Report to Ministry of Health

Emerging pollutants are thought to be responsible for the most significant share of environmental, human health and economic risk. Although the universe of chemical pollutants is enormous, we only monitor and have studied a minor fraction. The study of the fate of the emerging pollutants and their transformation products in wastewater-treatment plants (WWTP) is of paramount importance, since it can provide valuable information on the human consumption of various drugs. Sewage epidiomiology is the new field that was develloped for the estimation of illicit drug use based on measurements of urinary excreted illicit drugs and their metabolites in untreated wastewater. Within this approach, human metabolic excretion products resulting from drug consumption are rapidly collected and pooled by the sewage systems, providing valuable evidence of the amount and type of drug consumed by a population. The main objective of this research is the contribution to the current knowledge on the actual burden of micropollutants on the environment and on the effect they have on the human health

PEAKTRAMS: An automated computational approach for the simultaneous detection of features in reverse phase and hilic hrms screening

Comparison of chromatograms obtained in reserved phase (RP) liquid chromatography and hydrophilic interaction liquid chromatography (HILIC) can provide valuable information for the identification and confirmation of suspect and non-target compounds. The plausibility of the obtained chromatographic retention times (RTs) in both modes as well as the ψomparison of the MS/MS spectra are strong points to be considered. This work presents the development of a novel automatic approach for the identification of common peaks between RP and HILIC chromatograms. The core of the program is written in R-project while a simple and user friendly graphical user interface (GUI) was built in JAVA. The first step consists of the introduction of the target chromatograms of the same sample (one obtained by RP and one by HILIC) plus the corresponding blank chromatograms. Blank subtraction was performed first using an algorithm to find in each scan the common m/z features (with a given mass accuracy). This algorithm also considers the RTs (a tolerance interval is applied), so the subtraction takes place even with slight drifts in the RTs between target and blank chromatograms. After blank subtraction, two different lists are obtained with the detected peaks in both RP and HILIC modes. Subsequently, m/z values are compared and matches are listed. The developed workflow was validated with solvent standards and with spiked wastewater samples with a mixture of compounds with a wide range of physicochemical properties. Successful results were obtained for 26 out of the 27 evaluated substances, allowing the recording of the corresponding RTs in both RP and HILIC mode

Identification of biotransformation products of citalopram formed in activated sludge

Citalopram (CTR) is a highly consumed antidepressant which is removed incompletely by conventional wastewater treatment. Although it is highly detected in effluent wastewaters, little is known about its behavior and transformation processes that undergo during wastewater treatment. The present study aims to expand the knowledge on fate and transformation of CTR during the biological breakdown process. For this purpose, biotransformation batch reactors were set up to assess biotic, abiotic and sorption losses of this compound. One of the main objectives of the study was the identification of the formed transformation products (TPs) by applying suspect and non-target strategies based on liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). In this regard, the complementary use of reversed phase chromatography (RP) and hydrophilic interaction liquid chromatography (HILIC) in the identification of polar TPs, the deep evaluation of the obtained MS/MS spectra, as well as the use of in-house developed quantitative structure-retention relationship (QSRR) retention time prediction models provided valuable support to identification. Fourteen TPs were detected. Thirteen of them were tentatively identified. Four compounds were confirmed (N-desmethylCTR, CTR amide, CTR carboxylic acid and 3-oxo-CTR) through the purchase of the corresponding reference standard. Probable structures based on diagnostic evidence were proposed for the additional nine TPs. A transformation pathway for the biotransformation of CTR was proposed. The presence of the identified TPs was assessed in real wastewater samples through retrospective analysis resulting in the detection of five compounds. Finally, the potential ecotoxicological risk posed by CTR and its TPs to different trophic levels of aquatic organisms, exposed to the studied effluents, was evaluated by means of risk quotients

Dissolution and sorption processes on the surface of calcite in the presence of high Co2+ concentration

The interaction of the calcite surface with Co2+-rich aqueous solutions ([Co2+aq]initial = 1000 ppm, i.e., ca. 17 mM) was investigated by means of macroscopic experiments and surface spectroscopic techniques. In the case of the macroscopic experiments, calcite powder and monocrystals were immersed into solutions for different time periods (from 1 min to one month). The Ca concentrations in the filtrates was measured by means of atomic absorption spectrometry (AAS) while the interacted solids were studied using a combination of X-ray photoelectron spectroscopy (XPS) and 12C-rutherford backscattering spectrometry (12C-RBS). The macroscopic data showed a characteristic surface dissolution process, in parallel to the surface sorption processes. Adsorption and co-precipitation were seen for almost the entire immersion period for both calcite powder and monocrystals. The surface study by XPS (analyzed at a depth of approximately 12 nm) suggested that adsorption takes place in the first hour of the interaction, followed by incorporation of Co2+ into calcite surface layers, leading to the formation of a Co2+-bearing surface (co)precipitate, which occurs over a period of hours and days. The 12C-RBS measurements on calcite { 10 1 ¯ 4 } indicated that the thickness of this surface co-precipitate was 270 nm after one day and then stabilized at 320 nm after more than a week

An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model

Over the last century, outbreaks and pandemics have occurred with disturbing regularity, necessitating advance preparation and large-scale, coordinated response. Here, we developed a machine learning predictive model of disease severity and length of hospitalization for COVID-19, which can be utilized as a platform for future unknown viral outbreaks. We combined untargeted metabolomics on plasma data obtained from COVID-19 patients (n = 111) during hospitalization and healthy controls (n = 342), clinical and comorbidity data (n = 508) to build this patient triage platform, which consists of three parts: (i) the clinical decision tree, which amongst other biomarkers showed that patients with increased eosinophils have worse disease prognosis and can serve as a new potential biomarker with high accuracy (AUC = 0.974), (ii) the estimation of patient hospitalization length with ± 5 days error (R2 = 0.9765) and (iii) the prediction of the disease severity and the need of patient transfer to the intensive care unit. We report a significant decrease in serotonin levels in patients who needed positive airway pressure oxygen and/or were intubated. Furthermore, 5-hydroxy tryptophan, allantoin, and glucuronic acid metabolites were increased in COVID-19 patients and collectively they can serve as biomarkers to predict disease progression. The ability to quickly identify which patients will develop life-threatening illness would allow the efficient allocation of medical resources and implementation of the most effective medical interventions. We would advocate that the same approach could be utilized in future viral outbreaks to help hospitals triage patients more effectively and improve patient outcomes while optimizing healthcare resources

The NORMAN Association and the European Partnership for Chemicals Risk Assessment (PARC): let’s cooperate! [Commentary]

The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innovation programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemical risk assessors and managers together with scientists to accelerate method development and the production of necessary data and knowledge, and to facilitate the transition to next-generation evidence-based risk assessment, a non-toxic environment and the European Green Deal. The NORMAN Network is an independent, well-established and competent network of more than 80 organisations in the field of emerging substances and has enormous potential to contribute to the implementation of the PARC partnership. NORMAN stands ready to provide expert advice to PARC, drawing on its long experience in the development, harmonisation and testing of advanced tools in relation to chemicals of emerging concern and in support of a European Early Warning System to unravel the risks of contaminants of emerging concern (CECs) and close the gap between research and innovation and regulatory processes. In this commentary we highlight the tools developed by NORMAN that we consider most relevant to supporting the PARC initiative: (i) joint data space and cutting-edge research tools for risk assessment of contaminants of emerging concern; (ii) collaborative European framework to improve data quality and comparability; (iii) advanced data analysis tools for a European early warning system and (iv) support to national and European chemical risk assessment thanks to harnessing, combining and sharing evidence and expertise on CECs. By combining the extensive knowledge and experience of the NORMAN network with the financial and policy-related strengths of the PARC initiative, a large step towards the goal of a non-toxic environment can be taken

New perspectives on the renal slit diaphragm protein podocin

Podocin is a critical component of the glomerular filtration barrier, its mutations causing recessive steroid-resistant nephrotic syndrome. A GenBank analysis of the human podocin (NPHS2) gene resulted in the possible existence of a new splice variant of podocin in the kidney, missing the in-frame of exon 5, encoding the prohibitin homology domain. Using RT–polymerase chain reaction and immunoblotting followed by sequence analysis, we are for the first time able to prove the expression of a novel podocin isoform (isoform 2), exclusively and constitutively expressed in human podocytes. Furthermore, we reveal singular extrarenal podocin expression in human and murine testis. Our data show the Sertoli cells of the seminiferous tubules to be the origin of testicular podocin. Confocal laser microscopy illustrates the co-localization of podocin with filamentous actin within Sertoli cells, suggesting a role of podocin in the blood/testis barrier. These results led to the rationale to examine podocin expression in testes of men with Sertoli cell-only syndrome, a disorder characterized by azoospermia. Interestingly, we observed a complete down-regulation of podocin mRNA in Sertoli cell-only syndrome, indicating a possible role of podocin in the pathogenesis of this germinal aplasia. Men with Sertoli cell-only syndrome show normal renal podocin expression, suggesting an alternate regulation of the testicular promoter. Our findings may change the perception of podocin and give new insights into the ultrastructure of glomerular slit diaphragm and the blood/testis barrier

Making waves: collaboration in the time of SARS-CoV-2 - rapid development of an international co-operation and wastewater surveillance database to support public health decision-making

The presence of SARS-CoV-2 RNA in wastewater was first reported in March 2020. Over the subsequent months, the potential for wastewater surveillance to contribute to COVID-19 mitigation programmes has been the focus of intense national and international research activities, gaining the attention of policy makers and the public. As a new application of an established methodology, focused collaboration between public health practitioners and wastewater researchers is essential to developing a common understanding on how, when and where the outputs of this non-invasive community-level approach can deliver actionable outcomes for public health authorities. Within this context, the NORMAN SCORE "SARS-CoV-2 in sewage" database provides a platform for rapid, open access data sharing, validated by the uploading of 276 data sets from nine countries to-date. Through offering direct access to underpinning meta-data sets (and describing its use in data interpretation), the NORMAN SCORE database is a resource for the development of recommendations on minimum data requirements for wastewater pathogen surveillance. It is also a tool to engage public health practitioners in discussions on use of the approach, providing an opportunity to build mutual understanding of the demand and supply for data and facilitate the translation of this promising research application into public health practice. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.