Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Influence of surface oxidation on the quantification of polypropylene microplastics by pyrolysis gas chromatography mass spectrometry

The influence of photo-oxidation on the quantification of isotactic polypropylene by Pyrolysis Gas Chromatography/Mass Spectrometry (Pyr-GC/MS) was assessed. Beads (oval shape, ~5 mm) and fragments (irregular shaped, 250–50 μm and 500–1000 μm) were subjected to relatively harsh simulated accelerated weathering conditions (using a filtered xenon-arc reproducing sunlight's full spectrum) for up to 37 and 80 days, respectively. Samples collected (n = 10 replicates for each treatment) at increasing number of weathering days were analysed by Fourier-transform infrared spectroscopy with Attenuated Total Reflection (FTIR-ATR), scanning electron microscopy, and differential scanning calorimetry in order to assess the extent and the rate of degradation. The rate of surface oxidation occurred faster for fragments compared to beads, probably due to their higher surface area. Quantification of the polypropylene trimer (2,4-dimethyl-1-heptene) via double shot Pyr-GC/MS, showed that the signal of the trimer relative to the mass of polypropylene was reduced through weathering with a degradation rate of 1:3 faster for fragments over beads. Signal reduction and carbonyl index were correlated to show that polypropylene with a carbonyl index of ≥13 has a significantly reduced 2,4-dimethyl-1-heptene signal when compared to virgin material. Consequently, the quantification of polypropylene subjected to weathering under harsh conditions may be underestimated by 42% (fragments, carbonyl index: 18) to 49% (beads, carbonyl index: 30) when quantified by Pyr-GC/MS and using virgin polypropylene calibration standards. Pyrolysis at a lower temperature (350 °C) identified six degradation specific markers (oxidation products) that increased in concentration with weathering. Further comparisons between virgin and weathered microplastics may need to be considered to avoid underestimation of microplastic concentrations in future studies.</p

Structural flexibility of RNA as molecular basis for Hfq chaperone function

In enteric bacteria, many small regulatory RNAs (sRNAs) associate with the RNA chaperone host factor Q (Hfq) and often require the protein for regulation of target mRNAs. Previous studies suggested that the hexameric Escherichia coli Hfq (Hfq(Ec)) binds sRNAs on the proximal site, whereas the distal site has been implicated in Hfq-mRNA interactions. Employing a combination of small angle X-ray scattering, nuclear magnetic resonance and biochemical approaches, we report the structural analysis of a 1:1 complex of Hfq(Ec) with a 34-nt-long subsequence of a natural substrate sRNA, DsrA (DsrA(34)). This sRNA is involved in post-transcriptional regulation of the E. coli rpoS mRNA encoding the stationary phase sigma factor RpoS. The molecular envelopes of Hfq(Ec) in complex with DsrA(34) revealed an overall asymmetric shape of the complex in solution with the protein maintaining its doughnut-like structure, whereas the extended DsrA(34) is flexible and displays an ensemble of different spatial arrangements. These results are discussed in terms of a model, wherein the structural flexibility of RNA ligands bound to Hfq stochastically facilitates base pairing and provides the foundation for the RNA chaperone function inherent to Hfq

Integrated Transcriptome Map Highlights Structural and Functional Aspects of the Normal Human Heart

A systematic meta-analysis of the available gene expression profiling datasets for the whole normal human heart generated a quantitative transcriptome reference map of this organ. Transcriptome Mapper (TRAM) software integrated 32 gene expression profile datasets from different sources returning a reference value of expression for each of the 43,360 known, mapped transcripts assayed by any of the experimental platforms used in this regard. Main findings include the visualization at the gene and chromosomal levels of the classical description of the basic histology and physiology of the heart, the identification of suitable housekeeping reference genes, the analysis of stoichiometry of gene products, and the focusing on chromosome 21 genes, which are present in one excess copy in Down syndrome subjects, presenting cardiovascular defects in 30-40% of cases. Independent in vitro validation showed an excellent correlation coefficient (r\u2009=\u20090.98) with the in silico data. Remarkably, heart/non-cardiac tissue expression ratio may also be used to anticipate that effects of mutations will most probably affect or not the heart. The quantitative reference global portrait of gene expression in the whole normal human heart illustrates the structural and functional aspects of the whole organ and is a general model to understand the mechanisms underlying heart pathophysiology. J. Cell. Physiol. 9999: 1-12, 2016. \ua9 2016 Wiley Periodicals, Inc

Nanopillar force measurements reveal actin-cap-mediated YAP mechanotransduction

A robust nanopillar platform with increased spatial resolution reveals that perinuclear forces, originating from stress fibres spanning the nucleus of fibroblasts, are significantly higher on these nanostructured substrates than the forces acting on peripheral adhesions. Many perinuclear adhesions embrace several nanopillars at once, pulling them into β1-integrin- and zyxin-rich clusters, which are able to translocate in the direction of cell motion without losing their tensile strength. The high perinuclear forces are greatly reduced upon inhibition of cell contractility or actin polymerization and disruption of the actin cap by KASH dominant-negative mutant expression. LMNA null fibroblasts have higher peripheral versus perinuclear forces, impaired perinuclear β1-integrin recruitment, as well as YAP nuclear translocation, functional alterations that can be rescued by lamin A expression. These highly tensed actin-cap fibres are required for YAP nuclear signalling and thus play far more important roles in sensing nanotopographies and mechanochemical signal conversion than previously thought.ISSN:1465-7392ISSN:1476-467