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https://www.readbyqxmd.com/read/28214654/programmed-cell-death-protein-1-pd-1-inhibitor-therapy-in-patients-with-advanced-melanoma-and-preexisting-autoimmunity-or-ipilimumab-triggered-autoimmunity
#1
Ralf Gutzmer, Anika Koop, Friedegund Meier, Jessica C Hassel, Patrick Terheyden, Lisa Zimmer, Lucie Heinzerling, Selma Ugurel, Claudia Pföhler, Anja Gesierich, Elisabeth Livingstone, Imke Satzger, Katharina C Kähler
AIM: Programmed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-1i) in this patient population is limited. PATIENTS AND METHODS: Metastatic melanoma patients with preexisting autoimmune disorders or previous ipilimumab-triggered immune-related adverse events (irAE) undergoing treatment with PD-1i from seven German skin cancer centres were evaluated retrospectively with regard to flare of the preexisting autoimmunity and development of new, not preexisting irAE as well as response to PD-1i therapy...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28214526/recent-advances-in-human-genetics-and-epigenetics-of-adiposity-pathway-to-precision-medicine
#2
Tove Fall, Michael Mendelson, Elizabeth K Speliotes
Obesity is a heritable trait that contributes to substantial global morbidity and mortality. Here, we summarize findings from the last decade of genetic and epigenetic research focused on unravelling the underpinnings of adiposity. More than 140 genetic regions are now known to influence adiposity traits. The genetics of general adiposity, as measured by body mass index, and that of abdominal obesity, as measured by waist to hip ratio, have distinct biological backgrounds. Expression of genes associated with general adiposity are enriched in the nervous system...
February 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28214518/potentiating-slc-transporter-activity-emerging-drug-discovery-opportunities
#3
REVIEW
Marie-Laure Rives, Jonathan A Javitch, Alan D Wickenden
Maintaining the integrity of cellular membranes is critical to protecting metabolic activities and genetic information from the environment. Regulation of transport across membranes of essential chemicals, including water, nutrients, hormones and many drugs, is therefore key to cellular homeostasis and physiological processes. The two main transporter superfamilies are ATP-binding cassette (ABC) transporters that primarily function as efflux transporters, and the solute carrier (SLC) transporters. SLC transporters encompass 52 gene families with almost 400 different human transporter genes...
February 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28214506/comparison-of-the-extent-of-coronary-artery-disease-in-patients-with-versus-without-interatrial-block-and-implications-for-new-onset-atrial-fibrillation
#4
Bryce Alexander, Jimmy MacHaalany, Brandon Lam, Henri van Rooy, Sohaib Haseeb, Adrian Kuchtaruk, Benedict Glover, Antoni Bayés de Luna, Adrian Baranchuk
Interatrial block (IAB) represents delay or block of conduction between the atria. IAB has been shown to predict the development or recurrence of atrial fibrillation (AF) in various clinical scenarios. Few studies have examined the correlation between coronary artery disease and the prevalence of IAB and its impact on AF. The aim of this study was to determine if specific coronary artery lesions (location and number) are associated with the presence of IAB and development of new-onset AF. Retrospective analysis of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) to our institution...
January 25, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28214496/new-diagnostic-modalities-in-the-evaluation-of-lymphedema
#5
REVIEW
Thomas F O'Donnell, John C Rasmussen, Eva M Sevick-Muraca
OBJECTIVE: Currently, lymphedema (LED) is typically diagnosed clinically on the basis of a patient's history and characteristic physical findings. Whereas the diagnosis of LED is sometimes confirmed by lymphoscintigraphy (LSG), the technique is limited in both its ability to identify disease and to guide therapy. Recent advancements provide opportunities for new imaging techniques not only to assist in the diagnosis of LED, based on anatomic changes, but also to assess contractile function and to guide therapeutic intervention...
March 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28214459/molecular-biomarkers-of-knee-pathology
#6
Vanessa Cuellar, Eric Strauss
The identification of biomarkers has become increasingly important in our fundamental understanding of the molecular basis for disease and subsequently in the advancement of modern medicine. Biomarkers have been identified in a plethora of normal and pathologic conditions and are most often found in blood, tissue, or synovial fluid. Orthopaedic research has more recently focused on biomarkers of cartilage and joint diseases, with an emphasis on understanding the molecular underpinnings of their pathophysiology...
January 2017: Bulletin of the Hospital for Joint Diseases
https://www.readbyqxmd.com/read/28214406/advancing-access-and-equity-the-vision-of-a-new-generation-in-cancer-control
#7
André M Ilbawi, Elizabeth Ayoo, Afsan Bhadelia, Runcie C W Chidebe, Temidayo Fadelu, Cristian A Herrera, Han Win Htun, Nauman Arif Jadoon, Oluwafunmilola W James, Leana May, Mauricio Maza, Mellany Murgor, Yetty M Nency, Chukwuma Oraegbunam, Mandi Pratt-Chapman, Xiaojian Qin, Danielle Rodin, Neha Tripathi, Zoe Wainer, Mei Ling Yap
No abstract text is available yet for this article.
February 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28214386/management-and-prognosis-of-hcc-in-the-elderly-results-of-an-in-field-multicenter-cohort-study
#8
Mauro Borzio, Elena Dionigi, Alessandro Vitale, Angelo Rossini, Massimo Marignani, Fabio Fornari, Susanna Vicari, Ilario De Sio, Fabio Farinati, Emanuela Bertolini, Filippo Oliveri, Gioacchino Leandro, Giampiero Francica, Mario Mitra, Barbara Omazzi, Sergio Boccia, Andrea Salmi, Anna Toldi, Rodolfo Sacco
AIMS: This multicentre cohort study evaluated the role of aging on clinical characteristics, treatment allocation, and outcome of new HCCs, in clinical practice. MATERIAL AND METHODS: From September 2008, 541 patients aged > 70 years old (elderly group), and 527 ≤ 70 years old (non elderly group) with newly diagnosed HCC were consecutively enrolled in 30 Italian centres. Differences in clinical characteristics and treatment allocation between groups were described by a multivariable logistic regression model measuring the inverse probability weight to meet the elderly group...
February 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28214236/are-hospital-ed-transfers-less-likely-among-nursing-home-residents-with-do-not-hospitalize-orders
#9
Taeko Nakashima, Yuchi Young, Wan-Hsiang Hsu
OBJECTIVES: This study aims to examine whether an advance directive "Do Not Hospitalize" (DNH) would be effective in reducing hospital/emergency department (ED) transfers. Similar effects in residents with dementia were also examined. DESIGN: Cross-sectional study. SETTING/SUBJECTS: New York State (NYS) nursing home residents (n = 43,024). MEASUREMENTS AND ANALYSIS: The Minimum Data Set 2.0 was used to address the study aims...
February 14, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28214110/pediatric-echocardiographic-nomograms-what-has-been-done-and-what-still-needs-to-be-done
#10
REVIEW
Massimiliano Cantinotti, Shelby Kutty, Eliana Franchi, Marco Paterni, Marco Scalese, Giorgio Iervasi, Martin Koestenberger
Nomograms are essential tools for quantification in pediatric echocardiography. In the last few years, multiple sources highlight that nomograms employed for decades presented significant numerical and methodological limitations. As a result, widely different ranges of normality were generated, thus creating confusion in estimation of several cardiac diseases. New nomograms have recently been generated, overcoming some of the gaps of previous research: wider sample sizes (including neonates/infants), solid statistical/methodological plan, and availability of new data (chamber dimensions, many functional parameters)...
January 19, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28214023/using-aequorin-probes-to-measure-ca-2-in-intracellular-organelles
#11
REVIEW
María Teresa Alonso, Macarena Rodríguez-Prados, Paloma Navas-Navarro, Jonathan Rojo-Ruiz, Javier García-Sancho
Aequorins are excellent tools for measuring intra-organellar Ca(2+) and assessing its role in physiological and pathological functions. Here we review targeting strategies to express aequorins in various organelles. We address critical topics such as probe affinity tuning as well as normalization and calibration of the signal. We also focus on bioluminescent Ca(2+) imaging in nucleus or mitochondria of living cells. Finally, recent advances with a new chimeric GFP-aequorin protein (GAP), which can be used either as luminescent or fluorescent Ca(2+) probe, are presented...
January 16, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28213985/capillary-dynamics-driven-by-molecular-self-layering
#12
Pingkeng Wu, Alex Nikolov, Darsh Wasan
Capillary dynamics is a ubiquitous everyday phenomenon. It has practical applications in diverse fields, including ink-jet printing, lab-on-a-chip, biotechnology, and coating. Understanding capillary dynamics requires essential knowledge on the molecular level of how fluid molecules interact with a solid substrate (the wall). Recent studies conducted with the surface force apparatus (SFA), atomic force microscope (AFM), and statistical mechanics simulation revealed that molecules/nanoparticles confined into the film/wall surfaces tend to self-layer into 2D layer/s and even 2D in-layer with increased confinement and fluid volume fraction...
February 10, 2017: Advances in Colloid and Interface Science
https://www.readbyqxmd.com/read/28213833/molecular-imaging-in-synthetic-biology-and-synthetic-biology-in-molecular-imaging
#13
REVIEW
Assaf A Gilad, Mikhail G Shapiro
Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies...
February 17, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28213601/protocol-for-a-scoping-review-of-post-trial-extensions-of-randomised-controlled-trials-using-individually-linked-administrative-and-registry-data
#14
Tiffany Fitzpatrick, Laure Perrier, Andrea C Tricco, Sharon E Straus, Peter Jüni, Merrick Zwarenstein, Lisa M Lix, Mark Smith, Laura C Rosella, David A Henry
INTRODUCTION: Well-conducted randomised controlled trials (RCTs) provide the least biased estimates of intervention effects. However, RCTs are costly and time-consuming to perform and long-term follow-up of participants may be hampered by lost contacts and financial constraints. Advances in computing and population-based registries have created new possibilities for increasing the value of RCTs by post-trial extension using linkage to routinely collected administrative/registry data in order to determine long-term interventional effects...
February 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28213543/functional-characterization-of-a-28-kb-catabolic-island-from-pseudomonas-sp-m1-involved-in-biotransformation-of-%C3%AE-myrcene-and-related-plant-derived-volatiles
#15
Pedro Soares-Castro, Pedro Montenegro-Silva, Hermann J Heipieper, Pedro M Santos
Pseudomonas sp. M1 is able to mineralize highly hydrophobic and recalcitrant compounds such as benzene, phenol and their methylated/halogenated derivatives, as well as the backbone of several monoterpenes. The ability to use such spectrum of compounds as sole carbon source is, most probably, associated with a genetic background evolved under different environmental constraints. The outstanding performance of M1 strain regarding β-myrcene catabolism was elucidated in this work, with focus on the biocatalytical potential of β-myrcene-associated core-code, comprised in a 28-kb genomic island (GI), predicted to be organized in 8 transcriptional units...
February 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28213527/advancing-viral-rna-structure-prediction-measuring-the-thermodynamics-of-pyrimidine-rich-internal-loops
#16
Andy Phan, Katherine Mailey, Jessica Sakai, Xiaobo Gu, Susan J Schroeder
Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased towards small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with more than 6 nucleotides that occur frequently in viral RNA...
February 17, 2017: RNA
https://www.readbyqxmd.com/read/28213315/focal-adhesion-kinase-signaling-in-unexpected-places
#17
REVIEW
Elizabeth G Kleinschmidt, David D Schlaepfer
Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase first identified at extracellular matrix and integrin receptor cell adhesion sites and is a key regulator of cell movement. FAK is activated by a variety of stimuli. Herein, we discuss advances in conformational-associated FAK activation and dimerization mechanisms. Additionally, new roles have emerged for FAK signaling at cell adhesions, adherens junctions, endosomes, and the nucleus. In light of these new findings, we review how FAK activation at these sites is connected to the regulation of integrin recycling-activation, vascular permeability, cell survival, and transcriptional regulation, respectively...
February 14, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28213254/chips-how-to-build-and-implement-fluidic-devices-in-flow-based-systems
#18
Víctor Cerdà, Jessica Avivar, Daniel Moreno
The development of automatic analyzers based on flow techniques involves the use and continuous innovation of fluidic devices. New trends tend toward miniaturization of sophisticated fluidic platforms requiring continuous advances in this field. The availability of a mechanic and electronic workshop together with the know-how to build new fluidic devices provides the tools for the creation of innovative instrumentation and stimulates the creativity of analytical chemists. Thus, in this review we present how to build and use flow-based fluidic devices, together with the tools required, such as computerized controlled lathes, milling machines, laser engraver machines, low-temperature co-fired ceramics technology and 3D printers, highlighting their strong and weak points...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28212967/decision-making-on-medical-innovations-in-a-changing-health-care-environment-insights-from-accountable-care-organizations-and-payers-on-personalized-medicine-and-other-technologies
#19
Julia R Trosman, Christine B Weldon, Michael P Douglas, Patricia A Deverka, John B Watkins, Kathryn A Phillips
BACKGROUND: New payment and care organization approaches, such as those of accountable care organizations (ACOs), are reshaping accountability and shifting risk, as well as decision making, from payers to providers, within the Triple Aim context of health reform. The Triple Aim calls for improving experience of care, improving health of populations, and reducing health care costs. OBJECTIVES: To understand how the transition to the ACO model impacts decision making on adoption and use of innovative technologies in the era of accelerating scientific advancement of personalized medicine and other innovations...
January 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28212889/inhibition-of-proliferation-and-invasion-in-2d-and-3d-models-by-2-methoxyestradiol-in-human-melanoma-cells
#20
R R Massaro, F Faião-Flores, V W Rebecca, S Sandri, D K Alves-Fernandes, P C Pennacchi, K S M Smalley, S S Maria-Engler
Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and CyclinB1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assays, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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