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https://www.readbyqxmd.com/read/28716895/ctla4-promotes%C3%A2-tyk2-stat3-dependent-b-cell-oncogenecity
#1
Andreas Herrmann, Christoph Lahtz, Toshikage Nagao, Joo Y Song, Wing C Chan, Heehyoung Lee, Chanyu Yue, Thomas Look, Ronja Muelfarth, Wenzhao Li, Kurt Jenkins, John Williams, Lihua E Budde, Stephen J Forman, Larry W Kwak, Thomas Blankenstein, Hua Yu
Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is a well-established immune checkpoint for antitumor immune responses. The pro-tumorigenic function of CTLA4 is believed to be limited to T cell inhibition by countering the activity of the T cell co-stimulating receptor CD28. However, as we demonstrate here, there are two additional roles for CTLA4 in cancer, including via CTLA4 overexpression in diverse B cell lymphomas and in melanoma-associated B cells. CTLA4-CD86 ligation recruited and activated the JAK family member Tyk2, resulting in STAT3 activation and expression of genes critical for cancer immunosuppression and tumor growth and survival...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28698925/prolonged-perceived-stress-and-saliva-cortisol-in-a-large-cohort-of-danish-public-service-employees-cross-sectional-and-longitudinal-associations
#2
Sigurd Mikkelsen, Julie Lyng Forman, Samuel Fink, Marianne Agergaard Vammen, Jane Frølund Thomsen, Matias Brødsgaard Grynderup, Åse Marie Hansen, Linda Kaerlev, Henrik Albert Kolstad, Reiner Rugulies, Jens Peter Bonde
PURPOSE: It is well known that acute stress can lead to a transient increase in cortisol secretion, but the effects of prolonged stress on cortisol secretion are uncertain. This study examines the cross-sectional and longitudinal associations between prolonged perceived stress and salivary cortisol. METHODS: In 2007, 4467 Danish public service employees participated in a study of stress and mental health, and 3217 participated in a follow-up in 2009. Perceived stress during the past 4 weeks was assessed by Cohen's four item perceived stress scale...
July 11, 2017: International Archives of Occupational and Environmental Health
https://www.readbyqxmd.com/read/28697340/stabilization-of-the-c-myc-protein-by-camkii%C3%AE-promotes-t-cell-lymphoma
#3
Ying Gu, Jiawei Zhang, Xiaoxiao Ma, Byung-Wook Kim, Hailong Wang, Jinfan Li, Yi Pan, Yang Xu, Lili Ding, Lu Yang, Chao Guo, Xiwei Wu, Jun Wu, Kirk Wu, Xiaoxian Gan, Gang Li, Ling Li, Stephen J Forman, Wing-Chung Chan, Rongzhen Xu, Wendong Huang
Although high c-Myc protein expression is observed alongside MYC amplification in some cancers, in most cases protein overexpression occurs in the absence of gene amplification, e.g., T cell lymphoma (TCL). Here, Ca(2+)/calmodulin-dependent protein kinase II γ (CAMKIIγ) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). Furthermore, CAMKIIγ was shown to be essential for tumor maintenance. Inhibition of CAMKIIγ with a specific inhibitor destabilized c-Myc and reduced tumor burden...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28685861/suction-blister-lesions-and-epithelialization-monitored-by-optical-coherence-tomography
#4
M G Ahlström, L M R Gjerdrum, H F Larsen, C Fuchs, A L Sørensen, J L Forman, M S Ågren, M Mogensen
BACKGROUND/PURPOSE: Our objective was to assess epithelialization of suction blister lesions by optical coherence tomography (OCT) and benchmark it to histology using epidermal thickness (ET) as the primary outcome. METHODS: Thirty-two healthy volunteers were recruited to Study 1 and 2. One 10-mm suction blister was raised on each buttock, and the blister roof was excised. Lesions were covered with moisture-retaining dressing. In Study 1, the lesions were OCT-scanned on day 0 (D0), D2 and D4 and excised for histological examination...
July 7, 2017: Skin Research and Technology
https://www.readbyqxmd.com/read/28684221/exercise-training-for-prevention-and-treatment-of-heart-failure
#5
REVIEW
Nitin Kondamudi, Mark Haykowsky, Daniel E Forman, Jarett Berry, Ambarish Pandey
Heart Failure (HF) results in high healthcare costs and burdens for the United States both in respects to hospitalizations, therapies, and associated disability. The relative proportion of HF with preserved ejection fraction (HFpEF) compared with HF with reduced ejection fraction (HFrEF) is on the rise; HFpEF has already become the dominant form of HF and it continues to increase. The serious implications of these trends are compounded by a dearth of effective HFpEF therapies. While low physical activity, low cardiorespiratory fitness (CRF), and obesity, are risk factors for HF in general, they particularly predispose to HFpEF...
July 3, 2017: Progress in Cardiovascular Diseases
https://www.readbyqxmd.com/read/28683049/improving-readiness-and-reducing-costs-an-analysis-of-factors-that-influence-site-selection-for-army-outpatient-surgical-services
#6
Katherine E Little, Katie M Martinez, Jessica L Forman, Jason P Richter, Michael L Wade
The variable costs of providing surgical procedures for military beneficiaries are greater when care is rendered in the civilian purchased care network than when provided at a direct care military treatment facility (MTF). To reduce healthcare-related costs, retaining surgical services is a priority at MTFs across the U.S. Army Medical Command. This study is the first to identify factors significantly associated with outpatient surgical service site selection in the military health system (MHS). We analyzed 1,000,305 patient encounters in fiscal year 2014, of which 970,367 were direct care encounters and 29,938 were purchased care encounters...
July 2017: Journal of Healthcare Management / American College of Healthcare Executives
https://www.readbyqxmd.com/read/28680765/barriers-and-facilitators-to-ed-physician-use-of-the-test-and-treatment-for-bppv
#7
Kevin A Kerber, Jane Forman, Laura Damschroder, Steven A Telian, Angela Fagerlin, Patricia Johnson, Devin L Brown, Lawrence C An, Lewis B Morgenstern, William J Meurer
BACKGROUND: The test and treatment for benign paroxysmal positional vertigo (BPPV) are evidence-based practices supported by clinical guideline statements. Yet these practices are underutilized in the emergency department (ED) and interventions to promote their use are needed. To inform the development of an intervention, we interviewed ED physicians to explore barriers and facilitators to the current use of the Dix-Hallpike test (DHT) and the canalith repositioning maneuver (CRM). METHODS: We conducted semi-structured in-person interviews with ED physicians who were recruited at annual ED society meetings in the United States...
June 2017: Neurology. Clinical Practice
https://www.readbyqxmd.com/read/28678596/maternal-inflammatory-diet-and-adverse-pregnancy-outcomes-circulating-cytokines-and-genomic-imprinting-as-potential-regulators
#8
Lauren E McCullough, Erline E Miller, Laura E Calderwood, Nitin Shivappa, Susan E Steck, Michele R Forman, Michelle Mendez, Rachel Maguire, Bernard F Fuemmeler, Scott H Kollins, Staci Bilbo, Zhiqing Huang, Amy P Murtha, Susan K Murphy, James R Hébert, Cathrine Hoyo
Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII™)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI)...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28665923/non-invasive-continuous-cardiac-output-and-cerebral-perfusion-monitoring-in-term-infants-with-neonatal-encephalopathy-assessment-of-feasibility-and-reliability
#9
Eva Forman, Colm R Breatnach, Stephanie Ryan, Jana Semberova, Jan Miletin, Adrienne Foran, Afif El-Khuffash
BACKGROUND: None invasive hemodynamic monitoring of infants with neonatal encephalopathy (NE) undergoing therapeutic hypothermia (TH) would be a potentially useful clinical tool. We aimed assess the feasibility and reliability of non-invasive cardiac output monitoring (NICOM) and near infrared spectroscopy (NIRS) in this cohort. METHODS: NICOM and NIRS were commenced to measure cardiac output (CO), systemic vascular resistance (SVR), blood pressure (BP), and cerebral regional oxygen saturations (SctO2) during TH and rewarming...
June 30, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28655774/stabilization-of-a-nucleotide-binding-domain-of-the-cystic-fibrosis-transmembrane-conductance-regulator-yields-insight-into-disease-causing-mutations
#10
Robert M Vernon, P Andrew Chong, Hong Lin, Zhengrong Yang, Qingxian Zhou, Andrei A Aleksandrov, Jennifer E Dawson, John R Riordan, Christie G Brouillette, Patrick H Thibodeau, Julie D Forman-Kay
Characterization of the second nucleotide binding domain (NBD2) of the cystic fibrosis transmembrane conductance regulator (CFTR) has lagged behind research into the NBD1 domain, in part because NBD1 contains the F508del mutation which is the dominant cause of cystic fibrosis. Research on NBD2 has also been hampered by the overall instability of the domain and the difficulty of producing reagents. Nonetheless multiple disease-causing mutations reside in NBD2 and the domain is critical to CFTR function, since channel gating involves NBD1:NBD2 dimerization and NBD2 contains the catalytically active ATPase site in CFTR...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28650985/chronic-trichuris-muris-infection-causes-neoplastic-change-in-the-intestine-and-exacerbates-tumour-formation-in-apc-min-mice
#11
Kelly S Hayes, Laura J Cliffe, Alison J Bancroft, Simon P Forman, Seona Thompson, Cath Booth, Richard K Grencis
Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28649446/phenotypic-profiling-of-cftr-modulators-in-patient-derived-respiratory-epithelia
#12
Saumel Ahmadi, Zoltan Bozoky, Michelle Di Paola, Sunny Xia, Canhui Li, Amy P Wong, Leigh Wellhauser, Steven V Molinski, Wan Ip, Hong Ouyang, Julie Avolio, Julie D Forman-Kay, Felix Ratjen, Jeremy A Hirota, Johanna Rommens, Janet Rossant, Tanja Gonska, Theo J Moraes, Christine E Bear
Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis, a disease caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Heterogeneity in CFTR genotype-phenotype relationships in affected individuals plus the escalation of drug discovery targeting specific mutations highlights the need to develop robust in vitro platforms with which to stratify therapeutic options using relevant tissue. Toward this goal, we adapted a fluorescence plate reader assay of apical CFTR-mediated chloride conductance to enable profiling of a panel of modulators on primary nasal epithelial cultures derived from patients bearing different CFTR mutations...
April 14, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28646646/antileukemic-activity-and-cellular-effects-of-the-antimalarial-agent-artesunate-in-acute-myeloid-leukemia
#13
Bijender Kumar, Arjun Kalvala, Su Chu, Steven Rosen, Stephen J Forman, Guido Marcucci, Ching-Cheng Chen, Vinod Pullarkat
The artimisinins are a class of antimalarial compounds whose antiparasitic activity is mediated by induction of reactive oxygen species (ROS). Herein, we report that among the artimisinins, artesunate (ARTS), an orally bioavailable compound has the most potent antileukemic activity in AML models and primary patients' blasts. ARTS was most cytotoxic to the FLT3-ITD+ AML MV4-11 and MOLM-13 cells (IC50 values of 1.1 and 0.82μM respectively), inhibited colony formation in primary AML and MDS cells and augmented cytotoxicity of chemotherapeutics...
May 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28644306/the-associations-of-height-for-age-weight-for-age-and-weight-for-height-with-pediatric-acute-lymphoblastic-leukemia
#14
Jeremy M Schraw, Ann T Henson, Michael E Scheurer, Michele R Forman
Height at diagnosis has been analyzed in connection with acute lymphoblastic leukemia (ALL). Most prior studies have compared cases to national reference data derived from previous birth cohorts. Our objective was to determine the association of height-for-age Z score (HAZ) at time of diagnosis with the odds ratio (OR) of ALL in a case-control study (N=498) with a contemporaneous population of age-matched, sex-matched, and ethnicity-matched controls. We hypothesized that cases would have greater mean HAZ at time of diagnosis/interview, after adjustment for weight-for-age (WAZ) and weight-for-height (WHZ)...
July 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28634682/searching-for-the-sweet-spot-the-foot-rotation-and-parallel-engagement-of-ankle-ligaments-in-maximizing-injury-tolerance
#15
Bingbing Nie, Jason L Forman, Alexander R Mait, John-Paul Donlon, Matthew B Panzer, Richard W Kent
Ligament sprains, defined as tearing of bands of fibrous tissues within ligaments, account for a majority of injuries to the foot and ankle complex in field-based sports. External rotation of the foot is considered the primary injury mechanism of syndesmotic ankle sprains with concomitant flexion and inversion/eversion associated with particular patterns of ligament trauma. However, the influence of the magnitude and direction of loading vectors to the ankle on the in situ stress state of the ligaments has not been quantified in the literature...
June 20, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28632407/prediction-of-the-structural-response-of-the-femoral-shaft-under-dynamic-loading-using-subject-specific-finite-element-models
#16
Gwansik Park, Taewung Kim, Jason Forman, Matthew B Panzer, Jeff R Crandall
The goal of this study was to predict the structural response of the femoral shaft under dynamic loading conditions using subject-specific finite element (SS-FE) models and to evaluate the prediction accuracy of the models in relation to the model complexity. In total, SS-FE models of 31 femur specimens were developed. Using those models, dynamic three-point bending and combined loading tests (bending with four different levels of axial compression) of bare femurs were simulated, and the prediction capabilities of five different levels of model complexity were evaluated based on the impact force time histories: baseline, mass-based scaled, structure-based scaled, geometric SS-FE, and heterogenized SS-FE models...
June 20, 2017: Computer Methods in Biomechanics and Biomedical Engineering
https://www.readbyqxmd.com/read/28632058/assessment-of-model-based-image-matching-for-future-reconstruction-of-unhelmeted-sport-head-impact-kinematics
#17
Gregory J Tierney, Hamed Joodaki, Tron Krosshaug, Jason L Forman, Jeff R Crandall, Ciaran K Simms
Player-to-player contact inherent in many unhelmeted sports means that head impacts are a frequent occurrence. Model-Based Image-Matching (MBIM) provides a technique for the assessment of three-dimensional linear and rotational motion patterns from multiple camera views of a head impact event, but the accuracy is unknown for this application. The goal of this study is to assess the accuracy of the MBIM method relative to reflective marker-based motion analysis data for estimating six degree of freedom head displacements and velocities in a staged pedestrian impact scenario at 40 km/h...
February 28, 2017: Sports Biomechanics
https://www.readbyqxmd.com/read/28631214/identification-of-bufadienolides-from-the-boreal-toad-anaxyrus-boreas-active-against-a-fungal-pathogen
#18
Kelly Barnhart, Megan E Forman, Thomas P Umile, Jordan Kueneman, Valerie McKenzie, Irene Salinas, Kevin P C Minbiole, Douglas C Woodhams
Amphibian granular glands provide a wide range of compounds on the skin that defend against pathogens and predators. We identified three bufadienolides-the steroid-like compounds arenobufagin, gamabufotalin, and telocinobufagin-from the boreal toad, Anaxyrus boreas, through liquid chromatography mass spectrometry (LC/MS). Compounds were detected both after inducing skin gland secretions and in constitutive mucosal rinses from toads. We described the antimicrobial properties of each bufadienolide against Batrachochytrium dendrobatidis (Bd), an amphibian fungal pathogen linked with boreal toad population declines...
June 19, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28630561/human-rights-in-the-world-health-organization-views-of-the-director-general-candidates
#19
Benjamin Mason Meier
Before the 2017 election of the Director-General of WHO, and given the importance of human rights to global health governance through WHO, Health and Human Rights asked the three final candidates for their views on human rights, WHO's human rights mandate, and the role of human rights in WHO programming. These questions were developed by the author in collaboration with Audrey Chapman, Lisa Forman, Paul Hunt, Dainius Pūras, Javier Vasquez and Carmel Williams. Based on responses to these questions from each of the three candidates, this Perspective was originally published online on April 26, 2017...
June 2017: Health and Human Rights
https://www.readbyqxmd.com/read/28629877/the-effect-of-a-genetic-variant-on-quantitative-real-time-pcr-in-a-case-of-disseminated-adenovirus-infection
#20
Thomas J Gniadek, Michael T Forman, Isabella Martin, Ravit Arav-Boger, Alexandra Valsamakis
A patient developed disseminated adenovirus infection following bone marrow transplant. TaqMan real-time PCR showed reduced maximum fluorescence in the amplification curve from all plasma samples. Sequencing revealed three single nucleotide mismatches between the TaqMan probe and probe binding region. Real-time PCR with probe matching the isolate sequence showed normal amplification and a higher copy number result.
June 1, 2017: Diagnostic Microbiology and Infectious Disease
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