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https://www.readbyqxmd.com/read/28636208/a-phase-i-trial-of-prn1008-a-novel-reversible-covalent-inhibitor-of-bruton-s-tyrosine-kinase-in-healthy-volunteers
#1
Patrick F Smith, Janakan Krishnarajah, Philip A Nunn, Ron J Hill, Dane Karr, D Tam, Mohammad Masjedizadeh, Jens O Funk, Steve G Gourlay
AIM: To evaluate the safety, tolerability, and PK/PD of PRN1008, a novel BTK inhibitor, in healthy volunteers, and thus determine the dose range for future clinical studies. METHODS: This was a two-part randomized, placebo controlled study in healthy volunteers using a liquid formulation. Part I was a single ascending dose design with dose levels of 50 to 1200 mg (n=6 active, 2 placebo per cohort); Part II was a multiple ascending dose design, with dose regimens ranging from 300 mg to 900 mg daily, either qd or bd for 10 days...
June 21, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28636204/aerobic-exercise-training-for-adults-with-fibromyalgia
#2
REVIEW
Julia Bidonde, Angela J Busch, Candice L Schachter, Tom J Overend, Soo Y Kim, Suelen M Góes, Catherine Boden, Heather Ja Foulds
BACKGROUND: Exercise training is commonly recommended for individuals with fibromyalgia. This review is one of a series of reviews about exercise training for people with fibromyalgia that will replace the "Exercise for treating fibromyalgia syndrome" review first published in 2002. OBJECTIVES: • To evaluate the benefits and harms of aerobic exercise training for adults with fibromyalgia• To assess the following specific comparisons ० Aerobic versus control conditions (eg, treatment as usual, wait list control, physical activity as usual) ० Aerobic versus aerobic interventions (eg, running vs brisk walking) ० Aerobic versus non-exercise interventions (eg, medications, education) We did not assess specific comparisons involving aerobic exercise versus other exercise interventions (eg, resistance exercise, aquatic exercise, flexibility exercise, mixed exercise)...
June 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28636162/cobalt-catalyzed-ortho-c-h-functionalization-alkyne-annulation-of-benzylamine-derivatives-access-to-dihydroisoquinolines
#3
Angel Manu Martínez, Nuria Rodríguez, Ramon Gomez-Arrayas, Juan C Carretero
A practical picolinamide-directed C-H functionalization/alkyne annulation of benzylamine derivatives enabling the access to the previously elusive 1,4-dihydroisoquinoline skeleton was developed using molecular O2 as the sole oxidant and Co(OAc)2 as precatalyst. The method is compatible with both internal and terminal alkynes and shows high versatility and functional-group tolerance. Furthermore, full preservation of enantiopurity is observed when using non-racemic alpha-substituted benzylamine derivatives...
June 21, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28635957/itk-signalling-via-the-ras-irf4-pathway-regulates-the-development-and-function-of-tr1-cells
#4
Weishan Huang, Sabrina Solouki, Nicholas Koylass, Song-Guo Zheng, Avery August
Type 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635632/glucose-and-lipid-dysmetabolism-in-a-rat-model-of-prediabetes-induced-by-a-high-sucrose-diet
#5
Ana Burgeiro, Manuela G Cerqueira, Bárbara M Varela-Rodríguez, Sara Nunes, Paula Neto, Frederico C Pereira, Flávio Reis, Eugénia Carvalho
Glucotoxicity and lipotoxicity are key features of type 2 diabetes mellitus, but their molecular nature during the early stages of the disease remains to be elucidated. We aimed to characterize glucose and lipid metabolism in insulin-target organs (liver, skeletal muscle, and white adipose tissue) in a rat model treated with a high-sucrose (HSu) diet. Two groups of 16-week-old male Wistar rats underwent a 9-week protocol: HSu diet (n = 10)-received 35% of sucrose in drinking water; Control (n = 12)-received vehicle (water)...
June 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28635528/clinical-social-and-ethical-issues-associated-with-non-invasive-prenatal-testing-for-aneuploidy
#6
Blanche Griffin, Samantha Edwards, Lyn S Chitty, Celine Lewis
Non-invasive prenatal testing (NIPT), based on analysis of cell-free foetal DNA, is rapidly becoming a preferred method to screen for chromosomal aneuploidy with the technology now available in over 90 countries. This review provides an up-to-date discussion of the key clinical, social and ethical implications associated with this revolutionary technology. Stakeholders are positive about a test that is highly accurate, safe, can be perfomed early in pregnancy, identifies affected pregnancies that might otherwise have been missed and reduces the need for invasive testing...
February 9, 2017: Journal of Psychosomatic Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28634727/safety-and-efficacy-of-chemosaturation-in-patients-with-primary-and-secondary-liver-tumors
#7
Martha M Kirstein, Steffen Marquardt, Nils Jedicke, Silke Marhenke, Wolfgang Koppert, Michael P Manns, Frank Wacker, Arndt Vogel
BACKGROUND: Chemosaturation with percutaneous hepatic perfusion (CS-PHP; hepatic CHEMOSAT(®) delivery system; Delcath Systems Inc, USA) is a novel medical device, which delivers high doses of melphalan directly to the liver in patients with primary and secondary liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. The aim of this study was to analyze the safety and efficacy of the second-generation CS-PHP after 54 treatments at Hannover Medical School, Germany...
June 20, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28634682/searching-for-the-sweet-spot-the-foot-rotation-and-parallel-engagement-of-ankle-ligaments-in-maximizing-injury-tolerance
#8
Bingbing Nie, Jason L Forman, Alexander R Mait, John-Paul Donlon, Matthew B Panzer, Richard W Kent
Ligament sprains, defined as tearing of bands of fibrous tissues within ligaments, account for a majority of injuries to the foot and ankle complex in field-based sports. External rotation of the foot is considered the primary injury mechanism of syndesmotic ankle sprains with concomitant flexion and inversion/eversion associated with particular patterns of ligament trauma. However, the influence of the magnitude and direction of loading vectors to the ankle on the in situ stress state of the ligaments has not been quantified in the literature...
June 20, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28634669/yttrium-90-y-90-resin-microsphere-therapy-for-patients-with-unresectable-hepatocellular-carcinoma-a-single-center-experience
#9
Semra İnce, Bülent Karaman, Engin Alagoz, Nuri Karadurmuş, Hüseyin Şan, Cemal Nuri Erçin, Nuri Arslan
BACKGROUND/AIM: Selective intraarterial radionuclide therapy (SIRT) with yttrium-90 (Y-90) resin microspheres presently has successful results in primary or metastatic inoperable liver tumors. This procedure, which is also known as radioembolisation, delivers high doses of radiation selectively to hepatic tumors while minimum healthy liver exposure. The aim of this study was to present our clinical experience of radiomicrosphere therapy for the treatment of patients with unresectable hepatocellular carcinoma (HCC)...
June 20, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28634650/a-randomized-phase-ii-study-of-gemcitabine-plus-z-360-a-cck2-receptor-selective-antagonist-in-patients-with-metastatic-pancreatic-cancer-as-compared-with-gemcitabine-plus-placebo
#10
Makoto Ueno, Chung Pin Li, Masafumi Ikeda, Hiroshi Ishii, Nobumasa Mizuno, Taketo Yamaguchi, Tatsuya Ioka, Do Youn Oh, Wataru Ichikawa, Takuji Okusaka, Yutaka Matsuyama, Daichi Arai, Li Tzong Chen, Young Suk Park, Junji Furuse
BACKGROUND: We investigated the efficacy and safety of 60, 120, or 240 mg of Z-360, which is a highly potent cholecystokinin2-receptor-selective antagonist, combined with gemcitabine in patients with metastatic pancreatic cancer. METHODS: Patients were randomly assigned in a 1:1:1:1 ratio to one of four treatment groups. Patients received 1000 mg/m(2) gemcitabine for each cycle and Z-360 tablets of 60 mg (GZ 60 mg group), 120, 240 mg or placebo tablets (Gem group) orally twice daily...
June 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28634535/effectiveness-and-safety-of-daptomycin-in-patients-with-infective-endocarditis-undergoing-heart-valve-replacement-a-subgroup-analysis-from-real-world-data
#11
Achyut Guleri, Riccardo Utili, Pascal Dohmen, Kamal Hamed
BACKGROUND: European Cubicin(®) Outcomes Registry and Experience (EU-CORE) was a retrospective, non-interventional, multicenter registry that collected real-world clinical outcomes following daptomycin use for the treatment of Gram-positive infections. EU-CORE data from patients with infective endocarditis (IE) who underwent heart valve replacement were analysed. METHODS: Clinical outcomes were assessed as success (cured or improved), failure, or non-evaluable...
March 2017: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/28634433/the-draft-genome-of-the-non-host-associated-methanobrevibacter-arboriphilus-strain-dh1-encodes-a-large-repertoire-of-adhesin-like-proteins
#12
Anja Poehlein, Rolf Daniel, Henning Seedorf
Methanobrevibacter arboriphilus strain DH1 is an autotrophic methanogen that was isolated from the wetwood of methane-emitting trees. This species has been of considerable interest for its unusual oxygen tolerance and has been studied as a model organism for more than four decades. Strain DH1 is closely related to other host-associated Methanobrevibacter species from intestinal tracts of animals and the rumen, making this strain an interesting candidate for comparative analysis to identify factors important for colonizing intestinal environments...
2017: Archaea: An International Microbiological Journal
https://www.readbyqxmd.com/read/28634160/high-throughput-characterization-of-cascade-type-i-e-crispr-guide-efficacy-reveals-unexpected-pam-diversity-and-target-sequence-preferences
#13
Becky Xu Hua Fu, Michael Wainberg, Anshul Kundaje, Andrew Z Fire
Interactions between Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs and CRISPR-associated (Cas) proteins form an RNA-guided adaptive immune system in prokaryotes. The adaptive immune system utilizes segments of the genetic material of invasive foreign elements in the CRISPR locus. The loci are transcribed and processed to produce small CRISPR RNAs (crRNAs), with degradation of invading genetic material directed by a combination of complementarity between RNA and DNA and in some cases recognition of adjacent motifs called PAMs (Protospacer Adjacent Motifs)...
June 20, 2017: Genetics
https://www.readbyqxmd.com/read/28634129/state-of-the-art-review-of-biofuels-production-from-lignocellulose-by-thermophilic-bacteria
#14
REVIEW
Yujia Jiang, Fengxue Xin, Jiasheng Lu, Weiliang Dong, Wenming Zhang, Min Zhang, Hao Wu, Jiangfeng Ma, Min Jiang
Biofuels, including ethanol and butanol, are mainly produced by mesophilic solventogenic yeasts and Clostridium species. However, these microorganisms cannot directly utilize lignocellulosic materials, which are abundant, renewable and non-compete with human demand. More recently, thermophilic bacteria show great potential for biofuels production, which could efficiently degrade lignocellulose through the cost effective consolidated bioprocessing. Especially, it could avoid contamination in the whole process owing to its relatively high fermentation temperature...
June 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28633997/nicotinamide-inhibits-the-growth-of-p-falciparum-and-enhances-the-antimalarial-effect-of-artemisinin-chloroquine-and-pyrimethamine
#15
Sergey O Tcherniuk, Olga Chesnokova, Irina V Oleinikov, Andrew V Oleinikov
Nicotinamide (vitamin B3) - is a water soluble amide derivative of nicotinic acid, which has been used at high doses for a variety of therapeutic applications. However, its antimalarial effect has not been intensively explored. In this work we analysed the effect of nicotinamide alone and in combination with artemisinin, chloroquine andpyrimethamine on the growth of blood stages of P. falciparum. Our results demonstrate that nicotinamide effectively inhibits the growth of blood stage parasites with IC50 of 6...
June 17, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28633597/effect-of-t-2-toxin-injected-shrimp-muscle-extracts-on-mouse-macrophage-cells-raw264-7
#16
Zhanrui Huang, Yaling Wang, Mei Qiu, Lijun Sun, Jianmeng Liao, Rundong Wang, Xiaodong Sun, Siyuan Bi, Ravi Gooneratne
Following intramuscular injections of 0.1 mL, 3 mg kg(-1 )BW(-1)(1/10 LD50) T-2 toxin (T-2), the tissue concentration of T-2 in shrimp was quantitatively detected using LC-MS/MS. The biological half-time (t1/2) of T-2 in blood was 40.47 ± 0.24 min. The highest number of intramuscular T-2 shrimp could tolerate when given at blood t1/2 intervals was 4. The shrimps which were injected 5 T-2 died. The T-2 toxin highest accumulation was 0.471 ± 0.012 ng g(-1 )BW(-1). The effect of toxic shrimp muscle subjected to different processing conditions (high pressure, trifluoroacetic acid, acid and alkali digestions, artificial digestive juice [to simulate exposure to gastric and intestinal juices]) on mouse macrophage cells (RAW267...
February 10, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28633487/high-intensity-interval-training-hiit-improves-physical-performance-and-frailty-in-aged-mice
#17
Kenneth Ladd Seldeen, Ginger Lasky, Merced Maria Leiker, Manhui Pang, Kirkwood Ely Personius, Bruce Robert Troen
Sarcopenia and frailty are highly prevalent in older individuals, increasing the risk of disability and loss of independence. High intensity interval training (HIIT) may provide a robust intervention for both sarcopenia and frailty by achieving both strength and endurance benefits with lower time commitments than other exercise regimens. To better understand the impacts of HIIT during aging, we compared 24-month-old C57BL/6J sedentary mice with those that were administered 10-minute uphill treadmill HIIT sessions three times per week over 16 weeks...
June 17, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28633431/differential-effects-of-alcohol-on-memory-performance-in-adolescent-men-and-women-with-a-binge-drinking-history
#18
Concepción Vinader-Caerols, Andrew Talk, Adriana Montañés, Aránzazu Duque, Santiago Monleón
Aims: Binge drinking (BD) is characterized by intermittent consumption of large quantities of alcohol in short periods. This pattern of drinking is prevalent among adolescents, and has been associated with undermined learning and memory ability. This study investigates the relationships between a history of BD and the effects of acute exposure to alcohol on learning and memory performance in adolescent men and women. Methods: A high, acute dose of alcohol or control refreshment was administered to a sample of 172 adolescent undergraduate students, some of which had a history of BD and others of which had refrained from alcohol consumption...
June 17, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/28633427/genotypic-variation-in-tolerance-to-drought-stress-is-highly-coordinated-with-hydraulic-conductivity-photosynthesis-interplay-and-aquaporin-expression-in-field-grown-mulberry-morus-spp
#19
Kanubothula Sitarami Reddy, Kalva Madhana Sekhar, Attipalli Ramachandra Reddy
Hydraulic conductivity quantifies the efficiency of a plant to transport water from root to shoot and is a major constriction on leaf gas exchange physiology. Mulberry (Morus spp.) is the most economically important crop for sericulture industry. In this study, we demonstrate a finely coordinated control of hydraulic dynamics on leaf gas exchange characteristics in 1-year-old field-grown mulberry genotypes (Selection-13 (S13); Kollegal Local (KL) and Kanva-2 (K2)) subjected to water stress by withholding water for 20 days and subsequent recovery for 7 days...
June 14, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28633360/expression-properties-exhibit-correlated-patterns-with-the-fate-of-duplicated-genes-their-divergence-and-transcriptional-plasticity-in-saccharomycotina
#20
Florian Mattenberger, Beatriz Sabater-Muñoz, Christina Toft, Gaurav Sablok, Mario A Fares
Gene duplication is an important source of novelties and genome complexity. What genes are preserved as duplicated through long evolutionary times can shape the evolution of innovations. Identifying factors that influence gene duplicability is therefore an important aim in evolutionary biology. Here, we show that in the yeast Saccharomyces cerevisiae the levels of gene expression correlate with gene duplicability, its divergence, and transcriptional plasticity. Genes that were highly expressed before duplication are more likely to be preserved as duplicates for longer evolutionary times and wider phylogenetic ranges than genes that were lowly expressed...
June 15, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
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