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931.
Nakul Saxena Mikael Hartman Cheng-Har Yip Nirmala Bhoo-Pathy Lay Wai Khin Nur Aishah Taib Lai-Meng Looi Siew-Eng Lim Soo-Chin Lee Helena M. Verkooijen 《PloS one》2012,7(9)
Introduction
Lymph node ratio (LNR, i.e. the ratio of the number of positive nodes to the total number of nodes excised) is reported to be superior to the absolute number of nodes involved (pN stage) in classifying patients at high versus low risk of death following breast cancer. The added prognostic value of LNR over pN in addition to other prognostic factors has never been assessed.Methods
All patients diagnosed with lymph node positive, non-metastatic invasive breast cancer at the National University Hospital (Singapore) and University of Malaya Medical Center (Kuala Lumpur) between 1990–2007 were included (n = 1589). Overall survival of the patients was estimated by the Kaplan Meier method for LNR [categorized as low (>0 and <0.2), intermediate (0.2–0.65) and high (>0.65–1)] and pN staging [pN1, pN2 and pN3]. Adjusted overall relative mortality risks associated with LNR and pN were calculated by Cox regression. The added prognostic value of LNR over pN was evaluated by comparing the discriminating capacity (as indicated by the c statistic) of two multivariate models, one including pN and one including LNR.Results
LNR was superior to pN in categorizing mortality risks for women ≥60 years, those with ER negative or grade 3 tumors. In combination with other factors (i.e. age, treatment, grade, tumor size and receptor status), substituting pN by LNR did not result in better discrimination of women at high versus low risk of death, neither for the entire cohort (c statistic 0.72 [0.70–0.75] and 0.73 [0.71–0.76] respectively for pN versus LNR), nor for the subgroups mentioned above.Conclusion
In combination with other prognosticators, substitution of pN by LNR did not provide any added prognostic value for South East Asian breast cancer patients. 相似文献932.
Grace Su Yin Pang Farida Ithnin Yin Yee Wong Jing Bo Wang Yvonne Lim Alex Tiong Heng Sia Caroline Guat Lay Lee 《PloS one》2012,7(11)
Background
Fentanyl-induced emesis (FIE) is a distressing adverse effect in the postoperative setting. The genetic basis of FIE remains largely unknown, therefore, we examined whether it was associated with specific genetic variants of OPRM1, the gene encoding the main receptor target of fentanyl.Methods
In this prospective case-control study, 193 women undergoing gynaecological surgery under a standardized anaesthetic with a low emetogenic risk were enrolled. Inclusion and exclusion criteria were designed to select extreme phenotypes as well as to ensure that most major confounders for FIE were either excluded or present in all patients. To control for unforeseen intra- and postoperative confounders for FIE, only 161 patients were further analysed, out of which 10 were categorized as having FIE, defined by the presence of at least one of three symptoms: nausea, vomiting or retching that was likely to be fentanyl-related. To identify SNPs relevant to FIE in our population, DNA from 40 controls and 10 cases was sequenced at the following OPRM1 regions: 3 kbp of the promoter, main and alternative exons as well as 2 kbp of the 3′ downstream region. The genotype of the significant SNP was further determined in the remaining 111 controls.Results
The incidence of FIE was 6.2%. Initial sequencing of 10 cases and 40 controls identified 25 SNPs. Only rs540825, a non-synonymous SNP in the splice variant, MOR1X, showed a significant association with FIE post-Bonferroni correction. This SNP was further examined in the remaining 111 controls which confirmed its significant association with FIE (p = 0.019 post-Bonferroni, OR: 5.6, 95% CI: 1.42–21.91).Conclusions
This is the first report of an association between the occurrence of FIE in Chinese women undergoing gynaecological surgery and an OPRM1 splice variant SNP, rs540825. 相似文献933.
Wee Ling Heng Chong Hee Lim Ban Hock Tan Maciej Piotr Chlebicki Winnie Hui Ling Lee Tracy Seck Yeong Phang Lim 《PloS one》2012,7(12)
Background
In February 2012, the National Cardiovascular Homograft Bank (NCHB) became the first tissue bank outside of North America to receive accreditation from the American Association of Tissue Banks. From 2008 to 2009, NCHB had been decontaminating its cardiovascular homografts with penicillin and streptomycin. The antibiotic decontamination protocol was changed in January 2010 as amikacin and vancomycin were recommended, in order to cover bacteria isolated from post-recovery and post- antibiotic incubation tissue cultures.Aim
The objective of this study is to determine the optimal incubation conditions for decontamination of homografts by evaluating the potencies of amikacin and vancomycin in different incubation conditions. Retrospective reviews of microbiological results were also performed for homografts recovered from 2008 to 2012, to compare the effectiveness of penicillin-streptomycin versus the amikacin-vancomycin regimens.Methods
Based on microbiological assays stated in United States Pharmacopeia 31, potency of amikacin was evaluated by turbidimetric assay using Staphylococcus aureus, while vancomycin was by diffusion assay using Bacillus subtilis sporulate. Experiments were performed to investigate the potencies of individual antibiotic 6-hours post incubation at 4°C and 37°C and 4°C for 24 hours, after the results suggested that amikacin was more potent at lower temperature.Findings
Tissue incubation at 4°C for 24 hours is optimal for both antibiotics, especially for amikacin, as its potency falls drastically at 37°C.Conclusion
The decontamination regimen of amikacin-vancomycin at 4°C for 24 hours is effective. Nevertheless, it is imperative to monitor microbiological trends closely and evaluate the efficacy of current antibiotics regimen against emerging strains of micro-organisms. 相似文献934.
J Zhuo EH Tan B Yan L Tochhawng M Jayapal S Koh HK Tay SK Maciver SC Hooi M Salto-Tellez AP Kumar YC Goh YC Lim CT Yap 《PloS one》2012,7(8):e43594
Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin's influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites. 相似文献
935.
Gene delivery technologies to introduce foreign genes into highly differentiated mammalian cells have improved significantly over the last few decades. Relatively new techniques such as magnetic nanoparticle-based gene transfection technology are showing great promise in terms of its high transfection efficiency and wide-ranging research applications. We have developed a novel gene delivery technique, which uses magnetic nanoparticles moving under the influence of an oscillating magnetic array. Herein we successfully introduced short interfering RNA (siRNA) against green fluorescent protein (GFP) or actin into stably-transfected GFP-HeLa cells or wild-type HeLa and rat aortic smooth muscle cells, respectively. This gene silencing technique occurred in a dose- and cell density- dependent manner, as reflected using fluorescence intensity and adhesion assays. Furthermore, using endocytosis inhibitors, we established that these magnetic nanoparticle-nucleic acid complexes, moving across the cell surface under the influence of an oscillating magnet array, enters into the cells via the caveolae-mediated endocytic pathway. 相似文献
936.
Synonymous mutations are usually referred to as “silent”, but increasing evidence shows that they are not neutral in a wide range of organisms. We looked into the relationship between synonymous codon usage bias and residue importance of voltage-gated ion channel proteins in mice, rats, and humans. We tested whether translationally optimal codons are associated with transmembrane or channel-forming regions, i.e., the sites that are particularly likely to be involved in the closing and opening of an ion channel. Our hypothesis is that translationally optimal codons are preferred at the sites within transmembrane domains or channel-forming regions in voltage-gated ion channel genes to avoid mistranslation-induced protein misfolding or loss-of-function. Using the Mantel-Haenszel procedure, which applies to categorical data, we found that translationally optimal codons are more likely to be used at transmembrane residues and the residues involved in channel-forming. We also found that the conservation level at synonymous sites in the transmembrane region is significantly higher than that in the non-transmembrane region. This study provides evidence that synonymous sites in voltage-gated ion channel genes are not neutral. Silent mutations at channel-related sites may lead to dysfunction of the ion channel. 相似文献
937.
Objective
Between 1990 and 2010, the U.S ranking in neonatal mortality slipped from 29th to 45th among countries globally. Substantial subnational variation in newborn mortality also exists. Our objective is to measure the extent to which trends and subnational variation in early neonatal mortality reflect differences in the prevalence of risk factors (gestational age and birth weight) compared to differences in clinical care.Methods
Observational study using linked birth and death data for all births in the United States between 1996 and 2006. We examined health service area (HSA) level variation in the expected early neonatal mortality rate, based on gestational age (GA) and birth-weight (BW), and GA-BW adjusted mortality as a proxy for clinical care. We analyzed the relationship between selected health system indicators and GA-BW-adjusted mortality.Results
The early neonatal death (ENND) rate declined 12% between 1996 and 2006 (2.39 to 2.10 per 1000 live births). This occurred despite increases in risk factor prevalence. There was significant HSA-level variation in the expected ENND rate (Rate Ratio: 0.73–1.47) and the GA-BW adjusted rate (Rate ratio: 0.63–1.68). Accounting for preterm volume (defined as <34 weeks), the number of neonatologist and NICU beds, 25.2% and 58.7% of the HSA-level variance in outcomes was explained among all births and very low birth weight babies, respectively.Conclusion
Improvements in mortality could be realized through the expansion or reallocation of clinical neonatal resources, particularly in HSAs with a high volume of preterm births; however, prevention of preterm births and low-birth weight babies has a greater potential to improve newborn survival in the United States. 相似文献938.
939.
940.
JH Park P Darvin EJ Lim YH Joung DY Hong EU Park SH Park SK Choi ES Moon BW Cho KD Park HK Lee MJ Kim DS Park IM Chung YM Yang 《PloS one》2012,7(7):e40531