Evolution of Anxiety, Emotional Intelligence, and Effective Personality after COVID-19 among Spanish University Students.

The repercussions of the pandemic caused by the SARS-CoV-2 coronavirus over recent years have posed an unprecedented challenge for the whole of society, affecting the well-being of everyone. Among all the variables affected in relation to well-being, Anxiety, Emotional Intelligence, and Effective Personality (Self-Esteem, Academic Self-Realisation, Resolute Self-Efficacy, Social Self-Realisation) have been highlighted. The aim of this study is to assess the evolution of those variables across three temporal phases: pre-pandemic, during the pandemic, and up until the end of the study in April 2022. A study was conducted during these temporal phases with three cohorts from Spanish Universities. The cohorts were formed of people assessed for Anxiety (660 pre-pandemic, 460 during the pandemic, and 311 at the end of the study), Emotional Intelligence (355 pre-pandemic, 91 during the pandemic, 311 at the end of the study), and Effective Personality (708 pre-pandemic, 174 in 2018, 311 at the end of the study). Anxiety was assessed with the State-Trait Anxiety Inventory, Emotional Intelligence with the Trait Meta-Mood Scale and TMMS-24, and Effective Personality with the Cuestionario Personalidad Eficaz-Universidad (the Effective Personality Questionnaire-University). The results showed a rise in the state of anxiety during COVID-19, with a subsequent reduction two years into the pandemic; however, anxiety rates remained higher than before the pandemic. Emotional intelligence increased in the emotional attention factor, but diminished as regards both clarity and regulation. Effective Personality was at lower levels for all factors (Self-Esteem, Academic Self-Realisation, Resolute Self-Efficacy, Social Self-Realisation). The main conclusion was the need for assistance with the dimensions under study, in order to improve the well-being of university students after the serious effects caused by COVID-19.

Blood Immunophenotypes of Idiopathic Pulmonary Fibrosis: Relationship with Disease Severity and Progression.

(1) The role of the immune response in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remains controversial. We hypothesized that peripheral blood immune phenotypes will be different in IPF patients and may relate to the disease severity and progression. (2) Whole blood flow cytometry staining was performed at diagnosis in 32 IPF patients, and in 32 age- and smoking-matched healthy controls. Thirty-one IPF patients were followed up for one year and categorized as stable or progressors based on lung function, deterioration and/or death. At 18-60 months, immunophenotypes were characterized again. (3) The main results showed that: (1) compared to matched controls, at diagnosis, patients with IPF showed more neutrophils, CD8+HLA-DR+ and CD8+CD28- T cells, and fewer B lymphocytes and naïve T cells; (2) in IPF, circulating neutrophils, eosinophils and naïve T cells were associated with lung function abnormalities; (3) patients whose disease progressed during the 12 months of follow-up showed evidence of cytotoxic dysregulation, with increased CD8+CD28- T cells, decreased naïve T cells and an inverted CD4/CD8 ratio at baseline; and (4) blood cell alterations were stable over time in survivors. (4) IPF is associated with abnormalities in circulating immune cells, particularly in the cytotoxic cell domain. Patients with progressive IPF, despite antifibrotic therapy, present an over-activated and exhausted immunophenotype at diagnosis, which is maintained over time.

Lung immune signatures define two groups of end-stage IPF patients.

BACKGROUND: The role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial. METHODS: To investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26). Finally, differential gene expression and hypergeometric test were used to explore non-immune differences between clusters. RESULTS: We identified two clusters (C#1 and C#2) of IPF patients of similar size in the LTRC dataset. C#1 included 58 patients (53%) with enrichment in GSVA immune signatures, particularly cytotoxic and memory T cells signatures, whereas C#2 included 51 patients (47%) with an overall lower expression of GSVA immune signatures (results were validated by flow cytometry with similar unbiased clustering generation). Differential gene expression between clusters identified differences in cilium, epithelial and secretory cell genes, all of them showing an inverse correlation with the immune response signatures. Notably, both clusters showed distinct features despite clinical similarities. CONCLUSIONS: In end-stage IPF lung tissue, we identified two clusters of patients with very different levels of immune signatures and gene expression but with similar clinical characteristics. Weather these immune clusters differentiate diverse disease trajectories remains unexplored.

End-Stage Idiopathic Pulmonary Fibrosis Lung Microenvironment Promotes Impaired NK Activity.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic age-related chronic lung disease characterized by the accumulation of senescent cells. Whether impaired immune response is responsible for the accumulation of senescent cells in the IPF lung remains unknown. In this study, we characterized the NK phenotype in IPF lungs via flow cytometry using 5-dodecanoylaminofluorescein di-ß-d-galactopyranoside, markers of tissue residence, and chemokine receptors. The effect of the lung microenvironment was evaluated using lung fibroblast (LF) conditioned media (CM), and the bleomycin-induced pulmonary fibrosis mouse model was used to assess the in vivo relationship between NK cells and the accumulation of senescent cells. We found that NK cells from the lower lobe of IPF patients exhibited immune-senescent and impaired CD57-NKG2A+ phenotype. We also observed that culture of NK cells from healthy donors in CM from IPF lower lobe lung fibroblasts induced a senescent-like phenotype and impaired cytotoxic capacity. There is an impaired NK recruitment by LF, and NKs presented decreased migration toward their CM. In addition, NK cell-depleted mice treated with bleomycin showed increased collagen deposition and accumulation of different populations of senescent cells compared with controls. The IPF lung microenvironment induces a dysfunctional NK phenotype limiting the clearance of lung senescent cells and the resolution of lung fibrosis. We propose that impaired NK activity could be one of the mechanisms responsible for perpetuating the accumulation of senescent cells in IPF lungs.

Persistence of a SARS-CoV-2 T-cell response in patients with long COVID and lung sequelae after COVID-19.

1 year after an acute COVID-19 episode, patients with either lung sequelae or long COVID show a stronger SARS-CoV-2-specific T-cell response than fully recovered individuals, suggesting persistent cell stimulation by residual viral reservoirs https://bit.ly/40bPZm7.

Early events marking lung fibroblast transition to profibrotic state in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is an age-associated progressive lung disease with accumulation of scar tissue impairing gas exchange. Previous high-throughput studies elucidated the role of cellular heterogeneity and molecular pathways in advanced disease. However, critical pathogenic pathways occurring in the transition of fibroblasts from normal to profibrotic have been largely overlooked. METHODS: We used single cell transcriptomics (scRNA-seq) from lungs of healthy controls and IPF patients (lower and upper lobes). We identified fibroblast subclusters, genes and pathways associated with early disease. Immunofluorescence assays validated the role of MOXD1 early in fibrosis. RESULTS: We identified four distinct fibroblast subgroups, including one marking the normal-to-profibrotic state transition. Our results show for the first time that global downregulation of ribosomal proteins and significant upregulation of the majority of copper-binding proteins, including MOXD1, mark the IPF transition. We find no significant differences in gene expression in IPF upper and lower lobe samples, which were selected to have low and high degree of fibrosis, respectively. CONCLUSIONS: Early events during IPF onset in fibroblasts include dysregulation of ribosomal and copper-binding proteins. Fibroblasts in early stage IPF may have already acquired a profibrotic phenotype while hallmarks of advanced disease, including fibroblast foci and honeycomb formation, are still not evident. The new transitional fibroblasts we discover could prove very important for studying the role of fibroblast plasticity in disease progression and help develop early diagnosis tools and therapeutic interventions targeting earlier disease states.

SARS-CoV-2 T-cell response in COVID-19 convalescent patients with and without lung sequelae.

A specific T-cell response persists in the majority of COVID-19 patients 6 months after hospital discharge. This response is more prominent in those who required critical care during the acute COVID-19 episode but is reduced in patients with lung sequelae. https://bit.ly/3fBuVA4.

Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge.

BACKGROUND: Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge. METHODS: Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors. RESULTS: DLCO was < 80% ref. in 125 (58%) of patients, who were older, more frequently smokers, had hypertension, suffered more severe COVID-19 during hospitalization and refer persistent dyspnoea 6 months after discharge. Multivariate regression analysis showed that age ≥ 60 years and severity score of the acute episode ≥ 6 were independent risk factors of reduced DLCO 6 months after discharge. Levels of epithelial (SP-A, SP-D and SLPI) and endothelial (sICAM-1 and angiopoietin-2) markers were higher in patients with reduced DLCO, particularly in those with DLCO ≤ 50% ref. Circulating SP-A levels were associated with the occurrence of acute respiratory distress syndrome (ARDS), organizing pneumonia and pulmonary embolisms during hospitalization. CONCLUSIONS: Reduced DLCO is common in COVID-19 survivors 6 months after hospital discharge, especially in those older than 60 years with very severe acute disease. In these individuals, elevated levels of epithelial and endothelial markers suggest persistent lung damage.

A Mediation Model between Self-Esteem, Anxiety, and Depression in Sport: The Role of Gender Differences in Speleologists.

The scientific literature on mental health has found an association between physical activity and emotional wellbeing and recommends active leisure activities as a way of keeping stress under control. The purpose of this research study is to analyze the level of anxiety, the symptoms of depression and the level of self-esteem of people practicing speleology, as well as possible gender differences. This paper also attempts to understand whether self-esteem is associated with the presence of symptoms of depression in speleologists and whether anxiety has a mediating effect. We conduct a cross-sectional and descriptive research study with a sampling of 105 adult speleologists. The results reveal that the total mediation model is applicable, as self-esteem has a significant indirect association with depression through trait anxiety, as well as a partial mediation model that is applicable through state anxiety. This means that speleologists with high levels of self-esteem, who appreciate and value themselves adequately, reveal lower levels of trait anxiety, and this negatively influences their levels of depression (that is, a lower level of depressive symptoms). At the same time, speleologists with high levels of self-esteem, who appreciate and value themselves adequately, also reveal lower levels of state anxiety, which again has a negative impact on their levels of depression (with fewer symptoms of depression). Emotions such as anxiety, self-esteem, depression and their collateral effects are international topics of interest, which are relevant for people from all sporting backgrounds; therefore, value should be placed on supporting and carrying out further research into this topic.

Determination of Senescent Myofibroblasts in Precision-Cut Lung Slices.

Fibroblast-to-myofibroblast transdifferentiation and the acquisition of a senescent phenotype are hallmarks of fibrotic diseases. The study of the localization of senescent myofibroblasts as well as their interactions with other cell types in the fibrotic tissue has been hindered by the lack of methods to detect these cells in vivo. Here, we describe methods to detect tissue localization of senescent myofibroblasts in precision-cut lung slices (PCLS) by combining ß-galactosidase staining with immunofluorescence techniques.

The Association of Parental Interest in Entrepreneurship with the Entrepreneurial Interest of Spanish Youth.

As entrepreneurial interest is believed to represent a causal factor increasing entrepreneurship, research has begun to explore how family systems affect youth entrepreneurial interests. In the present study, we attempt to identify different types of family influence on the entrepreneurial interests of young people. A questionnaire was used to obtain data from 1633 Spanish adolescents (15 to 18 years old) and another questionnaire was used to obtain data from 839 parents. Principal component analysis identified unique family types and revealed that they have differential associations to entrepreneurial interest among youth. These findings reaffirm the influence of family on the entrepreneurial ecosystem and the promotion of an entrepreneurial family culture. This study further suggests that early attention should focus on the detection of entrepreneurial interest among youth so that actions can be implemented in the families to incentivize an entrepreneurial family culture.

Multi-level immune response network in mild-moderate Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an abnormal pulmonary and systemic immune response to tobacco smoking. Yet, how do immune cells relate within and between these two biological compartments, how the pulmonary infiltrate influences the lung transcriptome, and what is the role of active smoking vs. presence of disease is unclear. METHODS: To investigate these questions, we simultaneously collected lung tissue and blood from 65 individuals stratified by smoking habit and presence of the disease. The immune cell composition of both tissues was assessed by flow cytometry, whole lung transcriptome was determined with Affymetrix arrays, and we used Weighted Gene Co-expression Network Analysis (WGCNA) to integrate results. RESULTS: Main results showed that: (1) current smoking and the presence of COPD were both independently associated with a reduction in the proportion of lung T cells and an increase of macrophages, specifically those expressing CD80 + CD163+; (2) changes in the proportion of infiltrating macrophages, smoking status or the level of airflow limitation were associated to different WGCNA modules, which were enriched in iron ion transport, extracellular matrix and cilium organization gene ontologies; and, (3) circulating white blood cells counts were correlated with lung macrophages and T cells. CONCLUSIONS: Mild-moderated COPD lung immune infiltrate is associated with the active smoking status and presence of disease; is associated with changes in whole lung tissue transcriptome and marginally reflected in blood.

Smoking Impairs the Immunomodulatory Capacity of Lung-Resident Mesenchymal Stem Cells in Chronic Obstructive Pulmonary Disease.

Tobacco smoking is the main environmental risk factor for chronic obstructive pulmonary disease (COPD), but not all smokers develop the disease. A population of lung-resident mesenchymal stem cells (LR-MSCs) exist in healthy lungs, but how tobacco smoking affects them and their role in COPD have not been assessed yet. Using a sphere-based culture technique, we isolated LR-MSCs from lung tissue obtained from nonsmokers and current and former smokers with and without COPD (n = 53). The cells were characterized by flow cytometry and Affymetrix arrays. Their immunomodulatory capacity was assessed in vitro using cocultures with T cells and after preincubation with 2.5% and 5% cigarette smoke extract. We were able to isolate LR-MSCs expressing similar phenotypic markers in all of the study groups. LR-MSCs from current smokers with COPD expressed different levels of CX3CL1 and CCL5 cytokines, and were unable to modulate CD8+ T-cell proliferation. Preincubation of LR-MSCs with cigarette smoke extract reduced their immunomodulatory capacity. In conclusion, 1) LR-MSCs can be isolated in similar amounts from never-smokers and smokers with and without COPD; 2) their immunomodulatory capacity is impaired in current smokers with COPD, but not in those with normal lung function; and 3) this is reversible after smoking cessation and is reproducible in vitro.

Characterization, localization and comparison of c-Kit+ lung cells in never smokers and smokers with and without COPD.

BACKGROUND: c-Kit + lung stem cells have been described in the human healthy lung. Their potential relation with smoking and/or chronic obstructive pulmonary disease (COPD) is unknown. METHODS: We characterized and compared c-Kit+ cells in lung tissue of 12 never smokers (NS), 15 smokers with normal spirometry (S) and 44 COPD patients who required lung resectional surgery. Flow cytometry (FACS) was used to characterize c-Kit+ cells in fresh lung tissue disaggregates, and immunofluorescence (IF) for further characterization and to determine their location in OCT- embedded lung tissue. RESULTS: We identified 4 c-Kit+ cell populations, with similar proportions in NS, S and COPD: (1) By FACS, c-Kithigh/CD45+ cells (4.03 ± 2.97% (NS), 3.96 ± 5.30% (S), and 5.20 ± 3.44% (COPD)). By IF, these cells were tryptase+ (hence, mast cells) and located around the airways; (2) By IF, c-Kitlow/CD45+/triptase- (0.07 ± 0.06 (NS), 0.03 ± 0.02 (S), and 0.06 ± 0.07 (COPD) cells/field), which likely correspond to innate lymphoid cells; (3) By FACS, c-Kitlow/CD45-/CD34+ (0.95 ± 0.84% (NS), 1.14 ± 0.94% (S) and 0.95 ± 1.38% (COPD)). By IF these cells were c-Kitlow/CD45-/CD31+, suggesting an endothelial lineage, and were predominantly located in the alveolar wall; and, (4) by FACS, an infrequent c-Kitlow/CD45-/CD34- population (0.09 ± 0.14% (NS), 0.08 ± 0.09% (S) and 0.08 ± 0.11% (COPD)) compatible with a putative lung stem cell population. Yet, IF failed to detect them and we could not isolate or grow them, thus questioning the existence of c-Kit+ lung stem-cells. CONCLUSIONS: The adult human lung contains a mixture of c-Kit+ cells, unlikely to be lung stem cells, which are independent of smoking status and/or presence of COPD.

The inflammasome pathway in stable COPD and acute exacerbations.

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD). The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1) lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2) sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1) in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL)-1ß mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2) during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1ß, IL-18) were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD.

Network Analysis of Lung Transcriptomics Reveals a Distinct B-Cell Signature in Emphysema.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by a combination of airways disease (bronchiolitis) and parenchymal destruction (emphysema), whose relative proportion varies from patient to patient. OBJECTIVES: To explore and contrast the molecular pathogenesis of emphysema and bronchiolitis in COPD. METHODS: We used network analysis of lung transcriptomics (Affymetrix arrays) in 70 former smokers with COPD to compare differential expression and gene coexpression in bronchiolitis and emphysema. MEASUREMENTS AND MAIN RESULTS: We observed that in emphysema (but not in bronchiolitis) (1) up-regulated genes were enriched in ontologies related to B-cell homing and activation; (2) the immune coexpression network had a central core of B cell-related genes; (3) B-cell recruitment and immunoglobulin transcription genes (CXCL13, CCL19, and POU2AF1) correlated with emphysema severity; (4) there were lymphoid follicles (CD20(+)IgM(+)) with active B cells (phosphorylated nuclear factor-κB p65(+)), proliferation markers (Ki-67(+)), and class-switched B cells (IgG(+)); and (5) both TNFRSF17 mRNA and B cell-activating factor protein were up-regulated. These findings were by and large reproduced in a group of patients with incipient emphysema and when patients with emphysema were matched for the severity of airflow limitation of those with bronchiolitis. CONCLUSIONS: Our study identifies enrichment in B cell-related genes in patients with COPD with emphysema that is absent in bronchiolitis. These observations contribute to a better understanding of COPD pathobiology and may open new therapeutic opportunities for patients with COPD.