Cloning, characterization and analysis of cat and ben genes from the phenol degrading halophilic bacterium Halomonas organivorans.

Background: Extensive use of phenolic compounds in industry has resulted in the generation of saline wastewaters that produce significant environmental contamination; however, little information is available on the degradation of phenolic compounds in saline conditions. Halomonas organivorans G-16.1 (CECT 5995T) is a moderately halophilic bacterium that we isolated in a previous work from saline environments of South Spain by enrichment for growth in different pollutants, including phenolic compounds. PCR amplification with degenerate primers revealed the presence of genes encoding ringcleaving enzymes of the b-ketoadipate pathway for aromatic catabolism in H. organivorans. Findings: The gene cluster catRBCA, involved in catechol degradation, was isolated from H. organivorans. The genes catA, catB, catC and the divergently transcribed catR code for catechol 1,2-dioxygenase (1,2-CTD), cis,cis-muconate cycloisomerase, muconolactone delta-isomerase and a LysR-type transcriptional regulator, respectively. The benzoate catabolic genes (benA and benB) are located flanking the cat genes. The expression of cat and ben genes by phenol and benzoic acid was shown by RT-PCR analysis. The induction of catA gene by phenol and benzoic acid was also probed by the measurement of 1,2-CTD activity in H. organivorans growth in presence of these inducers. 16S rRNA and catA gene-based phylogenies were established among different degrading bacteria showing no phylogenetic correlation between both genes. Conclusions/Significance: In this work, we isolated and determined the sequence of a gene cluster from a moderately halophilic bacterium encoding ortho-pathway genes involved in the catabolic metabolism of phenol and analyzed the gene organization, constituting the first report characterizing catabolic genes involved in the degradation of phenol in moderate halophiles, providing an ideal model system to investigate the potential use of this group of extremophiles in the decontamination of saline environments

The role of grain size in AGN torus dust models

Fits the infrared spectra from the nuclear regions of AGN can place constraints on the dust properties, distribution, and geometry by comparison with models. However, none of the currently available models fully describe the observations of AGN currently available. Among the aspects least explored, here we focus on the role of dust grain size. We offer the community a new spectral energy distribution (SED) library, hereinafter [GoMar23] model, which is based on the two-phase torus model developed before with the inclusion of the grain size as a model parameter, parameterized by the maximum grain size Psize or equivalently the mass-weighted average grain size . We created 691,200 SEDs using the SKIRT code, where the maximum grain size can vary within the range Psize = 0.01 - 10.0um ( = 0.007 - 3.41um). We fit this new and several existing libraries to a sample of 68 nearby and luminous AGNs with Spitzer/IRS spectra dominated by AGN-heated dust. We find that the [GoMar23] model can adequately reproduce up to 85-88% of the spectra. The dust grain size parameter significantly improves the final fit in up to 90% of these spectra. Statistical tests indicate that the grain size is the third most important parameter in the fitting procedure (after the size and half opening angle of the torus). The requirement of a foreground extinction by our model is lower compared to purely clumpy models. We find that 41% of our sample requires that the maximum dust grain size is as large as Psize =10um (= 3.41um). Nonetheless, we also remark that disk+wind and clumpy torus models are still required to reproduce the spectra of a non-negligible fraction of objects, suggesting the need for several dust geometries to explain the infrared continuum of AGN. This work provides tentative evidence for dust grain growth in the proximity of the AGN.Comment: 26 pages, 14 figures, 4 tables, accepted for publication in A&

COVID-19 in hospitalized HIV-positive and HIV-negative patients: A matched study

Objectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization.This work was supported by the Instituto de Salud Carlos III (ISCII) (grant no. COV20/00108) and the Spanish AIDS Research Network (RD16/0025), which is included in the Spanish I+D+I Plan and is co- funded by ISCIII- Subdirección General de Evaluación and European Funding for Regional Development (FEDER)S

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice: A multicentre cohort study

Background: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014-2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) &lt; 50 copies/ml and &lt; 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (&lt; 50 or ≥ 50 copies/ml at the start of the regimen). Results: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL &lt; 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL &lt; 50 copies/ml, 85.7% and 80.0% had VL &lt; 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL &lt; 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL &lt; 50 copies/ml and 69.2% and 68.2% had VL &lt; 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads.The RIS cohort (CoRIS) is supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I + D + i and cofinanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER)”

Community-based screening of Chagas disease among Latin American migrants in a non-endemic country: an observational study

Background: Chagas disease is a parasitic disease endemic to Latin America, but it has become a disease of global concern due to migration flows. Asymptomatic carriers may host the parasite for years, without knowing they are infected. The aim of this study is to assess prevalence of Chagas disease and evaluate the participants' level of knowledge between Latin American migrants attending a community-based screening campaign. Methods: Three community-based campaigns were performed in Alicante (Spain) in 2016, 2017 and 2018, including educational chats and blood tests for Trypanosoma cruzi serology. Participants completed a questionnaire assessing knowledge about the mechanisms of transmission, disease presentation, diagnosis, and treatment. People seropositive for T. cruzi underwent diagnostic confirmation by two different tests. Results were analyzed by multivariable logistic regression and expressed as adjusted odds ratios (aORs), adjusting for age, sex, and time in Spain. Results: A total of 596 participants were included in the study; 17% were aged under 18 years. Prevalence in adults was 11% [54/496; 95% confidence interval (CI): 8.3-14.5%] versus 0% among children. All but one case were in Bolivians. Diagnosis was independently associated with having been born in Bolivia (aOR: 102, 95% CI: 13-781) and a primary school-level education (aOR: 2.40, 95% CI: 1.14-5.06). Of 54 people diagnosed with Chagas disease (most of whom were asymptomatic), 42 (77.7%) returned to the clinic at least once, and 24 (44.4%) received treatment. Multivariable analysis showed that coming from Argentina (aOR: 13, 95% CI: 1.61-1188) or Bolivia (aOR: 1.90, 95% CI: 1.19-3.39) and having received information about Chagas disease in Spain (aOR: 4.63, 95% CI: 2.54-8.97) were associated with a good level of knowledge on the disease. Having primary level studies (aOR: 0.59, 95% CI: 0.34-0.98) and coming from Ecuador (aOR: 4.63, 95% CI: 2.52-847) were independently associated with a lower level of knowledge. Conclusions: Community-based interventions are a good strategy for diagnosing neglected diseases such as Chagas disease in non-endemic countries and for identifying and treating infected, asymptomatic individuals.This study was partially supported by the third call for research grants (J-M.R.-R.) from the Institute of Health and Biomedical Research of Alicante (ISABIAL)/FISABIO Foundation (III convocatoria de ayudas a proyectos de investigación del Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) – Fundación FISABIO) (UGP-16-158); and by the collaborative agreement between ISABIAL/Fundación FISABIO and Fundación Mundo Sano-Spain, in accordance with the Sponsorship Law. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Asymptomatic Strongyloidiasis among Latin American Migrants in Spain: A Community-Based Approach

Strongyloides stercoralis infection is frequently underdiagnosed since many infections remain asymptomatic. Aim: To estimate the prevalence and characteristics of asymptomatic S. stercoralis infection in Latin American migrants attending a community-based screening program for Chagas disease in Spain. Methodology: Three community-based Chagas disease screening campaigns were performed in Alicante (Spain) in 2016, 2017, and 2018. Serological testing for S. stercoralis infection was performed using a non-automatized IVD-ELISA detecting IgG (DRG Instruments GmbH, Marburg, Germany). Results: Of the 616 migrants from Central and South America who were screened, 601 were included in the study: 100 children and adolescents (<18 years of age) and 501 adults. Among the younger group, 6 participants tested positive (prevalence 6%, 95% confidence interval [CI] 2.5% to 13.1%), while 60 adults did so (prevalence 12%, 95% CI 9.3% to 15.3%). S. stercoralis infection was more common in men than in women (odds ratio adjusted [ORa] 2.28, 95% CI 1.289 to 4.03) and in those from Bolivia (ORa 2.03, 95% CI 1.15 to 3.59). Prevalence increased with age (ORa 1.02, 95% CI 0.99 to 1.05). In contrast, a university education had a protective effect (ORa 0.29, 95% CI 0.31 to 0.88). Forty-one (41/66; 62.1%) of the total cases of S. stercoralis infection were treated at the health care center. Positive stool samples were observed in 19.5% of the followed-up positive cases. Conclusion: Incorporating serological screening for S. stercoralis into community-based screening for Chagas disease is a useful intervention to detect asymptomatic S. stercoralis infection in Central and South American migrants and an opportunity to tackle neglected tropical diseases in a transversal way. The remaining challenge is to achieve patients' adherence to the medical follow-up.This study was partially supported by the 3rd call for research project grants for the Institute of Health and Biometric Research of Alicante (ISABIAL)/FISABIO Foundation (UGP-16-158), and by the collaboration agreement regulated under the Law of Patronage between ISABIAL/FISABIO and the Foundation Mundo Sano, Spain.S

Pediatric Chagas disease in the non-endemic area of Madrid: A fifteen-year review (2004-2018)

Background: Chagas disease (CD) has become an emerging global health problem in association with the immigration of individuals from endemic areas (in LatinAmerica) to other countries.Spain is the country in Europe with the highest number of CD cases. Concerning pediatric CD, treatment is not only better tolerated by younger children but also has greater cure possibilities. The aim of this study was to describe clinical and epidemiological aspects of CD in a pediatric population diagnosed of 10 hospitals in the Community of Madrid during the 2004-2018 period, as well as the safety and efficacy of CD treatment on this population. Methodology/principal findings: A multicenter, retrospective, descriptive study was conducted. The studied population included all identified children under the age of 18 with a diagnosis of CD. Diagnosis was performed with a positive parasitological test (with subsequent confirmation) or confirmed persistence of positive serology beyond 9 months, for children younger than one year-old, and with two different positive serological tests, for children older than one. Fifty-one children were included (59% male; 50.9% born in Spain). All mothers were from Latin America. The median age at diagnosis was 0.7 months for those under one year of age, and 11.08 years for those older than one year-old. Only one case presented a symptomatic course (hydrops faetalis, haemodynamic instability at birth, ascites, anaemia). For 94% treatment was completed. Considering patients who received benznidazole (47), AE were recorded in 48,9%. Among the 32 patients older than one year-old treated with benznidazole, 18 (56.25%) had adverse events whereas in the 15 under one year, 5(33,3%) did. Eigtheen (78.2%) of the patients with benznidazole AE were older than one year-old(median age 11.4 years). Of the patients treated with nifurtimox (9), AE were reported in 3 cases (33,3%). Cure was confirmed in 80% of the children under one year-old vs 4.3% in those older (p<0.001). Loss to follow- up occurred in 35.3% of patients. Conclusions/significances: Screening programs of CD since birth allow early diagnosis and treatment, with a significantly higher cure rate in children treated before one year of age, with lower incidence of adverse events. The high proportion of patients lost to follow-up in this vulnerable population is of concern.S

Implementation of a mindfulness-based crisis intervention for frontline healthcare workers during the COVID-19 outbreak in a public general hospital in Madrid, Spain

Introduction: The COVID-19 outbreak is having an impact on the well-being of healthcare workers. Mindfulness-based interventions have shown effectiveness in reducing stress and fostering resilience and recovery in healthcare workers. There are no studies examining the feasibility of brief mindfulness-based interventions during the COVID-19 outbreak. Materials and Methods: This is an exploratory study with a post intervention assessment. We describe an on-site brief mindfulness intervention and evaluate its helpfulness, safety, and feasibility. Results: One thousand out of 7,000 (14%) healthcare workers from La Paz University Hospital in Madrid (Spain) participated in at least one session. One hundred and fifty out of 1,000 (15%) participants filled out a self-report questionnaire evaluating the helpfulness of the intervention for on-site stress reduction. Ninety two subjects (61%) participated in more than one session. Most of the participants were women (80%) with a mean age of 38.6 years. Almost half of the sample were nurses (46%). Sessions were perceived as being helpful with a mean rating of 8.4 on a scale from 0 to 10. Only 3 people (2%) reported a minor adverse effect (increased anxiety or dizziness). Discussion: Our data supports the utility, safety and feasibility of an on-site, brief mindfulness-based intervention designed to reduce stress for frontline health workers during a crisis. There is a need to continue testing this type of interventions, and to integrate emotion regulation strategies as an essential part of health workers' general training. Clinical Trial Registration number: NCT04555005

Outcomes and prognostic factors of adults with refractory or relapsed T-cell acute lymphoblastic leukemia included in measurable residual disease-oriented trials

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9–8.6) months, with a 4-year OS probability of 18% (95% CI, 9%–27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109–3.362), 2.958 (1.640–5.334), and 2.976 (1.157–7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.La Caixa" Foundation and ISCIII, Grant/ Award Number: PI19/01828; Generalitat de Catalunya (GRC), Grant/Award Number: 2017 SGR28