Rotifers as Models in Toxicity Screening of Chemicals and Environmental Samples

An important objective of aquatic ecotoxicology is to determine the effects of toxic compounds in organisms that play a central role in aquatic communities where rotifers have a large impact on several important ecological processes. The contribution of the rotifers to secondary production in many aquatic communities is substantial as they are often the larger fraction of zooplankton biomass at certain times of the year. In addition to the importance of their ecological roles in aquatic communities, the rotifers are attractive organisms for ecotoxicological studies by its short life cycles and rapid reproduction, their small size, and little volumes needed for culture and toxicity assays. The main end points used in ecotoxicological studies are mortality, reproduction, behavior, and biomarkers. Such parameters are included in international regulations from all over the world, where different species are used to evaluate the effect of environmental samples or chemical compounds. The high diversity of rotifers is an important issue because it can modify their relative susceptibility to toxicants. Thus, more studies are needed to know the relations and mechanisms involved in clonal variation, sensitivity, and development, which can be all assessed by state-of-the-art procedures

A prospective study of lung disease in a cohort of early rheumatoid arthritis patients

Lung disease is common in patients with rheumatoid arthritis (RA). The onset of lung involvement in RA is not well known. The objective is to describe the features and evolution of lung involvement in early RA, its relationship with disease activity parameters, smoking and treatments. Consecutive patients with early RA without respiratory symptoms were included and tracked for 5 years. Lung assessment included clinical, radiological and pulmonary function tests at diagnosis and during follow-up. Peripheral blood parameters (erythrocyte sedimentation rate, C reactive protein, rheumatoid factor and anti-citrullinated peptide autoantibodies) and scales of articular involvement, such as DAS28-CRP, were evaluated. 40 patients were included and 32 completed the 5-year follow up. 13 patients presented lung involvement in the initial 5 years after RA diagnosis, 3 of them interstitial lung disease. Significant decrease of diffusion lung transfer capacity of carbon monoxide over time was observed in six patients, 2 of them developed interstitial lung disease. DLCO decrease was correlated with higher values of CRP and ESR at diagnosis. Methotrexate was not associated with DLCO deterioration or lung disease development. Subclinical progressive lung disease correlates with RA activity parameters. Smoking status and methotrexate were not associated with development or progression of lung disease

Integration of Maps Enables a Cytogenomics Analysis of the Complete Karyotype in Solea senegalensis

The Pleuronectiformes order, which includes several commercially-important species, has undergone extensive chromosome evolution. One of these species is Solea senegalensis, a flatfish with 2n = 42 chromosomes. In this study, a cytogenomics approach and integration with previous maps was applied to characterize the karyotype of the species. Synteny analysis of S. senegalensis was carried out using two flatfish as a reference: Cynoglossus semilaevis and Scophthalmus maximus. Most S. senegalensis chromosomes (or chromosome arms for metacentrics and submetacentrics) showed a one-to-one macrosyntenic pattern with the other two species. In addition, we studied how repetitive sequences could have played a role in the evolution of S. senegalensis bi-armed (3, and 5-9) and acrocentric (11, 12 and 16) chromosomes, which showed the highest rearrangements compared with the reference species. A higher abundance of TEs (Transposable Elements) and other repeated elements was observed adjacent to telomeric regions on chromosomes 3, 7, 9 and 16. However, on chromosome 11, a greater abundance of DNA transposons was detected in interstitial BACs. This chromosome is syntenic with several chromosomes of the other two flatfish species, suggesting rearrangements during its evolution. A similar situation was also found on chromosome 16 (for microsatellites and low complexity sequences), but not for TEs (retroelements and DNA transposons). These differences in the distribution and abundance of repetitive elements in chromosomes that have undergone remodeling processes during the course of evolution also suggest a possible role for simple repeat sequences in rearranged regions

Matched cohort study on the efficacy of tocilizumab in patients with COVID-19

Background: Tocilizumab has been proposed as a treatment for the new disease COVID-19, however, there is not enough scientific evidence to support this treatment. The objective of this study is to analyze whether the use of tocilizumab is associated with respiratory improvement and a shorter time to discharge in patients with COVID-19 and lung involvement. Methods: Observational study on a cohort of 418 patients, admitted to three county hospitals in Catalonia (Spain). Patients admitted consecutively were included and followed until discharge or up to 30 days of admission. A sub-cohort of patients treated with tocilizumab and a sub-cohort of control patients were identified, matched by a large number of risk factors and clinical variables. Sub-cohorts were also matched by the number of other treatments for COVID-19 that patients received. Increment in SAFI (inspired oxygen fraction / saturation) 48 h after the start of treatment, and time to discharge, were the primary outcomes. Mortality, which was a secondary outcome, was analyzed in the total cohort, by using logistic regression models, adjusted by confounders. Results: There were 96 patients treated with tocilizumab. Of them, 22 patients could be matched with an equivalent number of control patients. The increment in SAFI from baseline to 48 h of treatment, was not significantly different between groups (tocilizumab: −0.04; control: 0.09; p = 0.636). Also, no difference in time to discharge was found between the two sub-cohorts (logrank test: p = 0.472). The logistic regression models, did not show an effect of tocilizumab on mortality (OR 0.99; p = 0.990). Conclusions: We did not find a clinical benefit associated with the use tocilizumab, in terms of respiratory function at 48 h of treatment, or time to discharge

Diagnostic delay of associated interstitial lung disease increases mortality in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main extra-articular organ affected is the lung, sometimes in the form of diffuse interstitial lung disease (ILD) and conditions the prognosis. A multicenter, observational, descriptive and cross-sectional study of consecutive patients diagnosed with RA-ILD. Demographic, analytical, respiratory functional and evolution characteristics were analyzed to evaluate the predictors of progression and mortality. 106 patients were included. The multivariate analysis showed that the diagnostic delay was an independent predictor of mortality (HR 1.11, CI 1.01-1.23, p = 0.035). Also, age (HR 1.33, 95% CI 1.09-1.62, p = 0.0045), DLCO (%) (HR 0.85, 95% CI 0.73-0.98, p = 0.0246), and final SatO2 (%) in the 6MWT (HR 0.62, 95% CI 0.39-0.99, p = 0.0465) were independent predictor variables of mortality, as well as GAP index (HR 4.65, 95% CI 1.59-13.54, p = 0.0051) and CPI index (HR 1.12, 95% CI 1.03-1.22, p = 0.0092). The withdrawal of MTX or LFN after ILD diagnosis was associated with disease progression in the COX analysis (HR 2.18, 95% CI 1.14-4.18, p = 0.019). This is the first study that highlights the diagnostic delay in RA-ILD is associated with an increased mortality just like happens in IPF

Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study

We would like to thank M Luisa Puertas-Martin and Isabel Manzano-Jimenez, nurses at the Unit of Mammary Pathology, General Surgery Service, San Cecilio University Hospital (Granada), without whose enthusiasm the enrolment of participants in Granada would still be stalled. We are indebted to all the women taking part in the study.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Trial registration ClinicalTrials.gov NCT03885648, 03/25/2019. Retrospectively registered.Background Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. Methods We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. Discussion: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease.This work is funded by grants PI-0538-2017 (Junta de Andalucía, Spain, to LF) and Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP) of the Institute of Health Carlos III -supported by European Regional Development Fund/FEDER (FIS-PI16/01812) (to MFF)

Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients

OBJECTIVE: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. METHODS: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. RESULTS: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. CONCLUSION: ABA appears to be an effective in RA-associated ILD.Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from ‘‘Instituto de Salud Carlos III’’ (ISCIII), Spain

Medical versus surgical approach to initial treatment in septic arthritis: A single spanish center’s 8-year experience

Objective The aim of this study was to compare the functional results of 2 different procedure types, medical or surgical used in treating native joint septic arthritis. Methods In this cohort study, we reviewed the clinical registries of patients admitted to a single third-level hospital with the diagnosis of septic arthritis during the period of January 1, 2008, to January 31, 2016. Results A total of 63 cases of septic arthritis were identified in which the initial approach for 49 patients was medical (arthrocentesis), whereas the initial approach for 14 patients was surgical (arthroscopy or arthrotomy). Of the 49 patients who received initial medical treatment (IMT), 15 patients (30%) later required surgical treatment because of poor progress. The median age of the patients was 60 (SD, 18) years. The group who received IMT were older than those who received initial surgical treatment (median, 64 years [interquartile range {IQR}, 54–76 years], vs. 48 years [IQR, 30–60 years]). There was a larger percentage of male patients in the surgical group (78% vs. 42% [p = 0.018]). Thirty percent of the medical group had been receiving corticosteroid treatment (p = 0.018). Results of complete recovery of joint functionality showed no significant differences after 1 year (68% with MT vs. 67% with ST, p = 0.91). Both groups had similar symptom duration until diagnosis, duration of antibiotic therapy (median, 30 days [IQR, 28–49 days], vs. 29.5 days [IQR, 27–49] days), and mortality rate (3 in the medical group). Conclusions The results of the study show that initial surgical treatment in patients with native joint septic arthritis is not superior to IMT. However, half of the patients with shoulder and hip infections treated with IMT eventually required surgical intervention, suggesting that perhaps this should be the preferred initial approach in these cases

Ozonización de aguas regeneradas en pomelo ´star ruby´. Comportamiento de la instalación y respuesta agronómica y fisiológica del cultivo. Póster

Durante la campaña 2019-2020, se llevó a cabo un experimento para evaluar el comportamiento de una instalación de ozonización a pie de parcela cuando se utilizan aguas de diferente naturaleza (Regenerada y Trasvase) y obtener resultados preliminares a nivel agronómico y fisiológico de un cultivo de pomelo en estas condiciones. La aplicación de ozono, se realizó entre los meses de junio y agosto mediante una instalación situada a pie de parcela, utilizando un generador de O3 de 20 gr/hora. Durante este periodo, se aplicó el O3 durante todo el tiempo de riego, menos en la fase de abonado y postabonado, para evitar posibles efectos indeseables sobre la fertilización. Durante el resto del año, los árboles fueron fertirrigados según criterio del agricultor, utilizando el agua disponible (nunca regenerada). Se evaluaron en continuo los valores redox durante todos los eventos de riego, a la entrada y la salida de la instalación, el volumen de agua aplicado, así como algunos parámetros de crecimiento vegetativo y del fruto y estado hídrico del cultivo. Los parámetros de producción y calidad, así como el estado nutricional del cultivo de la campaña, también fueron evaluados. Nuestros resultados denotan que las instalaciones utilizadas para la aplicación de un tratamiento de ozonización a pie de parcela, cuando se utilizan aguas regeneradas, pueden presentar dificultades derivadas de la naturaleza de estas aguas (elevados niveles de materia orgánica y otras sustancias altamente oxidables), lo que hace necesario un estudio más exhaustivo de estos sistemas para poder llevar a cabo un tratamiento eficaz de O3 en estas condiciones. Dimensionar adecuadamente la generación de O3 para cada instalación en función de la naturaleza de las aguas utilizadas e implementar sistemas que garanticen la presurización de la instalación y procuren la dosificación adecuada de medio ácido, pueden ser algunas de las recomendaciones a seguir para este tipo de instalaciones. Por otra parte, la respuesta agronómica y fisiológica, ante estos tratamientos requiere igualmente de un mayor y más largo estudio, para poder alcanzar resultados confiables.El trabajo ha sido financiado por el proyecto RIS3MUR REUSAGUA, financiado por la Consejería de Empresa, Industria y Portavocía de la Región de Murcia, en el marco del Programa Operativo FEDER 2014-2020

Challenges in the synthesis of corannulene-based non-planar nanographenes on Au(111) surfaces

The on-surface synthesis of non-planar nanographenes is a challenging task. Herein, with the aid of bond-resolving scanning tunneling microscopy (BRSTM) and density functional theory (DFT) calculations, we present a systematic study aiming at the fabrication of corannulene-based nanographenes via intramolecular cyclodehydrogenation on a Au(111) surface. The formation of non-planar targeted products is confirmed to be energetically unfavorable compared to the formation of planar/quasi-planar undesired competing monomer products. In addition, the activation of intermolecular coupling further inhibits the formation of the final targeted product. Although it was not possible to access the corannulene moiety by means of on-surface synthesis, partial cyclodehydrogenation of the molecular precursors was demonstrated.This work was financially supported by the Spanish Agencia Estatal de Investigacion (PID2019-107338RB-C62, PID2019-107338RB-C63, PID2019-110037GB-I00 and MAT2016-78293-C6; AEI/FEDER, UE), the Basque Government (IT-1255-19), the European Union’s Horizon 2020 Program (Grant No. 863098), the Xunta de Galicia (Centro singular de investigacion de Galicia accreditation 2019–2022, ED431G 2019/03), the European Union (European Regional Development Fund-ERDF), and European Union’s Horizon 2020 Research and Innovation Programme under the project MEMO (Grant No. 766864).Peer reviewe