Exploring adolescents' experiences of continuing to wear face masks during COVID-19: A qualitative descriptive study in Barcelona (Spain).

BACKGROUND: The COVID-19 pandemic prompted the use of face masks as a social distancing measure. Although evidence supports their effectiveness in preventing infection, it remains unclear why some adolescents choose to continue wearing them postpandemic, even when it is no longer mandatory. This study aims to explore adolescents' experiences of wearing face masks during the COVID-19 pandemic when their use was no longer mandatory. METHOD: In this exploratory qualitative study, data were collected from 16 adolescents through face-to-face semistructured interviews. The participants were asked about the reasons and feelings associated with continuing to wear masks, as well as the contexts in which they felt safe without a mask. The collected data were analysed using Braun and Clarke's thematic analysis. RESULTS: Three main themes were identified: (1) Navigating complex decision-making: balancing safety and self-image, (2) peer influence dynamics and (3) managing the future: weather dynamics and pandemic evolution. DISCUSSION: The potential implications of withdrawing COVID-19 preventive measures, such as mask-wearing, beyond the pandemic remain understudied. It is crucial to further investigate the perceptions related to wearing masks and its cessation, especially amongst vulnerable individuals. PATIENT OR PUBLIC CONTRIBUTION: Due to methodological constraints associated with participants' age, they were not engaged in the design, data analysis, data interpretation or manuscript preparation phases of the study.

The Impact of COVID-19 on Adolescents' Mental Health in Catalonia (Spain): A Qualitative Study.

This study aimed to understand the experiences of adolescents regarding the perceived impact of COVID-19 on their mental health in Catalonia (Spain). A qualitative exploratory methodology was used with a purposive sample of 30 high-school students regarding their experiences of the self-perceived impact of COVID-19 on their mental health. Data were thematically analyzed using Braun and Clarke method. Three main themes emerged from the data: (a) the challenge of living confined, (b) the footprint of COVID-19 on adolescents' mental health, and (c) school dynamics during the lockdown. The COVID-19 pandemic negatively impacted adolescents' mental health, and adolescents perceived a lack of emotional support from educational centers. Therefore, incorporating emotional support in educational centers and offering emotional self-management tools to young students should be a priority. School nurses can play an essential role in recognizing and managing emotional needs and being the natural link between educational and primary care centers.

Determinants of COVID-19 vaccine hesitancy among students and parents in Sentinel Schools Network of Catalonia, Spain.

Vaccine hesitancy is defined as a delay in acceptance of vaccines despite its availability, caused by many determinants. Our study presents the key reasons, determinants and characteristics associated with COVID-19 vaccine acceptability among students over 16 years and parents of students under 16 years and describe the COVID-19 vaccination among students in the settings of sentinel schools of Catalonia, Spain. This is a cross-sectional study that includes 3,383 students and the parents between October 2021 and January 2022. We describe the student's vaccination status and proceed a univariate and multivariate analysis using a Deletion Substitution Addition (DSA) machine learning algorithm. Vaccination against COVID-19 reached 70.8% in students under 16 years and 95.8% in students over 16 years at the end of the study project. The acceptability among unvaccinated students was 40.9% and 20.8% in October and January, respectively, and among parents was proportionally higher among students aged 5-11 (70.2%) in October and aged 3-4 (47.8%) in January. The key reason to not vaccinate themselves, or their children, were concern about side effects, insufficient research about the effect of the vaccine in children, rapid development of vaccines, necessity for more information and previous infection by SARS-CoV-2. Several variables were associated with refusal end hesitancy. For students, the main ones were risk perception and use of alternative therapies. For parents, the age of students, sociodemographic variables, socioeconomic impact related to the pandemic, and use of alternative therapies were more evident. Monitoring vaccine acceptance and refusal among children and their parents has been important to understand the interaction between different multilevel determinants and we hope it will be useful to improve public health strategies for future interventions in this population.

Corrigendum: Feasibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen self-testing in school and summer camp attendees.

[This corrects the article DOI: 10.3389/fped.2022.975454.].

The COVID-19 Sentinel Schools Network of Catalonia (CSSNC) project: Associated factors to prevalence and incidence of SARS-CoV-2 infection in educational settings during the 2020-2021 academic year.

The Sentinel Schools project was designed to monitor and evaluate the epidemiology of COVID-19 in Catalonia, gathering evidence for health and education policies to inform the development of health protocols and public health interventions to control of SARS-CoV-2 infection in schools. The aim of this study was to estimate the prevalence and incidence of SARS-CoV-2 infections and to identify their determinants among students and staff during February to June in the academic year 2020-2021. We performed two complementary studies, a cross-sectional and a longitudinal component, using a questionnaire to collect nominal data and testing for SARS-CoV-2 detection. We describe the results and perform a univariate and multivariate analysis. The initial crude seroprevalence was 14.8% (95% CI: 13.1-16.5) and 22% (95% CI: 18.3-25.8) for students and staff respectively, and the active infection prevalence was 0.7% (95% CI: 0.3-1) and 1.1% (95% CI: 0.1-2). The overall incidence for persons at risk was 2.73 per 100 person-month and 2.89 and 2.34 per 100 person-month for students and staff, respectively. Socioeconomic, self-reported knowledge, risk perceptions and contact pattern variables were positively associated with the outcome while sanitary measure compliance was negatively associated, the same significance trend was observed in multivariate analysis. In the longitudinal component, epidemiological close contact with SARS-CoV-2 infection was a risk factor for SARS-CoV-2 infection while the highest socioeconomic status level was protective as was compliance with sanitary measures. The small number of active cases detected in these schools suggests a low transmission among children in school and the efficacy of public health measures implemented, at least in the epidemiological scenario of the study period. The major contribution of this study was to provide results and evidence that help analyze the transmission dynamic of SARS-CoV-2 and evaluate the associations between sanitary protocols implemented, and measures to avoid SARS-CoV-2 spread in schools.

Monitoring of SARS-CoV-2 seroprevalence among primary healthcare patients in the Barcelona Metropolitan Area: the SeroCAP sentinel network protocol.

INTRODUCTION: SARS-CoV-2 seroprevalence studies are currently being recommended and implemented in many countries. Forming part of the COVID-19 monitoring and evaluation plan of the Catalan Government Health Department, our network aims to initiate a primary healthcare sentinel monitoring system as a surrogate of SARS-CoV-2 exposure in the Barcelona Metropolitan Area. METHODS AND ANALYSIS: The seroCAP is a serial cross-sectional study, which will be performed in the Barcelona Metropolitan Area to estimate antibodies against SARS-CoV-2. From February 2021 to March 2022, the detection of serum IgG antibodies against SARS-CoV-2 trimeric spike protein will be performed on a monthly basis in blood samples collected for diverse clinical purposes in three reference hospitals from the three Barcelona healthcare areas (BCN areas). The samples (n=2588/month) will be from patients attended by 30 primary healthcare teams at 30 basic healthcare areas (BHA). A lab software algorithm will systematically select the samples by age and sex. Seroprevalence will be estimated and monitored by age, sex, BCN area and BHA. Descriptive and cluster analysis of the characteristics and distribution of SARS-CoV-2 infections will be performed. Sociodemographic, socioeconomic and morbidity-associated factors will be determined using logistic regression. We will explore the association between seroprevalence, SARS-CoV-2 confirmed cases and the implemented measures using interrupted time series analysis. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University Institute Foundation for Primary Health Care Research Jordi Gol i Gurina ethics committee. An informed consent is not required regarding the approval of the secondary use of biological samples within the framework of the COVID-19 pandemic. A report will be generated quarterly. The final analysis, conclusions and recommendations will be shared with the stakeholders and communicated to the general public. Manuscripts resulting from the network will be submitted for publication in peer-reviewed journals.

Study protocol for monitoring SARS-CoV-2 infection and its determinants in Catalonia (Spain): an observational and participatory research approach in a Sentinel Network of Schools.

INTRODUCTION: Since the SARS-CoV-2 became of concern in January 2020, many preventive measures have been adopted in educational settings to ensure the control of COVID-19 pandemic among children and staff in schools. This study aims to set up a school sentinel surveillance network with the purpose of monitoring SARS-CoV-2 infection, seroprevalence as well as to analyse the impact of preventive interventions of SARS-CoV-2 in school settings. Additionally, we will assess diverse screening strategies in a cohort of students and school staff to monitor the screening acceptance and its potential impact. Altogether, we hope this study will enable the design of more effective strategies for the prevention of COVID-19 spread. METHODS AND ANALYSIS: The sentinel schools' study is a cross-sectional, school-based project including 26 participating sentinel schools in Catalonia (Spain). Children, adolescents and staff at the schools will be invited to participate. This project will be carried out from January 2021 to June 2022 as follows: (1) twice yearly serological testing and molecular SARS-CoV-2 detection and questionnaires covering SARS-CoV-2 symptoms, tests, health, knowledge, attitudes and behaviours; (2) an environmental evaluation carried out in different classrooms; (3) SARS-CoV-2 transmission dynamics and the impact of different variants among confirmed cases and classmates; (4) a participatory process by which the participants are invited to act as coinvestigators to evaluate prevention strategies and provide recommendations to improve COVID-19 prevention in schools. Descriptive analysis will be performed for the main variables collected. The incidence and seroprevalence will be calculated and the association with sociodemographic factors and school characteristics will be determined using multivariate logistic regression. ETHICS AND DISSEMINATION: Ethical approval was obtained from the IDIAPJGol and the Hospital Universitari Vall d'Hebron ethics committees. A report will be generated quarterly. Findings will be disseminated at national and international conferences and published in peer-reviewed journals.

Feasibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen self-testing in school and summer camp attendees.

Background: SARS-CoV-2 screening is one of the pillars of non-pharmaceutical preventive strategies to early identify and isolate infected individuals and therefore decrease community incidence. Methods: We assessed the feasibility of severe acute respiratory syndrome coronavirus 2 self-testing with antigen-detecting rapid diagnostic tests in attendees of educational settings. Results: A total of 305 students (88.15%) and 41 staff (11.85%) from 9 to 56 years old participated in the self-testing procedure and answered the survey at the end of the study. 91.3% (n = 313) did not need help, 96.1% of participants reported the same outcome as the healthcare workers. 94.5% strongly or slightly agree with the statement "I would repeat the experience". Conclusion: The study demonstrates that self-testing is acceptable and usable in children, adolescents and adults when the epidemiological situation may require a systematic screening of these populations, although supervision by health care or previously trained personnel is recommended for younger age groups.

The human-specific duplicated α7 gene inhibits the ancestral α7, negatively regulating nicotinic acetylcholine receptor-mediated transmitter release.

Gene duplication generates new functions and traits, enabling evolution. Human-specific duplicated genes in particular are primary sources of innovation during our evolution although they have very few known functions. Here we examine the brain function of one of these genes (CHRFAM7A) and its product (dupα7 subunit). This gene results from a partial duplication of the ancestral CHRNA7 gene encoding the α7 subunit that forms the homopentameric α7 nicotinic acetylcholine receptor (α7-nAChR). The functions of α7-nAChR in the brain are well defined, including the modulation of synaptic transmission and plasticity underlying normal attention, cognition, learning, and memory processes. However, the role of the dupα7 subunit remains unexplored at the neuronal level. Here, we characterize that role by combining immunoblotting, quantitative RT-PCR and FRET techniques with functional assays of α7-nAChR activity using human neuroblastoma SH-SY5Y cell variants with different dupα7 expression levels. Our findings reveal a physical interaction between dupα7 and α7 subunits in fluorescent protein-tagged dupα7/α7 transfected cells that negatively affects normal α7-nAChR activity. Specifically, in both single cells and cell populations, the [Ca2+]i signal and the exocytotic response induced by selective stimulation of α7-nAChR were either significantly inhibited by stable dupα7 overexpression or augmented after silencing dupα7 gene expression with specific siRNAs. These findings identify a new role for the dupα7 subunit as a negative regulator of α7-nAChR-mediated control of exocytotic neurotransmitter release. If this effect is excessive, it would result in an impaired synaptic transmission that could underlie the neurocognitive and neuropsychiatric disorders associated with α7-nAChR dysfunction.

An okadaic acid fragment analogue prevents nicotine-induced resistance to cisplatin by recovering PP2A activity in non-small cell lung cancer cells.

We herein report the design, synthesis, and functional impact of an okadaic acid (OA) small analogue, ITH12680, which restores the activity of phosphoprotein phosphatase 2A (PP2A), whose deficient activity has been implicated in nicotine-mediated tumor progression and chemoresistance in non-small cell lung cancer (NSCLC). For its design, we paid attention to the structure of the PP2A-OA complex, where the C16-C38 OA fragment confers PP2A affinity and selectivity, but it is not involved in the inhibitory effect. Confirming this hypothesis, PP2A activity was not inhibited by ITH12680. By contrast, the compound partially restored OA-exerted PP2A inhibition in vitro. Moreover, flow cytometry and immunoblotting experiments revealed that ITH12680 reversed nicotine-induced cisplatin resistance in NSCLC cells, as it prevented nicotine-induced reduction of Bax expression and inhibited nicotine-mediated activation of cell survival and proliferation kinases, Akt and ERK1/2. Our findings suggest that the rescue of nicotine-inhibited PP2A activity could diminish the resistance to cisplatin treatment observed in NSCLC patients who continue smoking.

Anti-tumoral activity of the human-specific duplicated form of α7-nicotinic receptor subunit in tobacco-induced lung cancer progression.

OBJECTIVES: Tobacco smoking is strongly correlated with the onset and progression of non-small cell lung cancer (NSCLC). By activating α7 nicotinic acetylcholine receptors (α7-nAChRs) in these tumors nicotine and its tobacco-derived nitrosamine, NNK, contribute to these oncogenic processes. Here, we investigated whether the human-specific duplicated form of the α7-nAChR subunit (dupα7) behaves as an endogenous negative regulator of α7-nAChR-mediated tumorigenic activity induced by tobacco in NSCLC cells, similarly to its influence on other α7-nAChR-controlled functions in non-tumor cells. METHODS: Two human NSCLC cell lines, lung adenocarcinoma (A549) and squamous cell carcinoma of the lung (SK-MES-1), both wild-type or with stable overexpression of dupα7 (A549dupα7 or SK-MES-1dupα7), were used to investigate in vitro anti-tumor activity of dupα7 on nicotine- or NNK-induced tumor progression. For this purpose, migration, proliferation or epithelial-mesenchymal transition (EMT) were examined. The anti-tumor effect of dupα7 on nicotine-promoted tumor growth, proliferation or angiogenesis was also assessed in vivo in an athymic mouse model implanted with A549dupα7 or A549 xenografts. RESULTS: Overexpression of dupα7 in both cell lines almost completely suppresses the in vitro tumor-promoting effects induced by nicotine (1 µM) or NNK (100 nM) in wild-type cells. Furthermore, in mice receiving nicotine, A549dupα7 xenografts show: (i) a significant reduction of tumor growth, and (ii) decreased expression of cell markers for proliferation (Ki67) or angiogenesis (VEGF) compared to A549 xenografts. CONCLUSION: Our study demonstrates, for the first time, the in vitro and in vivo anti-tumor capacity of dupα7 to block the α7-nAChR-mediated tumorigenic effects of tobacco in NSCLC, suggesting that up-regulation of dupα7 expression in these tumors could offer a potential new therapeutic target in smoking-related cancers.

Interaction of the α7-nicotinic subunit with its human-specific duplicated dupα7 isoform in mammalian cells: Relevance in human inflammatory responses.

The α7 nicotinic receptor subunit and its partially duplicated human-specific dupα7 isoform are coexpressed in neuronal and non-neuronal cells. In these cells, α7 subunits form homopentameric α7 nicotinic acetylcholine receptors (α7-nAChRs) implicated in numerous pathologies. In immune cells, α7-nAChRs are essential for vagal control of inflammatory response in sepsis. Recent studies show that the dupα7 subunit is a dominant-negative regulator of α7-nAChR activity in Xenopus oocytes. However, its biological significance in mammalian cells, particularly immune cells, remains unexplored, as the duplicated form is indistinguishable from the original subunit in standard tests. Here, using immunocytochemistry, confocal microscopy, coimmunoprecipitation, FRET, flow cytometry, and ELISA, we addressed this challenge in GH4C1 rat pituitary cells and RAW264.7 murine macrophages transfected with epitope- and fluorescent protein-tagged α7 or dupα7. We used quantitative RT-PCR of dupα7 gene expression levels in peripheral blood mononuclear cells (PBMCs) from patients with sepsis to analyze its relationship with PBMC α7 mRNA levels and with serum concentrations of inflammatory markers. We found that a physical interaction between dupα7 and α7 subunits in both cell lines generates heteromeric nAChRs that remain mainly trapped in the endoplasmic reticulum. The dupα7 sequestration of α7 subunits reduced membrane expression of functional α7-nAChRs, attenuating their anti-inflammatory capacity in lipopolysaccharide-stimulated macrophages. Moreover, the PBMC's dupα7 levels correlated inversely with their α7 levels and directly with the magnitude of the patients' inflammatory state. These results indicate that dupα7 probably reduces human vagal anti-inflammatory responses and suggest its involvement in other α7-nAChR-mediated pathophysiological processes.

Expression patterns for nicotinic acetylcholine receptor subunit genes in smoking-related lung cancers.

Cigarette smoking is associated with increased risk for all histologic types of lung cancer, but why the strength of this association is stronger for squamous cell carcinoma than adenocarcinoma of the lung (SQC-L, ADC-L) is not fully understood. Because nicotine and tobacco-specific nitrosamines contribute to carcinogenesis by activating nicotinic acetylcholine receptors (nAChRs) on lung tumors and epithelial cells, we investigated whether differential expression of nAChR subtypes in these tumors could explain their different association with smoking. Expression of nAChR subunit genes in paired tumor and non-tumor lung specimens from 40 SQC-L and 38 ADC-L patients was analyzed by quantitative PCR. Compared to normal lung, both tumors share: i) transcriptional dysregulation of CHRNA3/CHRNA5/CHRNB4 (α3, α5, ß4 subunits) at the chromosomal locus that predisposes to lung cancer; and ii) decreased expression of CHRFAM7A (dupα7 subunit); this last subunit negatively modulates α7-nAChR activity in oocytes. In contrast, CHRNA7 (α7 subunit) expression was increased in SQC-L, particularly in smokers and non-survivors, while CHRNA4 (α4 subunit) expression was decreased in ADC-L. Thus, over-representation of cancer-stimulating α7-nAChR in SQC-L, also potentiated by smoking, and under-representation of cancer-inhibiting α4ß2-nAChR in ADC-L could explain the different tobacco influences on the tumorigenic process in each cancer type.

A new IRAK-M-mediated mechanism implicated in the anti-inflammatory effect of nicotine via α7 nicotinic receptors in human macrophages.

Nicotine stimulation of α7 nicotinic acetylcholine receptor (α7 nAChR) powerfully inhibits pro-inflammatory cytokine production in lipopolysaccharide (LPS)-stimulated macrophages and in experimental models of endotoxemia. A signaling pathway downstream from the α7 nAChRs, which involves the collaboration of JAK2/STAT3 and NF-κB to interfere with signaling by Toll-like receptors (TLRs), has been implicated in this anti-inflammatory effect of nicotine. Here, we identifiy an alternative mechanism involving interleukin-1 receptor-associated kinase M (IRAK-M), a negative regulator of innate TLR-mediated immune responses. Our data show that nicotine up-regulates IRAK-M expression at the mRNA and protein level in human macrophages, and that this effect is secondary to α7 nAChR activation. By using selective inhibitors of different signaling molecules downstream from the receptor, we provide evidence that activation of STAT3, via either JAK2 and/or PI3K, through a single (JAK2/PI3K/STAT3) or two convergent cascades (JAK2/STAT3 and PI3K/STAT3), is necessary for nicotine-induced IRAK-M expression. Moreover, down-regulation of this expression by small interfering RNAs specific to the IRAK-M gene significantly reverses the anti-inflammatory effect of nicotine on LPS-induced TNF-α production. Interestingly, macrophages pre-exposed to nicotine exhibit higher IRAK-M levels and reduced TNF-α response to an additional LPS challenge, a behavior reminiscent of the 'endotoxin tolerant' phenotype identified in monocytes either pre-exposed to LPS or from immunocompromised septic patients. Since nicotine is a major component of tobacco smoke and increased IRAK-M expression has been considered one of the molecular determinants for the induction of the tolerant phenotype, our findings showing IRAK-M overexpression could partially explain the known influence of smoking on the onset and progression of inflammatory and infectious diseases.