Surveilling the SARS -CoV-2 in sewage: the catalan case

Introduction. Shortly after the outbreak of the COVID-19 pandemic, scientists renewed their interest on the application of wastewater-based epidemiology (WBE) to track the communal circulation of SARS-CoV-2 through the quantification of its genetic traces in sewage. At national scale, such strategy was firstly implemented in The Netherlands in February 2020 and, following the Dutch example, similar sewage surveillance programs were later put into action by other countries at different scales and coverages. At the time of writing, 58 countries are currently monitoring the circulation of SARS-CoV-2 in wastewater as reported at the COVID-Poops19 website. The purpose of this work is to describe the roadmap for the implementation of a wastewater surveillance network at a national scale and to discuss the main challenges faced during its functioning. Material and methods. It should be noted that all data generated are free for scientific use, and it can be downloaded from a public repository at the Zenodo website. The database is weekly updated and contains all molecular data obtained from the samples analyzed. Results. In Catalonia, a Spanish region of 7,5 million inhabitants, the Public Health Agency of the Catalan government and the Catalan Water Agency promoted and funded the implementation of the Catalan Surveillance Network of SARSCoV-2 in Sewage (SARSAIGUA) to provide information on the circulation of SARSCoV-2 at community level that complement epidemiological & clinical data. SARSAIGUA started in 2020 by monitoring 56 WWTPs that assist 193 municipalities, representing 80% of the Catalan population. Within less than 72 hours, weekly samples are collected, analyzed, and results reported to Health authorities and finally published in an on-line dashboard. After 19 months of monitoring, the normalized daily loads of SARS-CoV-2 genes in the 56 WWTPs monitored, fairly matched the sum of COVID-19 cases along the successive pandemic waves. Moreover, a good fit was obtained between the aggregated viral load (gen copies/day/100.000 inhabitants) and the epidemiological evolution of diagnosed cases in the municipalities, served by the monitored WWTPs (rxy=0.59). In 2021, SARSAIGUA started the monitoring of SARS-CoV-2 variants by sequencing sewage samples every two weeks using Oxford nanopore technology and ARCTIC primers targeting the S gene. The deployment of this sequencing approach has allowed to track the introduction and spread of the Omicron variant and the concomitant wane of the Delta variant across the territory. Conclusions. Overall, and despite the difficulties and limitations associated to the inherent complexity of wastewater, the usefulness of WBE to rapidly detect viral transmission at community level is very helpful to Health authorities to better manage the pandemic situation. This is particularly relevant under the current scenario, where new emerging SARS-CoV-2 variants with higher fitness and transmission potential outcompete old ones in a weekly time scale. Acknowledgment. The research was realised in the JPIAMR projects: (PhageLand) – 22.80013.8007.1

Identification and characterization of Cardiac Glycosides as senolytic compounds

Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.We thank Matthias Drosten, Alejo Efeyan and Sean Morrison for plasmids. F.T-M. is a postdoctoral fellow from CONACYT (cvu 268632); P.P. is a predoctoral fellow from Xunta de Galicia; M.C. is a "Miguel Servet II" investigator (CPII16/00015). P.P.-R. receives support from a program by the Deputacion de Coruna (BINV-CS/2019). Work in the laboratory of M.C. is funded by grant RTI2018-095818-B-100 (MCIU/AEI/FEDER, UE). P.J.F.-M. is funded by the IMDEA Food Institute, the Ramon Areces Foundation, (CIVP18A3891), and a Ramon y Cajal Award (MICINN) (RYC-2017-22335). M.P.I. is funded by Talento Modalidad-1 Program Grant, Madrid Regional Government (#2018-T1/BIO-11262). F.P. was funded by a Long Term EMBO Fellowship (ALTF-358-2017) and F.H-G. was funded by the PhD4MD Programme of the IRB, Hospital Clinic and IDIBAPS. Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and "laCaixa" Foundation.S

Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations and clinical impact

Recent evidence suggests that complex karyotype (CK) defined by the presence of 653 chromosomal aberrations (structural and/or numerical) identified by chromosome banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges towards routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with 655 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcome, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and or TP53 mutations, TP53abs) and the expression of somatically hypermutated (M-CLL) or unmutated (U-CLL) immunoglobulin heavy variable genes (IGHV). Thus, they contrasted CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs and IGHV gene somatic hypermutation status, we propose a novel hierarchical model where patients with high-CK exhibit the worst prognosis, while M-CLL lacking CK or TP53abs as well as CK with +12,+19 show the longest overall survival. In conclusion, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with 655 chromosomal aberrations emerges as prognostically adverse, independently of other biomarkers. Prospective clinical validation is warranted before finally incorporating high-CK in risk stratification of CLL

Luz / LLum

En aquest quart volum, gran diversitat d'autores i autors aporten píndoles de microliteratura, de gèneres variats, amb què l'Institut Universitari d'Estudis Feministes i de Gènere Purificación Escribano vol respondre al desafiament per l'eradicació de la violència contra les dones

The Catalan Surveillance Network of SARS-CoV-2 in Sewage: design, implementation, and performance

Wastewater-based epidemiology has shown to be an efficient tool to track the circulation of SARS-CoV-2 in communities assisted by wastewater treatment plants (WWTPs). The challenge comes when this approach is employed to help Health authorities in their decision-making. Here, we describe the roadmap for the design and deployment of SARSAIGUA, the Catalan Surveillance Network of SARS-CoV-2 in Sewage. The network monitors, weekly or biweekly, 56 WWTPs evenly distributed across the territory and serving 6 M inhabitants (80% of the Catalan population). Each week, samples from 45 WWTPs are collected, analyzed, results reported to Health authorities, and finally published within less than 72 h in an online dashboard ( https://sarsaigua.icra.cat ). After 20 months of monitoring (July 20-March 22), the standardized viral load (gene copies/day) in all the WWTPs monitored fairly matched the cumulative number of COVID-19 cases along the successive pandemic waves, showing a good fit with the diagnosed cases in the served municipalities (Spearman Rho = 0.69). Here we describe the roadmap of the design and deployment of SARSAIGUA while providing several open-access tools for the management and visualization of the surveillance data.The authors wish to thank the staff from all the WWTPs monitored for their help and technical support during the sampling campaigns. The authors acknowledge the funding received from the ACA and the ASPCAT from the Catalan Government (Generalitat de Catalunya). ICRA authors acknowledge the funding provided by the Generalitat de Catalunya through the Consolidated Research Group grants ICRA-ENV 2017 SGR 1124 and ICRA-TiA 2017 SGR 1318. ICRA researchers also thank the funding from the CERCA program of the Catalan Government.Peer reviewe

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Multi-scale investigation of occurrence, fate, removal and biodegradation of pharmaceutical contamination in wastewater treatment and river systems

Human and veterinary pharmaceuticals have been recognized as ubiquitous water microcontaminants with potential subtle detrimental effects on aquatic organisms. The majority of pharmaceutical compounds, after being consumed and excreted, end up in municipal WWTPs, which are not typically designed for complete pharmaceutical removal. Therefore, effluents from WWTPs constitute a low concentration, but continuous source of pharmaceutically active compounds to the aquatic environment. The main objective of the thesis is to acquire and provide with knowledge not only on the occurrence of pharmaceutical compounds in wastewater, but on their biodegradation within WWTPs and their discharge into the receiving media. The obtained results demonstrate conventional wastewater treatment’s variable efficiency when removing the pharmaceutical compounds load and the advance treatment’s contribution to their overall removal. It has also been possible to model the behaviour of a selected pharmaceutical and its transformation products. And it also includes investigation of an antibiotic’s impact on the bacterial community performance, and the antibiotic resistance genes phenomenon. Finally, the role and usefulness of proteomics when investigating the possible proteins involved on the biodegradation pathways of certain pharmaceutical compoundsEls compostos farmacèutics d’ús humà i animal s’han identificat com a microcontaminants aquàtics omnipresents amb possibles efectes nocius sobre el medi ambient. La major part d’aquests compostos, un cop consumits i excretats, van a parar a les EDARs, que no estan dissenyades per eliminar-los completament. En conseqüència, els efluents d’aquestes esdevenen un flux, poc concentrat però constant, de fàrmacs cap al medi aquàtic. L’objectiu principal d’aquest treball és el d’adquirir i proporcionar coneixement pel que fa tant a la presència d’aquests compostos farmacèutics a les aigües residuals, com a la seva degradació en EDARs i la seva descàrrega al medi receptor. Els resultats obtinguts demostren la variabilitat en l’eficàcia dels tractaments convencionals d’aigües residuals i la contribució dels processos avançats a l’hora d’eliminar els fàrmacs. També s’ha aconseguit modelar el comportament d’un fàrmac i dels seus productes de transformació. S'ha abordat també, l’impacte d’un antibiòtic sobre la comunitat bacteriana a nivell microbiològic i el fenomen dels gens de resistència antibiòtica. I, finalment, el paper de tècniques proteòmiques a l’hora de buscar possibles proteïnes involucrades en el procés de biodegradació de certs compostos farmacèutic

Projecte de viabilitat de la proposta de gestió de les aigües pluvials al municipi de Begur

Estudi sobre les riuades provocades per les pluges torrencials al municipi de Begur i proposta d’un projecte alternatiu més sostenible respecte al creat per l’Ajuntament sobre la gestió d’aquestes aigües pluvial

Pharmaceuticals occurrence in a WWTP with significant industrial contribution and its input into the river system

Occurrence and removal of 81 representative Pharmaceutical Active Compounds (PhACs) were assessed in a municipal WWTP located in a highly industrialized area, with partial water reuse after UV tertiary treatment and discharge to a Mediterranean river. Water monitoring was performed in an integrated way at different points in the WWTP and river along three seasons. Consistent differences between therapeutic classes were observed in terms of influent concentration, removal efficiencies and seasonal variation. Conventional (primary and secondary) treatment was unable to completely remove numerous compounds and UV-based tertiary treatment played a complementary role for some of them. Industrial activity influence was highlighted in terms of PhACs presence and seasonal distribution. Even if global WWTP effluent impact on the studied river appeared to be minor, PhACs resulted widespread pollutants in river waters. Contamination can be particularly critical in summer in water scarcity areas, when water flow decreases considerabl