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https://www.readbyqxmd.com/read/29245084/application-of-analytical-quality-by-design-principles-for-the-determination-of-alkyl-p-toluenesulfonates-impurities-in-aprepitant-by-hplc-validation-using-total-error-concept
#1
Constantinos K Zacharis, Elli Vastardi
In the research presented we report the development of a simple and robust liquid chromatographic method for the quantification of two genotoxic alkyl sulphonate impurities (namely methyl p-toluenesulfonate and isopropyl p-toluenesulfonate) in Aprepitant API substances using the Analytical Quality by Design (AQbD) approach. Following the steps of AQbD protocol, the selected critical method attributes (CMAs) were the separation criterions between the critical peak pairs, the analysis time and the peak efficiencies of the analytes...
December 7, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29244865/the-arabidopsis-thaliana-f-box-gene-hawaiian-skirt-is-a-new-player-in-the-microrna-pathway
#2
Xuebin Zhang, Dasuni Jayaweera, Janny L Peters, Judit Szecsi, Mohammed Bendahmane, Jeremy A Roberts, Zinnia H González-Carranza
In Arabidopsis, the F-box HAWAIIAN SKIRT (HWS) protein is important for organ growth. Loss of function of HWS exhibits pleiotropic phenotypes including sepal fusion. To dissect the HWS role, we EMS-mutagenized hws-1 seeds and screened for mutations that suppress hws-1 associated phenotypes. We identified shs-2 and shs-3 (suppressor of hws-2 and 3) mutants in which the sepal fusion phenotype of hws-1 was suppressed. shs-2 and shs-3 (renamed hst-23/hws-1 and hst-24/hws-1) carry transition mutations that result in premature terminations in the plant homolog of Exportin-5 HASTY (HST), known to be important in miRNA biogenesis, function and transport...
2017: PloS One
https://www.readbyqxmd.com/read/29243391/bayesian-molecular-dating-opening-up-the-black-box
#3
Lindell Bromham, Sebastián Duchêne, Xia Hua, Andrew M Ritchie, David A Duchêne, Simon Y W Ho
Molecular dating analyses allow evolutionary timescales to be estimated from genetic data, offering an unprecedented capacity for investigating the evolutionary past of all species. These methods require us to make assumptions about the relationship between genetic change and evolutionary time, often referred to as a 'molecular clock'. Although initially regarded with scepticism, molecular dating has now been adopted in many areas of biology. This broad uptake has been due partly to the development of Bayesian methods that allow complex aspects of molecular evolution, such as variation in rates of change across lineages, to be taken into account...
December 15, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29242827/abrupt-shift-in-the-observed-runoff-from-the-southwestern-greenland-ice-sheet
#4
Andreas P Ahlstrøm, Dorthe Petersen, Peter L Langen, Michele Citterio, Jason E Box
The recent decades of accelerating mass loss of the Greenland ice sheet have arisen from an increase in both surface meltwater runoff and ice flow discharge from tidewater glaciers. Despite the role of the Greenland ice sheet as the dominant individual cryospheric contributor to sea level rise in recent decades, no observational record of its mass loss spans the 30-year period needed to assess its climatological state. We present for the first time a 40-year (1975-2014) time series of observed meltwater discharge from a >6500-km2 catchment of the southwestern Greenland ice sheet...
December 2017: Science Advances
https://www.readbyqxmd.com/read/29242739/healthy-food-availability-among-food-sources-in-rural-maryland-counties
#5
Elizabeth A Campbell, Myra J Shapiro, Claire Welsh, Sara N Bleich, Laura K Cobb, Joel Gittelsohn
Most studies examining the association of the food environment and health outcomes have focused on urban settings. However, rural adults and children have high rates of obesity, which may be related to their food environments. This study examines the food environment in 7 rural counties in Maryland. A cross-sectional study was conducted at 244 retail food stores from 2012 to 2013. Data on store-level characteristics were collected and a healthy food availability index (HFAI) ranging from 0 to 31 points was calculated for each store...
2017: Journal of Hunger & Environmental Nutrition
https://www.readbyqxmd.com/read/29242531/long-noncoding-rna-expression-profile-reveals-lncrnas-signature-associated-with-extracellular-matrix-degradation-in-kashin-beck-disease
#6
Cuiyan Wu, Huan Liu, Feng'e Zhang, Wanzhen Shao, Lei Yang, Yujie Ning, Sen Wang, Guanghui Zhao, Byeong Jae Lee, Mikko Lammi, Xiong Guo
Kashin-Beck disease (KBD) is a deformative, endemic osteochondropathy involving degeneration and necrosis of growth plates and articular cartilage. The pathogenesis of KBD is related to gene expression and regulation mechanisms, but long noncoding RNAs (lncRNAs) in KBD have not been investigated. In this study, we identified 316 up-regulated and 631 down-regulated lncRNAs (≥ 2-fold change) in KBD chondrocytes using microarray analysis, of which more than three-quarters were intergenic lncRNAs and antisense lncRNAs...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29241826/trabecular-health-of-vertebrae-based-on-anisotropy-in-trabecular-architecture-and-collagen-apatite-micro-arrangement-after-implantation-of-intervertebral-fusion-cages-in-the-sheep-spine
#7
Takuya Ishimoto, Katsuhisa Yamada, Hiroyuki Takahashi, Masahiko Takahata, Manabu Ito, Takao Hanawa, Takayoshi Nakano
Healthy trabecular bone shows highly anisotropic trabecular architecture and the preferential orientation of collagen and apatite inside a trabecula, both of which are predominantly directed along the cephalocaudal axis. This makes trabecular bone stiff in the principally loaded direction (cephalocaudal axis). However, changes in these anisotropic trabecular characteristics after the insertion of implant devices remain unclear. We defined the trabecular architectural anisotropy and the preferential orientation of collagen and apatite as parameters of trabecular bone health...
December 11, 2017: Bone
https://www.readbyqxmd.com/read/29241697/opening-the-black-box-of-endocrine-disruption-of-brain-development-lessons-from-the-characterization-of-bisphenol-a
#8
REVIEW
Dinushan Nesan, Laronna C Sewell, Deborah M Kurrasch
Bisphenol A (BPA) is among the best-studied endocrine disrupting chemicals, known to act via multiple steroid hormone receptors to mediate a myriad of cellular effects. Pre-, peri-, and postnatal BPA exposure have been linked to a variety of altered behaviors in multiple model organisms, ranging from zebrafish to frogs to mammalian models. Given that BPA can cross the human placental barrier and has been found in the serum of human fetuses during gestation, BPA has been postulated to adversely affect ongoing neurodevelopment, ultimately leading to behavioral disorders later in life...
December 11, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/29241564/chrysanthemum-mads-box-transcription-factor-cmanr1-modulates-lateral-root-development-via-homo-heterodimerization-to-influence-auxin-accumulation-in-arabidopsis
#9
Cui-Hui Sun, Jian-Qiang Yu, Li-Zhu Wen, Yun-Hui Guo, Xia Sun, Yu-Jin Hao, Da-Gang Hu, Cheng-Shu Zheng
Root system architecture is an important agronomic trait by which plants both acquire water and nutrients from the soil and adapt to survive in a complex environment. The adaptation of plant root systems to environmental constraints largely depends on the growth and development of lateral roots (LRs). MADS-box transcription factors (TFs) are important known regulators of plant growth, development, and response to environmental stimuli. However, the potential mechanisms by which they regulate LRs development remain poorly understood...
January 2018: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29241538/an-elongin-cullin-socs-box-complex-regulates-stress-induced-serotonergic-neuromodulation
#10
Xicotencatl Gracida, Michael F Dion, Gareth Harris, Yun Zhang, John A Calarco
Neuromodulatory cells transduce environmental information into long-lasting behavioral responses. However, the mechanisms governing how neuronal cells influence behavioral plasticity are difficult to characterize. Here, we adapted the translating ribosome affinity purification (TRAP) approach in C. elegans to profile ribosome-associated mRNAs from three major tissues and the neuromodulatory dopaminergic and serotonergic cells. We identified elc-2, an Elongin C ortholog, specifically expressed in stress-sensing amphid neuron dual ciliated sensory ending (ADF) serotonergic sensory neurons, and we found that it plays a role in mediating a long-lasting change in serotonin-dependent feeding behavior induced by heat stress...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29241433/long-run-trends-in-antidepressant-use-among-youths-after-the-fda-black-box-warning
#11
Nilay Kafali, Ana Progovac, Sherry Shu-Yeu Hou, Benjamin Lê Cook
OBJECTIVE: In October 2004, the Food and Drug Administration directed pharmaceutical companies to issue a black box warning about the potential link between the use of antidepressants and suicidal ideation among children. This study analyzed long-run trends in antidepressant use among children before and after the black box warning for those with and without severe psychological impairment. METHODS: The analysis used data from the Medical Expenditure Panel Survey for children ages five to 17, covering years 2000-2011 (N=75,819)...
December 15, 2017: Psychiatric Services: a Journal of the American Psychiatric Association
https://www.readbyqxmd.com/read/29241196/calycosin-inhibits-the-migration-and-invasion-of-human-breast-cancer-cells-by-down-regulation-of-foxp3-expression
#12
Shuangxi Li, Yafei Wang, Chan Feng, Guoli Wu, Yu Ye, Jing Tian
BACKGROUND/AIMS: Calycosin, a phytoestrogenic compound, has recently emerged as a promising antitumor drug. It has been shown that calycosin suppresses growth and induces apoptosis of breast cancer cells. However, the effect of calycosin on migration and invasion of breast cancer cells and the underlying molecular mechanisms have not been elucidated. METHODS: Human breast cancer cells MCF-7 and T47D were treated with, or without, different doses (0, 6.25, 12.5, 25, 50, 100 or 150 μM) of calycosin, and the viability of different groups was determined by MTT assay...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29241180/high-mobility-group-box1-inhibitor-glycyrrhizic-acid-attenuates-kidney-injury-in-streptozotocin-induced-diabetic-rats
#13
Hong Zhang, Ru Zhang, Juan Chen, Min Shi, Wei Li, Xiangcheng Zhang
BACKGROUND/AIMS: High mobility group box 1 (HMGB1) is an important mediator of the inflammatory response. It has been implicated in the pathogenesis of autoimmune diseases, atherosclerosis, and obesity. However, the effects of HMGB1 on diabetic nephropathy remain unclear. Here, we investigated the potential roles and mechanisms of an HMGB1 inhibitor, glycyrrhizic acid (GA), in renal injury with the streptozotocin (STZ)-induced rat model. METHODS: The diabetic rat was generated by intraperitoneal injection of STZ and then treated with the HMGB1 inhibitor GA or saline for 8 weeks...
November 15, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29241031/the-protective-effect-of-dexmedetomidine-on-lps-induced-acute-lung-injury-through-the-hmgb1-mediated-tlr4-nf-%C3%AE%C2%BAb-and-pi3k-akt-mtor-pathways
#14
Lu Meng, Longyun Li, Shan Lu, Kai Li, Zhenbo Su, Yunyun Wang, Xiaodi Fan, Xuyang Li, Guoqing Zhao
The aim of present study was to evaluate the protective effects of dexmedetomidine (DEX) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and investigate its possible mechanisms mediated by HMGB1. In vivo, pulmonary pathology observation and myeloperoxidase (MPO) activity were also examined to evaluate the protective effect of DEX in the lungs. Tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF), serum and lung tissues LPS-induced rats were detected...
December 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29240728/state-laws-regarding-indoor-public-use-retail-sales-and-prices-of-electronic-cigarettes-u-s-states-guam-puerto-rico-and-u-s-virgin-islands-september-30-2017
#15
Kristy Marynak, Brandon Kenemer, Brian A King, Michael A Tynan, Allison MacNeil, Elizabeth Reimels
Electronic cigarettes (e-cigarettes) are the most frequently used tobacco product among U.S. youths, and past 30-day e-cigarette use is more prevalent among high school students than among adults (1,2). E-cigarettes typically deliver nicotine, and the U.S. Surgeon General has concluded that nicotine exposure during adolescence can cause addiction and can harm the developing adolescent brain (2). Through authority granted by the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration (FDA) prohibits e-cigarette sales to minors, free samples, and vending machine sales, except in adult-only facilities (3)...
December 15, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/29240649/electronic-fetal-monitoring-documentation-connecting-points-for-quality-care-and-communication
#16
Rebecca L Cypher
Contemporaneous, complete, and objective documentation is the foundation for continuity of patient care and facilitates communication between all levels of healthcare clinicians. The impact of electronic fetal monitoring on obstetric safety has become a high priority, with documentation being essential to evaluating care quality. Over several decades, electronic fetal monitoring documentation has reached a higher level of precision because paper is being replaced with health information technology that incorporates system's features such as checklists, drop-down boxes, and decision analysis...
December 13, 2017: Journal of Perinatal & Neonatal Nursing
https://www.readbyqxmd.com/read/29240330/regulating-black-box-medicine
#17
W Nicholson Price
Data drive modern medicine. And our tools to analyze those data are growing ever more powerful. As health data are collected in greater and greater amounts, sophisticated algorithms based on those data can drive medical innovation, improve the process of care, and increase efficiency. Those algorithms, however, vary widely in quality. Some are accurate and powerful, while others may be riddled with errors or based on faulty science. When an opaque algorithm recommends an insulin dose to a diabetic patient, how do we know that dose is correct? Patients, providers, and insurers face substantial difficulties in identifying high-quality algorithms; they lack both expertise and proprietary information...
2017: Michigan Law Review
https://www.readbyqxmd.com/read/29239235/assessing-self-reported-disability-in-a-low-literate-population-with-chronic-low-back-pain-cross-cultural-adaptation-and-psychometric-testing-of-igbo-roland-morris-disability-questionnaire
#18
Chinonso N Igwesi-Chidobe, Chinwe Obiekwe, Isaac O Sorinola, Emma L Godfrey
PURPOSE: Cross-culturally adapt and validate the Igbo Roland Morris Disability Questionnaire. METHOD: Cross-cultural adaptation, test-retest, and cross-sectional psychometric testing. Roland Morris Disability Questionnaire was forward and back translated by clinical/non-clinical translators. An expert committee appraised the translations. Twelve participants with chronic low back pain pre-tested the measure in a rural Nigerian community. Internal consistency using Cronbach's alpha; test-retest reliability using intra-class correlation coefficient and Bland-Altman plot; and minimal detectable change were investigated in a convenient sample of 50 people with chronic low back pain in rural and urban Nigeria...
December 14, 2017: Disability and Rehabilitation
https://www.readbyqxmd.com/read/29238164/a-novel-transdermal-nanoethosomal-gel-of-betahistine-dihydrochloride-for-weight-gain-control-in-vitro-and-in-vivo-characterization
#19
Shahira F El-Menshawe, Adel Ahmed Ali, Abdelkhalk Ali Halawa, Ahmed Sg Srag El-Din
Background: Betahistine dihydrochloride (BDH) is a histamine analog used to control weight gain, with short elimination half-life and gastric irritation as side effects. Objective: The aim of the current investigation is to formulate and optimize a topical BDH ethosomal gel for weight gain control. Materials and methods: Box-Behnken design was applied to study the effect of independent variables: phosphatidylcholine (PC), propylene glycol (PG), and ethanol on vesicle size; entrapment efficiency; % drug release; and flux...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29238041/foxo1-is-a-regulator-of-mhc-ii-expression-and-anti-tumor-effect-of-tumor-associated-macrophages
#20
Jing-Bo Yang, Zhi-Bin Zhao, Qing-Zhi Liu, Tai-Dou Hu, Jie Long, Kai Yan, Zhe-Xiong Lian
Macrophages are a critical component in host immune responses against tumor. In this work we investigated the role of forkhead box O1 (FoxO1) in the transcriptional regulation in macrophages, which affects the anti-tumor functions of tumor-associated macrophages (TAMs). First, we showed that TAMs expressed reduced levels of FoxO1, which was associated with their protumoral M2 polarization state. The suppression of FoxO1 expression in TAM was induced by the hypoxic condition in the tumor microenviroment. Next, we confirmed that FoxO1 positively regulates MHC-II genes by binding to the promoter region of Ciita gene, the master activator of multiple MHC-II genes...
December 14, 2017: Oncogene
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