654 research outputs found

    Association Of Nitric Oxide Synthase And Matrix Metalloprotease Single Nucleotide Polymorphisms With Preeclampsia And Its Complications.

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    Preeclampsia is one of the leading causes of maternal and neonatal morbidity and mortality in the world, but its appearance is still unpredictable and its pathophysiology has not been entirely elucidated. Genetic studies have associated single nucleotide polymorphisms in genes encoding nitric oxide synthase and matrix metalloproteases with preeclampsia, but the results are largely inconclusive across different populations. To investigate the association of single nucleotide polymorphisms (SNPs) in NOS3 (G894T, T-786C, and a variable number of tandem repetitions VNTR in intron 4), MMP2 (C-1306T), and MMP9 (C-1562T) genes with preeclampsia in patients from Southeastern Brazil. This prospective case-control study enrolled 77 women with preeclampsia and 266 control pregnant women. Clinical data were collected to assess risk factors and the presence of severe complications, such as eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. We found a significant association between the single nucleotide polymorphism NOS3 T-786C and preeclampsia, independently from age, height, weight, or the other SNPs studied, and no association was found with the other polymorphisms. Age and history of preeclampsia were also identified as risk factors. The presence of at least one polymorphic allele for NOS3 T-786C was also associated with the occurrence of eclampsia or HELLP syndrome among preeclamptic women. Our data support that the NOS3 T-786C SNP is associated with preeclampsia and the severity of its complications.10e013669

    Pathophysiological Mechanisms In Gaseous Therapies For Severe Malaria.

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    Over 200 million people worldwide suffer from malaria every year, a disease that causes 584,000 deaths annually. In recent years, significant improvements have been achieved on the treatment of severe malaria, with intravenous artesunate proving superior to quinine. However, mortality remains high at 8% in children and 15% in adults in clinical trials, and even worse in the case of cerebral malaria (18% and 30%, respectively). Moreover, some individuals who do not succumb to severe malaria present long-term cognitive deficits. These observations indicate that strategies focused only on parasite killing fail to prevent neurological complications and deaths associated with severe malaria, possibly because clinical complications are associated in part with a cerebrovascular dysfunction. Consequently, different adjunctive therapies aimed at modulating malaria pathophysiological processes are currently being tested. However, none of these therapies has shown unequivocal evidence in improving patients' clinical status. Recently, key studies have shown that gaseous therapies based mainly on nitric oxide (NO), carbon monoxide (CO) and hyperbaric (pressurized) oxygen (HBO) alter vascular endothelium dysfunction and modulate host immune response to infection. Considering gaseous administration as a promising adjunctive treatment against severe malaria cases, we review here the pathophysiological mechanisms and the immunological aspects of such therapies.8

    Registering the evolutionary history in individual-based models of speciation

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    Understanding the emergence of biodiversity patterns in nature is a central problem in biology. Theoretical models of speciation have addressed this question in the macroecological scale, but little has been done to connect microevolutionary processes with macroevolutionary patterns. Knowledge of the evolutionary history allows the study of patterns underlying the processes being modeled, revealing their signatures and the role of speciation and extinction in shaping macroevolutionary patterns. In this paper we introduce two algorithms to record the evolutionary history of populations and species in individual-based models of speciation, from which genealogies and phylogenies can be constructed. The first algorithm relies on saving ancestor–descendant relationships, generating a matrix that contains the times to the most recent common ancestor between all pairs of individuals at every generation (the Most Recent Common Ancestor Time matrix, MRCAT). The second algorithm directly records all speciation and extinction events throughout the evolutionary process, generating a matrix with the true phylogeny of species (the Sequential Speciation and Extinction Events, SSEE). We illustrate the use of these algorithms in a spatially explicit individual-based model of speciation. We compare the trees generated via MRCAT and SSEE algorithms with trees inferred by methods that use only genetic distance between individuals of extant species, commonly used in empirical studies and applied here to simulated genetic data. Comparisons between trees are performed with metrics describing the overall topology, branch length distribution and imbalance degree. We observe that both MRCAT and distance-based trees differ from the true phylogeny, with the first being closer to the true tree than the second.Facultad de Ciencias Naturales y Muse

    Characterization of oral enterobacteriaceae prevalence and resistance profile in chronic kidney disease patients undergoing peritoneal dialysis

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    Chronic Kidney Disease (CKD) is a growing public-health concern worldwide. Patients exhibit compromised immunity and are more prone to infection than other populations. Therefore, oral colonization by clinically relevant members of the Enterobacteriaceae family, major agents of both nosocomial and dialysis-associated infections with frequent prevalence of antibiotic resistances, may constitute a serious risk. Thus, this study aimed to assess the occurrence of clinically relevant enterobacteria and their antibiotic resistance profiles in the oral cavity of CKD patients undergoing peritoneal dialysis (CKD-PD) and compare it to healthy controls. Saliva samples from all the participants were cultured on MacConkey Agar and evaluated regarding the levels of urea, ammonia, and pH. Bacterial isolates were identified and characterized for antibiotic resistance phenotype and genotype. The results showed that CKD-PD patients exhibited significantly higher salivary pH, urea, and ammonia levels than controls, that was accompanied by higher prevalence and diversity of oral enterobacteria. Out of all the species isolated, only the prevalence of Raoultella ornithinolytica varied significantly between groups, colonizing the oral cavity of approximately 30% of CKD-PD patients while absent from controls. Antibiotic resistance phenotyping revealed mostly putative intrinsic resistance phenotypes (to amoxicillin, ticarcillin, and cephalothin), and resistance to sulfamethoxazole (~43% of isolates) and streptomycin (~17%). However, all isolates were resistant to at least one of the antibiotics tested and multidrug resistance isolates were only found in CKD-PD group (31,6%). Mobile genetic elements and resistance genes were detected in isolates of the species Raoultella ornithinolytica, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, and Enterobacter asburiae, mostly originated from CKD-PD patients. PD-related infection history revealed that Enterobacteriaceae were responsible for ~8% of peritonitis and ~ 16% of exit-site infections episodes in CKD-PD patients, although no association was found to oral enterobacteria colonization at the time of sampling. The results suggest that the CKD-induced alterations of the oral milieu might promote a dysbiosis of the commensal oral microbiome, namely the proliferation of clinically relevant Enterobacteriaceae potentially harboring acquired antibiotic resistance genes. This study highlights the importance of the oral cavity as a reservoir for pathobionts and antibiotic resistances in CKD patients undergoing peritoneal dialysis.info:eu-repo/semantics/publishedVersio

    Black box modelling of a latent heat thermal energy storage system coupled with heat pipes

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    This paper presents black box models to represent a LHTESS (Latent Heat Thermal Energy Storage System) coupled with heat pipes, aimed at increasing the storage performance and at decreasing the time of charging/discharging. The presented storage system is part of a micro solar CHP plant and the developed model is intended to be used in the simulation tool of the overall system, thus it has to be accurate but also fast computing. Black box data driven models are considered, trained by means of numerical data obtained from a white box detailed model of the LHTESS and heat pipes system. A year round simulation of the system during its normal operation within the micro solar CHP plant is used as dataset. Then the black box models are trained and finally validated on these data. Results show the need for a black box model that can take into account the different seasonal performance of the LHTESS. In this analysis the best fit was achieved by means of Random Forest models with an accuracy higher than 90%

    Acacia wood fractionation using deep eutectic solvents: extraction, recovery, and characterization of the different fractions

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    The selective extraction and recovery of different lignocellulosic molecules of interest from forestry residues is increasing every day not only to satisfy the needs of driving a society toward more sustainable approaches and materials (rethinking waste as a valuable resource) but also because lignocellulosic molecules have several applications. For this purpose, the development of new sustainable and ecologically benign extraction approaches has grown significantly. Deep eutectic solvents (DESs) appear as a promising alternative for the processing and manipulation of biomass. In the present study, a DES formed using choline chloride and levulinic acid (ChCl:LA) was studied to fractionate lignocellulosic residues of acacia wood (Acacia dealbata Link), an invasive species in Portugal. Different parameters, such as temperature and extraction time, were optimized to enhance the yield and purity of recovered cellulose and lignin fractions. DESs containing LA were found to be promising solvent systems, as the hydrogen bond donor was considered relevant in relation to lignin extraction and cellulose concentration. On the other hand, the increase in temperature and extraction time increases the amount of extracted material from biomass but affects the purity of lignin. The most promising DES system, ChCELA in a ratio of 1:3, was found to not significantly depolymerize the extracted lignin, which presented a similar molecular weight to a la-aft lignin. Additionally, the P-31 NMR results revealed that the extracted lignin has a high content of phenolic OH groups, which favor its reactivity. A mixture of ChCl:LA may be considered a fully renewable solvent, and the formed DES presents good potential to fractionate wood residues.info:eu-repo/semantics/publishedVersio

    Oral colonization by yeasts in HIV-positive patients in Brazil

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    INTRODUCTION: In HIV-infected patients, colonization of the oral cavity by potential pathogenic yeast may lead to development of systemic fungemia. We evaluated the prevalence of yeast in the oral cavity of Brazilian HIV-positive patients and verified whether or not the species characterized were enzymatically active. Furthermore, the species identified were tested for their susceptibility to antifungal treatment. METHODS: Patient saliva and oropharyngeal candidiasis samples were collected from 60 seropositive HIV patients and identified by the API20C system. Enzymatic activity was evaluated by the production of proteinase and phospholipase. Susceptibility to antifungal treatments were determined using the broth microdilution method. RESULTS: the most commonly isolated species were C. albicans (51.56%) followed by non-albicans Candida species (43.73%), Trichosporon mucoides (3.12%) and Kodamaea ohmeri (1.56%). Oral colonization by association of different species was observed in 42% of the patients. Enzymatic activity was verified in most of species isolated, except for C. glabrata, C. lusitaniae and C. guilliermondii. Resistance to Fluconazole and Amphotericin B was observed in isolates of C. albicans, C. glabrata, C. parapsilosis, C. krusei, and K. ohmeri. CONCLUSION: HIV-positive patients are orally colonized by single or multiple species of yeast that are occasionally resistant to Fluconazole or Amphotericin B.INTRODUÇÃO: Em pacientes infectados pelo HIV, a colonização da cavidade bucal por leveduras patogênicas pode levar ao desenvolvimento de fungemias. No presente estudo, avaliamos a prevalência de leveduras na cavidade bucal de pacientes HIV-positivos e verificamos se as espécies isoladas foram enzimaticamente ativas. Além disso, as espécies identificadas foram testadas quanto à suscetibilidade a antifúngicos. MÉTODOS: Amostras de saliva e de candidose orofaríngea foram coletadas de 60 pacientes soropositivos para HIV e identificados pelo sistema API20C. A atividade enzimática foi avaliada pela produção de proteinase e fosfolipase. A suscetibilidade a antifúngicos foi determinada utilizando o método de microdiluição em caldo. RESULTADOS: As espécies mais comumente isoladas foram C. albicans (51,56%), seguido por espécies de Candida não-albicans (43,73%), Trichosporon mucoides (3,12%) e Kodamaea ohmeri (1,56%). A colonização bucal por associação de diferentes espécies foi observada em 42% dos pacientes. A atividade enzimática foi verificada na maioria das espécies isoladas, com exceção de C. glabrata, C. lusitaniae e C. guilliermondii. Resistência ao fluconazol e anfotericina B foi observada em isolados de C. albicans, C. glabrata, C. parapsilosis, C. krusei, e K. ohmeri. CONCLUSÃO: Os pacientes HIV-positivos são colonizados por espécies únicas ou múltiplas de levedura que ocasionalmente são resistentes ao fluconazol ou anfotericina B

    Enzyme replacement therapy with galsulfase in 34 children younger than five years of age with MPS VI

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    Background: Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme (R), BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age.Methods: Data from patients who initiated treatment at <5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated.Results: A significant negative correlation was seen with treatment with ERT and urinary GAG levels. of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved.Conclusions: the prescribed dosage of 1 mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease progression and treatment efficacy and safety in this young patient population. (C) 2013 Elsevier Inc. All rights reserved.BioMarin Pharmaceutical Inc.ShireGenzymeBioMarinFiocruz MS, Inst Nacl Saude Mulher Crianca & Adolescente Fern, Ctr Genet Med, BR-22250020 Rio de Janeiro, RJ, BrazilUniv Fed Bahia, Serv Genet Med, Salvador, BA, BrazilHosp Albert Sabin, Fortaleza, Ceara, BrazilUniv Fed Mato Grosso do Sul, Fac Med, Campo Grande, MS USAUniv São Paulo, Inst Crianca, São Paulo, BrazilHosp Barao de Lucena, Recife, PE, BrazilUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilCtr Reabilitacao Infantil, Natal, RN, BrazilHosp Univ Maranhao, Sao Luis, MA, BrazilUniversidade Federal de São Paulo, Ctr Referencia Erros Inatos Metab, São Paulo, SP, BrazilHosp São Paulo, Enzyme Replacement Therapy Serv, Hosp & Maternidade Celso Pierro, São Paulo, BrazilUniv Fed Rio Grande do Norte, HOSPED, Hosp Pediat Prof Heriberto Ferreira Bezerra, Natal, RN, BrazilUniv Fortaleza, Fortaleza, Ceara, BrazilUniv Fed Rio Grande do Norte, BR-59072970 Natal, RN, BrazilUniv Fed Triangulo Mineiro, Uberaba, MG, BrazilHosp Clin Acre, Rio Branco, AC, BrazilUniv Fed Espirito Santo, HUCAM, Vitoria, ES, BrazilUniversidade Federal de São Paulo, Ctr Referencia Erros Inatos Metab, São Paulo, SP, BrazilHosp São Paulo, Enzyme Replacement Therapy Serv, Hosp & Maternidade Celso Pierro, São Paulo, BrazilWeb of Scienc
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