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https://www.readbyqxmd.com/read/28337200/metabolic-hallmarks-of-tumor-and-immune-cells-in-the-tumor-microenvironment
#1
REVIEW
Kathrin Renner, Katrin Singer, Gudrun E Koehl, Edward K Geissler, Katrin Peter, Peter J Siska, Marina Kreutz
Cytotoxic T lymphocytes and NK cells play an important role in eliminating malignant tumor cells and the number and activity of tumor-infiltrating T cells represent a good marker for tumor prognosis. Based on these findings, immunotherapy, e.g., checkpoint blockade, has received considerable attention during the last couple of years. However, for the majority of patients, immune control of their tumors is gray theory as malignant cells use effective mechanisms to outsmart the immune system. Increasing evidence suggests that changes in tumor metabolism not only ensure an effective energy supply and generation of building blocks for tumor growth but also contribute to inhibition of the antitumor response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28336242/pacritinib-versus-best-available-therapy-for-the-treatment-of-myelofibrosis-irrespective-of-baseline-cytopenias-persist-1-an-international-randomised-phase-3-trial
#2
Ruben A Mesa, Alessandro M Vannucchi, Adam Mead, Miklos Egyed, Anita Szoke, Aleksandr Suvorov, Janos Jakucs, Andrew Perkins, Ritam Prasad, Jiri Mayer, Judit Demeter, Peter Ganly, Jack W Singer, Huafeng Zhou, James P Dean, Peter A Te Boekhorst, Jyoti Nangalia, Jean-Jacques Kiladjian, Claire N Harrison
BACKGROUND: Available therapies for myelofibrosis can exacerbate cytopenias and are not indicated for patients with severe thrombocytopenia. Pacritinib, which inhibits both JAK2 and FLT3, induced spleen responses with limited myelosuppression in phase 1/2 trials. We aimed to assess the efficacy and safety of pacritinib versus best available therapy in patients with myelofibrosis irrespective of baseline cytopenias. METHODS: This international, multicentre, randomised, phase 3 trial (PERSIST-1) was done at 67 sites in 12 countries...
March 20, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28335733/effects-of-short-term-hyperoxia-on-erythropoietin-levels-and-microcirculation-in-critically-ill-patients-a-prospective-observational-pilot-study
#3
Abele Donati, Elisa Damiani, Samuele Zuccari, Roberta Domizi, Claudia Scorcella, Massimo Girardis, Alessia Giulietti, Arianna Vignini, Erica Adrario, Rocco Romano, Laura Mazzanti, Paolo Pelaia, Mervyn Singer
BACKGROUND: The normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of 'relative hypoxia' which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients. METHODS: In this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO2) ≤0...
March 23, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28334336/ophthalmic-screening-patterns-among-youths-with-diabetes-enrolled-in-a-large-us-managed-care-network
#4
Sophia Y Wang, Chris A Andrews, Thomas W Gardner, Michael Wood, Kanakadurga Singer, Joshua D Stein
Importance: Ophthalmic screening to check for diabetic retinopathy (DR) is important to prevent vision loss in persons with diabetes. The American Academy of Ophthalmology recommends that ophthalmic screening for DR occur beginning at 5 years after initial diabetes diagnosis for youths with type 1 diabetes; the American Diabetes Association recommends screening of youths with type 2 diabetes at the time of initial diagnosis. To our knowledge, it is unknown to what extent youths with diabetes obtain eye examinations in accordance with these guidelines...
March 23, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28333757/the-septic-shock-3-0-definition-and-trials-a-vasopressin-and-septic-shock-trial-experience
#5
James A Russell, Terry Lee, Joel Singer, John H Boyd, Keith R Walley
OBJECTIVES: The Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L...
March 22, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28329870/application-of-imaging-techniques-to-cases-of-drug-induced-crystal-nephropathy-in-preclinical-studies
#6
B Lenz, A Brink, M Siam, A De Paepe, S Bassett, A Eichinger-Chapelon, P Maliver, R Neff, U Niederhauser, B Steinhuber, R Zurbach, T Singer, C Funk, F Schuler, M Albassam, S Schadt
A number of drugs can cause precipitates within renal tubules leading to crystal nephropathy. Crystal nephropathy is usually an exposure-related finding and is not uncommon in preclinical studies, where high doses are tested. An understanding of the nature of precipitates is important for human risk assessment and further development. Our aim was to investigate the ability of various imaging techniques to detect the presence of drugs or metabolites in renal crystals. We applied matrix-assisted laser desorption/ionization - Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) imaging, Raman and infrared microspectroscopy, scanning electron microscopy coupled with energy dispersive X-ray (SEM/EDX) spectroscopy and standard histopathology to cases of drug-induced crystal nephropathy, induced in rodents and primates by four compounds...
February 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28328668/burn-wound-healing-and-tissue-engineering
#7
Adam J Singer, Steven T Boyce
No abstract text is available yet for this article.
March 16, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28325869/s-jonathan-singer-a-man-who-loved-ideas-and-detested-walls
#8
Russell F Doolittle
No abstract text is available yet for this article.
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28325303/inhibition-of-egf-uptake-by-nephrotoxic-antisense-drugs-in%C3%A2-vitro-and-implications-for-preclinical-safety-profiling
#9
Annie Moisan, Marcel Gubler, Jitao David Zhang, Yann Tessier, Kamille Dumong Erichsen, Sabine Sewing, Régine Gérard, Blandine Avignon, Sylwia Huber, Fethallah Benmansour, Xing Chen, Roberto Villaseñor, Annamaria Braendli-Baiocco, Matthias Festag, Andreas Maunz, Thomas Singer, Franz Schuler, Adrian B Roth
Antisense oligonucleotide (AON) therapeutics offer new avenues to pursue clinically relevant targets inaccessible with other technologies. Advances in improving AON affinity and stability by incorporation of high affinity nucleotides, such as locked nucleic acids (LNA), have sometimes been stifled by safety liabilities related to their accumulation in the kidney tubule. In an attempt to predict and understand the mechanisms of LNA-AON-induced renal tubular toxicity, we established human cell models that recapitulate in vivo behavior of pre-clinically and clinically unfavorable LNA-AON drug candidates...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28324604/imaging-the-dynamics-of-cell-wall-polymer-deposition-in-the-unicellular-model-plant-penium-margaritaceum
#10
David Domozych, Anna Lietz, Molly Patten, Emily Singer, Berke Tinaz, Sandra C Raimundo
The unicellular green alga, Penium margaritaceum, represents a novel and valuable model organism for elucidating cell wall dynamics in plants. This organism's cell wall contains several polymers that are highly similar to those found in the primary cell walls of land plants. Penium is easily grown in laboratory culture and is effectively manipulated in various experimental protocols including microplate assays and correlative microscopy. Most importantly, Penium can be live labeled with cell wall-specific antibodies or other probes and returned to culture where specific cell wall developmental events can be monitored...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28322222/white-matter-maturation-is-associated-with-the-emergence-of-theory-of-mind-in-early-childhood
#11
Charlotte Grosse Wiesmann, Jan Schreiber, Tania Singer, Nikolaus Steinbeis, Angela D Friederici
The ability to attribute mental states to other individuals is crucial for human cognition. A milestone of this ability is reached around the age of 4, when children start understanding that others can have false beliefs about the world. The neural basis supporting this critical step is currently unknown. Here, we relate this behavioural change to the maturation of white matter structure in 3- and 4-year-old children. Tract-based spatial statistics and probabilistic tractography show that the developmental breakthrough in false belief understanding is associated with age-related changes in local white matter structure in temporoparietal regions, the precuneus and medial prefrontal cortex, and with increased dorsal white matter connectivity between temporoparietal and inferior frontal regions...
March 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28320167/caffeine-creatine-grin2a-and-parkinson-s-disease-progression
#12
David K Simon, Cai Wu, Barbara C Tilley, Katja Lohmann, Christine Klein, Haydeh Payami, Anne-Marie Wills, Michael J Aminoff, Jacquelyn Bainbridge, Richard Dewey, Robert A Hauser, Susen Schaake, Jay S Schneider, Saloni Sharma, Carlos Singer, Caroline M Tanner, Daniel Truong, Peng Wei, Pei Shieen Wong, Tianzhong Yang
Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28317509/using-claims-data-to-examine-hospital-readmission-risk-in-patients-with-schizophrenia-and-comorbid-marijuana-use-disorders
#13
Mary E Slaughter, Coreen Farris, Mark I Singer, Kathleen A Smyth, Mendel E Singer
OBJECTIVE: Few epidemiologic studies have examined marijuana use disorder and repeated hospitalizations related to schizophrenia. To address this gap, this study examines time to readmission by indicators for recent marijuana use disorder in the presence of alcohol use disorder (AUD) and other drug use disorder. METHOD: Our sample consisted of 4,349 patients with a primary diagnosis of schizophrenia spectrum disorder (SSD) in 2005 in individually linked California Health Care Cost and Utilization Project (CA HCUP) data...
March 2017: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/28317215/practice-requirements-for-psychotherapeutic-treatment-of-cancer-patients-in-the-outpatient-setting-a-survey-among-certified-psychotherapists-in-germany
#14
Susanne Singer, Erika Kojima, Jutta Beckerle, Bernhard Kleining, Erhard Schneider, Katrin Reuter
PURPOSE: The aim of this study was to delineate the challenges psychotherapists encounter when they treat cancer patients and how they organise their practices to be able to treat them. METHODS: A random sample of certified psychotherapists, licensed by the health authorities, with training in psycho-oncology, was asked to complete a questionnaire covering the following issues: therapists' qualifications, organisation of the practice, dealing with appointment cancellations, financing, and networking...
March 20, 2017: Psycho-oncology
https://www.readbyqxmd.com/read/28314658/management-of-chronic-inducible-urticaria-according-to-the-guidelines-a-prospective-controlled-study
#15
Emek Kocatürk, Pelin Kuteyla Can, Pırıl Etikan Akbas, Mehmet Copur, Ece Nur Degirmentepe, Kübra Kızıltac, Ralfi Singer
BACKGROUND: The recommended treatment approach in chronic inducible urticarias (CIndU) is the same as that for chronic spontaneous urticaria (CSU). But there is a lack of controlled trials assessing efficacy of available treatment options. OBJECTIVE: We aimed to evaluate the efficacy of treatment algorithm recommended by the guidelines and comparison of treatment responses in CIndU vs CSU. METHODS: This prospective parallel group controlled study included 70 CIndU and 66 CSU patients...
March 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28306595/update-on-maintenance-therapy-for-granulomatosis-with-polyangiitis-and-microscopic-polyangiitis
#16
Ora Singer, W Joseph McCune
PURPOSE OF REVIEW: The antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitides are a group of rare systemic diseases. The past several years have seen major therapeutic advances in the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The success rate in induction of remission is high, but reducing the high incidence of relapses remains a therapeutic challenge. RECENT FINDINGS: Studies have shown no improvement in relapse rates in GPA and MPA over the past 2 decades...
March 16, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28302673/pneumococcal-vaccine-response-after-exposure-to-parasites-in-utero-in-infancy-or-mid-childhood
#17
Monica Nayakwadi Singer, Claire Heath, Jackson Muinde, Virginia Gildengorin, Francis M Mutuku, David Vu, Dunstan Mukoko, Christopher L King, Indu J Malhotra, Charles H King, A Desirée LaBeaud
BACKGROUND AND OBJECTIVE: Streptococcus pneumoniae is a leading cause of mortality before age 5, but few studies examine details of childhood response to pneumococcal vaccine in less-developed settings. Although malnutrition, HIV, and concurrent infections can impair response, evidence suggests that chronic parasitic infections can also contribute to poor vaccination results. The objective of this study was to determine whether response to pneumococcal vaccine varied among children either exposed to parasitic infections in utero, previously infected in infancy, or infected at the time of immunization...
March 16, 2017: Pediatrics
https://www.readbyqxmd.com/read/28301697/managing-opioid-withdrawal-for-hospital-patients-in-custody
#18
Connie R Shi, Manjinder S Kandola, Matthew Tobey, Elizabeth Singer
Dr. Brown, a hospitalist, admits Mark, a patient transferred from a local jail for management of cellulitis. The patient, who was taken into custody two days prior to hospital admission, has a history of intravenous heroin use. Mark explains that he had been prescribed buprenorphine-naloxone maintenance therapy for opioid use disorder for several years prior to being arrested and had not used other opioids during that time. As a policy, the jail where Mark is detained does not prescribe opioid agonists, and his maintenance therapy was stopped upon his arrival there...
March 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28296810/activation-associated-accelerated-apoptosis-of-memory-b-cells-in-critically-ill-patients-with-sepsis
#19
Manu Shankar-Hari, David Fear, Paul Lavender, Tracey Mare, Richard Beale, Chad Swanson, Mervyn Singer, Jo Spencer
OBJECTIVE: Sepsis is life-threatening organ dysfunction due to dysregulated host responses to infection. Current knowledge of human B-cell alterations in sepsis is sparse. We tested the hypothesis that B-cell loss in sepsis involves distinct subpopulations of B cells and investigated mechanisms of B-cell depletion. DESIGN: Prospective cohort study. SETTING: Critical care units. PATIENTS: Adult sepsis patients without any documented immune comorbidity...
March 14, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28295562/locked-nucleic-acid-lna-based-single-stranded-oligonucleotides-are-not-genotoxic
#20
Guérard Melanie, Zeller Andreas, Koller Erich, Marchand Christine, Müller B Martina, Weile Christian, Schuler Franz, Singer Thomas, Tessier Yann
Over the last decade, single stranded oligonucleotides (ON) have gained increased attention as a new drug modality. Because the assessment of genotoxicity risk during early development of pharmaceuticals is essential, we evaluated the potential of locked nucleic acids (LNA)-ONs to induce DNA damage in L5178Y tk(+/-) cells both with the mouse lymphoma assay (MLA) and the micronucleus test (MNT). Further, the MLA was performed to assess gene and chromosome mutation over 3 and 24h (± metabolic activation). In addition, the MNT was performed to assess, in addition, a potential aneugenic liability...
March 10, 2017: Environmental and Molecular Mutagenesis
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