand Patil
OBJECTIVE: To compare two molar distalization devices, the Pendulum appliance (PA) and the Jones Jig (JJ) in dental Class II patients. MATERIALS AND METHODS: Pretreatment and postdistalization lateral cephalograms and study models of 20 subjects (6 males, 14 females) Class II malocclusion subjects were examined. PA and JJ group both consisted of 10 patients each with a mean pretreatment age of 12 years 1 month for females and 12 years 5 months for males. The PA and the JJ appliance were activated once in a month until Class II molar relationship was corrected to a super Class I molar relationship in both groups...
July 2017: European Journal of Dentistry
https://www.readbyqxmd.com/read/28931987/enhancement-of-motor-skill-learning-by-a-combination-of-ideal-model-observation-and-self-observation
#20
Hitomi Nishizawa, Teiji Kimura
[Purpose] In sports physical therapy, video of a patient's movement or of a skilled model's movement has been used as observational learning methods for injury prevention and movement modification. Positive effects of model video observation have been reported. This study aimed to clarify the effect on motor skill learning using a combination of model-observation and self-observation, which is thought to act as an enhanced method for active error detection by comparing model-observation and self-observation alone for acquisition of correct sports movement...
September 2017: Journal of Physical Therapy Science
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