Nucleotide-Binding Oligomerization Domain 1 (NOD1) Agonists Prevent SARS-CoV-2 Infection in Human Lung Epithelial Cells through Harnessing the Innate Immune Response.

The lung is prone to infections from respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A challenge in combating these infections is the difficulty in targeting antiviral activity directly at the lung mucosal tract. Boosting the capability of the respiratory mucosa to trigger a potent immune response at the onset of infection could serve as a potential strategy for managing respiratory infections. This study focused on screening immunomodulators to enhance innate immune response in lung epithelial and immune cell models. Through testing various subfamilies and pathways of pattern recognition receptors (PRRs), the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family was found to selectively activate innate immunity in lung epithelial cells. Activation of NOD1 and dual NOD1/2 by the agonists TriDAP and M-TriDAP, respectively, increased the number of IL-8+ cells by engaging the NF-κB and interferon response pathways. Lung epithelial cells showed a stronger response to NOD1 and dual NOD1/2 agonists compared to control. Interestingly, a less-pronounced response to NOD1 agonists was noted in PBMCs, indicating a tissue-specific effect of NOD1 in lung epithelial cells without inducing widespread systemic activation. The specificity of the NOD agonist pathway was confirmed through gene silencing of NOD1 (siRNA) and selective NOD1 and dual NOD1/2 inhibitors in lung epithelial cells. Ultimately, activation induced by NOD1 and dual NOD1/2 agonists created an antiviral environment that hindered SARS-CoV-2 replication in vitro in lung epithelial cells.

Investigación científica en el campo de la infancia: consideraciones sobre la aplicabilidad de los requisitos éticos / Scientific research study on childhood: considerations on the applicability of ethical requirements / Pesquisa científica no campo da infância: considerações sobre a aplicabilidade dos requisitos éticos

El artículo aborda un tema particularmente sensible para la investigación científica como lo son los estudios que involucran directamente a niños y niñas. El valor social y la relevancia científica de la investigación en este campo es indudable, sin embargo, su justificación requiere especial detenimiento en las condiciones para el ejercicio de sus derechos antes, durante y después del proceso de investigación. La naturalización de su denominación como "población vulnerable" y el ejercicio de su autonomía relativa, son dos dimensiones principales aquí. El artículo navega por preguntas que no se resuelven aquí precisamente, ¿qué garantías para el proceso efectivo de asentimiento informado?, ¿cómo acompañar en la toma de decisiones sin sustituir al niño y la niña? Sin embargo, sí avanza en la instalación de dilemas y aspectos conceptuales y reflexivos sustantivos en la práctica científica.

The article deals with a particularly sensitive topic for scientific research, such as research studies that directly involve boys and girls. The social value and scientific relevance of research in this field is unquestionable; however, its justification requires special care regarding the conditions of children's rights before, during and after the research process. The naturalization of their denomination as a "vulnerable population" and the exercise of their relative autonomy are the two main dimensions of this study. This paper explores questions that are not answered in it precisely: what guarantees informed consent during the effective process? How to accompany the decision making process without replacing the boy and the girl? However, the study makes progress regarding the setting of substantive conceptual and reflective dilemmas and aspects in scientific practice.

O artigo trata de um tema particularmente sensível para a pesquisa científica, os estudos que envolvem diretamente meninos e meninas. O valor social e a relevância científica da pesquisa neste campo é inquestionável, porém, sua justificativa requer cuidados especiais nas condições de exercício dos direitos da criancas, durante e após o processo de pesquisa. A naturalização de sua denominação como "população vulnerável" e o exercício de sua autonomia relativa são as duas dimensões principais deste paper. O artigo explora por questões que não são aqui resolvidas de forma precisa: quais sao as garantias para o processo efetivo de assentimento informado? Como acompanhar o proceso da tomada de decisões sem substituir o menino e a menina? No entanto, realizamos um avanço na instalação de dilemas e aspectos conceituais e reflexivos substantivos na prática científica.

Remodeling the bladder tumor immune microenvironment by mycobacterial species with changes in their cell envelope composition.

Intravesical BCG instillation after bladder tumor resection is the standard treatment for non-muscle invasive bladder cancer; however, it is not always effective and frequently has undesirable side effects. Therefore, new strategies that improve the clinical management of patients are urgently needed. This study aimed to comprehensively evaluate the bladder tumor immune microenvironment profile after intravesical treatment with a panel of mycobacteria with variation in their cell envelope composition and its impact on survival using an orthotopic murine model to identify more effective and safer therapeutic strategies. tumor-bearing mice were intravesically treated with a panel of BCG and M. brumae cultured under different conditions. Untreated tumor-bearing mice and healthy mice were also included as controls. After mycobacterial treatments, the infiltrating immune cell populations in the bladder were analysed by flow cytometry. We provide evidence that mycobacterial treatment triggered a strong immune infiltration into the bladder, with BCG inducing higher global absolute infiltration than M. brumae. The induced global immune microenvironment was strikingly different between the two mycobacterial species, affecting both innate and adaptive immunity. Compared with M. brumae, BCG treated mice exhibited a more robust infiltration of CD4+ and CD8+ T-cells skewed toward an effector memory phenotype, with higher frequencies of NKT cells, neutrophils/gMDSCs and monocytes, especially the inflammatory subset, and higher CD4+ TEM/CD4+ Treg and CD8+ TEM/CD4+ Treg ratios. Conversely, M. brumae treatment triggered higher proportions of total activated immune cells and activated CD4+ and CD8+ TEM cells and lower ratios of CD4+ TEM cells/CD4+ Tregs, CD8+ TEM cells/CD4+ Tregs and inflammatory/reparative monocytes. Notably, the mycobacterial cell envelope composition in M. brumae had a strong impact on the immune microenvironment, shaping the B and myeloid cell compartment and T-cell maturation profile and thus improving survival. Overall, we demonstrate that the bladder immune microenvironment induced by mycobacterial treatment is species specific and shaped by mycobacterial cell envelope composition. Therefore, the global bladder immune microenvironment can be remodelled, improving the quality of infiltrating immune cells, the balance between inflammatory and regulatory/suppressive responses and increasing survival.

Mycobacterial surface characters remodeled by growth conditions drive different tumor-infiltrating cells and systemic IFN-γ/IL-17 release in bladder cancer treatment.

The mechanism of action of intravesical Mycobacterium bovis BCG immunotherapy treatment for bladder cancer is not completely known, leading to misinterpretation of BCG-unresponsive patients, who have scarce further therapeutic options. BCG is grown under diverse culture conditions worldwide, which can impact the antitumor effect of BCG strains and could be a key parameter of treatment success. Here, BCG and the nonpathogenic Mycobacterium brumae were grown in four culture media currently used by research laboratories and BCG manufacturers: Sauton-A60, -G15 and -G60 and Middlebrook 7H10, and used as therapies in the orthotopic murine BC model. Our data reveal that each mycobacterium requires specific culture conditions to induce an effective antitumor response. since higher survival rates of tumor-bearing mice were achieved using M. brumae-A60 and BCG-G15 than the rest of the treatments. M. brumae-A60 was the most efficacious among all tested treatments in terms of mouse survival, cytotoxic activity of splenocytes against tumor cells, higher systemic production of IL-17 and IFN-É£, and bladder infiltration of selected immune cells such as ILCs and CD4TEM. BCG-G15 triggered an antitumor activity based on a massive infiltration of immune cells, mainly CD3+ (CD4+ and CD8+) T cells, together with high systemic IFN-É£ release. Finally, a reduced variety of lipids was strikingly observed in the outermost layer of M. brumae-A60 and BCG-G15 compared to the rest of the cultures, suggesting an influence on the antitumor immune response triggered. These findings contribute to understand how mycobacteria create an adequate niche to help the host subvert immunosuppressive tumor actions.

Embracing complexity in Drosophila cancer models.

Cancer continues to be a leading cause of death worldwide, largely due to metastases and cachexia. It is a complex disease that is commonly associated with a variety of comorbidities. With global increases in ageing populations and obesity, multimorbidity is a rapidly growing clinical issue in the context of cancer. Cancer is also genetically heterogeneous, with a tumour's unique profile determining its incidence of metastasis, degree of cachexia and response to therapeutics. These complexities of human cancer are difficult to replicate in animal models and are, in part, responsible for the failures in translational cancer research. In this Perspective, we highlight the fruit fly, Drosophila melanogaster, as a powerful model organism to investigate multimorbidity and tumour diversity. We also highlight how harnessing these complexities in Drosophila can, potentially, enhance cancer research and advance therapeutic discoveries.

Photoprotection and Photostability of a New Lignin-Gelatin-Baccharis antioquensis-Based Hybrid Biomaterial.

The aim of this study was to develop a new hybrid biomaterial that could photo-stabilize and improve the photoprotective capacity of a Baccharis antioquensis extract. Different combinations of lignin/gelatin/natural extract were applied to prepare hybrid biomaterial nanoparticles (NPs), which were then incorporated into an emulsion. The in vitro photoprotection and photostability were evaluated. The methanolic extract showed high phenolic content (646.4 ± 9.5 mg GAE/g dry extract) and a DPPH radical assay revealed that the antiradical capacity of the extract (0.13 to 0.05 g extract/mmol DPPH) was even better than that of BHT. The particle size of the hybrid biomaterial ranged from 100 to 255 nm; a polydispersity index (PdI) between 0.416 and 0.788 is suitable for topical use in dermocosmetic products. The loading capacity of the extract ranged from 27.0 to 44.5%, and the nanoparticles (NPs) showed electrostatic stability in accordance with the zeta potential value. We found that the formulation based on lignin: extract (1:1 ratio) and gelatin: lignin: extract (0.5:0.5:1 ratio) demonstrated photoprotection qualities with a sun protection factor (SPF) ranging from 9.4 to 22.6. In addition, all the hybrid NP-formulations were time-stable with %SPFeff and %UVAPFeff greater than 80% after exposure to 2 h of radiation. These results suggest that the hybrid biopolymer-natural extract improved the photoprotection and photostability properties, as well as the antiradical capacity, of the B. antioquensis extract, and may be useful for trapping high polyphenol content from natural extracts, with potential application in cosmeceutical formulations.

Impact of Long-Term Cryopreservation on Blood Immune Cell Markers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Biomarker Discovery.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmune disorder characterized by numerous symptoms of unknown etiology. The ME/CFS immune markers reported so far have failed to generate a clinical consensus, perhaps partly due to the limitations of biospecimen biobanking. To address this issue, we performed a comparative analysis of the impact of long-term biobanking on previously identified immune markers and also explored additional potential immune markers linked to infection in ME/CFS. A correlation analysis of marker cryostability across immune cell subsets based on flow cytometry immunophenotyping of fresh blood and frozen PBMC samples collected from individuals with ME/CFS (n = 18) and matched healthy controls (n = 18) was performed. The functionality of biobanked samples was assessed on the basis of cytokine production assay after stimulation of frozen PBMCs. T cell markers defining Treg subsets and the expression of surface glycoprotein CD56 in T cells and the frequency of the effector CD8 T cells, together with CD57 expression in NK cells, appeared unaltered by biobanking. By contrast, NK cell markers CD25 and CD69 were notably increased, and NKp46 expression markedly reduced, by long-term cryopreservation and thawing. Further exploration of Treg and NK cell subsets failed to identify significant differences between ME/CFS patients and healthy controls in terms of biobanked PBMCs. Our findings show that some of the previously identified immune markers in T and NK cell subsets become unstable after cell biobanking, thus limiting their use in further immunophenotyping studies for ME/CFS. These data are potentially relevant for future multisite intervention studies and cooperative projects for biomarker discovery using ME/CFS biobanked samples. Further studies are needed to develop novel tools for the assessment of biomarker stability in cryopreserved immune cells from people with ME/CFS.

Combined assessment of peritumoral Th1/Th2 polarization and peripheral immunity as a new biomarker in the prediction of BCG response in patients with high-risk NMIBC.

Intravesical Bacille Calmette-Guérin (BCG) remains the most effective treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), unfortunately there is no validated biomarker to predict clinical outcome. Here we tried to explore the possibility that a combination of the density of peritumoral infiltrating cells (Th1, Th2 and PD-L1) and the composition of peripheral immune cells (neutrophil and lymphocyte counts) could generate a more reliable prognostic biomarker. Twenty-two patients with high-risk NMIBC treated with BCG (10 BCG nonresponders and 12 BCG responders) were selected. BCG responders had significantly lower level of peritumoral T-bet+ cells with an associated higher GATA-3+/T-bet+ ratio (p = 0.04, p = 0.02, respectively). Furthermore, the immune polarization in tissue (GATA-3+/T-bet+ ratio) adjusted for the systemic inflammation (neutrophil-to-lymphocyte ratio) showed a significantly higher association with the BCG response (p = 0.004). A survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with a lower T-bet+/Lymphocyte ratio and higher GTR/NLR (p = 0.01). No association was observed between peritumoral PD-L1+ expression and the BCG response. In conclusion, alterations in overall immune function, both local and systemic, may influence the therapeutic response to BCG, therefore a combined analysis of tumoral (Th2/Th1 ratio) and peripheral (NLR) immune composition prior to treatment may be a promising approach to predict the BCG response in high-risk NMIBC patients.

Estudio de estabilidad acelerado en café verde: una aproximación sensorial / Accelerated stability test in green coffee: A sensory approach / Estudo da estabilidade acelerada em café verde: uma abordagem sensorial

Resumen Introducción: el café verde es un producto del mercado mundial cuyo precio es determinado por sus características sensoriales en taza; sin embargo, estos atributos cambian durante el almacenamiento, convirtiendo esta etapa de la cadena productiva en una etapa crucial para garantizar la calidad del producto. Objetivo: en este trabajo se buscó determinar el impacto de diversos factores de almacenamiento en la calidad sensorial y física del café verde colombiano, bajo condiciones de estabilidad acelerada y natural. Materiales y métodos: cerezas maduras de café de la misma cosecha fueron procesadas en paralelo por dos métodos postcosecha para obtener café lavado y semilavado, después se sometieron a diferentes tratamientos de almacenamiento. Resultados: el café verde almacenado en condiciones ambientales presentó notas propias de reposo, la densidad y los parámetros del color cambiaron de diferente manera en los dos tipos de café. El comportamiento del café verde en almacenamiento acelerado varió en función de los métodos de beneficio; en el café lavado, el almacenamiento con humedad afecto los atributos sensoriales y alteró la densidad, el % HR y los parámetros de color L* y b*; en el café semilavado, el oxígeno fue el factor de mayor impacto, afectando también la densidad y el color. Conclusiones: diferentes métodos de beneficio de café no solo dan lugar a diferencias en los perfiles de la calidad sensorial, sino que también condicionan el comportamiento del grano de café verde durante el almacenamiento.

Abstract Introduction: Green coffee i s a product of the world market whose price is determined by its sensory characteristics in the cup; however, these attributes change during storage, turning this stage of the production chain into a crucial stage to guarantee product quality. Objective: In the present work we sought to determine the impact of various storage factors on the sensory and physical quality of Colombian green coffee, under conditions of accelerated and natural stability. Materials and methods: Mature coffee cherries from the same harvest were processed in parallel by two post-harvest methods to obtain washed and semi-washed coffee, and then they were subjected to different storage treatments. Results: It was found that green coffee stored under environmental conditions had the characteristic notes of rest; in addition, density and color parameters changed differently in the two types of coffee. The behavior of green coffee in accelerated storage treatments varied according to the processing methods. For the case of washed coffee, storage with humidity negatively affected sensory attributes and also altered density, the RH % and color parameters L* and b*; for the semi-washed coffee, oxygen was the factor that promoted the greatest sensory changes, also affecting density and color. Conclusions: Different coffee post-harvest processes not only give rise to differences in the profiles of sensory quality but also condition the behavior of green coffee bean during storage.

Resumo Introdução: O café verde é um produto do mercado mundial cuj o preço é determinado pelas suas características sensoriais na xícara; no entanto, estes atributos mudam durante o armazenamento, tornando esta etapa da cadeia produtiva em uma etapa crucial para garantir a qualidade do produto. Objetivo: em este trabalho se procura determinar o impacto de diversos fatores de armazenamento na qualidade sensorial e física do café verde colombiano, sob condições de estabilidade acelerada e natural. Materiais e métodos: cerejas maduras do café da mesma colheita foram processadas em paralelo pelos métodos pós-colheita para obter café lavado e semi-lavado, despois someteram-se a diferentes tratamentos de armazenamento. Resultados: o café verde armazenado em condições ambientais apresentou notas próprias de repouso, a densidade e os parâmetros da color mudaram de diferente maneira nos dois tipos de café. O comportamento do café verde em armazenamento acelerado variou em função dos métodos de benefício; no café lavado, o armazenamento com umidade afetou os atributos sensoriais e alterou a densidade, o %HR e os parâmetros da color L* e b*; no café semi-lavado, o oxigénio foi o fator de maior impacto, afetando também a densidade e a color. Conclusões: diferentes processos de pós-colheita do café não só produziriam diferenças nos perfis de qualidade sensorial, mas também condicionam o comportamento do grão de café verde durante o armazenamento.

Adaptación y construcción de identidad en jóvenes con parálisis cerebral: un estudio cualitativo de enfoque biográfico / Adaptation and identity construction of young people with cerebral palsy: a qualitative study with a biographical approach

Introducción: El proceso de adaptación a la situación de discapacidad y la identidad, son variables psicológicas que pueden incidir en la participación e inclusión social de jóvenes en situación de discapacidad y que han sido poco estudiadas en nuestro país. Objetivo: Analizar las experiencias de vida que los jóvenes con parálisis cerebral (PC) destacan en su adaptación a la situación de discapacidad y su construcción de identidad. Método: Estudio cualitativo de análisis de contenido con enfoque biográfico, en una muestra intencionada de 5 jóvenes con diagnóstico de PC, sin compromiso cognitivo, entre 18 y 21 años de edad, usuarios activos de Teletón. Resultados: Las experiencias asociadas a estrategias parentales, participación con pares, procedimientos invasivos en la rehabilitación inciden en el proceso de construcción de identidad y la adaptación a la situación de discapacidad. La adaptación aparece como un proceso fluctuante a lo largo del desarrollo evolutivo, con componentes afectivos y cognitivos. Conclusiones: El proceso de adaptación a la situación de discapacidad progresa hacia construir significados trascendentales y positivos sobre sí mismos. Los resultados sugieren la necesidad de diseñar intervenciones de apoyo en periodos críticos del desarrollo psicológico para promover el bienestar de usuarios de servicios de rehabilitación integrales.

Adaptation and identity construction of young people with cerebral palsy. A qualitative study with a biographical approach Introduction: The psychological process of adaptation to disability and personal identity has an influence on social participation and inclusion of young people with disabilities; however it has been poorly researched in Chile. Objective: To analyze life experiences that young people with cerebral palsy (CP) highlight in their process of adapting to disability and identity construction. Method: Qualitative study of content analysis with a biographical approach, in an intentional sample of 5 young people diagnosed with CP, without cognitive impairment, ages ranging from 19 to 21 years, active users of Teletón Institute. Results: The experience related to parental strategies, relationship with peers, invasive procedures during the rehabilitation process, have an incidence on the processes of identity construction and adaptation to the disability. Adaptation appears as a process with fluctuations in intensity throughout the evolutionary development with emotional and cognitive components. Conclusions: The process of adaptation to the disability progresses to the construction of relevant and positive significance about themselves. The results suggest the need to design interventions to provide support in critical periods of psychological development in order to promote the wellbeing of the users of integral rehabilitations services.

Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice.

The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses of ex vivo splenocytes cultured with mycobacteria antigens. In both BCG- and M. brumae-treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used.

Elevated humoral response to cytomegalovirus in HIV-infected individuals with poor CD4+ T-cell immune recovery.

Some HIV-infected c-ART-suppressed individuals show incomplete CD4+ T-cell recovery, abnormal T-cell activation and higher mortality. One potential source of immune activation could be coinfection with cytomegalovirus (CMV). IgG and IgM levels, immune activation, inflammation and T-cell death in c-ART-suppressed individuals with CD4+ T-cell counts >350 cells/µL (immunoconcordant, n = 133) or <350 cells/µL (immunodiscordant, n = 95) were analyzed to evaluate the effect of CMV humoral response on immune recovery. In total, 27 HIV-uninfected individuals were included as controls. In addition, the presence of CMV IgM antibodies was retrospectively analyzed in 58 immunoconcordant individuals and 66 immunodiscordant individuals. Increased CMV IgG levels were observed in individuals with poor immune reconstitution (p = 0.0002). Increased CMV IgG responses were significantly correlated with lower nadir and absolute CD4+ T-cell counts. In contrast, CMV IgG responses were positively correlated with activation (HLA-DR+) and death markers in CD4+ T-cells and activated memory CD8+ T-cells (CD45RA-CD38+). Longitudinal subanalysis revealed an increased frequency of IgM+ samples in individuals with poor CD4+ T-cell recovery, and an association was observed between retrospective IgM positivity and the current level of IgG. The magnitude of the humoral immune response to CMV is associated with nadir CD4+ T-cell counts, inflammation, immune activation and CD4+ T-cell death, thus suggesting that CMV infection may be a relevant driving force in the increased morbidity/mortality observed in HIV+ individuals with poor CD4+ T-cell recovery.

Estabilidad de antocianinas durante el almacenamiento de jugos de arándanos / Anthocyanins stability during storage of blueberries juice

Antecedentes: Los arándanos y productos de arándano tienen alto valor nutricional, especialmente por su alto contenido de antocianinas. Estas son potentes antioxidantes y poseen alta capacidad de secuestrar radicales libres. Así, los arándanos y productos de arándanos han resultado atractivos para los consumidores interesados en alimentos funcionales. Sin embargo, los tratamientos térmicos y posterior almacenamiento de productos alimenticios influyen en el contenido de antocianinas. La cinética de degradación de las antocianinas puede ser evaluada desde una perspectiva termodinámica, basada en funciones como energía libre, entalpía, entropía y energía de activación. Objetivos: Se estudió el efecto de la pasteurización y la estabilidad de antocianinas presentes en jugos de arándanos, sin pasteurizar y pasteurizados, durante el almacenamiento. Métodos: Jugos de arándanos sin pasteurizar y pasteurizados fueron almacenados a -18, 0, 5 y 10°C durante 148 días. A intervalos de tiempos se cuantificó la concentración de antocianinas monoméricas totales. Se realizó un Análisis de Componentes Principales y los resultados experimentales se ajustaron a modelos cinéticos de orden cero y uno, y a los modelos de Arrhenius y Eyring. Resultados: La pasteurización provocó disminución del 28,5% en la concentración inicial de antocianinas monoméricas totales, mientras que para todas las temperaturas estudiadas, la disminución de antocianinas en función del tiempo de almacenamiento siguió una cinética de primer orden. En el jugo sin pasteurizar, la constante de velocidad de degradación varió entre 0,0080 - 0,0084 días-1 y el tiempo de vida media, entre 75 - 87 días. En el jugo pasteurizado, la constante de velocidad de degradación varió entre 0,0023 - 0,0060 días-1 y el tiempo de vida media, entre 116-301 días. En éste la energía de activación, la energía libre de Gibbs, entalpía y entropía de activación fueron 44,66 kJ/mol, 83,80 kJ/mol, 42,35 kJ/mol y -139,09 J/mol.K, respectivamente". Conclusiones: El tratamiento de pasteurización provocó disminución del 28,5% en la concentración de antocianinas monoméricas totales iniciales de los jugos de arándano. La estabilidad de las antocianinas durante el almacenamiento fue mayor en los jugos pasteurizados, siendo mayor cuando se almacenaron a 0°C; mientras que en los jugos pasteurizados almacenados a -18°C las antocianinas mostraron menor estabilidad.

Background: The blueberries and blueberry products has great nutritional value, primarily because it has high anthocyanin content. Anthocyanins are potent antioxidants and have high radical-scavenging activities. Thus, the blueberry and blueberry products has become very appealing to consumers interested in functional foods. However, the anthocyanins content is affected by heat treatment and subsequent storage. The kinetics degradation of anthocyanins can be evaluated from a thermodynamic perspective, based on activation functions such as free energy, enthalpy, entropy and activation energy. Objectives: pasteurization effect and anthocyanins stability were studied during storage of pasteurized and nonpasteurized blueberries juices. Methods: Pasteurized and non-pasteurized blueberries juices were store at -18, 0, 5 and 10°C during 148 days. Total monomeric anthocyanins concentration was quantified at different times. Principal Components Analysis was performed and experimental results were adjusted to zero and first-order kinetic models as well as to Arrhenius and Eyring ones. Results: A decrease in total monomeric anthocyanins original concentration was 28.5 % due to pasteurization while for all temperatures studied, the reduction followed a first-order kinetic during storage. Degradation rate constant varied between 0.0080 - 0.0084 days-1 and half-life, 75 - 87 days for non-pasteurized juices, whereas these parameters were among 0.0023 - 0.0060 days-1 and 116 - 301 days, respectively for pasteurized ones. Activation energy was 44.66 kJ/mol while Gibbs free energy, enthalpy and entropy were 83.80 kJ/ mol, 42.35 kJ/mol and -139.09 J/mol. K respectively, for the latter juices. Conclusions: Pasteurization caused in a 28.5 % loss of initial total monomeric anthocyanins. Anthocyanins stability was higher in pasteurized blueberries juices and resulted even bigger when store at 0°C, while in pasteurized juices stored -18 ° C were less stable anthocyanins.

Single oral dose of maraviroc does not prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers.

OBJECTIVE: Maraviroc (MVC) is a potential candidate for 'on demand' preexposure prophylaxis. In the present study, we evaluated the efficacy of a single oral dose of MVC to prevent ex-vivo HIV-1 infection of rectal tissue in humans. DESIGN AND METHODS: Eight HIV-1-negative healthy volunteers received a single oral dose of MVC (300 or 600 mg), and two additional volunteers received tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, 300/200 mg) for 10 days. Rectal biopsies were performed prior to the ex-vivo challenge (day 0), at day 7 (4 h after MVC) or after 10 days with TDF/FTC. Rectal biopsies were infected ex-vivo, and viral inhibition and CCR5 occupancy was analyzed. MVC concentration in plasma and rectal tissue was measured just after biopsy and after viral incubation. RESULTS: Ex-vivo rectal tissue protection with MVC was incomplete in all but two participants, whereas TDF/FTC avoided ex-vivo infection in the two controls. Median dose-normalized concentration of MVC was significantly higher in rectal tissue than in plasma (561.1 and 155.1 ng/ml, respectively). A significant loss of MVC during the virus incubation (about 60%) and a low CCR5 occupancy (approximately 45%) were detected in rectal cells. CONCLUSIONS: An ex-vivo challenge with a single oral dose of MVC does not prevent ex-vivo infection of human rectal mucosa. The lack of prophylactic efficacy observed suggests that 'on demand' MVC preexposure prophylaxis would not prevent rectal HIV-1 transmission.

Estudios para el aprovechamiento potencial de hojas de Guadua angustifolia Kunth (Poaceae), para el sector cosmético / Studies for the potential utilization of Guadua angustifolia Kunth (Poaceae) leaves for the cosmetic sector

Introducción: el aprovechamiento de residuos agroindustriales es una práctica que se trata de implementar por el impacto ambiental que representa. Objetivo: realizar un análisis bromatológico y fitoquimico de las hojas de Guadua y evaluar el efecto de algunas variables implicadas en el proceso de obtención del materia vegetal que puedan afectar el rendimiento y la actividad antioxidante del extracto hidroalcohólico. Métodos: se identificó cualitativamente los metabolitos secundarios presentes en las hojas y se complementó con un estudio bromatológico según normas AOAC. Mediante diseños de comparación simple y diseño factorial 22, se determinó la influencia del proceso de secado (natural y controlado), el tamaño de partícula (120 µm y 64 µm), edad de los cultivos (3-4 años) y el tiempo de almacenamiento de las hojas secas y molidas (1 y 6 meses) sobre el rendimiento de extracción y la actividad antioxidante ( Folin Ciocalteu y DPPH) del extracto hidroalcohólico. Resultados: las hojas secas revelan presencia de compuestos con actividad antioxidante (flavonoides y fenoles) y un 2,4 por ciento de nitrógeno menor al reportado para otros bambús. A partir de las hojas se puede obtener un extracto hidroalcohólico con un rendimiento hasta del 10,6 por ciento y con actividad antioxidante hasta de 9,2 mg ácido gálico/100g y 14,5 mg Trolox /100g. Se observó que la propiedad antioxidante del extracto hidroalcohólico y el rendimiento de extracción no varían con la edad de los cultivos (3-4 años) de donde provienen las hojas, ni con el método de secado, ni con el tiempo de almacenamiento de las hojas, mientras que si cambian con el tamaño de partícula. Conclusión: las hojas de Guadua por su actividad antioxidante son una materia prima potencial para ser usada en la industria cosmética(AU)

Introduction: the use of agro-industrial wastes is a practice that has been implemented by the environmental impact it represents. Objective: to perform a bromatological and phytochemical analysis of Guadua leaves and to evaluate the effect of some variables involved in the process of obtaining plant material that may affect the yield and the antioxidant activity of hydroalcoholic extract. Methods: secondary metabolites in the leaves were qualitatively identified and then supplemented with bromatologic study according to AOAC standards. Through a simple comparison designs and factorial design 22, there was determined the influence of the drying process (natural and controlled), the particle size (120 and 64 µm), crop age (3-4 years) and storage time of the dried and ground leaves (1 and 6 months) on the extraction yield and antioxidant activity (DPPH Folin and Ciocalteu) of hydroalcoholic extract. Results: dried leaves revealed the presence of compounds with antioxidant activity (flavonoids and phenols) and 2,4 percent nitrogen less than reported for other bamboo trees. From the leaves, one can obtain a hydroalcoholic extract with yield up to 10,6 percent and antioxidant activity up to 9,2 mg gallic acid / 100g and Trolox 14,5 mg / 100g. It was observed that neither age of the cultures (3-4 years) from leaves, the drying method, nor the time storage of leaves affect antioxidant properties and the extraction yield of hydroalcoholic extract, whereas these properties did change with the particle size. Conclusions: Guadua leaves, for their antioxidant activity, are a potential raw material for use in the cosmetics industry(AU)

Transient increment of HTLV-2 proviral load in HIV-1-co-infected patients during treatment intensification with raltegravir.

BACKGROUND: Numerous studies have analyzed the effects of raltegravir intensification on HIV-1 viral replication in infected individuals receiving suppressive combined antiretroviral treatment (cART). Nevertheless, there are only two studies on the effect of raltegravir in HTLV-1 infection, and none in HTLV-2. OBJECTIVE: To study the effect of raltegravir on HTLV-2 infection in HIV-1-co-infected individuals. STUDY DESIGN: This retrospective longitudinal study included four HTLV-2-HIV-1-co-infected individuals who received raltegravir-based cART during 48 weeks and 11 HTLV-2-HIV-1-co-infected individuals under cART without raltegravir during 48 weeks. HTLV-2 proviral load, CD4 and CD8 count and frequency were analyzed. RESULTS: HTLV-2 proviral load significantly increased at week 24 compared to baseline among all the patients who received raltegravir (p=0.003), while no significant increases were found in the control group. No significant variation in either CD8 or CD4 counts was found during the follow up in both groups. CONCLUSIONS: Raltegravir induced a transient increment on total HTLV-2 DNA proviral load in HTLV-2/HIV-1-coinfected individuals on suppressive cART after 24 weeks.

Factores emocionales y físicos relacionados a padecimientos neuromusculoesqueléticos en estudiantes de práctica clínica de la Facultad de Odontología Universidad de El Salvador / Emotional and physical factors related to neuromusculoskeletal disorders in clinical practice students of the Faculty of Dentistry, University of El Salvador. PhD thesis, University of El Salvador

La odontología está catalogada como uno de los ejercicios profesionales más estresantes y los padecimientos neuromusculoesqueléticos son problemas médicos frecuentes que pueden estar relacionados con la práctica clínica diaria. Objetivo: Determinar los factores emocionales y físicos relacionados a padecimientos neuromusculoesqueléticos en estudiantes de práctica clínica de la Facultad de Odontología Universidad de El Salvador. Materiales y Métodos: Se evaluaron 68 estudiantes del área clínica de los ciclos IX y XI, con edades entre los 21 a 32 años, 24 masculinos y 44 femeninos a través de una guía de observación se evaluaron las posturas adoptadas de trabajo y tensión muscular por movimientos estáticos y repetitivos, y para determinar el factor emocional se utilizó la escala de Maslach; y un cuestionario para determinar los padecimientos neuromusculoesqueléticos. Resultados: De 68 estudiantes evaluados en la subescala de agotamiento emocional, 38% presentaron un nivel alto, 25 % agotamiento intermedio y 36 % no presentaron agotamiento. El 75% mostró posturas inadecuadas durante la práctica clínica; los síntomas más frecuentes son dolor en el 89% de estudiantes seguido del espasmo con un 60% estos síntomas y signos se presentaron mayormente en espalda, cuello y hombros, mientras que el adormecimiento ocupa el tercer lugar con el 38% presentándose en dedos 17.65%) y espalda (14.75%). Conclusiones: Si existe relación entre factores emocionales (agotamiento mental y emocional) y padecimientos neuromusculoesqueléticos con un valor 0.006, También el factor físico posición de muslos con dolor de espalda presentó una relación significativa con un valor exacto de 0.046. No así con movimientos estáticos y repetitivos ya que en las diferentes pruebas dio un valor mayor a 0.05.

Dentistry is ranked as one of the most stressfull professional exercises related to neuromusculoskeletal disorders are common medical problems that may be related to daily clinical practice. Objective: To determine the emotional and physical factors related to neuromusculoskeletal disorders in clinical practice students of the Faculty of Dentistry University of El Salvador. Materials and Methods: 68 students of the clinical area IX and XI cycles were evaluated, aged 21 to 32 years, 24 male and 44 female through an observation working postures adopted and muscle tension were evaluated by static and repetitive movements, and to determine emotional Maslach scale factor was used, and questionnaire to determine and neuromusculoskeletal disorders. Results: Of 68 students tested in the subscale of emotional exhaustion, 38% had a high level, 25% intermediate and 36% depletion showed no fatigue. 75% had inadequate postures during clinical practice, the most common symptoms are pain in 81% of students continued to spasm, with 60% of these symptoms and signs are mostly presented in back, neck and shoulders. While the numbness is third with 38% appearing in fingers (17.65%) and back (14.75%). Results: Of 68 students tested in the subscale of emotional exhaustion, 38% had a high level, 25% intermediate and 36% depletion showed no exhaustion. 75% had inadequate postures during clinical practice; the most common symptoms are pain in 81% of students continued to spasm, Conclusions: There is relationship between emotional factors (mental and emotional exhaustion) and neuromusculoskeletal conditions with p value 0.006, also the physical factor position thighs with back pain had a significant relationship with an exact value of 0.046. Not so with static and repetitive movements as in the different test gave a p-value greater than 0.05.

Extracción y caracterización reológica del mucílago de Malvaviscus penduliflorus (San Joaquín) / Extraction and rheological characterization of Malvaviscus penduliflorus (sleeping hibiscus) mucilage

Introducción: los mucílagos presentan amplias e importantes aplicaciones en la industria farmacéutica, alimenticia y cosmética, entre otras. Los atributos primordiales de estos compuestos poliméricos es que son biocompatibles, económicos y fácilmente disponibles. Objetivos: desarrollar un método para la extracción del mucílago de hojas de San Joaquín y describir el comportamiento reológico de este. Métodos: se emplearon 5 procedimientos para la obtención del mucílago, que corresponden a extracción por ebullición, por baño de María, por microondas, por ultrasonido y por reflujo. posteriormente, se realizó la caracterización reológica de los mucílagos a temperatura de 25 ºC, el rendimiento de estos se valoró mediante la determinación de la viscosidad de las soluciones; también se verificó la concordancia con los resultados por el método reológico, aplicando un ensayo gravimétrico, en el cual se precipitó el mucílago utilizando etanol para después secarlo y pesarlo. Resultados: se obtuvieron 5 soluciones que contenían mucílago, las cuales presentaban color café claro y aspecto viscoso; se determinó el reograma para cada solución, en los cuales se observó que la solución más viscosa era la obtenida por reflujo y que todas las curvas presentaban un comportamiento pseudoplástico. Con la técnica gravimétrica se obtuvieron 5 precipitados secos de color similar al de las soluciones. Conclusiones: la técnica apropiada para la extracción del mucílago de San Joaquín es el reflujo, este resultado se demostró mediante reometría y gravimetría; el comportamiento reológico del hidrocoloide es no newtoniano con propiedades de flujo pseudoplástico, lo cual lo cataloga como un material potencial para la estabilización de dispersiones coloidales.

Introduction: mucilages have a variety of important applications in the food, pharmaceutical and cosmetic industries, among others. The main advantage of these polymeric compounds is that they are biocompatible, economical and easily available.Objectives: develop a method to extract mucilage from sleeping hibiscus leaves and describe its rheological behavior. Methods: five procedures were applied to obtain the mucilage: boiling, bain-marie, microwave, ultrasound and reflux. Rheological characterization of the mucilages was then conducted at a temperature of 25ºC. Their yield was assessed through determination of the viscosity of solutions. Agreement with the results was verified with the rheological method, applying a gravimetric assay in which the mucilage was first precipitated with ethanol, and then dried and weighed. Results: five light-brown, viscous solutions were obtained that contained mucilage. Determination was conducted of the rheogram for each solution, which showed that the most viscous solution was the one obtained by reflux, and that all curves presented pseudoplastic behavior. Five dry precipitates were obtained with the gravimetric technique. Their color was similar to that of solutions. Conclusions: the appropriate technique to extract mucilage from sleeping hibiscus is refluxing. This result was demonstrated by rheometry and gravimetry. The rheological behavior of the hydrocolloid is non-Newtonian with pseudoplastic flux properties, which makes it a potential material for the stabilization of colloidal dispersions.

Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome.

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability. METHODS: Immunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups. RESULTS: CFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals. CONCLUSIONS: Our findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS.