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Dosage sensitivity

Sahin Naqvi, Daniel W Bellott, Kathy S Lin, David C Page
Mammalian X and Y Chromosomes evolved from an ordinary autosomal pair. Genetic decay of the Y led to X Chromosome inactivation (XCI) in females, but some Y-linked genes were retained during the course of sex chromosome evolution, and many X-linked genes did not become subject to XCI. We reconstructed gene-by-gene dosage sensitivities on the ancestral autosomes through phylogenetic analysis of microRNA (miRNA) target sites and compared these preexisting characteristics to the current status of Y-linked and X-linked genes in mammals...
February 15, 2018: Genome Research
Rekha Yamini Kosuru, Md Aashique, Aisha Fathima, Amrita Roy, Soumen Bera
AIM: To understand the effects of gallic acid (GA) on ampicillin (Amp) sensitive or resistant strain of Pseudomonas sp. and also in modulating the corresponding biofilms. METHODOLOGY: The cell viability was determined by broth dilution, dry weight and CFU assays. Biofilm formation was measured by crystal violet assay while oxygen consumption rate was measured to verify the metabolic status of the cells. The membrane damage and drug efflux/accumulation were studied by fluorimetric assays...
February 15, 2018: Future Microbiology
Antoine Iannessi, Hubert Beaumont, Christophe Hebert, Claire Dittlot, Marie Noëlle Falewee
OBJECTIVE: The measure of body surface area (BSA) is a standard for planning optimal dosing in oncology. This index is derived from a model having questionable performances. In this study, we proposed measurement of BSA from whole body CT images (iBSA). We tested the reliability of iBSA assessments and simulated the impact of our approach on patient chemotherapy dosage planning. METHODS: We first evaluated accuracy and precision of iBSA in measuring 14 phantom and 11 CT test-retest images...
2018: PloS One
Andrew D Wiese, Marie R Griffin, William Schaffner, C Michael Stein, Robert A Greevy, Edward F Mitchel, Carlos G Grijalva
Background: Although certain opioid analgesics have immunosuppressive properties and increase the risk for infections in animals, the clinical effects of prescription opioid use on infection risk among humans are unknown. Objective: To test the hypothesis that prescription opioid use is an independent risk factor for invasive pneumococcal disease (IPD). Design: Nested case-control study. Setting: Tennessee Medicaid database linked to Medicare and Active Bacterial Core surveillance system databases (1995 to 2014)...
February 13, 2018: Annals of Internal Medicine
Chunhong Liu, Tao Yu, Zhuo Xing, Xiaoling Jiang, Yichen Li, Annie Pao, Justin Mu, Paul K Wallace, George Stoica, Andrei V Bakin, Y Eugene Yu
Individuals with Down syndrome (DS) frequently have hematopoietic abnormalities, including transient myeloproliferative disorder and acute megakaryoblastic leukemia which are often accompanied by acquired GATA1 mutations that produce a truncated protein, GATA1s. The mouse has been used for modeling DS based on the syntenic conservation between human chromosome 21 (Hsa21) and three regions in the mouse genome located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. To assess the impact of the dosage increase of Hsa21 gene orthologs on the hematopoietic system, we characterized the related phenotype in the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ model which carries duplications spanning the entire Hsa21 orthologous regions on Mmu10, Mmu16 and Mmu17, and the Dp(10)1Yey /+; Dp(16)1Yey /+; Dp(17)1Yey/+ ; Gata1 Yeym2 model which carries a Gata1s mutation we engineered...
January 12, 2018: Oncotarget
Lorenzo A Saraiva, Florence P Castelan, Bruna L Gomes, Eduardo Purgatto, Beatriz R Cordenunsi-Lysenko
Brazil is a major producer and consumer of various banana types. Thap Maeo is a promising cultivar for the market due to its resistance to Black and Yellow Sigatoka disease. However, a lack of information and postharvest technologies concerning Thap Maeo physiology seems to be a significant problem limiting its expansion in the market. Thus, this study aims to establish Thap Maeo fruit's physical, biochemical, and physiological aspects, defining the best ethylene dosage for treatment considering fruit ripening parameters...
March 2018: Food Research International
Meade Haller, Jason Au, Marisol O'Neill, Dolores J Lamb
Genitourinary (GU) birth defects are among the most common yet least studied congenital malformations. Congenital anomalies of the kidney and urinary tract (CAKUTs) have high morbidity and mortality rates and account for ∼30% of structural birth defects. Copy number variation (CNV) mapping revealed that 16p11.2 is a hotspot for GU development. The only gene covered collectively by all of the mapped GU-patient CNVs was MYC-associated zinc finger transcription factor (MAZ), and MAZ CNV frequency is enriched in nonsyndromic GU-abnormal patients...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jonas Alex Morales Saute, Laura Bannach Jardim
Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant multiple neurological systems degenerative disorder caused by a CAG repeat expansion at ATXN3 gene. Only a few treatments were evaluated in randomized clinical trials (RCT) in SCA3/MJD patients, with a lack of evidence for both disease-modifying and symptomatic therapies. The present chapter discuss in detail major methodological issues for planning future RCT for SCA3/MJD. There are several potential therapies for SCA3/MJD with encouraging preclinical results...
2018: Advances in Experimental Medicine and Biology
Lei Chen, Yanting He, Zhixian Lei, Chenling Gao, Qing Xie, Ping Tong, Zian Lin
Core-shell structured magnetic covalent organic framework (Fe3O4@COF) nanocomposites were synthesized via a facile approach at room temperature and explored as an absorbent for magnetic solid-phase extraction (MSPE) of bisphenols (BPs) from human serum sample. The as-prepared Fe3O4@COF nanocomposites with core-shell structure possessed high specific surface area (181.36m2/g), uniform mesoporous size (~ 3.6nm), high saturation magnetization (42.7emu/g), and excellent thermal and chemical stability, rendering it as an ideal adsorbent with high adsorption efficiency and size selectivity...
May 1, 2018: Talanta
Muthupandian Saravanan, Tsehaye Asmalash, Atsebaha Gebrekidan, Dawit Gebreegziabiher, Tadele Araya, Haftamu Hilekiros, Hamed Barabadi, Kumaresan Ramanathan
BACKGROUND: Human Immuno deficiency Virus (HIV) infection has attained pandemic level due to its complexity on both the HIV infection cycle and on the targets for drug delivery. This limits medication and consequently requires prominent and promising drug delivery systems to be invented. Notably, various nanomaterial have been studied to enhance effective delivery of the antiretroviral drugs for HIV prevention, diagnosis and cure. Some of these nanomaterials are liposomes, dendrimers, inorganic nanoparticles (NPs), polymeric micelles, natural and synthetic polymers...
February 8, 2018: Pharmaceutical Nanotechnology
Beata Aleksiūnienė, Egle Preiksaitiene, Aušra Morkūnienė, Laima Ambrozaitytė, Algirdas Utkus
Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23...
February 9, 2018: Cytogenetic and Genome Research
Hong Tran, Hongxiao Zhu, Xiaowei Wu, Gunjune Kim, Christopher R Clarke, Hailey Larose, David C Haak, Shawn D Askew, Jacob N Barney, James H Westwood, Liqing Zhang
Deoxyribonucleic acid (DNA) methylation is an epigenetic alteration crucial for regulating stress responses. Identifying large-scale DNA methylation at single nucleotide resolution is made possible by whole genome bisulfite sequencing. An essential task following the generation of bisulfite sequencing data is to detect differentially methylated cytosines (DMCs) among treatments. Most statistical methods for DMC detection do not consider the dependency of methylation patterns across the genome, thus possibly inflating type I error...
February 8, 2018: Genes
Ku-Chou Chang, Jen-Wen Hung, Hsuei-Chen Lee, Chu-Ling Yen, Ching-Yi Wu, Chung-Lin Yang, Yu-Ching Huang, Pei-Li Lin, Hui-Hsuan Wang
BACKGROUND: It remains unclear whether rehabilitation has an impact on reducing the long-term risk of mortality or readmission following stroke or transient ischemic attack (TIA). OBJECTIVES: To investigate the association between the dosage and continuation of rehabilitation and the risk of outcome events (OEs) after stroke or TIA. RESEARCH DESIGN: A retrospective cohort study using Taiwan's National Health Insurance database. SUBJECTS: In total, 4594 patients admitted with first-ever acute stroke or TIA were followed-up for 32 months...
February 6, 2018: Medical Care
Mahmoud A Omar, Abdel-Maaboud I Mohamed, Sayed M Derayea, Mohamed A Hammad, Abobakr A Mohamed
A new, selective and sensitive spectrofluorimetric method was designed for the quantitation of doxazosin (DOX), terazosin (TER) and alfuzosin (ALF) in their dosage forms and human plasma. The method adopts efficient derivatization of the studied drugs with ortho-phthalaldehyde (OPA), in the presence of 2-mercaptoethanol in borate buffer (pH9.7) to generate a highly fluorescent isoindole derivatives, which can strongly enhance the fluorescence intensities of the studied drugs, allowing their sensitive determination at 430nm after excitation at 337nm...
February 1, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Bradley E Chipps, Paul Newbold, Ian Hirsch, Frank Trudo, Mitchell Goldman
BACKGROUND: Patients with severe asthma can have eosinophilic inflammation and/or allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody being developed for patients with severe, uncontrolled asthma with eosinophilic inflammation. OBJECTIVE: To investigate the efficacy of benralizumab by atopic status and serum immunoglobulin E (IgE) concentrations. METHODS: We analyzed pooled results from the SIROCCO (NCT01928771) and CALIMA (NCT01914757) Phase III studies...
January 31, 2018: Annals of Allergy, Asthma & Immunology
Mathilde Duchesne, Aurore Danigo, Laurence Richard, Jean-Michel Vallat, Shahram Attarian, Pierre-Marie Gonnaud, Arnaud Lacour, Yann Péréon, Tania Stojkovic, Klaus-Armin Nave, Viviane Bertrand, Serguei Nabirotchkin, Daniel Cohen, Claire Demiot, Laurent Magy
Charcot-Marie-Tooth disease type 1A (CMT1A), the most common form of Charcot-Marie-Tooth diseases, is a demyelinating neuropathy caused by a deletion encompassing the gene coding for PMP22, a myelin protein of the peripheral nervous system. Although myelinated fibers are mostly involved in CMT1A, some patients experience neuropathic pain. We thus investigated whether unmyelinated fibers are lost in CMT1A. Skin biopsies were taken from the distal portion of the leg of 80 patients with CMT1A as part of the PXT30003-01 study and processed for quantification of intraepidermal nerve fiber density (IENFD)...
February 2, 2018: Journal of Neuropathology and Experimental Neurology
Ahmed M E Khalil, Osama Eljamal, Bidyut Baran Saha, Nobuhiro Matsunaga
Nanoscale zero-valent iron (nZVI) is a versatile treatment reagent that should be utilized in an effective application for nitrate remediation in water. For this purpose, a laboratory-scale continuous-flow system (LSCFS) was developed to evaluate nZVI performance in removal of nitrate in different contaminated-water bodies. The equipment design (reactor, settler, and polisher) and operational parameters of the LSCFS were determined based on nZVI characterization and nitrate reduction kinetics. Ten experimental runs were conducted at different dosages (6, 10 and 20 g) of nZVI-based reagents (nZVI, bimetallic nZVI-Cu, CuCl2-added nZVI)...
January 18, 2018: Chemosphere
J Marto, P Pinto, M Fitas, L M Gonçalves, A J Almeida, H M Ribeiro
The safety profile of the ingredients used in topical dosage forms and its evaluation is an issue of utmost importance. A suitable equilibrium between safety and efficacy is crucial before promoting a dermatological product. The aim of this work was to assess the safety and biological effects of starch-based vehicles (St-BV) used in such products. The hazard, exposure and dose-response assessment were used to characterize the risk of each ingredient. The EpiSkin™ assay and human repeat insult patch tests were performed to compare the theoretical safety assessment to in vitro and in vivo data...
January 31, 2018: Toxicology and Applied Pharmacology
Shiming Ding, Qin Sun, Xiang Chen, Qing Liu, Dan Wang, Juan Lin, Chaosheng Zhang, Daniel C W Tsang
Iron redox cycle plays a primary role in controlling the mobility of P in sediments. It is crucial to better understand how lanthanum (La) modified bentonite (LMB, Phoslock®), an increasingly employed capping agent, immobilizes P from sediments by altering Fe redox-coupled P cycling. Batch adsorption experiments found that LMB effectively adsorbed Fe(II) with a capacity of 8.51 mg g-1. Fe(II)-preloaded LMB effectively retained P during a 518-hour equilibration, while up to 16.7% of adsorbed P was release-sensitive in LMB without Fe(II) preloading...
February 1, 2018: Water Research
Tânia A P Fernandes, João P Aguiar, Ana I Fernandes, João F Pinto
A simple, accurate and sensitive high-performance liquid chromatography (HPLC) method was developed, validated and applied to the determination of either theophylline or paracetamol in milk-based samples. The method allowed drug quantification in fresh and powdered milk with a relatively short run time of analysis and it was also successfully applied to the quantification of the drugs in solid dosage forms intended for pediatric use. Moreover, the main significant advantages over other published works are the simplicity of the sample preparation, reduced assay time and sample loss...
December 2017: Journal of Pharmaceutical Analysis
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