Presence of microplastics in the groundwater of volcanic islands, El Hierro and La Palma (Canary Islands).

The increasing amount of plastic litter worldwide is a serious problem for the environment and its biodiversity, ecosystems, animal and human welfare and the economy. The degradation of these plastics leads to microplastics (MPs), which have been reported for the first time in groundwater in the Canary archipelago. This research investigates the presence of MPs at nine different points on La Palma and El Hierro, where samples were collected in galleries, wells and springs during the month of December 2022. Six different polymers were found with Fourier transform infrared spectroscopy (FTIR) - polypropylene (PP), polyethylene (PE), cellulose (CEL), polyethylene terephthalate (PET), polystyrene (PS) and polymethyl methacrylate (PMMA). The particle concentrations found ranged from 1 to 23 n/L, with a maximum particle size of 1900 µm, the smallest being 35 µm. PP and PE were the most common polymers found in the analysis, associated with the use of packaging, disposable products, textiles and water pipes, related to poorly maintained sewerage networks where leaks occur, allowing these MPs to escape into the environment and end up in groundwater. The detection of microplastic pollution in groundwater emphasises environmental hazards, including biodiversity disruption and water source contamination. Additionally, it presents potential risks to human health by transferring contaminants into the food chain and through respiratory exposure.

Cellular Immunity of SARS-CoV-2 in the Borriana COVID-19 Cohort: A Nested Case-Control Study.

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry-based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination.

Symplasmic and transmembrane zinc transport is modulated by cadmium in the Cd/Zn hyperaccumulator Sedum alfredii.

This study investigated the influence of Cd (25 µM) on Zn accumulation in a hyperaccumulating (HE) and a non-hyperaccumulating (NHE) ecotype of Sedum alfredii Hance at short-term supply of replete (Zn5, 5 µM) and excess (Zn400, 400 µM) Zn. Cd inhibited Zn accumulation in both ecotypes, especially under Zn400, in organs with active metal sequestration, i.e. roots of NHE and shoots of HE. Direct biochemical Cd/Zn competition at the metal-protein interaction and changes in transporter gene expression contributed to the observed accumulation patterns in the roots. Specifically, in HE, Cd stimulated SaZIP4 and SaPCR2 under Zn5, but downregulated SaIRT1 and SaZIP4 under Zn400. However, Cd downregulated related transporter genes, except for SaNRAMP1, in NHE, irrespective of Zn. Cadmium stimulated casparian strip (CSs) development in NHE, as part of the defense response, while it had a subtle effect on the (CS) in HE. Moreover, Cd delayed the initiation of the suberin lamellae (SL) in HE, but stimulated SL deposition in NHE under both Zn5 or Zn400. Changes in suberization were mainly ascribed to suberin-biosynthesis-related genes and hormonal signaling. Altogether, Cd regulated Zn accumulation mainly via symplasmic and transmembrane transport in HE, while Cd inhibited both symplasmic and apoplasmic Zn transport in NHE.

Comparative study of emerging pollutants of interest in the groundwater of the volcanic islands of La Palma and El Hierro (Canary Islands).

Emerging pollutants (EPs) include a wide array of chemical compounds, as well as some microorganisms, which presence was unknown or unmeasurable until recently, or have recently started to be considered a threat towards the environment or animal and human health. No clear or homogeneous regulations exist for their measurement or control, and efforts should be made to assess their presence and offer solutions for their safe management, as well as to achieve an optimal protection of water resources. A previous study performed by our research group thoroughly studied a wide profile of EPs in El Hierro Island (Canary Islands) for the first time. Now, we present the study of the same panel of 70 EPs in La Palma Island (Canary Islands). 14 samples were collected in 2021, at different locations in La Palma island, representing seven municipalities (Los Llanos de Aridane, Santa Cruz de la Palma, El Paso, Breña Baja, Tazacorte, Barlovento and Fuencaliente) and four installation types (Piezometers/Wells, Wastewater Treatment Plant (WWTP), Water Gallery and Water Springs). High performance liquid chromatography-mass spectrometry (HPLC-MS) was performed to analyse the EP array, which included five chemical families: UV filters, UV blockers/stabilizers, parabens, Pharmaceutical Active Compounds (PhACs) and pesticides. Subsequently, a comprehensive descriptive and statistical analysis, including different tests was performed on the data obtained. Heterogeneous concentration levels of the EPs studied were found based on municipality and installation type among the island, with some of the PhACs and UV blockers/stabilizers showing very high levels, especially at Breña Baja and wastewater treatment plants (WWTPs). It is worth noting that some of the samples comprised within the WWTPs category were collected outside the treatment plant, after water has been treated, so they should not bear dangerous concentrations of any hazardous compound. The high presence of two pesticides, imidacloprid (ranging from 68.7 to 24,896.5 ng⋅L-1) and acetamiprid (ranging from 1010.7 to 5168.1 ng⋅L-1) was worth highlighting too. In addition, three EP concentration clusters were found to virtually divide the island based on mathematical percentiles of EP mean concentrations, which can help gain more insight into the contamination status of the island and measures that could be taken for their management. Finally, a comparison between La Palma results and the profile observed at El Hierro by our research group was presented. Altogether, the study performed calls for a need to take actions towards avoiding entrance of EPs in the water cycle, and not just focusing on remediation strategies once they have reached the groundwater, freshwater or soil.

Impacto de la pandemia en varias enfermedades infecciosas con patrones epidemiológicos distintos de estacionalidad, transmisión y edad / mpact of the pandemic on various infectious diseases with different epidemiological patterns of seasonality, transmission and age

Fundamentos: la pandemia de la covid-19 ha tenido un fuerte impacto sobre otras enfermedades infecciosas. El objetivo de este trabajo fue analizar los cambios epidemiológicos acaecidos durante la pandemia en ocho enfermedades infecciosas con patrones epidemiológicos distintos: la gripe; virus respiratorio sincitial; rotavirus; neumococo; campylobacter; salmonella no tifoidea; gonococia; herpes zóster.métodos: a partir de la red de vigilancia microbiológica, se trazó la serie temporal de casos desde enero de 2017 a marzo de 2023. Se distinguieron tres periodos: prepandemia (referencia), pandemia e inicio de la pospandemia. Se analizó la distribución por edad y sexo en esos periodos. Se calcularon las tasas de incidencia y las razones de tasas (rt). Se estimaron esas rt globales y sus intervalos de confianza al 95% por cada año de edad en menores de cinco años. Resultados: se encontraron diferencias estadísticamente significativas en el impacto que la pandemia tuvo en cada una de esas enfermedades. Algunas, tras un periodo de silencio epidémico, revelaron un repunte intenso pospandémico. Incrementaron la rt global postpandémica la gripe (2,4), vrs (1,9) y gonococia (3,1); recuperó su nivel prepandémico el rotavirus (1,07); y disminuyeron el neumococo (0,84), campylobacter (0,83) y salmonella (0,60). En menores de cinco años, los patrones fueron específicos y hete-rogéneos para cada enfermedad.conclusiones: el impacto de la pandemia es muy diferente en estas enfermedades. Las infecciones víricas estacionales pediá-tricas y de transmisión respiratoria son las que más se ven afectadas, pero con patrones de recuperación de la normalidad distintos. Las infecciones bacterianas gastrointestinales sufren menos variaciones, salvo el rotavirus. La gonococia no interrumpe su tendencia al aumento avistada ya en la prepandemia. El herpes zóster muestra un ligero incremento pospandémico. Se han estudiado varias enfermedades con distinto patrón epidemiológico durante un periodo suficiente para observar cómo se produce la salida de la fase aguda de la pandemia.(AU)

Background: the covid-19 pandemic has had a strong impact on other infectious diseases. The aim of this paper was to analyze the epidemiological changes that occurred during the pandemic in eight infectious diseases with different epidemiological patterns: influenza, respiratory syncytial virus, rotavirus, pneumococcus, campylobacter, non-typhoid salmonella, gonorrhea and herpes zoster.methods: from the microbiological surveillance network, the time series of cases was traced from january 2017 to march 2023. Three periods were distinguished: reference, pandemic and beginning of the post-pandemic. The distribution by age and sex in these periods was analyzed. Incidence rates and rate ratios (rr) were calculated. These rrs and their 95% confidence intervals were estimated overall and by year of age in children under five years of age. Results: statistically significant differences were found in the impact that the pandemic had on each of these diseases. Some, after a period of epidemic silence, have revealed an intense post-pandemic rebound. The post-pandemic global rt increased for influenza (2.4), rsv (1.9) and gonorrhea (3.1); rotavirus recovered its pre-pandemic level (1.07); and pneumococcus (0.84), campylobacter (0.83) and salmonella (0.60) decreased. In children under 5 years of age, the patterns were specific and heterogeneous for each disease.conclusions: the impact of the pandemic is very different in these diseases. Pediatric and respiratory-transmitted seasonal viral infections are the ones that are most affected, but with different patterns of recovery to normality. Gastrointestinal bacterial infections suffer fewer variations, except for rotavirus. Gonorrhea do not interrupt its increasing trend seen in the pre-pandemic. Shingles show a slight post-pandemic increase. Several diseases with different epidemiological patterns have been studied for a sufficient period to observe how the acute phase of the pandemic emerges.(AU)

[Impact of the pandemic on various infectious diseases with different epidemiological patterns of seasonality, transmission and age]. / Impacto de la pandemia en varias enfermedades infecciosas con patrones epidemiológicos distintos de estacionalidad, transmisión y edad.

OBJECTIVE: The COVID-19 pandemic has had a strong impact on other infectious diseases. The aim of this paper was to analyze the epidemiological changes that occurred during the pandemic in eight infectious diseases with different epidemiological patterns: influenza, respiratory syncytial virus, rotavirus, pneumococcus, Campylobacter, non-typhoid Salmonella, gonorrhea and herpes zoster. METHODS: From the Microbiological Surveillance Network, the time series of cases was traced from January 2017 to March 2023. Three periods were distinguished: reference, pandemic and beginning of the post-pandemic. The distribution by age and sex in these periods was analyzed. Incidence rates and rate ratios (RR) were calculated. These RRs and their 95% confidence intervals were estimated overall and by year of age in children under five years of age. RESULTS: Statistically significant differences were found in the impact that the pandemic had on each of these diseases. Some, after a period of epidemic silence, have revealed an intense post-pandemic rebound. The post-pandemic global RT increased for influenza (2.4), RSV (1.9) and gonorrhea (3.1); rotavirus recovered its pre-pandemic level (1.07); and pneumococcus (0.84), Campylobacter (0.83) and Salmonella (0.60) decreased. In children under 5 years of age, the patterns were specific and heterogeneous for each disease. CONCLUSIONS: The impact of the pandemic is very different in these diseases. Pediatric and respiratory-transmitted seasonal viral infections are the ones that are most affected, but with different patterns of recovery to normality. Gastrointestinal bacterial infections suffer fewer variations, except for rotavirus. Gonorrhea do not interrupt its increasing trend seen in the pre-pandemic. Shingles show a slight post-pandemic increase. Several diseases with different epidemiological patterns have been studied for a sufficient period to observe how the acute phase of the pandemic emerges.

OBJECTIVE: La pandemia de la COVID-19 ha tenido un fuerte impacto sobre otras enfermedades infecciosas. El objetivo de este trabajo fue analizar los cambios epidemiológicos acaecidos durante la pandemia en ocho enfermedades infecciosas con patrones epidemiológicos distintos: la gripe; virus respiratorio sincitial; rotavirus; neumococo; Campylobacter; Salmonella no tifoidea; gonococia; herpes zóster. METHODS: A partir de la Red de Vigilancia Microbiológica, se trazó la serie temporal de casos desde enero de 2017 a marzo de 2023. Se distinguieron tres periodos: prepandemia (referencia), pandemia e inicio de la pospandemia. Se analizó la distribución por edad y sexo en esos periodos. Se calcularon las tasas de incidencia y las razones de tasas (RT). Se estimaron esas RT globales y sus intervalos de confianza al 95% por cada año de edad en menores de cinco años. RESULTS: Se encontraron diferencias estadísticamente significativas en el impacto que la pandemia tuvo en cada una de esas enfermedades. Algunas, tras un periodo de silencio epidémico, revelaron un repunte intenso pospandémico. Incrementaron la RT global postpandémica la gripe (2,4), VRS (1,9) y gonococia (3,1); recuperó su nivel prepandémico el rotavirus (1,07); y disminuyeron el neumococo (0,84), Campylobacter (0,83) y Salmonella (0,60). En menores de cinco años, los patrones fueron específicos y heterogéneos para cada enfermedad. CONCLUSIONS: El impacto de la pandemia es muy diferente en estas enfermedades. Las infecciones víricas estacionales pediátricas y de transmisión respiratoria son las que más se ven afectadas, pero con patrones de recuperación de la normalidad distintos. Las infecciones bacterianas gastrointestinales sufren menos variaciones, salvo el rotavirus. La gonococia no interrumpe su tendencia al aumento avistada ya en la prepandemia. El herpes zóster muestra un ligero incremento pospandémico. Se han estudiado varias enfermedades con distinto patrón epidemiológico durante un periodo suficiente para observar cómo se produce la salida de la fase aguda de la pandemia.

Effect of tourist activity on wastewater quality in selected wastewater treatment plants in the Balearic Islands (Spain).

Unregulated sewage discharge into the sea poses a considerable danger to marine ecosystems, with coastal regions being particularly vulnerable to this because of the impact of tourism. This issue is amplified during the summer season, as the Balearic Islands are a heavily frequented destination. This study aims to determine the water quality in five different wastewater treatment plants (WWTPs) representative on the islands. For this purpose, we analysed several parameters, including biochemical oxygen demand (BOD), chemical oxygen demand (COD), treated water flow, suspended solids (SS), nitrates (N) and phosphorus (P), at the inlet and outlet of the WWTPs for 5 years. We set particular thresholds for each parameter and documented any breach by comparing the findings with the existing regulations. The least favourable results indicate non-compliance regarding N and P levels throughout the entire study period, as well as a lack of reduction percentage. Furthermore, flow analysis reflects the significant influence of tourism on water quality, with notable increases in both population and treated water volume during the peak tourist season. Overall, the investigation offers a robust foundation for comprehending water quality in relation to coastal landscape in the Balearic Islands. It pinpoints significant worry spots and underscores tourism's immediate impact on this ecological feature.

Gastroesophageal reflux after sleeve gastrectomy: The dimension of the problem.

Sleeve gastrectomy is a safe and effective bariatric surgery in terms of weight loss and longterm improvement or resolution of comorbidities. However, its achilles heel is the possible association with the development with the novo and/or worsening of pre-existing gastroesophageal reflux disease. The anatomical and mechanical changes that this technique induces in the esophagogastric junction, support or contradict this hypothesis. Questions such as «what is the natural history of gastroesophageal reflux in the patient undergoing gastric sleeve surgery?¼, «how many patients after vertical gastrectomy will develop gastroesophageal reflux?¼ and «how many patients will worsen their previous reflux after this technique?¼ are intended to be addressed in the present article.

Progress and harmonization of gene editing to treat human diseases: Proceeding of COST Action CA21113 GenE-HumDi.

The European Cooperation in Science and Technology (COST) is an intergovernmental organization dedicated to funding and coordinating scientific and technological research in Europe, fostering collaboration among researchers and institutions across countries. Recently, COST Action funded the "Genome Editing to treat Human Diseases" (GenE-HumDi) network, uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech firms, and patient advocacy groups. GenE-HumDi's primary objective is to expedite the application of genome editing for therapeutic purposes in treating human diseases. To achieve this goal, GenE-HumDi is organized in several working groups, each focusing on specific aspects. These groups aim to enhance genome editing technologies, assess delivery systems, address safety concerns, promote clinical translation, and develop regulatory guidelines. The network seeks to establish standard procedures and guidelines for these areas to standardize scientific practices and facilitate knowledge sharing. Furthermore, GenE-HumDi aims to communicate its findings to the public in accessible yet rigorous language, emphasizing genome editing's potential to revolutionize the treatment of many human diseases. The inaugural GenE-HumDi meeting, held in Granada, Spain, in March 2023, featured presentations from experts in the field, discussing recent breakthroughs in delivery methods, safety measures, clinical translation, and regulatory aspects related to gene editing.

Reductive carboxylation epigenetically instructs T cell differentiation.

Protective immunity against pathogens or cancer is mediated by the activation and clonal expansion of antigen-specific naive T cells into effector T cells. To sustain their rapid proliferation and effector functions, naive T cells switch their quiescent metabolism to an anabolic metabolism through increased levels of aerobic glycolysis, but also through mitochondrial metabolism and oxidative phosphorylation, generating energy and signalling molecules1-3. However, how that metabolic rewiring drives and defines the differentiation of T cells remains unclear. Here we show that proliferating effector CD8+ T cells reductively carboxylate glutamine through the mitochondrial enzyme isocitrate dehydrogenase 2 (IDH2). Notably, deletion of the gene encoding IDH2 does not impair the proliferation of T cells nor their effector function, but promotes the differentiation of memory CD8+ T cells. Accordingly, inhibiting IDH2 during ex vivo manufacturing of chimeric antigen receptor (CAR) T cells induces features of memory T cells and enhances antitumour activity in melanoma, leukaemia and multiple myeloma. Mechanistically, inhibition of IDH2 activates compensating metabolic pathways that cause a disequilibrium in metabolites regulating histone-modifying enzymes, and this maintains chromatin accessibility at genes that are required for the differentiation of memory T cells. These findings show that reductive carboxylation in CD8+ T cells is dispensable for their effector response and proliferation, but that it mainly produces a pattern of metabolites that epigenetically locks CD8+ T cells into a terminal effector differentiation program. Blocking this metabolic route allows the increased formation of memory T cells, which could be exploited to optimize the therapeutic efficacy of CAR T cells.

Dyke-impounded fresh groundwater resources in coastal and island volcanic aquifers: Learning from the Canary Islands (Spain).

Freshwater in coastal and island aquifers is a valuable resource whose availability is strongly conditioned by heterogeneity. More than 80 % of the Earth's surface is of volcanic origin, but the effect of volcanic dykes on the geometry of the saline interface that separates freshwater from seawater is still underexplored. This paper analyzes the impact of volcanic dykes on the depth of the saline interface in coastal and island aquifers and, subsequently, on the availability of fresh groundwater. Hydrogeological and hydrochemical data from a gallery, perpendicularly crossing several tens of dykes, were integrated with numerical modeling on the volcanic island of El Hierro (Canary Islands, Spain). Measured hydraulic heads demonstrated that the presence of dykes increased the hydraulic gradient by more than an order of magnitude, with respect to an adjacent area not affected by dykes. Numerical assessment confirmed that the lower the hydraulic conductivity of the dykes, the greater the depth of the saline interface inland. This impact led to fresh groundwater reserves increasing inland, relative to a hypothetical case without dykes. Numerical simulations also demonstrated that dykes can prevent salinization of production wells in coastal and island aquifers, if they are correctly located. Locating production wells far enough inland in an area affected by dykes allowed a higher freshwater extraction rate than if dykes did not exist; near the coastline, the effect tended to be the opposite. These results will be key to improving the management of fresh groundwater resources in coastal volcanic aquifers, and especially on volcanic islands such as the Hawaiian Islands or the Macaronesian archipelagos.

The genesis of an extremely acidic perched aquifer within roasted pyrite waste in a fully urbanized area (Zaragoza, Spain).

Contaminated groundwater is a serious problem in developed countries. The abandonment of industrial waste may lead to acid drainage affecting groundwater and severely impacting the environment and urban infrastructure. We examined the hydrogeology and hydrochemistry of an urban area in Almozara (Zaragoza, Spain); built over an old industrial zone, with pyrite roasting waste deposits, there were acid drainage problems in underground car parks. Drilling and piezometer construction, and groundwater samples revealed the existence of a perched aquifer within old sulfide mill tailings, where the building basements interrupted groundwater flow, leading to a water stagnation zone that reached extreme acidity values (pH < 2). A groundwater flow reactive transport model was developed using PHAST to reproduce flow and groundwater chemistry, in order to be used as a predictive tool for guiding remediation actions. The model reproduced the measured groundwater chemistry by simulating the kinetically controlled pyrite and portlandite dissolution. The model predicts that an extreme acidity front (pH < 2), coincident with the Fe (III) pyrite oxidation mechanism taking dominance, is propagating by 30 m/year if constant flow is assumed. The incomplete dissolution of residual pyrite (up to 18 % dissolved) predicted by the model indicates that the acid drainage is limited by the flow regime rather than sulfide availability. The installation of additional water collectors between the recharge source and the stagnation zone has been proposed, together with periodic pumping of the stagnation zone. The study findings are expected to serve as a useful background for the assessment of acid drainage in urban areas, since urbanization of old industrial land is rapidly increasing worldwide.

Inhaled lipid nanocarriers for pulmonary delivery of glucocorticoids: Previous strategies, recent advances and key factors description.

In view of the strong anti-inflammatory activity of glucocorticoids (GC) they are used in the treatment of almost all inflammatory lung diseases. In particular, inhaled GC (IGC) allow high drug concentrations to be deposited in the lung and may reduce the incidence of adverse effects associated with systemic administration. However, rapid absorption through the highly absorbent surface of the lung epithelium may limit the success of localized therapy. Therefore, inhalation of GC incorporated into nanocarriers is a possible approach to overcome this drawback. In particular, lipid nanocarriers, which showed high pulmonary biocompatibility and are well known in the pharmaceutical industry, have the best prospects for pulmonary delivery of GC by inhalation. This review provides an overview of the pre-clinical applications of inhaled GC-lipid nanocarriers based on several key factors that will determine the efficiency of local pulmonary GC delivery: 1) stability to nebulization, 2) deposition profile in the lungs, 3) mucociliary clearance, 4) selective accumulation in target cells, 5) residence time in the lung and systemic absorption and 6) biocompatibility. Finally, novel preclinical pulmonary models for inflammatory lung diseases are also discussed.

Thermoplastic starch/polyvinyl alcohol blends modification by citric acid-glycerol polyesters.

Thermoplastic starch/polyvinyl alcohol (TPS/PVA) films have limitations for being used in long-term applications due to starch retrogradation. This leads to plasticizer migration, especially when low molecular weight plasticizers such as glycerol, are used. In this work, we employed mixtures of oligomers based on glycerol citrates with higher molecular weight than glycerol as plasticizers for potato-based TPS/PVA blends obtained by melt-mixing. This constitutes an alternative to reduce plasticizer migration while keeping high swelling degree, and to provide high mechanical performance. The novelty lies in the usage of these oligomers by melt-mixing technique, aspect not deeply explored previously and that represents the first step towards industrial scalability. Prior to the blending process, oligomers mixtures were prepared with different molar ratios of citric acid (0-40 mol%) and added them. This minimizes the undesirable hydrolysis effect of free carboxylic groups on starch chains. The results demonstrated that the migration of plasticizers in TPS/PVA blends decreased by up to 70 % when the citric acid content increased. This reduction was attributed to the higher molecular weight (the majority in the range 764-2060 Da) and the 3D structure of the oligomers compared to using raw glycerol. Furthermore, the films exhibited a 150 % increase in Young's modulus and tensile strength without a reduction in elongation at break, while maintaining a high gel content, due to a moderate crosslinking.

Lentiviral vectors for inducible, transactivator-free advanced therapy medicinal products: Application to CAR-T cells.

Controlling transgene expression through an externally administered inductor is envisioned as a potent strategy to improve safety and efficacy of gene therapy approaches. Generally, inducible ON systems require a chimeric transcription factor (transactivator) that becomes activated by an inductor, which is not optimal for clinical translation due to their toxicity. We generated previously the first all-in-one, transactivator-free, doxycycline (Dox)-responsive (Lent-On-Plus or LOP) lentiviral vectors (LVs) able to control transgene expression in human stem cells. Here, we have generated new versions of the LOP LVs and have analyzed their applicability for the generation of inducible advanced therapy medicinal products (ATMPs) with special focus on primary human T cells. We have shown that, contrary to all other cell types analyzed, an Is2 insulator must be inserted into the 3' long terminal repeat of the LOP LVs in order to control transgene expression in human primary T cells. Importantly, inducible primary T cells generated by the LOPIs2 LVs are responsive to ultralow doses of Dox and have no changes in phenotype or function compared with untransduced T cells. We validated the LOPIs2 system by generating inducible CAR-T cells that selectively kill CD19+ cells in the presence of Dox. In summary, we describe here the first transactivator-free, all-one-one system capable of generating Dox-inducible ATMPs.

First emerging pollutants profile in groundwater of the volcanic active island of El Hierro (Canary Islands).

Emerging pollutants (EPs) are substances present in wastewater that have not been studied, previously, leading to ambiguity in regulations for their presence in water resources. Territories that are highly dependent on groundwater resources are at a high risk of suffering the consequences of EP contamination due to their dependence on good quality groundwater for agriculture, drinking, and other uses. A relevant example is El Hierro (Canary Islands), which was declared a biosphere reserve by the UNESCO in 2000 and is almost completely powered by renewable energies. Using high performance liquid chromatography-mass spectrometry, the concentrations of 70 EPs were assessed at 19 sampling points on El Hierro. The results indicated that no pesticides were present in groundwater; however, varied concentration levels of ultraviolet (UV) filters, UV stabilizers/blockers and pharmaceutically active compounds (PhACs) were found, with La Frontera being the most contaminated municipality. With regard to the different installation types, piezometers and wells were the ones showing the highest concentrations for most EPs. Interestingly, the depth of sampling correlated positively with EP concentration, and four different clusters virtually dividing the island into two areas could be identified based on the presence of each EP. More studies should be performed to ascertain why a few of the EPs showed considerably high concentrations at different depths. The results obtained highlight the need to, not only implement remediation measures once EPs have reached the soil and aquifers, but also to avoid their incorporation into the water cycle via homes, animal husbandry, agriculture, industry, and wastewater treatment plants (WWTPs).

ABO Blood Groups and Incidence of COVID-19 in the Mass Gathering Events in Borriana (Spain), March 2020: A Retrospective Cohort Study.

Our objective was to estimate the incidence of COVID-19 and the ABO blood Groups in the mass-gathering events (MGEs) during the Falles Festival in Borriana (Spain) from 6-10 March 2020. We conducted a population-based retrospective cohort study and measured anti-SARS-CoV-2 antibodies and the ABO of participants. We performed laboratory COVID-19 tests and obtained the ABO in 775 subjects (72.8% of the original exposed cohort): O-group (45.2%), A-group (43.1%), B-group (8.5%) and AB-group (3.4%). Adjusted for confounding factors, including COVID-19 exposure during the MGEs, attack rates of COVID-19 for each ABO group were 55.4%, 59.6%, 60.2%, and 63.7%. The adjusted relative risks were for O-group 0.93 (95% Confidence Interval [CI] 0.83-1.04), for A-group 1.06 (95% CI 0.94-1.18), for B-group 1.04 (95%CI 0.88-1.24), and for AB-group 1.11 (95% CI 0.81-1.51) with no significant differences. Conclusions: Our results suggest no effect of ABO on COVID-19 incidence. We observed weak but not significant protection of the O-group and not a significantly greater infection risk for the remaining groups compared with the O-group. More studies are needed to resolve the controversies regarding the association between ABO and COVID-19.

Heterogeneity-Driven Hydrodynamics Conditions the Hydrochemistry of Spring Water in Volcanic Islands.

Perched aquifers represent significant unexploited groundwater reserves in volcanic islands and contain valuable freshwater resources. These water reserves provide critical resources to indigenous populations suffering water scarcity. Groundwater discharged from a perched aquifer into two adjacent (14 m) springs in the volcanic summits constituted by basaltic and pyroclastic deposits of Gran Canaria Island (Spain) was examined. Based on springs discharge data, a three-dimensional groundwater flow and solute transport model of the investigated perched aquifer was calibrated to reproduce its hydraulic regime, as well as to explain the hydrochemical and isotopic composition of its main discharge systems, the studied springs. Groundwater flow simulations effectively replicated flow paths of the two springs affected by the existing geological heterogeneities, with differential travel times of 246 and 130 years, respectively, and with a convergent flow toward them partially explaining the averaged differences in electrical conductivity, δ18 O, and tritium observed between the springs. It can be concluded that, although water quality in both springs is similar and homogenous, as they come from the same aquifer system, geological heterogeneities in the upper elevation volcanic areas is likely the cause for the differences in the residence times of the two springs, which suggests that the flow regimes for the two springs are independent. The chemistry of the two springs, however, is essentially the same, with the exception of tritium, which is used to ascertain residence time.