Accumulation, distribution pattern and potential contamination of sulphur in vineyard soils of the Valdepeñas protected denomination origin.

Soil is the basis for almost all global agriculture and the medium in which most terrestrial biological activity occurs. Viticulture represents an important agricultural practice in the Castilla-La Mancha (CLM) community. In this region, there are several protected denominations of origin (PDO), the largest being Valdepeñas. This paper describes the accumulation pattern of sulphur (S) in the vineyard soils of this PDO. Samples were collected from 90 vineyard soil profiles. Sulphur content was determined using an X-ray Fluorescence spectrometer in the solid mode on a powdered aliquot of each sample. The results indicated that the total S in soils varied from 0.54 to 6.90 (g·kg-1) in surface soil (0-30 cm) and from 0.39 to 2.80 (g·kg-1) on the subsurface layer (30-80 cm). When comparing the mean values of surface horizons to the subsurface horizons, S content lowered as soil depth increased. Kurtosis exceeded 45 % in all cases, which indicates a wide variability of concentrations. These findings can be explained by the continuous fertiliser and fungicide applications (and therefore S) in these production systems. Using the geoaccumulation index (Igeo), most soils were included in Class 0 (Igeo <0) and were, thus, S uncontaminated; only a few points can be considered pollutants. The obtained results should contribute to extend the scarce existing database on S in Mediterranean regions like that herein studied.

The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. METHODS: Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. RESULTS: Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. CONCLUSIONS: The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain.

Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: a report from the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP)

Purpose The COVID-19 pandemic has forced healthcare stakeholders towards challenging decisions. We analyse the impact of the pandemic on the conduct of phase I–II trials for paediatric cancer during the first month of state of alarm in Spain. Methods A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products, and legal aspects. Results All units suffered personnel shortages and difficulties in enrolling patients, treatment continuity, or performing trial assessments. Monitoring activity was frequently postponed (73%), and 49% of on-going trials interrupted recruitment. Only two patients could be recruited during this period (75% reduction in the expected rate). Conclusions The COVID-19 crisis has significantly impacted clinical research practice and access to innovation for children with cancer. Structural and functional changes are under way to better cope with the expected future restrictions (AU)

Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: a report from the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: The COVID-19 pandemic has forced healthcare stakeholders towards challenging decisions. We analyse the impact of the pandemic on the conduct of phase I-II trials for paediatric cancer during the first month of state of alarm in Spain. METHODS: A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products, and legal aspects. RESULTS: All units suffered personnel shortages and difficulties in enrolling patients, treatment continuity, or performing trial assessments. Monitoring activity was frequently postponed (73%), and 49% of on-going trials interrupted recruitment. Only two patients could be recruited during this period (75% reduction in the expected rate). CONCLUSIONS: The COVID-19 crisis has significantly impacted clinical research practice and access to innovation for children with cancer. Structural and functional changes are under way to better cope with the expected future restrictions.

Blood Pressure, Congestion and Heart Failure with Preserved Ejection Fraction Among Patients with and Without Type 2 Diabetes Mellitus. A Cluster Analysis Approach from the Observational Registry DICUMAP.

INTRODUCTION: The association of patients with heart failure (HF) and preserved ejection fraction (HFpEF) and with type 2 diabetes mellitus (T2DM) is strong and related additionally to blood pressure (BP). AIMS: To analyze distinctive clinical profiles among patients with HFpEF both with and without T2DM. METHODS: The study was based on a Spanish National Registry (multicenter and prospective) of patients with HF (DICUMAP), that enrolled outpatients with HF who underwent an ambulatory BP monitoring (ABPM) and then were followed-up for 1 year. We categorized patients according to the presence/absence of T2DM then building different clusters based on K-medoids algorithm. RESULTS: 103 patients were included. T2DM was present in 44.7%. The patients with T2DM were grouped into two clusters and those without T2DM into three. All patients with T2DM had kidney disease and anemia. Among them, cluster 2 had higher systolic blood pressure and pulse pressure (PP) with a bad outcome (p = 0.03) regarding HF mortality and readmissions, influenced by eGFR (HR 0.93, 95% CI 0.97-0.87, p = 0.04), and hemoglobin (HR 0.65, 95% CI 0.71-0.63, p = 0.03). Among those without T2DM, cluster 3 had a pathological ABPM pattern with the highest PP, cluster 4 was slightly similar to cluster 2, and cluster 5 expressed a more benign pattern without differences on both, HF mortality and readmissions. CONCLUSIONS: Patients with HFpEF and T2DM expressed two different profiles depending on neurohormonal activation and arterial stiffness with prognostic implications. Patients without T2DM showed three profiles depending on ABPM pattern, kidney disease and PP without prognostic repercussion.

¿Es siempre el tratamiento con hierro oral la mejor opción terapéutica? / Is oral Iron therapy always the best option?

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ECLIM-SEHOP, a new platform to set up and develop international academic clinical trials for childhood cancer and blood disorders in Spain.

INTRODUCTION: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. METHODS: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. RESULTS: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. CONCLUSIONS: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.

Hemoconcentración como predictor de supervivencia al año de ingreso por insuficiencia cardiaca aguda en el registro RICA / Hemoconcentration as a prognostic factor after hospital discharge in acute heart failure in the RICA registry

Objetivo: diferentes estudios señalan que la consecución de una mayor hemoconcentración en pacientes ingresados por insuficiencia cardiaca (IC) aguda mejora el pronóstico a lo largo del año siguiente al episodio índice. El objetivo de este estudio es evaluar si el grado de hemoconcentración a los 3 meses tras el ingreso por IC también tiene valor pronóstico de reingreso y/o mortalidad en los 12 meses siguientes al ingreso. Pacientes y método: cohorte prospectiva multicéntrica de 1.659 pacientes con IC. El grupo hemoconcentración (305 pacientes) se situó en el cuartil superior de la muestra distribuida en función del aumento de la hemoglobina en el mes 3 tras el alta con respecto a la hemoglobina en el ingreso por IC. Resultados: seguimiento medio hasta el primer evento fue de 294 días, fallecieron 487 pacientes y reingresaron 1.125. El grupo hemoconcentración mostró un riesgo menor de mortalidad o de reingreso por cualquier causa (RR=0,75; IC 95%: 0,51-1,09 y RR=0,86; IC 95%: 0,70-1,05), si bien la significación estadística se perdió tras el análisis multivariado. Sin embargo, esta significación se mantuvo para otros factores con reconocido efecto negativo sobre el pronóstico en pacientes con IC, como son la edad y la clase funcional. Conclusiones: el grado de hemoconcentración a los 3 meses tras el ingreso por IC no tiene valor pronóstico de reingreso o muerte en el año siguiente

Objective: several studies have reported that a higher degree of hemoconcentration in patients admitted for the treatment of acute heart failure (HF) constitutes a favorable prognostic factor in the year following the index episode. The objective of this study was to evaluate whether the highest degree of hemoconcentration at 3 months after admission for HF is also a prognostic factor for mortality and/or readmission in the 12 months after admission. Patients and method: the hemoconcentration group was the upper quartile of the sample distributed according to hemoglobin increase at month 3 after discharge with respect to hemoglobin at the time of admission for HF in a multicenter prospective cohort of 1,659 subjects with HF. Results: the mean follow-up until the first event was 294 days, and a total of 487 deaths and 1,125 readmissions were recorded. The hemoconcentration group had a lower risk of mortality or readmission for any cause (RR=0.75, 95% CI: 0.51-1.09 and RR=0.86, 95% CI: 0.70-1.05), although statistical significance was lost after multivariate analysis, while it was retained for other factors with recognized negative impact on the prognosis of patients with HF, such as age and functional class. Conclusions: the degree of hemoconcentration at 3 months after admission for HF is not prognostic of readmission or death in the subsequent year

Hemoconcentration as a prognostic factor after hospital discharge in acute heart failure in the RICA registry. / Hemoconcentración como predictor de supervivencia al año de ingreso por insuficiencia cardiaca aguda en el registro RICA.

OBJECTIVE: Several studies have reported that a higher degree of hemoconcentration in patients admitted for the treatment of acute heart failure (HF) constitutes a favorable prognostic factor in the year following the index episode. The objective of this study was to evaluate whether the highest degree of hemoconcentration at 3 months after admission for HF is also a prognostic factor for mortality and/or readmission in the 12 months after admission. PATIENTS AND METHOD: The hemoconcentration group was the upper quartile of the sample distributed according to hemoglobin increase at month 3 after discharge with respect to hemoglobin at the time of admission for HF in a multicenter prospective cohort of 1,659 subjects with HF. RESULTS: The mean follow-up until the first event was 294 days, and a total of 487 deaths and 1,125 readmissions were recorded. The hemoconcentration group had a lower risk of mortality or readmission for any cause (RR=0.75, 95% CI: 0.51-1.09 and RR=0.86, 95% CI: 0.70-1.05), although statistical significance was lost after multivariate analysis, while it was retained for other factors with recognized negative impact on the prognosis of patients with HF, such as age and functional class. CONCLUSIONS: The degree of hemoconcentration at 3 months after admission for HF is not prognostic of readmission or death in the subsequent year.

Does mercury presence in soils promote their microbial activity? The Almadenejos case (Almadén mercury mining district, Spain).

Mercury is considered a very toxic element and important efforts are currently being made aimed at reduce or even eliminating its usage. Despite this trend, there are still sites where contamination by this metal is very marked, especially in the mining environment of Almadén where it has been exploited for thousands of years. The several forms in which Hg occurs in the soil interact differently with the organisms that live in/on it. The soil is a place where many biotic and abiotic variables act together. Through a detailed study of the edaphic characteristics of a decommissioned metallurgical enclosure, the presence of different chemical forms of Hg, the study of microbial activity (DHA) and, finally, parameters of the vegetation cover, such as specific distribution and biomass, we have tried to elucidate the effect of the presence of Hg in this precinct with a very high Hg pollution. The obtained results showed the affection patterns by which the different measured parameters vary, with special incidence to the microbial activity of the topsoil and to the specific distribution of the plants found in the studied area. The statistical multivariate analysis showed that significant correlations have been found between soil Hg fractions and between Hg fractions in plants; furthermore, soil conditions seem to be not related with Hg transfer from soils to plants. Biomass and DHA data indicate that the studied area is not affected by the presence of Hg species and lacks the expected toxic effects on the living organisms.

Corrigendum: Clinical and Molecular Heterogeneity of RTEL1 Deficiency.

[This corrects the article on p. 449 in vol. 8, PMID: 28507545.].

Clinical and Molecular Heterogeneity of RTEL1 Deficiency.

Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p.Trp456Cys, p.Ile425Thr, p.Cys1244ProfsX17, p.Pro884_Gln885ins53X13, and one with novel heterozygous mutation p.Val796AlafsX4. The most unifying features were hypocellular BMF in 6/6 and B-/NK-cell lymphopenia in 5/6 patients. In addition, three patients with homozygous mutations p.Trp456Cys or p.Ile425Thr also suffered from immunodeficiency, cerebellar hypoplasia, and enteropathy, consistent with Hoyeraal-Hreidarsson syndrome. Chromosomal breakage resembling a homologous recombination defect was detected in patient-derived fibroblasts but not in hematopoietic compartment. Notably, in both cellular compartments, differential expression of 1243aa and 1219/1300aa RTEL1 isoforms was observed. In fibroblasts, response to ionizing irradiation and non-homologous end joining were not impaired. Telomeric circles did not accumulate in patient-derived primary cells and lymphoblastoid cell lines, implying alternative pathomechanisms for telomeric loss. Overall, RTEL1-deficient cells exhibited a phenotype of replicative exhaustion, spontaneous apoptosis and senescence. Specifically, CD34+ cells failed to expand in vitro, B-cell development was compromised, and T-cells did not proliferate in long-term culture. Finally, we report on the natural history and outcome of our patients. While two patients died from infections, hematopoietic stem cell transplantation (HSCT) resulted in sustained engraftment in two patients. Whether chemotherapy negatively impacts on the course and onset of other DC-related symptoms remains open at present. Early-onset lung disease occurred in one of our patients after HSCT. In conclusion, RTEL deficiency can show a heterogeneous clinical picture ranging from mild hypocellular BMF with B/NK cell lymphopenia to early-onset, very severe, and rapidly progressing cellular deficiency.

Documento de consenso de la Sociedad Española de Cardiología y la Sociedad Española de Medicina Interna sobre el diagnóstico y tratamiento del déficit de hierro en la insuficiencia cardíaca / Consensus Document of the Spanish Society of Cardiology and the Spanish Society of Internal Medicine on the diagnosis and treatment of iron deficiency in heart failure

El déficit de hierro en los pacientes con insuficiencia cardiaca es un problema médico que últimamente suscita un interés particular. Esto se debe a la publicación de varios ensayos clínicos que demuestran que la administración de hierro intravenoso en estos pacientes mejora su capacidad funcional, e incluso reduce los ingresos por descompensación de insuficiencia cardiaca. Sin embargo, la aplicación de la evidencia aportada por estos estudios en la práctica clínica es aún controvertida, tanto en los criterios diagnósticos del déficit de hierro, absoluto y funcional, como en la forma óptima de reposición del hierro. Este artículo es un documento de consenso que integra las recomendaciones de las Sociedades Españolas de Medicina Interna y Cardiología en el que se revisa la evidencia científica y se propone un protocolo de actuación diagnóstica y terapéutica del déficit de hierro en la insuficiencia cardiaca (AU)

Iron deficiency in patients with heart failure is a medical problem of recent particular interest. This interest has resulted from the publication of several clinical trials that demonstrated that the administration of intravenous iron to such patients improved their functional capacity and even reduced the number of hospitalisations for heart failure decompensation. However, applying the evidence from these studies in clinical practice is still controversial, both in terms of the diagnostic criteria for iron deficiency (absolute and functional) and the optimal method for iron replenishment. This article is a consensus document that integrates the recommendations of the Spanish Society of Internal Medicine and the Spanish Society of Cardiology. The article reviews the scientific evidence and proposes a diagnostic and therapeutic performance protocol for iron deficiency in heart failure (AU)

Consensus Document of the Spanish Society of Cardiology and the Spanish Society of Internal Medicine on the diagnosis and treatment of iron deficiency in heart failure. / Documento de consenso de la Sociedad Española de Cardiología y la Sociedad Española de Medicina Interna sobre el diagnóstico y tratamiento del déficit de hierro en la insuficiencia cardíaca.

Iron deficiency in patients with heart failure is a medical problem of recent particular interest. This interest has resulted from the publication of several clinical trials that demonstrated that the administration of intravenous iron to such patients improved their functional capacity and even reduced the number of hospitalisations for heart failure decompensation. However, applying the evidence from these studies in clinical practice is still controversial, both in terms of the diagnostic criteria for iron deficiency (absolute and functional) and the optimal method for iron replenishment. This article is a consensus document that integrates the recommendations of the Spanish Society of Internal Medicine and the Spanish Society of Cardiology. The article reviews the scientific evidence and proposes a diagnostic and therapeutic performance protocol for iron deficiency in heart failure.

Environmental assessment of potential toxic trace element contents in the inundated floodplain area of Tablas de Daimiel wetland (Spain).

Contamination of aquatic systems with potentially toxic trace elements (PTEs) is a major problem throughout the world. The National Park Tablas de Daimiel (NPTD) is considered to make up one of the two most important wetlands in the Biosphere Reserve called "Wet Spot." Since PTEs are good indicator of the prevailing environmental conditions and possible contamination, soil samples collected from 43 sites were analyzed in order to investigate the levels and its distribution of these elements, in the inundated floodplain area of the NPTD wetland. In addition, some physicochemical parameters such as pH, electrical conductivity and organic matter were measured. The total concentrations of 32 trace elements were determined by X-ray fluorescence. The results show that there was accumulation of lead (Pb), tin (Sn), selenium (Se), antimony (Sb), copper (Cu), vanadium (V), nickel (Ni), zinc (Zn), arsenic (As), strontium (Sr) and zirconium (Zr)-in some cases at high concentrations. The interpolated maps showed that the distributions of some of these elements and in some cases the trend in spatial variability are pronounced and decrease from the inlet to the outlet. The values for some elements are higher than the reference values, which is consistent with contamination (some values are higher by a factor of more than 10 compared to the reference). In the case of iodine (I), the levels at some sample points are significantly more than ten times the reference; Se appears in the range from 1.0 to 9.8 mg/kg, with an average value of 3.1 mg/kg, and these can be considered as seleniferous soils. The concentrations found are consistent with the introduction in the wetland of pollution by human activities, such as agricultural non-point sources, uncontrolled fertilization over many years, treatment with urban wastewater and other possible sources.

Fluorination of an antiepileptic drug: A self supporting transporter by oxygen enrichment mechanism.

Drug therapy of seizures involves producing high levels of antiepileptic drugs in the blood. Drug must enter the brain by crossing from the blood into the brain tissue, called a transvascular route (TVR). Even before the drug can reach the brain tissue, factors such as systemic toxicity, macrophage phagocytises and reduction in oxygen content limit the success of this TVR. Encapsulating the drug within a nano scale delivering system, synthesising drugs with low molecular weight are the best mechanisms to deliver the drug to the brain. But through this article, we have explored a possibility of attaching a molecule 4-(trifluoromethyl) benzoic acid (TFMBA), that possess more number of fluorine atom, to benzodiazepine (BDZ) resulting in an ionic salt (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine5,11(10H,11aH)-dione with 4-(trifluoromethyl)benzoic acid. By this way, reducing the toxicity of BDZ than the conventional anti-epileptic drugs (AEDs), increasing the solubility, reducing the melting point, enriching the TVR with excess oxygen content with the support of fluorine. With all these important prerequisites fulfilled, the drug along with the attached molecule is expected to travel more comfortably through the TVR without any external support than any other conventional AEDs. FTIR, (1)H NMR, (13)C NMR, HRMS spectroscopy, HRTEM and In vitro cytotoxicity analysis supports this study.