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https://www.readbyqxmd.com/read/28088839/pharmacokinetic-pharmacodynamic-modeling-of-the-pde4-inhibitor-tak-648-in-type-2-diabetes-early-translational-approaches-for-human-dose-prediction
#1
N Plock, S Vollert, M Mayer, G Hanauer, G Lahu
TAK-648 is a PDE4 inhibitor with demonstrated preclinical antidiabetic properties. Our objective was to develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for human type 2 diabetes (T2D) dose prediction using HbA1c results from a db/db mouse study. Estimated parameters in combination with tPDE4i values calculated for the clinical roflumilast dose of 500 μg were used to translate preclinical effects of TAK-648 to required exposure in humans. A first-in-human study with single TAK-648 doses of 0...
January 15, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28088838/re-evaluation-of-phenotypic-expression-in-differentiated-type-early-adenocarcinoma-of-the-stomach
#2
Masato Hayakawa, Ken Nishikura, Yoichi Ajioka, Yutaka Aoyagi, Shuji Terai
A total of 313 cases of differentiated-type early gastric adenocarcinomas, including 113 cases of small-sized carcinoma (5< × ≤10 mm) and 121 cases of microcarcinoma (0< × ≤5 mm), were examined immunohistochemically to clarify the phenotypic expressions. They were classified into four categories (gastric phenotype (G-type), intestinal phenotype, gastrointestinal phenotype, and null phenotype) by a two-step process: the phenotype based on an immunoprofile of mucin core proteins (MUCs) with CDX2 (w/...
January 15, 2017: Pathology International
https://www.readbyqxmd.com/read/28088807/posterior-versus-anterior-circulation-stroke-in-young-adults-a-comparative-study-of-stroke-aetiologies-and-risk-factors-in-stroke-among-young-fabry-patients-sifap1
#3
Bettina von Sarnowski, Ulf Schminke, Ulrike Grittner, Christian Tanislav, Tobias Böttcher, Michael G Hennerici, Turgut Tatlisumak, Jukka Putaala, Manfred Kaps, Franz Fazekas, Christian Enzinger, Arndt Rolfs, Christof Kessler
BACKGROUND: Although 20-30% of all strokes occur in the posterior circulation, few studies have explored the characteristics of patients with strokes in the posterior compared to the anterior circulation so far. Especially data on young patients is missing. METHODS: In this secondary analysis of data of the prospective multi-centre European sifap1 study that investigated stroke and transient ischemic attack (TIA) patients aged 18-55 years, we compared vascular risk factors, stroke aetiology, presence of white matter hyperintensities (WMH) and cerebral microbleeds (CMB) between patients with ischaemic posterior circulation stroke (PCS) and those having suffered from anterior circulation stroke (ACS) based on cerebral MRI...
January 14, 2017: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/28088804/monitoring-noninvasive-ventilation-in-patients-with-obesity-hypoventilation-syndrome-comparison-between-ventilator-built-in-software-and-respiratory-polygraphy
#4
Ramon Fernandez Alvarez, Claudio Rabec, Gemma Rubinos Cuadrado, Juan Alejandro Cascon Hernandez, Patricia Rodriguez, Marjolaine Georges, Pere Casan
BACKGROUND: Polygraphy (PG) remains the standard method of assessing noninvasive ventilation (NIV) effectiveness. Built-in software (BIS) of recent NIV equipment provides estimates of some ventilator parameters, but their usefulness is unclear. OBJECTIVES: To assess the reliability of BIS compared with PG in a cohort of obesity hypoventilation syndrome (OHS) patients on NIV. METHODS: Thirty stable OHS patients on NIV were evaluated in an outpatient setting with simultaneous PG and BIS recordings...
January 14, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28088798/the-intracranial-b2leed3s-score-and-the-risk-of-intracranial-hemorrhage-in-ischemic-stroke-patients-under-antiplatelet-treatment
#5
Pierre Amarenco, Leila Sissani, Julien Labreuche, Eric Vicaut, Marie Germaine Bousser, Angel Chamorro, Marc Fisher, Ian Ford, Kim M Fox, Michael G Hennerici, Heinrich Mattle, Peter M Rothwell, Philippe Gabriel Steg, Hans-Christoph Diener, Ralph L Sacco, Jacoba P Greving, Ale Algra
BACKGROUND: Chronic antiplatelet therapy in the post-acute phase of non-cardioembolic ischemic stroke is limited by the risk of intracranial hemorrhage (ICH) complications. METHODS: We developed an ICH risk score based on the PERFORM trial cohort (n = 19,100), which included patients with a non-cardioembolic ischemic stroke or transient ischemic attack, and externally validated this score in one contemporary trial of very similar size and inclusion criteria, the PRoFESS trial (n = 20,332 patients)...
January 14, 2017: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/28088797/automated-interpretation-of-pulmonary-function-tests-in-adults-with-respiratory-complaints
#6
Marko Topalovic, Stefan Laval, Jean-Marie Aerts, Thierry Troosters, Marc Decramer, Wim Janssens
BACKGROUND: The use of pulmonary function tests is primarily based on expert opinion and international guidelines. Current interpretation strategies are using predefined cutoffs for the description of a typical pattern. OBJECTIVES: We aimed to explore the predicted disease outcome based on the American Thoracic Society/European Respiratory Society (ATS/ERS) interpreting strategy. Subsequently, we investigated whether an unbiased machine learning framework integrating lung function with clinical variables may provide alternative decision trees resulting in a more accurate diagnosis...
January 12, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28088784/a-phase-i-clinical-study-of-autologous-dendritic-cell-therapy-in-patients-with-relapsed-or-refractory-multiple-myeloma
#7
Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Joon Haeng Rhee, Frank Emmrich, Je-Jung Lee
Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088782/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-sorafenib
#8
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
The combination of pemetrexed and sorafenib has significant clinical activity against a wide variety of tumor types in patients and the present studies were performed to determine whether sildenafil enhances the killing potential of [pemetrexed + sorafenib]. In multiple genetically diverse lung cancer cell lines, sildenafil enhanced the lethality of [pemetrexed + sorafenib]. The three-drug combination reduced the activities of AKT, mTOR and STAT transcription factors; increased the activities of eIF2α and ULK-1; lowered the expression of MCL-1, BCL-XL, thioredoxin and SOD2; and increased the expression of Beclin1...
January 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088775/diagnostic-accuracy-of-glycated-hemoglobin-for-post-transplantation-diabetes-mellitus-after-kidney-transplantation-systematic-review-and-meta-analysis
#9
Ana Laura Pimentel, Gabriela Cavagnolli, Joíza Lins Camargo
BACKGROUND: Early detection of post-transplantation diabetes mellitus (PTDM) allows prompt clinical and pharmacological interventions, reducing the chance of adverse outcomes. We conducted a systematic review and meta-analysis to determine the overall diagnostic accuracy of glycated hemoglobin (HbA1c) for the diagnosis of renal PTDM. METHODS: We searched MEDLINE, Embase and SCOPUS up to June 2016. Studies that included adults without previous diabetes were selected if they reported an oral glucose tolerance test as a reference test, HbA1c levels measured by standardized methods and data necessary for drawing 2 × 2 tables...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088772/thrombospondin-immune-regulation-and-the-kidney
#10
Claudio Ponticelli, Hans-Joachim Anders
Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF-β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF-β activation but regulates matrix remodeling and inflammation in experimental kidney disease...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088762/the-super-n-motifs-model-a-novel-alignment-free-approach-for-representing-and-comparing-rna-secondary-structures
#11
Jean-Pierre Séhi Glouzon, Jean-Pierre Perreault, Shengrui Wang
MOTIVATION: Comparing ribonucleic acid (RNA) secondary structures of arbitrary size uncovers structural patterns that can provide a better understanding of RNA functions. However, performing fast and accurate secondary structure comparisons is challenging when we take into account the RNA configuration (i.e. linear or circular), the presence of pseudoknot and G-quadruplex (G4) motifs and the increasing number of secondary structures generated by high-throughput probing techniques. To address this challenge, we propose the super-n-motifs model based on a latent analysis of enhanced motifs comprising not only basic motifs but also adjacency relations...
January 14, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28088761/amplification-of-unscheduled-dna-synthesis-signal-enables-fluorescence-based-single-cell-quantification-of-transcription-coupled-nucleotide-excision-repair
#12
Franziska Wienholz, Wim Vermeulen, Jurgen A Marteijn
Nucleotide excision repair (NER) comprises two damage recognition pathways: global genome NER (GG-NER) and transcription-coupled NER (TC-NER), which remove a wide variety of helix-distorting lesions including UV-induced damage. During NER, a short stretch of single-stranded DNA containing damage is excised and the resulting gap is filled by DNA synthesis in a process called unscheduled DNA synthesis (UDS). UDS is measured by quantifying the incorporation of nucleotide analogues into repair patches to provide a measure of NER activity...
January 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28088759/how-accurate-are-accurate-force-fields-for-b-dna
#13
Pablo D Dans, Ivan Ivani, Adam Hospital, Guillem Portella, Carlos González, Modesto Orozco
Last generation of force-fields are raising expectations on the quality of molecular dynamics (MD) simulations of DNA, as well as to the belief that theoretical models can substitute experimental ones in several cases. However these claims are based on limited benchmarks, where MD simulations have shown the ability to reproduce already existing 'experimental models', which in turn, have an unclear accuracy to represent DNA conformation in solution. In this work we explore the ability of different force-fields to predict the structure of two new B-DNA dodecamers, determined herein by means of (1)H nuclear magnetic resonance (NMR)...
January 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28088755/hispanic-mothers-beliefs-regarding-hpv-vaccine-series-completion-in-their-adolescent-daughters
#14
A M Roncancio, K K Ward, C C Carmack, B T Muñoz, F L Cribbs
Rates of human papillomavirus (HPV) vaccine series completion among adolescent Hispanic females in Texas in 2014 (∼39%) lag behind the Healthy People 2020 goal (80%). This qualitative study identifies Hispanic mothers' salient behavioral, normative and control beliefs regarding having their adolescent daughters complete the vaccine series. Thirty-two mothers of girls (aged 11-17) that had received at least one dose of the HPV vaccine, completed in-depth interviews. Six girls had received one dose of the HPV vaccine, 10 girls had received two doses, and 16 girls had received all three doses...
January 14, 2017: Health Education Research
https://www.readbyqxmd.com/read/28088751/chip-based-digital-surface-plasmon-resonance-sensing-platform-for-ultrasensitive-biomolecular-detection
#15
Ming-Yang Pan, Kuang-Li Lee, Likarn Wang, Pei-Kuen Wei
A chip-based ultrasensitive surface plasmon resonance (SPR) sensor in a checkerboard nanostructure on plastic substrates is presented for digital detection. The sensing elements on the checkerboard are composed of silver-capped nanoslit arrays, which were fabricated using the thermal-embossing nanoimprint method, to meet the demand for low-cost and rapid fabrication. Sharp Fano resonances in the optimized nanoslit arrays provide high-intensity sensitivities (20,000% per refractive index unit), with an element size of 12...
January 7, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28088750/continuous-minimally-invasive-alcohol-monitoring-using-microneedle-sensor-arrays
#16
A M Vinu Mohan, Joshua Ray Windmiller, Rupesh K Mishra, Joseph Wang
The present work describes an attractive skin-worn microneedle sensing device for the minimally invasive electrochemical monitoring of subcutaneous alcohol. The device consists of an assembly of pyramidal microneedle structures integrated with Pt and Ag wires, each with a microcavity opening. The microneedle aperture was modified by electropolymerizing o-phenylene diamine onto the Pt wire microtransducer, followed by the immobilization of alcohol oxidase (AOx) in an intermediate chitosan layer, along with an outer Nafion layer...
January 10, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28088748/a-dna-probe-based-on-phosphorescent-resonance-energy-transfer-for-detection-of-transgenic-35s-promoter-dna
#17
Jinzhi Lv, Yanming Miao, Jiajia Yang, Jin Qin, Dongxia Li, Guiqin Yan
A QDs-DNA nano-probe was made by combining Mn-doped ZnS room-temperature phosphorescence (RTP) quantum dots (QDs) and DNA. Then an RTP sensor for quantitative detection of genetically-modified mark sequence cauliflower mosaic virus 35S promoter (Ca MV 35S) DNA was built on basis of phosphorescent resonance energy transfer (PRET). The underlying principles were that a QDs-DNA water-soluble nano-probe was built by connecting single-strand DNA to the surfaces of QDs via a ligand exchange method. This probe had good RTP performance and could well identify Ca MV 35S...
January 7, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28088740/associations-between-adverse-childhood-experiences-student-teacher-relationships-and-non-medical-use-of-prescription-medications-among-adolescents
#18
Myriam Forster, Amy L Gower, Iris W Borowsky, Barbara J McMorris
OBJECTIVE: Few studies have investigated associations between adverse childhood experiences (ACE) and nonmedical use of prescription medication (NMUPM) in population-based samples of adolescents, and even fewer have examined whether promotive factors might buffer these effects. The present study assesses the direct effects of ACE and positive student-teacher relationships on NUMPD and whether positive student-teacher relationships moderate this association. DESIGN: Data were from the 2013 Minnesota Student Survey (MSS), an in-school survey administered every three years to students throughout Minnesota...
January 6, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28088737/the-hemostatic-effect-study-of-cirsium-setosum-on-regulating-%C3%AE-1-ars-via-mediating-norepinephrine-synthesis-by-enzyme-catalysis
#19
Nianwei Chang, Yanmei Li, Mengge Zhou, Jie Gao, Yuanyuan Hou, Min Jiang, Gang Bai
BACKGROUND: Cirsium setosum (CS) is the aboveground part of Cephalanoplos segetum Kitam. Although it has been used as a hemostatic treatment for thousands of years and is still in use today, the mechanism of CS on regulating ARs is still not clear. PURPOSE: In this study, we aimed to clarify the mechanism of CS on regulating ARs. METHODS: We developed a simple method based on UPLC/Q-TOF MS combined adrenergic receptor dual-luciferase reporter assay systems for the rapid determination of active constituents in CS...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088723/discovery-and-metagenomic-analysis-of-an-anammox-bacterial-enrichment-related-to-candidatus-brocadia-caroliniensis-in-a-full-scale-glycerol-fed-nitritation-denitritation-separate-centrate-treatment-process
#20
Hongkeun Park, Ariane C Brotto, Mark C M van Loosdrecht, Kartik Chandran
A distinctive red biofilm was observed in a glycerol-fed digester liquid effluent treatment process coupling partial nitrification (nitritation) and partial denitrification (denitritation) processes. Based on initial phylogenetic screening using 16S rRNA clone libraries and quantitative polymerase chain reaction, the biofilm was enriched in novel anaerobic ammonium oxidizing bacteria (AMX/anammox) closely related to Candidatus "Brocadia caroliniensis". The metabolic functionality of the C. "Brocadia caroliniensis" enrichment was further explored using high-throughput sequencing and de novo metagenome assembly...
January 6, 2017: Water Research
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