Validation of the inventory: lockdown and its impact on the university Community.

BACKGROUND: Significant consequences of COVID-19 within academic/professional life are, at the psychological level, related to worry, tension, stress; coping strategies and lifestyle changes. This study describes the process of design and validation of an inventory (QPIC), which aims to assess the psychological impact that a situation of confinement can produce among university students and teachers. METHODS: Design of the instrument and psychometric tests. A sample of 862 students and 229 professors affiliated to Spanish and Colombian universities was used. Data were collected in April 2020 with the request of the favourable Bioethics Committee IR/2020. RESULTS: Six experts carried out the content validation. A confirmatory factor analysis of the theoretical dimensions proposed for the scales was performed and the internal consistency of each of the three initial scales was confirmed (0.866, 0.813 and 0.834). CONCLUSION: A rigorous and reliable instrument is achieved, consisting of two final scales: (a) Worry, tension and stress scale (b) Coping scale, which helps to measure individual psychological effects in housebound situations. It is an instrument designed, constructed ad hoc to assess the impact of confinement and subjected to validation. The factor structure and reliability of the instrument are examined and good psychometric properties are obtained. The application of this inventory will make it possible to assess the impact on people's mental health during a period of confinement.

COVID-19 Infection among Nursing Students in Spain: The Risk Perception, Perceived Risk Factors, Coping Style, Preventive Knowledge of the Disease and Sense of Coherence as Psychological Predictor Variables: A Cross Sectional Survey.

The exploration of patterns of health beliefs about COVID-19 among nursing students may be beneficial to identify behaviors, attitudes and knowledge about contagion risk. We sought to analyze the variables of risk perception, perceived risk factors, coping style, sense of coherence and knowledge of preventive measures as possible predictors of having suffered from COVID-19. Participants were nursing students from 13 universities in Spain. Sociodemographic and health variables were collected. To test the independent variables, the Perception Risk Coping Knowledge (PRCK-COVID-19) scale was created and validated because there was no specific survey for young people adapted to the pandemic situation of COVID-19. It was validated with adequate psychometric properties. A total of 1562 students (87.5% female, mean age 21.5 ± 5.7 years) responded. The high perception of the risk of contagion, the high level of knowledge and a coping style focused on the situation were notable. Significant differences by gender were found in the coping styles, problem-focused, avoidance and knowledge scales, with women scoring higher in all categories. The multiple regression analysis was significant (F = 3.68; p < 0.001). The predictor variables were the coping styles subscale search for support and the intrinsic and extrinsic perceived risk factors. Our model predicts that nursing students with a social support-based coping style are at a higher risk of becoming infected with COVID-19, based on their own health belief model.

Design and Validation of a Questionnaire on Risk Perception, Coping Behaviors and Preventive Knowledge against COVID-19 among Nursing Students.

As shown in the previous literature, in view of the future responsibilities of nursing professionals and the consequences for healthcare, it is of great interest to examine their risk perceptions, coping behaviors, and sense of coherency during the COVID-19 pandemic. The purpose of this study is to design and to validate a specific questionnaire that evaluates the factors relating to perceived risk, coping behaviors, and preventive knowledge against COVID-19 infection among nursing students from Spain. This is a psychometric study of a questionnaire's design and its validation in 1562 nursing students at 16 undergraduate nursing institutions in Spain. An ad-hoc survey was designed by a panel of six experts drawing from the literature. After a trial test, the questionnaire was formed with four scales (perception, risk, coping, and knowledge of preventive practices for COVID-19), with a total of 69 items. The final questionnaire was composed of 52 items grouped into four scales, with good psychometric properties to measure risk perception (Cronbach's alpha 0.735), factors related to perceived risk (Cronbach's alpha 0.653), coping behaviors (Cronbach's alpha 0.80), and knowledge of preventive practices against COVID-19 (Cronbach's alpha 0.77). This questionnaire, specifically designed and validated for nursing students, is the first to address four important areas in the development of preventive measures against COVID-19.

Design of the EBE-ST Questionnaire among Nursing Students: Multicenter Study from Eight Universities in Spain.

BACKGROUND: Twenty years after the degree in nursing was introduced in Spain, the subject of evidence-based nursing is still unstructured and unestablished in most faculties. Moreover, there are hardly any rigorous studies at a national level that evaluate the current state of this competence in our faculties. Understanding the starting point is essential for the curricular design to ensure that evidence-based practice is implemented among future professionals. AIM: To design and validate an evidence-based nursing competency questionnaire for fourth-year nursing students. METHODS: A specific questionnaire was developed and validated (EBE-ST). A cross-sectional survey design with psychometric validation of an instrument. Participants were 304 senior year nursing students from eight universities in Spain (2020). RESULTS: The EBE-ST questionnaire is composed of 33 items that determine eight factors. It presents adequate reliability and validity (alpha = 0.882), measuring knowledge, attitudes and the practical application of evidence-based practice. CONCLUSIONS: We have created an instrument with good psychometric properties to measure evidence-based practice competence among senior nursing students. The heterogeneity of knowledge regarding evidence-based nursing in our country suggests that further reflection is warranted on the incorporation of this topic during undergraduate training. We have designed and validated an evidence-based nursing competency questionnaire specific to nursing students.

Diabetes Mellitus en pacientes pediátricos con Fibrosis Quística / Diabetes Mellitus in pediatric patients with Cystic Fibrosis

Introducción: La Fibrosis Quística (FQ) es una enfermedad hereditaria recesiva que afecta a varios órganos, fundamentalmente de los aparatos respiratorio y digestivo. La Diabetes Relacionada con la Fibrosis Quística (DRFQ) es una de sus principales complicaciones.Objetivos: Estudiar las complicaciones específicas de los pacientes pediátricos que padecen DRFQ y cómo afectan a su calidad de vida. Comparar las tasas de mortalidad de los pacientes pediátricos con FQ y con DRFQ. Poner de manifiesto la importancia del personal de enfermería en el manejo de los pacientes pediátricos con DRFQ.Metodología: Se llevó a cabo una revisión bibliográfica sistemática. Se incluyeron estudios publicados, en inglés y castellano, durante los últimos 10 años, y que analizaban una muestra de población de entre 0 y 9 años con FQ y/o DRFQ.Resultados: Se utilizaron 4 bases de datos para la búsqueda sistemática. Se analizaron 10 artículos para la resolución de los objetivos.Conclusiones: Las complicaciones que provocan la DRFQ, y los cuidados que requieren afectan a la calidad de vida de los pacientes. La progresión del diagnóstico y los tratamientos ha hecho que mejore su calidad de vida y que la diferencia de mortalidad entre los pacientes con FQ y con DRFQ se reduzca. El personal enfermero que atiende a los niños con DRFQ es un recurso de información esencial para los pacientes y sus familias. Las enfermeras deben transmitir la importancia de la adhesión a los tratamientos para conseguir una mejor calidad de vida

Introduction: Cystic Fibrosis (CF) is a hereditary recessive disease that affects several organs, mainly within the respiratory and digestive systems. Cystic Fibrosis Related Diabetes (CFRD) is one of its main complications.Objectives: To study the specific complications of pediatric patients suffering from CFRD and how they affect a patient's quality of life. To compare the mortality rates of pediatric patients with CF and with CFRD. To highlight the importance of nurses in the management of pediatric patients with CFRD.Methodology: A systematic bibliographic review was conducted. We included studies, in English and Spanish, published over the last 10 years, which analysed a population aged between 0 and 9 years old with CF and/or CFRD.Results: Four databases were used for the systematic search. We analysed 10 articles to address the objectives.Conclusions: The complications caused by CFRD and the care that patients require affect the patient's quality of life. Progress both with diagnosis and with treatment has improved the quality of life of patients, and has contributed to reductions in the difference between the mortality rates of patients with CF and without CFRD. Nurses who care for children with CFRD are essential as an information resource for patients and their families. Nurses must convey the importance of therapeutic adherence to achieve a better quality of life

Candida albicans beta-glucan exposure is controlled by the fungal CEK1-mediated mitogen-activated protein kinase pathway that modulates immune responses triggered through dectin-1.

Innate immunity to Candida albicans depends upon the recognition of molecular patterns on the fungal cell wall. However, the masking of major components such as beta-glucan seems to be a mechanism that fungi have evolved to avoid immune cell recognition through the dectin-1 receptor. Although the role of C. albicans mitogen-activated protein kinase (MAPK) pathways as virulence determinants has been established previously with animal models, the mechanism involved in this behavior is largely unknown. In this study we demonstrate that a disruption of the C. albicans extracellular signal-regulated kinase (ERK)-like 1 (CEK1)-mediated MAPK pathway causes enhanced cell wall beta-glucan exposure, triggering immune responses more efficiently than the wild type, as measured by dectin-1-mediated specific binding and human dendritic cell (hDC)- and macrophage-mediated phagocytosis, killing, and activation of intracellular signaling pathways. At the molecular level, the disruption of CEK1 resulted in altered spleen tyrosine kinase (Syk), Raf-1, and ERK1/2 activations together with IkappaB degradation on hDCs and increased dectin-1-dependent activator protein 1 (AP-1) activation on transfected cells. In addition, concurring with these altered pathways, we detected increased reactive oxygen species production and cytokine secretion. In conclusion, the CEK1-mediated MAPK pathway is involved in beta-glucan exposure in a fungal pathogen, hence influencing dectin-1-dependent immune cell recognition, thus establishing this fungal intracellular signaling route as a promising novel therapeutic target.

Structural requirements for multimerization of the pathogen receptor dendritic cell-specific ICAM3-grabbing non-integrin (CD209) on the cell surface.

The myeloid C-type lectin dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN, CD209) recognizes oligosaccharide ligands on clinically relevant pathogens (HIV, Mycobacterium, and Aspergillus). Alternative splicing and genomic polymorphism generate DC-SIGN mRNA variants, which have been detected at sites of pathogen entrance and transmission. We present evidence that DC-SIGN neck variants are expressed on dendritic and myeloid cells at the RNA and protein levels. Structural analysis revealed that multimerization of DC-SIGN within a cellular context depends on the lectin domain and the number and arrangement of the repeats within the neck region, whose glycosylation negatively affects oligomer formation. Naturally occurring DC-SIGN neck variants differ in multimerization competence in the cell membrane, exhibit altered sugar binding ability, and retain pathogen-interacting capacity, implying that pathogen-induced cluster formation predominates over the basal multimerization capability. Analysis of DC-SIGN neck polymorphisms indicated that the number of allelic variants is higher than previously thought and that multimerization of the prototypic molecule is modulated in the presence of allelic variants with a different neck structure. Our results demonstrate that the presence of allelic variants or a high level of expression of neck domain splicing isoforms might influence the presence and stability of DC-SIGN multimers on the cell surface, thus providing a molecular explanation for the correlation between DC-SIGN polymorphisms and altered susceptibility to HIV-1 and other pathogens.

AM3 modulates dendritic cell pathogen recognition capabilities by targeting DC-SIGN.

AM3 (Inmunoferon) is an orally effective immunomodulator that influences the regulatory and effector functions of the immune system whose molecular mechanisms of action are mostly unknown. We hypothesized that the polysaccharide moiety of AM3 (IF-S) might affect immune responses by modulating the lectin-dependent pathogen recognition abilities of human dendritic cells. IF-S inhibited binding of viral, fungal, and parasite pathogens by human monocyte-derived dendritic cells in a dose-dependent manner. IF-S specifically impaired the pathogen recognition capabilities of DC-SIGN, as it reduced the attachment of Candida, Aspergillus, and Leishmania to DC-SIGN transfectants. IF-S also inhibited the interaction of DC-SIGN with both its cellular counterreceptor (intercellular adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120 protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV trans-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN internalization in DCs without affecting mannose receptor expression, and (1)D saturation transfer difference nuclear magnetic resonance demonstrated that IF-S directly interacts with DC-SIGN on the cell surface. Therefore, the polysaccharide moiety of AM3 directly influences pathogen recognition by dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is the target for an immunomodulator and imply that the adjuvant and immunomodulatory actions of AM3 are mediated, at least in part, by alteration of the DC-SIGN functional activities.

RUNX3 negatively regulates CD36 expression in myeloid cell lines.

CD36 is a member of the scavenger receptor type B family implicated in the binding of lipoproteins, phosphatidylserine, thrombospondin-1, and the uptake of long-chain fatty acids. On mononuclear phagocytes, recognition of apoptotic cells by CD36 contributes to peripheral tolerance and prevention of autoimmunity by impairing dendritic cell (DC) maturation. Besides, CD36 acts as a coreceptor with TLR2/6 for sensing microbial diacylglycerides, and its deficiency leads to increased susceptibility to Staphylococcus aureus infections. The RUNX3 transcription factor participates in reprogramming DC transcription after pathogen recognition, and its defective expression leads to abnormally accelerated DC maturation. We present evidence that CD36 expression is negatively regulated by the RUNX3 transcription factor during myeloid cell differentiation and activation. In molecular terms, RUNX3 impairs the activity of the proximal regulatory region of the CD36 gene in myeloid cells through in vitro recognition of two functional RUNX-binding elements. Moreover, RUNX3 occupies the CD36 gene proximal regulatory region in vivo, and its overexpression in myeloid cells results in drastically diminished CD36 expression. The down-regulation of CD36 expression by RUNX3 implies that this transcription factor could impair harmful autoimmune responses by contributing to the loss of pathogen- and apoptotic cell-recognition capabilities by mature DCs.

p38 mitogen-activated protein kinase mediates the Fas-induced mitochondrial death pathway in CD8+ T cells.

The p38 mitogen-activated protein kinase (MAPK) signaling pathway can be activated by a variety of stress stimuli such as UV radiation and osmotic stress. The regulation and role of this pathway in death receptor-induced apoptosis remain unclear and may depend on the specific death receptor and cell type. Here we show that binding of Fas ligand to Fas activates p38 MAPK in CD8+ T cells and that activation of this pathway is required for Fas-mediated CD8+ T-cell death. Active p38 MAPK phosphorylates Bcl-xL and Bcl-2 and prevents the accumulation of these antiapoptotic molecules within the mitochondria. Consequently, a loss of mitochondrial membrane potential and the release of cytochrome c lead to the activation of caspase 9 and, subsequently, caspase 3. Therefore, the activation of p38 MAPK is a critical link between Fas and the mitochondrial death pathway and is required for the Fas-induced apoptosis of CD8+ T cells.

DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production.

The generation of pathogen-specific immune responses is dependent on the signaling capabilities of pathogen-recognition receptors. DC-SIGN is a C-type lectin that mediates capture and internalization of viral, bacterial, and fungal pathogens by myeloid dendritic cells. DC-SIGN-interacting pathogens are thought to modulate dendritic cell maturation by interfering with intracellular signaling from Toll-like receptor molecules. We report that engagement of DC-SIGN by specific antibodies does not promote dendritic cell maturation but induces ERK1/2 and Akt phosphorylation without concomitant p38MAPK activation. DC-SIGN ligation also triggers PLCgamma phosphorylation and transient increases in intracellular calcium in dendritic cells. In agreement with its signaling capabilities, a fraction of DC-SIGN molecules partitions within lipid raft-enriched membrane fractions both in DC-SIGN-transfected and dendritic cells. Moreover, DC-SIGN in dendritic cells coprecipitates with the tyrosine kinases Lyn and Syk. The relevance of the DC-SIGN-initiated signals was demonstrated in monocyte-derived dendritic cells, as DC-SIGN cross-linking synergizes with TNF-alpha for IL-10 release and enhances the production of LPS-induced IL-10. These results demonstrate that DC-SIGN-triggered intracellular signals modulate dendritic cell maturation. Since pathogens stimulate Th2 responses via preferential activation of ERK1/2, these results provide a molecular explanation for the ability of DC-SIGN-interacting pathogens to preferentially evoke Th2-type immune responses.

DC-SIGN mediates the binding of Aspergillus fumigatus and keratinophylic fungi by human dendritic cells.

Human contact with fungi does not usually lead to pathological consequences, as the immune system manages to defeat the invader pathogens. Nevertheless, under immune suppression, fungi overcome immune defenses and cause diseases that range from nonserious colonizations of keratinizated tissue (Dermatophytosis) to life threatening disseminated infections (Aspergillosis). Host defenses against fungi rely on innate and adaptative responses, with dendritic cell (DC) and macrophage surface receptors having a major role in the recognition of fungal pathogens and in the orchestration of an effective immune response. DC-SIGN is a C-type lectin involved in the recognition of bacterial, viral and parasitic pathogens, as well as in interactions between cells of the immune system. Its expression is restricted to DCs and subsets of macrophages. Here we show that DC-SIGN mediates the binding and capture of Aspergillus fumigatus and keratinophylic fungi, including Chrysosporium tropicum, by human DCs, describe the requirements of these interactions and discuss their potential involvement in the onset and persistence of pulmonary fungal infections.

Regulated recruitment of DC-SIGN to cell-cell contact regions during zymosan-induced human dendritic cell aggregation.

Zymosan is a beta-glucan, mannan-rich yeast particle widely used to activate the inflammatory response of immune cells. We studied the zymosan-binding potential of human dendritic cells (hDCs) by using specific carbohydrate inhibitors and blocking monoclonal antibodies. We show that DC-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN) is a major nonopsonic recognition receptor for zymosan on hDCs. Indeed, blocking of DC-SIGN inhibited the inflammatory response of DCs to zymosan. We compared the zymosan-binding capacity of hDC-SIGN to that of Dectin-1 and complement receptor 3 (CR3), which are receptors involved in the nonopsonic recognition of these yeast-derived particles. Dectin-1- and DC-SIGN-K562 cells bound to zymosan particles, whereas CR3-K562 cells did not. DC-SIGN and Dectin-1 were also expressed in COS cells to compare their ability to trigger particle internalization in a nonphagocytic cell line. DC-SIGN transfectants were unable to internalize bound particles, indicating that DC-SIGN is primarily involved in recognition but not in particle internalization. Zymosan induced a rapid DC aggregation that was accompanied by a dramatic change of DC-SIGN distribution in the plasma membrane. Under resting conditions, DC-SIGN was diffusely distributed through the cell surface, displaying clusters at the free leading edge. Upon zymosan treatment, DC-SIGN was markedly redistributed to cell-cell contacts, supporting an adhesion role in DC-DC interactions. The mechanism(s) supporting DC-SIGN-mediated intercellular adhesion were further investigated by using DC-SIGN-K562 aggregation. DC-SIGN was highly concentrated at points of cell-cell contact, suggesting a role for enhanced avidity during DC-SIGN-mediated intercellular adhesion.

Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin mediates binding and internalization of Aspergillus fumigatus conidia by dendritic cells and macrophages.

Aspergillus fumigatus is responsible for a large percentage of nosocomial opportunistic fungal infections in immunocompromised hosts, especially during cytotoxic chemotherapy and after bone marrow transplantation, and is currently a major direct cause of death in leukemia patients. Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a type II C-type lectin that functions as an adhesion receptor and is used by viral and bacterial pathogens to gain access to human DC. We report that DC-SIGN specifically interacts with clinical isolates of A. fumigatus. DC-SIGN-dependent binding of A. fumigatus conidia can be demonstrated with stable transfectants and monocyte-derived DC and is inhibited by anti-DC-SIGN Abs. Binding and internalization of A. fumigatus conidia correlates with DC-SIGN cell surface expression levels and is abolished in the presence of A. fumigatus-derived cell wall galactomannans. The clinical relevance of this interaction is emphasized by the presence of DC-SIGN in lung DC and alveolar macrophages, and further illustrated by the DC-SIGN-dependent attachment of A. fumigatus conidia to the cell membrane of IL-4-treated monocyte-derived macrophages. Our results suggest the involvement of DC-SIGN in the initial stages of pulmonary infection as well as in fungal spreading during invasive aspergillosis.

Regulated expression of the pathogen receptor dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin in THP-1 human leukemic cells, monocytes, and macrophages.

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a type II C-type lectin that functions as an adhesion receptor and mediates binding and internalization of pathogens such as virus (human immunodeficiency virus, hepatitis C), bacteria (Mycobacterium), fungi, and parasites. DC-SIGN expression in vivo is primarily restricted to interstitial dendritic cells (DC) and certain tissue macrophages. We now report that leukemic THP-1 cells, widely used as a model for monocyte-macrophage differentiation, express very low basal levels of DC-SIGN and that DC-SIGN expression in THP-1 cells is regulated during differentiation. Differentiation-inducing agents (phorbol ester, bryostatin) conveyed THP-1 cells with the ability to up-regulate DC-SIGN mRNA levels and cell surface expression in response to interleukin-4 (IL-4) or IL-13. DC-SIGN up-regulation required a functional JAK-STAT signaling pathway, was inhibited in the presence of lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha), and conferred THP-1 cells with increased pathogen recognition and T cell stimulatory capabilities. The up-regulation of DC-SIGN on THP-1 cells resembles its inducible expression on monocytes and macrophages, where DC-SIGN expression is also induced by IL-4/IL-13 and negatively regulated by TNF-alpha, LPS, and vitamin D(3). These results point to THP-1 cells as a useful cellular system to characterize the pathogen-binding capabilities of DC-SIGN and to dissect the molecular mechanisms that control its regulated and tissue-specific expression in myeloid dendritic cells, and the results suggest that DC-SIGN constitutes a marker for both DC and alternatively activated macrophages.