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https://www.readbyqxmd.com/read/29777772/improving-maraviroc-oral-bioavailability-by-formation-of-solid-drug-nanoparticles
#1
Alison C Savage, Lee M Tatham, Marco Siccardi, Trevor Scott, Manoli Vourvahis, Andrew Clark, Steve P Rannard, Andrew Owen
Oral drug administration remains the preferred approach for treatment of HIV in most patients. Maraviroc (MVC) is the first in class co-receptor antagonist, which blocks HIV entry into host cells. MVC has an oral bioavailability of approximately 33%, which is limited by poor permeability as well as affinity for CYP3A and several drug transporters. While once-daily doses are now the favoured option for HIV therapy, dose-limiting postural hypotension has been of theoretical concern when administering doses high enough to achieve this for MVC (particularly during coadministration of enzyme inhibitors)...
May 16, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29777582/comparative-study-of-liraglutide-and-insulin-glargine-on-glycemic-control-and-pancreatic-%C3%AE-cell-function-in-db-db-mice
#2
Yanli Li, Jia Zheng, Yunfeng Shen, Wangen Li, Meimei Liu, Jun Wang, Surong Zhu, Meihua Wu
BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age...
May 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29777573/quantiferon-cytomegalovirus-assay-a-potentially-useful-tool-in-the-evaluation-of-cmv-specific-cd8-t-cell-reconstitution-in-pediatric-hematopoietic-stem-cell-transplant-patients
#3
Bilio Paouri, Alexandra Soldatou, Eftihia Petrakou, Maria Theodosaki, Charalampos Tsentidis, Katerina Kaisari, Christina Oikonomopoulou, Minos Matsas, Eugenios Goussetis
Pediatric HSCT recipients are at high risk for CMV reactivation due to their immature immune system and therapy following transplantation. Reconstitution of CMV-specific T-cell immunity is associated with control and protection against CMV. The clinical utility of monitoring CMV-specific CMI to predict CMV viremia in pediatric HSCT patients using the Quantiferon-CMV (QIAGEN® ) test was investigated prospectively. Thirty-seven pediatric allogeneic HSCT recipients were enrolled from 3/2010-6/2012. CMV viremia was detected via weekly real-time PCR...
May 18, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29777455/combined-preoperative-albi-and-fib-4-is-associated-with-recurrence-of-hepatocellular-carcinoma-after-curative-hepatectomy
#4
Rui Liao, De-Wei Li, Cheng-You Du, Ming Li
BACKGROUND AND PURPOSE: Chronic inflammatory response is a risk factor for hepatocarcinogenesis and recurrence. This study aimed to develop a nomogram incorporating the combined albumin-bilirubin (ALBI) and fibrosis-4 (FIB-4) scores and the peritumoral inflammation score (PIS) to predict postoperative recurrence-free survival (RFS) of hepatocellular carcinoma (HCC). METHODS: The prognostic roles of preoperative ALBI and FIB-4 scores for HCC recurrence were investigated, and a nomogram was developed...
May 18, 2018: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/29777291/growth-of-asymptomatic-intracranial-fusiform-aneurysms-incidence-and-risk-factors
#5
Jusun Moon, Young Dae Cho, Dong Hyun Yoo, Jeongjun Lee, Hyun-Seung Kang, Won-Sang Cho, Jeong Eun Kim, Li Zhang, Moon Hee Han
PURPOSE: Growth of intracranial fusiform aneurysms (IFA) may become clinically problematic through a mass effect or rupture. We investigated the growth rate and factors contributing to growth in asymptomatic untreated IFA. METHOD: As a retrospective review, we assessed patients diagnosed with asymptomatic IFA between August 2000 and September 2014, all untreated. No acute or symptomatic dissecting lesions were considered. Clinical and serial angiographic follow-up data were analyzed, defining growth as expansion > 2 mm in one or more dimensions...
May 18, 2018: Clinical Neuroradiology
https://www.readbyqxmd.com/read/29777252/noninvasively-evaluating-the-grading-and-idh1-mutation-status-of-diffuse-gliomas-by-three-dimensional-pseudo-continuous-arterial-spin-labeling-and-diffusion-weighted-imaging
#6
Tingting Liu, Guang Cheng, Xiaowei Kang, Yibin Xi, Yuanqiang Zhu, Kai Wang, Chao Sun, Jing Ye, Ping Li, Hong Yin
PURPOSE: To noninvasively evaluate the value of three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) and diffusion-weighted imaging (DWI) in diffuse gliomas grading as well as isocitrate dehydrogenase (IDH) 1 mutation status. METHODS: Fifty-six patients with pathologically confirmed diffuse gliomas with preoperative 3D pCASL and DWI were enrolled in this study. The Student's t test and Mann-Whitney U test were used to evaluate differences in parameters of DWI and 3D pCASL between low and high grade as well as between mutant and wild-type IDH1 diffuse gliomas; receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance...
May 18, 2018: Neuroradiology
https://www.readbyqxmd.com/read/29777062/brock-malignancy-risk-calculator-for-pulmonary-nodules-validation-outside-a-lung-cancer-screening-population
#7
Kaman Chung, Onno M Mets, Paul K Gerke, Colin Jacobs, Annemarie M den Harder, Ernst T Scholten, Mathias Prokop, Pim A de Jong, Bram van Ginneken, Cornelia M Schaefer-Prokop
OBJECTIVE: To assess the performance of the Brock malignancy risk model for pulmonary nodules detected in routine clinical setting. METHODS: In two academic centres in the Netherlands, we established a list of patients aged ≥40 years who received a chest CT scan between 2004 and 2012, resulting in 16 850 and 23 454 eligible subjects. Subsequent diagnosis of lung cancer until the end of 2014 was established through linking with the National Cancer Registry...
May 18, 2018: Thorax
https://www.readbyqxmd.com/read/29777022/further-studies-to-support-the-use-of-coproporphyrin-i-and-iii-as-novel-clinical-biomarkers-for-evaluating-the-potential-for-organic-anion-transporting-polypeptide-oatp-1b1-and-oatp1b3-inhibition
#8
Hong Shen, Lisa Christopher, Yurong Lai, Jiachang Gong, Hamza Kandoussi, Samira Garonzik, Vidya Perera, Tushar Garimella, W Griffith Humphreys
In a recent study, limited to South Asian Indian subjects (n=12), coproporphyrin I and III (CPI and CPIII) demonstrated properties appropriate for an OATP1B endogenous probe (Lai et al., 2016). The current studies were conducted in healthy volunteers of mixed ethnicities, including black, white, and Hispanic subjects to better understand the utility of these biomarkers in broader populations. After oral administration with 600 mg rifampin, AUC(0-24h) values were 2.8-, 3.7- and 3.6-fold higher than predose levels for CPI and 2...
May 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29776961/mr-proadm-as-a-prognostic-marker-in-patients-with-st-segment-elevation-myocardial-infarction-danami-3-a-danish-study-of-optimal-acute-treatment-of-patients-with-stemi-substudy
#9
Alexander C Falkentoft, Rasmus Rørth, Kasper Iversen, Dan E Høfsten, Henning Kelbæk, Lene Holmvang, Martin Frydland, Mikkel M Schoos, Steffen Helqvist, Anna Axelsson, Peter Clemmensen, Erik Jørgensen, Kari Saunamäki, Hans-Henrik Tilsted, Frants Pedersen, Christian Torp-Pedersen, Klaus F Kofoed, Jens P Goetze, Thomas Engstrøm, Lars Køber
BACKGROUND: Midregional proadrenomedullin (MR-proADM) has demonstrated prognostic potential after myocardial infarction (MI). Yet, the prognostic value of MR-proADM at admission has not been examined in patients with ST-segment-elevation MI (STEMI). METHODS AND RESULTS: The aim of this substudy, DANAMI-3 (The Danish Study of Optimal Acute Treatment of Patients with ST-segment-elevation myocardial infarction), was to examine the associations of admission concentrations of MR-proADM with short- and long-term mortality and hospital admission for heart failure in patients with ST-segment-elevation myocardial infarction...
May 18, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29776852/indications-for-mars-mri-in-patients-treated-with-articular-surface-replacement-xl-total-hip-arthroplasty
#10
James W Connelly, Vincent P Galea, Inari Laaksonen, Sean J Matuszak, Rami Madanat, Orhun Muratoglu, Henrik Malchau
BACKGROUND: The purpose of this study was to identify which patient and clinical factors are predictive of adverse local tissue reaction (ALTR) and to use these factors to create a highly sensitive algorithm for indicating metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) in Articular Surface Replacement (ASR) XL total hip arthroplasty patients. Our secondary aim was to compare our algorithm to existing national guidelines on when to take MARS-MRI in metal-on-metal total hip arthroplasty patients...
April 19, 2018: Journal of Arthroplasty
https://www.readbyqxmd.com/read/29776564/the-prognostic-value-of-high-sensitivity-c-reactive-protein-in-a-multi-ethnic-population-after-10-years-of-follow-up-the-multi-ethnic-study-of-atherosclerosis-mesa
#11
Miguel Cainzos-Achirica, Michael D Miedema, John W McEvoy, Mary Cushman, Zeina Dardari, Philip Greenland, Khurram Nasir, Matthew J Budoff, Mouaz H Al-Mallah, Joseph Yeboah, Roger S Blumenthal, Josep Comin-Colet, Michael J Blaha
BACKGROUND: The prognostic value of hsCRP in contemporary multi-ethnic populations is unclear, particularly in statin users. The aim of this study was to characterize the prognostic utility of hsCRP for atherosclerotic CVD (ASCVD) risk prediction in a multi-ethnic population including non-users and users of statins followed for >13 years. Associations with heart failure (HF), atrial fibrillation (AF), venous thromboembolism (VTE), cancer, and all-cause death were also examined. METHODS AND RESULTS: We evaluated 6757 participants from the Multi-Ethnic Study of Atherosclerosis (MESA; 1002 using statins at baseline), median follow-up 13...
August 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29776390/development-of-a-normal-tissue-complication-probability-ntcp-model-for-radiation-induced-hypothyroidism-in-nasopharyngeal-carcinoma-patients
#12
Ren Luo, Vincent W C Wu, Binghui He, Xiaoying Gao, Zhenxi Xu, Dandan Wang, Zhining Yang, Mei Li, Zhixiong Lin
BACKGROUND: The objectives of this study were to build a normal tissue complication probability (NTCP) model of radiation-induced hypothyroidism (RHT) for nasopharyngeal carcinoma (NPC) patients and to compare it with other four published NTCP models to evaluate its efficacy. METHODS: Medical notes of 174 NPC patients after radiotherapy were reviewed. Biochemical hypothyroidism was defined as an elevated level of serum thyroid-stimulating hormone (TSH) value with a normal or decreased level of serum free thyroxine (fT4) after radiotherapy...
May 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29776319/biometric-factors-associated-with-the-visual-performance-of-a-high-addition-multifocal-intraocular-lens
#13
Joaquín Fernández, Manuel Rodríguez-Vallejo, Javier Martínez, Ana Tauste, David P Piñero
Purpose/Aim: To evaluate the impact of ocular parameters on the visual performance achieved with the multifocal intraocular lens (IOL) Bi-Flex M 677MY. MATERIALS AND METHODS: 26 subjects were included in the current study. Several physiological variables were retrieved from the 3-month follow-up visit, including pupil diameter and distance from pupil center to the vertex normal of the anterior cornea (µ). These variables were also obtained in the preoperative visit. Binocular and monocular visual acuity defocus curves were measured at 1 and 3 months after surgery, respectively...
May 18, 2018: Current Eye Research
https://www.readbyqxmd.com/read/29776316/a-systematic-review-and-combined-analysis-of-therapeutic-drug-monitoring-studies-for-oral-paliperidone
#14
Georgios Schoretsanitis, Edoardo Spina, Christoph Hiemke, Jose de Leon
This article includes a combined analysis of therapeutic drug monitoring (TDM) studies and a review of the marketer's data on pharmacological mechanisms. Areas covered: An article search led to the inclusion of 21 paliperidone studies in the systematic review plus 2 case reports. Paliperidone clearance was calculated from: 1) steady-state studies using concentration/dose (C/D) ratios, and 2) single-dose studies describing 24-hour area under the curve calculations. The marketed extended-release formulation has 28% bioavailability...
May 18, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29775997/improved-acmg-compliant-in-silico-prediction-of-pathogenicity-for-missense-substitutions-encoded-by-tp53-variants
#15
Cristina Fortuno, Paul A James, Erin L Young, Bing Feng, Magali Olivier, Tina Pesaran, Sean V Tavtigian, Amanda B Spurdle
Clinical interpretation of germline missense variants represents a major challenge, including those in the TP53 Li-Fraumeni syndrome gene. Bioinformatic prediction is a key part of variant classification strategies. We aimed to optimize the performance of the Align-GVGD tool used for p53 missense variant prediction, and compare its performance to other bioinformatic tools (SIFT, PolyPhen-2) and ensemble methods (REVEL, BayesDel). Reference sets of assumed pathogenic and assumed benign variants were defined using functional and/or clinical data...
May 18, 2018: Human Mutation
https://www.readbyqxmd.com/read/29775811/determination-of-docetaxel-in-dried-blood-spots-by-lc-ms-ms-method-development-validation-and-clinical-application
#16
S Raymundo, V V Muller, N B Andriguetti, M Tegner, A C Artmann, H M Kluck, M A Franzoi, R M M Vilela, G Schwartsmann, R Linden, M V Antunes
In this study, a LC-MS/MS method for the measurement of docetaxel in Dried Blood Spots (DBS) samples was developed and validated. Docetaxel was extracted from 8 mm DBS punch with a mixture of methanol and acetonitrile (9:1, v/v). The chromatographic separation occurred in an Acquity® C18 column (150 × 2.1 mm, 1.7 μm) eluted with a mixture of water and acetonitrile plus 0.1% formic acid (45:55, v/v). Total analytical run time was 7 min. The method was linear from 50 to 3000 ng ml-1 . Precision assays showed CV% < 9...
May 15, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29775421/probability-of-heat-intolerance-standardized-interpretation-of-heat-tolerance-testing-results-versus-specialist-judgment
#17
Haggai Schermann, Erin Craig, Einat Yanovich, Itay Ketko, Gary Kalmanovich, Ran Yanovich
CONTEXT:   The heat-tolerance test (HTT) is a screening tool for secondary prevention of exertional heat illness by the Israel Defense Forces. To discern participant tolerance, recruits are exposed to intermediate environmental and exercise stresses, and their physiological responses, core temperature, and heart rate are monitored. When their physiological measures rise at a higher rate or exceed the upper levels of absolute values compared with other participants, heat intolerance (HI) is diagnosed...
April 2018: Journal of Athletic Training
https://www.readbyqxmd.com/read/29775114/oxygen-dependency-of-mitochondrial-metabolism-indicates-outcome-of-newborn-brain-injury
#18
Gemma Bale, Subhabrata Mitra, Isabel de Roever, Magdalena Sokolska, David Price, Alan Bainbridge, Roxana Gunny, Cristina Uria-Avellanal, Giles S Kendall, Judith Meek, Nicola J Robertson, Ilias Tachtsidis
There is a need for a method of real-time assessment of brain metabolism during neonatal hypoxic-ischaemic encephalopathy (HIE). We have used broadband near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation and metabolic changes in 50 neonates with HIE undergoing therapeutic hypothermia treatment. In 24 neonates, 54 episodes of spontaneous decreases in peripheral oxygen saturation (desaturations) were recorded between 6 and 81 h after birth. We observed differences in the cerebral metabolic responses to these episodes that were related to the predicted outcome of the injury, as determined by subsequent magnetic resonance spectroscopy derived lactate/N-acetyl-aspartate...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29775022/-establishment-of-the-characterization-of-an-adult-digits-in-noise-test-based-on-internet
#19
B E Qi, T B Zhang, X X Fu, G P Li
Objective: The aim of this study is to explore the sensitivity and specificity of the internet-based digital noise threshold (DIN) test for detecting noise-induced hearing loss, expecting to provide a rapid and effective screening tool for clinical application. Method: This study enrolled 50 adult subjects, of which 34 were normal hearing (NH), 16 patients with sensorineural hearing loss (SNHL). Pure-tone audiometry, acoustic immittance and DIN test were tested respectively. Pearson's correlation coefficient was used to analyze the correlation between NH and SNHL...
February 2018: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29774987/an-increased-percentage-of-myeloid-cd34-bone-marrow-cells-stratifies-intermediate-ipss-r-myelodysplastic-syndrome-patients-into-prognostically-significant-groups
#20
T-H Chen-Liang, A M Casado-Prieto, V Campos-Rodríguez, A M Hurtado, M L Amigo, M D García-Malo, V Vicente, F J Ortuño, A Jerez
INTRODUCTION: The Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndromes (MDS) has established an intermediate category where a disease-modifying intervention is a matter of debate. Flow cytometry allows us to determine a fraction of immature myeloid cells in a semiautomated procedure. The aim of this study, mirroring IPSS-R study inclusion criteria, was to test whether bone marrow (BM) CD34+My percentage has independent prognostic value in the MDS setting...
May 18, 2018: International Journal of Laboratory Hematology
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