Induction of immunogenic cell death of cancer cells through nanoparticle-mediated dual chemotherapy and photothermal therapy.

The use of nanomedicines to induce immunogenic cell death is a new strategy that aims to increase tumor immunogenicity and thereby prime tumors for further immunotherapies. In this study, we developed a nanoparticle formulation for combinatory chemotherapy and photothermal therapy based only on materials previously used in FDA-approved products and investigated the effect of the combinatory therapy on the growth inhibition and induction of immunogenic cell death in human MDA-MB-231 breast cancer cells. The formulation consists of ~108-nm nanoparticles made of poly(lactic acid)-b-methoxy poly(ethylene glycol) which carry doxorubicin for chemotherapy and indocyanine green for photothermal therapy. A 0.3 mg/mL suspension of NPs increased the medium temperature up to 10 °C upon irradiation with an 808-nm diode laser. In vitro studies showed that combination of laser assisted indocyanine green-mediated photothermal therapy and doxorubicin-mediated chemotherapy effectively eradicated cancer cells and resulted in the highest level of damage-associated molecular pattern presentation (calreticulin, high mobility group box 1, and adenosine triphosphate) compared to the individual treatments alone. These results demonstrate that our nanoparticle-mediated combinatory approach led to the most intense immunogenic cell death when compared to individual chemotherapy or photothermal therapy, making it a potent option for future in vivo studies in combination with cancer immunotherapies.

IL12 p35 and p40 subunit genes administered as pPAL plasmid constructs do not improve protection of pPAL-LACK vaccine against canine leishmaniasis.

Leishmania infantum causes zoonotic visceral leishmaniasis (ZVL) in the Mediterranean basin and South America. The parasite has been shown to co-infect HIV patients and an outbreak in central Spain was reported in the last decade. Therfore, ZVL is a public health problem, dogs being the parasite's reservoir. We have developed a DNA vaccine based on the L. infantum activated protein kinase A receptor (LACK) using different plasmid vectors and vaccinia virus strains as vehicles. Recently, we have generated an antibiotic resistance marker-free plasmid vector called pPAL. Homologous pPAL-LACK prime-boost vaccination protects Beagle dogs as well as a heterologous plasmid-virus regime. For both reasons, pPAL improves safety. IL12 was described to trigger Th1 response through IFN-γ production in infected dogs, being a good candidate for cytokine therapy in conventional treatment-unresponsive dogs. Herein, we report a complete protection study in dogs through inoculation of genes encoding for the p35 and p40 subunits which compose canine IL12 in combination with the LACK gene. A homologous plasmid-plasmid regime using independent pPAL constructs for each gene was inoculated in a 15-day interval. The infectious challenge using L. infantum promastigotes was successful. The outcome was pPAL-LACK vaccine protection suppression by IL12 administration. The important implications of this finding are discussed in the manuscript.

First report of Libyostrongylus douglassii (Strongylida: Trichostrongylidae) in ostriches (Struthio camelus) from Mexico.

Nematodes of the Libyostrongylus genus are hematophagous parasites found under the ostrich's proventriculus membrane: they are frequent and can cause 50% of mortality in chicks and occasionally death in adults. With the aim of determining the presence of the Libyostrongylus genus in two private collections, one located in Ayapango, State of Mexico and the other in Amacuzac, Morelos, a total of 27 fecal samples were collected between August and December of 2016. Samples were analyzed using the flotation technique. The eggs were quantified using the McMaster technique. Positive samples were cultured to obtain infective larvae and to be identified by their morphometric characteristics. Only 18 samples collected in Ayapango were positive to Libyostrongylus douglassii. This is the first time that L. douglassii is reported in Mexico.

A Proposal for Local $k$ Values for $k$ -Nearest Neighbor Rule.

The k -nearest neighbor ( k -NN) classifier is one of the most widely used methods of classification due to several interesting features, including good generalization and easy implementation. Although simple, it is usually able to match and even outperform more sophisticated and complex methods. One of the problems with this approach is fixing the appropriate value of k . Although a good value might be obtained using cross validation, it is unlikely that the same value could be optimal for the whole space spanned by the training set. It is evident that different regions of the feature space would require different values of k due to the different distributions of prototypes. The situation of a query instance in the center of a class is very different from the situation of a query instance near the boundary between two classes. In this brief, we present a simple yet powerful approach to setting a local value of k . We associate a potentially different k to every prototype and obtain the best value of k by optimizing a criterion consisting of the local and global effects of the different k values in the neighborhood of the prototype. The proposed method has a fast training stage and the same complexity as the standard k -NN approach at the testing stage. The experiments show that this simple approach can significantly outperform the standard k -NN rule for both standard and class-imbalanced problems in a large set of different problems.

Phylogenetic Analysis of Hepatitis B Virus Genotypes Circulating in Different Risk Groups of Panama, Evidence of the Introduction of Genotype A2 in the Country.

The Hepatitis B Virus (HBV) can cause acute or chronic infection it is also associated with the development of liver cancer, thousands of new infections occur on a yearly basis, and many of these cases are located in certain areas of the Caribbean and Latin America. In these areas, the HBV prevalence is still high which makes this virus a serious public health concern to the entire region. Studies performed in Panama suggest a complex pattern in the distribution of HBV among the country's different risk groups. We use phylogenetic analysis in order to determine which HBV genotypes were circulating in these specific groups; for this we used a fragment of the PreS2/2 region of the HBV genome. Subsequently whole HBV genome sequences were used for Bayesian analysis of phylodynamics and phylogeography. Two main genotypes were found: genotype A (54.5%) and genotype F (45.5%). There was a difference in the distribution of genotypes according to risk groups: 72.9% of high risk groups were associated to genotype A, and 55.0% of samples of genotype F were associated to the low risk group (p<0.002). The Bayesian analysis of phylogeny-traits association revealed a statistically significant geographical association (p<0.0001) with both genotypes and different regions of the country. The Bayesian time of most recent common ancestor analysis (tMRCA) revealed a recent tMRCA for genotype A2 circulating in Panama (1997, 95% HPD: 1986-2005), when it is compared with Panamanian genotype F1c sequences (1930, 95% HPD: 1810 - 2005). These results suggest a possible change in the distribution of HBV genotypes in Panama and Latin America as a whole. They also serve to encourage the implementation of vaccination programs in high-risk groups, in order to prevent an increase in the number of new HBV cases in Latin America and worldwide.

Nueva causa de arrastre presistólico: extrasistolia-PR largo / New cause of presystolic drag: long PR extrasystoles

No disponible

Insuficiencia aórtica en ventrículo derecho / Aortic regurgitation directed toward right ventricle

No disponible

[Violence in the transformation of systems of work in Colombia]. / La violencia en las transformaciones de los sistemas de trabajo en Colombia.

The phenomenon of the organizational violence is extent and complex; this is due to the multiplicity of factors and of elements of individual, economic, social and political order that there take place. This work approaches initially the problem of the violence in general then to try to specify the problem of the work violence. Today this one is a wide field of investigation nevertheless in Colombia even it remains to do efforts to understand this phenomenon in an environment of political and social violence, in the frame of which rapid transformations are happening in the forms of organization of the work. Our method of work this one based on the accomplishment of semi-structured interviews with workers who have experienced some form of violence in the work. The analysis allows identifying some of the precursor agents of violence in the organizations and the manifestation forms of these have inside of the organizations.

La violencia en las transformaciones de los sistemas de trabajo en Colombia / Violence in the transformation of systems of work in Colombia

El fenómeno de la violencia organizacional es de gran amplitud y complejidad. Esto se debe a la multiplicidad de factores y de elementos de orden individual, económico, social y político que allí tienen lugar. Este trabajo aborda inicialmente el problema de la violencia en general para luego tratar de precisar el problema de la violencia en el trabajo. Hoy día este es un campo amplio de investigación. Sin embargo en Colombia aun resta hacer esfuerzos para comprender este fenómeno en un entorno de marcado por la violencia política y social, en el marco de las cuales se están sucediendo rápidas transformaciones en las formas de organización del trabajo. Nuestro método de trabajo está basado en la realización de entrevistas semi-directivas con trabajadores que han experimentado alguna forma de violencia en el trabajo. El análisis desarrollado permite identificar algunos de los agentes precursores de violencia en las organizaciones y las formas de manifestación de estas tienen en el seno de las organizaciones.

The phenomenon of the organizational violence is extent and complex; this is due to the multiplicity of factors and of elements of individual, economic, social and political order that there take place. This work approaches initially the problem of the violence in general then to try to specify the problem of the work violence. Today this one is a wide field of investigation nevertheless in Colombia even it remains to do efforts to understand this phenomenon in an environment of political and social violence, in the frame of which rapid transformations are happening in the forms of organization of the work. Our method of work this one based on the accomplishment of semi- structured interviews with workers who have experienced some form of violence in the work. The analysis allows identifying some of the precursor agents of violence in the organizations and the manifestation forms of these have inside of the organizations.

Phyllodistomum folium (Trematoda: Gorgoderidae) infecting zebra mussels (Dreissena polymorpha) in the Ebro River, Spain.

Zebra mussels (Dreissena polymorpha) were first found in the Ebro River (Spain) in Ribaroja reservoir, in the summer of 2001. This paper reports a study to detect parasites in this bivalve species. From September 2003 to August 2004, a total of 1380 zebra mussels were collected and dissected or sectioned in paraffin and haematoxylin and eosin staining. We observed the presence of Phyllodistomum folium (Olfers, 1816) in two hosts (prevalence 0.14%). Sporocysts containing metacercariae were located within the gill lamellae. One of the mussels was collected in January and the other one in July. In both cases the shell length was >2 cm. P. folium had not been previously reported in Spain and D. polymorpha is its only known intermediate host. It represents a new invasive species in this river basin, presumably introduced together with the zebra mussels.

Markovian chemicals "in silico" design (MARCH-INSIDE), a promising approach for computer-aided molecular design I: discovery of anticancer compounds.

A simple stochastic approach, designed to model the movement of electrons throughout chemical bonds, is introduced. This model makes use of a Markov matrix to codify useful structural information in QSAR. The self-return probabilities of this matrix throughout time ((SR)pi(k)) are then used as molecular descriptors. Firstly, a calculation of (SR)pi(k) is made for a large series of anticancer and non-anticancer chemicals. Then, k-Means Cluster Analysis allows us to split the data series into clusters and ensure a representative design of training and predicting series. Next, we develop a classification function through Linear Discriminant Analysis (LDA). This QSAR discriminates between anticancer compounds and non-active compounds with a correct global classification of 90.5% in the training series. The model also correctly classified 86.07% of the compounds in the predicting series. This classification function is then used to perform a virtual screening of a combinatorial library of coumarins. In this connection, the biological assay of some furocoumarins, selected by virtual screening using the present model, gives good results. In particular, a tetracyclic derivative of 5-methoxypsoralen (5-MOP) has an IC50 against HL-60 tumoral line around 6 to 10 times lower than those for 8-MOP and 5-MOP (reference drugs), respectively. Finally, application of Iso-contribution Zone Analysis (IZA) provides structural interpretation of the biological activity predicted with this QSAR.

Protection in dogs against visceral leishmaniasis caused by Leishmania infantum is achieved by immunization with a heterologous prime-boost regime using DNA and vaccinia recombinant vectors expressing LACK.

A heterologous prime-boost vaccination regime with DNA and recombinant vaccinia virus (rVV) vectors expressing relevant antigens has been shown to enhance specific cellular immune responses and to elicit protection against a variety of pathogens in animal models. In this paper, we describe the effectiveness of the prime-boost strategy by immunizing dogs with a plasmid carrying the gene for the LACK antigen from Leishmania infantum (DNA-LACK) followed by a booster with a rVV containing the same gene (rVV-LACK). Thereafter, animals were challenged with L. infantum to induce visceral leishmaniasis (VL). In the vaccinated dogs as compared with the controls, the outcome of the infection after challenge with a high inoculum (10(8)) of L. infantum stationary promastigotes was assessed by tissue parasite load, specific anti-Leishmania antibody production, cytokine level and development of clinical signs of leishmaniasis. We observed a 60% protection against infection in dogs immunized by DNA-LACK prime/rVV/-LACK boost while two doses of DNA-LACK did not elicit protection against the disease. The interleukin 4 (IL-4), interferon gamma (IFNgamma) and IL-12 (p40 subunit) cytokine mRNA expression profiles in PBMC as well as lymphocyte proliferative response and the IgG2/IgG1 ratios specific for LACK suggest that in vaccinated animals there is triggering of cellular immune responses. This type of DNA/rVV prime/boost immunization approach may have utility against visceral leishmaniasis in dogs.