Study of the presence and environmental risk of organic contaminants policed by the European Union and other organic compounds in the water resources of a region overlapping protected areas: The Guadiaro River basin (southern Spain).

The study presented here is a first qualitative assessment of the occurrence of organic contaminants contemplated and not yet contemplated in European Union environmental legislation in water resources in the little anthropized Guadiaro River basin (70% of its area is covered by natural vegetation), in southern Spain. Water samples were collected from four carbonate aquifers, two detrital aquifers and four surface water courses and were analyzed for (i) 171 organic contaminants, (ii) major ions and (iii) stable isotopes (δ18OH2O, δ2HH2O, δ13CDIC). An environmental risk assessment was conducted through calculation of risk quotients comparing measured concentrations with ecotoxicological data found in the literature. Twenty-five organic contaminants were detected, at least once, including pesticides, pharmaceuticals, drugs of abuse and polycyclic aromatic hydrocarbons (PAHs). Cocaine and its main metabolite were detected in 85% and 95% of water samples, respectively (0.001-0.18 µg/L and 0.004-0.6 µg/L, respectively). Pyrene (PAH) was found in all water samples (0.001-0.015 µg/L) and forest fires were pointed out as a potential diffuse source. Relationship between rivers and aquifers is reflected by the distribution of organic contaminants, essentially the drugs of abuse. Concentration of contaminants were generally higher in groundwater samples, especially from detrital aquifers, potentially due to an accumulation process promoted by irrigation-return flows and by its slow dynamic compared to that of karstic systems. Pyrene concentration was also higher in some springs from karstic aquifers. Hence, calculated risk quotients were in general higher in groundwater, meaning that the threat to surface aquatic systems can grow as aquifers increase their influence on the water courses as the dry season progresses. The relationship between δ13CDIC and most organic contaminants (especially pyrene) reveal the role of the soil as storage media.

Respirometric tests in a combined UASB-MBR system treating wastewater containing emerging contaminants at different OLRs and temperatures: Biokinetic analysis.

This research focuses on the application of respirometric techniques to provide new insights into the biokinetic behaviour of bacterial species developed in an Upflow Anaerobic Sludge Blanked -UASB reactor combined with a membrane bioreactor -MBR, treating urban wastewater with emerging contaminants frequently found in this kind of effluents. The lab-scale pilot plant was operated at different metabolic and operational conditions by limiting the organic loading rate- OLR of the influent. In a first stage, the MBR was performed with suspended biomass, while in a second stage bio-supports were introduced to operate coexisting suspended and fixed biomass. From the results of the microscopic monitoring of sludge, it was concluded that the decrease in OLR resulted in a greater disintegration of the floc structure, more dispersed growth, and a low presence of inter-floccular bonds. However, no effect of toxicity or inhibition of microorganisms caused by the presence of emerging contaminants -ECs was determined. Kinetic modelling was carried out to study the behaviour of the system. The results showed a slowing down of biomass degradative capacity at low OLR stages and operating at low temperatures of mixed liquor. In addition, a decrease in oxygen consumption was observed with decreasing biodegradable substrate, resulting in lower degradation of organic matter. Mean values of specific oxygen uptake rate and heterotrophic biomass yield at low OLR were SOUR end = 1.49 and 1.15 mg O2· g MLVSS-1 h-1 and YH,MLSSV end = 0.48 and 0.28 mg MLVSS· mg COD-1substrate at stage 1 (suspended biomass) and stage 2 (suspended and supported biomass), respectively. From the analysis of the endogenous decomposition constant (kd), a higher cell lysis was determined operating with suspended biomass (kd = 0.03 d-1) in comparison to the operation coexisting suspended and supported biomass (kd = 0.01 d-1). Heterotrophic biomass yield values (YH, MLVSS = 0.48 ± 0.06, 0.40 ± 0.01 and 0.29 ± 0.01 mg MLVSS· mg COD-1substrate at high, medium and low OLR) showed lower sludge production at low OLR due to the influence of substrate limitation on cell growth.

Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience. / Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

Carbamazepine removal from low-strength municipal wastewater using a combined UASB-MBR treatment system.

An Upflow Anaerobic Sludge Blanket reactor combined with a two-stage membrane bioreactor were operated for 193 days in order to evaluate the biological removal of carbamazepine (CBZ) from low-strength municipal wastewater. The system worked in three different organic load stages (0.7 ± 0.1 kg COD·m-3·d-1, 0.4 ± 0.1 kg COD·m-3·d-1 and 0.1 ± 0.0 kg COD·m-3·d-1) to assess the impact of the influent OLR on operational parameters such as anaerobic and aerobic sludge retention time (SRT), acidity, volatile fatty acids (VFAs), biomass activity or biogas production. The highest carbamazepine removals were achieved during the anaerobic stage (UASB reactor), reaching averages of 48.9%, 48.0% and 38.2% operating at high, medium and low OLR, respectively. The aerobic treatment (MBR) served as post-treatment, improving the removals, and the global UASB-MBR system reached averages of 70.0%, 59.6% and 49.8% when the influent was at medium and low OLR, respectively. The results demonstrate the potential of combined biological systems on the removal of recalcitrant pharmaceuticals.

Real-world effectiveness and safety of apremilast in psoriasis at 52 weeks: a retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Little has been published on the real-world effectiveness and safety of apremilast in psoriasis. OBJECTIVES: To evaluate the effectiveness, safety and drug survival of apremilast at 52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice. METHODS: Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018. RESULTS: We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI-75 (≥75% reduction in PASI score) and 26.5% achieved PASI-90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems. CONCLUSIONS: Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.

Multiscale design of ZnO nanostructured photocatalysts.

A systematic investigation of the photocatalytic activity (PCA) of nanostructured ZnO films showed how this is directly affected by the films' morphology at different scales, from the macroscale morphology of films (e.g. thickness and surface area), to the microscale feature arrangement (e.g. aligned vs. randomly oriented structures or interpenetrated ones), to the nanoscale structure (e.g. crystal size and orientation). The interest in immobilizing photocatalysts in water treatment stems from concerns about the potential toxicity of their slurry form, which requires expensive downstream removal. Immobilisation, though, leads to a reduction in PCA, generally attributed to a lower surface area. By reducing the films' feature size to the nanoscale, an immobilized photocatalyst with high surface area can be achieved. At this scale, however, feature structuring and morphology become important as they determine the interaction between light and the photocatalytic material. In this work, nanostructured ZnO films with different morphology, arrangement and structure were produced by electrochemical anodization of zinc and were tested using the degradation of phenol in a batch reactor as a model system. Results show that the PCA for immobilized catalysts can be optimised by controlling microscale arrangement (light absorbance capacity) and nanoscale structure (crystal size and orientation) rather than macroscale morphology (surface area). These results provide a clear direction to maximising the photocatalytic activity of immobilised photocatalysts for the removal of organic pollutants from water.

Impact of growth temperature on exopolysaccharide production and probiotic properties of Lactobacillus paracasei strains isolated from kefir grains.

EPS-producing LAB are widely used in the dairy industry since these polymers improve the viscosity and texture of the products. Besides, EPS might be responsible for several health benefits attributed to probiotic strains. However, growth conditions (culture media, temperature, pH) could modify EPS production affecting both technological and probiotic properties. In this work, the influence of growth temperature on EPS production was evaluated, as well as the consequences of these changes in the probiotic properties of the strains. All Lactobacillus paracasei strains used in the study showed changes in EPS production caused by growth temperature, evidenced by the appearance of a high molecular weight fraction and an increment in the total amount of produced EPS at lower temperature. Nevertheless, these changes do not affect the probiotic properties of the strains; L. paracasei strains grown at 20 °C, 30 °C and 37 °C were able to survive in simulated gastrointestinal conditions, to adhere to Caco-2 cells after that treatment and to modulate the epithelial innate immune response. The results suggest that selected L. paracasei strains are new probiotic candidates that can be used in a wide range of functional foods in which temperature could be used as a tool to improve the technological properties of the product.

Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis.

BACKGROUND: Few reported studies compare drug survival in moderate-to-severe psoriasis vulgaris. OBJECTIVES: To describe and compare drug survival of systemic drugs, including biologic agents (infliximab, etanercept, adalimumab and ustekinumab) and classical drugs (acitretin, ciclosporin and methotrexate) in moderate-to-severe psoriasis. METHODS: This was a multicenter, prospective, cohort study of patients receiving systemic therapies between 2008 and 2013 in 12 hospitals in Spain. Baseline data and drug discontinuation were collected. Drug survival is presented using Kaplan-Meier survival curves. We compared adjusted risk ratios of serious adverse events (AEs) with results of survival analysis for AEs. RESULTS: A total of 1956 patients were included for analysis (1240 exposed to biologics during follow-up and 1076 to classic therapies). Median follow-up time was 3.3 years (0.0-5.1 years). There were 2209 discontinuations out of 3640 therapy cycles started. The main reason for discontinuation was lack of efficacy (36.4%) and remission (27.2%). Biologics showed a higher drug survival than classics and the pattern of survival results for all outcomes (positive or negative) were very similar. Adjusted risk ratios of serious AEs did not agree with results of survival analysis. LIMITATIONS: A limitation is that this is an observational study with potential selection bias. CONCLUSION: Survival as a proxy measure of drug safety in psoriasis is inadequate.

Does the treatment ladder for systemic therapy in moderate to severe psoriasis only go up? The percentage of patients with severe psoriasis on biologics increases over time.

BACKGROUND: With the advent of biologic drugs in the management of moderate to severe psoriasis, there may have been a shift in therapeutic approach from rotational strategies to a unidirectional progression from topical treatments to the highest rung of the therapeutic ladder. We studied the frequency of switching from classic to biologic therapy and vice versa in a cohort of patients with psoriasis over a period of up to 5 years. METHODS: Patients are included in the BIOBADADERM prospective registry when they are first prescribed any specific conventional or biologic systemic treatment. The data for each patient refer to the follow-up period from the time they entered the cohort until October 2013. To describe the pattern of switches from classic to biologic therapy and vice versa, we used the data in the registry on the first day of every 365-day period following the date each patient was included in the cohort. RESULTS: In total, 47.3% of the patients (926/1956) were prescribed a classic systemic drug and 52.7% (1030/1956) a biologic agent on entry into the study. Of the 741 patients who accumulated 5 years of follow-up, 21.9% (155) were receiving nonbiologic drugs and 78.1% (553) were on biologic therapy on the first day of their 5th year of follow-up. CONCLUSIONS: The proportion of patients receiving biologic therapy increased with longer follow-up.

Spanish Consensus Document on the Treatment Algorithm for Rosacea. / Documento de consenso español para el algoritmo de tratamiento de la rosácea.

Recent scientific evidence and the incorporation of new drugs into the therapeutic arsenal against rosacea have made it necessary to review and update treatment criteria and strategies. To this end, a panel of 15 dermatologists, all experts in rosacea, was formed to share experiences and discuss treatment options, response criteria, and changes to treatment. Based on a critical review of the literature and a discussion of the routine practices of Spanish dermatologists, the panel proposed and debated different options, with consideration of the experience of professionals and the preferences of patients or equality criteria. Following validation of the proposals, the final recommendations were formulated and, together with the evidence from the main international guidelines and studies, used to produce this consensus document. The goal of this consensus document is to provide dermatologists with practical recommendations for the management of rosacea.

Lactobacillus plantarum CIDCA 8327: An α-glucan producing-strain isolated from kefir grains.

Lactobacillus plantarum CIDCA 8327 is an exopolysaccharide (EPS)-producer strain isolated from kefir with promising properties for the development of functional foods. The aim of the present study was to characterize the structure of the EPS synthesized by this strain grown in skim milk or semidefined medium (SDM). Additionally, genes involved in EPS synthesis were detected by PCR. L. plantarum produces an EPS with a molecular weight of 104Da in both media. When grown in SDM produce an heteropolysaccharide composed mainly of glucose, glucosamine and rhamnose meanwhile the EPS produced in milk was composed exclusively of glucose indicating the influence of the sugar source. FTIR spectra of this EPS showed signals attributable to an α-glucan. Both by 1H NMR and methylation analysis it was possible to determine that this polysaccharide is a branched α-(1→4)-d-glucan composed of 80% linear α-(1→4)-d-glucopyranosyl units and 19% (1→4)-d-glucopyranosyl units substituted at O-3 by single α-d-glucopyranosil residues.

Lycopene, resveratrol, vitamin C and FeSO4 increase damage produced by pro-oxidant carcinogen 4-nitroquinoline-1-oxide in Drosophila melanogaster: Xenobiotic metabolism implications.

4-nitroquinoline-1-oxide (4-NQO) is a pro-oxidant carcinogen bioactivated by xenobiotic metabolism (XM). We investigated if antioxidants lycopene [0.45, 0.9, 1.8 µM], resveratrol [11, 43, 172 µM], and vitamin C [5.6 mM] added or not with FeSO4 [0.06 mM], modulate the genotoxicity of 4-NQO [2 mM] with the Drosophila wing spot test standard (ST) and high bioactivation (HB) crosses, with inducible and high levels of cytochromes P450, respectively. The genotoxicity of 4-NQO was higher when dissolved in an ethanol - acetone mixture. The antioxidants did not protect against 4-NQO in any of both crosses. In the ST cross, resveratrol [11 µM], vitamin C and FeSO4 resulted in genotoxicity; the three antioxidants and FeSO4 increased the damage of 4-NQO. In the HB cross, none of the antioxidants, neither FeSO4, were genotoxic. Only resveratrol [172 µM] + 4-NQO increased the genotoxic activity in both crosses. We concluded that the effects of the antioxidants, FeSO4 and the modulation of 4-NQO were the result of the difference of Cyp450s levels, between the ST and HB crosses. We propose that the basal levels of the XM's enzymes in the ST cross interacted with a putative pro-oxidant activity of the compounds added to the pro-oxidant effects of 4-NQO.

Intensive groundwater use: a silent revolution that cannot be ignored.

Over the last decades, agriculture in arid and semi-arid countries has experienced a true "silent revolution" of intensive groundwater use. Millions of independent farmers worldwide have chosen to become increasingly dependent on the reliability of groundwater resources, and as a result their countries have reaped abundant social and economic benefits. Data from several countries shows that groundwater irrigation presents a much greater efficiency, than surface water irrigation systems, thus contributing to fulfil the motto of "more crops and jobs per drop". If this situation is confirmed globally, the usual world water visions have to be reviewed. However, the "silent revolution" has been carried out with scarce control on the part of governmental water agencies, and thus a series of unwanted effects have developed in certain places. While these by no means justify the pervasive "hydromyths" and obsolete paradigms that voice the frailty of groundwater, appropriate management of groundwater resources remains a worldwide challenge. This paper provides an overview of these issues, and concludes with the necessity there is to educate all levels of society on the importance of groundwater and to create bottom-up user associations to manage aquifers as common pool resources.

Does concurrent drug intake affect the long-term outcome of group cognitive behaviour therapy in panic disorder with or without agoraphobia?

The present study investigated the impact of pre-existing pharmacotherapy regimes on the long-term outcome of brief intensive group cognitive-behavioural therapy (BIGCBT) in the treatment of panic disorder with or without agoraphobia in 106 patients (74 females). Forty patients were allocated to BIGCBT without medication, 40 to BIGCBT plus anti-anxiety medication, 10 to BIGCBT plus anti-depressant medication and 16 to BIGCBT plus combined anti-anxiety and anti-depressant medications. The mean follow-up period was 3.2 yr and ranged from 1.1 to 6.2 yr. The results demonstrated that patients who received BIGCBT concurrent with pre-existing medication regimes did not differ significantly (P > 0.001) from each other or from patients who underwent BIGCBT without medication on any of the dependent measures either at pre-treatment assessment or long-term follow-up. However, BIGCBT (with or without pharmacotherapy) was associated with significant (P < 0.001) long-term improvements in frequency of panic attacks, avoidance behaviour and questionnaire measures of anxiety, depression and agoraphobia. Furthermore, the large majority (80%) of patients in the BIGCBT without medication group remained medication-free at long-term follow-up. Of those patients who underwent BIGCBT concurrent with pre-existing pharmacotherapy, a large percentage (44%) reported no longer taking medication for their condition at long-term follow-up. Overall, it is concluded that pre-existing medication regimes (anti-anxiety, anti-depressant or combinations of these) do not significantly enhance or detract from the long-term outcome of a BIGCBT program used in the treatment of panic disorder and agoraphobia.

Microsurgical extrahepatic cholestasis in the rat: a long-term study.

An experimental model of microsurgical cholestasis is studied as an alternative to the most frequently used surgical techniques, based on the section of the common bile duct. This microsurgical technique consists of the resection of the extrahepatic biliary tract, that is, of the common bile duct in continuity with the bile ducts that drain the four lobes of the rat liver. At 30 days of evolution, rats with microsurgical cholestasis do not develop biliary pseudocysts or intraperitoneal hilar hepatopulmonary abscesses and show an increase (p < 0.001) in total bilirubin (9.50 +/- 1.50 mg/dL vs. 1.60 +/- 0.35 mg/dL), bile acids (225 +/- 87 micromol/L vs. 12.5 +/- 14.50 micromol/L), gamma-glutamyltranspeptidase (375 +/- 143 U/L vs. 8 +/- 11 U/L), and alkaline phosphatase (73 +/- 25 U/L vs. 23 +/- 4 U/L) levels. The histological study shows fibrosis with biliary proliferation. The microsurgical cholestasis technique is a valid alternative to other techniques and can be an adequate experimental model for the study of etiopathogenic mechanisms of obstructive jaundice and especially to study extrahepatic biliary atresia.

Comparison between one and three doses a week of recombinant erythropoietin in very low birth weight infants.

OBJECTIVE: To compare transfusion requirements and erythropoietic response in preterms between schedules of rEPO administration once or three times per week, using the same weekly dose. STUDY DESIGN: Prospective, randomized trial including infants weighing <1500 g at birth and/or were 32 weeks' gestation: Group 1 (60 infants) received subcutaneous rEPO at 250 units kg(-1) per dose, three times weekly for 6 weeks; Group 2 (59 infants), at 750 units kg(-1) per dose, once weekly for 6 weeks. Efficacy was evaluated based on the transfusion requirement, hemoglobin changes, reticulocyte counts, serum transferrin receptor (sTfR) and serum ferritin. The frequency of adverse effects was registered in both groups. RESULT: A total of 13 infants were transfused in each group (relative risk: 0.98; 95% confidence interval: 0.4 to 2.3). Phlebotomy loss and red blood cell transfusion volumes received were similar in both groups. Hemoglobin levels were lower at end of study in Group 2 (10.6±1.5 g dl(-1) versus 11.5±1.4 g dl(-1); P<0.003). At end of study, reticulocyte counts and sTfR values increased and serum ferritin values decreased, without significant differences between the two groups. Incidence of complications was similar in both groups. CONCLUSION: The once-weekly rEPO schedule for very low birth weight infants proved as effective as the three-times-weekly schedule, in relation to erythropoietic stimulus and transfusion requirement.