Mesenchymal Stromal Cells from Perinatal Tissues as an Alternative for Ex Vivo Expansion of Hematopoietic Progenitor and Stem Cells from Umbilical Cord Blood.

Umbilical cord blood (UCB) serves as a source of hematopoietic stem and progenitor cells (HSPCs) utilized in the regeneration of hematopoietic and immune systems, forming a crucial part of the treatment for various benign and malignant hematological diseases. UCB has been utilized as an alternative HSPC source to bone marrow (BM). Although the use of UCB has extended transplantation access to many individuals, it still encounters significant challenges in selecting a histocompatible UCB unit with an adequate cell dose for a substantial proportion of adults with malignant hematological diseases. Consequently, recent research has focused on developing ex vivo expansion strategies for UCB HSPCs. Our results demonstrate that co-cultures with the investigated mesenchymal stromal cells (MSCs) enable a 10- to 15-fold increase in the cellular dose of UCB HSPCs while partially regulating the proliferation capacity when compared to HSPCs expanded with early acting cytokines. Furthermore, the secretory profile of UCB-derived MSCs closely resembles that of BM-derived MSCs. Moreover, both co-cultures exhibit alterations in cytokine secretion, which could potentially impact HSPC proliferation during the expansion process. This study underscores the fact that UCB-derived MSCs possess a remarkably similar supportive capacity to BM-derived MSCs, implying their potential use as feeder layers in the ex vivo expansion process of HSPCs.

Effect of neoadjuvant chemotherapy on tumor immune infiltration in breast cancer patients: Systematic review and meta-analysis.

The tumor immune infiltrate has an impact on cancer control and progression, additionally a growing body of evidence has proposed the role of neoadjuvant chemotherapy in modulating the contexture of the tumor immune infiltrate. Here, we performed a systematic review to evaluate the effect of chemotherapy in the immune infiltration of breast cancer tumors. We systematically searched Pubmed/MEDLINE, EMBASE, CENTRAL, and BVS databases with a cutoff date of 11/06/2022. Studies in patients with pathological diagnosis of BC, whose first line of treatment was only NAC, were included. Only published experimental studies that measured tumor immune infiltrate before and after NAC by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHQ), or transcriptome were included. Reviews, studies with animal models and in-vitro models were excluded. Studies in which BC was not the primary tumor or studies with patients who received other types of neoadjuvant therapy were also excluded. The NIH quality assessment tool for before and after studies without control was used. We included 32 articles that evaluated the proximal tumor microenvironment before and after neoadjuvant chemotherapy in 2072 patients who received NAC as first line of treatment and who were evaluated for immune infiltrate in the pre- and post-chemotherapy tumor sample. Results were divided into two major categories immune cells and in-situ expression of immune checkpoints and cytokines. Qualitative synthesis was performed with the 32 articles included, and in nine of them a quantitative analysis was achieved, resulting in six meta-analyses. Despite high heterogeneity among the articles regarding treatment received, type of tumor reported, and techniques used to evaluate immune infiltrate, we found a significant decrease of TILs and FoxP3 expression after neoadjuvant chemotherapy. The study protocol was registered in PROSPERO 2021 (Protocol ID: CRD42021243784) on 6/29/2021.

Neoadjuvant chemotherapy modulates exhaustion of T cells in breast cancer patients.

Breast cancer is the leading cause of cancer deaths in women worldwide. It has been observed that the incidence of breast cancer increases linearly with age after 45, which suggest a link between cancer, aging, and senescence. A growing body of evidence indicates that the immunosuppressive tumor network in breast cancer patients can lead to T-cell exhaustion and senescence. Cytotoxic chemotherapy is a common treatment for many cancers, and it is hypothesized that its efficacy may be related to immune activation. However, the effects of neoadjuvant chemotherapy on T-cell dysfunction in breast cancer patients are not fully understood. This study aimed to evaluate the impact of neoadjuvant chemotherapy on the expression of exhaustion and senescence markers in T cells in women with breast cancer. Our results showed that T cells from breast cancer patients have a reduced ability to respond to stimulation in-vitro and an increased expression of senescence and exhaustion-associated markers, such as TIM-3, LAG3, and CD57. Furthermore, we found that neoadjuvant chemotherapy has an immunomodulatory effect and reduces the expression of exhaustion markers. Our observations of the immune phenotype of T cells during neoadjuvant chemotherapy treatment highlight its ability to stimulate the immune system against cancer. Therefore, monitoring the response of T cells during chemotherapy may enable early prediction of clinical response.

Phenomenological-based model of glucose transport from liver to abdominal subcutaneous adipose tissue.

BACKGROUND: A good treatment for type 1 diabetes mellitus (T1DM) requires accurate measurements of blood glucose levels. Continuous glucose monitors (CGM) measure the glucose concentration in the interstitial fluid of the abdominal subcutaneous adipose tissue. However, glucose measured in the abdominal interstitial fluid does not represent blood glucose concentrations accurately due to the complex blood transport through the body and glucose diffusion in interstitial fluid. METHODS: To gain insight into this problem, a phenomenological-based semiphysical model (PBSM) of glucose transport by volumetric flow and diffusion from the bloodstream to interstitial fluid was constructed. A published 10-step modeling procedure was used to obtain a model for glucose transport time through the blood vessels and from the blood capillaries to the interstitial fluid, glucose diffusion within the interstitial fluid, and glucose diffusion through the semipermeable coating of the sensor needle. For this model, a healthy person is considered at rest with average parameters. RESULTS: The simulations performed using the PBSM allow obtaining the glucose transport time from the liver to the sensor needle. In this way, it is possible to reconstruct an accurate dynamic measurement of blood glucose from the measurements in the interstitial fluid of the abdominal subcutaneous adipose tissue. CONCLUSIONS: PBSMs with parameters interpretability illustrate the connection of glucose concentrations in the interstitial fluid with that currently in the blood. Implementing this model in a CGM will result in more reliable measurements of blood glucose levels for T1DM treatment.

Transforming growth factor-ß-regulated mTOR activity preserves cellular metabolism to maintain long-term T cell responses in chronic infection.

Antigen-specific CD8+ T cells in chronic viral infections and tumors functionally deteriorate, a process known as exhaustion. Exhausted T cells are sustained by precursors of exhausted (Tpex) cells that self-renew while continuously generating exhausted effector (Tex) cells. However, it remains unknown how Tpex cells maintain their functionality. Here, we demonstrate that Tpex cells sustained mitochondrial fitness, including high spare respiratory capacity, while Tex cells deteriorated metabolically over time. Tpex cells showed early suppression of mTOR kinase signaling but retained the ability to activate this pathway in response to antigen receptor signals. Early transient mTOR inhibition improved long-term T cell responses and checkpoint inhibition. Transforming growth factor-ß repressed mTOR signaling in exhausted T cells and was a critical determinant of Tpex cell metabolism and function. Overall, we demonstrate that the preservation of cellular metabolism allows Tpex cells to retain long-term functionality to sustain T cell responses during chronic infection.

Human immune response to SARS-CoV-2: What is known? A scoping review / Respuesta inmune humana al SARS-CoV-2: ¿Qué se conoce? Una scoping review

Monitoring literature on the broad spectrum of the human immune response to SARS-CoV-2 is important to understand the mechanisms and progression of COVID-19. The present study undertakes a scoping review of the literature on human immune response to SARS-CoV-2 to determine the characteristics of innate and adaptive responses, as well as biomarkers and cells that play a role in the development of the infection. We searched papers in MEDLINE/PUBMED and EMBASE databases published since December 1st 2019 to to April 9th 2020 from which we selected 56 for this study. We found that the immune response is characterized by high levels of acute phase reactants, neutrophilia, low levels of NKs and eosinophils, lymphopenia, cytokine storm syndrome, exhausted T cells, impaired cytotoxic response, inadequate helper response and production of specific antibodies; concluding that immune dysregulation correlates with disease severity and high mortality.

El seguimiento de la literatura sobre la respuesta inmune humana al SARS-CoV-2 es importante para comprender los mecanismos y la progresión de COVID-19. En el presente estudio se realizó un Scoping Review de la literatura sobre la respuesta inmune humana al SARS-CoV-2 para determinar las características de la respuesta inmune innata y adaptativa, así como biomarcadores y células que juegan un papel en el desarrollo de la infección. Buscamos artículos en las bases de datos MEDLINE / PUBMED y EMBASE publicados desde el 1 de diciembre de 2019 hasta el 9 de abril de 2020, de los cuales seleccionamos 56 publicaciones para este estudio. Encontramos que la respuesta inmune se caracteriza por altos niveles de reactantes de fase aguda, neutrofilia, bajos niveles de NKs y eosinófilos, linfopenia, síndrome de tormenta de citoquinas, linfocitos T agotados, respuesta citotóxica alterada, respuesta T helper inadecuada y producción de anticuerpos específicos. En conclusión, el desequilibrio inmune se correlaciona con la severidad y la mortalidad de la enfermedad.

Immunosenescence Study of T Cells: A Systematic Review.

Background: Aging is accompanied by alterations in immune response which leads to increased susceptibility to infectious diseases, cancer, autoimmunity, and inflammatory disorders. This decline in immune function is termed as immunosenescence; however, the mechanisms are not fully elucidated. Experimental approaches of adaptive immunity, particularly for T cells, have been the main focus of immunosenescence research. This systematic review evaluates and discusses T cell markers implicated in immunosenescence. Objective: To determine the best flow cytometry markers of circulating T cells associated with immunosenescence. Methods: We systematically queried PubMed, MEDLINE, EBSCO, and BVS databases for original articles focused on two age groups of healthy humans: 18-44 (young adults) and >60 (older adults) years. In accordance with the Cochrane methodology, we synthesized data through qualitative descriptions and quantitative random effects meta-analysis due to extensive heterogeneity. Results: A total of 36 studies conducted in the last 20 years were included for the qualitative analysis and four out of these studies were used to perform the meta-analysis. A significant decrease in naïve T cell subset was observed in older adults compared to young adults. Primary markers used to identify senescent cells were loss of CD28 and increased expression of CD57 and KLRG1 in terminally-differentiated memory T cell subset in older adults. Moreover, we observed an increase in proinflammatory cytokines and decrease in telomere length in old adult T cells. It was not possible to perform quantitative synthesis on cell markers, cytokines, and telomere length because of the significant variations between the groups, which is attributed to differences in protocols and unreported measurements, thus generating a high risk of bias. Conclusions: Heterogeneity among studies in terms of data report, measurement techniques and high risk of bias were major impediments for performing a robust statistical analysis that could aid the identification of eligible flow cytometry markers of immunosenescence phenotype in T cells.

Homophobic Attitudes and Associated Factors Among Adolescents: A Comparison of Six Latin American Countries.

Homophobic attitudes are still very common in the world, although there are large differences between countries. This study analyzed the responses of almost 30,000 8th- and 9th-grade students from six countries who participated in the Latin American component of the International Civic and Citizenship Education Study. Higher levels of homophobia were found in the Dominican Republic, Guatemala, and Paraguay than in Chile, Colombia, and Mexico. Homophobic attitudes were positively associated with being male, having lower levels of empathy, spending less time with friends and the media, having aggressive attitudes, and being more religious, in particular non-Catholic Christian.

Actitudes y dinámicas de robo en uncolegio de nivel socioeconómico medio-alto / Theft attitudes and dynamics in an upper-middle socioeconomic level school / Atitudes e dinâmica de roubo numa escola do nível socioeconômico médio-alto

El robo escolar es un problema muy común en colegios de todas las localidades de Bogotá. Con el propósito de profundizar sobre este fenómeno, se realizaron encuestas, entrevistas y grupos focales con noventa estudiantes de un colegio privado de nivel socioeconómico medio-alto. Los resultados indicaron que los robos en este colegio se realizan, por lo general, de manera espontánea e individual, y que los objetos robados se utilizan para uso personal y no para la venta. A pesar de que la mayoría de los estudiantes rechazan los robos, algunos minimizan su gravedad cuando la víctima tiene muchos recursos o presume de sus posesiones, o si ha dejado sus objetos descuidados. Estos resultados contrastan con un estudio similarrealizado previamente en una escuela con presencia de pandillas juveniles, el cual mostró que los robos eran realizados de manera planeada por grupos de estudiantes que dividían sus roles y vendían lo robado por fuera del colegio. A pesar de las diferencias entre colegios, la presente investigación resalta la necesidad de que se tomen en serio las denuncias de los estudiantes, se apliquen normas de manera consistente, se promueva empatía frente a las víctimas y se cuestionen justificaciones que minimizan la gravedad de los robos.

School theft is a very common problem at schools in all areas of Bogota. For the purpose of delving into this issue,surveys, interviews and focus groups were carried out with ninety students of a private upper-middle socioeconomic level school, and results showed that robberies and thefts taking place there are generally of a spontaneous and individual nature, and stolen objects intended for personal use, not for sale.Nevertheless, although most students reject these activities, they tend to minimize their seriousness particularly if the victims own significant resources or boast about their possessions or tend to be careless and leave their things behind. In contrast, the results of a similar study previously carried out in a school affected with the presence of youth gangs showed that thefts were carefully planned by groups of students playing different roles; stolen objects were then sold outside tablishments, current research stresses the fact that student complaints need to be taken seriously and empathy promoted towards the victims; rules must be applied consistently while questioning and rejecting any justifications leading to minimize the seriousness of these acts.

O roubo escolar é um problema comum nas escolas em todas as localidades de Bogotá. Para investigar esse fenômeno, realizaramse foram pesquisas, entrevistas e grupos focais com noventa alunos de uma escola privada de nível socioeconômico médio-alto. Os resultados indicaram que os roubos nesta escola são feitos, em geral, de jeito individual e espontâneo e que os objetos roubados são usados para uso pessoal e não para venda. Enquanto a maioria dos alunos rejeita o roubo, alguns minimizam sua gravidade quando a vítima tem muitos recursos ou gaba-se das suas posses, ou se deixou seus objetos abandonados. Esses resultados contrastam com um estudo semelhante realizado anteriormente em uma escola com a presença de gangues de jovens, que mostrou que os roubos foram feitos na maneira pretendida por grupos de estudantes que dividiam seus papéis e vendiam os objetos roubados fora da escola. Apesar das diferenças entre escolas, esta pesquisa destaca a necessidade de que as queixas dos alunos levamse a sério, usam-se as regras consistentemente, promovase a empatia com as vítimas e desafiemse as justificativas que minimizam a gravidade dos roubos.

Calidad del informe de solicitud de estudio anatomopatológico y motivos de consulta en cirugía menor ambulatoria de atención primaria / Quality of the report requesting an anatomopathological study and reasons for consultation in out-patient minor surgery in primary care

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