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https://www.readbyqxmd.com/read/29785570/phase-1b-investigation-of-the-mek-inhibitor-binimetinib-in-patients-with-advanced-or-metastatic-biliary-tract-cancer
#1
R S Finn, D H Ahn, M M Javle, B R Tan, C D Weekes, J C Bendell, A Patnaik, G N Khan, D Laheru, R Chavira, J Christy-Bittel, E Barrett, M B Sawyer, Tanios S Bekaii-Saab
Background The MAPK pathway plays a central role in regulation of several cellular processes, and its dysregulation is a hallmark of biliary tract cancer (BTC). Binimetinib (MEK162), a potent, selective oral MEK1/2 inhibitor, was assessed in patients with advanced BTC. Patients and Methods An expansion cohort study in patients who received ≤1 line of therapy for advanced BTC was conducted after determination of the maximum tolerated dose in this Phase 1 trial. Patients received binimetinib 60 mg twice daily...
May 22, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29771386/immunotherapy-in-cns-cancers-the-role-of-immune-cell-trafficking
#2
Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden...
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29753454/response-of-a-local-hospital-to-a-burn-disaster-contributory-factors-leading-to-zero-mortality-outcomes
#3
Eng-Kean Yeong, Ciaran P O'Boyle, Hui-Fu Huang, Hao-Chih Tai, Yen-Chun Hsu, Shu-Yang Chuang, Yu-Feng Wu, Che-Wei Chang, Tom J Liu, Hong-Shiee Lai
OBJECTIVE: To investigate the outcomes of a local healthcare system in managing a burn mass casualty incident (BMCI). METHODS: Thirty-three victims admitted to the National Taiwan University Hospital within 96h of the explosion were included in the study. Data were recorded on: patient demographics, Baux score, laboratory data, management response, treatment strategies, and outcomes. Case notes from June 27, 2015 to November 2015 were reviewed with a focus on fluid resuscitation, ventilation support, nutrition, infection control, sepsis treatment, and wound closure plan...
May 9, 2018: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/29752757/subcutaneous-immunotherapy-suppresses-th2-inflammation-and-induces-neutralizing-antibodies-but-sublingual-immunotherapy-suppresses-airway-hyperresponsiveness-in-grass-pollen-mouse-models-for-allergic-asthma
#4
Laura Hesse, Uilke Brouwer, Arjen H Petersen, Renée Gras, Lisette Bosman, Jens Brimnes, Joanne N G Oude Elberink, Antoon J M van Oosterhout, Martijn C Nawijn
BACKGROUND: Both subcutaneous and sublingual allergen immunotherapy (SCIT and SLIT) have been shown to effectively suppress allergic manifestations upon allergen exposure, providing long term relief from symptoms in allergic disorders including allergic asthma. Clinical studies directly comparing SCIT and SLIT report a different kinetics and magnitude of immunological changes induced during treatment. Comparative studies into the mechanisms underlying immune suppression in SCIT and SLIT are lacking...
May 12, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29735482/cd71-erythroid-suppressor-cells-promote-fetomaternal-tolerance-through-arginase-2-and-pdl-1
#5
Cole Delyea, Najmeh Bozorgmehr, Petya Koleva, Garett Dunsmore, Shima Shahbaz, Vivian Huang, Shokrollah Elahi
Survival of the allogeneic pregnancy depends on the maintenance of immune tolerance to paternal alloantigens at the fetomaternal interface. Multiple localized mechanisms contribute to the fetal evasion from the mother's immune rejection as the fetus is exposed to a wide range of stimulatory substances such as maternal alloantigens, microbes and amniotic fluids. In this article, we demonstrate that CD71+ erythroid cells are expanded at the fetomaternal interface and in the periphery during pregnancy in both humans and mice...
May 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29729496/progressive-increase-in-allergen-concentration-abrogates-immune-tolerance-in-ovalbumin-induced-murine-model-of-chronic-asthma
#6
Gurupreet S Sethi, Amarjit S Naura
Persistent inflammation and remodeling of airways are the major hallmarks of asthma. Though airway inflammation diminishes in ovalbumin (OVA)-based mouse model of chronic asthma owing to immune-tolerance linked with repeated allergen exposure, which limits the application of the disease model. Accordingly, the present study was designed to develop a murine model of chronic asthma which presents persistent airway inflammation coupled with remodeling traits. Herein, OVA-sensitized BALB/c mice were challenged with increasing (modified protocol) or constant concentration (conventional protocol) of the allergen for 6 weeks; 3 times/week...
May 2, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29709915/hydrogen-peroxide-reducing-factor-released-by-pc12d-cells-increases-cell-tolerance-against-oxidative-stress
#7
Asami Muraishi, Emi Haneta, Yoshiro Saito, Yutaka Hitomi, Mamoru Sano, Noriko Noguchi
PC12D cells, a subline of rat adrenal pheochromocytoma PC12 cells, extend neurites rapidly in response to differentiation stimuli and are used to investigate the molecular mechanisms of neurite extension. In the present study, we found significant tolerance of PC12D cells against Parkinson's disease-related stimuli such as dopamine and 6-hydroxydopamine; this tolerance was significantly decreased by a change in the medium. Conditioned medium from PC12D cells induced tolerance against oxidative stress, which suggests that cytoprotective factor may be released by PC12D cells into the culture medium...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29705882/severe-peritoneal-sclerosis-after-repeated-pressurized-intraperitoneal-aerosol-chemotherapy-with-oxaliplatin-pipac-ox-report-of-two-cases-and-literature-survey
#8
M Graversen, S Detlefsen, P Pfeiffer, L Lundell, M B Mortensen
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new laparoscopic administration of chemotherapy for peritoneal metastasis (PM). PIPAC is repeated every 5th week, and seems to stabilize or improve quality of life, and might improve survival. So far, PIPAC has been well tolerated. With this paper, we aim to highlight a potential severe adverse reaction, as we describe the first cases of severe peritoneal sclerosis (SPS) caused by PIPAC. Patients with isolated PM were included in a prospective PIPAC protocol...
April 28, 2018: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/29686857/population-specific-transcriptional-differences-associated-with-freeze-tolerance-in-a-terrestrial-worm
#9
Tjalf E de Boer, Dick Roelofs, Riet Vooijs, Martin Holmstrup, Mónica J B Amorim
Enchytraeus albidus is a terrestrial earthworm widespread along the coasts of northern Europe and the Arctic. This species tolerates freezing of body fluids and survives winters in a frozen state. Their acclimatory physiological mechanisms behind freeze tolerance involve increased fluidity of membrane lipids during cold exposure and accumulation of cryoprotectants (glucose) during the freezing process. Gene regulatory processes of these physiological responses have not been studied, partly because no gene expression tools were developed...
April 2018: Ecology and Evolution
https://www.readbyqxmd.com/read/29576392/clinical-outcome-and-cerebrospinal-fluid-profiles-in-patients-with-tick-borne-encephalitis-and-prior-vaccination-history
#10
Thorsten Lenhard, Daniela Ott, Nurith J Jakob, Francisco Martinez-Torres, Caspar Grond-Ginsbach, Uta Meyding-Lamadé
BACKGROUND: Tick-borne encephalitis (TBE) is endemic in southern and eastern districts of Germany. Approximately 10-14% of the infected individuals suffer from long-term disability and in 1.5-3.6% the course is fatal. Two well-tolerated vaccines are available, which provide high protection and which have been confirmed in several field studies. Here we investigate clinical course, long-term outcome and cerebrospinal fluid (CSF) characteristics of TBE cases with a prior history of any vaccination as well as real vaccination breakthrough (VBT)...
March 1, 2018: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/29500050/spiculosiphon-oceana-foraminifera-a-new-bio-indicator-of-acidic-environments-related-to-fluid-emissions-of-the-zannone-hydrothermal-field-central-tyrrhenian-sea
#11
Letizia Di Bella, Michela Ingrassia, Virgilio Frezza, Francesco L Chiocci, Raffaella Pecci, Rossella Bedini, Eleonora Martorelli
The new record of a shallow-water submarine hydrothermal field (<150 m w.d.) in the western Mediterranean Sea (Tyrrhenian Sea, Italy) allows us to study CO2 fluid impact on benthic foraminifers. Benthic foraminifers calcification process is sensitive to ocean acidification and to local chemical and physical parameters of seawater and pore water. Thus, foraminifers can record specific environmental conditions related to hydrothermal fluids, but at present their response to such activity is poorly defined...
May 2018: Marine Environmental Research
https://www.readbyqxmd.com/read/29435291/efficacy-and-safety-of-doceaqualip-in-a-patient-with-locally-advanced-cervical-cancer-a-case-report
#12
Rammohan Prasanna, Deepak Bunger, Mujtaba A Khan
The standard of care for locally advanced cervical cancer has been the combination of a taxane with platinum based therapy. Conventional docetaxel is known to cause hypersensitivity reactions, fluid retention and other toxicities due to polysorbate-80 and ethanol. Corticosteroid premedication prior to docetaxel administration is required to prevent these toxicities, however, toxicities are still observed, sometimes fatal, despite premedication. DoceAqualip, a nanosomal docetaxel lipid suspension, developed with lipids generally regarded as safe (GRAS) by the US Food and Drug Administration, is devoid of polysorbate-80 and ethanol...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29431121/methotrexate-limits-inflammation-through-an-a20-dependent-cross-tolerance-mechanism
#13
Cristina Municio, Ángeles Dominguez-Soto, Sara Fuentelsaz-Romero, Amalia Lamana, Nuria Montes, Víctor D Cuevas, Raquel García Campos, José L Pablos, Isidoro González-Álvaro, Amaya Puig-Kröger
OBJECTIVES: Methotrexate (MTX) is the anchor drug for treatment of rheumatoid arthritis (RA), but the mechanism of its anti-inflammatory action is not fully understood. In RA, macrophages display a proinflammatory polarisation profile that resembles granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages and the response to MTX is only observed in thymidylate synthase+ GM-CSF-dependent macrophages. To determine the molecular basis for the MTX anti-inflammatory action, we explored toll-like receptor (TLR), RA synovial fluid (RASF) and tumour necrosis factor receptor (TNFR)-initiated signalling in MTX-exposed GM-CSF-primed macrophages...
May 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29428309/mycoplasma-genitalium-can-modulate-the-local-immune-response-in-patients-with-endometriosis
#14
Guilherme B Campos, Lucas M Marques, Izadora S Rezende, Maysa S Barbosa, Mauricio S Abrão, Jorge Timenetsky
OBJECTIVE: To detect Mollicutes in women with endometriosis and healthy peritoneal tissues and evaluate the participation of these bacteria in the immune response during endometriosis. DESIGN: Cross-sectional study. SETTING: University hospitals. PATIENT (S): Women with endometriosis (n = 73) and without endometriosis (n = 31). INTERVENTION(S): Endocervical swabs, peritoneal fluid, and biopsied lesions of endometriosis of women with endometriosis (study group) and healthy peritoneal tissues (control group) were collected during surgery...
March 2018: Fertility and Sterility
https://www.readbyqxmd.com/read/29425781/single-fluid-filled-intragastric-balloon-safe-and-effective-for-inducing-weight-loss-in-a-real-world-population
#15
Eric J Vargas, Carl M Pesta, Ahmad Bali, Eric Ibegbu, Fateh Bazerbachi, Rachel L Moore, Vivek Kumbhari, Reem Z Sharaiha, Trace W Curry, Gina DosSantos, Ramsey Schmitz, Abhishek Agnihotri, Aleksey A Novikov, Tracy Pitt, Margo K Dunlap, Andrea Herr, Louis Aronne, Erin Ledonne, Hoda C Kadouh, Lawrence J Cheskin, Manpreet S Mundi, Andres Acosta, Christopher J Gostout, Barham K Abu Dayyeh
BACKGROUND & AIMS: The Orbera intragastric balloon (OIB) is a single fluid-filled intragastric balloon approved for induction of weight loss and treatment of obesity. However, little is known about the effectiveness and safety of outside clinical trials, and since approval, the Food and Drug Administration has issued warnings to health care providers about risk of balloon hyperinflation requiring early removal, pancreatitis, and death. We analyzed data on patients who have received the OIB since its approval to determine its safety, effectiveness, and tolerance in real-world clinical settings...
February 7, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29393671/importance-of-maternal-diet-in-the-training-of-the-infant-s-immune-system-during-gestation-and-lactation
#16
P V Jeurink, K Knipping, F Wiens, K Barańska, B Stahl, J Garssen, B Krolak-Olejnik
Latest forecasts predict that half of the European population will be allergic within the coming 15 years, with food allergies contributing substantially to the total burden; preventive measures are urgently needed. Unfortunately, all attempted alimentary strategies for primary prevention of allergic diseases through allergen avoidance so far have failed. This also holds true for the prevention of food allergies in breastfed infants by the common practice of excluding certain foods with allergenic potential from the maternal diet...
February 2, 2018: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/29367271/functional-plasticity-of-the-gut-and-the-malpighian-tubules-underlies-cold-acclimation-and-mitigates-cold-induced-hyperkalemia-in-drosophila-melanogaster
#17
Gil Y Yerushalmi, Lidiya Misyura, Heath A MacMillan, Andrew Donini
At low temperatures, Drosophila , like most insects, lose the ability to regulate ion and water balance across the gut epithelia, which can lead to a lethal increase of [K+ ] in the hemolymph (hyperkalemia). Cold acclimation, the physiological response to a prior low temperature exposure, can mitigate or entirely prevent these ion imbalances, but the physiological mechanisms that facilitate this process are not well understood. Here, we test whether plasticity in the ionoregulatory physiology of the gut and Malpighian tubules of Drosophila may aid in preserving ion homeostasis in the cold...
March 19, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29358315/effector-t-cells-in-multiple-sclerosis
#18
REVIEW
Belinda J Kaskow, Clare Baecher-Allan
Multiple sclerosis (MS) has long been considered a CD4 T-cell disease, primarily because of the findings that the strongest genetic risk for MS is the major histocompatibility complex (MHC) class II locus, and that T cells play a central role in directing the immune response. The importance that the T helper (Th)1 cytokine, interferon γ (IFN-γ), and the Th17 cytokine, interleukin (IL)-17, play in MS pathogenesis is indicated by recent clinical trial data by the enhanced presence of Th1/Th17 cells in central nervous system (CNS) tissue, cerebrospinal fluid (CSF), and blood, and by research on animal models of MS, such as experimental autoimmune encephalomyelitis (EAE)...
April 2, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29341311/decreased-thermal-sweating-of-central-sudomotor-mechanism-in-african-and-korean-men
#19
Jeong Beom Lee, Jeong Ho Kim
OBJECTIVE: Tropical natives sweat less and preserve more body fluid than temperate natives, tolerating heat stress. However, the mechanisms involved in such sweating reduction have not been fully elucidated. We examined the sudomotor responses of men of African (n = 36) and Korean (n = 41) ancestry during hot water (43 °C) leg immersion (central sudomotor response). Correlations between mean body temperature, basal metabolic rate (BMR), and sweat rate were also examined. METHODS: All procedures were done in an automated climate chamber...
January 17, 2018: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/29219787/modification-of-the-biomedicus-centrifugal-pump-to-provide-continuous-irrigation-for-neuroendoscopy-technical-note
#20
Joyce Koueik, Brandon G Rocque, Jordan Henry, Taryn Bragg, Jennifer Paul, Bermans J Iskandar
Continuous irrigation is an important adjunct for successful intraventricular endoscopy, particularly for complex cases. It allows better visualization by washing out blood and debris, improves navigation by expanding the ventricles, and assists with tissue dissection. A method of irrigation delivery using a centrifugal pump designed originally for cardiac surgery is presented. The BioMedicus centrifugal pump has the desirable ability to deliver a continuous laminar flow of fluid that excludes air from the system...
February 2018: Journal of Neurosurgery. Pediatrics
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