Carbon dioxide rebreathing in non-invasive ventilation. Analysis of masks, expiratory ports and ventilatory modes

Background and Aim. Carbon dioxide (CO2) rebreathing is a complication of non-invasive ventilation (NIV). Our objectives were to evaluate the ability of masks with exhaust vents (EV) to avoid rebreathing while using positive pressure (PP) NIV with different levels of expiratory pressure (EPAP). Concerning volume-cycled NIV, we aimed to determine whether cylindrical spacers located in the circuit generate rebreathing. Materials and methods. 5 healthy volunteers were evaluated. Bi-level PP was used with 3 nasal and 2 facial masks with and without EV. Spacers of increasing volume attached to nasal hermetic masks were evaluated with volume NIV. Inspired CO2 fraction was analyzed. Results. Rebreathing was zero with all nasal masks and EPAP levels. Using facial masks 1 volunteer showed rebreathing. There was no rebreathing while using all the spacers. Conclusions. In healthy volunteers, nasal and facial masks with EV prevent rebreathing. In addition, the use of spacers did not generate this undesirable phenomenon

Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis

The introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population is small. There is a need to discover new potential actionable genetic lesions, to which end, non-conventional cancer pathways, such as RNA editing, are worth exploring. Herein we show that the adenosine-toinosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein. From a growth and invasion standpoint, the depletion of ADAR1 expression in amplified cells reduces their tumorigenic potential in cell culture and mouse models, whereas its overexpression has the opposite effects. From a functional perspective, ADAR1 overexpression enhances the editing frequencies of target transcripts such as NEIL1 and miR-381. In the clinical setting, patients with early-stage lung cancer, but harboring ADAR1 gene amplification, have poor outcomes. Overall, our results indicate a role for ADAR1 as a lung cancer oncogene undergoing gene amplification-associated activation that affects downstream RNA editing patterns and patient prognosis.This work was supported by the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 268626—EPINORC project, the Grant agreement number HEALTH-F2-2010-258677—CURELUNG project, the Spanish Ministry of Economy and Competitiveness (MINECO Projects no. SAF2011-22803, PI13-01339 and SAF2014-55000- R), the Institute of Health Carlos III (ISCIII)—PI10/02992, Ministerio de Educación, Ciencia e Innovación Grant SAF2010-14935, the Cellex Foundation, the National Cancer Center Research and Development Fund (NCC Biobank: 23 A-1) and the Health and Science Departments of the Catalan Government (Generalitat de Catalunya) AGAUR—project no. 2009SGR1315 and 2014SGR633.Peer Reviewe

Comparison of Engineering Wake Models with CFD Simulations

The engineering wake models by Jensen [1] and Frandsen et al. [2] are assessed for different scenarios simulated using Large Eddy Simulation and the Actuator Line method implemented in the Navier-Stokes equations. The scenarios include the far wake behind a single wind turbine, a long row of turbines in an atmospheric boundary layer, idealised cases of an infinitely long row of wind turbines and infinite wind farms with three different spacings. Both models include a wake expansion factor, which is calibrated to fit the simulated wake velocities. The analysis highlights physical deficiencies in the ability of the models to universally predict the wake velocities, as the expansion factor can be fitted for a given case, but with not apparent transition between the cases. 1

Comparative study of T84 and T84SF human colon carcinoma cells: in vitro and in vivo ultrastructural and functional characterization of cell culture and metastasis

To better understand the relationship between tumor heterogeneity, differentiation, and metastasis, suitable experimental models permitting in vitro and in vivo studies are necessary. A new variant cell line (T84SF) exhibiting an altered phenotype was recently selected from a colon cancer cell line (T84) by repetitive plating on TNF-alpha treated human endothelial cells and subsequent selection for adherent cells. The matched pair of cell lines provides a useful system to investigate the extravasation step of the metastatic cascade. Since analysis of morphological differences can be instructive to the understanding of metastatic potential of tumor cells, we compared the ultrastructural and functional phenotype of T84 and T84SF cells in vitro and in vivo. The reported ultrastructural features evidence differences between the two cell lines; selected cells showed a marked pleomorphism of cell size and nuclei, shape, and greater surface complexity. These morphological differences were also coupled with biochemical data showing a distinct tyrosine phosphorylation-based signaling, an altered localization of beta-catenin, MAPK, and AKT activation, as well as an increased expression in T84SF cells of Bcl-X-L, a major regulator of apoptosis. Therefore, these cell lines represent a step forward in the development of appropriate models in vitro and in vivo to investigate colon cancer progression

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Carcinogenicity of cobalt, antimony compounds, and weapons-grade tungsten alloy

The complete evaluation of the carcinogenicity of cobalt, antimony compounds, and weapons-grade tungsten alloy will be published in Volume 131 of the IARC Monographs.[Excerpt] In March, 2022, a Working Group of 31 scientists from 13 countries met remotely at the invitation of the International Agency for Research on Cancer (IARC) to finalise their evaluation of the carcinogenicity of nine agents: cobalt metal (without tungsten carbide or other metal alloys), soluble cobalt(II) salts, cobalt(II) oxide, cobalt(II,III) oxide, cobalt(II) sulfide, other cobalt(II) compounds, trivalent antimony, pentavalent antimony, and weapons-grade tungsten (with nickel and cobalt) alloy. For cobalt metal and the cobalt compounds, particles of all sizes were included in the evaluation. These assessments will be published in Volume 131 of the IARC Monographs.1 Cobalt metal and soluble cobalt(II) salts were classified as “probably carcinogenic to humans” (Group 2A) based on “sufficient” evidence for cancer in experimental animals and “strong” mechanistic evidence in human primary cells. Cobalt(II) oxide and weapons-grade tungsten alloy were classified as “possibly carcinogenic to humans” (Group 2B) based on “sufficient” evidence in experimental animals. Trivalent antimony was classified as “probably carcinogenic to humans” (Group 2A), based on “limited” evidence for cancer in humans, “sufficient” evidence for cancer in experimental animals, and “strong” mechanistic evidence in human primary cells and in experimental systems. Cobalt(II,III) oxide, cobalt(II) sulfide, other cobalt(II) compounds, and pentavalent antimony were each evaluated as “not classifiable as to its carcinogenicity to humans” (Group 3).[...

Eligibility criteria for Menopausal Hormone Therapy (MHT): a position statement from a consortium of scientific societies for the use of MHT in women with medical conditions. MHT Eligibility Criteria Group

This project aims to develop eligibility criteria for menopausal hormone therapy (MHT). The tool should be similar to those already established for contraception A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by women with medical conditions based on the best available evidence. The project was developed in two phases. As a first step, we conducted 14 systematic reviews and 32 metanalyses on the safety of MHT (in nine areas: age, time of menopause onset, treatment duration, women with thrombotic risk, women with a personal history of cardiovascular disease, women with metabolic syndrome, women with gastrointestinal diseases, survivors of breast cancer or of other cancers, and women who smoke) and on the most relevant pharmacological interactions with MHT. These systematic reviews and metanalyses helped inform a structured process in which a panel of experts defined the eligibility criteria according to a specific framework, which facilitated the discussion and development process. To unify the proposal, the following eligibility criteria have been defined in accordance with the WHO international nomenclature for the different alternatives for MHT (category 1, no restriction on the use of MHT; category 2, the benefits outweigh the risks; category 3, the risks generally outweigh the benefits; category 4, MHT should not be used). Quality was classified as high, moderate, low or very low, based on several factors (including risk of bias, inaccuracy, inconsistency, lack of directionality and publication bias). When no direct evidence was identified, but plausibility, clinical experience or indirect evidence were available, "Expert opinion" was categorized. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, has been defined. This will provide health professionals with a powerful decision-making tool that can be used to manage menopausal symptoms