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Existe la necesidad de legislar y mejorar las normas jurídicas sobre protección y defensa del consumidor y/o usuario a la vez de impulsar, una cultura de paz y de consumo con la particularidad de protegerlo, máxime cuando puede resultar afectado en sus legítimos intereses, en medio de la asimetría informativa o de desequilibrio, frente a la ventajosa situación del proveedor, el cual es llamado a evitar conductas infractoras, por lo que se debe poner especial atención a la relación y situación presentada en torno al consumo. Resulta justificable frenar la violencia creciente y desde luego acudir en auxilio del más débil, como en todo orden de cosas, y en perspectiva jurídica no se puede permitir la violencia ni el ejercicio abusivo por acción u omisión del derecho, para ninguna persona y en este caso en particular, tampoco permitir semejante actuación del proveedor en el mercado. Luego, se parte del presupuesto de vulnerabilidad del consumidor y amparar la soberanía de éste, debiendo tener presente que en la economía social de mercado, reconocida constitucionalmente en Perú y en concordancia con el Código de Protección y Defensa del Consumidor, se debe interpretar la protección en el sentido más favorable al consumidor. A su turno, le corresponde al Estado cumplir el rol tuitivo en favor de los consumidores; es decir, no se trata de velar únicamente por el crecimiento económico, sino de allanar el camino a la justicia social también es estos aspectos; de allí la necesidad de contar con ajustes legislativos e instrumentos, como el libro de reclamaciones que faciliten superar las controversias de manera directa y célere

A large portion of the Indian population cannot simply access healthcare facilities. Private hospitals located in and around towns and cities are the primary providers of medical care. Because of this, patients in remote towns and villages must travel great distances to receive basic and specialized medical care. It has been noted that consumers only seek medical attention from a doctor or other medical professional when all other home cures have failed to relieve their symptoms. This is likely due to a lack of understanding as well as other behavioural variables. A novel approach to ensembling was created by the researchers. Results from experiments validate the effectiveness of the proposed strategy in boosting the classification accuracy. The disease prediction system developed in this study showed promising results and has use in the early detection of chronic diseases. The increasing death toll from chronic illness can be combated with the help of these prototypes. The introduction of these chronic disease prediction systems in primary care settings would be a major improvement in healthcare quality. The scope of this study will be broadened to incorporate the creation of prediction models for other diseases.

Reduction of extensive CO2 emissions is one of the key challenges that our society must overcome in order to minimize the effects of global warming and climate change. In this respect, electrochemical reduction of CO2 via redox enzymes is believed to be a promising route to minimize global CO2 concentrations, as they specifically catalyze the selective CO2 reduction in a reversible way at low potentials and mild conditions. In this work, we describe the effective anchoring of the enzyme Desulfovibrio vulgaris Hildenborough FdhAB formate dehydrogenase using electrostatic interactions favoring oriented immobilization, to the surface of MWCNTs-modified low density graphite electrodes with subsequent protection of the enzyme with polyethyleneimine (PEI) polymer. The synergistic effect of MWCNTs and PEI has been studied. High catalytic current densities, up to −230 μA cm−2, as well as a high operational stability of 11 h of continuous long-term measurements, were achieved.

Preliminary testing of PEGPH20/shIDO-ST in autochthonous KPC-Brca1 mouse model. PMN and DAPI immunofluorescence staining of an autochthonous tumor section from a KPC-Brca1 mouse treated with PEGPH20/shIDO-ST. Tumor was excised, flash frozen, sectioned, and stained 5 days following treatment. Central DAPI negative region of tumor with neutrophils (red) is depicted at 10X magnification with DAPI+ tumor cells (blue) at upper right (T).

Supplementary Figure 3 describes the ability of X8768 expressing bacterial luciferase to colonize tumors and peripheral tissues, as well as how HA degradation affects vasculature in PANC-1 tumors.

Supplementary Table 1 describes the parental strains and mutations used to generate attenuated ST strains.

Supplementary Figure 1 describes BHs expression in uninduced ST strains as well as the predicted localization of BHs. Viability of bHs-expressing ST strains is analyzed.

Supplementary Figure 2 describes the ability of X8768-BHs to degrade HA from fixed human PC-3 prostate cancer cells.

Supplementary Figure 4 shows that treatment with X8768-BHs does not degrade HA is non-tumor tissues, and does not affaect total cellular content of tumor tissue where HA was degraded.

Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases. In addition, CD8+ T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC. Cancer Immunol Res; 3(9); 1096–107. ©2015 AACR.

PDF file, 128K, Depletion of myeloid-derived suppressive cells.

PDF file, 197K, Antitumor activity of intracranial CNT-CpG.

PDF file, 73K, In vitro CNT-CpG activity assay.

Purpose: Recently, we showed that intratumoral delivery of low-dose, immunostimulatory CpG oligodeoxynucleotides conjugated with carbon nanotubes (CNT-CpG) was more effective than free CpG and not only eradicated intracranial (i.c.) gliomas but also induced antitumor immunity that protected mice from subsequent i.c. or systemic tumor rechallenge. Here, we examined whether the same “intracerebral immunotherapy” strategy could be applied to the treatment of metastatic brain tumors.Experimental Design: Mice with both i.c. and s.c. melanomas were injected intratumorally with CNT-CpG into either location. Antitumor responses were assessed by flow cytometry, bioluminescent imaging, and animal survival.Results: When given s.c., CNT-CpG response was mostly local, and it only modestly inhibited the growth of i.c. melanomas. However, i.c. CNT-CpG abrogated the growth of not only brain but also s.c. tumors. Furthermore, compared with s.c. injections, i.c. CNT-CpG elicited a stronger inflammatory response that resulted in more potent antitumor cytotoxicity and improved in vivo trafficking of effector cells into both i.c. and s.c. tumors. To investigate factors that accounted for these observations, CNT-CpG biodistribution and cellular inflammatory responses were examined in both tumor locations. Intracranial melanomas retained the CNT-CpG particles longer and were infiltrated by Toll-like receptor (TLR-9)–positive microglia. In contrast, myeloid-derived suppressive cells were more abundant in s.c. tumors. Although depletion of these cells before s.c. CNT-CpG therapy enhanced its cytotoxic responses, antitumor responses to brain melanomas were unchanged.Conclusions: These findings suggest that intracerebral CNT-CpG immunotherapy is more effective than systemic therapy in generating antitumor responses that target both brain and systemic melanomas. Clin Cancer Res; 18(20); 5628–38. ©2012 AACR.

Supplementary Figure 2 from Enhancement of Cancer Vaccine Therapy by Systemic Delivery of a Tumor-Targeting Salmonella-Based STAT3 shRNA Suppresses the Growth of Established Melanoma Tumors

Supplementary Figure 1 from Enhancement of Cancer Vaccine Therapy by Systemic Delivery of a Tumor-Targeting Salmonella-Based STAT3 shRNA Suppresses the Growth of Established Melanoma Tumors

Supplemental Figures. S1: Chemokine/Cytokine Quantification in Serum and in Tumor Microenvironment. S2: Blocking of CXCR3 suppresses the infiltration of CD8 T cell. S3: Administration of 7DW8-5 results in activation of NKT cells, NK cells, and DC in mouse spleen.

Supplemental Methods

PDF file - 221K, Supplemental Figs: 1. Transformation of VNP20009 with shIDO does not enhance its infectivity 2. ShIDO-ST reduces the formation of melanoma lung metastases. 3. Frequency of Gr1+CD11b+ cells in organs of tumor-bearig mice receiving PBS, shScr-ST, or shIDO-ST treatment. 4. Apoptotic CD45+ subsets in tumors of shIDO-ST treated mice includes CD4+ and CD8+ cells. 5. Hypoxia alone does not induce apoptosis in shIDO-ST-infected B16F10 cells. 6. ShIDO-ST treatment suppresses subcutaneous (s.c.) Pan02 tumor growth in C57BL/6 mice. Supplemental Methods: Flow cytometry and statistics

Generating antitumor responses through the inhibition of tumor-derived immune suppression represents a promising strategy in the development of cancer immunotherapeutics. Here, we present a strategy incorporating delivery of the bacterium Salmonella typhimurium (ST), naturally tropic for the hypoxic tumor environment, transformed with a small hairpin RNA (shRNA) plasmid against the immunosuppressive molecule indoleamine 2,3-dioxygenase 1 (shIDO). When systemically delivered into mice, shIDO silences host IDO expression and leads to massive intratumoral cell death that is associated with significant tumor infiltration by polymorphonuclear neutrophils (PMN). shIDO-ST treatment causes tumor cell death independently of host IDO and adaptive immunity, which may have important implications for use in immunosuppressed patients with cancer. Furthermore, shIDO-ST treatment increases reactive oxygen species (ROS) produced by infiltrating PMNs and, conversely, PMN immunodepletion abrogates tumor control. Silencing of host IDO significantly enhances S. typhimurium colonization, suggesting that IDO expression within the tumor controls the immune response to S. typhimurium. In summary, we present a novel approach to cancer treatment that involves the specific silencing of tumor-derived IDO that allows for the recruitment of ROS-producing PMNs, which may act primarily to clear S. typhimurium infection, but in the process also induces apoptosis of surrounding tumor tissue resulting in a vigorous antitumor effect. Cancer Res; 72(24); 6447–56. ©2012 AACR.

Hyaluronic acid (HA) is highly elevated in breast cancers compared to normal breast tissue and is associated with increased tumor aggressiveness and poor prognosis. HA interacts with cell-trafficking CD44 receptors to promote tumor cell migration and proliferation and regulates both pro- and anti-inflammatory cytokine production through tumor-associated macrophages. The highly negative charge of HA enables its uptake of vast amounts of water that greatly increases the tumor interstitial fluidic pressure, which, combined with the presence of other extracellular matrix components such as collagen, results in tumor stroma with abnormal vasculature, hypoxia, and increased drug resistance. Thus, the degradation of HA in breast cancer may attenuate growth and improve permeability to anticancer agents. Previous methods to deplete tumor HA have resulted in significant off-tumor effects due to the systemic use of mammalian hyaluronidases. To overcome this, we developed a hyaluronidase-secreting Salmonella typhimurium (YS-HAse) that specifically and preferentially colonizes tumors to deplete HA. We show that the systemic administration of YS-HAse in immunocompetent murine models of breast cancer enhances tumor perfusion, controls tumor growth, and restructures the tumor immune contexture. These studies highlight the utility of YS-HAse as a novel microbial-based therapeutic that may also be combined with existing therapeutic approaches.

Semiartificial approaches to renewable fuel synthesis exploit the integration of enzymes with synthetic materials for kinetically efficient fuel production. Here, a CO

El objetivo de este artículo es identificar los diferentes tipos de victimización que sufren las niñas, los niños y adolescentes migrantes en Chile en variados ámbitos de su vida y que ocurren de modo simultáneo, cruzando variables de procedencia nacional, territorio, edad y/o sexo-género, a fin de discutir la pertinencia del enfoque de la polivictimización. Se aplicó un cuestionario cuantitativo validado internacionalmente, pero adaptado a la realidad local. La muestra fue de 136 niñas, niños y adolescentes migrantes de 6 a 17 años de edad, residentes en las cuatro regiones del país con mayor población migrante. Se concluye que la niñez migrante sufre mayormente victimización indirecta en sus barrios, discriminación y violencia de parte del grupo de pares, a su vez, emergen nuevas áreas, como la violencia institucional y el ámbito familiar.

Este libro nace desde la necesidad de muchos investigadores interesados en poder conocer metodologías que se hayan aplicado al campo de los imaginarios y representaciones, las cuales pueden servir como orientación para sus proyectos o para inspirar ideas o “modos de hacer”. Más que un manual, Investigación sensible. Metodologías para el estudio de imaginarios y representaciones sociales lleva implícito un trasfondo epistemológico sobre una de las corrientes de pensamiento que ha venido formando escuela en Iberoamérica y cimentando un acercamiento responsable al conocimiento, desde el investigador que busca conocer y sentir la realidad como parte de sí mismo, una investigación sensible, en la que si debe existir sesgo este será por adentrarse y decir lo que se ve sin una supuesta neutralidad axiológica, sino con un compromiso por el bienestar y la dignidad de las personas. En el panorama amplio de esta obra se presentan una serie de métodos y esquemas analíticos, tales como la hermenéutica, la semiótica, el análisis de discurso y de contenido, la teoría fundamentada, los métodos mixtos, la etnografía y netnografía, las técnicas grupales y la entrevista. Los que se entrecruzan con diferentes campos de investigación o diferentes aplicaciones, por ejemplo: los estudios urbanos, el arte, el ámbito educativo, las imágenes, la mitología, el curso de vida y la memoria.

Pancreatic cancer is considered one of the most lethal cancers in the US. It contributes to an estimated 47,000 deaths annually and is predicted to surpass prostate, breast and colorectal cancers as the leading cause of cancer-related death. Although major advancements in cancer treatment have improved outcomes for many cancer types, survival rate for pancreatic cancer has not improved in nearly four decades despite tremendous effort. One attribute of pancreatic cancer that is considered a major barrier to effective treatment is the formation of fibrotic tissue around tumor cells known as desmoplasia. A number of promising approaches have been developed to deplete fibrotic components in pancreatic tumors to enhance drug delivery, some of which have been tested in clinical trials of advanced, unresectable pancreatic cancer. Here, we discuss previous efforts, shortcomings and new considerations for developing more effective agents to eliminate desmoplasia.