Set up and validation of a method to analyse microplastics in stool and small intestine samples.

The contamination of microplastics in humans is of increasing concern. Therefore, the aim of this study was to develop effective methods to determine the concentration and types of microplastics entering human digestive system. To study levels of MPs contamination in humans, an excellent indicator are stools. Indeed, stools, and thus the digestive system, can be an excellent indicator of the level of MPs contamination in humans. Hence, objective was to find effective methods to extract, quantify and characterize microplastics in stool and small intestine samples. The samples studied were human stools and pig jejunum (which has human-like characteristics). The methods were optimized by observing extraction efficiency, compatibility by Fourier-transform infrared spectroscopy (FTIR) characterization and non-deformation of the microplastics. The steps of the procedure were: • Sampling to avoid plastic contamination • Non-aggressive chemical and enzymatic digestion • Counting and characterization The methods were optimized and validated, observing recovery and repeatability. Therefore, two simple, effective methods with high analytical performance have been developed. The MPs present in the stool and intestine samples were counted by stereoscopic microscope and characterized by FTIR, finding several types of MPs such as synthetic cellulose, polyethylene, polypropylene, polystyrene, and polyethylene terephthalate, among others.

Human exposure to elements through consumption of raw and cooked fish in an urban region of the central Brazilian Amazon biome: Health risks.

Fish is an important source of animal protein for local communities in the Amazon basin, whose food safety must be assured. However, certain potential toxicants elements, can bioaccumulate in fish species, which inhabit anthropogenically polluted waters, ultimately posing a risk to human health. In the present study, the concentrations of nine elements (Al, As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) were determined in raw and cooked samples of eight fish species consumed in Santarém (northern Brazil, Amazon biome). The potential for non- carcinogenic human health risks linked to the consumption of cooked fish were evaluated for adults and children in two different scenarios. Four carnivores, three omnivores and one detritivore, all of them regularly marketed and consumed by the Santarém population, were the target species. The safety reference values set by national and international guidelines for humans, in both raw and cooked preparations, were used. In most cases, the cooking process showed a trend to increase elements concentrations compared to raw samples, however the differences were not significant. Moreover, the risk assessment showed danger for children in relation to Hg from the consumption of fish, in both scenarios evaluated. For adults, in one of the scenarios, there was a health risk associated to Hg as a result of carnivorous fish consumption. In a context of combined exposure to all elements, children were at risk when consuming fish, especially carnivorous and omnivorous species. For adults, the mixture of elements posed a risk to health human only for carnivorous fish consumption. The results reveal an environmental scenario of Hg contamination, which requires monitoring actions to preserve the aquatic biodiversity and human health in the Brazilian Amazon biome.

Contamination level, spatial distribution, and sources of potentially toxic elements in indoor settled household dusts in Tehran, Iran.

Tehran, the capital city of Iran, has been facing air pollution for several decades due to rapid urbanization, population growth, improper vehicle use, and the low quality of fuels. In this study, 31 indoor dust samples were collected passively from residential and commercial buildings located in the central and densely populated districts of the city. These samples were analyzed after preparation to measure the concentration of elements (As, Be, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Se, Sr, V, Zn). Statistical data analyses were employed to compare their relationship across various uses, variations, and for source identification. Geochemical indices of contamination factor (CF) and pollution load index (PLI) were utilized to evaluate the degree of contamination. The mean concentrations of Zn, Cu, and Pb (938, 206, and 176 µg g-1, respectively) are 6, 5, and 3 times higher than their mean values in worldwide urban soils. Additionally, Cd, Mo, and Ni showed concentrations about 1.5 times higher, while As, Co, Cr, Mn, and Sr fell within the range of reference soils. Be, V, and Sb displayed remarkably lower mean values. Building use did not significantly influence element levels in indoor deposited dust except for Pb and Zn. A comparison of indoor concentrations with previously published data for outdoor dusts revealed higher enrichments of Mo, Cu, Pb, and Ni, while As, Cd, and Zn showed lower enrichments in street dust samples. The order of CF values indicated Hg > Zn > Cd > Pb > Cu > As > Ni > Cr > Co > V. For Hg, Zn, Pb, Cd, and Cu, all or almost all samples exhibited very high contamination. PLI values were consistently higher than 1, indicating contamination in all samples. Multivariate statistical analysis and Tehran's specific geological location suggested that mafic-intermediate volcanic rocks are primary sources for Cr, Cu, Fe, and Ni (PC1). As, Pb, and V (PC2) were attributed to fossil fuel combustion in vehicles and residential buildings. Pb is a legacy metal remaining from the use of leaded gasoline, which was phased out in the 1990s. Zn (PC3) is derived from vehicle tires.

Evolution in the frontline treatment of patients with chronic lymphocytic leukemia: experience from one European center.

Treatment of chronic lymphocytic leukemia (CLL) has dramatically evolved over the last decades thanks to the introduction of targeted therapies. We aimed to describe retrospectively the evolution in the frontline prescription in the CLL patients from our institution. As a secondary objective, the impact of frontline therapy on the time-to-next-treatment (TTNT) and overall survival (OS). After a median of 6.4 years (0.1-36.4) of follow-up from diagnosis, 323 of 780 CLL patients (41.4%) required therapy. Alkylating agents in monotherapy (chlorambucil) were the most used until 2012, and from then, chemoimmunotherapy. Since 2018, targeted therapies were the most common therapeutic strategy (74.1%). Patients who received targeted therapies had significantly longer TTNT compared to other regimens. In the multivariable analyses, mutated IGHV genes targeted therapies and chemoimmunotherapy regimens were related to longer TTNT, and sex female, age younger than 65, and mutated IGHV genes were associated with better OS.

Tracing the fate of microplastic in wastewater treatment plant: A multi-stage analysis of treatment units and sludge.

Microplastic (MP) pollution is ubiquitous in the environment presenting a global problem for both scientists and the general public. One of the major pathways of MPs entering the natural environment is through wastewater treatment plants (WWTPs). Once MPs reach the natural environment, they are posing threat to aquatic ecosystems and public health. The aim of this study is to investigate the concentration, morphology, and composition of MPs in different treatment units of a WWTP. Sampling included different points across WWTP in the water and sludge lines. Pre-treatment of the samples consists of advanced Fenton oxidation, and alkaline and enzymatic digestion followed by density separation. Once the particles were isolated, their morphology and size were studied using a stereoscopic and optical microscope followed by final confirmation with ATR-FTIR and micro-FTIR spectroscopy. Microplastic particle concentrations exhibit significant reductions as water undergoes treatment in the WWTP. For summer sampling, concentrations decreased from 351 MP/L (influent) to 35 MP/L (primary clarifier), 32 MP/L (biological reactor), and 13 MP/L (2.3 MP/L) (secondary clarifier). Similarly, winter sampling showed reductions from 403 MP/L (influent) to 159 MP/L (primary clarifier), 178 MP/L (biological reactor), and 26 MP/L (5.6 MP/L) (secondary clarifier). Removal efficiency of WWTP is high and exceeds 96%. The most abundant morphology is fibers followed by fragments and films. Polymers such as PE, synthetic cellulose, PP, PVC, PE-PP, PEEA, PA, acrylamide, and PES are widely detected in different units of WWTP. The number of MPs that are avoided from being emitted into the environment through direct water discharge was estimated to be 9.1 × 1012 MP/year. Removed MPs tend to accumulate in the sludge that is used for agricultural purposes although it should be managed as waste properly, avoiding the transition of MPs pollutants to terrestrial ecosystems adding to the number of MPs that will inevitably end up in receiving water bodies through direct WWTP effluent discharge that was set in 5.1 × 1010 MP/year in the studied WWTP.

Clothing as a potential exposure source of trace elements during early life.

In recent years, the interest in determining the chemical composition of textile products has increased among the scientific community and regulatory agencies, driven by toxicological issues and environmental concerns. Chemical elements are naturally present in clothing as natural fibers or intentionally added during manufacture. Some of them show physical-chemical properties that allow their absorption through the skin. In addition, chronic situations increase the dermal exposure capacity. Because of age-specific behavioral characteristics and underdeveloped physiological function, children may be especially sensitive to exposure to trace elements. This study aimed to analyze the levels of twenty trace elements in 120 clothing items commercialized in Spain. Textile products for pregnant women and children <36 months old were included. The potential health implication of this dermal exposure in early life was also evaluated. Aluminum, zinc, and titanium showed the highest concentrations, with median levels of 27.6, 5.6, and 4.2 mg/kg, respectively. Since chromium is employed as a metal complex dye in synthetic fibers, high levels of this element were found in black polyester. Dermal exposure to titanium, which is a ubiquitous element in clothes made of synthetic fibers, was associated with a hazard quotient (HQ) higher than the threshold value (HQ > 1), with values of 1.13 for pregnant women and 1.22 for newborns. On the other hand, HQ values of other elements and cancer risks were lower than the recommended values. Assessing early-life exposure to toxic elements can help to identify potential sources and to prevent or reduce human exposure, mainly in vulnerable groups.

Multidrug-resistant Enterobacter spp. in wastewater and surface water: Molecular characterization of ß-lactam resistance and metal tolerance genes.

Among the ESKAPE group pathogens, Enterobacter spp. is an opportunistic Gram-negative bacillus, widely dispersed in the environment, that causes infections. In the present study, samples of hospital wastewater, raw and treated urban wastewater, as well as surface receiving water, were collected to assess the occurrence of multidrug-resistant (MDR) Enterobacter spp. A molecular characterization of ß-lactam antibiotic resistance and metal tolerance genes was performed. According to identification by MALDI-TOF MS, 14 isolates were obtained: 7 E. bugandensis, 5 E. kobei, and 2 E. cloacae. The isolates showed resistance mainly to ß-lactam antibiotics, including those used to treat infections caused by MDR bacteria. Multiple antibiotic resistance index was calculated for all isolates. It allowed verify whether sampling points showed a high risk due to antibiotic resistant Enterobacter spp., as well as to determine if the isolates have been in environments with a frequent antibiotic use. Twelve isolates showed ß-lactam antibiotic resistance gene, being the blaKPC widely detected. Regarding metal tolerance, 13 isolates showed at least two genes that encode metal tolerance mechanisms. Overall, metal tolerance mechanisms to silver, copper, mercury, arsenic and tellurium were found. New data on metal tolerance mechanisms dispersion and antibiotic-resistance characterization of the E. bugandensis and E. kobei species were here provided. The occurrence of MDR Enterobacter spp. in analyzed samples draws attention to an urgent need to put control measures into practice. It also evidences waterborne spread of clinically important antibiotic-resistant bacteria recognized as critical priority pathogens.

Screening of microplastics in water and sludge lines of a drinking water treatment plant in Catalonia, Spain.

Microplastics (MPs) are emerging pollutants detected everywhere in the environment, with the potential to harm living organisms. The present study investigated the concentration, morphology, and composition of MPs, between 20 µm and 5 mm, in a drinking water treatment plant (DWTP) located close to Barcelona (Catalonia, NE Spain). The sampling included different units of the DWTP, from influent to effluent as well as sludge line. Sampling strategy, filtration, allows sampling of large volumes of water avoiding sample contamination, and during 8 h in order to increase the representativeness of MPs collected. The pre-treatment of the samples consisted of advanced oxidation with Fenton's reagent and hydrogen peroxide, followed by density separation of the particles with zinc chloride solution. Visual identification was performed with an optical and stereoscopic microscope with final Fourier-transform infrared spectroscopic (FTIR) confirmation. MPs were found in all DWTP samples, with concentrations from 4.23 ± 1.26 MPs/L to 0.075 ± 0.019 MPs/L in the influent and effluent of the plant, respectively. The overall removal efficiency of the plant was 98.3%. The most dominant morphology was fibers followed by fragments and films. Twenty-two different polymer types were identified and synthetic cellulose, polyester, polyamide, polypropylene, polyethylene, polyurethane, and polyacrylonitrile were the most common. Although MPs could be incorporated from the distribution network, MPs intake from drinking water from this DWTP was not an important route compared to fish and seafood ingestion.

Optimising the management of patients with multiple myeloma in Spain: A measurement of the social return on investment.

OBJECTIVE: The aim of this study was to reach a consensus on a set of proposals to optimise the disease management of Multiple myeloma (MM) within the Spanish National Health System (SNHS) and to apply the Social Return on Investment (SROI) method to estimate their social impact. METHODS: A Multidisciplinary Working Team (MWT) including MM main stakeholders was organised. A survey was administered to gather information from patients regarding the impact of MM on different life domains. A forecast-type SROI analysis, with a 1-year timeframe, was applied. RESULTS: Fifteen proposals were selected, to optimise MM management, including actions for early diagnosis, psychological support, improvement of information for patients and quick access to palliative care, among others. The implementation of these proposals would benefit patients, their informal caregivers and the SNHS. The investment required would amount to 10.32 million euros with a social return of 43.31 million euros: 4.2 euros for each euro invested. According to the sensitivity analysis, this ratio could range from 3.38 to 5.20 euros from the worst to the best-case scenario. CONCLUSIONS: The current management of MM could be optimised by implementing a set of proposals that would most likely result in an overall positive social return.

Levels of microplastics and their characteristics in molluscs from North-West Mediterranean Sea: Human intake.

Microplastics (MPs) are accessible for organisms with active filter feeding strategies, as are many marine molluscs, which live attached or semi-buried in sediments. In the present study, MPs (from 0.02 to 5 mm) concentration, morphology, and composition were determined in consumed mollusc species of the Catalan coast (NW Mediterranean Sea). Microplastic concentrations, morphologic characteristics and composition were studied according to species, catchment zones and depuration condition. Finally, human intake of MPs through molluscs' consumption was determined. >2300 individuals were analysed, being 1460 MPs extracted and their size, and polymeric composition registered. Big oysters and mussels showed the highest MPs concentration by individual, with levels of 22.8 ± 14.4 and 18.6 ± 23.0 MPs/individual, respectively. Mean annual MPs (≥20 µm) consumption for adult population was estimated in 8103 MPs/year, with a 95th percentile of 19,418 MPs/year. It suggests that the consumption of molluscs is an important route of MPs exposure for the Catalan population.

The EHA Research Roadmap: Immune-based Therapies for Hematological Malignancies.

In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1-2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European Hematology Research. the 11 EHA Research Roadmap sections include normal hematopoiesis; malignant lymphoid diseases; malignant myeloid diseases; anemias and related diseases; platelet disorders; blood coagulation and hemostatic disorders; transfusion medicine; infections in hematology; hematopoietic stem cell transplantation; CAR-T and Other cell-based immune therapies; and gene therapy.

Microplastics levels, size, morphology and composition in marine water, sediments and sand beaches. Case study of Tarragona coast (western Mediterranean).

Mediterranean Sea has been proposed as the sixth greatest accumulation zone for marine litter and the most affected regarding to microplastics (MPs). Tarragona (Catalonia, NE Spain) coastal region suffers high pressure due to urbanization, tourism, industrial harbour and petrochemical/plastic industries. The present study aims to quantify and characterize in size, morphology and composition the MPs present in sandy beaches, marine sediments, and surface seawaters of Tarragona coastal region. MPs mean abundance were 1.30 items/m3 in surface seawaters, 32.4 items/kg in marine sediments, and 10.7 items/kg in sandy beaches. Polyester fibres were dominant MPs in bottom sediments and seawater meanwhile polyethylene and polypropylene fragments were the main MPs in beaches. The fibres balls associated with bottom sediments, organic matter and plankton were abundant, masking the real quantity of fibres in each reservoir. The abundance by volume of seawater MPs was higher to those found in oceanic areas and similar to other areas of Mediterranean Sea, corroborating that Western Mediterranean Sea as a region of MPs accumulation. MPs composition and abundance suggested the input of numerous land-base-sources, WWTP (wastewater treatment plants) effluents discharges, and emissaries as the most important. Marine MPs pollution were studied from an integrative point of view, that includes superficial sea water, sand from beaches and sediments. The dynamics of MPs in Tarragona coast were characterized by seawater as the media that receive and facilitate dispersion and fragmentation. The shoreline acts as an intermediate reservoir with constant weathering and active exchange with seawater surface and the sediments acts as a significant sink for medium MPs sizes. It is necessary to develop protocols and guidelines for MPs analysis to obtain harmonized and comparable results.

Allogeneic stem cell transplantation as a curative option in relapse/refractory diffuse large B cell lymphoma: Spanish multicenter GETH/GELTAMO study.

We performed a retrospective multicenter study including 140 patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) from March 1995 to November 2018. Our objective was to analyze long term outcomes. Seventy-four percent had received a previous auto-SCT (ASCT) and the median number of lines pre-allo-SCT was 3 (range 1-9). Three year-event free survival (EFS) and overall survival (OS) were 38% and 44%, respectively. Non-relapse mortality (NRM) at day 100 was 19%. Cumulative incidence of grade III-IV acute graft versus host disease (GVHD) at day 100 was 16% and moderate/severe chronic GVHD at 3 years 34%. Active disease at allo-SCT (HR 1.95, p = 0.039) (HR 2.19, p = 0.019), HCT-CI ≥ 2 (2.45, p = 0.002) (HR 2.33, p = 0.006) and donor age >37 years (HR 2.75, p = 0.014) (HR 1.98, p = 0.043) were the only independent variables both for PFS and OS, respectively. NRM was significantly modified by HCT-CI ≥ 2 (HR 4.8, p = 0.008), previous ASCT (HR 4.4, p = 0.048) and grade III-IV acute GVHD on day 100 (HR 6.13, p = 0.016). Our data confirmed that allo-SCT is a curative option for patients with R/R DLBCL, displaying adequate results for fit patients with chemosensitive disease receiving an allo-SCT from a young donor.

Characterization of airborne particles and cytotoxicity to a human lung cancer cell line in Guangzhou, China.

Air pollution by airborne particles is a serious health problem worldwide. The present study was aimed at investigating the concentrations and composition of total suspended particles (TSPs) and PM2.5 at various industrial/commercial sites of Guangzhou, a megacity of Southern China. Major and trace elements, ions and carbonaceous fraction were determined and main components were calculated. In addition, in order to assess the potential toxic on the respiratory system of these PM, cytotoxicity of size-fractionated particles (PM10-5.6, PM5.6-3.3, PM3.3-1.1, PM1.1-0.43) for a human lung cancer cell line (A549) was also investigated. Correlations between PM constituents and toxicity were assessed. Median levels of TSPs and PM2.5 in industrial/commercial sites were 206 and 57.7 µg/m3, respectively. Nickel, Cu, Mo, Mn, Pb, and Ti were the most abundant metals in TSPs and PM2.5. Industrial activities and coal combustion were the most important sources of carbonaceous particles in the zone. MTT assays showed that PM10-5.6 and PM1.1-0.43 had the highest and the lowest cytotoxicity to A549 cell lines, respectively. Inhalable particles around the manufacturing of metal facilities and formal waste treatment plants showed a high cytotoxicity to A549 cell lines. In general terms, no significant correlations were found between main components of PM and toxicity. However, W showed a significant correlation with cell viability.

Performance of Chlorella Vulgaris Exposed to Heavy Metal Mixtures: Linking Measured Endpoints and Mechanisms.

Microalgae growth inhibition assays are candidates for referent ecotoxicology as a fundamental part of the strategy to reduce the use of fish and other animal models in aquatic toxicology. In the present work, the performance of Chlorella vulgaris exposed to heavy metals following standardized growth and photosynthesis inhibition assays was assessed in two different scenarios: (1) dilutions of single heavy metals and (2) an artificial mixture of heavy metals at similar levels as those found in natural rivers. Chemical speciation of heavy metals was estimated with Visual MINTEQ software; free heavy metal ion concentrations were used as input data, together with microalgae growth and photosynthesis inhibition, to compare different effects and explain possible toxicity mechanisms. The final goal was to assess the suitability of the ecotoxicological test based on the growth and photosynthesis inhibition of microalgae cultures, supported by mathematic models for regulatory and decision-making purposes. The C. vulgaris algae growth inhibition test was more sensitive for As, Zn, and Pb exposure whereas the photosynthesis inhibition test was more sensitive for Cu and Ni exposure. The effects on growth and photosynthesis were not related. C. vulgaris evidenced the formation of mucilaginous aggregations at lower copper concentrations. We found that the toxicity of a given heavy metal is not only determined by its chemical speciation; other chemical compounds (as nutrient loads) and biological interactions play an important role in the final toxicity. Predictive mixture effect models tend to overestimate the effects of metal mixtures in C. vulgaris for both growth and photosynthesis inhibition tests. Growth and photosynthesis inhibition tests give complementary information, and both are a fast, cheap, and sensitive alternative to animal testing. More research is needed to solve the challenge of complex pollutant mixtures as they are present in natural environments, where microalgae-based assays can be suitable monitoring tools for pollution management and regulatory purposes.

Feasibility of thiotepa addition to the fludarabine-busulfan conditioning with tacrolimus/sirolimus as graft vs host disease prophylaxis.

In classical reduced-intensity conditioning (RIC) regimens, including the fludarabine and busulphan (BF) combination, sirolimus and tacrolimus (SIR-TAC) as graft vs host disease (GVHD) prophylaxis has shown acceptable results. The outcomes of SIR-TAC in a more intense RIC regimen as Thiotepa-fludarabine-busulfan (TBF) have been hardly investigated. This retrospective study included all consecutive patients receiving an allogeneic hematopoietic stem cell transplantation for myeloid malignancies (January 2009-2017) conditioned with either TBF or BF and receiving SIR-TAC. Patients receiving TBF presented higher non-relapse mortality (31.6 vs 12.3%, p = .01), along with shorter overall survival (51.8% vs 77.8%, p < .01) at 2 years than patients treated with BF. There were no significant differences in the cumulative incidence of grade II-IV acute GVHD or moderate-severe chronic GVHD or relapse between both groups. These results suggest that TBF does not seem to improve the traditional RIC BF regimen, at least when associated with SIR-TAC prophylaxis.

Essential and toxic elements in human milk concentrate with human milk lyophilizate: A preclinical study.

Concentrated human milk (HM-concentrate) can be obtained from the simple and inexpensive method of donated breast milk direct lyophilization. A previous study reported that HM-concentrate contains the adequate amount of main macro- and micronutrients for use as a nutritional resource for preterm infants with very low birth weight admitted to neonatal intensive care units. However, further details need to be elucidated about HM-concentrate composition, particularly its content of essential and potentially toxic trace elements. Therefore, this study aimed to determine the concentration of essential and toxic elements in human milk considered baseline (HM-baseline) and HM-concentrate, as well as to quantify changes in concentration of these elements after the HM concentration process. The concentration of Aluminum, Arsenic, Cadmium, Chromium, Iron, Mercury, Manganese, Nickel, Lead, Selenium, Tin, and Thallium was analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Moreover, Bayesian linear mixed effect models were applied to estimate the mean difference between HM-baseline and HM-concentrate samples. After comparison (HM-concentrate versus HM-baseline), a significant increase in concentration was observed only for Manganese (0.80 µg/L; 95% CrI [0.16; 1.43]) and Selenium (6.74 µg/L; 95% CrI [4.66; 8.86]), while Lead concentration (-6.13 µg/L; 95% CrI [-8.63; -3.61]) decreased. This study provides latest and reliable information about HM composition. After milk concentration by lyophilization, there was a significant increase only in the essential elements Manganese and Selenium. The essential micronutrient content in HM-concentrate was similar or higher than that in preterm mothers' milk, which suggests it is viable for nutritional support of preterm infants. In addition, the low concentrations of potentially toxic elements in HM-concentrate indicates that it is safe for consumption by premature newborns.

Correction to: Update on management and progress of novel therapeutics for R/R AML: an Iberian expert panel consensus.

After publication of this paper, the authors determined that an additional information in the funding section was missing.