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991.
992.
Jiah Lim Yoojin Song Jung-Hee Jang Chul-Ho Jeong Sooyeun Lee Byoungduck Park Young Ho Seo 《Archives of pharmacal research》2018,41(10):967-976
Aspirin is one of the oldest drugs for the treatment of inflammation, fever, and pain. It is reported to covalently modify COX-2 enzyme by acetylating a serine amino acid residue. By virtue of aspirin’s acetylating potential, we for the first time developed novel acetyl-donating HDAC inhibitors. In this study, we report the design, synthesis, in silico docking study, and biological evaluation of acetyl-donating HDAC inhibitors. The exposure of MDA-MB-231 cells with compound 4c significantly promotes the acetylation of α-tubulin and histone H3, which are substrates of HDAC6 and HDAC1, respectively. In silico docking simulation also indicates that compound 4c tightly binds to the deep substrate-binding pocket of HDAC6 by coordinating the active zinc ion in a bidentate manner and forming hydrogen bond interactions with Ser531 and His573 amino acid residues. In particular, compound 4c (GI50?=?147 μM) affords the significant enhancement of anti-proliferative effect on MDA-MB-231 cells, compared with its parent compound 2c (GI50?>?1000 μM) and acetyl-donating group deficient compound 6 (GI50?=?554 μM). Overall, compound 4c presents a novel strategy for developing acetyl-donating HDAC inhibitors. 相似文献
993.
Anti‐viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus‐related hepatocellular carcinoma: real‐world east and west experience
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V. L. Chen M.‐L. Yeh A. K. Le M. Jun W. K. Saeed J. D. Yang C.‐F. Huang H. Y. Lee P.‐C. Tsai M.‐H. Lee N. Giama N. G. Kim P. P. Nguyen H. Dang H. A. Ali N. Zhang J.‐F. Huang C.‐Y. Dai W.‐L. Chuang L. R. Roberts D. W. Jun Y.‐S. Lim M.‐L. Yu M. H. Nguyen 《Alimentary pharmacology & therapeutics》2018,48(1):44-54
994.
Reshma A. Merchant R. M. van Dam L. W. L. Tan M. Y. Lim J. L. Low J. E. Morley 《The journal of nutrition, health & aging》2018,22(9):1060-1065
Introduction
Low levels of 25-hydroxyvitamin D (25(OH)D) has been associated with many negative health outcomes including falls and fractures. 25(OH)D is largely bound to vitamin D binding protein (VDBP). There is increasing evidence that free or bioavailable 25(OH)D may be a better measure of vitamin D deficiency.Objective
To determine the prevalence of 25(OH)D deficiency and VDBP levels in multi-ethnic population, and its impact on muscle strength.Design and methods
Cross-sectional study of older adults in Western region of Singapore. 295 participants from three ethnic groups were selected from the Healthy Older People Everyday (HOPE) cohort for measurements of total 25(OH)D and VDBP levels. Total 25(OH)D, VDBP, frailty status, Timed-Up-and-Go (TUG) and grip strength (GS) were assessed. Albumin, free and bioavailable 25(OH)D were only available for 256 participants.Results
53% of Malay and 55% of Indians were deficient in 25(OH)D compared with 18.2% of ethnic Chinese participants. Chinese also had higher total 25(OH)D concentrations with a mean of 29.1 ug/l, (p = <0.001). Chinese had the lowest level of VDBP (169.6ug/ml) followed by Malay (188.8 ug/ml) and Indian having the highest (220.1 ug/ml). Calculated bioavailable and free 25(OH)D levels were significantly higher in Chinese, followed by Malays and Indians, which also correlated with better grip strength measures amongst the Chinese.Conclusion
The Malays and Indians had overall lower free, bioavailable and total 25(OH)D compared with ethnic Chinese. Chinese ethnic group also had the lowest VDBP and better overall grip strength.995.
Elizabeth?Sutton Julian?Bion Cassie?Aldridge Amunpreet?Boyal Janet?Willars Carolyn?TarrantEmail authorView authors OrcID profile 《BMC health services research》2018,18(1):1015
Background
The increased mortality risk associated with weekend admission to hospital (the ‘weekend effect’) has been reported across many health systems. More recently research has focused on causal mechanisms. Variations in the organisation and delivery of in-hospital care between weekends and weekdays have been identified, but this is not always to the detriment of weekend admissions, and the impact on mortality is uncertain. The insights of frontline staff and patients have been neglected. This article reports a qualitative study of patients and clinicians, to explore their views on quality and safety of care at weekends.Methods
We conducted focus groups and interviews with clinicians and patients with experience of acute medical care, recruited from three UK hospital Trusts. We analysed the data using a thematic analysis approach, aided by the use of NVivo, to explore quality and safety of care at weekends.Results
We held four focus groups and completed six in-depth interviews, with 19 clinicians and 12 patients. Four threats to quality and safety were identified as being more prominent at weekends, relating to i) the rescue and stabilisation of sick patients; ii) monitoring and responding to deterioration; iii) timely accurate management of the therapeutic pathway; iv) errors of omission and commission.Conclusions
At weekends patients and staff are well aware of suboptimal staffing numbers, skill mix and access to resources at weekends, and identify that emergency admissions are prioritised over those already hospitalised. The consequences in terms of quality and safety and patient experience of care are undesirable. Our findings suggest the value of focusing on care processes and systems resilience over the weekends, and how these can be better supported, even in the limited resource environment that exists in many hospitals at weekends.996.
997.
Laura Dwyer-Lindgren Ellen R. Squires Stephanie Teeple Gloria Ikilezi D. Allen Roberts Danny V. Colombara Sarah Katherine Allen Stanley M. Kamande Nicholas Graetz Abraham D. Flaxman Charbel El Bcheraoui Kristjana Asbjornsdottir Gilbert Asiimwe Ângelo Augusto Orvalho Augusto Baltazar Chilundo Caroline De Schacht Sarah Gimbel Carol Kamya Faith Namugaya Felix Masiye Cremildo Mauieia Yodé Miangotar Honoré Mimche Acácio Sabonete Haribondhu Sarma Kenneth Sherr Moses Simuyemba Aaron Chisha Sinyangwe Jasim Uddin Bradley H. Wagenaar Stephen S. Lim 《Population health metrics》2018,16(1):13
Background
The under-5 mortality rate (U5MR) is an important metric of child health and survival. Country-level estimates of U5MR are readily available, but efforts to estimate U5MR subnationally have been limited, in part, due to spatial misalignment of available data sources (e.g., use of different administrative levels, or as a result of historical boundary changes).Methods
We analyzed all available complete and summary birth history data in surveys and censuses in six countries (Bangladesh, Cameroon, Chad, Mozambique, Uganda, and Zambia) at the finest geographic level available in each data source. We then developed small area estimation models capable of incorporating spatially misaligned data. These small area estimation models were applied to the birth history data in order to estimate trends in U5MR from 1980 to 2015 at the second administrative level in Cameroon, Chad, Mozambique, Uganda, and Zambia and at the third administrative level in Bangladesh.Results
We found substantial variation in U5MR in all six countries: there was more than a two-fold difference in U5MR between the area with the highest rate and the area with the lowest rate in every country. All areas in all countries experienced declines in U5MR between 1980 and 2015, but the degree varied both within and between countries. In Cameroon, Chad, Mozambique, and Zambia we found areas with U5MRs in 2015 that were higher than in other parts of the same country in 1980. Comparing subnational U5MR to country-level targets for the Millennium Development Goals (MDG), we find that 12.8% of areas in Bangladesh did not meet the country-level target, although the country as whole did. A minority of areas in Chad, Mozambique, Uganda, and Zambia met the country-level MDG targets while these countries as a whole did not.Conclusions
Subnational estimates of U5MR reveal significant within-country variation. These estimates could be used for identifying high-need areas and positive deviants, tracking trends in geographic inequalities, and evaluating progress towards international development targets such as the Sustainable Development Goals.998.
999.
Dong Kyu Lim Changyeun Mo Dong-Kyu Lee Nguyen Phuoc Long Jongguk Lim Sung Won Kwon 《Yao wu shi pin fen xi = Journal of food and drug analysis.》2018,26(1):260-267
The authenticity determination of white rice is crucial to prevent deceptive origin labeling and dishonest trading. However, a non-destructive and comprehensive method for rapidly discriminating the geographical origins of white rice between countries is still lacking. In the current study, we developed a volatile organic compound based geographical discrimination method using headspace solid-phase microextraction coupled to gas chromatography–mass spectrometry (HS-SPME/GC–MS) to discriminate rice samples from Korea and China. A partial least squares discriminant analysis (PLS-DA) model exhibited a good classification of white rice between Korea and China (accuracy = 0.958, goodness of fit = 0.937, goodness of prediction = 0.831, and permutation test p-value = 0.043). Combining the PLS-DA based feature selection with the differentially expressed features from the unpaired t-test and significance analysis of microarrays, 12 discriminatory biomarkers were found. Among them, hexanal and 1-hexanol have been previously known to be associated with the cultivation environment and storage conditions. Other hydrocarbon biomarkers are novel, and their impact on rice production and storage remains to be elucidated. In conclusion, our findings highlight the ability to rapidly discriminate white rice from Korea and China. The developed method maybe useful for the authenticity and quality control of white rice. 相似文献
1000.
Duck Soo Lim Tae Hyun Roh Min Kook Kim Yong Chan Kwon Seul Min Choi Seung Jun Kwack 《Journal of toxicology and environmental health. Part A》2018,81(12):465-480
N-nitrosamines and their precursors found in cosmetics may be carcinogenic in humans. Thus the aim of this study was to carry out risk assessment for N-nitrosamines (N-nitrosodiethanolamine [NDELA], N-nitrosodiethylamine [NDEA]) and amines (triethanolamine [TEA], diethanolamine [DEA]) levels in cosmetics determined using validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) procedures. NDELA and NDEA concentrations were present at levels of “not detected” (N.D.) to 596.5 μg/kg and N.D. to 40.9 μg/kg, respectively. TEA and DEA concentrations ranged from N.D. to 860 μg/kg and N.D. to 26.22 μg/kg, respectively. The nitrite concentration (3–2250 mg/l), number of nitrosating agents to a maximum 5, and pH (3.93–10.09) were also assessed. The impact of N-nitrosamine formation on the levels of TEA, DEA, nitrite, and other nitrosating agents was also examined. N-nitrosamine concentrations correlated with the number of nitrosating agents and nitrite concentrations. Data demonstrated that higher nitrite concentrations and a greater number of nitrosating agents increased NDELA and NDEA yields. Further, the presence of TEA and DEA exerted a significant influence on N-nitrosamine formation. Risk assessments, including the margin of exposure (MOE) and lifetime cancer risk (LCR) for N-nitrosamines and margin of safety (MOS) for amines, were calculated using product type, use pattern, and concentrations. Exposure to maximum amounts of NDELA and NDEA resulted in MOE > 10,000 (based upon the benchmark dose lower confidence limit 10%) and LCR <1 × 10?5, respectively. In addition, TEA and DEA concentrations in cosmetic samples resulted in MOS values >100. Therefore, no apparent safety concerns were associated with cosmetic products containing NDELA, NDEA, TEA, and DEA in this study. However, since amines and nitrosating agents produce carcinogenic nitrosamines, their use in cosmetics needs to be minimized to levels as low as technically feasible. 相似文献