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https://www.readbyqxmd.com/read/28938444/lack-of-lrp5-signaling-in-osteoblasts-sensitizes-male-mice-to-diet-induced-disturbances-in-glucose-metabolism
#1
Soohyun P Kim, Julie L Frey, Zhu Li, Brian C Goh, Ryan C Riddle
Wnt signaling through the Lrp5 co-receptor regulates osteoblast maturation, matrix mineralization, and intermediary metabolism. In the mature osteoblast, signals downstream of Lrp5 are required for normal long-chain fatty acid β-oxidation and mice rendered deficient for this co-receptor in osteoblasts and osteocytes accumulate body fat with elevated serum lipid levels, but retain normal insulin sensitivity. In this study, we challenged Lrp5 mutant mice with a high fat diet to determine if they are more susceptible to diet-induced disturbances in glucose homeostasis...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938298/safety-and-efficacy-of-epidural-analgesia
#2
Elke M E Bos, Markus W Hollmann, Philipp Lirk
PURPOSE OF REVIEW: Epidural analgesia remains a widely used analgesic technique. This article aims to assess the safety of epidural analgesia by balancing efficacy and complications, of epidural analgesia for acute, labor and chronic pain. RECENT FINDINGS: Main indications for epidural analgesia include major open abdominal surgery, thoracotomy and labor analgesia. Past and current literature show that epidural analgesia leads to statistically significant, but possibly clinically less meaningful, reductions in pain scores compared with intravenous analgesia...
September 21, 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28937172/gold-i-catalyzed-synthesis-of-2-substituted-indoles-from-2-alkynylnitroarenes-with-diboron-as-reductant
#3
Wenqiang Fu, Kai Yang, Jinglong Chen, Qiuling Song
An efficient method for the synthesis of 2-substituted indoles via a diboron/base promoted tandem reductive cyclization of o-alkynylnitroarene under Au catalysis conditions has been disclosed. This reaction is efficient and convenient, affording 2-substituted indoles with broad functional groups tolerance and excellent yields.
September 22, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28936772/proteome-characterization-of-copper-stress-responses-in-the-roots-of-sorghum
#4
Swapan Kumar Roy, Seong-Woo Cho, Soo Jeong Kwon, Abu Hena Mostafa Kamal, Dong-Gi Lee, Kabita Sarker, Moon-Soon Lee, Zhanguo Xin, Sun-Hee Woo
Copper (Cu) is a important micronutrient for plants, but it is extremely toxic to plants at high concentration and can inactivate and disturb protein structures. To explore the Cu stress-induced tolerance mechanism, the present study was conducted on the roots of sorghum seedlings exposed to 50 and 100 µM CuSO4 for 5 days. Accumulation of Cu increased in roots when the seedlings were treated with the highest concentration of Cu(2+) ions (100 μM). Elevated Cu concentration provoked notable reduction of Fe, Zn, Ca, and Mn uptake in the roots of sorghum seedlings...
September 21, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28936766/use-of-lactobacilli-in-cereal-legume-fermentation-and-as-potential-probiotics-towards-phytate-hydrolysis
#5
Girish K Amritha, G Venkateswaran
Phytate is a potent inhibitor of mineral absorption in humans occurring in plant-based food. Application of lactobacilli that produce phytate-degrading enzymes (phytases) to reduce phytate is an interesting yet a not much explored sector of research. Therefore, phytate dephosphorylation by Lactobacillus plantarum MTCC 1325 was evaluated. Cells at stationary phase showed phytase activity which was maximal at 24 h of growth. Glucose concentration and the type of phosphorous source in the media modulated the enzyme activity...
September 21, 2017: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/28936221/metabolite-profiling-of-barley-grains-subjected-to-water-stress-to-explain-the-genotypic-difference-in-drought-induced-impacts-on-malting-quality
#6
Xiaojian Wu, Kangfeng Cai, Guoping Zhang, Fanrong Zeng
Grain weight and protein content will be reduced and increased, respectively, when barley is subjected to water stress after anthesis, consequently deteriorating the malt quality. However, such adverse impact of water stress differs greatly among barley genotypes. In this study, two Tibetan wild barley accessions and two cultivated varieties differing in water stress tolerance were used to investigate the genotypic difference in metabolic profiles during grain-filling stage under drought condition. Totally, 71 differently accumulated metabolites were identified, including organic acids, amino acids/amines, and sugars/sugar alcohols...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28935478/development-and-validation-of-a-cell-based-assay-for-the-detection-of-neutralizing-antibodies-against-recombinant-insulins
#7
Sanjukta Chatterjee, Laxmikant Vashishta, Vinit S Waichale, Vivek G Nayak, Ramakrishnan Melarkode, Charles M Donnelly, Patrick T Vallano, Narendra Chirmule, Nilanjan Sengupta
Recombinant biopharmaceuticals can induce generation of anti-drug antibodies, which could potentially neutralize therapeutic drug activity. In this report, we describe development and validation of a cell-based assay for detection of neutralizing antibodies (Nab) against insulin and insulin analogues. In order to achieve clinically meaningful sensitivity the method used an early signalling event, insulin induced insulin receptor phosphorylation as the endpoint. Percentage insulin receptor phosphorylation in cell lysates was measured using ECL based ELISA...
September 18, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28935291/efficacy-and-safety-of-hyperbaric-oxygen-therapy-used-in-patients-with-diabetic-foot-a-meta-analysis-of-randomized-clinical-trials
#8
REVIEW
Di Zhao, Shaowei Luo, Wencan Xu, Jun Hu, Shaoda Lin, Nasui Wang
PURPOSE: The efficacy and safety profile of hyperbaric oxygen therapy (HBOT) in patients with diabetic foot ulcer have been controversial in recent years. Our meta-analysis was undertaken to evaluate the efficacy and safety profile of HBOT in patients with diabetic foot ulcer. METHODS: We searched the PubMed, Cochrane Library, EMBASE, and Clinical Trials.gov databases for controlled trials. The efficacy end points included the incidence of healed ulcers, major amputations, minor amputations, and reduction in the ulcer wound area...
September 18, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28935000/effect-of-early-life-gut-mucosal-compromise-on-disease-progression-in-nod-mice
#9
Katja M Bendtsen, Camilla Hf Hansen, Lukasz Krych, Karsten Buschard, Helene Farlov, Axel K Hansen
Disease expression in spontaneous nonobese diabetic (NOD) mice depends on environmental stimuli such as stress, diet, and gut microbiota composition. We evaluated a brief, early-life gut intervention in which pups were weaned to low-dose dextran sulfate sodium (DSS). We hypothesized that the mucus-reducing effect of this compound and subsequent increased host-bacterial contact would delay disease onset and decrease insulitis due to enhanced oral tolerance. However, disease incidence did not differ between groups, although median survival (time point when 50% of the mice are still alive) of the control group was 184 d compared with 205 d for DSS-treated mice...
October 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28934680/a-phase-1-study-of-the-janus-kinase-2-jak2-v617f-inhibitor-gandotinib-ly2784544-in-patients-with-primary-myelofibrosis-polycythemia-vera-and-essential-thrombocythemia
#10
Srdan Verstovsek, Ruben A Mesa, Mohamed E Salama, Li Li, Celine Pitou, Fabio P Nunes, Gregory L Price, Jennifer L Giles, Deborah N D'Souza, Richard A Walgren, Josef T Prchal
Mutations in Janus kinase 2 (JAK2) are implicated in the pathogenesis of Philadelphia-chromosome negative myeloproliferative neoplasms, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Gandotinib (LY2784544), a potent inhibitor of JAK2 activity, shows increased potency for the JAK2(V617F) mutation. The study had a standard 3+3 dose-escalation design to define the maximum-tolerated dose. Primary objectives were to determine safety, tolerability, and recommended oral daily dose of gandotinib for patients with JAK2(V617F)-positive myelofibrosis, essential thrombocythemia, or polycythemia vera...
August 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28932906/safety-study-and-therapeutic-drug-monitoring-of-the-oral-tablet-formulation-of-posaconazole-in-patients-with-haematological-malignancies
#11
C Boglione-Kerrien, S Picard, C Tron, S Nimubona, J-P Gangneux, S Lalanne, F Lemaitre, E Bellissant, M-C Verdier, A Petitcollin
PURPOSE: Posaconazole is a triazole antifungal widely used for prophylaxis of invasive fungal disease (IFI). Posaconazole tablets allow reaching higher plasma levels than the oral suspension, but safety data with this formulation in real life are scarce. This study aimed at evaluating the safety profile, the pharmacokinetic variability, and the concentration-toxicity relationship of posaconazole tablets in patients with haematological malignancies. METHODS: Sixty neutropenic patients treated with posaconazole tablets for prophylaxis of IFI were prospectively included in the study...
September 20, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28932728/laparoscopic-gastrojejunostomy-versus-duodenal-stenting-in-unresectable-gastric-cancer-with-gastric-outlet-obstruction
#12
Sa-Hong Min, Sang-Yong Son, Do-Hyun Jung, Chang-Min Lee, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim
PURPOSE: To compare the outcome between laparoscopic gastrojejunostomy (LapGJ) and duodenal stenting (DS) in terms of oral intake, nutritional status, patency duration, effect on chemotherapy and survival. METHODS: Medical records of 115 patients, who had LapGJ or duodenal stent placement between July 2005 and September 2015 in Seoul National University Bundang Hospital, have been reviewed retrospectively. Oral intake was measured with Gastric Outlet Obstruction Scoring System...
September 2017: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/28932628/a-novel-in-silico-framework-to-improve-mhc-i-epitopes-and-break-the-tolerance-to-melanoma
#13
Cristian Capasso, Aniket Magarkar, Victor Cervera-Carascon, Manlio Fusciello, Sara Feola, Martin Muller, Mariangela Garofalo, Lukasz Kuryk, Siri Tähtinen, Lucio Pastore, Alex Bunker, Vincenzo Cerullo
Tolerance toward tumor antigens, which are shared by normal tissues, have often limited the efficacy of cancer vaccines. However, wild type epitopes can be tweaked to activate cross-reactive T-cell clones, resulting in antitumor activity. The design of these analogs (i.e., heteroclitic peptides) can be difficult and time-consuming since no automated in silico tools are available. Hereby we describe the development of an in silico framework to improve the selection of heteroclitic peptides. The Epitope Discovery and Improvement System (EDIS) was first validated by studying the model antigen SIINFEKL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931072/high-prevalence-of-non-dipping-blood-pressure-and-vascular-stiffness-in-hiv-infected-south-africans-on-antiretrovirals
#14
M S Borkum, J M Heckmann, K Manning, J A Dave, N S Levitt, B L Rayner, N Wearne
BACKGROUND: HIV-infected individuals are at increased risk of tissue inflammation and accelerated vascular aging ('inflamm-aging'). Abnormal diurnal blood pressure (BP) rhythms such as non-dipping may contribute to an increased risk of cardiovascular and cerebrovascular events in HIV infected individuals. However, little data exists on ambulatory blood pressure (ABP) and measures of vascular stiffness in the black African HIV infected population. METHODS: This is a cross-sectional analysis of otherwise well, HIV infected outpatients on ART for >5 years...
2017: PloS One
https://www.readbyqxmd.com/read/28929491/capecitabine-based-treatment-of-a-patient-with-a-novel-dpyd-genotype-and-complete-dihydropyrimidine-dehydrogenase-deficiency
#15
Linda M Henricks, Ester J Siemerink, Hilde Rosing, Judith Meijer, Susan M Goorden, Abeltje M Polstra, Lida Zoetekouw, Annemieke Cats, Jan H Schellens, André B van Kuilenburg
Fluoropyrimidines are frequently used anti-cancer drugs. It is known that patients with reduced activity of dihydropyrimidine dehydrogenase (DPD), the key metabolic enzyme in fluoropyrimidine inactivation, are at increased risk of developing severe fluoropyrimidine-related toxicity. Upfront screening for DPD deficiency and dose reduction in patients with partial DPD deficiency is recommended and improves patient safety. For patients with complete DPD deficiency, fluoropyrimidine-treatment has generally been discouraged...
September 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28929226/transcriptome-profiling-of-fully-open-flowers-in-a-frost-tolerant-almond-genotype-in-response-to-freezing-stress
#16
Batool Hosseinpour, Sadegh Sepahvand, Kazem Kamali Aliabad, MohammadReza Bakhtiarizadeh, Ali Imani, Reza Assareh, Seyed Alireza Salami
Spring frost is a major limiting abiotic stress for the cultivation of almonds [Prunus dulcis (Mill.)] in Mediterranean areas or the Middle East. Spring frost, in particular, damages almond fully open flowers, resulting to significant reduction in yield. Little is known about the genetic factors expressed after frost stress in Prunus spp. as well as in almond fully open flowers. Here, we provide the molecular signature of pistils of fully open flowers from a frost-tolerant almond genotype. The level of frost tolerance in this genotype was determined for all three flowering stages and was confirmed by comparing it to two other cultivars using several physiological analyses...
September 19, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28926816/phycoremediation-of-landfill-leachate-with-the-chlorophyte-chlamydomonas-sp-sw15arl-and-evaluation-of-toxicity-pre-and-post-treatment
#17
Andrea Paskuliakova, Ted McGowan, Steve Tonry, Nicolas Touzet
Landfill leachate treatment is an ongoing challenge in the wastewater management of existing sanitary landfill sites due to the complex nature of leachates and their heavy pollutant load. There is a continuous interest in treatment biotechnologies with expected added benefits for resource recovery; microalgal bioremediation is seen as promising in this regard. Toxicity reduction of landfill leachate subsequent to phycoremediation was investigated in this study. The treatment eventuated from the growth of the ammonia tolerant microalgal strain Chlamydomonas sp...
September 15, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28926295/efficacy-and-safety-assessment-of-acute-sports-related-traumatic-soft-tissue-injuries-using-a-new-ibuprofen-medicated-plaster-results-from-a-randomized-controlled-clinical-trial
#18
Hans-Georg Predel, Mark P Connolly, Aomesh Bhatt, Bruno Giannetti
OBJECTIVE: To investigate the efficacy and safety of a recently developed ibuprofen medicated plaster in the treatment of acute sports impact injuries/contusions. METHODS: In this double-blind, multi-center, placebo-controlled, parallel group, phase 3 study (EudraCT Number: 2012-003257-2) patients (n=132; ages 18 to 60 years) diagnosed with acute sports-related traumatic blunt soft tissue injury/contusion to the upper or lower limbs were randomized to receive either ibuprofen 200 mg plaster (n=64) or placebo plaster (n=68)...
September 19, 2017: Physician and Sportsmedicine
https://www.readbyqxmd.com/read/28926170/efficacy-and-safety-of-saxagliptin-in-combination-with-metformin-as-initial-therapy-in-chinese-patients-with-type-2-diabetes-results-from-the-start-study-a-multicenter-randomized-double-blind-active-controlled-phase-3-trial
#19
Jingtao Dou, Jianhua Ma, Jun Liu, Changjiang Wang, Eva Johnsson, Hui Yao, June Zhao, Changyu Pan
OBJECTIVE: To assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy-naïve Chinese patients with type 2 diabetes mellitus and inadequate glycemic control (HbA1c 8.0-12.0%). RESEARCH DESIGN AND METHODS: In this multicenter, double-blind, active-controlled study (The START study: NCT02273050), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo, or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/day over 8 weeks...
September 19, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28926159/randomized-controlled-feasibility-trial-of-intranasal-ketamine-compared-to-intranasal-fentanyl-for-analgesia-in-children-with-suspected-extremity-fractures
#20
Stacy L Reynolds, Kathleen K Bryant, Jonathan R Studnek, Melanie Hogg, Connell Dunn, Megan A Templin, Charity G Moore, James R Young, Katherine Rivera Walker, Michael S Runyon
OBJECTIVE: We compared the tolerability and efficacy of intranasal sub-dissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger non-inferiority trial that could investigate the potential opioid sparing effects of intranasal ketamine. METHODS: This randomized controlled trial compared intranasal ketamine 1 mg/kg to intranasal fentanyl 1.5 μg/kg in children 4-17 years old with acute pain from suspected, isolated extremity fractures presenting to an urban level II pediatric trauma center from December 2015 to November 2016...
September 19, 2017: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
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