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https://www.readbyqxmd.com/read/29458155/determining-risk-of-colorectal-cancer-and-starting-age-of-screening-based-on-lifestyle-environmental-and-genetic-factors
#1
Jihyoun Jeon, Mengmeng Du, Robert E Schoen, Michael Hoffmeister, Polly A Newcomb, Sonja I Berndt, Bette Caan, Peter T Campbell, Andrew T Chan, Jenny Chang-Claude, Graham G Giles, Jian Gong, Tabitha A Harrison, Jeroen R Huyghe, Eric J Jacobs, Li Li, Yi Lin, Loïc Le Marchand, John D Potter, Flora Qu, Stephanie A Bien, Niha Zubair, Robert J Macinnis, Daniel D Buchanan, John L Hopper, Yin Cao, Reiko Nishihara, Gad Rennert, Martha L Slattery, Duncan C Thomas, Michael O Woods, Ross L Prentice, Stephen B Gruber, Yingye Zheng, Hermann Brenner, Richard B Hayes, Emily White, Ulrike Peters, Li Hsu
BACKGROUND & AIMS: Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening. METHODS: We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005...
February 16, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29458152/controversies-in-endoscopic-eradication-therapy-for-barrett-s-esophagus
#2
Srinadh Komanduri, V Raman Muthusamy, Sachin Wani
Advances in Endoscopic Eradication Therapy for Barrett's Esophagus associated neoplasia have resulted in a significant paradigm shift in diagnosis and management of this complex disease. A robust body of literature critically evaluating outcomes of resection and ablative strategies has allowed gastroenterologists to make quality, evidence based decisions for their patients. Despite this progress, there are still many unanswered questions and challenges that remain. Ultimately, identification of a cost-effective screening modality, biomarkers for risk stratification, and strides to eliminate post surveillance endoscopy after EET are essential to reach our long term goal for eradication of esophageal adenocarcinoma...
February 16, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29458148/untimely-oxidative-stress-in-%C3%AE-cells-leads-to-diabetes-role-of-circadian-clock-in-%C3%AE-cell-function
#3
REVIEW
J Lee, K Ma, M Moulik, V Yechoor
Diabetes results from a loss of β-cell function. With the number of people with diabetes reaching epidemic proportions globally, understanding mechanisms that are contributing to this increasing prevalence is critical. One such factor has been circadian disruption, with shift-work, light pollution, jet-lag, increased screen time, all acting as potential contributory factors. Though circadian disruption has been epidemiologically associated with diabetes and other metabolic disorders for many decades, it is only recently that there has been a better understanding of the underlying molecular mechanisms...
February 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29458143/suv39h2-promotes-colorectal-cancer-proliferation-and-metastasis-via-tri-methylation-of-the-slit1-promoter
#4
Wendi Shuai, Jiangxue Wu, Shuai Chen, Ranyi Liu, Zhihua Ye, Chunmei Kuang, Xiang Fu, Gaoyuan Wang, Yingchang Li, Qihua Peng, Wei Shi, Yizhuo Li, Qianghua Zhou, Wenlin Huang
Suppressor of variegation 3-9 homolog 2 (SUV39H2) is a member of the SUV39H subfamily of lysine methyltransferases. Its role in colorectal cancer (CRC) proliferation and metastasis has remained unexplored. Here, we determined that SUV39H2 was upregulated in CRC tissues compared with that in adjacent non-neoplastic tissues. Further statistical analysis revealed that high SUV39H2 expression was strongly associated with distant metastasis (P = 0.016) and TNM stage (P = 0.038) and predicted a shorter overall survival (OS; P = 0...
February 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29458128/aggregation-prone-regions-in-hypk-help-it-to-form-sequestration-complex-for-toxic-protein-aggregates
#5
Debasish Kumar Ghosh, Ajit Roy, Akash Ranjan
Protein aggregates result from altered structural conformations and they can perturb cellular homeostasis. Prevention mechanisms, which function against protein aggregation by modulatory processes, are diverse and redundant. In this study, we have characterized Huntingtin interacting protein K (HYPK) as a global aggregation-regulatory protein. We report the mechanistic details of how HYPK's aggregation-prone regions allow it to sense and prevent other toxic protein's aggregation by forming unique annular-shaped sequestration complexes...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458108/the-relaxin-receptor-as-a-therapeutic-target-perspectives-from-evolution-and-drug-targeting
#6
REVIEW
Ross A D Bathgate, Martina Kocan, Daniel J Scott, M Akhter Hossain, Sara V Good, Sergey Yegorov, Jan Bogerd, Paul Gooley
The peptide relaxin was first identified as an important circulating hormone during pregnancy over 90 years ago. Research over many years defined the numerous biological roles that relaxin plays throughout pregnancy in many mammalian species. These important biological actions have led to the testing of relaxin as a therapeutic agent for a number of indications. The discovery of the relaxin receptor, RXFP1, in 2002 facilitated the better understanding of the cellular targets of relaxin, its mechanism of action and enabled the development of relaxin mimetics and screening for small molecule agonists...
February 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29458095/rapid-loop-mediated-isothermal-amplification-detection-of-coeliac-disease-risk-alleles
#7
Michael Erlichster, Jason A Tye-Din, Michael D Varney, Efstratios Skafidas, Patrick Kwan
Human leukocyte antigen (HLA) genotyping has become a useful investigation in the diagnostic work-up of coeliac disease (CD), with utility in risk stratification and screening. However, broad application of this technology has been hindered by the cost and time burden of conventional laboratory-based assays. We have developed and validated CD-loop-mediated isothermal amplification (CD-LAMP), a LAMP assay, which enables rapid identification of the signature CD risk genotypes, HLA-DQ2.5, HLA-DQ8, HLA-DQ2.2, and HLA-DQA1*05...
February 16, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29458080/transcriptomic-and-phenotypic-profiling-in-developing-zebrafish-exposed-to-thyroid-hormone-receptor-agonists
#8
Derik E Haggard, Pamela D Noyes, Katrina M Waters, Robert L Tanguay
There continues to be a need to develop in vivo high-throughput screening (HTS) and computational methods to screen chemicals for interaction with the estrogen, androgen, and thyroid pathways and as complements to in vitro HTS assays. This study explored the utility of an embryonic zebrafish HTS approach to identify and classify endocrine bioactivity using phenotypically-anchored transcriptome profiling. Transcriptome analysis was conducted on zebrafish embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at concentrations that elicited adverse malformations or mortality at 120 hours post-fertilization in 80% of animals exposed...
February 16, 2018: Reproductive Toxicology
https://www.readbyqxmd.com/read/29458062/an-unexpected-degradation-pathway-of-a-1-2-4-triazolo-4-3-a-pyridine-derivative-the-formation-of-two-cationic-pseudodimers-of-an-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-inhibitor-drug-candidate-in-a-stressed-capsule-formulation
#9
Yande Huang, Qinggang Wang, Yongmei Wu
Degradation of an active pharmaceutical ingredient (API), a 2-(3-(1-(4-chlorophenyl)cyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-8-yl)propan-2-ol hydrochloride salt, was observed in a capsule formulation stressed at 50°C or 40°C/75% relative humidity conditions for one month. Two unknown degradants were identified as cationic pseudodimers of the API via accurate mass liquid chromatography-mass spectrometry and one- and two-dimensional NMR analyses. A plausible degradation pathway of the API was postulated which led to the identification of two key N-oxide degradants in the stressed capsule formulation at trace levels...
February 16, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29458004/real-time-analysis-of-cleavage-and-religation-activity-of-human-topoisomerase-1-based-on-ternary-fluorescence-resonance-energy-transfer-dna-substrate
#10
Zhenxing Wang, Hui Ouyang, Cinzia Tesauro, Alessio Ottaviani, Yong He, Paola Fiorani, Hui Xie, Alessandro Desideri, Zhifeng Fu
Human topoisomerase 1B is a ubiquitous and essential enzyme involved in relaxing the topological state of supercoiled DNA to allow the progression of fundamental DNA metabolism. Its enzymatic catalytic cycle consists of cleavage and religation reaction. A ternary fluorescence resonance energy transfer biosensor based on a suicide DNA substrate conjugated with three fluorophores has been developed to monitor both cleavage and religation Topoisomerase I catalytic function. The presence of fluorophores does not alter the specificity of the enzyme catalysis on the DNA substrate...
February 16, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29457996/the-tyg-index-cutoff-point-and-its-association-with-body-adiposity-and-lifestyle-in-children
#11
Sarah A Vieira Ribeiro, Poliana C A Fonseca, Cristiana S Andreoli, Andréia Q Ribeiro, Helen H M Hermsdorff, Patrícia F Pereira, Silvia E Priore, Sylvia C C Franceschini
OBJECTIVE: To investigate the factors associated with insulin resistance in children aged 4-7 years, and to identify the cutoff point of the triglyceride-glucose index for the prediction of IR in this population. METHODS: A cross-sectional study was conducted with 403 children from a retrospective cohort. Insulin resistance was also evaluated in a sub-sample using the HOMA index. Four indicators of body adiposity were assessed: body mass index, waist-to-height ratio, and the percentages of total and central body fat...
February 16, 2018: Jornal de Pediatria
https://www.readbyqxmd.com/read/29457969/an-evaluation-of-the-operational-model-when-applied-to-quantify-functional-selectivity
#12
Xiao Zhu, David B Finlay, Michelle Glass, Stephen B Duffull
BACKGROUND AND PURPOSE: Functional selectivity describes the ability of ligands to differentially regulate multiple signalling pathways when coupled to a single receptor and the operational model is commonly used to analyse these data. Here, we assess the mathematical properties of the operational model and evaluate the impact of fixing parameters on model performance. EXPERIMENTAL APPROACH: The operational model was evaluated using both a mathematical identifiability analysis and simulation...
February 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29457916/systematic-review-of-psychiatric-signs-in-niemann-pick-disease-type-c
#13
Olivier Bonnot, Hans-Hermann Klünemann, Christian Velten, Juan Vicente Torres Martin, Mark Walterfang
OBJECTIVES: We conducted the first systematic literature review and analysis of psychiatric manifestations in Niemann-Pick disease type C (NPC) to describe: 1) time of occurrence of psychiatric manifestations relative to other disease manifestations; 2) frequent combinations of psychiatric, neurological and visceral disease manifestations. METHODS: A systematic EMBase literature search was conducted to identify, collate and analyze published data from patients with NPC associated with psychiatric symptoms, published between January 1967 and November 2015...
February 19, 2018: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/29457893/kinetics-thermodynamics-and-mechanism-of-a-novel-biphasic-solvent-for-co2-capture-from-flue-gas
#14
Shihan Zhang, Yao Shen, Peijing Shao, Jianmeng Chen, Lidong Wang
The main issue related to the deployment of amine-based absorption process for CO2 capture from flue gas is its intensive energy penalty. Therefore, this study screened a novel biphasic solvent, comprising a primary amine e.g., triethylenetetramine (TETA) and a tertiary amine e.g., N, N-dimethylcyclohexylamine (DMCA), to reduce the energy consumption. The TETA-DMCA blend exhibited high cyclic capacity of CO2 absorption, favorable phase separation behavior, and low regeneration heat. Kinetic analysis showed that the gas- and liquid-side mass transfer resistances were comparable in the lean solution of TETA-DMCA at 40oC, whereas the liquid-side mass transfer resistance became dominant in the rich solution...
February 19, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29457887/synthesis-of-highly-substituted-imidazole-uracil-containing-molecules-via-ugi-4cr-and-passerini-3cr
#15
Rudrakshula Madhavachary, Tryfon Zarganes-Tzitzikas, Pravin Patil, Katarzyna Kurpiewska, Justyna Kalinowska-Tłuścik, Alexander Dömling
The synthesis of uracil/thymine containing tetra/tri-substituted imidazoles were demonstrated using Ugi/Passerini-reaction fol-lowed by a post-cyclization reaction sequence. The approach enables the one-pot facile construction of diverse compounds in moderate to excellent yields (47-82%). The 5-fluorouracil and 5-methyluracil moieties afford potentially bioactive molecules with drug-like properties. These scaffolds are being utilized in the screening deck of the European Lead Factory.
February 19, 2018: ACS Combinatorial Science
https://www.readbyqxmd.com/read/29457879/the-good-the-bad-and-the-ugly-of-luminex-donor-specific-cross-match
#16
M Chowdhry, R N Makroo, Y Thakur, V Sharma, M Singh, M Kumar
The presence of donor specific antibodies directed against human leukocyte antigen significantly influences renal transplant due to antibody mediated rejection (AMR). We performed the screening of pre-renal transplant patients for preformed anti HLA antibodies using Antihuman globulin augmented-CDC crossmatch (AHG-CDCXm), Luminex donor specific crossmatch (LumXm) and HLA antibody screening. Seven hundred and fifty four patients were assessed for LumXm. HLA antibody screening was possible in 325 out of 754 cases...
February 19, 2018: HLA
https://www.readbyqxmd.com/read/29457878/genetic-determinants-of-heart-failure-facts-and-numbers
#17
EDITORIAL
Frauke S Czepluch, Bernd Wollnik, Gerd Hasenfuß
The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying the so-called genetic predisposition. Genetic contribution to heart failure is highly heterogenous and complex. For any patient with a likely inherited heart failure syndrome, genetic counselling is recommended and important. In the last few years, novel sequencing technologies (named next-generation sequencing - NGS) have dramatically improved the availability of molecular testing, the efficiency of genetic analyses, and moreover reduced the cost for genetic testing...
February 19, 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29457841/erectile-dysfunction-they-don-t-talk-we-don-t-ask
#18
A Rakovac Tisdall, T F J King, W A W Mahmood, C S Keat, R Ali, R Abdin, C M Koo, M Alali, S Sreenan, J H McDermott
Erectile dysfunction is an under-reported complication of diabetes mellitus affecting over half of male patients [1]. Although many men with diabetes consider that erectile dysfunction has a negative influence on their quality of life, they are reluctant to report it; and while most would like treatment, they prefer physicians to start the conversation [2-4]. Erectile dysfunction predicts future cardiovascular disease, and screening for erectile dysfunction is advocated in several cardiovascular risk assessment algorithms [5]...
February 19, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29457831/low-t3-syndrome-as-a-predictor-of-poor-prognosis-in-chronic-lymphocytic-leukemia
#19
Rui Gao, Rui-Ze Chen, Yi Xia, Jin-Hua Liang, Li Wang, Hua-Yuan Zhu, Jia-Zhu Wu, Lei Fan, Jian-Yong Li, Tao Yang, Wei Xu
Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels...
February 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29457811/liquid-crystalline-behaviour-of-self-assembled-laponite%C3%A2-pll-peg-nanocomposites
#20
P Xu, Y Lan, Z Xing, E Eiser
Synthetic LAPONITE®-clay particles with platelet-like shape display strong aging when dispersed in aqueous solutions, preventing the latter from reaching their natural liquid-crystalline equilibrium state. Here we introduce a facile method that successfully prevents this aging behaviour and enables accessing the systems' liquid-crystal and crystalline phases. We graft the comb-like polymer PLL-PEG (poly(l-lysine)-g-poly(ethylene glycol)) onto the clay surfaces from solution, thereby screening the negative surface charges and thus ensuring steric stabilisation...
February 19, 2018: Soft Matter
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