Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival.
We performed standard pairwise ...and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012).
We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available 25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33–0.81, P-value for effect=0.004, number needed to treat 74, I2=0% with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14–0.64) and desflurane (OR=0.43, 95% credible interval 0.21–0.82) were individually associated with a reduction in mortality when compared with TIVA.
Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The analysis and combination of data from different gamma-ray instruments involves the use of collaboration proprietary software and case-by-case methods. The effort of defining a common data format ...for high-level data, namely event lists and instrument response functions (IRFs), has recently started for very-high-energy gamma-ray instruments, driven by the upcoming Cherenkov Telescope Array (CTA). In this work we implemented this prototypical data format for a small set of MAGIC, VERITAS, FACT, and H.E.S.S. Crab nebula observations, and we analyzed them with the open-source gammapy software package. By combining data from Fermi-LAT, and from four of the currently operating imaging atmospheric Cherenkov telescopes, we produced a joint maximum likelihood fit of the Crab nebula spectrum. Aspects of the statistical errors and the evaluation of systematic uncertainty are also commented upon, along with the release format of spectral measurements. The results presented in this work are obtained using open-access on-line assets that allow for a long-term reproducibility of the results.
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FMFMET, NUK, UL, UM, UPUK
ABSTRACT
We present a measurement of the extragalactic background light (EBL) based on a joint likelihood analysis of 32 gamma-ray spectra for 12 blazars in the redshift range z = 0.03–0.944, ...obtained by the MAGIC telescopes and Fermi-LAT. The EBL is the part of the diffuse extragalactic radiation spanning the ultraviolet, visible, and infrared bands. Major contributors to the EBL are the light emitted by stars through the history of the Universe, and the fraction of it that was absorbed by dust in galaxies and re-emitted at longer wavelengths.
The EBL can be studied indirectly through its effect on very high energy photons that are emitted by cosmic sources and absorbed via γγ interactions during their propagation across cosmological distances. We obtain estimates of the EBL density in good agreement with state-of-the-art models of the EBL production and evolution. The 1σ upper bounds, including systematic uncertainties, are between 13 per cent and 23 per cent above the nominal EBL density in the models. No anomaly in the expected transparency of the Universe to gamma-rays is observed in any range of optical depth. We also perform a wavelength-resolved EBL determination, which results in a hint of an excess of EBL in the 0.18–0.62 $\mu\mathrm{ m}$ range relative to the studied models, yet compatible with them within systematics.
Premature failures in metals can arise from the local reduction of the fracture toughness when brittle phases precipitate. Precipitation can be enhanced at the grain and phase boundaries and be ...promoted by stress concentration causing a shift of the terminal solid solubility. This paper provides the description of a model to predict stress-induced precipitation along phase interfaces in one-phase and two-phase metals. A phase-field approach is employed to describe the microstructural evolution. The combination between the system expansion caused by phase transformation, the stress field and the energy of the phase boundary is included in the model as the driving force for precipitate growth. In this study, the stress induced by an opening interface crack is modelled through the use of linear elastic fracture mechanics and the phase boundary energy by a single parameter in the Landau potential. The results of the simulations for a hydrogenated (
α
+
β
) titanium alloy display the formation of a precipitate, which overall decelerates in time. Outside the phase boundary, the precipitate mainly grows by following the isostress contours. In the phase boundary, the hydride grows faster and is elongated. Between the phase boundary and its surrounding, the matrix/hydride interface is smoothened. The present approach allows capturing crack-induced precipitation at phase interfaces with numerical efficiency by solving one equation only. The present model can be applied to other multi-phase metals and precipitates through the use of their physical properties and can also contribute to the efficiency of multi-scale crack propagation schemes.
Novel prognostic biomarkers and therapeutic strategies are urgently required for malignant melanoma. Ecto-5-prime-nucleotidase (NT5E; CD73) overexpression has been reported in several human cancers. ...The mechanism(s) underlying deregulated expression and the clinical consequences of changes in expression are not known.
We used RT-PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse expression and regulation of NT5E in malignant melanoma cell lines and primary and metastatic melanomas.
NT5E is subject to epigenetic regulation in melanoma. NT5E mRNA is downregulated by methylation-dependent transcriptional silencing in the melanoma cell lines SKMel2, SKMel23, WM35, Mel501, Mel505 and C81-61 and expression is reactivated by azacytidine. In contrast, the CpG island is unmethylated and the gene expressed in cultured normal melanocytes. In clinical cases of melanoma, methylation in the NT5E CpG island occurs in both primary and metastatic melanomas and correlates with transcriptional downregulation of NT5E mRNA. Relapse with metastatic disease, particularly to the visceral sites and brain, is more common in primary melanomas lacking NT5E methylation. Primary melanomas with methylation in NT5E show limited metastatic potential or more commonly metastasise predominantly to nodal sites rather than viscera and brain (P=0.01).
Deregulation of NT5E expression in melanoma occurs via epigenetic changes in the NT5E CpG island. Confirmation of our results in larger clinical series would support the candidacy of NT5E as a clinical biomarker in melanoma, which could be applied in both primary and relapsed disease. Inhibition of NT5E may have therapeutic potential in melanoma, particularly in patients with more aggressive disease metastatic to viscera or the brain.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Arginine deprivation, either by nutritional starvation or exposure to ADI-PEG20, induces adaptive transcriptional upregulation of ASS1 and ASL in glioblastoma multiforme ex vivo cultures and cell ...lines. This adaptive transcriptional upregulation is blocked by neoplasia-specific CpG island methylation in either gene, causing arginine auxotrophy and cell death. In cells with methylated ASS1 or ASL CpG islands, ADI-PEG20 initially induces a protective autophagic response, but abrogation of this by chloroquine accelerates and potentiates cytotoxicity. Concomitant methylation in the CpG islands of both ASS1 and ASL, observed in a subset of cases, confers hypersensitivity to ADI-PEG20. Cancer stem cells positive for CD133 and methylation in the ASL CpG island retain sensitivity to ADI-PEG20. Our results show for the first time that epigenetic changes occur in both of the two key genes of arginine biosynthesis in human cancer and confer sensitivity to therapeutic arginine deprivation. We demonstrate that methylation status of the CpG islands, rather than expression levels per se of the genes, predicts sensitivity to arginine deprivation. Our results suggest a novel therapeutic strategy for this invariably fatal central nervous system neoplasm for which we have identified robust biomarkers and which overcomes the limitations to conventional chemotherapy imposed by the blood/brain barrier.
BACKGROUND:Despite increasing interest in prepectoral implant-based reconstruction to avoid animation deformity (AD), the prevalence of this deformity and patient attitudes toward it have not been ...extensively studied. The purpose of this study was to report on AD in the breast reconstruction population and identify those at highest risk.
METHODS:A retrospective chart review was completed for patients at least 6 months postoperative from subpectoral, implant-based breast reconstruction using acellular dermal matrix in the lower pole. Patient age, BMI, and implant size were collected. A questionnaire was distributed to the patients. Returned questionnaires were compiled and data were analyzed.
RESULTS:Eighty-four of 108 patients (77.8%) returned the questionnaire with 62 (75.6%) reporting AD; 75.6% of patients were aware of AD, 14.6% considered it moderate, and 11% considered it severe. No statistically significant differences in age, body mass index, implant size, or athleticism were found between those who noted AD versus those who did not. Forty-one of 79 patients (51.9%) would have been interested in an initial surgical procedure without AD; interest dropped significantly if the alternative surgery involved increased risk, cost, or additional stages of reconstruction.
CONCLUSION:The prevalence of AD in subpectoral implant-based breast reconstruction is significantly higher than in subpectoral augmentation. The majority of patients expressed interest in an alternative procedure to avoid AD unless it involved increased risk, cost, or additional surgeries. We found insignificant differences in age, athleticism, BMI, and implant size between patients who note AD and those who do not. Further study is necessary to better define patients at risk for AD to guide patient-centered breast reconstruction.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Reply: The Superficial Vein–Only DIEP Flap Park, Jungwon; Nigro, Lauren C.; Chang, Bernard
Plastic and reconstructive surgery (1963),
10/2023, Volume:
152, Issue:
4
Journal Article
The genomic bases of the adipose tissue abnormalities induced by chronic positive calorie excess have been only partially elucidated. We adopted a genome-wide approach to directly test whether ...long-term high-fat diet (HFD) exposure affects the DNA methylation profile of the mouse adipose tissue and to identify the functional consequences of these changes.
We have used epididymal fat of mice fed either high-fat (HFD) or regular chow (STD) diet for 5 months and performed genome-wide DNA methylation analyses by methylated DNA immunoprecipitation sequencing (MeDIP-seq). Mouse Homeobox (Hox) Gene DNA Methylation PCR, RT-qPCR and bisulphite sequencing analyses were then performed.
Mice fed the HFD progressively expanded their adipose mass accompanied by a significant decrease in glucose tolerance (P<0.001) and insulin sensitivity (P<0.05). MeDIP-seq data analysis revealed a uniform distribution of differentially methylated regions (DMR) through the entire adipocyte genome, with a higher number of hypermethylated regions in HFD mice (P<0.005). This different methylation profile was accompanied by increased expression of the Dnmt3a DNA methyltransferase (Dnmt; P<0.05) and the methyl-CpG-binding domain protein Mbd3 (P<0.05) genes in HFD mice. Gene ontology analysis revealed that, in the HFD-treated mice, the Hox family of development genes was highly enriched in differentially methylated genes (P=0.008). To validate this finding, Hoxa5, which is implicated in fat tissue differentiation and remodeling, has been selected and analyzed by bisulphite sequencing, confirming hypermethylation in the adipose tissue from the HFD mice. Hoxa5 hypermethylation was associated with downregulation of Hoxa5 mRNA and protein expression. Feeding animals previously exposed to the HFD with a standard chow diet for two further months improved the metabolic phenotype of the animals, accompanied by return of Hoxa5 methylation and expression levels (P<0.05) to values similar to those of the control mice maintained under standard chow.
HFD induces adipose tissue abnormalities accompanied by epigenetic changes at the Hoxa5 adipose tissue remodeling gene.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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