Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery

ObjectivesAnti-inflammatory effects of tranexamic acid and aprotinin, used to abate perioperative blood loss, are reported and might be of substantial clinical relevance. The study of messenger ribonucleic acid synthesis provides a valuable asset in evaluating the inflammatory pathways involved.MethodsWhole-blood messenger ribonucleic acid expression of 114 inflammatory genes was compared pre- and postoperatively in 35 patients randomized to receive either placebo, tranexamic acid, or aprotinin. These results were further confirmed by reverse transcription–polymerase chain reaction.ResultsOf the 23 genes exhibiting independently altered postoperative gene expression levels, 8 were restricted to the aprotinin group only (growth differentiation factor 3, interleukin 19, interleukin 1 family member 7, transforming growth factor α, tumor necrosis factor superfamily 10, tumor necrosis factor superfamily 12, tumor necrosis factor superfamily 13B, vascular endothelial growth factor α), whereas both aprotinin and tranexamic acid altered gene expression of 3 genes as compared with placebo (FMS-related tyrosine kinase 3 ligand, growth differentiation factor 5, interferon-α8). In general, less upregulation of pro-inflammatory, and more upregulation of anti-inflammatory, genes was observed for patients treated with antifibrinolytics. Gene expression affected by aprotinin coded mostly for proteins that function through serine proteases.ConclusionsThis study demonstrates that the use of tranexamic acid and aprotinin results in altered inflammatory pathways on the genomic expression level. We further demonstrate that the use of aprotinin leads to significant attenuation of the immune response, with several inhibitory effects restricted to the use of aprotinin only. The results aid in a better understanding of the targets of these drugs, and add to the discussion on which antifibrinolytic can best be used in the cardiac surgical patient

Toward complete oral cavity cancer resection using a handheld diffuse reflectance spectroscopy probe

This ex-vivo study evaluates the feasibility of diffuse reflectance spectroscopy (DRS) for discriminating tumor from healthy tissue, with the aim to develop a technology that can assess resection margins for the presence of tumor cells during oral cavity cancer surgery. Diffuse reflectance spectra were acquired on fresh surgical specimens from 28 patients with oral cavity squamous cell carcinoma. The spectra (400 to 1600 nm) were detected after illuminating tissue with a source fiber at 0.3-, 0.7-, 1.0-, and 2.0-mm distances from a detection fiber, obtaining spectral information from different sampling depths. The spectra were correlated with histopathology. A total of 76 spectra were obtained from tumor tissue and 110 spectra from healthy muscle tissue. The first- A nd second-order derivatives of the spectra were calculated and a classification algorithm was developed using fivefold cross validation with a linear support vector machine. The best results were obtained by the reflectance measured with a 1-mm source-detector distance (sensitivity, specificity, and accuracy are 89%, 82%, and 86%, respectively). DRS can accurately discriminate tumor from healthy tissue in an ex-vivo setting using a 1-mm source-detector distance. Accurate validation methods are warranted for larger sampling depths to allow for guidance during oral cavity cancer excision.</p

Kiloparsec-scale gaseous clumps and star formation at z = 5–7

We investigate the morphology of the [Cii] emission in a sample of “normal” star-forming galaxies at 5 < z < 7:2 in relation to their UV (rest-frame) counterpart. We use new ALMA observations of galaxies at z 6 7, as well as a careful re-analysis of archival ALMA data. In total 29 galaxies were analysed, 21 of which are detected in [Cii]. For several of the latter the [Cii] emission breaks into multiple components. Only a fraction of these [Cii] components, if any, is associated with the primary UV systems, while the bulk of the [Cii] emission is associated either with fainter UV components, or not associated with any UV counterpart at the current limits. By taking into account the presence of all these components, we find that the L[CII]-SFR relation at early epochs is fully consistent with the local relation, but it has a dispersion of 0.48 0.07 dex, which is about two times larger than observed locally. We also find that the deviation from the local L[CII]-SFR relation has a weak anti-correlation with the EW(Ly ). The morphological analysis also reveals that [Cii] emission is generally much more extended than the UV emission. As a consequence, these primordial galaxies are characterised by a [Cii] surface brightness generally much lower than expected from the local [CII] SFR relation. These properties are likely a consequence of a combination of di erent e ects, namely: gas metallicity, [Cii] emission from obscured star-forming regions, strong variations of the ionisation parameter, and circumgalactic gas in accretion or ejected by these primeval galaxies.European Research Council RM acknowledges ERC Advanced Grant 695671 ‘QUENCH’. AF acknowledges support from the ERC Advanced Grant INTERSTELLAR H2020/740120

Isolation of ‘Candidatus Nitrosocosmicus franklandus’, a novel ureolytic soil archaeal ammonia oxidiser with tolerance to high ammonia concentration

Acknowledgements The authors would like to thank Mr Kevin Mackenzie and Mrs Gillian Milne (University of Aberdeen) for technical support with scanning electron microscopy, and Dr Robin Walker for access to the Woodlands Field experimental plots at the SRUC,Craibstone Estate, Aberdeen. Funding This work was financially supported by Natural Environmental Research Council (standard grants NE/I027835/1 and NE/L006286/1 and fellowship NE/J019151/1), EC Marie Curie ITN NORA, Grant Agreement No. 316472, the AXA Research Fund and the Centre for Genome Enabled Biology and Medicine, University of Aberdeen.Peer reviewedPublisher PD

The tubarial salivary glands:A potential new organ at risk for radiotherapy

Introduction: The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy. Materials and methods: The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated. Results: All 100 patients demonstrated a demarcated bilateral PSMA-positive area (average length 4 cm). Histology and 3D reconstruction confirmed the presence of PSMA-expressing, predominantly mucous glands with multiple draining ducts, predominantly near the torus tubarius. In the head-neck cancer patients, the mean RT dose to the gland area was significantly associated with physician-rated posttreatment xerostomia and dysphagia >= grade 2 at 12 months (0.019/gy, 95%CI 0.005-0.033, p =.007; 0.016/gy, 95%CI 0.001-0.031, p =.036). Follow-up at 24 months had similar results. Conclusion: The human body contains a pair of previously overlooked and clinically relevant macroscopic salivary gland locations, for which we propose the name tubarial glands. Sparing these glands in patients receiving RT may provide an opportunity to improve their quality of life. (C) 2020 The Authors. Published by Elsevier B.V

The course of health-related quality of life in the first 2 years after a diagnosis of head and neck cancer:the role of personal, clinical, psychological, physical, social, lifestyle, disease-related, and biological factors

Purpose: The aim of this prospective cohort study was to estimate the relationship between the course of HRQOL in the first 2 years after diagnosis and treatment of head and neck cancer (HNC) and personal, clinical, psychological, physical, social, lifestyle, HNC-related, and biological factors. Methods: Data were used from 638 HNC patients of the NETherlands QUality of life and BIomedical Cohort study (NET-QUBIC). Linear mixed models were used to investigate factors associated with the course of HRQOL (EORTC QLQ-C30 global quality of life (QL) and summary score (SumSc)) from baseline to 3, 6, 12, and 24 months after treatment. Results: Baseline depressive symptoms, social contacts, and oral pain were significantly associated with the course of QL from baseline to 24 months. Tumor subsite and baseline social eating, stress (hyperarousal), coughing, feeling ill, and IL-10 were associated with the course of SumSc. Post-treatment social contacts and stress (avoidance) were significantly associated with the course of QL from 6 to 24 months, and social contacts and weight loss with the course of SumSc. The course of SumSc from 6 to 24 months was also significantly associated with a change in financial problems, speech problems, weight loss, and shoulder problems between baseline and 6 months. Conclusion: Baseline clinical, psychological, social, lifestyle, HNC-related, and biological factors are associated with the course of HRQOL from baseline to 24 months after treatment. Post-treatment social, lifestyle, and HNC-related factors are associated with the course of HRQOL from 6 to 24 months after treatment.</p

Cold dust and low [O iii]/[C ii] ratios: an evolved star-forming population at redshift 7

We present new ALMA Band 8 (rest-frame 90 μm) continuum observations of three massive (M⋆ ≈ 1010 M⊙) galaxies at z ≈ 7 previously detected in [C II]158 μm and underlying dust continuum emission in the Reionization Era Bright Emission Line Survey (REBELS). We detect dust emission from two of our targets in Band 8 (REBELS-25 and REBELS-38), while REBELS-12 remains undetected. Through optically thin modified blackbody fitting, we determine dust temperatures of Tdust ≈ 30 − 35 K in both of the dual-band detected targets, indicating they are colder than most known galaxies at z ∼ 7. Moreover, their inferred dust masses are large (Mdust ≈ 108 M⊙), albeit still consistent with models of high-redshift dust production. We furthermore target and detect [O III]88 μm emission in both REBELS-12 and REBELS-25, and find L[O III]/L[C II] ≈ 1 − 1.5 – low compared to the L[O III]/L[C II] ≳ 2 − 10 observed in the known z ≳ 6 population thus far. We argue the lower line ratios are due to a comparatively weaker ionizing radiation field resulting from the less starbursty nature of our targets, although the possibility of REBELS-12 being a merger of an [O III]-bright and [O III]-faint component prevents the unambiguous interpretation of its [O III]/[C II] ratio. Nevertheless, a low burstiness forms a natural explanation for the cold dust temperatures and low [O III]λλ4959, 5007 + Hβ equivalent widths of REBELS-25 and REBELS-38. Overall, these observations provide evidence for the existence of a massive, dust-rich galaxy population at z ≈ 7 which has previously experienced vigorous star formation, but is currently forming stars in a steady, as opposed to bursty, manner

Baseline and early digital [¹⁸F]FDG PET/CT and multiparametric MRI contain promising features to predict response to neoadjuvant therapy in locally advanced rectal cancer patients:a pilot study

Objective In this pilot study, we investigated the feasibility of response prediction using digital [18F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial. Methods Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [18F]FDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P ≤ 0.2, promising predictive features for response were selected. Results Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features. Conclusion Both multiparametric MRI and [18F]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT.</p