Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro.

Viral subunit vaccines are a safer and more tolerable alternative to whole inactivated virus vaccines. However, they often come with limited efficacy, necessitating the use of adjuvants. Using free and particle-bound viral antigens, we assessed whether size affects the uptake of those antigens by human monocyte-derived dendritic cells (Mo-DCs) and whether differences in uptake affect their capacity to stimulate cytokine production by T cells. To this end, influenza antigens and hepatitis B surface antigen (HBsAg) were covalently conjugated to polystyrene particles of 500 nm and 3 µm. Cellular uptake of the antigens, either unconjugated or conjugated, and their capacity to stimulate T cells within a population of human peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. Conjugation of both antigens to particles significantly increased their uptake by Mo-DCs. Moreover, both the 500 nm and 3 µm influenza conjugates induced significantly higher numbers of cytokine-producing CD4+ T cells and induced increased production of the pro-inflammatory cytokines IFNγ and TNFα. In contrast, conjugation of HBsAg to particles did not notably affect the T cell response. In conclusion, conjugation of antigen to 500 nm and 3 µm particles leads to increased antigen uptake by human Mo-DCs, although the capacity of such conjugates to induce T cell stimulation likely depends on the immunological status of the PBMC donor.

Diagnóstico de pacientes con sospecha de COVID-19: ¿Cuál es el rol de la TC de tórax? / Diagnosis of patients with suspected COVID-19: What is the role of chest CT?

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Personality and anxiety are related to health-related quality of life in unruptured intracranial aneurysm patients selected for non-intervention: A cross sectional study.

BACKGROUND: Personality traits and mental health problems have been previously reported in unruptured intracranial aneurysm (UIA) patients; however, few studies have clarified the relations between these variables and health-related quality of life (HRQoL). This study was designed to characterize the personality traits, HRQoL and mental health of patients with UIA and to evaluate whether personality has an influence on HRQoL and whether this is mediated by the patients' emotional symptoms. METHODS: Sixty-three patients with UIAs (mean age 62.6 years, 83.9% women) answered questionnaires for depression, anxiety, HRQoL and personality traits between June 2016 and May 2019. RESULTS: Eight percent of the sample had depression, and 27.4% had anxiety. Participants showed high levels of responsibility, kindness and neuroticism and low levels of extraversion and openness. HRQoL scores were normal compared with the Colombian population. Structural equation analysis showed that patients' HRQoL was negatively affected by anxiety levels and that the latter are associated with the patient's personality, where neuroticism is directly associated with symptomatology and inversely associated with extraversion. CONCLUSIONS: The results of this study showed the importance of personality and emotional symptoms in the HRQoL of UIA patients. These results are important for developing strategies for psychological counseling in patients with UIAs.

A PBMC-Based System to Assess Human T Cell Responses to Influenza Vaccine Candidates In Vitro.

Vaccine development is an expensive and time-consuming process that heavily relies on animal models. Yet, vaccine candidates that have previously succeeded in animal experiments often fail in clinical trials questioning the predictive value of animal models. Alternative assay systems that can add to the screening and evaluation of functional characteristics of vaccines in a human context before embarking on costly clinical trials are therefore urgently needed. In this study, we have established an in vitro system consisting of long-term cultures of unfractionated peripheral blood mononuclear cells (PBMCs) from healthy volunteers to assess (recall) T cell responses to vaccine candidates. We observed that different types of influenza vaccines (whole inactivated virus (WIV), split, and peptide vaccines) were all able to stimulate CD4 and CD8 T cell responses but to different extents in line with their reported in vivo properties. In-depth analyses of different T cell subsets revealed that the tested vaccines evoked mainly recall responses as indicated by the fact that the vast majority of the responding T cells had a memory phenotype. Furthermore, we observed vaccine-induced activation of T follicular helper cells, which are associated with the induction of humoral immune responses. Our results demonstrate the suitability of the established PBMC-based system for the in vitro evaluation of memory T cell responses to vaccines and the comparison of vaccine candidates in a human immune cell context. As such, it can help to bridge the gap between animal experiments and clinical trials and assist in the selection of promising vaccine candidates, at least for recall antigens.

Factores psicosociales asociados al estrés en profesores universitarios colombianos

Resumen Objetivo: evaluar los factores psicosociales asociados al estrés en una muestra de profesores de una universidad privada colombiana. Método: Estudio descriptivo correlacional de una muestra intencional de 61 profesores (rango de edad 25 a 63 años; 65,6 % hombres). Se utilizaron el cuestionario de salud del paciente PHQ-9, Cuestionario de Ansiedad generalizada GAD-7, Escala de estrés percibido PSS-14 y un cuestionario sobre factores psicosociales laborales. Adicionalmente se midió la presión arterial. Resultados: El 21,3 % de los profesores presentan niveles significativos de estrés. Hay mayor necesidad de trabajar en casa, interferencia familia-trabajo y trabajo-familia en profesores con estrés, mientras que el control es menor. Cabe anotar que estos profesores también presentan mayor sintomatología emocional. El modelo final mostró que la necesidad de trabajar en casa y la interferencia familia - trabajo explican el 45,6 % de la varianza en el estrés laboral de los profesores.

Abstract Objective: to evaluate the psychosocial factors associated with stress in a sample of professors from a private Colombian university. Method: Correlational descriptive study of an intentional sample of 61 professors (age range 25 to 63 years, 65,6 % men). The patient's health questionnaire PHQ-9, Generalized Anxiety Questionnaire GAD-7, Perceived Stress Scale PSS-14 and a questionnaire of psychosocial work factors were used. In addition, blood pressure measurements were taken. Results: 21,3 % of professors had significant levels of stress. There are more need to work at home, family-work and work-family interference in professors with stress, while control is lower. It should be noted that these teachers also have greater emotional symptoms. The final model showed that the need to work at home and the family - work interference explain 45,6 % of the variance in teachers' work stress.

Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations.

Vaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune system and the link between innate and adaptive responses. Their activation by vaccines is an essential step in vaccine-induced immune responses. We have systematically evaluated the suitability of two different human DC-based systems, namely the DC-cell line MUTZ-3 and primary monocyte-derived DCs (Mo-DCs) to screen immunopotentiating properties of vaccine candidates. Two different influenza vaccine formulations, whole inactivated virus (WIV) and subunit (SU), were used as model antigens as they represent a high immunogenic and low immunogenic vaccine, respectively. MUTZ-3 cells were restricted in their ability to respond to different stimuli. In contrast, Mo-DCs readily responded to WIV and SU in a vaccine-specific way. WIV stimulation elicited a more vigorous induction of activation markers, immune response-related genes and secretion of cytokines involved in antiviral responses than the SU vaccine. Furthermore, Mo-DCs differentiated from freshly isolated and freeze/thawed peripheral blood mononuclear cells (PBMCs) showed a similar capacity to respond to different vaccines. Taken together, we identified human PBMC-derived Mo-DCs as a suitable platform to evaluate vaccine-induced immune responses. Importantly, we show that fresh and frozen PBMCs can be used indistinctly, which strongly facilitates the routine use of this system. In vitro vaccine pre-screening using human Mo-DCs is thus a promising approach for evaluating the immunopotentiating capacities of new vaccine formulations that have not yet been tested in humans.

Trypanosome species in neo-tropical bats: biological, evolutionary and epidemiological implications.

Bats (Chiroptera) are the only mammals naturally able to fly. Due to this characteristic they play a relevant ecological role in the niches they inhabit. These mammals spread infectious diseases from enzootic to domestic foci. Rabbies, SARS, fungi, ebola and trypanosomes are the most common pathogens these animals may host. We conducted intensive sampling of bats from the phyllostomidae, vespertilionidae and emballonuridae families in six localities from Casanare department in eastern Colombia. Blood-EDTA samples were obtained and subsequently submitted to analyses of mitochondrial and nuclear genetic markers in order to conduct barcoding analyses to discriminate trypanosome species. The findings according to the congruence of the three molecular markers suggest the occurrence of Trypanosoma cruzi cruzi (51%), T. c. marinkellei (9%), T. dionisii (13%), T. rangeli (21%), T. evansi (4%) and T. theileri (2%) among 107 positive bat specimens. Regarding the T. cruzi DTUs, we observed the presence of TcI (60%), TcII (15%), TcIII (7%), TcIV (7%) and TcBAT (11%) being the first evidence to our concern of the foreseen genotype TcBAT in Colombia. These results allowed us to propose reliable hypotheses regarding the ecology and biology of the bats circulating in the area including the enigmatic question whether TcBAT should be considered a novel DTU. The epidemiological and evolutionary implications of these findings are herein discussed.

Genetic structure of Trypanosoma cruzi in Colombia revealed by a High-throughput Nuclear Multilocus Sequence Typing (nMLST) approach.

BACKGROUND: Chagas disease is a systemic pathology caused by Trypanosoma cruzi. This parasite reveals remarkable genetic variability, evinced in six Discrete Typing Units (DTUs) named from T. cruzi I to T. cruzi VI (TcI to TcVI). Recently newly identified genotypes have emerged such as TcBat in Brazil, Colombia and Panama associated to anthropogenic bats. The genotype with the broadest geographical distribution is TcI, which has recently been associated to severe cardiomyopathies in Argentina and Colombia. Therefore, new studies unraveling the genetic structure and natural history of this DTU must be pursued. RESULTS: We conducted a spatial and temporal analysis on 50 biological clones of T. cruzi I (TcI) isolated from humans with different clinical phenotypes, triatomine bugs and mammal reservoirs across three endemic regions for Chagas disease in Colombia. These clones were submitted to a nuclear Multilocus Sequence Typing (nMLST) analysis in order to elucidate its genetic diversity and clustering. After analyzing 13 nuclear housekeeping genes and obtaining a 5821 bp length alignment, we detected two robust genotypes within TcI henceforth named TcIDOM (associated to human infections) and a second cluster associated to peridomestic and sylvatic populations. Additionaly, we detected putative events of recombination and an intriguing lack of linkage disequilibrium. CONCLUSIONS: These findings reinforce the emergence of an enigmatic domestic T. cruzi genotype (TcIDOM), and demonstrates the high frequency of recombination at nuclear level across natural populations of T. cruzi. Therefore, the need to pursue studies focused on the diferential virulence profiles of TcI strains. The biological and epidemiological implications of these findings are herein discussed.

Understanding the role of dogs (Canis lupus familiaris) in the transmission dynamics of Trypanosoma cruzi genotypes in Colombia.

The dog (Canis lupus familiaris) is the most important domestic reservoir of Chagas disease, a zoonosis that affects more than 10 million people in Latin America. Trypanosoma cruzi, the etiologic agent of the disease, displays remarkable genetic variability, as indicated by its six genotypes (TcI-TcVI). A pilot study was conducted to establish the prevalence of T. cruzi among the canine population by analyzing 80 dogs. We report the identification of the TcI, TcII, TcIV and TcVI genotypes as single infections. TcI/TcII and TcI/TcIV presented as mixed infections and included the presence of Trypanosoma angel. The implications of this distribution are herein discussed. Based on the molecular epidemiology findings, this study suggests a plausible role for canine synanthropism in the transmission of T. cruzi.