Neurocognitive correlates of semantic memory navigation in Parkinson's disease.

Cognitive studies on Parkinson's disease (PD) reveal abnormal semantic processing. Most research, however, fails to indicate which conceptual properties are most affected and capture patients' neurocognitive profiles. Here, we asked persons with PD, healthy controls, and individuals with behavioral variant frontotemporal dementia (bvFTD, as a disease control group) to read concepts (e.g., 'sun') and list their features (e.g., hot). Responses were analyzed in terms of ten word properties (including concreteness, imageability, and semantic variability), used for group-level comparisons, subject-level classification, and brain-behavior correlations. PD (but not bvFTD) patients produced more concrete and imageable words than controls, both patterns being associated with overall cognitive status. PD and bvFTD patients showed reduced semantic variability, an anomaly which predicted semantic inhibition outcomes. Word-property patterns robustly classified PD (but not bvFTD) patients and correlated with disease-specific hypoconnectivity along the sensorimotor and salience networks. Fine-grained semantic assessments, then, can reveal distinct neurocognitive signatures of PD.

Trombosis venosa y de senos cerebrales en recién nacidos y niños / Venous and cerebral sinus thrombosis in newborns and children

Resumen Introducción : La trombosis de venas y senos venosos cerebrales (TVSC) constituye una causa conocida, aun que subestimada de ictus en la infancia. Su diagnóstico requiere un alto índice de sospecha, una correcta in terpretación de la neuroimagen e interrelación entre el clínico y el radiólogo. Objetivo : Analizar las manifestaciones clínicas, fac tores de riesgo y neuroimagen de recién nacidos (RN) y niños menores de 15 años con TVSC. Métodos: Estudio descriptivo, retrospectivo, multi céntrico, de una serie consecutiva de casos de menores de 15 años que ingresaron por TVSC entre el 1 de enero del 2010 y el 1 de marzo de 2022. Resultados : El estudio incluyó 51 pacientes: 39% con síntomas agudos y 59% subagudos. En los RN predomi naron síntomas encefalopáticos y convulsiones, mien tras en los niños elementos de hipertensión endocranea na (HTEC). Se identificaron factores de riesgo en el 90% de los casos. La resonancia magnética con angiografía en tiempo venoso confirmó el diagnóstico en el 80%, siendo el seno recto el más afectado en RN y el seno lateral en niños. Se encontraron complicaciones hemorrágicas en 30.5%, siendo más frecuentes en los RN. Se inició anti coagulación en el 82% sin complicaciones. Las secuelas estuvieron presentes en 44.4% de RN y 37.9% de niños, siendo más frecuentes y graves en los RN. Conclusiones : Para realizar un diagnóstico precoz es fundamental pensar en TVSC en RN con síntomas en cefalopáticos y/o convulsiones y en mayores con clínica de HTEC en presencia de enfermedades predisponentes o desencadenantes.

Abstract Introduction : Cerebral venous sinus thrombosis (CVST) is a well-known, although underestimated, cause of stroke in childhood. Its diagnosis requires a high index of suspicion, a correct interpretation of neuroim aging studies and an interrelation between clinicians and radiologists. The clinical features, risk factors and neuroimaging of children under 15 years of age with CVST were analyzed. Methods : multicenter, retrospective, descriptive, study of a consecutive series of cases of children under 15 years of age, who were admitted due to CVST between January 1st, 2010, and March 1st, 2022. Results : The study included 51 patients: 39% with acute symptoms and 59% with subacute symptoms. Newborns predominantly presented encephalopathic symptoms and seizures, while children exhibited signs of intracranial hypertension (ICH). Risk factors were 96 identified in 90% of the cases. Magnetic resonance with angiography in venous time confirmed the diagnosis in 80% of the patients, with the straight sinus being the most affected in newborns and the lateral sinus in chil dren. Hemorrhagic complications were found in 30.5%, being more frequent in newborns. Anticoagulation was initiated in 82% without complications. Sequelae were present in 44.4% of newborns and 37.9% of children, being more frequent and severe in newborns. Conclusions : To make an early diagnosis, it is essen tial to consider CVST in newborns with encephalopathic symptoms and/or seizures, and in children with signs of ICH in the presence of predisposing or triggering conditions.

[Venous and cerebral sinus thrombosis in newborns and children]. / Trombosis venosa y de senos cerebrales en recién nacidos y niños.

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) is a well-known, although underestimated, cause of stroke in childhood. Its diagnosis requires a high index of suspicion, a correct interpretation of neuroimaging studies and an interrelation between clinicians and radiologists. The clinical features, risk factors and neuroimaging of children under 15 years of age with CVST were analyzed. METHODS: multicenter, retrospective, descriptive, study of a consecutive series of cases of children under 15 years of age, who were admitted due to CVST between January 1st, 2010, and March 1st, 2022. RESULTS: The study included 51 patients: 39% with acute symptoms and 59% with subacute symptoms. Newborns predominantly presented encephalopathic symptoms and seizures, while children exhibited signs of intracranial hypertension (ICH). Risk factors were identified in 90% of the cases. Magnetic resonance with angiography in venous time confirmed the diagnosis in 80% of the patients, with the straight sinus being the most affected in newborns and the lateral sinus in children. Hemorrhagic complications were found in 30.5%, being more frequent in newborns. Anticoagulation was initiated in 82% without complications. Sequelae were present in 44.4% of newborns and 37.9% of children, being more frequent and severe in newborns. CONCLUSIONS: To make an early diagnosis, it is essential to consider CVST in newborns with encephalopathic symptoms and/or seizures, and in children with signs of ICH in the presence of predisposing or triggering conditions.

Introducción: La trombosis de venas y senos venosos cerebrales (TVSC) constituye una causa conocida, aunque subestimada de ictus en la infancia. Su diagnóstico requiere un alto índice de sospecha, una correcta interpretación de la neuroimagen e interrelación entre el clínico y el radiólogo. OBJETIVO: Analizar las manifestaciones clínicas, factores de riesgo y neuroimagen de recién nacidos (RN) y niños menores de 15 años con TVSC. Métodos: Estudio descriptivo, retrospectivo, multicéntrico, de una serie consecutiva de casos de menores de 15 años que ingresaron por TVSC entre el 1 de enero del 2010 y el 1 de marzo de 2022. RESULTADOS: El estudio incluyó 51 pacientes: 39% con síntomas agudos y 59% subagudos. En los RN predominaron síntomas encefalopáticos y convulsiones, mientras en los niños elementos de hipertensión endocraneana (HTEC). Se identificaron factores de riesgo en el 90% de los casos. La resonancia magnética con angiografía en tiempo venoso confirmó el diagnóstico en el 80%, siendo el seno recto el más afectado en RN y el seno lateral en niños. Se encontraron complicaciones hemorrágicas en 30.5%, siendo más frecuentes en los RN. Se inició anticoagulación en el 82% sin complicaciones. Las secuelas estuvieron presentes en 44.4% de RN y 37.9% de niños, siendo más frecuentes y graves en los RN. CONCLUSIONES: Para realizar un diagnóstico precoz es fundamental pensar en TVSC en RN con síntomas encefalopáticos y/o convulsiones y en mayores con clínica de HTEC en presencia de enfermedades predisponentes o desencadenantes.

Biofilm formation on polyethylene microplastics and their role as transfer vector of emerging organic pollutants.

Microplastic (MP)-colonizing microorganisms are important links for the potential impacts on environmental, health, and biochemical circulation in various ecosystems but are not yet well understood. In addition, biofilms serve as bioindicators for the evaluation of pollutant effects on ecosystems. This study describes the ability of three polyethylene-type microplastics, white (W-), blue (B-), and fluorescent blue (FB-) MPs, to support microbial colonization of Pseudomonas aeruginosa, the effect of mixed organic contaminants (OCs: amoxicillin, ibuprofen, sertraline, and simazine) on plastic-associated biofilms, and the role of biofilms as transfer vectors of such emerging pollutants. Our results showed that P. aeruginosa had a strong ability to produce biofilms on MPs, although the protein amount of biomass formed on FB-MP was 1.6- and 2.4-fold higher than that on B- and W-MP, respectively. When OCs were present in the culture medium, a decrease in cell viability was observed in the W-MP biofilm (65.0%), although a general impairing effect of OCs on biofilm formation was ruled out. Microbial colonization influenced the ability of MPs to accumulate OCs, which was higher for FB-MP. In particular, the sorption of amoxicillin was lower for all bacterial-colonized MPs than for the bare MPs. Moreover, we analysed oxidative stress production to assess the impact of MPs or MPs/OCs on biofilm development. The exposure of biofilms to OCs induced an adaptive stress response reflected in the upregulation of the katB gene and ROS production, particularly on B- and FB-MP. This study improves our understanding of MP biofilm formation, which modifies the ability of MPs to interact with some organic pollutants. However, such pollutants could hinder microbial colonization through oxidative stress production, and thus, considering the key role of biofilms in biogeochemical cycles or plastic degradation, the co-occurrence of MPs/OCs should be considered to assess the potential risks of MPs in the environment.

Transcriptomic and physiological effects of polyethylene microplastics on Zea mays seedlings and their role as a vector for organic pollutants.

The widespread employment of plastics in recent decades has resulted in the accumulation of plastic residues in all ecosystems. Their presence and degradation into small particles such as microplastics (MPs) may have a negative effect on plant development and therefore on crop production. In this study, the effects of two types of polyethylene MPs on Zea mays seedlings cultured in vitro were analysed. In addition, four organic pollutants (ibuprofen, simazine, sertraline, and amoxicillin) were adsorbed by the MPs to evaluate their capacity as other contaminant vectors. The development of the plants was negatively affected by MPs alone or with the organic compounds. The strongest effect was observed in the W-MPs treatments, with a reduction in leaf and root length near 70%. Chlorophyll content was also differentially affected depending on the treatment. Transcriptome analysis showed that MPs affected gene expression in the roots of maize seedlings. As observed in the physiological parameters analysed, some gene expression changes were associated with specific treatments, such as changes in sugar transport genes in the B-MIX treatment. These results contribute to a better understanding of the molecular mechanisms of plants in regard to plastic stress responses.

Copper and Chromium toxicity is mediated by oxidative stress in Caenorhabditis elegans: The use of nanoparticles as an immobilization strategy.

Environmental contamination by heavy metals (HMs) has impelled searching for stabilization strategies, where the use of zero-valent iron nanoparticles (nZVI) is considered a promising option. We have evaluated the combined effect of Cu(II)-Cr(VI) on two Caenorhabditis elegans strains (N2 and RB1072 sod-2 mutant) in aqueous solutions and in a standard soil, prior and after treatment with nZVI (5% w/w). The results showed that HMs aqueous solutions had an intense toxic effect on both strains. Production of reactive oxygen species and enhanced expression of the heat shock protein Hsp-16.2 was observed, indicating increased HM-mediated oxidative stress. Toxic effects of HM-polluted soil on worms were higher for sod-2 mutant than for N2 strain. However, nZVI treatment significantly diminished all these effects. Our findings highlighted C. elegans as a sensitive indicator for HMs pollution and its usefulness to assess the efficiency of the nanoremediation strategy to decrease the toxicity of Cu(II)-Cr(VI) polluted environments.

Assessing the role of polyethylene microplastics as a vector for organic pollutants in soil: Ecotoxicological and molecular approaches.

Microplastics (MPs), pharmaceuticals and pesticides are emerging pollutants with proposed negative impacts on the environment. Rising interest in investigations of MPs is likely related to their potential to accumulate in agricultural systems as the base of the food chain. We applied an integrated approach using classic bioassays and molecular methods to evaluate the impact associated with a mixture of three types of polyethylene (PE) microbeads, namely, white (W), blue (B), and fluorescent blue (FB), and their interactions with pollutants (OCs), including ibuprofen (IB), sertraline (STR), amoxicillin (AMX) and simazine (SZ), on different soil organisms. PE-MPs exhibited different abilities for the adsorption of each OC; W selectively adsorbed higher amounts of SZ, whereas B and FB preferably retained AMX. Standard soil was artificially contaminated with OCs and MPs (alone or combined with OCs) and incubated for 30 days. The presence of MPs or MPs and OCs (MIX) in soil did not produce any effect on Caenorhabditis elegans endpoint growth, reproduction, or survival. Inhibition of leaf growth in Zea mays was detected, but this negative effect declined over time, while the inhibition of root growth increased, especially when OCs (32%) or MIX (47%) were added. Moreover, the expression of the antioxidant genes CAT 1, SOD-1A and GST 1 on plants was affected by the treatments studied. The addition of MPs or MIX significantly affected the soil bacterial phylogenetic profile, which selectively enriched members of the bacterial community (particularly Proteobacteria). The predicted functional profiles of MP/MIX samples indicated a potential impact on the carbon and nitrogen cycle within the soil environment. Our results indicate that MPs and their capability to act as pollutant carriers affect soil biota; further studies should be carried out on the bioavailability of OCs adsorbed by microplastics and how long it takes to leach these OCs into different organisms and/or ecosystems.

[Actinomyces sp. brain abscess: a rare infection in children. A case report]. / Absceso cerebral por Actinomyces sp.: una infección infrecuente en niños. A propósito de un caso.

Despite advances in diagnostic and treatment techniques, intracranial infections remain serious diseases with an estimated incidence of between 0.3 and 1.3 cases/100,000 inhabitants. We present a previously healthy patient with an intraoperative diagnostic of brain abscess, in whom although the culture showed polymicrobial development, Actinomyces sp was presumptively identified in the pathological anatomy. Given this finding, prolonged combined antibiotic therapy was performed with good evolution. Absceso cerebral por Actinomyces sp.: una infección infrecuente en niños. A propósito de un caso Actinomyces sp. brain abscess: a rare infection in children. A case report The presentation of this suppurative process was nonspecific and the contribution of the anatomopathology in the etiological diagnosis was relevant. The identification of an unusual microorganism defined the need to deepen the identification of predisposing factors.

A pesar de los avances en las técnicas de diagnóstico y tratamiento, las infecciones intracraneanas son aún enfermedades graves con una incidencia estimada entre 0,3 y 1,3 casos por cada 100 000 habitantes. Se presenta un paciente previamente sano con un absceso cerebral de diagnóstico intraoperatorio en quien, si bien el cultivo evidenció desarrollo polimicrobiano, se identificó presuntivamente Actinomyces sp. en la anatomía patológica. Dado este hallazgo, se realizó antibioticoterapia combinada prolongada con buena evolución. La presentación de este proceso supurado fue inespecífica y la contribución de la anatomía patológica en el diagnóstico etiológico fue relevante. La identificación de un microorganismo inhabitual definió la necesidad de profundizar en la determinación de factores predisponentes.

Whole genome sequencing reveals a frameshift mutation and a large deletion in YY1AP1 in a girl with a panvascular artery disease.

BACKGROUND: Rare diseases are pathologies that affect less than 1 in 2000 people. They are difficult to diagnose due to their low frequency and their often highly heterogeneous symptoms. Rare diseases have in general a high impact on the quality of life and life expectancy of patients, which are in general children or young people. The advent of high-throughput sequencing techniques has improved diagnosis in several different areas, from pediatrics, achieving a diagnostic rate of 41% with whole genome sequencing (WGS) and 36% with whole exome sequencing, to neurology, achieving a diagnostic rate between 47 and 48.5% with WGS. This evidence has encouraged our group to pursue a molecular diagnosis using WGS for this and several other patients with rare diseases. RESULTS: We used whole genome sequencing to achieve a molecular diagnosis of a 7-year-old girl with a severe panvascular artery disease that remained for several years undiagnosed. We found a frameshift variant in one copy and a large deletion involving two exons in the other copy of a gene called YY1AP1. This gene is related to Grange syndrome, a recessive rare disease, whose symptoms include stenosis or occlusion of multiple arteries, congenital heart defects, brachydactyly, syndactyly, bone fragility, and learning disabilities. Bioinformatic analyses propose these mutations as the most likely cause of the disease, according to its frequency, in silico predictors, conservation analyses, and effect on the protein product. Additionally, we confirmed one mutation in each parent, supporting a compound heterozygous status in the child. CONCLUSIONS: In general, we think that this finding can contribute to the use of whole genome sequencing as a diagnosis tool of rare diseases, and in particular, it can enhance the set of known mutations associated with different diseases.

Bioassays to assess the ecotoxicological impact of polyethylene microplastics and two organic pollutants, simazine and ibuprofen.

Research on the environmental impact of plastics, especially on the effect of microplastics (MPs), has become a priority issue in recent years, mainly in terrestrial ecosystems where there is a lack of studies. This work aims to assess the impact of two types of polyethylene MPs, white microbeads (W) and fluorescent blue microbeads (FB), and their interactions with two contaminants, ibuprofen (Ib) and simazine (Sz), on different organisms. A set of bioassays for Vibrio fischeri, Caenorhabditis elegans and Lactuca sativa was carried out, which helped to establish the ecotoxicological impact of those pollutants. C. elegans showed the least sensitivity, while V. fischeri and L. sativa showed a high toxicological response to MPs alone. We found that W and FB induced an inhibition of 27% and 5.79%, respectively, in V. fischeri, and the growth inhibition rates were near 70% in L. sativa for both MPs. MPs exhibited a potential role as contaminant vectors in V. fischeri since the inhibition caused by W-Ib or W-Sz complexes was near 39%. The W-Sz complex significantly reduced leaf development in L. sativa, and a reduction of 30% in seed germination was detected when the complex FB-Sz was tested. This study reveals the importance of designing a complete set of analyses with organisms from different trophic levels, considering the great variability in the effects of MPs and the high number of relevant factors.

Ecotoxicogenomic analysis of stress induced on Caenorhabditis elegans in heavy metal contaminated soil after nZVI treatment.

Soil contamination by heavy metals (HMs) is an environmental problem, and nanoremediation by using zero-valent iron nanoparticles (nZVI) has attracted increasing interest. We used ecotoxicological test and global transcriptome analysis with DNA microarrays to assess the suitability of C. elegans as a useful bioindicator to evaluate such strategy of nanoremediation in a highly polluted soil with Pb, Cd and Zn. The HMs produced devastating effect on C. elegans. nZVI treatment reversed this deleterious effect up to day 30 after application, but the reduction in the relative toxicity of HMs was lower at day 120. We stablished gene expression profile in C. elegans exposed to the polluted soil, treated and untreated with nZVI. The percentage of differentially expressed genes after treatment decreases with exposure time. After application of nZVI we found decreased toxicity, but increased biosynthesis of defensive enzymes responsive to oxidative stress. At day 14, when a decrease in toxicity has occurred, genes related to specific heavy metal detoxification mechanisms or to response to metal stress, were down regulated: gst-genes, encoding for glutathione-S-transferase, htm-1 (heavy metal tolerance factor), and pgp-5 and pgp-7, related to stress response to metals. At day 120, we found increased HMs toxicity compared to day 14, whereas the transcriptional oxidative and metal-induced responses were attenuated. These findings indicate that the profiled gene expression in C. elegans may be considered as an indicator of stress response that allows a reliable evaluation of the nanoremediation strategy.

Evaluation of nanoremediation strategy in a Pb, Zn and Cd contaminated soil.

We addressed the efficiency of a nanoremediation strategy using zero-valent iron nanoparticles (nZVI), in a case of co-mingled heavy metals (HM) pollution (Pb, Cd and Zn). We applied a combined set of physical-chemical, toxicological and molecular analyses to assess the effectiveness and ecosafety of nZVI (5% w/w) for environmental restoration. After 120 days, nZVI showed immobilization capacity for Pb (20%), it was scarcely effective for Zn (8%) and negligibly effective for Cd. The HMs immobilization in the nZVI treated soils (compared to control soil), reaches its maximum after 15 days (T3) as reflected in the decrease of HM toxicity towards V. fischeri. The overall abundance of the microbial community was similar in both sets of samples during all experiment, although an increase in the number of metabolically active bacteria was recorded 15 days post treatment. We studied the induced impact of nanoremediation on the soil microbial community structure by Next Generation Sequencing (NGS). Even when higher HM immobilization was recorded, no significant recovery of the microbial community structure was found in nZVI-treated soil. The most marked nZVI-induced structural shifts were observed at T3 (increase in the Firmicutes population with a decrease in Gram-negative bacteria). Predictive metagenomic analysis using PICRUSt showed differences among the predicted metagenomes of nZVI-treated and control soils. At T3 we found decrease in detoxification-related proteins or over-representation of germination-related proteins; after 120 days of nZVI exposure, higher abundance of proteins involved in regulation of cellular processes or sporulation-related proteins was detected. This study highlights the partial effectiveness of nanoremediation in multiple-metal contaminated soil in the short term. The apparent lack of recovery of biodiversity after application of nZVI and the decreased effectiveness of nanoremediation over time must be carefully considered to validate this technology when assurance of medium- to long-term immobilization of HMs is required.

New insights into the impact of nZVI on soil microbial biodiversity and functionality.

Nanoscale zero-valent iron (nZVI) is a strong reducing agent used for in situ remediation of soil. The impacts of nZVI (5-10% w/w) on the soil microbial biodiversity and functionality of two soils (Lufa 2.2 and 2.4) were assessed. Illumina MiSeq technology was used to evaluate the structure of soil microbiomes after 21 days of exposure. Proteobacteria, Verrucomicrobia, Firmicutes and Actinobacteria were the most abundant phyla in both soils. However, the dynamics of bacterial community composition following nZVI addition differed. nZVI exposure induced pronounced shifts in the microbial composition of soil 2.4, but not in soil 2.2; an increase in Verrucomicrobia abundance was the unique common taxonomic pattern observed in both soils. The PICRUSt approach was applied to predict the functional composition of each metagenome. Environmental information processing function (membrane transport) was decreased in both nZVI-spiked soils, although soil 2.4 samples were enriched in functions involved in cellular processes and metabolism. The effects of nZVI on autochthonous bacterial communities clearly varied with the soil type assessed; changes at the phylogenetic level appeared to be more abundant than those observed at the functional level, and thus, the overall effort of the soil ecosystem might involve the maintenance of functionality following nZVI exposure.

Primera experiencia de tratamiento con everolimus en un paciente con esclerosis tuberosa y astrocitoma subependimario de células gigantes en Uruguay / First experience of everolimus in patients with tuberous sclerosis and subependymal giant cell astrocytoma in Uruguay

Resumen: El complejo esclerosis tuberosa (CET) es una enfermedad genética multisistémica determinada por la pérdida de función del complejo hamartina/tuberina. Esto causa activación del m-TOR con formación de tumores como el astrocitoma subependimario de células gigantes (SEGA). El everolimus inhibe el m-TOR reduciendo el tamaño de los SEGA. El objetivo de este trabajo es mostrar la experiencia del primer caso de SEGA tratado con everolimus en Uruguay. Caso: Escolar de 6 años, con desarrollo normal, sin epilepsia y portador de CET. A los 5 años instala hipertensión intracraneana por hidrocefalia secundaria al SEGA. Se realiza cirugía lográndose resección parcial, con remanente tumoral de 14.3cm³. Se inició everolimus evidenciando las resonancias magnéticas de control una reducción del tamaño tumoral del 54.5% al mes, del 65.5% a los 3 meses y del 68.5% a los 6 meses de iniciado el tratamiento. Presentó efectos secundarios menores (aftas bucales, infecciones respiratorias altas). La buena respuesta obtenida aporta evidencia del uso del everolimus como tratamiento complementario a la cirugía en los pacientes con SEGA.

Abstract: Tuber sclerosis complex (TSC) is a multisystemic genetic disease caused by a loss of function of hamartin/tuberin complex. This results in an m-TOR activation with tumor formation, among which is subependymal giant cell astrocytoma (SEGA). Everolimus inhibits m-TOR reducing SEGA size. The objective of this work is to show the first experience of SEGA treatment with everolimus in Uruguay. Case: 6 years old boy with TSC, with normal development and no history of seizures. At the age of 5 he installed intracranial hypertension due to hydrocephalus secondary to a SEGA. With surgery tumor was partially resect, with a 14.3cm³ tumor remnant. Treatment with everolimus was iniciated with a tumor size reduction of 54.5% after the first month of treatment, 65.5% after 3 months and 68.5% after 6 months. He had minor secondary effects (mouth ulcerations and upper respiratory tract infections). Good response in this patient shows evidence of possible use of everolimus as an adjuvant terapy to surgery in SEGA.

Molecular stress responses to nano-sized zero-valent iron (nZVI) particles in the soil bacterium Pseudomonas stutzeri.

Nanotoxicological studies were performed in vitro using the common soil bacterium Pseudomonas stutzeri to assess the potentially toxic impact of commercial nano-sized zero-valent iron (nZVI) particles, which are currently used for environmental remediation projects. The phenotypic response of P. stutzeri to nZVI toxicity includes an initial insult to the cell wall, as evidenced by TEM micrographs. Transcriptional analyses using genes of particular relevance in cellular activity revealed that no significant changes occurred among the relative expression ratios of narG, nirS, pykA or gyrA following nZVI exposure; however, a significant increase in katB expression was indicative of nZVI-induced oxidative stress in P. stutzeri. A proteomic approach identified two major defence mechanisms that occurred in response to nZVI exposure: a downregulation of membrane proteins and an upregulation of proteins involved in reducing intracellular oxidative stress. These biomarkers served as early indicators of nZVI response in this soil bacterium, and may provide relevant information for environmental hazard assessment.

Integrating classical and molecular approaches to evaluate the impact of nanosized zero-valent iron (nZVI) on soil organisms.

Nanosized zero-valent iron (nZVI) is a new option for the remediation of contaminated soil and groundwater, but the effect of nZVI on soil biota is mostly unknown. In this work, nanotoxicological studies were performed in vitro and in two different standard soils to assess the effect of nZVI on autochthonous soil organisms by integrating classical and molecular analysis. Standardised ecotoxicity testing methods using Caenorhabditis elegans were applied in vitro and in soil experiments and changes in microbial biodiversity and biomarker gene expression were used to assess the responses of the microbial community to nZVI. The classical tests conducted in soil ruled out a toxic impact of nZVI on the soil nematode C. elegans in the test soils. The molecular analysis applied to soil microorganisms, however, revealed significant changes in the expression of the proposed biomarkers of exposure. These changes were related not only to the nZVI treatment but also to the soil characteristics, highlighting the importance of considering the soil matrix on a case by case basis. Furthermore, due to the temporal shift between transcriptional responses and the development of the corresponding phenotype, the molecular approach could anticipate adverse effects on environmental biota.

Características epidemiológicas de la pluripatología y su influencia en la utilización de servicios sanitarios a partir de una Encuesta de Salud. Madrid, 2007 / Epidemiological features of comorbidity and its influence on the use of health services from health survey Madrid 2007, Spain

Fundamentos: La acumulación de patologías crónicas en unmismo paciente es cada vez más frecuente, por lo que se está convirtiendoen un problema de salud pública. Los objetivos de este estudioson describir la prevalencia de pluripatología en la población, suscaracterísticas epidemiológicas y su influencia en la utilización deservicios sanitarios a partir de la Encuesta Regional de Salud deMadrid (ERSM2007) y comparar dos indicadores de pluripatología.Métodos: Estudio descriptivo transversal. Se analizó laERSM2007 (n=12.190 mayores de 15 años). Se elaboraron dos indicadores:la presencia de 2 o más Problemas Crónicos (PC) y la existenciade 2 o más categorías clínicas afectadas según una definiciónde Paciente Pluripatológico (PP). Otras variables analizadas fueron:sexo, edad, clase social, nivel de estudios, índice de masa corporal,actividad física, consumos de alcohol y de tabaco, y la utilización deservicios sanitarios. Se realizó un análisis descriptivo, bivariado ymultivariado mediante regresión logística con el cálculo de oddsratios (OR) e intervalos de confianza del 95%.Resultados: La prevalencia de pluripatología medida con PC fue23,7% en hombres y 37,3% en mujeres y con PP fue 5,4% y 8,0% respectivamente.La pluripatología aumentó con la edad, con el bajo niveleducativo (OR=2,0; 1,4-2,8, en mujeres sin estudios o primarios respectoa universitarios), con la obesidad (OR=2,6; 1,9-3,3, en obesas respectoa mujeres de peso normal), y con el consumo previo de alcohol y detabaco. La mayor asociación se observó con PP y el ingreso hospitalario(OR=4,1 ; 3,0-5,5 en hombres y OR=3,3 ; 2,6-4,3 en mujeres)...(AU)

Background: The accumulation of chronic conditions in a samepatient is increasingly more frequent for which is becoming aproblem of public health. The objectives of this study are to describethe prevalence of comorbidity in the population, its epidemiologicalcharacteristics and its influence in the utilization of health servicesfrom the Regional Health Survey of Madrid (ERSM2007) and tocompare two indicators of comorbidity.Methods: Cross-sectional study. The ERSM2007 was analyzed(n=12.190 over 15 years old). Two indicators were developed: thepresence of 2 or more chronic conditions (PC) and the existence of 2or more affected clinical categories according to a definition ofcomorbiditied patient (PP). Other variables analyzed were: sex, age,social class, education, body mass index, physical activity, alcoholand tobacco consumption, and the utilization of health services. Adescriptive analysis was carried out, bivariate and multivariate bymeans of logistic regression with odds ratios (OR) and confidenceintervals of 95%.Outcomes: The prevalence of comorbidity measured with PCwas 23.7% in men and 37.3% in women and with PP was 5.4% and8.2% respectively. Comorbidity increased with age, with loweducational level (OR=2,0; 1,4-2,8, in women without or withprimary studies regarding university degree), with obesity (OR=2,6;1,9-3,3, in obese women with regard to normal weighted women),and with the previous alcohol and tobacco consumption. The highestassociation was observed between PP and hospitalization (OR=4,1;3,0-5,5 in men and OR=3,3; 2,6-4,3 in women)...(AU)

[Epidemiological features of comorbidity and its influence on the use of health services from Health Survey Madrid 2007, Spain]. / Características epidemiológicas de la pluripatología y su influencia en la utilización de servicios sanitarios a partir de una encuesta de salud. Madrid, 2007.

BACKGROUND: The accumulation of chronic conditions in a same patient is increasingly more frequent for which is becoming a problem of public health. The objectives of this study are to describe the prevalence of comorbidity in the population, its epidemiological characteristics and its influence in the utilization of health services from the Regional Health Survey of Madrid (ERSM2007) and to compare two indicators of comorbidity. METHODS: Cross-sectional study. The ERSM2007 was analyzed (n=12.190 over 15 years old). Two indicators were developed: the presence of 2 or more chronic conditions (PC) and the existence of 2 or more affected clinical categories according to a definition of comorbidited patient (PP). Other variables analyzed were: sex, age, social class, education, body mass index, physical activity, alcohol and tobacco consumption, and the utilization of health services. A descriptive analysis was carried out, bivariate and multivariate by means of logistic regression with odds ratios (OR) and confidence intervals of 95%. OUTCOMES: The prevalence of comorbidity measured with PC was 23.7% in men and 37.3% in women and with PP was 5.4% and 8.2% respectively. Comorbidity increased with age, with low educational level (OR=2.0; 1.4-2.8, in women without or with primary studies regarding university degree), with obesity (OR=2.6; 1.9-3.3, in obese women with regard to normal weighted women), and with the previous alcohol and tobacco consumption. The highest association was observed between PP and hospitalization (OR=4.1; 3.0-5.5 in men and OR=3.3; 2.6-4.3 in women). CONCLUSIONS: The prevalence of comorbidity was higher in women, in older people, with smaller level of studies or in more disadvantaged social classes. Comorbidity was associated with the obesity and with consumption of tobacco or alcohol. The utilization of the healthcare services enlarged with the comorbidity. These indicators can be complementary, because of their differential association with each healthcare level.

Interstitial cells of Cajal in the urethra are cGMP-mediated targets of nitrergic neurotransmission.

While interstitial cells of Cajal (ICC) in the urethra respond to nitric oxide (NO) donors by increasing cGMP, it remains unclear whether urethral ICC are functionally innervated by nitrergic nerves. We have addressed this issue in the rat and sheep urethra, where cGMP production and relaxation were compared in preparations subjected to electrical field stimulation (EFS; 2 Hz, 4 min) of nitrergic nerves or to exogenous S-nitroso-L-cysteine (SNC; 0.1 mM, 4 min). Upon EFS, cGMP immunoreactivity (cGMP-ir) was observed in both smooth muscle cells (SMC) and in spindle-shaped cells that contained c-kit and vimentin, features of ICC. Similarly, cGMP-ir was preferentially, but inconsistently, found in ICC of the outer muscle layer on exposure to SNC. We found separate functional groups of ICC within the urethra. Thus only ICC present in the muscle layers (ICC-M) but not those in the serosa (ICC-SR) and lamina propia (ICC-LP) seem to be specifically influenced by activation of neuronal NO synthase (nNOS). Thus the increase in cGMP-ir in the ICC-M induced by EFS was prevented by Nomega-nitro-L-arginine and ODQ. Urethral ICC did not express nNOS, although they were closely associated with nitrergic nerves. cGMP-ir was also present in the urothelium (in the rat but not in the sheep) and the vascular endothelium but not in neural structures, such as the nerve trunks and nerve terminals. Together, these results suggest a model of parallel innervation in which both SMC and ICC-M are effectors of nerve-released NO in the urethra.