Genotoxicity evaluation of individual cigarette smoke toxicants using the in vitro γH2AX assay by High Content Screening

AbstractCigarette smoke is a complex mixture consisting of more than 5600 identified chemical constituents of which approximately 150 have been identified so far as “tobacco smoke toxicants”. Proposals made by the World Health Organisation Framework Convention on Tobacco Control mandate the lowering of nine tobacco smoke priority toxicants, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosonornicotine (NNN), and benzo[a]pyrene (B[a]P) and monitoring the levels of a further nine including cadmium.Here, we evaluated the genotoxic potential in human bronchial epithelial BEAS-2B cells of four cigarette smoke toxicants; NNK, NNN, B[a]P and cadmium using the novel in vitro γH2AX assay by High Content Screening (HCS). We also examined the genotoxicity of binary mixtures of NNK and NNN reporting their relative contribution to the genotoxic end-point.The results of this preliminary assessment showed that the in vitro γH2AX assay by HCS could be used as a pre-screening tool to detect and quantify the genotoxicity effect of cigarette smoke toxicants individually and in binary mixture. Moreover, the data produced could contribute to the prioritisation of toxicant reduction research in modified tobacco products

A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria

Multi-drug resistance; Risk factor; ColonizationResistencia a múltiples fármacos; Factor de riesgo; ColonizaciónResistència a múltiples fàrmacs; Factor de risc; ColonitzacióObjective. Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation. Material and methods. A systematic literature review was developed to identify RFs associated with infection progression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert’s experience. Results. A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation. Conclusion. The results of this study may contribute to the early identification of CRGNB colonized patients at higher risk of infection development, favouring time-to-effective therapy and improving health outcomes.This study was funded by Shionogi S.L.U

Página web orientada a la evaluación “in silico” de nuevas sustancias con interés biológico

El principal objetivo que nos planteamos fue proporcionar a los alumnos, tanto de Grado cómo de Posgrado, un entorno de aprendizaje virtual adaptativo donde poner en práctica los conocimientos de toxicología adquiridos en las clases teóricas, complementando e incrementando así el conocimiento aplicado. Y que los alumnos adquieran experiencia práctica en el manejo de datos toxicológicos y herramientas virtuales que cada día están más presentes en la vida profesional, llevando a cabo procedimientos experimentales predictivos y evaluaciones toxicológicas in silico con herramientas reales. Para ello se planteó diseñar y elaborar una página web donde se engloben todos aquellos enlaces de herramientas validadas para realizar análisis toxicológicos on-line, y de esta manera, responder a la necesidad de crear un entorno de fácil acceso que incluya las numerosas herramientas a las que se puede acceder, con el valor añadido de los tutoriales o textos explicativos para su comprensión y utilización. Con todo ello, el principal objetivo es lograr que los alumnos aprendan, no solo a cómo usar e interpretar los datos, sino también a la aplicación potencial de dichos datos obtenidos a través de los sistemas in silico

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Pollen beetle (Astylus atromaculatus)-associated gastroenteric disease in cattle: report of 6 natural outbreaks

Astylus atromaculatus is a pollen beetle native to South America, commonly found in crop flowers. Experimental intoxication of sheep and guinea pigs by this beetle resulting in fibrinonecrotizing enteritis has been reported. We describe here 6 natural outbreaks of intoxication in cattle associated with consumption of alfalfa (5 of 6) and mixed native (1 of 6) pastures heavily contaminated with A. atromaculatus. The outbreaks occurred during the summer (January–February) of 2023 in Argentina (n = 4) and Uruguay (n = 2), in beef cattle under extensive or semi-extensive rearing systems, with overall cumulative incidence and mortality of 22.3% and 17.8%, respectively. The main clinical signs included acute onset of anorexia, lethargy, hyperthermia, hindlimb weakness, reluctance to move, and diarrhea, for up to 15 d. In 2 outbreaks, sudden death was observed. Eight Hereford, Angus, and/or crossbreed heifers, cows, steers, and/or calves were autopsied. Gross and microscopic findings included multifocal necrosis with fibrinous pseudomembranes in the forestomachs and/or small and large intestines. Fragments or whole specimens of A. atromaculatus were identified in the ruminal content of all animals. Testing for multiple gastroenteric pathogens was negative as was testing of A. atromaculatus for cantharidin and batrachotoxin. GC-MS and LC-MS/MS performed on the beetles did not identify any known toxic compounds. Based on the exposure to A. atromaculatus–contaminated pasture, gross and microscopic lesions, and negative results of all testing for multiple gastroenteric pathogens, a diagnosis of intoxication by A. atromaculatus is proposed. Disease caused by A. atromaculatus consumption has not been reported previously in cattle, to our knowledge.EEA BalcarceFil: García, Juan Agustin. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina.Fil: Livio, Juan M. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina.Fil: Matto, Carolina. Ministerio de Ganadería, Agricultura y Pesca. Laboratorio Regional Noroeste; Uruguay.Fil: Dutra, Fernando. Laboratorio Regional Este; Uruguay.Fil: Scioli, María Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina.Fil: Giannitti, Federico. Instituto Nacional de Investigación Agropecuaria. Estación Experimental La Estanzuela; Uruguay.Fil: Langston, James. University of California. School of Veterinary Medicine; Estados Unidos.Fil: Poppenga, Robert H. University of California. School of Veterinary Medicine; Estados Unidos.Fil: Cantón, Germán José. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina.Fil: Uzal, Francisco. University of California. School of Veterinary Medicine; Estados Unidos