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MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that both cellular (Th1/Th17) and antibody (IgG/IgA) responses to UTI89 were induced in MV140-immunized mice. MV140 vaccination resulted in an early increased clearance of UTI89 viable bacteria in the bladder and urine following transurethral infection. This was accompanied by a highly significant increase in CD4+ T cells in the bladder and an increase in urinary neutrophils. Collectively, our results support that MV140 induces cross-reactive humoral and cellular immune responses and cross-protection against UPEC strains.
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Background: Recurrent urinary tract infection (rUTI) remains a major health burden for women. A randomized, double-blind, placebo-controlled trial (RCT; NCT02543827) reported that female patients with rUTI receiving a sublingual vaccine, MV140, had a reduction in rUTI and increase in UTI-free rate compared with placebo. Objective: To determine the impact of MV140 on the personal burden of disease in women with rUTI using secondary endpoint data from the pivotal RCT evaluating MV140. Design setting and participants: In the primary RCT, female patients with rUTI enrolled in Spain and UK (from October 2015 to April 2019) were randomized to placebo (6 mo) or MV140 (3 or 6 mo), and followed for 12 mo. Individuals analyzed in this secondary analysis included those in the placebo and 3-mo (recommended dose) groups. Intervention: A polybacterial sublingual vaccine, MV140 (four inactivated whole-cell bacteria-Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis), or placebo. Outcome measurements and statistical analysis: Symptom severity scoring, antibiotic use, safety, and multiple aspects of quality of life (QoL; Short-Form Questionnaire [SF-36]) were assessed. Results and limitations: Compared with the placebo group (n = 76), the 3-mo vaccinated group (n = 74) experienced fewer overall UTI symptoms (mean symptom score 102.2 ± 222.9 vs 194.2 ± 178.8; p = 0.0002), fewer days on antibiotics (12.4 ± 17.7 vs 28.7 ± 25.2; p = 0.0001), and improved total, general, and physical SF-36 QoL improvement (differences in means for total SF-36 score 15.7; 95% confidence interval [CI] 8.80, 22.64; p < 0.0001), with only social function QoL showing no impact (4.07; 95% CI -4.93, 13.08; p = 0.3744). Conclusions: Three months of MV140 is associated with a reduction of the personal burden of UTI by reducing overall UTI symptoms and antibiotic use, improving QoL in women with rUTI. Patient summary: Three months of MV140 vaccine, which has previously been shown to reduce the risk of urinary tract infection safely, is associated with a reduction in the personal burden of disease.
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MV140 is a mucosal vaccine of inactivated whole bacteria (E. coli, K. pneumoniae, E. faecalis, P. vulgaris) with clinical efficacy against recurrent urinary tract infections (UTIs). Here, MV140 was evaluated in a murine model of acute uropathogenic E. coli (UPEC)-induced UTI using the UTI89 strain. MV140 vaccination resulted in UPEC clearance, concomitant with increased influx of myeloid cells in urine, CD4+ T cells in the bladder, and a systemic adaptive immune response to both MV140-containing E. coli and UTI89.
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Introduction: Conventional or biologic disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment for systemic autoimmune disease (SAD). Infectious complications are a major concern in their use. Objective: To evaluate the clinical benefit of sublingual mucosal polybacterial vaccines (MV130 and MV140), used to prevent recurrent respiratory and urinary tract infections, in patients with SAD and secondary recurrent infections following conventional or biologic DMARDs. Methods: An observational study in SAD patients with recurrent respiratory tract infections (RRTI) and/or recurrent urinary tract infections (RUTI) was carried out. All patients underwent mucosal (sublingual) vaccination with MV130 for RRTI or with MV140 for RUTI daily for 3 months. Clinical evaluation was assessed during 12 months of follow-up after the first dose, i.e., 3 months under treatment and 9 months once discontinued, and compared with the previous year. Results: Forty-one out of 55 patients completed 1-year follow-up. All patients were on either conventional or biologic DMARDs. A significant decrease in the frequency of RUTI (p<0.001), lower respiratory tract infections (LRTI) (p=0.009) and upper respiratory tract infections (URTI) (p=0.006) at 12-mo with respect to the previous year was observed. Antibiotic prescriptions and unscheduled medical visits decreased significantly (p<0.020) in all groups. Hospitalization rate also declined in patients with RRTI (p=0.019). The clinical benefit demonstrated was concomitant to a significant increase in both anti-S. pneumoniae IgA and IgG antibodies following MV130 vaccination. Conclusions: Sublingual polybacterial vaccines prevent recurrent infections in patients with SAD under treatment with immunosuppressant therapies, supporting a broad non-specific anti-infectious effect in these patients.
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Enfermedades Autoinmunes/tratamiento farmacológico , Vacunas Bacterianas/inmunología , Inmunosupresores/uso terapéutico , Reinfección/prevención & control , Infecciones del Sistema Respiratorio/prevención & control , Infecciones Urinarias/prevención & control , Vacunación , Adulto , Anciano , Enfermedades Autoinmunes/inmunología , Vacunas Bacterianas/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: A major concern in the care of common variable immunodeficiency (CVID) patients is the persistence of subclinical or recurrent respiratory tract infections (RRTI) despite adequate trough IgG levels, which impacts the quality of life (QoL) and morbidity. Therefore, the development of new approaches to prevent and treat infection, especially RRTI, is necessary. OBJECTIVES: We conducted a clinical observational study from May, 2016 to December, 2017 in 20 CVID patients; ten of these patients had a history of RRTI and received the polybacterial preparation MV130, a trained immunity-based vaccine (TIbV) to assess its impact on their QoL and prognosis. METHODS: Subjects with RRTI received MV130 for 3 months and were followed up to 12 months after initiation of the treatment. The primary endpoint was a reduction in RRTI at the end of the study. We analyzed the pharmacoeconomic impact on the RRTI group before and after immunotherapy by estimating the direct and indirect costs, and assessed CVID-QoL and cytokine profile. Specific antibody responses to the bacteria contained in MV130 were measured. RESULTS: The RRTI-group treated with TIbV MV130 showed a significant decrease in infection rate (p = 0.006) throughout the 12 months after initiation of the treatment. A decrease in antibiotic use and unscheduled outpatient visits was observed (p = 0.005 and p = 0.002, respectively). Significant increases in anti-pneumococcus and anti-MV130 IgA antibodies (p = 0.039 both) were detected after 12 months of MV130. Regarding the CVID QoL questionnaire, an overall decrease in the score by more than 50% was observed (p < 0.05) which demonstrated that patients experienced an improvement in their QoL. The pharmacoeconomic analysis showed that the real annual direct costs decreased up to 4 times per patient with the prophylactic intervention (p = 0.005). CONCLUSION: The sublingual administration of the TIbV MV130 significantly reduced the rate of respiratory infections, antibiotic use and unscheduled visits, while increasing specific IgA responses in CVID patients. Additionally, the CVID population felt that their QoL was improved, and a decrease in expenses derived from health care was predicted.
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Infectious complications are a major cause of morbidity and mortality in B-cell hematological malignancies (HM). Prophylaxis for recurrent infections in HM patients with antibody deficiency consists of first-line antibiotics and when unsuccessful, gammaglobulin replacement therapy (IgRT). Recent knowledge of trained immunity-based vaccines (TIbV), such as the sublingual polybacterial formulation MV130, has shown a promising strategy in the management of patients with recurrent infections. We sought to determine the clinical benefit of MV130 in a cohort of HM patients with recurrent respiratory tract infections (RRTIs) who underwent immunization with MV130 for 3 months. Clinical information included the frequency of infections, antibiotic use, number of visits to the GP and hospitalizations previous and after MV130 immunotherapy. Improvement on infection rate was classified as: clear (>60% reduction of infection), partial (26%-60%) and low (≤25%) improvement. Fifteen HM patients (aged 42 to 80 years; nine females) were included in the study. All patients reduced their infection rate. Analysis of paired data revealed that the median (range, min - max) of respiratory infectious rate significantly decreased from 4.0 (8.0-3.0) to 2.0 (4.0-0.0) (p<0.001) at 12 months of MV130. A clear clinical improvement was observed in 53% (n = 8) of patients, partial improvement in 40% (n = 6) and low improvement in 7% (n = 1). These data correlated with a decrease on antibiotic consumption from 3.0 (8.0-1.0) to 1.0 (2.0-0.0) (p = 0.002) during 12 months after initiation of treatment with MV130. The number of infectious-related GP or emergency room visits declined from 4.0 (8.0-2.0) to 2.0 (3.0-0.0) (p<0.001), in parallel with a reduction in hospital admissions due to infections (p = 0.032). Regarding safety, no adverse events were observed. On the other hand, immunological assessment of serum IgA and IgG levels demonstrated an increase in specific antibodies to MV130-contained bacteria following MV130 immunotherapy. In conclusion, MV130 may add clinical benefit reducing the rate of infections and enhancing humoral immune responses in these vulnerable patients.
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Antígenos Bacterianos/administración & dosificación , Vacunas Bacterianas/administración & dosificación , Neoplasias Hematológicas/inmunología , Infecciones del Sistema Respiratorio/prevención & control , Vacunas Combinadas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/efectos adversos , Vacunas Bacterianas/efectos adversos , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/diagnóstico , Humanos , Inmunidad Humoral , Inmunoglobulina A/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Proyectos Piloto , Reinfección , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/microbiología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Vacunas Combinadas/efectos adversosRESUMEN
Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ- and IL-17A-producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.
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Antígenos Bacterianos/administración & dosificación , Antígenos Fúngicos/administración & dosificación , Infecciones Bacterianas/prevención & control , Vacunas Bacterianas/administración & dosificación , Candidiasis Vulvovaginal/terapia , Vacunas Fúngicas/administración & dosificación , Infecciones Urinarias/prevención & control , Vacunas Combinadas/administración & dosificación , Animales , Antígenos Bacterianos/inmunología , Antígenos Fúngicos/inmunología , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/metabolismo , Infecciones Bacterianas/microbiología , Vacunas Bacterianas/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Candidiasis Vulvovaginal/inmunología , Candidiasis Vulvovaginal/metabolismo , Candidiasis Vulvovaginal/microbiología , Células Cultivadas , Técnicas de Cocultivo , Citocinas/metabolismo , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Femenino , Vacunas Fúngicas/inmunología , Humanos , Activación de Linfocitos/efectos de los fármacos , Ratones Endogámicos BALB C , Fenotipo , Infecciones Urinarias/inmunología , Infecciones Urinarias/metabolismo , Infecciones Urinarias/microbiología , Vacunación , Vacunas Combinadas/inmunologíaRESUMEN
Recurrent respiratory tract infections (RRTIs) are the first leading cause of community- and nosocomial-acquired infections. Antibiotics remain the mainstay of treatment, enhancing the potential to develop antibiotic resistances. Therefore, the development of new alternative approaches to prevent and treat RRTIs is highly demanded. Daily sublingual administration of the whole heat-inactivated polybacterial preparation (PBP) MV130 significantly reduced the rate of respiratory infections in RRTIs patients, however, the immunological mechanisms of action remain unknown. Herein, we study the capacity of MV130 to immunomodulate the function of human dendritic cells (DCs) as a potential mechanism that contribute to the clinical benefits. We demonstrate that DCs from RRTIs patients and healthy controls display similar ex vivo immunological responses to MV130. By combining systems biology and functional immunological approaches we show that MV130 promotes the generation of Th1/Th17 responses via receptor-interacting serine/threonine-protein kinase-2 (RIPK2)- and myeloid-differentiation primary-response gene-88 (MyD88)-mediated signalling pathways under the control of IL-10. In vivo BALB/c mice sublingually immunized with MV130 display potent systemic Th1/Th17 and IL-10 responses against related and unrelated antigens. We elucidate immunological mechanisms underlying the potential way of action of MV130, which might help to design alternative treatments in other clinical conditions with high risk of recurrent infections.
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Vacunas Bacterianas/inmunología , Células Dendríticas/inmunología , Interleucina-10/inmunología , Factor 88 de Diferenciación Mieloide/metabolismo , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/metabolismo , Infecciones del Sistema Respiratorio/prevención & control , Células TH1/inmunología , Células Th17/inmunología , Adulto , Anciano , Animales , Células Cultivadas , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/microbiología , Transducción de Señal/inmunologíaRESUMEN
BACKGROUND: Allergen immunotherapy (AIT) is the only curative treatment for allergy. AIT faces pitfalls related to efficacy, security, duration, and patient compliance. Novel vaccines overcoming such inconveniences are in demand. OBJECTIVES: We sought to study the immunologic mechanisms of action for novel vaccines targeting dendritic cells (DCs) generated by coupling glutaraldehyde-polymerized grass pollen allergoids to nonoxidized mannan (PM) compared with glutaraldehyde-polymerized allergoids (P) or native grass pollen extracts (N). METHODS: Skin prick tests and basophil activation tests with N, P, or PM were performed in patients with grass pollen allergy. IgE-blocking experiments, flow cytometry, confocal microscopy, cocultures, suppression assays, real-time quantitative PCR, ELISAs, and ELISpot assays were performed to assess allergen capture by human DCs and T-cell responses. BALB/c mice were immunized with PM, N, or P. Antibody levels, cytokine production by splenocytes, and splenic forkhead box P3 (FOXP3)(+) regulatory T (Treg) cells were quantified. Experiments with oxidized PM were also performed. RESULTS: PM displays in vivo hypoallergenicity, induces potent blocking antibodies, and is captured by human DCs much more efficiently than N or P by mechanisms depending on mannose receptor- and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-mediated internalization. PM endorses human DCs to generate functional FOXP3(+) Treg cells through programmed death ligand 1. Immunization of mice with PM induces a shift to nonallergic responses and increases the frequency of splenic FOXP3(+) Treg cells. Mild oxidation impairs these effects in human subjects and mice, demonstrating the essential role of preserving the carbohydrate structure of mannan. CONCLUSIONS: Allergoids conjugated to nonoxidized mannan represent suitable vaccines for AIT. Our findings might also be of the utmost relevance to development of therapeutic interventions in other immune tolerance-related diseases.
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Alérgenos/inmunología , Antígeno B7-H1/metabolismo , Células Dendríticas/inmunología , Mananos , Extractos Vegetales , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Vacunas/inmunología , Adyuvantes Inmunológicos , Alérgenos/metabolismo , Alergoides , Animales , Anticuerpos/inmunología , Anticuerpos Bloqueadores/inmunología , Citocinas/metabolismo , Células Dendríticas/metabolismo , Humanos , Tolerancia Inmunológica/inmunología , Ratones , Poaceae/inmunología , Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica Estacional/metabolismoRESUMEN
Distinguishing T cell epitope distribution patterns is relevant for epitope-vaccine design. To that end, we invest0069gated the distribution of known CD8 T cell epitopes from Hepatitis C Virus, Human Immunodeficiency Virus-1 and Influenza A Virus using χ(2) statistics. We found that epitopes are not distributed in the viral proteomes proportionally to the size of the source proteins. Specifically, capsid and matrix proteins pack significantly more epitopes than those expected by their size. Such non-homogeneous distribution cannot be accounted by underlying MHC I-peptide binding preferences nor it is related to sequence variability. Instead, we propose that it might be related to preferential protein translation/biosynthesis. Overall, these results support the prioritization of structural antigens for epitope identification and vaccine design.
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Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Epítopos de Linfocito T/inmunología , Virus ARN/metabolismo , Proteínas Virales/biosíntesis , Sitios de Unión , Secuencia Conservada , Antígenos HLA/inmunología , Humanos , Virus ARN/inmunología , Virus ARN/fisiología , Proteínas Virales/química , Proteínas Virales/inmunologíaRESUMEN
BACKGROUND: Proteasomes play a central role in the major histocompatibility class I (MHCI) antigen processing pathway. They conduct the proteolytic degradation of proteins in the cytosol, generating the C-terminus of CD8 T cell epitopes and MHCI-peptide ligands (P1 residue of cleavage site). There are two types of proteasomes, the constitutive form, expressed in most cell types, and the immunoproteasome, which is constitutively expressed in mature dendritic cells. Protective CD8 T cell epitopes are likely generated by the immunoproteasome and the constitutive proteasome, and here we have modeled and analyzed the cleavage by these two proteases. RESULTS: We have modeled the immunoproteasome and proteasome cleavage sites upon two non-overlapping sets of peptides consisting of 553 CD8 T cell epitopes, naturally processed and restricted by human MHCI molecules, and 382 peptides eluted from human MHCI molecules, respectively, using N-grams. Cleavage models were generated considering different epitope and MHCI-eluted fragment lengths and the same number of C-terminal flanking residues. Models were evaluated in 5-fold cross-validation. Judging by the Mathew's Correlation Coefficient (MCC), optimal cleavage models for the proteasome (MCC = 0.43 ± 0.07) and the immunoproteasome (MCC = 0.36 ± 0.06) were obtained from 12-residue peptide fragments. Using an independent dataset consisting of 137 HIV1-specific CD8 T cell epitopes, the immunoproteasome and proteasome cleavage models achieved MCC values of 0.30 and 0.18, respectively, comparatively better than those achieved by related methods. Using ROC analyses, we have also shown that, combined with MHCI-peptide binding predictions, cleavage predictions by the immunoproteasome and proteasome models significantly increase the discovery rate of CD8 T cell epitopes restricted by different MHCI molecules, including A*0201, A*0301, A*2402, B*0702, B*2705. CONCLUSIONS: We have developed models that are specific to predict cleavage by the proteasome and the immunoproteasome. These models ought to be instrumental to identify protective CD8 T cell epitopes and are readily available for free public use at http://imed.med.ucm.es/Tools/PCPS/.
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Biología Computacional/métodos , Epítopos de Linfocito T/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Animales , Antígenos CD8/genética , Antígenos CD8/inmunología , Bases de Datos Genéticas , Epítopos de Linfocito T/inmunología , Genes MHC Clase I , Humanos , Complejo de la Endopetidasa Proteasomal/químicaRESUMEN
No disponible
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Humanos , Masculino , Adolescente , Serositis/etiología , Lupus Eritematoso Sistémico/inducido químicamente , Pirazolonas/efectos adversos , Dipirona/efectos adversosRESUMEN
The transport of peptides to the endoplasmic reticulum by the transporter associated with antigen processing (TAP) is a necessary step towards determining CD8 T cell epitopes. In this work, we have studied the predictive performance of support vector machine models trained on single residue positions and residue combinations drawn from a large dataset consisting of 613 nonamer peptides of known affinity to TAP. Predictive performance of these TAP affinity models was evaluated under 10-fold cross-validation experiments and measured using Pearson's correlation coefficients (R(p)). Our results show that every peptide position (P1-P9) contributes to TAP binding (minimum R(p) of 0.26 +/- 0.11 was achieved by a model trained on the P6 residue), although the largest contributions to binding correspond to the C-terminal end (R(p) = 0.68 +/- 0.06) and the P1 (R(p) = 0.51 +/- 0.09) and P2 (0.57 +/- 0.08) residues of the peptide. Training the models on additional peptide residues generally improved their predictive performance and a maximum correlation (R(p) = 0.89 +/- 0.03) was achieved by a model trained on the full-length sequences or a residue selection consisting of the first 5 N- and last 3 C-terminal residues of the peptides included in the training set. A system for predicting the binding affinity of peptides to TAP using the methods described here is readily available for free public use at http://imed.med.ucm.es/Tools/tapreg/.
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Transportadoras de Casetes de Unión a ATP/metabolismo , Péptidos/metabolismo , Secuencia de Aminoácidos , Inteligencia Artificial , Bases de Datos de Proteínas , Modelos Biológicos , Péptidos/química , Unión Proteica , Transporte de ProteínasRESUMEN
Más de 1,000,000 de niños, la mitad de la población infantilvive por debajo de la línea de pobreza, 1 de cada 2 niños.Estos niños tienen grandes carencias a nivel de: nutrición,agua potable y saneamiento, salud, educación, vivienda einformación. En Uruguay, 50 por ciento de los niños se encuentranpor debajo de la línea de pobreza. Por esto, a nivelsalud, no podemos dejar de pensar en estos niños.En cuanto al extracto social. La Homeopatía es unapráctica privada que les llega a los extractos sociales más altosde la población. En un estudio que realizamos en el 2005,a propósito de nuestros pacientes pediátricos, en donde recibimospacientes de bajos recursos a demanda, vimos queestudiando la procedencia socioeconómica, el 68 por cientocorrespondió a extractos técnico-profesional y altos, el19 por ciento corresponden a padres obreros y solamenteel 6 por ciento provienen de comunidades carenciadas.A este amplio número de personas en situación depobreza, con sus necesidades básicas insatisfechas, que tienenmucho más riesgo de enfermar y/o morir y cuyas vidasse desarrollan en un marco social sumamente agresivo, laHomeopatía no llega.Por lo que junto con un grupo de colegas que trabajanhace varios años en policlínicos descentralizados concomunidades carenciadas resolvimos llevar la Homeopatía ala comunidad de menores recursos.
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Humanos , Preescolar , Niño , Países en Desarrollo , Brotes de Enfermedades , Medicina Familiar y Comunitaria , Homeopatía , Signos y Síntomas , América Latina/etnologíaRESUMEN
Más de 1,000,000 de niños, la mitad de la población infantilvive por debajo de la línea de pobreza, 1 de cada 2 niños.Estos niños tienen grandes carencias a nivel de: nutrición,agua potable y saneamiento, salud, educación, vivienda einformación. En Uruguay, 50 por ciento de los niños se encuentranpor debajo de la línea de pobreza. Por esto, a nivelsalud, no podemos dejar de pensar en estos niños.En cuanto al extracto social. La Homeopatía es unapráctica privada que les llega a los extractos sociales más altosde la población. En un estudio que realizamos en el 2005,a propósito de nuestros pacientes pediátricos, en donde recibimospacientes de bajos recursos a demanda, vimos queestudiando la procedencia socioeconómica, el 68 por cientocorrespondió a extractos técnico-profesional y altos, el19 por ciento corresponden a padres obreros y solamenteel 6 por ciento provienen de comunidades carenciadas.A este amplio número de personas en situación depobreza, con sus necesidades básicas insatisfechas, que tienenmucho más riesgo de enfermar y/o morir y cuyas vidasse desarrollan en un marco social sumamente agresivo, laHomeopatía no llega.Por lo que junto con un grupo de colegas que trabajanhace varios años en policlínicos descentralizados concomunidades carenciadas resolvimos llevar la Homeopatía ala comunidad de menores recursos.
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Humanos , Preescolar , Niño , Homeopatía , Países en Desarrollo , Síntomatología , Brotes de Enfermedades , Medicina Familiar y Comunitaria , América Latina/etnologíaRESUMEN
We have developed PVS (Protein Variability Server), a web-based tool that uses several variability metrics to compute the absolute site variability in multiple protein-sequence alignments (MSAs). The variability is then assigned to a user-selected reference sequence consisting of either the first sequence in the alignment or a consensus sequence. Subsequently, PVS performs tasks that are relevant for structure-function studies, such as plotting and visualizing the variability in a relevant 3D-structure. Neatly, PVS also implements some other tasks that are thought to facilitate the design of epitope discovery-driven vaccines against pathogens where sequence variability largely contributes to immune evasion. Thus, PVS can return the conserved fragments in the MSA-as defined by a user-provided variability threshold-and locate them in a relevant 3D-structure. Furthermore, PVS can return a variability-masked sequence, which can be directly submitted to the RANKPEP server for the prediction of conserved T-cell epitopes. PVS is freely available at: http://imed.med.ucm.es/PVS/.
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Epítopos de Linfocito T/química , Proteínas/inmunología , Alineación de Secuencia/métodos , Análisis de Secuencia de Proteína , Programas Informáticos , Vacunas contra el SIDA/química , Epítopos de Linfocito B/química , Internet , Conformación Proteica , Interfaz Usuario-Computador , Proteínas Virales/químicaRESUMEN
Immunoinformatics is an emerging new field that benefits from computational analyses and tools that facilitate the understanding of the immune system. A large number of immunoinformatics resources such as immune-related databases and analysis software are available through the World Wide Web for the benefit of the research community. However, immunoinformatics developments have sometimes remained isolated from mainstream bioinformatics. Therefore, there is clearly a need for integration, which will empower the exchange of data and annotations within the scientific community in a quick and efficient fashion. Here, we have chosen the Distributed Annotation System (DAS), for integrating in house annotations on experimental and predicted HLA I-restriction elements of CD8 T-cell epitopes with sequence and structural information.
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Las ciencias sociales contemporáneas han asumido como una manera de abordar las temáticas teóricas y prácticas, su correspondencia con el proceso histórico que transcurre. El debate sobre los contenidos del proceso de globalización pasa por diferentes acepciones y posturas. En este ensayo se define el proceso de globalización a partir de características especificas: como un proceso inédito, como una forma de mundialización en sus contenidos económicos; además, las dimensiones políticas, culturales e informacionales, entre otras; que permiten expresar la diversidad y a la vez, la conjunción de los componentes que lo integran
Asunto(s)
Humanos , Cooperación Internacional , Posmodernismo , TrabajoRESUMEN
El pensamiento complejo de Edgar Morín, significa para las ciencias sociales, un aporte metodológico, por la incorporación de latransdisciplinariedad, la multidimensionalidad, y, lo que hemos llamado doble dialecticidad . Estas claves metodológicas, constituyen aspectos epistemológicos importantes. Cuando se hace necesario, contestar al pensamiento posmoderno, en su postulación del fin de la ciencia ; es posible responder: El pensamiento complejo de Edgar Morín, puede referenciarse como la ciencia, después del fin de la ciencia . Los autores y corrientes que influyen el pensamiento moriniano, van de las ciencias formales y experimentales, a las ciencias sociales. La corriente constructivista, la filosofía, la antropología, el mito, Nietzstche y todo el abanico teórico que incluyen sus investigaciones, rinden cuenta de la transdisciplinariedad que se asume. Su paradigma decomplejidad, está del lado de las integraciones multidimensionales: biológico-cultural, especie-individuo y sociedad-individuo. En el diálogo orden y caos, la posibilidad de ser pensados conjuntamente y el recurso de volver a los escritos anteriores, para ser redefinidos, apuntan a una doble dialéctica. Cerca de la fenomenología y lejos de la ontología, lo que Morín termina ofreciendo con El Método, constituye una nueva vertiente del pensamiento social contemporáneo. A distancia de cualquier reduccionismo disciplinar y compartiendo con el paradigma determinista de la ciencia clásica; el pensamiento complejo de Morín, constituye una crítica a la ciencia moderna. Su vinculación con el constructivismo, lo exime de toda asociación con el sujeto trascendente de la modernidad y a la vez, el hombre está presente como homo sapiens y homo demens