Thermal degradation of polymethyl methacrylate in multiple extrusions

Se presentan los resultados del estudio cinético de la degradación térmica del Polimetíl Metacrilato – PMMA, tanto virgen como procesado por extrusión hasta cinco ciclos de reprocesamiento, en una extrusora monohusillo. Después de cada reprocesamiento se tomó una muestra para análisis. A estas muestras se les determinó la temperatura de transición vítrea (por DSC), índice de fluidez y la temperatura máxima de pérdida de peso (por TGA). Los resultados del análisis termogravimétrico se utilizaron para determinar el triplete cinético por medio de métodos isoconversionales, no isoconversionales, y dinámicos. Se encontró que las curvas TG, DTG y de conversión, se desplazan a la derecha al aumentar la velocidad de calentamiento. También se encontró que los métodos no isoconversionales diferenciales presentaron valores de energía de activación mayores a los métodos integrales. La energía de activación aumentó con el reprocesamiento y la probabilidad o fracción de colisión aumenta con la velocidad de calentamiento. Abstract This work presents a kinetic study of thermal degradation of polymethyl metacrylate (PMMA). This material was subject of five extrusion cycles in a single barrel screw extruder, and results for raw and reprocessed material are presented. Glass transition temperature (by DSC), melt flow index, and temperature of maximum weight loss rate (by TGA) were determined in samples taken after each reprocessing. Results from thermogravimetric analysis were used to get the kinetic triplet by isoconversional, non-isoconversional, and dynamic methods as it is reported in literature. It was found that heating shifts to the right TG, DTG, and conversion curves. Activation energy values found with non-isoconversional differential methods tend to be higher than those found with integral methods. Also the activation energy increased with reprocessing, while the probability or collision factor increased with the heating rate

Rattus norvegicus como indicador de la circulación de Capillaria hepatica y Taenia taeniaeformis en la Plaza Minorista de Medellín, Colombia

Introduction. Rattus norvegicus, the Norway rat, plays a pivotal role in the maintenance and spread of several zoonotic bacterial, viral and parasitic pathogens of public health interest. The presence of helminthic infections near susceptible human populations can, under appropriate environmental conditions, become a risk factor for their transmission.Objective. Frequencies of infection were reported for Capillaria hepatica and larval forms of Taenia taeniaeformis in wild rats (R. norvegicus) captured in an urban area.Materials and methods. Two hundred and fifty-four adult specimens of R. norvegicus were collected in an urban zone of Medellín, Colombia. The livers of 54 specimens that showed macroscopic hepatic lesions during necropsy were examined by conventional histopathology.Results. The frequency of infestation with C. hepatica was 20.1% (51/254). Six livers (2.4%) were also positive for larvae of T. taeniaeformis. Livers infested with C. hepatica exhibited adult or juvenile parasites and oval eggs with bipolar opercula, and were associated with mild to moderate multifocal granulomatous hepatitis with leucocyte infiltrate. Granulomatous lesions and calcified residual fibroses were found with eggs but without adult parasites. Those animals with cysticerci of T. taeniaeformis showed a high frequency of hepatic cysts containing larvae as well as inflammed and fibrotic lesions.Conclusion. Zoonotic helminths circulate at high frequency in R. norvegicus that occur in urban environments. Further research about the distribution of these parasites will determine the level of health threat they present for susceptible human and domestic animal populations. doi: http://dx.doi.org/10.7705/biomedica.v32i4.442Introducción. Rattus norvegicus cumple un papel epidemiológico en el mantenimiento y dispersión de agentes zoonóticos bacterianos, virales y parasitarios de interés en salud pública. La presencia de infección por helmintos en especies Rattus cercanas a poblaciones expuestas en condiciones ambientales propicias, puede convertirse en un factor de riesgo de transmisión.Objetivo. Reportar la frecuencia de infección con Capillaria hepatica y formas larvarias de Taenia taeniaeformis en ratas silvestres (R. norvegicus) capturadas en una zona urbana de Medellín.Materiales y métodos. Se capturaron 254 ejemplares de R. norvegicus. Los hígados de 54 ejemplares que presentaron lesión hepática macroscópica durante la necropsia, fueron examinados por histopatología convencional.Resultados. La frecuencia de infección por C. hepatica fue de 20,1 % (51/254). Seis hígados fueron también positivos para larvas de T. taeniaeformis con una frecuencia de 2,4 % (6/254). Los hígados infestados con C. hepatica exhibían parásitos en el estadio adulto o juvenil y huevos ovalados conopérculos bipolares, asociados con hepatitis granulomatosa leve a moderada multifocal y acompañada por infiltrado leucocitario. Se observaron lesiones granulomatosas en resolución y fibrosis residual o calcificada que contenía huevos. Donde se encontraron cisticercos de T. taeniaeformis, el hallazgo más frecuente fueron quistes hepáticos que contenían larvas, y lesiones inflamatorias y fibróticas.Conclusión. Estos resultados indican que helmintos de potencial zoonótico circulan en R. norvegicus de ambientes urbanos. Debe investigarse la verdadera distribución de estos parásitos, para determinar el riesgo potencial que corren las poblaciones animales y humanas expuestas a adquirir este tipo de infecciones. doi: http://dx.doi.org/10.7705/biomedica.v32i4.442

Immunolocalisation of P2Y receptors in the rat eye

Nucleotides present an important role in ocular physiology which has been demonstrated by recent works that indicate their involvement in many ocular processes. P2Y are important among P2 receptors since they can control tear production, corneal wound healing, aqueous humour dynamics and retinal physiology. Commercial antibodies have allowed us to investigate the distribution of P2Y receptors in the cornea, anterior and posterior chamber of the eye and retina. The P2Y1 receptor was present mainly in cornea, ciliary processes, and trabecular meshwork. The P2Y2 receptors were present in cornea, ciliary processes and retinal pigmented epithelium. P2Y4 was present in cornea, ciliary processes, photoreceptors, outer plexiform layer and ganglion cell layer. The P2Y6 presented almost an identical distribution as the P2Y4 receptor. The P2Y11 was also detectable in the retinal pigmented epithelium. The detailed distribution of the receptors clearly supports the recent findings indicating the relevant role of nucleotides in the ocular function

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival