Differential recovery ability from infections by two blood parasite genera in males of a Mediterranean lacertid lizard after an experimental translocation.

Different blood parasites can co-infect natural populations of lizards. However, our knowledge of the host's ability to recover from them (i.e., significantly reduce parasitemia levels) is scarce. This has interest from an ecological immunology perspective. Herein, we investigate the host recovery ability in males of the lizard Psammodromus algirus infected by parasite genera Schellackia and Karyolysus. The role of lizard hosts is dissimilar in the life cycle of these two parasites, and thus different immune control of the infections is expected by the vertebrate host. As Schellackia performs both sexual and asexual reproduction cycles in lizards, we expect a better immune control by its vertebrate hosts. On the contrary, Karyolysus performs sexual reproductive cycles in vectors, hence we expect lower immune control by the lizards. We carried out a reciprocal translocation experiment during the lizards' mating season to evaluate both parasitemia and leukocyte profiles in male lizards, being one of the sampling plots close to a road with moderate traffic. These circumstances provide a combination of extrinsic (environmental stress) and intrinsic factors (reproductive vs. immune trade-offs) that may influence host's recovery ability. We recaptured 33% of the lizards, with a similar proportion in control and translocated groups. Karyolysus infected 92.3% and Schellackia 38.5% of these lizards. Hosts demonstrated ability to significantly reduce parasitemia of Schellackia but not of Karyolysus. This suggests, in line with our predictions, a differential immune relationship of lizards with these parasites, at time that supports that parasites with different phylogenetic origins should be analyzed separately in investigations of their effects on hosts. Furthermore, lizards close to the road underwent a stronger upregulation of lymphocytes and monocytes when translocated far from the road, suggesting a putative greater exposure to pathogens in the latter area.

Efficacy of chestnut and quebracho wood extracts to control Salmonella in poultry.

AIMS: The study was aimed to evaluate the antibacterial activity and efficacy of chestnut and quebracho wood extracts against Salmonella by in vitro assays and in vivo trials. METHODS AND RESULTS: The extracts showed inhibitory activity against Salmonella determined by the minimum inhibitory concentration method as well as on the adhesion and invasion of S. Gallinarum (SG) and S. Enteritidis (SE) in Caco-2 cells. Also, transmission electron microscopy revealed that extract-treated Salmonella showed disruption of cell walls and membranes, damage of the cytoplasm and tannin-protein aggregations. In addition, efficacy of the extracts to control SG and SE was evaluated in experimental infection trials in laying hens and broilers respectively. SE excretion was significantly reduced on days 5 (P < 0·01) and 12 (P < 0·025) only in the quebracho group. In the fowl typhoid infection model, hens that received the chestnut extract showed a significantly reduced mortality (P < 0·05). CONCLUSIONS: Our results evidence that these alternative natural products may be a useful tool to control Salmonella in poultry. SIGNIFICANCE AND IMPACT OF THE STUDY: Salmonella is a zoonotic pathogen usually associated with poultry production. This study provides information about the mechanism of antibacterial effects of chestnut and quebracho wood extracts to control Salmonella in poultry.

Effectiveness and safety of perampanel as early add-on treatment in patients with epilepsy and focal seizures in the routine clinical practice: Spain prospective study (PERADON).

OBJECTIVE: Perampanel (PER) has been shown to be effective as an adjunctive therapy for controlling refractory focal-onset seizures (FOS). However, the information as early add-on for the treatment of FOS in the clinical practice is still scarce and must be further assessed. METHODS: An observational prospective study was conducted to evaluate the effectiveness of early add-on PER, assessed as 50% responders (seizure frequency reduced by at least 50% during the last 3 months as compared with baseline) rate at 6 and 12 months, in patients with FOS in the routine clinical practice of Spain. RESULTS: One hundred and thirteen patients (mean age: 40.3 years, 51.3% male) with FOS received PER as early add-on (1st add-on: 37.2% and 2nd: 62.8%) for a mean exposure of 11 months (mean PER dose: 6.3 mg/day at month 12). At 6 months, 50.4% and 20.4% of the patients were responders and seizure-free (respectively) relative to baseline (3 months prior to PER initiation), and at 12 months, 68.1% and 26.5% of the patients were responders and seizure-free (respectively), relative to baseline (3 months prior to PER initiation). The retention rate at 6 and 12 months was 83.2% and 80.5%, respectively. The percentage of seizure-free patients at 12 months was significantly (p = 0.033) higher when PER was added as first vs. second add-on. The number of concomitant antiepileptic drugs (AEDs) was significantly reduced from baseline to 6 and 12 months (p = 0.001). Treatment was simplified in 23.9% of patients at the end of the observation period. Drug-related adverse events (AEs), most mild or moderate, were reported in 30.1% of patients, with irritability (8%) and dizziness (7.1%) as the most frequent ones. CONCLUSIONS: This is the first observational, prospective study to evaluate efficacy and safety of early adjunctive treatment with PER in patients with focal epilepsy at 12 months. Perampanel demonstrated a good efficacy and safety profile when used at a median dose of 6 mg/day, regardless of the combination with other AEDs. Adverse events were mild or moderate, with dizziness being the most frequent one.

Utilidad del Trabecular Bone Score en la valoración del riesgo de fractura osteoporótica / Usefulness of the Trabecular Bone Score for assessing the risk of osteoporotic fracture

Introducción y objetivos. El Trabecular Bone Score (TBS) es una técnica de imagen que evalúa el estado de la microarquitectura trabecular. Resultados preliminares sugieren que, junto a la valoración de la densidad mineral ósea, podría mejorar la estimación del riesgo de fractura ostoporótica. El objetivo de este estudio fue analizar los valores de TBS y su relación con las características clínicas, densidad mineral ósea y antecedentes de fracturas en una cohorte de mujeres posmenopáusicas. Material y métodos. Analizamos 2.257 mujeres posmenopáusicas procedentes de la cohorte FRODOS, constituida para determinar los factores de riesgo de fractura osteoporótica mediante una encuesta clínica y densitometría ósea con morfometría vertebral. Se aplicó el TBS a las imágenes densitométricas. Valores de TBS ≤1,230 se consideraron indicativos de microarquitectura degradada. Se realizó una regresión lineal simple y múltiple para determinar los factores asociados con este índice. Resultados. El valor medio de TBS en L1-L4 fue de 1,203±0,121. El 55,3% de las mujeres presentaban valores de microarquitectura degradada. En el análisis de regresión lineal múltiple los factores asociados a los valores bajos de TBS fueron la edad, el peso, la altura, escala T de columna lumbar, tratamiento con glucocorticoides, presencia de diabetes tipo 2 y antecedentes de fractura por fragilidad. Conclusiones. El TBS mostró valores de microarquitectura degradada en las participantes de la cohorte FRODOS y se asoció a factores antropométricos, valor bajo de densidad mineral ósea, presencia de fracturas, antecedentes de diabetes mellitus tipo 2 y uso de glucocorticoides

Introduction and objectives. The trabecular bone score (TBS) is an imaging technique that assesses the condition of the trabecular microarchitecture. Preliminary results suggest that TBS, along with the bone mineral density assessment, could improve the calculation of the osteoporotic fracture risk. The aim of this study was to analyse TBS values and their relationship with the clinical characteristics, bone mineral density and history of fractures of a cohort of posmenopausal women. Material and methods. We analysed 2,257 posmenopausal women from the FRODOS cohort, which was created to determine the risk factors for osteoporotic fracture through a clinical survey and bone densitometry with vertebral morphometry. TBS was applied to the densitometry images. TBS values ≤1230 were considered indicative of degraded microarchitecture. We performed a simple and multiple linear regression to determine the factors associated with this index. Results. The mean TBS value in L1-L4 was 1.203±0.121. Some 55.3% of the women showed values indicating degraded microarchitecture. In the multiple linear regression analysis, the factors associated with low TBS values were age, weight, height, spinal T-score, glucocorticoid treatment, presence of type 2 diabetes and a history of fractures due to frailty. Conclusions. TBS showed microarchitecture degradation values in the participants of the FRODOS cohort and was associated with anthropometric factors, low bone mineral density values, the presence of fractures, a history of type 2 diabetes mellitus and the use of glucocorticoids

Usefulness of the Trabecular Bone Score for assessing the risk of osteoporotic fracture. / Utilidad del Trabecular Bone Score en la valoración del riesgo de fractura osteoporótica.

INTRODUCTION AND OBJECTIVES: The trabecular bone score (TBS) is an imaging technique that assesses the condition of the trabecular microarchitecture. Preliminary results suggest that TBS, along with the bone mineral density assessment, could improve the calculation of the osteoporotic fracture risk. The aim of this study was to analyse TBS values and their relationship with the clinical characteristics, bone mineral density and history of fractures of a cohort of posmenopausal women. MATERIAL AND METHODS: We analysed 2,257 posmenopausal women from the FRODOS cohort, which was created to determine the risk factors for osteoporotic fracture through a clinical survey and bone densitometry with vertebral morphometry. TBS was applied to the densitometry images. TBS values ≤1230 were considered indicative of degraded microarchitecture. We performed a simple and multiple linear regression to determine the factors associated with this index. RESULTS: The mean TBS value in L1-L4 was 1.203±0.121. Some 55.3% of the women showed values indicating degraded microarchitecture. In the multiple linear regression analysis, the factors associated with low TBS values were age, weight, height, spinal T-score, glucocorticoid treatment, presence of type 2 diabetes and a history of fractures due to frailty. CONCLUSIONS: TBS showed microarchitecture degradation values in the participants of the FRODOS cohort and was associated with anthropometric factors, low bone mineral density values, the presence of fractures, a history of type 2 diabetes mellitus and the use of glucocorticoids.

Use of Plant Extracts as an Effective Manner to Control Clostridium perfringens Induced Necrotic Enteritis in Poultry.

Necrotic enteritis (NE) is an important concern in poultry industry since it causes economic losses, increased mortality, reduction of bird welfare, and contamination of chicken products for human consumption. For decades, the use of in-feed antimicrobial growth promoters (AGPs) has been the main strategy to control intestinal pathogens including Clostridium perfringens (CP), the causative agent of NE. However, the use of AGPs in animal diet has been linked to the emergence and transmission of antimicrobial resistance through food-borne microorganisms, which has led to the ban of AGPs in many countries. This scenario has challenged the poultry industry to search for safer alternative products in order to prevent NE. In this context, the utilization of natural plant extracts with antimicrobial properties appears as a promising and feasible tool to control NE in chicken. In this paper, we review the scientific studies analyzing the potential of plant extracts as alternative feed additives to reduce NE in poultry, with focus on two types of plant products that arise as promising candidates: tannins and essential oils. Some of these products showed antimicrobial activity against CP and coccidia in vitro and in vivo and are able to increase productive performance, emulating the bioactive properties of AGPs.

Hydrolyzable and condensed tannins resistance in Clostridium perfringens.

Tannins added in the diet are being used to improve nutrition and health in farm animals as an alternative to antibiotic growth promoters and to control enteric clostridial diseases. However, the capacity of Clostridium perfringens to develop resistance under the selective pressure of tannins is unknown. The purpose of this study was to determine if C. perfringens possess the ability to develop resistance against tannins in comparison with antimicrobial agents. Susceptibility for 7 AGPs (antimicrobial growth promoters), 9 therapeutic antimicrobials and 2 tannin based extracts was determined for 30 C. perfringens strains isolated from poultry and cattle. Two susceptible strains were selected and cultured in presence of sub-inhibitory concentrations of tannins and AGPs for resistant sub-populations selection. Tannin resistance of C. perfringens isolates from both animal species revealed no statistically significant differences in MICs (minimum inhibitory concentration). Poultry isolates showed higher MICs to several AGPs compared with cattle isolates. All isolates were susceptible to the therapeutic antimicrobials tested, but avian isolates showed a significantly lower susceptibility to these antimicrobials which was highly correlated with an increased resistance to bacitracin and others AGPs. In-vitro selection of resistant clones suggests that C. perfringens was unable to develop resistance against tannins at least compared to AGPs like bacitracin and avilamycin. Avian origin strains, which were previously exposed to antibiotics showed higher resistance, compared to cattle origin strains. These results suggest that the evolution of resistance against tannins in C. perfringens would be more difficult and slower than to the determined AGPs.

Toll-like receptor 4 contributes to vascular remodelling and endothelial dysfunction in angiotensin II-induced hypertension.

BACKGROUND AND PURPOSE: Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular structural, mechanical and functional alterations. EXPERIMENTAL APPROACH: AngII was infused (1.44 mg · kg(-1) · day(-1), s.c.) for 2 weeks in C57BL6 mice, treated with a neutralizing anti-TLR4 antibody or IgG (1 µg · day(-1); systolic BP (SBP) and aortic cytokine levels were measured. Structural, mechanical and contractile properties of aortic and mesenteric arterial segments were measured with myography and histology. RT-PCR and Western blotting were used to analyse these tissues and cultured vascular smooth muscle cells (VSMC) from hypertensive rats (SHR). KEY RESULTS: Aortic TLR4 mRNA levels were raised by AngII infusion. Anti-TLR4 antibody treatment of AngII-treated mice normalised: (i) increased SBP and TNF-α, IL-6 and CCL2 levels; (ii) vascular structural and mechanical changes; (iii) altered aortic phenylephrine- and ACh-induced responses; (iv) increased NOX-1 mRNA levels, superoxide anion production and NAD(P)H oxidase activity and effects of catalase, apocynin, ML-171 and Mito-TEMPO on vascular responses; and (v) reduced NO release and effects of L-NAME on phenylephrine-induced contraction. In VSMC, the MyD88 inhibitor ST-2825 reduced AngII-induced NAD(P)H oxidase activity. The TLR4 inhibitor CLI-095 reduced AngII-induced increased phospho-JNK1/2 and p65 NF-κB subunit nuclear protein expression. CONCLUSIONS AND IMPLICATIONS: TLR4 up-regulation by AngII contributed to the inflammation, endothelial dysfunction, vascular remodelling and stiffness associated with hypertension by mechanisms involving oxidative stress. MyD88-dependent activation and JNK/NF-κB signalling pathways participated in these alterations.

Control of predators in industrial scale microalgae cultures with Pulsed Electric Fields.

This work describes the utilization of Pulsed Electric Fields to control the protozoan contamination of a microalgae culture, in an industrial 2.7 m(3) microalgae photobioreactor. The contaminated culture was treated with Pulsed Electric Fields, PEF, for 6h with an average of 900 V/cm, 65 µs pulses of 50 Hz. Working with recirculation, all the culture was uniformly exposed to the PEF throughout the assay. The development of the microalgae and protozoan populations was followed and the results showed that PEF is effective on the selective elimination of protozoa from microalgae cultures, inflicting on the protozoa growth halt, death or cell rupture, without affecting microalgae productivity. Specifically, the results show a reduction of the active protozoan population of 87% after 6h treatment and 100% after few days of normal cultivation regime. At the same time, microalgae growth rate remained unaffected.

Identification of potential clinically significant drug interactions in HIV-infected patients: a comprehensive therapeutic approach.

OBJECTIVES: The aim of the study was to determine the prevalence of potential clinically significant drug interactions (CSDIs) in HIV-positive individuals and to identify associated risk factors. METHODS: A cross-sectional study was conducted including all HIV-infected out-patients attending the Pharmacy Service of a regional reference hospital in Murcia, south-eastern Spain. The complete treatment was screened for possible CSDIs using the Spanish College of Pharmacists' online software resource, bot. Additionally, the severity level of the CSDIs involving antiretroviral (ARV) drugs was compared with that established in the specific antiretroviral database InteraccionesHIV.com. Multivariate logistic regression was used to identify associated risk factors. RESULTS: Two hundred and sixty-eight patients were included in the study. A total of 292 potential drug interactions were identified, of which 102 (34.9%) were CSDIs, of which 52.9% involved ARV drugs. Seven therapeutic drug classes were involved in 75% of CSDIs (protease inhibitors, benzodiazepines, nonsteroidal anti-inflammatory drugs, nonnucleoside reverse transcriptase inhibitors, corticosteroids, antithrombotics and proton pump inhibitors). Factors independently associated with CSDIs were treatment with more than five drugs [odds ratio (OR) 15.1; 95% confidence interval (CI) 6.3-36.2], and treatment with a protease inhibitor (OR 5.3; 95% CI 2.4-11.74). CONCLUSIONS: The findings of this study suggest that the prevalence of clinically relevant drug-drug interactions is high in HIV-infected patients, and could represent a major health problem. Awareness, recognition and management of drug interactions are important in optimizing the pharmaceutical care of HIV-infected patients and helping to prevent adverse events and/or loss of efficacy of the drugs administered.

[Risk prescription associated to treatment at home of the elderly patient when admitted to the hospital]. / Prescripciones de riesgo asociadas al tratamiento domiciliario del paciente anciano al ingreso hospitalario.

OBJECTIVE: To determine the prevalence, the incidence of error, and the potential harm associated to particular prescriptions identified as a risk for medication error in the home treatment of elderly patients admitted to the hospital, as well as factors associated to their occurrence. MATERIAL AND METHODS: Cross-sectional, descriptive study. Patients aged 65 years and older, being admitted to the hospital from the emergency department in the last quarter of 2009. The SPSS software version 15.0 was used for the statistical analysis. RESULTS: 324 patients were included in the study. 1,176 (47%) prescriptions were identified as risk prescriptions in 91% of the patients. The most relevant risk prescription was prescription of high-risk medications (51.5% patients) that accounted for an error incidence of 88/100 patients with high-risk medications, being severe in 68 patients. Factors associated to the occurrence of moderate/high risk error due to risk prescriptions were suffering from a chronic respiratory illness, diabetes or polymedication. CONCLUSIONS: Actions aimed at decreasing the errors due to high risk medications should be prioritized.

Objetivo: Determinar la prevalencia, la incidencia de error y el daño potencial asociado a determinadas prescripciones señaladas como de riesgo de error de medicación en el tratamiento domiciliario de pacientes ancianos que ingresan en el hospital, así como los factores asociados a su aparición. Material y métodos: Estudio transversal descriptivo. Se incluyeron los pacientes de edad igual o mayor a 65 años que ingresaron en el hospital desde el servicio de urgencias durante el último trimestre de 2009.Para el análisis estadístico se utilizó el programa SPSSv15.0. Resultados: Se incluyeron en el estudio 324 pacientes. Se identificaron 1176 (47%) prescripciones de riesgo en el 91% de los pacientes. La prescripción de riesgo más relevante fue la prescripción de medicamentos de alto riesgo (51.5% pacientes) que presentó una incidencia de error de 88/100 pacientes con medicamentos de alto riesgo, de los cuales en 68 pacientes fue grave. Los factores asociados a la presencia de error grave/moderado ocasionado por prescripciones de riesgo fueron tener enfermedad respiratoria crónica o diabetes y la polimedicación. Conclusiones: Se deben priorizar actuaciones dirigidas a disminuir errores por medicamentos de alto riesgo.

Prescripciones de riesgo asociadas al tratamiento domiciliario del paciente anciano al ingreso hospitalario / Risk prescriptions associated to treatment at home of the elderly patient when admitted to the hospital

Objetivo: Determinar la prevalencia, la incidencia de error y el daño potencial asociado a determinadas prescripciones señaladas como de riesgo de error de medicación en el tratamiento domiciliario de pacientes ancianos que ingresan en el hospital, así como los factores asociados a su aparición. Material y métodos: Estudio transversal descriptivo. Se incluyeron los pacientes de edad igual o mayor a 65 años que ingresaron en el hospital desde el servicio de urgencias durante el último trimestre de 2009. Para el análisis estadístico se utilizó el programa SPSSv15.0. Resultados: Se incluyeron en el estudio 324 pacientes. Se identificaron 1176 (47%) prescripciones de riesgo en el 91% de los pacientes. La prescripción de riesgo más relevante fue la prescripción de medicamentos de alto riesgo (51.5% pacientes) que presentó una incidencia de error de 88/100 pacientes con medicamentos de alto riesgo, de los cuales en 68 pacientes fue grave. Los factores asociados a la presencia de error grave/moderado ocasionado por prescripciones de riesgo fueron tener enfermedad respiratoria crónica o diabetes y la polimedicación. Conclusiones: Se deben priorizar actuaciones dirigidas a disminuir errores por medicamentos de alto riesgo (AU)

Objective: To determine the prevalence, the incidence of error, and the potential harm associated to particular prescriptions identified as a risk for medication error in the home treatment of elderly patients admitted to the hospital, as well as factors associated to their occurrence. Material and methods: Cross-sectional, descriptive study. Patients aged 65 years and older, being admitted to the hospital from the emergency department in the last quarter of 2009. The SPSS software version 15.0 was used for the statistical analysis. Results: 324 patients were included in the study. 1,176 (47%) prescriptions were identified as risk prescriptions in 91% of the patients. The most relevant risk prescription was prescription of high-risk medications (51.5% patients) that accounted for an error incidence of 88/100 patients with high-risk medications, being severe in 68 patients. Factors associated to the occurrence of moderate/high risk error due to risk prescriptions were suffering from a chronic respiratory illness, diabetes or polymedication. Conclusions: Actions aimed at decreasing the errors due to high risk medications should be prioritized (AU)

Sudden death syndrome in adult cows associated with Clostridium perfringens type E.

Clostridium perfringens type E is considered a rare toxinotype and an infrequent cause of enterotoxemia of lambs, calves, and rabbits. Until now, only cases of young animal of C. perfringens type E bovine enterotoxemia, characterized by hemorrhagic enteritis and sudden death, have been reported. The present report details the genotypic characterization of C. perfringens type E isolates obtained from intestinal samples of adult cattle during an outbreak of enterotoxemia in Argentina. The sequences of several housekeeping genes of these isolates were analyzed and compared with those obtained from calves in North America showing a clonal unique lineage.

Solid-state Marx based two-switch voltage modulator for the On-Line Isotope Mass Separator accelerator at the European Organization for Nuclear Research.

A new circuit topology is proposed to replace the actual pulse transformer and thyratron based resonant modulator that supplies the 60 kV target potential for the ion acceleration of the On-Line Isotope Mass Separator accelerator, the stability of which is critical for the mass resolution downstream separator, at the European Organization for Nuclear Research. The improved modulator uses two solid-state switches working together, each one based on the Marx generator concept, operating as series and parallel switches, reducing the stress on the series stacked semiconductors, and also as auxiliary pulse generator in order to fulfill the target requirements. Preliminary results of a 10 kV prototype, using 1200 V insulated gate bipolar transistors and capacitors in the solid-state Marx circuits, ten stages each, with an electrical equivalent circuit of the target, are presented, demonstrating both the improved voltage stability and pulse flexibility potential wanted for this new modulator.