A study to determine the reactions of patients and their families to the concept of progressive care in their community hospital.

Thesis (M.S.)--Boston Universit

Human metapneumovirus: Mechanisms and molecular targets used by the virus to avoid the immune system

Indexación: Scopus.This work was supported by Comisión Nacional de Investigación Científica y Tecnolígica (CONICYT) N◦21151028 and FONDECYT (N◦1070352 and N◦1170964) and the Millennium Institute on Immunology and Immunotherapy (P09/016-F).Human metapneumovirus (hMPV) is a respiratory virus, first reported the year 2001. Since then, it has been described as one of the main etiological agents that causes acute lower respiratory tract infections (ALRTIs), which is characterized by symptoms such as bronchiolitis, wheezing and coughing. Susceptible population to hMPV-infection includes newborn, children, elderly and immunocompromised individuals. This viral agent is a negative-sense, single-stranded RNA enveloped virus, that belongs to the Pneumoviridae family and Metapneumovirus genus. Early reports-previous to 2001-state several cases of respiratory illness without clear identification of the responsible pathogen, which could be related to hMPV. Despite the similarities of hMPV with several other viruses, such as the human respiratory syncytial virus or influenza virus, mechanisms used by hMPV to avoid the host immune system are still unclear. In fact, evidence indicates that hMPV induces a poor innate immune response, thereby affecting the adaptive immunity. Among these mechanisms, is the promotion of an anergic state in T cells, instead of an effective polarization or activation, which could be induced by low levels of cytokine secretion. Further, the evidences support the notion that hMPV interferes with several pattern recognition receptors (PRRs) and cell signaling pathways triggered by interferon-associated genes. However, these mechanisms reported in hMPV are not like the ones reported for hRSV, as the latter has two non-structural proteins that are able to inhibit these pathways. Several reports suggest that viral glycoproteins, such as G and SH, could play immune-modulator roles during infection. In this work, we discuss the state of the art regarding the mechanisms that underlie the poor immunity elicited by hMPV. Importantly, these mechanisms will be compared with those elicited by other common respiratory viruses. © 2018 Frontiers Media S.A. All rights reserved.https://www.frontiersin.org/articles/10.3389/fimmu.2018.02466/ful

Inducing Tumor Immunity through the Selective Engagement of Activating Fcγ Receptors on Dendritic Cells

Induction of tumor-specific immunity requires that dendritic cells (DCs) efficiently capture and present tumor antigens to result in the expansion and activation of tumor-specific cytotoxic T cells. The transition from antigen capture to T cell stimulation requires a maturation signal; in its absence tolerance, rather than immunity may develop. While immune complexes (ICs) are able to enhance antigen capture, they can be poor at inducing DC maturation, naive T cell activation and protective immunity. We now demonstrate that interfering with the inhibitory signal delivered by FcγRIIB on DCs converts ICs to potent maturation agents and results in T cell activation. Applying this approach to immunization with DCs pulsed ex-vivo with ICs, we have generated antigen-specific CD8+ T cells in vivo and achieved efficient protective immunity in a murine melanoma model. These data imply that ICs may normally function to maintain tolerance through the binding to inhibitory FcγRs on DCs, but they can be converted to potent immunogenic stimuli by selective engagement of activating FcγRs. This mechanism suggests a novel approach to the development of tumor vaccines

Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

Indexación: Web of Science; Scopus.The Human Respiratory Syncytial Virus (hRSV) is a major cause of acute lower respiratory tract infections (ARTIs) and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F), the Glycoprotein (G), and the Small Hydrophobic (SH) protein, which are located on the virus surface. In addition, the Nucleoprotein (N), Phosphoprotein (P) large polymerase protein (L) part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M) protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2). HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.https://www.frontiersin.org/articles/10.3389/fcimb.2017.00367/ful

Intestinal microbiota influences non-intestinal related autoimmune diseases

Indexación: Scopus.The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases. © 2018 Opazo, Ortega-Rocha, Coronado-Arrázola, Bonifaz, Boudin, Neunlist, Bueno, Kalergis and Riedel.https://www.frontiersin.org/articles/10.3389/fmicb.2018.00432/ful

Statistical explanation of the protective effect of four COVID-19 vaccine doses in the general population

ObjectivesTo assess the effectiveness of four doses of the vaccine against SARS-CoV-2 in the general population and the impact of this on the severity of the disease by age group.MethodsBy using data from the health authority public data base, we build statistical models using R and the GAMLSS library to explain the behavior of new SARS-CoV-2 infections, active COVID-19 cases, ICU bed requirement total and by age group, and deaths at the national level.ResultsThe four doses of vaccine and at least the interaction between the first and second doses were important explanatory factors for the protective effect against COVID-19. The R2 for new cases per day was 0.5644 and for occupied ICU beds the R2 is 0.9487. For occupied ICU beds for >70 years R2 is 0.9195 and with the interaction between 4 doses as the main factor.ConclusionsAlthough the increase in the number of vaccine doses did not adequately explain the decrease in the number of COVID-19 cases, it explained the decrease in ICU admissions and deaths nationwide and by age group

Heme oxygenase-1 as a modulator of intestinal inflammation development and progression

Indexación: Scopus.Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease. © 2018 Sebastián, Salazar, Coronado-Arrázola, Schultz, Vallejos, Berkowitz, álvarez-Lobos, Riedel, Kalergis and Bueno.https://www.frontiersin.org/articles/10.3389/fimmu.2018.01956/ful

Insercion de un producto regional en Mexico. Caso: Ciruela Deshidratada

109 p.La importancia de contar con un sector exportador moderno, que cuente con las herramientas eficientes para una correcta toma de decisiones es fundamental para el despegue del país y a través de este proyecto se pretende entregar un aporte a este objetivo. En una primera parte se realiza una mirada a la evolución de la economía mexicana para seguir con un análisis de los beneficios que presentan los diversos acuerdos que ha suscrito nuestro país en su política de apertura comercial para luego introducirnos en los mercados metas, sus proyecciones y funcionamiento, a la vez que se recopilo información sobre el marco de regulaciones y estándares de comercio e importaciones. Cabe mencionar que es de suma importancia tener un conocimiento acabado de la logística de exportación y sus costos, situación que también es analizada en este proyecto, para finalizar con la realización de un plan de marketing , el cual contempla las diversas variables que actúan e influyen en el proceso de exportación, todo lo anterior con el fin de entregar una herramienta, una investigación aplicada; la cual puede ser de utilidad para los empresarios de la región y en consecuencia un beneficio para el país

Neurologic Alterations Due to Respiratory Virus Infections

Central Nervous System (CNS) infections are one of the most critical problems in public health, as frequently patients exhibit neurologic sequelae. Usually, CNS pathologies are caused by known neurotropic viruses such as measles virus (MV), herpes virus and human immunodeficiency virus (HIV), among others. However, nowadays respiratory viruses have placed themselves as relevant agents responsible for CNS pathologies. Among these neuropathological viruses are the human respiratory syncytial virus (hRSV), the influenza virus (IV), the coronavirus (CoV) and the human metapneumovirus (hMPV). These viral agents are leading causes of acute respiratory infections every year affecting mainly children under 5 years old and also the elderly. Up to date, several reports have described the association between respiratory viral infections with neurological symptoms. The most frequent clinical manifestations described in these patients are febrile or afebrile seizures, status epilepticus, encephalopathies and encephalitis. All these viruses have been found in cerebrospinal fluid (CSF), which suggests that all these pathogens, once in the lungs, can spread throughout the body and eventually reach the CNS. The current knowledge about the mechanisms and routes used by these neuro-invasive viruses remains scarce. In this review article, we describe the most recent findings associated to neurologic complications, along with data about the possible invasion routes of these viruses in humans and their various effects on the CNS, as studied in animal models

A Herpes Simplex Virus Type 2 Deleted for Glycoprotein D Enables Dendritic Cells to Activate CD4+ and CD8+ T Cells

Herpes simplex virus type 2 (HSV-2) is highly prevalent in the human population producing significant morbidity, mainly because of the generation of genital ulcers and neonatal encephalitis. Additionally, HSV-2 infection significantly increases the susceptibility of the host to acquire HIV and promotes the shedding of the latter in the coinfected. Despite numerous efforts to create a vaccine against HSV-2, no licensed vaccines are currently available. A long-standing strategy, based on few viral glycoproteins combined with adjuvants, recently displayed poor results in a Phase III clinical study fueling exploration on the development of mutant HSV viruses that are attenuated in vivo and elicit protective adaptive immune components, such as antiviral antibodies and T cells. Importantly, such specialized antiviral immune components are likely induced and modulated by dendritic cells, professional antigen presenting cells that process viral antigens and present them to T cells. However, HSV interferes with several functions of DCs and ultimately induces their death. Here, we propose that for an attenuated mutant virus to confer protective immunity against HSV in vivo based on adaptive immune components, such virus should also be attenuated in dendritic cells to promote a robust and effective antiviral response. We provide a background framework for this idea, considerations, as well as the means to assess this hypothesis. Addressing this hypothesis may provide valuable insights for the development of novel, safe, and effective vaccines against herpes simplex viruses