Chagas disease reactivation in a heart transplant patient infected by domestic Trypanosoma cruzi discrete typing unit I (TcIDOM)

Background Trypanosoma cruzi, causative agent of Chagas disease, displays high intraspecific genetic diversity: six genetic lineages or discrete typing units (DTUs) are currently recognized, termed TcI through TcVI. Each DTU presents a particular distribution pattern across the Americas, and is loosely associated with different transmission cycles and hosts. Several DTUs are known to circulate in Central America. It has been previously suggested that TcI infection is benign and does not lead to chronic chagasic cardiomyopathy (CCC). Findings In this study, we genotyped T. cruzi parasites circulating in the blood and from explanted cardiac tissue of an El Salvadorian patient who developed reactivation Chagas disease while on immunosuppressive medications after undergoing heart transplant in the U.S. as treatment for end-stage CCC. Parasite typing was performed through molecular methods (restriction fragment length polymorphism of polymerase reaction chain amplified products, microsatellite typing, maxicircle sequence typing and low-stringency single primer PCR, [LSSP-PCR]) as well as lineage-specific serology. We show that the parasites infecting the patient belong to the TcI DTU exclusively. Our data indicate that the parasites isolated from the patient belong to a genotype frequently associated with human infection throughout the Americas (TcI DOM ). Conclusions Our results constitute compelling evidence in support of TcI DTU’s ability to cause end-stage CCC and help dispel any residual bias that infection with this lineage is benign, pointing to the need for increased surveillance for dissemination of this genotype in endemic regions, the USA and globally

Eficiencia mecánica de pedaleo en ciclistas de diferente nivel competitivo

La eficiencia muscular (gruesa, neta y delta) es una variable determinante del rendimiento en ciclismo, y mejora con el entrenamiento. Ningún trabajo previo ha mostrado diferencias en eficiencia mecánica (index of effectiveness, cociente entre los impulsos mecánico propulsivo y total) entre ciclistas de diferente nivel competitivo. Este fue el principal objetivo del presente trabajo. Participaron 11 ciclistas profesionales y 23 ciclistas amateurs que realizaron pruebas a 200, 250 y 300 W de potencia (cadencia fija a 90 rpm). La fuerza y el impulso mecánico positivo y negativo durante el pedaleo, así como la cinemática 2D de la pierna derecha fueron registradas. Los resultados muestran que no existiendo diferencias en las medidas antropométricas y de las bicicletas de los dos grupos de ciclistas, los profesionales obtuvieron más de eficiencia mecánica que los amateurs (1.5%, 2.1% y 2.4%, respectivamente). Esto se debió fundamentalmente a su menor fuerza e impulso negativos a todas las potencias. El tobillo fue la única articulación que sistemáticamente modificó su patrón de movimiento con el incremento de potencia. La eficiencia mecánica de pedaleo es también un factor determinante del nivel de rendimiento deportivo en ciclismo. Futuros estudios deben analizar la influencia del entrenamiento en esta variable.Muscular efficiency (e.g. gross, net and delta efficiency) is a key factor of cycling performance, and it improves after a training period. No previous study showed differences on mechanical efficiency (e.g. index of effectiveness and positive/negative impulses ratio) between cyclists of different competition level. Eleven professional cyclists and twenty-three amateur cyclists participated in this study. They performed three sets of pedalling at 200, 250 and 300 W (90 rpm). Both torque and impulse (negative and positive) were registered simultaneously with 2D kinematics in the right leg. Results show similar anthropometrical characteristics and similar bicycle dimensions in the two groups. Professional cyclists obtained more mechanical efficiency than amateur cyclists (1.5%, 2.1% and 2.4%, respectively). The lower minimum torque and lower negative impulse at all intensities justified these differences. Ankle was the only one joint which systematically altered its movement pattern when intensity was increased. Mechanical efficiency is too a key factor of performance in cycling. Future studies should evaluate the influence of training on this variable.Peer ReviewedAward-winnin

Supplementation of lamb diets with vitamin E and rosemary extracts on meat quality parameters

BACKGROUND Supranutritional supplementation of lamb diets with alpha-tocopherol is an effective method to reduce lipid oxidation and colour deterioration in meat products. However, alternative antioxidant sources have been proposed to replace the supranutritional vitamin E applications. RESULTS Indoor concentrate-fed Rasa Aragonesa male lambs (n = 480) were supplemented with increasing levels of all-rac-alpha-tocopheryl acetate (0.25, 0.5, 1.0 g kg(-1) compound feed), rosemary extract (0.20, 0.40, or 0.80 g kg(-1) compound feed), or rosemary extract embedded in a fat matrix (0.20, 0.40, or 0.80 g kg(-1) compound feed) for 14 days before slaughter. The longissimus thoracis et lumborum muscle from three lambs per pen (18 lambs per treatment) were modified-atmosphere packaged (70% O-2 + 30% CO2) and maintained under retail conditions for 14 days. Supranutritional supplementation with antioxidants had no effect (P > 0.05) on average daily weight gain, feed intake, and feed efficiency. Rosemary extract supplementation (with or without fat embedment) had no effect on lipid oxidation, myoglobin forms, or colour stability parameters, regardless of the dose. All vitamin E supplementation levels significantly affected lipid oxidation, colour stability (L*, C*, and h), myoglobin forms, and meat discoloration parameters compared with non-supplemented lambs. CONCLUSIONS This study demonstrates that, unlike vitamin E, neither dose nor protection of the rosemary extract had an effect on lipid oxidation or meat colour stability of lambs during the 14 days of storage under retail conditions

Spatio-temporal variability of mid-size pelagic fishes in the Gulf of Cadiz shelf waters in relation to climatic and environmental drivers

Understanding spatio-temporal distribution patterns of mid-size pelagic fish species (MSPF) is of great interest from the standpoint of both their management and conservation. MSPF inhabiting in the Gulf of Cadiz (SW Iberian Peninsula, Atlantic Ocean) are relevant because they contribute to a large number of individuals captured by the different fishing métiers operating in the area. So far, information on their spatial distribution and temporal changes remain scarce in the study area despite their implications in their stock discrimination and management. Herein, temporal changes of the distribution patterns of abundance and their response to environmental drivers of five MSPF (Scomber colias, Scomber scombrus, Trachurus trachurus, Trachurus mediterraneus and Trachurus picturatus) off the Gulf of Cadiz (GoC) are analyzed from acoustic surveys data for the period 2007-2017. In particular, we evaluated intra- and inter-specific overlapping over time and space using four spatial indices. The species’ abundance and distribution were estimated and mapped by applying geostatistical techniques taking into account autocorrelation between observations. Furthermore, analyses including environmental variables were tested to explain such spatial fluctuations. The main findings showed a progressive reduction of their distribution area in all species over time except for T. trachurus. The only species overlapping in space and time wasbetween T. picturatus and S. colias. The distribution areas of S. colias and T. mediterraneus were notably reduced and showed northern/southern preferences over the years. The main environmental variables shaping the abundance and distribution of each species were found to be chlorophyll and temperature. Climatic indices such as NAO and AMO affected MSPF by reducing or increasing their spatial distribution. Finally, we discuss implications of our findings to contribute to the implementation of the Marine Strategy Framework Directive in the frame of implementing an effective ecosystem approach to fisheries management in the region

Selective oxidation of alkyl and aryl glyceryl monoethers catalysed by an engineered and immobilised glycerol dehydrogenase

Enzymes acting over glyceryl ethers are scarce in living cells, and consequently biocatalytic transformations of these molecules are rare despite their interest for industrial chemistry. In this work, we have engineered and immobilised a glycerol dehydrogenase from Bacillus stearothermophilus (BsGlyDH) to accept a battery of alkyl/aryl glyceryl monoethers and catalyse their enantioselective oxidation to yield the corresponding 3-alkoxy/aryloxy-1-hydroxyacetones. QM/MM computational studies decipher the key role of D123 in the oxidation catalytic mechanism, and reveal that this enzyme is highly enantioselective towards S-isomers (ee > 99%). Through structure-guided site-selective mutagenesis, we find that the mutation L252A sculpts the active site to accommodate a productive configuration of 3-monoalkyl glycerols. This mutation enhances the kcat 163-fold towards 3-ethoxypropan-1, 2-diol, resulting in a specific activity similar to the one found for the wild-type towards glycerol. Furthermore, we immobilised the L252A variant to intensify the process, demonstrating the reusability and increasing the operational stability of the resulting heterogeneous biocatalyst. Finally, we manage to integrate this immobilised enzyme into a one-pot chemoenzymatic process to convert glycidol and ethanol into 3-ethoxy-1-hydroxyacetone and (R)-3-ethoxypropan-1, 2-diol, without affecting the oxidation activity. These results thus expand the uses of engineered glycerol dehydrogenases in applied biocatalysis for the kinetic resolution of glycerol ethers and the manufacturing of substituted hydroxyacetones. This journal i

Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer

Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide. DNA methylation is the most studied epigenetic alteration, occurring through a methyl radical addition to the cytosine base adjacent to guanine. Many tumor genes are inactivated by DNA methylation in gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil. All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples were surgically obtained at the João de Barros Barreto University Hospital, State of Pará, and were stored at -80°C before DNA extraction. Patients had never been submitted to chemotherapy or radiotherapy, nor did they have any other diagnosed cancer. None of the gastric cancer samples presented methylated DNA sequences for ANAPC1 and TP53. CDKN2A methylation was not detected in any normal gastric mucosa; however, the CDKN2A promoter was methylated in 30.4% of gastric cancer samples, with 35% methylation in diffuse-type and 26.9% in intestinal-type cancers. CDKN2A methylation was associated with the carcinogenesis process for ~30% diffuse-type and intestinal-type compared to non-neoplastic samples. Thus, ANAPC1 and TP53 methylation was probably not implicated in gastric carcinogenesis in our samples. CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FINEP/CT-INFRAFAEPAUniversidade Federal do Piauí Colegiado de BiomedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MorfologiaUniversidade Federal do Pará Instituto de Ciências Biológicas Laboratório de Citogenética HumanaHospital João de Barros Barreto Serviço de CirurgiaInstituto de Investigaciones BiomedicasUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de GenéticaUNIFESP, EPM, Depto. de MorfologiaFINEP/CT-INFRA: 0927-03SciEL

Determination of meloxicam in human plasma administrated with four drugs by LC method: application to a pilot bioavailability study

The development and validation of a simple and accurate method by HPLC-UV to quantify meloxicam (MLX) in human plasma and its application to comparative bioavailability study between MLX formulation and manipulated meloxicam + prednisone + cyclobenzaprine + diacerein + hidroxychloroquine is described. MLX and the internal standard (piroxicam) were extracted from plasma using protein precipitation. Chromatographic separation of meloxicam, piroxicam, other active ingredients, diacerein metabolite (Rhein) and plasma interferents was achieved with a C18 column, using a mobile phase of 20 mM sodium Hydrogen pH 3.0 and acetonitrile, with detection at 360 nm and retention times of 4.7, 3.7 and 4.1 min, respectively. The method was linear over the concentration range of 50 to 3000 ng/mL, meloxicam and piroxicam had an average recovery from plasma of 96 and 97 %, respectively. The precision and accuracy (intra-, inter-day) were less than 6 %. The method was successfully applied to a pilot pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years

[Abstract] OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/μL, 19% CD4 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability

65. Physical and clinical dosimetry by means of Monte Carlo using a process distribution tool

The choice of the most appropriate strategy in a Radiotherapy treatment is mainly based on the use of a planning system. With the introduction of new techniques (conformal and/or small fields, asymmetrical and non coplanar beams, true 3D calculations, IMRT) the trustworthiness of the algorithms is being questioned. An alternative verification procedure is every time more necessary to warranty a treatment delivery. The reliability of Monte Carlo is generally accepted. However, its clinical use has not been operative due to the high CPU times needed. During the last few years our objective has been focussed to reduce this time by means of new process distribution techniques. Tnis drop has made it feasible, not only the physical dosimetry under special conditions, but also a numerous variety of clinical cases: photon and electron conformal fields, Radiosurgery and IMRT. The carried out procedure is presented. Furthermore, experimental dosimetry data as well as conventional TPS calculations are compared with Monte Carlo simulations