Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Diagnóstico do estado de conservação do fundo Governo Superior Civil do Arquivo Nacional da República de Cuba

The study aims to conduct a comprehensive assessment of the “Gobierno Superior Civil” collection in order to determine deteriorations present, analyze the conditions of the vault where documents are kept, and evaluate temperature, relative humidity, and lighting conditions in the room. During 2013, the average values of temperature and relative humidity inside the vault were 29 °C and 59%, respectively. Illuminance values did not exceed those allowed for paper documents (50 lux), except when it came from artificial light on cloudy days. 312 bundles, from a total of 1677, were analyzed using the Diagnos program. Such bundles are composed almost entirely of rag paper written with iron gall ink. The predominant deteriorations were dirt, yellowing, brittle paper, with cracks and creases, and documents damaged due to oxidation of iron gall ink.El objetivo del estudio fue realizar el diagnóstico integral del fondo Gobierno Superior Civil para determinar los deterioros que presenta, analizar las condiciones del depósito donde se conserva y evaluar el comportamiento de la temperatura, la humedad relativa y la iluminancia en el local durante el 2013. En este año, los valores promedio de temperatura y humedad relativa en el interior del depósito fueron de 29 °C y 59 %, respectivamente. Los valores de iluminancia no sobrepasaron los permitidos para documentos en papel (50 lux) solo cuando proviene de la luz artificial en días nublados. De un total de 1677 legajos, se analizaron 312 empleando el programa Diagnos. Tales legajos están conformados casi en su totalidad por papel de trapo y fueron escritos con tinta ferrogálica. Los deterioros predominantes fueron suciedad, amarillamiento, papeles quebradizos, con roturas, con dobleces y documentos afectados por la oxidación de las tintas ferrogálicas.O objetivo do estudo foi realizar o diagnóstico integral do fundo Governo Superior Civil para determinar as deteriorações que se apresentam, para analisar as condições do depósito onde se conserva e avaliar o comportamento da temperatura, a umidade relativa e a iluminância no local durante o ano de 2013. Neste ano, os valores aproximados de temperatura e umidade relativa no interior do depósito foram de 29 °C e 59 %, respectivamente. Os valores de iluminância não ultrapassaram os permitidos para documentos em papel (50 lux) somente quando provém da luz artificial em dias nublados. De um total de 1677 ficheiros, se analisaram 312 empregando o programa Diagnos. Estes ficheiros estão conformados quase totalmente por papel de trapo e foram escritos com tinta ferrogálica. As deteriorações predominantes foram sujeira, amarelecimento, papel quebradiço, com roturas, com dobras e documentos afetados pela oxidação das tintas ferrogálicas

Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity

Artículo de publicación ISIChagas disease is one of the most neglected tropical diseases in the world, affecting nearly 15 million people, primarily in Latin America. Only two drugs are used for the treatment of this disease, nifurtimox and benznidazole. These drugs have limited efficacy and frequently induce adverse effects, limiting their usefulness. Consequently, new drugs must be found. In this study, we demonstrated the in vitro trypanocidal effects of a series of four gallic acid derivatives characterized by a gallate group linked to a triphenylphosphonium (TPP+) moiety (a delocalized cation) via a hydrocarbon chain of 8, 10, 11, or 12 atoms (TPP+-C-8, TPP+C10, TPP+-C-11, and TPP+-C-12, respectively). We analyzed parasite viability in isolated parasites (by MTT reduction and flow cytometry) and infected mammalian cells using T. cruzi Y strain trypomastigotes. Among the four derivatives, TPP+-C-10 and TPP+-C-12 were the most potent in both models, with EC50 values (in isolated parasites) of 1.0 +/- 0.6 and 1.0 +/- 0.7 mu M, respectively, and were significantly more potent than nifurtimox (EC50 = 4.1 +/- 0.6 mu M). At 1 mu M, TPP+-C-10 and TPP+-C-12 induced markers of cell death, such as phosphatidylserine exposure and propidium iodide permeabilization. In addition, at 1 mu M, TPP+-C-10 and TPP+-C-12 significantly decreased the number of intracellular amastigotes (TPP+-C-10: 24.3%, TPP+-C-12: 19.0% of control measurements, as measured by DAPI staining) and the parasite's DNA load (C-10: 10%, C-12: 13% of control measurements, as measured by qPCR). Based on the previous mode of action described for these compounds in cancer cells, we explored their mitochondrial effects in isolated trypomastigotes. TPP+-C-10 and TPP+-C-12 were the most potent compounds, significantly altering mitochondrial membrane potential at 1 mu M (measured by JC-1 fluorescence) and inducing mitochondrial transition pore opening at 5 mu M. Taken together, these results indicate that the TPP+-C-10 and TPP+-C-12 derivatives of gallic acid are promising trypanocidal agents with mitochondrial activity.Consejo Nacional de Ciencia y Tecnologia (CONICYT-Chile) FONDECYT 11110182 FONDECYT 1130772 FONDECYT 1130189 Academy Insertion Grant 791220004 Vicerrectoria de Investigacion y Desarrollo, Universidad de Chile U-INICIA 11/07 U-INICIA 201

Chemical structure of the TPP+ derivatives.

<p>The structures of triphenyl(8-((3,4,5-trihydroxybenzoyl)oxy)-octyl) phosphonium bromide (TPP⁺-C₈), triphenyl(10-((3,4,5-trihydroxybenzoyl)oxy)-decyl) phosphonium bromide (TPP⁺-C₁₀), triphenyl(11-((3,4,5-trihydroxybenzoyl)oxy)-undecyl) phosphonium bromide (TPP⁺-C₁₁), and triphenyl(12-((3,4,5-trihydroxybenzoyl)oxy)-dodecyl) phosphonium bromide (TPP⁺-C₁₂) are shown. For details regarding their synthesis, see Jara <i>et al</i> (2014).</p

Effect of TPP⁺ derivatives on the parasite load in <i>T</i>. <i>cruzi</i>-infected cells.

<p>RAW 264.7 cells were infected with <i>T</i>. <i>cruzi</i> trypomastigotes (Y strain); the cells were treated for 48 hours with the different derivatives, and the parasite load was assessed by qPCR. The results are expressed as the relative quantification of the parasite DNA and mammalian DNA, with a ratio of 1 assigned to the control. Treated cells were compared with the control using the ^∆∆C_T method. *: <i>p</i> < 0.05; **: <i>p</i> < 0.01; and ***: <i>p</i> < 0.001, compared with the control, based on one-way ANOVA with Dunnett’s post-test.</p

Effect of TPP⁺ derivatives on the mitochondrial transmembrane potential (ΔΨ_m) of <i>T</i>. <i>cruzi</i>.

<p><i>T</i>. <i>cruzi</i> trypomastigotes were exposed to the different TPP⁺ derivatives for 2 hours, and ΔΨ_m was evaluated through JC-1 fluorescence using a flow cytometer. <b>A.</b> Representative frequency histogram of the fluorescence emitted at 590 nm. Upper panel: trypomastigotes exposed to 0.1 μM of the TPP⁺ derivatives. Lower panel: trypomastigotes exposed to 1 μM of the TPP⁺ derivatives. In both panels, FCCP (100 μM, 15 minutes before measurement) is shown as a positive control. Control: grey line, TPP⁺-C₈: red line, TPP⁺-C₁₀: blue line, TPP⁺-C₁₁: orange line, TPP⁺-C₁₂: green line, FCCP: black dashed line. AU: Arbitrary Units of Fluorescence. <b>B.</b> Quantification of the ratio between the 590 and 490 nm fluorescence emissions in trypomastigotes exposed to the TPP⁺ derivatives. The ratios were calculated using the fluorescence medians obtained from the histograms. The results are expressed as the mean ± SD of three independent experiments, each performed in triplicate. *: <i>p</i> < 0.05 and ***: <i>p</i> < 0.001, compared with the control, based on one-way ANOVA with Dunnett’s post-test.</p

Effect of TPP⁺ derivatives on markers of cell death in <i>Trypanosoma cruzi</i>.

<p><i>T</i>. <i>cruzi</i> trypomastigotes (Y strain, 10⁷/mL) were exposed to TPP⁺-C₈, TPP⁺-C₁₀, TPP⁺- C₁₁, or TPP⁺-C₁₂ at 0.1, 0.5, or 1 μM for 24 hours. The measurement of cell death markers (Annexin-V linkage and propidium iodide incorporation) was performed by flow cytometry. <b>A.</b> Representative dot plot showing the effect of TPP⁺ derivatives at 0.5 μM. The numbers within the quadrants indicate the percentage of double-negative, Annexin-V+, propidium iodide+, or double-positive cells. <b>B.</b> Quantification of viable cells (double negative) after 24 hours of exposure to the different derivatives. The bars represent the mean ± SD of three independent experiments, each performed in triplicate. *: <i>p</i> < 0.05 and ***: <i>p</i> < 0.001, compared with the control, based on one-way ANOVA with Dunnett’s post-test.</p

Effect of TPP⁺ derivatives on the opening of mitochondrial permeability transition pore.

<p><i>T</i>. <i>cruzi</i> trypomastigotes were loaded with calcein AM dye and CoCl₂ and exposed to the different TPP⁺ derivatives for 1 hour. Transition pore opening was then evaluated using a flow cytometer based on the quenching of mitochondrial calcein fluorescence. <b>A.</b> Representative frequency histogram of the fluorescence emitted at 515 nm. Both panels show calcein fluorescence in intact cells (grey area). Cytosolic fluorescence was quenched by the addition of CoCl₂, allowing visualization of the fluorescence from <i>T</i>. <i>cruzi</i> mitochondria (black line). The median fluorescence intensity of cells incubated with calcein AM and CoCl₂ was used as a control. As a positive control, we incubated the cells with 0.5 μM ionomycin (black dashed line). Parasites were also incubated with TPP⁺-C₈ (red line), TPP⁺-C₁₀ (blue line), TPP⁺-C₁₁ (orange line), and TPP⁺-C₁₂ (green line). Upper panel: trypomastigotes exposed to 1 μM of the TPP⁺ derivatives. Lower panel: trypomastigotes exposed to 5 μM of the TPP+ derivatives. AU: Arbitrary Units of Fluorescence. <b>B.</b> Quantification of the median fluorescence at 515 nm. The results were calculated using the median fluorescence obtained from the histograms and normalized assuming 100% fluorescence of the controls. The results are expressed as the mean ± SD of three independent experiments, each performed in triplicate. *: <i>p</i> < 0.05 and ***: <i>p</i> < 0.001, compared with the control, based on one-way ANOVA with Dunnett’s post-test.</p

Effect of TPP⁺ derivatives on the amastigote number in <i>T</i>. <i>cruzi</i>-infected cells.

<p>VERO cells were infected with <i>T</i>. <i>cruzi</i> trypomastigotes (Y strain). The cells were treated for 48 hours with the different derivatives, and the parasite load was then assessed by DAPI staining and fluorescence microscopy visualization. <b>A.</b> Representative images showing the effect of the different TPP+ derivatives on the intracellular amastigote number. All of the compounds shown were used at 1 μM. The white arrows show amastigote nuclei stained with DAPI. <b>B.</b> Quantification of the effect of TPP⁺ derivatives on VERO cells infected with <i>T</i>. <i>cruzi</i>. For each condition, performed in triplicate, at least five images were taken. The left panel shows the percentage of infected cells in each microscopic field photographed. The right panel shows the number of amastigotes per infected cell in each microscopic field photographed. For all of the graphs in the figure, the results are expressed as the mean ± SD of three independent experiments, each performed in triplicate. ***: <i>p</i> < 0.001 compared with the control, based on one-way ANOVA with Dunnett’s post-test.</p

La voz de octubre

Decidimos detenernos en la pregunta que indaga por la emoción. ¿Cuál fue la emoción que experimentamos con el suceso y qué sentimiento la describe? La pregunta por la emoción y el sentimiento que la nombra es la pregunta que surge de lo vivido, que por su fuerza se trasforma en una vivencia, cuyo significado tejido con las posibles respuestas será duradero. Nos preguntamos, entonces, ¿qué fue lo que sentimos durante lo vivido? ¿Qué produjo en nuestro espíritu esos 12 días? Nos detuvimos en la pregunta, teníamos que hospedarnos en ella, hundirnos en su vacío y quebrar ahí cualquier certeza previa, cualquier respuesta mecánica que la aniquile. Detenerse en la cadencia de la pregunta nos devuelve a nuestra circunstancia de indigencia, de seres que aparecimos en el cosmos sin respuestas. Solo desde allí es posible el surgimiento de la voluntad que imagine las respuestas que tejan el sentido de nuestra vida, de los acontecimientos que la constituyen y nos proyecten un destino común