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https://www.readbyqxmd.com/read/29144985/a-phase-1-2-study-of-rigosertib-in-patients-with-myelodysplastic-syndromes-mds-and-mds-progressed-to-acute-myeloid-leukemia
#1
Shyamala C Navada, Steven M Fruchtman, Rosalie Odchimar-Reissig, Erin P Demakos, Michael E Petrone, Patrick S Zbyszewski, James F Holland, Lewis R Silverman
This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m(2)/day in 14-day cycles...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29143665/cardiopulmonary-and-inflammatory-biomarkers-in-heartworm-disease
#2
REVIEW
Elena Carretón, Rodrigo Morchón, José Alberto Montoya-Alonso
In heartworm disease, several biomarkers of cardiopulmonary injury and inflammatory activity have been studied during the recent years. D-dimer is a fibrin degradation product present after a clot is degraded, which has been reported to provide support for the diagnosis of pulmonary thromboembolism in heartworm disease. Furthermore, concentrations increment with increased disease severity and during the adulticide treatment. This increase in concentration has proved to be valuable. Cardiac biomarkers troponin I, myoglobin and NT-proBNP demonstrated presence of myocardial injury and heart failure, especially in chronic infections, which in some cases, slightly improve after the adulticide treatment...
November 9, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29142492/early-changes-in-platelet-size-and-number-in-patients-with-acute-coronary-syndrome
#3
Zora Sušilović Grabovac, Darija Baković, Mislav Lozo, Irena Pintarić, Željko Dujić
A strong relationship exists between acute coronary syndrome (ACS) and platelets (PLTs) volume. Mean platelet volume (MPV) is a parameter of PLT functions and a marker for increased PLT activation. The aim of this study was to determine early changes in number of total PLT and MPV in different manifestation of ACS and to find out predictive value of MPV in the spectrum of ACS. This was a prospective study. One hundred thirty-four ACS patients were enrolled, 76 of them finished the study. PLT and MPV in patients with unstable angina, non-ST elevation, and ST elevation myocardial infarctions were determined on arrival and 1, 3, 72 hours, and 7 days after the admission to hospital...
December 2017: International Journal of Angiology: Official Publication of the International College of Angiology, Inc
https://www.readbyqxmd.com/read/29142132/identification-of-a-small-molecule-that-compromises-the-structural-integrity-of-viroplasms-and-rotavirus-double-layered-particles
#4
Catherine Eichwald, Giuditta De Lorenzo, Elisabeth M Schraner, Guido Papa, Michela Bollati, Paolo Swuec, Matteo de Rosa, Mario Milani, Eloise Mastrangelo, Mathias Ackermann, Oscar R Burrone, Francesca Arnoldi
Despite the availability of two attenuated vaccines, rotavirus (RV) gastroenteritis remains an important cause of mortality among children in developing countries causing about 215,000 infant deaths annually. Currently, there are no specific antiviral therapies available. RV is a non-enveloped virus with a segmented double-stranded RNA genome. Viral genome replication and assembly of transcriptionally active double-layered particles (DLPs) take place in cytoplasmic viral structures called viroplasms. In this study, we describe strong impairment of the early stages of RV replication induced by a small molecule known as RNA polymerase III inhibitor, ML-60218 (ML)...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142122/adaptive-immune-responses-following-senecavirus-a-infection-in-pigs
#5
Mayara F Maggioli, Steve Lawson, Marcelo de Lima, Lok R Joshi, Tatiane C Faccin, Fernando V Bauermann, Diego G Diel
Senecavirus A (SVA), an emerging picornavirus of swine, causes vesicular disease (VD) that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Many aspects of SVA interactions with the host and the host immune responses to infection, however, remain unknown. In the present study, humoral and cellular immune responses to SVA were evaluated following infection in pigs. We show that SVA infection elicited an early and robust neutralizing antibody (NA) response, which coincided with and was strongly correlated with VP2- and VP3-specific IgM responses...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29140155/persistent-prevention-of-oxaliplatin-induced-peripheral-neuropathy-using-calmangafodipir-pledox-%C3%A2-a-placebo-controlled-randomised-phase-ii-study-pliant
#6
Bengt Glimelius, Nebojsa Manojlovic, Per Pfeiffer, Baadur Mosidze, Galina Kurteva, Mia Karlberg, Devalingam Mahalingam, Peter Buhl Jensen, Jan Kowalski, Marie Bengtson, Malin Nittve, Jacques Näsström
PURPOSE: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC). PATIENT AND METHODS: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2), oxaliplatin 85 mg/m(2) and 5-fluorouracil 2400 mg/m(2) continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible...
November 15, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29139135/phase-1-study-of-quizartinib-in-combination-with-induction-and-consolidation-chemotherapy-in-patients-with-newly-diagnosed-acute-myeloid-leukemia
#7
Jessica K Altman, James M Foran, Keith W Pratz, Denise Trone, Jorge E Cortes, Martin S Tallman
Novel therapies have potential to improve outcomes in patients with acute myeloid leukemia (AML) harboring FLT3-ITD mutations that have high risk of relapse and poor survival following standard of care (SOC) cytarabine/anthracycline-based induction/consolidation chemotherapy. Quizartinib is a selective and highly potent FLT3 inhibitor that has shown strong single-agent activity in relapsed or refractory (R/R) AML. This phase 1, open-label, sequential group dose-escalation trial (NCT 01390337) is the first evaluating safety and tolerability of quizartinib in combination with SOC chemotherapy in newly diagnosed AML (ndAML)...
November 15, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29138340/phase-i-study-of-chimeric-antigen-receptor-modified-t-cells-in-patients-with-egfr-positive-advanced-biliary-tract-cancers
#8
Yelei Guo, Kai-Chao Feng, Yang Liu, Zhiqiang Wu, Hanren Dai, Qing-Ming Yang, Yao Wang, Hejin Jia, Weidong Han
PURPOSE: This study is an expanded and parallel clinical trial of epidermal growth factor receptor (EGFR)-specific chimeric antigen receptor-engineered autologous T (CART) cell immunotherapy (NCT01869166) to assess the safety and activity of CART-EGFR cell therapy in EGFR-positive advanced unresectable, relapsed/metastatic biliary tract cancers (BTCs). PATIENTS AND METHODS: Patients with EGFR-positive (>50%) advanced unresectable, relapsed/metastatic BTCs were enrolled...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29137933/cd4-t-cell-differentiation-in-chronic-viral-infections-the-tfh-perspective
#9
REVIEW
Laura A Vella, Ramin S Herati, E John Wherry
CD4(+) T cells play a critical role in the response to chronic viral infections during the acute phase and in the partial containment of infections once chronic infection is established. As infection persists, the virus-specific CD4(+) T cell response begins to shift in phenotype. The predominant change described in both mouse and human studies of chronic viral infection is a decrease in detectable T helper type (Th)1 responses. Some Th1 loss is due to decreased proliferative potential and decreased cytokine production in the setting of chronic antigen exposure...
November 11, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29137610/hemoglobin-stimulates-the-expression-of-adamts-5-and-adamts-9-by-synovial-cells-a-possible-cause-of-articular-cartilage-damage-after-intra-articular-hemorrhage
#10
Takuya Tajima, Tomohisa Sekimoto, Nami Yamaguchi, Noboru Taniguchi, Syuji Kurogi, Masugi Maruyama, Etsuo Chosa
BACKGROUND: ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) proteins play an important pathological role in matrix degeneration. Aggrecan degradation is a significant and critical event in early-stage osteoarthritis. To determine the effect of hemoglobin (Hb) on the ability of synovial tissues to produce ADAMTS family members, we examined the influence of Hb by synovial cells in an in vitro experimental system. METHODS: Synovial tissues were obtained from five young patients with meniscal injury under arthroscopic surgery...
November 14, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29136317/il-7-receptor-heterogeneity-as-a-mechanism-for-repertoire-change-during-post-depletional-homeostatic-proliferation-and-its-relation-to-costimulation-blockade-resistant-rejection
#11
He Xu, Victoria A Bendersky, Todd V Brennan, Jaclyn R Espinosa, Allan D Kirk
Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated with terminally differentiated T cells. Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevents CoBRR. We hypothesized that cells in late phases of differentiation would be selectively less capable of repopulating post-depletion than more naïve phenotypes, providing a potential mechanism by which lymphocyte depletion and repopulation could reduce the risk of CoBRR...
November 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29136283/population-pk-analyses-of-ubrogepant-mk-1602-a-cgrp-receptor-antagonist-enriching-in-clinic-plasma-pk-sampling-with-outpatient-dried-blood-spot-sampling
#12
Chi-Chung Li, Marissa Dockendorf, Ken Kowalski, Bei Yang, Yang Xu, Iris Xie, Huub Jan Kleijn, Rolien Bosch, Christopher Jones, Bob Thornton, Eugene E Marcantonio, Tiffini Voss, Kevin P Bateman, Prajakti A Kothare
Merck & Co., Inc. (Kenilworth, New Jersey) has recently published an integrated strategy for implementation of dried blood spots (DBS) in late-stage trials for population pharmacokinetic (PK) modeling. We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine. At the time of implementation, ubrogepant was entering phase 2 development. DBS was implemented to acquire PK information proximal to an acute migraine event to enable exposure-response modeling...
November 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29134249/early-siv-and-hiv-infection-promotes-the-lilrb2-mhc-i-inhibitory-axis-in-cdcs
#13
Lamine Alaoui, Gustavo Palomino, Sandy Zurawski, Gerard Zurawski, Sixtine Coindre, Nathalie Dereuddre-Bosquet, Camille Lecuroux, Cecile Goujard, Bruno Vaslin, Christine Bourgeois, Pierre Roques, Roger Le Grand, Olivier Lambotte, Benoit Favier
Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs...
November 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29133706/a-randomized-placebo-controlled-trial-of-progesterone-with-or-without-hypothermia-in-patients-with-acute-severe-traumatic-brain-injury
#14
Sumit Sinha, Amol Raheja, Neha Samson, Keshav Goyal, Sanjeev Bhoi, Arul Selvi, Pushpa Sharma, Bhawani Shankar Sharma
OBJECTIVE: Among newer neuroprotectant modalities, hypothermia and progesterone have shown a beneficial role in preliminary studies enrolling patients with severe traumatic brain injury (sTBI). The primary objective of this study was to evaluate the efficacy of progesterone with or without prophylactic hypothermia in acute sTBI patients. MATERIALS AND METHODS: This is a prospective, outcome assessor, statistician blinded, randomized, and placebo-controlled phase II trial of progesterone with or without hypothermia (factorial design)...
November 2017: Neurology India
https://www.readbyqxmd.com/read/29133384/estrogen-and-high-fat-diet-induced-alterations-in-c57bl-6-mice-endometrial-transcriptome-profile
#15
Yali Cheng, Qiaoying Lv, Bingying Xie, Bingyi Yang, Weiwei Shan, Chengcheng Ning, Bing Li, Liying Xie, Chao Gu, Xuezhen Luo, Xiaojun Chen, Qin Zhu
Unopposed estrogen stimulation and insulin resistance are known to play important roles in endometrial cancer (EC), but the interaction between these two factors and how they contribute to endometrial lesions are not completely elucidated. To investigate the endometrial transcriptome profile and the associated molecular pathway alterations, we established an ovariectomized C57BL/6 mouse model treated with subcutaneous implantation of 17-β estradiol (E2) pellet and/or high-fat diet (HFD) for 12 weeks to mimic sustained estrogen stimulation and insulin resistance...
November 13, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29133014/incorporation-of-brentuximab-vedotin-into-first-line-treatment-of-advanced-classical-hodgkin-s-lymphoma-final-analysis-of-a-phase-2-randomised-trial-by-the-german-hodgkin-study-group
#16
Dennis A Eichenauer, Annette Plütschow, Stefanie Kreissl, Martin Sökler, Johannes C Hellmuth, Julia Meissner, Stephan Mathas, Max S Topp, Karolin Behringer, Wolfram Klapper, Georg Kuhnert, Markus Dietlein, Carsten Kobe, Michael Fuchs, Volker Diehl, Andreas Engert, Peter Borchmann
BACKGROUND: A high proportion of patients with relapsed classical Hodgkin's lymphoma achieve a response with the antibody-drug conjugate brentuximab vedotin, and the drug is well tolerated. We modified the escalated BEACOPP regimen (eBEACOPP; bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and implemented brentuximab vedotin with the aim to reduce toxic effects while maintaining the protocol's efficacy. METHODS: We did an open-label, multicentre, randomised phase 2 study at 20 study sites in Germany...
November 10, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29131400/evaluation-of-3-serological-tests-for-early-detection-of-leptospira-specific-antibodies-in-experimentally-infected-dogs
#17
J Lizer, S Velineni, A Weber, M Krecic, P Meeus
BACKGROUND: Leptospirosis in dogs is a disease of global importance. Early detection and appropriate therapeutic intervention are necessary to resolve infection and prevent zoonotic transmission. However, its diagnosis is hindered by nonspecific clinical signs and lack of rapid diagnostic tests of early infection. Recently, 2 rapid point-of-care tests (WITNESS Lepto [WITNESS Lepto, Zoetis LLC, Kalamazoo, MI, USA] and SNAP Lepto [SNAP Lepto, IDEXX Laboratories, Westbrook, ME, USA]) for detection of Leptospira-specific antibodies in canine sera were developed...
November 13, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29127325/acinar-injury-and-early-cytokine-response-in-human-acute-biliary-pancreatitis
#18
Aparna Jakkampudi, Ramaiah Jangala, Ratnakar Reddy, Sasikala Mitnala, G Venkat Rao, Rebala Pradeep, D Nageshwar Reddy, Rupjyoti Talukdar
Clinical acute pancreatitis (AP) is marked by an early phase of systemic inflammatory response syndrome (SIRS) with multiorgan dysfunction (MODS), and a late phase characterized by sepsis with MODS. However, the mechanisms of acinar injury in human AP and the associated systemic inflammation are not clearly understood. This study, for the first time, evaluated the early interactions of bile acid induced human pancreatic acinar injury and the resulting cytokine response. We exposed freshly procured resected human pancreata to taurolithocolic acid (TLCS) and evaluated for acinar injury, cytokine release and interaction with peripheral blood mononuclear cells (PBMCs)...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29123878/investigation-of-japan-disaster-medical-assistance-team-response-guidelines-assuming-catastrophic-damage-from-a-nankai-trough-earthquake
#19
Hideaki Anan, Hisayoshi Kondo, Osamu Akasaka, Kenichi Oshiro, Mitsunobu Nakamura, Tetsuro Kiyozumi, Norihiko Yamada, Masato Homma, Kazuma Morino, Shinichi Nakayama, Yasuhiro Otomo, Yuichi Koido
Aim: Transporting critically ill patients outside of disaster-affected areas for treatment is an important activity of Japan Disaster Medical Assistance Teams (DMATs). We investigated whether this activity is possible after possible catastrophic damage from a Nankai Trough earthquake. Methods: Japan was divided into three areas based on the level of predicted damage (definitely, possibly, and non-affected areas). A survey of DMATs and the locations of emergency base hospitals and intensive care units (ICUs) in each area was carried out, and the ability to support disaster areas was investigated...
July 2017: Acute Medicine & Surgery
https://www.readbyqxmd.com/read/29123515/dietary-intervention-with-%C3%AE-lactoglobulin-derived-peptides-and-a-specific-mixture-of-fructo-oligosaccharides-and-bifidobacterium-breve-m-16v-facilitates-the-prevention-of-whey-induced-allergy-in-mice-by-supporting-a-tolerance-prone-immune-environment
#20
Atanaska I Kostadinova, Alba Pablos-Tanarro, Mara A P Diks, Betty C A M van Esch, Johan Garssen, Léon M J Knippels, Linette E M Willemsen
Cow's milk allergy (CMA) prevails in infants and brings increased risk of developing other allergic diseases. Oral administration of specific β-lactoglobulin (BLG)-derived peptides (PepMix) and a specific blend of short- and long-chain fructo-oligosaccharides and Bifidobacterium breve M-16V (FF/Bb) was found to partially prevent CMA development in mice. In this study, we aimed to expand the knowledge on the preventive potential and the underlying mechanisms of this approach. Three-week-old female C3H/HeOuJ mice were orally exposed to PepMix±FF/Bb prior to a 5-week oral sensitization with whole whey and cholera toxin as an adjuvant...
2017: Frontiers in Immunology
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