Multi-target analysis of cytostatics in hospital effluents over a 9-month period

The consumption of cytostatics, pharmaceuticals prescribed in chemotherapy, is increasing every year and worldwide, along with the incidence of cancer. The presence and the temporal evolution of cytostatics in wastewaters from a Portuguese hospital center was evaluated through a 9-month sampling campaign, comprising a total of one hundred and twenty-nine samples, collected from May 2019 to February 2020. Eleven cytostatics out of thirteen pharmaceuticals were studied, including flutamide, mycophenolate mofetil and mycophenolic acid, which have never been monitored before. Target analytes were extracted and quantified by solid-phase extraction coupled to liquid-chromatography-tandem mass spectrometry analysis; the method was fully validated. All pharmaceuticals were detected in at least one sample, bicalutamide being the one found with higher frequency (detected in all samples), followed by mycophenolic acid, which was also the compound detected at higher concentrations (up to 5340 ± 211 ng/L). Etoposide, classified as carcinogenic to humans, was detected in 60% of the samples at concentrations up to 142 ± 15 ng/L. The risk from exposure to cytostatics was estimated for aquatic organisms living in receiving bodies. Cyclophosphamide, doxorubicin, etoposide, flutamide, megestrol and mycophenolic acid are suspected to induce risk. Long-term and synergic effects should not be neglected, even for the cytostatics for which no risk was estimated

Photocatalytic degradation of endocrine disruptor compounds under simulated solar light

Nanostructured titanium materials with high UV-visible activity were synthesized in the collaborative project Clean Water FP7. In this study, the efficiency of some of these catalysts to degrade endocrine disruptor compounds, using bisphenol A as the model compound, was evaluated. Titanium dioxide P25 (AEROXIDE® TiO2, Evonik Degussa) was used as the reference. The photocatalytic degradation was carried out under the UV part of a simulated solar light (280–400 nm) and under the full spectrum of a simulated solar light (200 nm-30 μm). Catalytic efficiency was assessed using several indicators such as the conversion yield, the mineralization yield, by-product formation and the endocrine disruption effect of by-products. The new synthesized catalysts exhibited a significant degradation of bisphenol A, with the so-called ECT-1023t being the most efficient. The intermediates formed during photocatalytic degradation experiments with ECT-1023t as catalyst were monitored and identified. The estrogenic effect of the intermediates was also evaluated in vivo using a ChgH-GFP transgenic medaka line. The results obtained show that the formation of intermediates is related to the nature of the catalyst and depends on the experimental conditions. Moreover, under simulated UV, in contrast with the results obtained using P25, the by-products formed with ECT-1023t as catalyst do not present an estrogenic effect.We are grateful for the funding of the European Commission through the Clean Water Project which is a Collaborative Project (Grant Agreement number 227017) co-funded by the Research DG of the European Commission within the joint RTD activities of the Environment and NMP Thematic Prioritie

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar