An integrated approach for the efficient separation of specialty compounds from biomass of the marine microalgae Amphidinium carterae.

An amphidinol-prioritized fractioning approach was for the first time developed to isolate multiple specialty metabolites such as amphidinols, carotenoids and fatty acids using the biomass of the marine microalgae Amphidinium carterae. The biomass was produced in a raceway photobioreactor and the exhausted culture media were reused, thus fulfilling sustainability criteria employing a circular economy concept. The integrated bioactive compounds-targeted approach presented here consisted of four steps with which recovery percentages of carotenoids, fatty acids and amphidinols of 97%, 82% and 99 %, respectively, were achieved. The proposed process was proved to be a better extraction system for this microalga than another based on a sequential gradient partition with water and four water-immiscible organic solvents (hexane, carbon tetrachloride, dichloromethane and n-butanol). The proposed process could be scaled-up as a commercial solid-phase extraction technology well-established for industrial bioprocesses.

Improved extraction of bioactive compounds from biomass of the marine dinoflagellate microalga Amphidinium carterae.

The extraction of three families of compounds (carotenoids, fatty acids and amphidinols) from the biomass of two strains of Amphidinium carterae (ACRN03 and Dn241EHU) was improved by tuning cell disruption and solvent extraction operations. The extraction of carotenoids was evaluated using alkaline saponification (0%-60% KOH d.w.) at different temperatures (25-80 °C). High levels of carotenoids were obtained at 60 °C using freeze-dried biomass, not subjected to cell disruption methods. The ACRN03 strain required 20% KOH whereas the Dn241EHU strain did not require saponification since carotenoid degradation was observed. The extraction efficiencies were determined with a wide range of pure solvents and mixtures thereof. Two empirical non-linear equations were used to correlate extraction percentages for each family of compounds with the Hildebrand solubility parameter (δT) and the polarity index of the solvents (PI). Thresholds of δT and PI of around 20 MPa1/2 and 6, respectively, were determined for the extraction of amphidinols, consistent with antiproliferative activity measurements.

Assessment of multi-step processes for an integral use of the biomass of the marine microalga Amphidinium carterae.

Sustainable dinoflagellate microalgae-based bioprocess designed to produce secondary metabolites (SMs) with interesting bioactivities are attracting increasing attention. However, dinoflagellates also produce other valuable bioproducts (e.g polyunsaturated fatty acids, carotenoids, etc.) that could be recovered and should therefore be taken into account in the bioprocess. In this study, biomass of the marine dinoflagellate microalga Amphidinium carterae was used to assess and optimise three different methods in order to obtain three families of high-value biochemical compounds present in the biomass. The existing processes encompassed a multi-step extraction process for carotenoids, fatty acids and APDs individually and are optimized for the integral valorization of raw A. carterae biomass, with SMs being the primary target compounds. Total process recovery yields were 97% for carotenoids, 80% for total fatty acids and 100% for an extract rich in APDs (not purified).

Registro informatizado de la telangiectasia hemorrágica hereditaria (Registro RiHHTa) en España: objetivos, métodos y resultados preliminares / Computerized registry of patients with hemorrhagic hereditary telangiectasia (RiHHTa Registry) in Spain: Objectives, methods, and preliminary results

Introducción: La telangiectasia hemorrágica hereditaria (HHT, por sus siglas en inglés) es una enfermedad minoritaria con herencia autosómica dominante que provoca una afectación vascular sistémica. Material y método: Tras la elaboración de un registro nacional español multicéntrico, denominado RiHHTa, se describen las principales manifestaciones clínicas y procedimientos diagnósticos de los primeros pacientes introducidos. Resultados: Se han introducido datos de 141 pacientes, de los que 91 (64,5%) eran mujeres. La edad media al diagnóstico fue de 42 años. Las mutaciones en el gen ACVRL1 predominaron sobre el gen ENG. El síntoma inicial fue la epistaxis recurrente en 130 (92,2%) pacientes y en 3 (2,1%), el absceso cerebral. Se detectaron fístulas arteriovenosas (AV) pulmonares en 36 (45%) de los 79 pacientes a los que se les practicó una angio-TC torácica. En 36 (45%) de estos 79 afectados no se había detectado paso de contraste en la ecocardiografía o este era grado 1. En 43 (67,2%) de los 64 pacientes con una angio-TC abdominal se detectaron malformaciones vasculares hepáticas, mayoritariamente telangiectasias, fístulas AV y arterio-portales, y extrahepáticas en 14 (10%) sujetos. Se realizó cribado de malformación AV cerebral a más de la mitad de los pacientes, detectándose en un 3,9%. La parte del tubo digestivo más afectada fue la superior (95%). Conclusión: El Registro RiHHTa permite identificar puntos de mejora en el manejo de los pacientes con HHT. Se ha detectado un uso inadecuado de la angio-TC torácica y la utilidad de la angio-TC abdominal para definir los subtipos de afectación vascular hepática y detectar afectación vascular extrahepática

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is a rare disease with autosomal dominant inheritance that causes systemic vascular affectation. Material and method: After development a multicentric Spanish national registry, called RiHHTa, main clinical manifestations and diagnostic procedures of the first patients introduced are described. Results: 141 patients were included, of which 91 (64.5%) were women. The mean age at diagnosis was 42 years. Mutations in the ACVRL1 gene predominated over the ENG gene. The initial symptom was recurrent epistaxis in 130 (92.2%) patients and in three (2.1%), brain abscess. Pulmonary arteriovenous (AV) fistula were detected in 36 (45%) of the 79 patients who underwent thoracic CT angiography. The contrast echocardiography detected very few bubbles (grade I) or none, in 36 (45%) of these 79 affected patients. In 43 (67.2%) of the 64 patients with an abdominal CT angiography, hepatic vascular malformations were detected, mostly telangiectasias, AV and arterio-portal fistula, and extrahepatic in 14 (10%) subjects. More than half of the patients were screened for the presence of brain arteriovenous malformations which was found in 3.9% of them. The upper part of the intestinal tube was the most (95%) affected region. Conclusion: The RiHHTa Registry allows improving the management of patients with HHT. An inadequate use of thoracic CT angiography and the usefulness of abdominal CT angiography has been detected in order to define subtypes of hepatic vascular involvement and detect extrahepatic vascular involvement

Tratamiento en la enfermedad de Fabry / Treatment in Fabry disease

La enfermedad de Fabry es una enfermedad ligada al cromosomaX causada por un déficit de alfa-galactosidasaA. Esto da como resultado la acumulación de glicoesfingolípidos en todas las células y tejidos. Todos los varones deben tratarse con reemplazo enzimático en caso de presentar niveles muy bajos o indetectables de alfa-galactosidasaA. Las mujeres portadoras y los varones con niveles mínimos de alfa-galactosidasaA deben tratarse si existe afectación renal, neurológica o cardíaca. Para terapia de reemplazo enzimático existen dos formulaciones intravenosas, agalsidasa alfa y agalsidasa beta, que muestran una eficacia y seguridad similares. Los pacientes con mutaciones susceptibles del gen alfa-galactosidasaA pueden tratarse con migalastat oral. El migalastat es una molécula que facilita el paso de alfa-galactosidasaA a los lisosomas, produciendo aumento de actividad del enzima. Los pacientes tratados con migalastat muestran mejoras significativas en la masa del ventrículo izquierdo y en los síntomas gastrointestinales

Fabry disease is an X-linked inborn disease caused by deficit of alpha-galactosidaseA. This results in accumulation of glycosphingolipids in all cells and tissues. All males should receive enzyme replacement treatment in case of very low or undetectable levels of alpha-galactosidaseA. Female carriers and males with marginally levels of alpha-galactosidaseA should be treated in case of renal, neurologic o cardiac manifestations. There are two intravenous formulations of human recombinant enzyme, agalsidase alpha and agalsidase beta, showing similar efficacy and safety. Patients with amenable mutations of alpha-galactosidase can be treated with oral migalastat hydrochloride. Migalastat hydrochloride is a pharmacological chaperone that facilitates trafficking of alpha-galactosidaseA to lysosomes increasing enzyme activity. Patients treated with migalastat hydrochloride had significant improvements in left ventricular mass and gastrointestinal symptoms

Computerized registry of patients with hemorrhagic hereditary telangiectasia (RiHHTa Registry) in Spain: Objectives, methods, and preliminary results. / Registro informatizado de la telangiectasia hemorrágica hereditaria (Registro RiHHTa) en España: objetivos, métodos y resultados preliminares.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is a rare disease with autosomal dominant inheritance that causes systemic vascular affectation. MATERIAL AND METHOD: After development a multicentric Spanish national registry, called RiHHTa, main clinical manifestations and diagnostic procedures of the first patients introduced are described. RESULTS: 141 patients were included, of which 91 (64.5%) were women. The mean age at diagnosis was 42 years. Mutations in the ACVRL1 gene predominated over the ENG gene. The initial symptom was recurrent epistaxis in 130 (92.2%) patients and in three (2.1%), brain abscess. Pulmonary arteriovenous (AV) fistula were detected in 36 (45%) of the 79 patients who underwent thoracic CT angiography. The contrast echocardiography detected very few bubbles (grade I) or none, in 36 (45%) of these 79 affected patients. In 43 (67.2%) of the 64 patients with an abdominal CT angiography, hepatic vascular malformations were detected, mostly telangiectasias, AV and arterio-portal fistula, and extrahepatic in 14 (10%) subjects. More than half of the patients were screened for the presence of brain arteriovenous malformations which was found in 3.9% of them. The upper part of the intestinal tube was the most (95%) affected region. CONCLUSION: The RiHHTa Registry allows improving the management of patients with HHT. An inadequate use of thoracic CT angiography and the usefulness of abdominal CT angiography has been detected in order to define subtypes of hepatic vascular involvement and detect extrahepatic vascular involvement.

Treatment in Fabry disease. / Tratamiento en la enfermedad de Fabry.

Fabry disease is an X-linked inborn disease caused by deficit of alpha-galactosidaseA. This results in accumulation of glycosphingolipids in all cells and tissues. All males should receive enzyme replacement treatment in case of very low or undetectable levels of alpha-galactosidaseA. Female carriers and males with marginally levels of alpha-galactosidaseA should be treated in case of renal, neurologic o cardiac manifestations. There are two intravenous formulations of human recombinant enzyme, agalsidase alpha and agalsidase beta, showing similar efficacy and safety. Patients with amenable mutations of alpha-galactosidase can be treated with oral migalastat hydrochloride. Migalastat hydrochloride is a pharmacological chaperone that facilitates trafficking of alpha-galactosidaseA to lysosomes increasing enzyme activity. Patients treated with migalastat hydrochloride had significant improvements in left ventricular mass and gastrointestinal symptoms.

Transición desde la asistencia pediátrica a la adulta en pacientes con mucopolisacaridosis / Transition from paediatric care to adult care for patients with mucopolysaccharidosis

Las mucopolisacaridosis son enfermedades multisistémicas que requieren para su atención equipos multidisciplinares amplios. Por ello se hacen necesarias recomendaciones específicas para la transición de la edad pediátrica a la adulta en este grupo de pacientes. Para la superación de las barreras que pudieran surgir durante la transición, los autores consideran esencial realizar un plan flexible con un coordinador de todo el proceso, sistematizar la información a través de un informe de alta pediátrico estandarizado, formar al paciente y su familia sobre la enfermedad y mostrar las características del sistema sanitario en esta nueva etapa. El objetivo final es que al concluir la transición a la edad adulta se haya maximizado la autonomía y el potencial de desarrollo del paciente y este reciba una atención sanitaria adecuada durante dicho periodo de transición (AU)

Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition (AU)

Transition from paediatric care to adult care for patients with mucopolysaccharidosis. / Transición desde la asistencia pediátrica a la adulta en pacientes con mucopolisacaridosis.

Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition.

Exploring Institutional Mechanisms for Scientific Input into the Management Cycle of the National Protected Area Network of Peru: Gaps and Opportunities.

Understanding how to improve decision makers' use of scientific information across their different scales of management is a core challenge for narrowing the gap between science and conservation practice. Here, we present a study conducted in collaboration with decision makers that aims to explore the functionality of the mechanisms for scientific input within the institutional setting of the National Protected Area Network of Peru. First, we analyzed institutional mechanisms to assess the scientific information recorded by decision makers. Second, we developed two workshops involving scientists, decision makers and social actors to identify barriers to evidence-based conservation practice. Third, we administered 482 questionnaires to stakeholders to explore social perceptions of the role of science and the willingness to collaborate in the governance of protected areas. The results revealed that (1) the institutional mechanisms did not effectively promote the compilation and application of scientific knowledge for conservation practice; (2) six important barriers hindered scientific input in management decisions; and (3) stakeholders showed positive perceptions about the involvement of scientists in protected areas and expressed their willingness to collaborate in conservation practice. This collaborative research helped to (1) identify gaps and opportunities that should be addressed for increasing the effectiveness of the institutional mechanisms and (2) support institutional changes integrating science-based strategies for strengthening scientific input in decision-making. These insights provide a useful contextual orientation for scholars and decision makers interested in conducting empirical research to connect scientific inputs with operational aspects of the management cycle in other institutional settings around the world.

Clinical characteristics of adult patients with inborn errors of metabolism in Spain: A review of 500 cases from university hospitals.

Patients with inborn errors of metabolism (IEMs) have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification. The most prevalent group of IEMs was amino acid disorders, with 108 (21.6%) patients diagnosed with phenylketonuria. Lysosomal storage disorders were the second group, in which 32 (6.4%) and 25 (5%) patients had Fabry disease and Gaucher disease respectively. The great clinical heterogeneity, the significant delay in diagnosis after symptom onset, the existence of some degree of physical dependence in a great number of patients, the need for a multidisciplinary and coordinated approach, and the lack of specific drug treatment are common features in this group of conditions.

Acute and chronic effects of magnetic microparticles potentially used in lake restoration on Daphnia magna and Chironomus sp.

Magnetic microparticles (MPs) have been recently proposed as a new and promising tool for restoring eutrophicated waters. In this study, we analyzed the acute (immobilization) and chronic effects of iron (Fe) MPs on Daphnia magna and on the benthic macroinvertebrate Chironomus sp. In the chronic toxicity tests the offspring production (male and female) in D. magna and the mortality of larvae and pupae, and adult emergence in Chironomus sp. experiments were used as the endpoints. The concentration of MPs that caused 50% of immobilized individuals (EC50) in the acute toxicity test was much higher in D. magna (0.913g MPs l-1) than in Chironomus sp. (0.445g MPs l-1). The results of chronic toxicity tests in D. magna showed that in presence of dissolved Fe (dFe), parthenogenetic reproduction was significantly affected, while no significant effect on mortality of larvae and pupae and on adult emergence was detected in Chironomus sp. test. Taking into account both that long-term exposure is not likely to occur and the regular dose of MPs potentially used in a restoration plan, we conclude that MPs is a riskless (no toxic effect on planktonic and benthic organisms) and efficient (high P adsorption capacity) tool for lake restoration.

IFITM3 and severe influenza virus infection. No evidence of genetic association.

Influenza virus infection (IVI) is typically subclinical or causes a self-limiting upper respiratory disease. However, in a small subset of patients IVI rapidly progresses to primary viral pneumonia (PVP) with respiratory failure; a minority of patients require intensive care unit admission. Inherited and acquired variability in host immune responses may influence susceptibility and outcome of IVI. However, the molecular basis of such human factors remains largely elusive. It has been proposed that homozygosity for IFITM3 rs12252-C is associated with a population-attributable risk of 5.4 % for severe IVI in Northern Europeans and 54.3 % for severe H1N1pdm infection in Chinese. A total of 148 patients with confirmed IVI were considered for recruitment; 118 Spanish patients (60 of them hospitalized with PVP) and 246 healthy Spanish individuals were finally included in the statistical analysis. PCR-RFLP was used with confirmation by Sanger sequencing. The allele frequency for rs12252-C was found to be 3.5 % among the general Spanish population. We found no rs12252-C homozygous individuals in our control group. The only Spanish patient homozygous for rs12252-C had a neurological disorder (a known risk factor for severe IVI) and mild influenza. Our data do not suggest a role of rs12252-C in the development of severe IVI in our population. These data may be relevant to recognize whether patients homozygous for rs12252-C are at risk of severe influenza, and hence require individualized measures in the case of IVI.

Subaerial biofilms on granitic historic buildings: microbial diversity and development of phototrophic multi-species cultures.

Microbial communities of natural subaerial biofilms developed on granitic historic buildings of a World Heritage Site (Santiago de Compostela, NW Spain) were characterized and cultured in liquid BG11 medium. Environmental barcoding through next-generation sequencing (Pacific Biosciences) revealed that the biofilms were mainly composed of species of Chlorophyta (green algae) and Ascomycota (fungi) commonly associated with rock substrata. Richness and diversity were higher for the fungal than for the algal assemblages and fungi showed higher heterogeneity among samples. Cultures derived from natural biofilms showed the establishment of stable microbial communities mainly composed of Chlorophyta and Cyanobacteria. Although most taxa found in these cultures were not common in the original biofilms, they are likely common pioneer colonizers of building stone surfaces, including granite. Stable phototrophic multi-species cultures of known microbial diversity were thus obtained and their reliability to emulate natural colonization on granite should be confirmed in further experiments.

Sesquiterpenes, flavonoids, shikimic acid derivatives and pyrrolizidine alkaloids from Senecio kingii Hook.

Twenty-four compounds including eleven eremophilanolides (1-11), one eremophilane (13), five shikimic acid derivatives (14-18), six flavonoids (19-24), and the macrocyclic unsaturated pyrrolizidine alkaloid integerrimine (25) were isolated from Senecio kingii, an endemic species from the Magallanes Region (Chile). Compounds 3, 5, 6, 8-11 and 13-18 have not been previously reported as natural products. Their molecular structures were determined by NMR spectroscopic analysis and comparison with published NMR data. An X-ray-analysis of compound 3 has been performed. Their insecticidal and antifungal activities were tested, being compound 3 the strongest insect antifeedant. Compounds 6, 9 and 18 were moderate antifungals.

Physiological strategies contributing to the coexistence of two predatory species of stoneflies: Dinocras cephalotes and Perla bipunctata.

Our study focuses on the oxidative state of two aquatic insects of the order Plecoptera belonging to the family Perlidae, namely Dinocras cephalotes (Curtis, 1827) and Perla bipunctata Pictet, 1833. These species are widely distributed throughout the Western Palearctic region and coexist in the stream where individuals for this study come from. We highlight the physiological strategies of these two different predator species of stoneflies, showing a higher accumulation of lipid reserves in P. bipunctata, higher glucose levels in the body tissues of D. cephalotes and a higher capacity of the antioxidant enzymes in P. bipunctata, what provides it a protection against oxidation of lipids, which are greater in this species. This leads to a similar oxidative state in both species. Based on these results is discussed how two close related species developing a very similar ecological role in the same habitat can achieve a similar fitness with differences in their physiological strategies.

Tratamiento de espasmos musculares en el paciente con ataxia de Friedreich con bomba de infusión intratecal de baclofeno: a propósito de un caso / No disponible

No disponible

Interaction between PARP-1 and HIF-2α in the hypoxic response.

Hypoxia-inducible factors (HIFs) mediate the transcriptional adaptation of hypoxic cells. The extensive transcriptional programm regulated by HIFs involves the induction of genes controlling angiogenesis, cellular metabolism, cell growth, metastasis, apoptosis, extracellular matrix remodeling and others. HIF is a heterodimer of HIF-α and HIF-ß subunits. In addition to HIF-1α, HIF-2α has evolved as an isoform that contributes differently to the hypoxic adaptation by performing non-redundant functions. Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein involved in the control of DNA repair and gene transcription by modulating chromatin structure and acting as part of gene-specific enhancer/promoter-binding complexes. Previous results have shown that PARP-1 regulates HIF-1 activity. In this study, we focused on the cross-talk between HIF-2α and PARP-1. By using different approaches to suppress PARP-1, we show that HIF-2α mRNA expression, protein levels and HIF-2-dependent gene expression, such as ANGPTL4 and erythropoietin (EPO), are regulated by PARP-1. This regulation occurs at both the transcriptional and post-trancriptional level. We also show a complex formation between HIF-2α with PARP-1. This complex is sensitive to PARP inhibition and seems to protect against the von Hippel-Lindau-dependent HIF-2α degradation. Finally, we show that parp-1(-/-) mice display a significant reduction in the circulating hypoxia-induced EPO levels, number of red cells and hemoglobin concentration. Altogether, these results reveal a complex functional interaction between PARP-1 and the HIF system and suggest that PARP-1 is involved in the fine tuning of the HIF-mediated hypoxic response in vivo.

Relationship between brain and liver oxidative state and maximum lifespan potential of different fish species.

The aim of the present study is to determine whether a relationship exists between the maximum lifespan potential (MLSP) of different fish species (Squalius pyrenaicus, Cyprinus carpio, Carassius auratus, Luciobarbus sclateri and Oncorhynchus mykiss) and the oxidative state of brain and liver. For this purpose, the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferase (GST) and DT-diaphorase (NAD(P)H:quinone oxidoreductase1) were measured together with the lipid peroxidation degree (malondialdehyde, MDA) in liver and brain tissues of the collected species. Only the brain tissue manifested a higher activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase in addition to a negative correlation between the values of MDA and MLSP among the different fish species. Hypotheses are proposed from the analysis of the obtained results that open new areas of research and converge on the importance of the theory of free radicals in the processes that condition the maximum life expectancy of an animal species.

Indole alkaloids from Geissospermum reticulatum.

Ten indole alkaloids were isolated from Geissospermum reticulatum, seven (1-7) from the leaves and three (8-10) from the bark. Seven were aspidospermatan-type alkaloids (1-3, 5-9), including four (5-8) with a 1-oxa-3-cyclopentene group in their molecule, which we named geissospermidine subtype. Compounds 1-3, 5-8, and 10 had not been reported previously as natural products, while 4 and 9 were the known alkaloids O-demethylaspidospermine and flavopereirine. Their structures were determined by spectroscopic techniques including 1D and 2D NMR experiments (COSY, NOESY, HSQC, HMBC). Additionally, X-ray crystallographic analyses of 1, 2, and 6 were performed. Antiparasitic activities of the ethanolic and alkaloidal extracts and of the pure alkaloids were tested against Trypanosoma cruzi and Leishmania infantum. In general, the extracts exhibited selective action and were more active against Leishmania than against Trypanosoma. Alkaloid 4 was also very active against L. infantum.