Prevalence of potentially thermophilic microorganisms in biofilms from greenhouse-enclosed drip irrigation systems

Drip irrigation systems using reclaimed water often present clogging events of biological origin. Microbial communities in biofilms from microirrigation systems of an experimental greenhouse in Almería, SE Spain, which used two different qualities of water (treated wastewater and reclaimed water), were analyzed by denaturing gradient gel electrophoresis and subsequent sequencing of amplified 16S rRNA gene bands. The most remarkable feature of all biofilms was that regardless of water origin, sequences belonging to Firmicutes were prevalent (53.5 % of total mean band intensity) and that almost all sequences recovered had some similarity (between 80.2 and 97 %) to thermophilic microorganisms. Mainly, sequences were closely related to potentially spore-forming organisms, suggesting that microbial communities able to grow at high temperatures were selected from the microbiota present in the incoming water. These pioneer results may contribute to improve management strategies to minimize the problems associated to biofouling in irrigation systems

Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA-ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 +/- 18.6 months) and long-term (38.5 +/- 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as >= 2 lobar ICHs and >= 5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH

Characteristics and outcomes of adult patients in the PETHEMA registry with relapsed or refractory FLT3-ITD mutation-positive acute myeloid leukemia

This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant.This study was supported by Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Valencia, Spain [CB16/12/00284]

Influence of contaminant-spiked polyethylene-type microplastics on the growth and primary production of the freshwater phytoplankton species Scenedesmus armatus and Microcystis aeruginosa

Microplastic pollution and its ecological impact on the aquatic environment are a current focus of research in the scientific community. These microplastics may adsorb contaminants discharged into the aquatic environment, thereby serving as a sink and source for the dissemination of these associated chemical contaminants. However, knowledge about the potential risks of microplastics and associated chemical contaminants on aquatic biota, especially on primary freshwater producers, remains to be explored. In this study, the impact of a polyethylene microplastic type (MP) associated with amoxicillin, ibuprofen, sertraline and simazine (OCs) on the cell growth and photosynthetic activity of the green algae Scenedesmus armatus and the cyanobacteria Microcystis aeruginosa was evaluated after 28 days of exposure. The results show that all the organic contaminants and their respective MP-OC complexes induced stress on cell growth after 28 days of exposure, except when the cyanobacterial strain was exposed to amoxicillin and ibuprofen. Similarly, photosynthetic activity was affected by exposure to MP-OC complexes, with the most evident effect on cellular respiration in the cyanobacterial strain and on net photosynthesis in the green algae strain. Additionally, the ability of the M. aeruginosa strain to synthesize microcystin was significantly reduced. These results show that the formation of MP-OC complexes could reduce their adverse effects, although there is wide variability depending on both the type of organic contaminant and the photosynthetic organisms involved, so further studies are needed to better understand the interactions between these aquatic contaminants

Serum micrornas as tool to predict early response to benralizumab in severe eosinophilic asthma

Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as NFKB2, NFATC3, DUSP1, DUSP2, DUSP5 and DUSP16. In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.This manuscript was funded by Fondo de Investigación Sanitaria–FIS and FEDER (Fondo Europeo de Desarrollo Regional) [PI15/00803, PI18/00044, and FI16/00036], CIBER de Enfermedades Respiratorias (CIBERES), Merck Health Foundation funds, and Ministerio de Ciencia, Innovación y Universidades (RTC-2017-6501-1

Utility of circulating serum miRNA profiles to evaluate the potential risk and severity of immune-mediated inflammatory disorders

Immune-mediated inflammatory disorders (IMID) are a group of diseases that present inflammation as a major pathogenic mechanism. They affect 15% of the population and pose a heavy socio-economic burden. Despite the growing knowledge on the etiopathogenesis of these diseases and the marked improvement in their management, there is a lack of predictive markers of IMID development or severity suitable for early diagnosis and adjustment of treatment intensity. The possibility that certain circulating miRNA profiles could be used as biomarkers of risk of development and/or severity of several autoimmune diseases has fuelled the interest in using them to improve the selection of successful treatments. The multi-pronged approach proposed here sought to reveal circulating miRNAs and miRNA signatures that could act as new predictive biomarkers of IMID development and severity. Our results showed that the circulating levels of miR-19b and miR-26b were significantly decreased (p &lt; 0.001) in IMID patients compared to controls. Furthermore, receiver operating characteristic (ROC) curve analysis showed that these miRNAs were suitable discriminators capable to identify an IMID, with areas under the curve (AUC) of 0.85 and 0.83, respectively. In addition, we established that miR-19a and miR-143 were significantly increased in IMID patients with severe disease (p &lt; 0.05). In summary, our findings identify two different miRNA signatures. One of them is associated with the presence of IMIDs and could lead to the development of tools for their early detection. The second signature is able to discriminate between mild and severe forms of these disorders and could be a putative tool to select patient candidates for a more intense treatment.This work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PIE13-0041, PI16-02091 and PI19-00584 (funded by Ministerio de Economía y Competitividad (MINECO), Instituto de Salud Carlos III (ISCIII)), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12) to MM; also by grants RD16/0011/0012 and PI18/0371 from MINECO, ISCIII to IGA; PI17/01972 (MINECO, ISCIIII) to E. D; and Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Fundación BBVA a equipos de Investigación Científica 2018 and from “la Caixa Banking Foundation” under the project code HR17-00016 to F·S.M and cofinanced by FEDER fund

Patients’ Opinions about Knowing Their Risk for Depression and What to Do about It. The PredictD-Qualitative Study

[Background] The predictD study developed and validated a risk algorithm for predicting the onset of major depression in primary care. We aimed to explore the opinion of patients about knowing their risk for depression and the values and criteria upon which these opinions are based. [Methods] A maximum variation sample of patients was taken, stratified by city, age, gender, immigrant status, socio-economic status and lifetime depression. The study participants were 52 patients belonging to 13 urban health centres in seven different cities around Spain. Seven Focus Groups (FGs) were given held with primary care patients, one for each of the seven participating cities. [Results] The results showed that patients generally welcomed knowing their risk for depression. Furthermore, in light of available evidence several patients proposed potential changes in their lifestyles to prevent depression. Patients generally preferred to ask their General Practitioners (GPs) for advice, though mental health specialists were also mentioned. They suggested that GPs undertake interventions tailored to each patient, from a “patient-centred” approach, with certain communication skills, and giving advice to help patients cope with the knowledge that they are at risk of becoming depressed. [Conclusions] Patients are pleased to be informed about their risk for depression. We detected certain beliefs, attitudes, values, expectations and behaviour among the patients that were potentially useful for future primary prevention programmes on depression.This work was supported by grants from the Andalusian Council of Health [grant reference: 2008/0195][www.juntadeandalucia.es/fundacionprogres​oysalud]; the Department of Health of the Basque Government [grant reference: 2008/111021][www.osakidetza.euskadi.net]; the Spanish Network of Primary Care Research “redIAPP” (RD06/0018), the “Aragón group” (RD06/0018/0020), the “Sant Joan de Deu group” (RD07/0018/0017), “Bizkaya group” (RD07/0018/0018), “Castilla-León group” (RD07/0018/0027) and the “SAMSERAP group” (RD06/0018/0039 and CTS-587) [www.rediapp.org]

SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes

Pancreatic beta cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here, we report that succinate receptor 1 (SUCNR1) is expressed in beta cells and is upregulated in hyperglycemic states in mice and humans. We found that succinate acted as a hormone -like metabolite and stimulated insulin secretion via a SUCNR1-GqPKC-dependent mechanism in human beta cells. Mice with beta cell-specific Sucnr1 deficiency exhibited impaired glucose tolerance and insulin secretion on a high -fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet -induced insulin resistance. Patients with impaired glucose tolerance showed an enhanced nutrition -related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states

Microbial communities of the olive mill wastewater sludge stored in evaporation ponds: The resource for sustainable bioremediation

Olive Mill Wastewater (OMW) is a polluting residue from the olive oil industry. It is usually stored in open-air unprotected evaporation ponds where their sediments accumulate. This study compares the characteristics of OMW sludges stored for long-time in evaporation ponds and assesses their impact on the underlying soil layer. Physicochemical parameters, toxicity bioassays, and full characterization of the microbial community were analyzed. The extension of the polluting effects was assessed by analysis of toxicity, microbial biomass carbon, and respiration. Geostatistics was used to predict their spatial distribution. Organic matter and polyphenol content besides toxicity levels determine variations between OMW sludges and have a high impact on the microbiota they contain. The microbial community was abundant, diverse, and functionally active. However, the biodegradability of the sludges was hindered by the toxicity levels. Toxicity and biomass carbon were higher on the surface of the ponds than in the soil layer revealing a reduced leach flow and depletion of contaminants. The natural microbiota might be biostimulated by means of applying sustainable and feasible biological treatments in order to favor the OMW sludges bioremediation. These results open up the possibility of solving the environmental concern caused by its storage in similar scenarios, which are common in olive oil-producing countries

Survival in male COVID-19 patients linked to testosterone recovery

Infection with SARS-CoV-2 portends a broad range of outcomes, from a majority of asymptomatic cases or mild clinical courses to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty and co-morbidities such as obesity, diabetes or cardiovascular disease. A precise knowledge is still lacking of the molecular and biological mechanisms that may explain the association of severe disease with male sex. Here, we show that testosterone trajectories are highly accurate individual predictors (AUC of ROC = 0.928, p < 0.0001) of survival in male COVID-19 patients. Longitudinal determinations of blood levels of luteinizing hormone (LH) and androstenedione suggest an early modest inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by either full recovery in survivors or a peripheral failure in lethal cases. Moreover, failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and decrease of non-classical monocytes. The strong association of recovery or failure to reinstate testosterone levels with survival or death from COVID-19 in male patients is suggestive of a significant role of testosterone status in the immune responses to COVID-19.This study was funded by grants from the Ministerio de Ciencia e Innovacion (RTI2018-096055-B-I00), Consejo Superior de Investigaciones Cientificas COVID-19 Research Fund (CSIC-COV19-006, CSIC-COV19-201), Agencia de Gestio Ajuts Universitaris i de Recerca (2020PANDE00048 and 2017SGR 1411 GRC), Plan Nacional de I+D (PID-107139RB-C21) and Instituto Nacional de la Salud Carlos III (PI18/00346 and COVID-19_00416).N