HLA A*24:02-restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes.

CD8+ T cells destroy insulin-producing pancreatic ß cells in type 1 diabetes through HLA class I-restricted presentation of self-antigens. Combinatorial peptide library screening was used to produce a preferred peptide recognition landscape for a patient-derived T cell receptor (TCR) that recognized the preproinsulin-derived (PPI-derived) peptide sequence LWMRLLPLL in the context of disease risk allele HLA A*24:02. Data were used to generate a strong superagonist peptide, enabling production of an autoimmune HLA A*24:02-peptide-TCR structure by crystal seeding. TCR binding to the PPI epitope was strongly focused on peptide residues Arg4 and Leu5, with more flexibility at other positions, allowing the TCR to strongly engage many peptides derived from pathogenic bacteria. We confirmed an epitope from Klebsiella that was recognized by PPI-reactive T cells from 3 of 3 HLA A*24:02+ patients. Remarkably, the same epitope selected T cells from 7 of 8 HLA A*24+ healthy donors that cross-reacted with PPI, leading to recognition and killing of HLA A*24:02+ cells expressing PPI. These data provide a mechanism by which molecular mimicry between pathogen and self-antigens could have resulted in the breaking of self-tolerance to initiate disease.

Healthcare and Epidemiological Surveillance Costs of Hepatitis A Outbreaks in Spain in Regions with and without Universal Hepatitis A Vaccination of Children during 2010-2018.

The aim of this study was to evaluate and compare hepatitis A outbreak-associated healthcare and epidemiological surveillance costs in Spain in two types of autonomous regions during 2010-2018: (1) regions with a prevention strategy based on universal hepatitis A vaccination of children and vaccination of high-risk population groups (Catalonia) and (2) regions with a prevention strategy based on vaccinating high-risk population groups (Castile and Leon, Murcia, Navarra, Community of Madrid, Community of Valencia). Healthcare costs were determined based on the resources used to treat hepatitis A outbreak-associated cases and hospitalizations. Epidemiological surveillance costs were calculated from the resources used during surveillance activities. The ratios for total, healthcare and epidemiological surveillance costs (regions without universal hepatitis A vaccination of children vs. Catalonia) were used to compare the two hepatitis A prevention strategies. From 2010 to 2018, the total, healthcare and epidemiological surveillance costs per million population were 1.75 times (EUR 101,671 vs. EUR 58,032), 1.96 times (EUR 75,500 vs. EUR 38,516) and 1.34 times greater (EUR 26,171 vs. EUR 19,515) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. The ratios tended to increase over time during 2010-2018. In 2015-2018, total, healthcare and epidemiological surveillance costs per million population were 2.68 times (EUR 69,993 vs. EUR 26,158), 2.86 times (EUR 53,807 vs. EUR 18,825) and 2.21 times greater (EUR 16,186 vs. EUR 7333) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. These findings suggest that universal hepatitis A vaccination of children could reduce hepatitis A outbreak-associated costs.

Clostridium and Cryptosporidium outbreak linked to a splash pad.

BACKGROUND: . Splash pads for recreational purposes are widespread. Using these pads can pose a health risk if they lack installation regulation and water quality supervision. Our aim was to describe a waterborne disease outbreak caused by Clostridium perfringens and Cryptosporidium spp. in a Barcelona district and the measures taken for its control. METHODS: . On August 2018, 71 cases of acute gastroenteritis were detected, affecting people who used a splash pad or were in contact with a user. Microbiological and environmental investigations were carried out. A descriptive analysis of the sample and Poisson regression models adjusted for age and sex were performed, obtaining frequencies, median values, and adjusted prevalence ratios with their 95% confidence intervals. RESULTS: The median age of the cases was 6.7 years, 27 (38%) required medical care, and three (4.2%) were hospitalized. The greater the number of times a person entered the area, the greater the number of symptoms and their severity. Nineteen (76%) of the 25 stool samples collected from cases showed the presence of one or both pathogens. Environmental investigations showed deficiencies in the facilities and identified the presence of both species in the splash pad. Health education and hygiene measures were carried out, and 14 days after the closure of the facilities, no more cases related to the pad were recorded. CONCLUSIONS: . Specific regulations are needed on the use of splash pads for recreational purposes. Until these regulations are in place, these types of facility should comply with the regulations that apply to swimming pools and spas, including those related to the design of the tanks, water recirculation systems, and adequate disinfection systems.

Impact of the Universal Implementation of Adolescent Hepatitis B Vaccination in Spain.

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991-1993 and in 1994-1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014-2021 was lower for regions that started adolescent vaccination in 1991-1993 rather than in 1994-1996 (IRR 0.76; 95% CI 0.72-0.83; p < 0.001). In the 20-29 age group, incidence in regions that started adolescent vaccination in 1991-1993 was also lower (IRR 0.87; 95% CI 0.77-0.98; p = 0.02 in 2005-2013 and IRR 0.71; 95% CI 0.56-0·90; p < 0.001 in 2014-2021). Anti-HBc prevalence in the 35-39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.

State of open science in cancer research.

PURPOSE: This study has been focused on assessing the Open Science scenario of cancer research during the period 2011-2021, in terms of the derived scientific publications and raw data dissemination. METHODS: A cancer search equation was executed in the Science Citation Index-Expanded, collecting the papers signed by at least one Spanish institution. The same search strategy was performed in the Data Citation Index to describe dataset diffusion. RESULTS: 50,822 papers were recovered, 71% of which belong to first and second quartile journals. 59% of the articles were published in Open Access (OA) journals. The Open Access model and international collaboration positively conditioned the number of citations received. Among the most productive journals stood out Plos One, Cancers, and Clinical and Translational Oncology. 2693 genomics, proteomics and metabolomics datasets were retrieved, being Gene Expression Omnibus the favoured repository. CONCLUSIONS: There has been an increase in oncology publications in Open Access. Most were published in first quartile journals and received higher citations than non-Open Access articles, as well as when oncological investigation was performed between international research teams, being relevant in the context of Open Science. Genetic repositories have been the preferred for sharing oncology datasets. Further investigation of research and data sharing in oncology is needed, supported by stronger Open Science policies, to achieve better data sharing practices among three scientific main pillars: researchers, publishers, and scientific organizations.

Effectiveness of Influenza Vaccination and Early Antiviral Treatment in Reducing Pneumonia Risk in Severe Influenza Cases.

INTRODUCTION: Influenza vaccination may be effective in preventing influenza infection and may reduce the risk of influenza-associated pneumonia. The study aim was to evaluate the effect of influenza vaccination in preventing pneumonia when it failed to prevent influenza hospitalization. METHODS: This was a case-control study comparing hospitalized cases of influenza with and without pneumonia in patients aged ≥18 years in 16 hospitals in Catalonia over 10 influenza seasons (2010-11 to 2019-20). Data on sociodemographic, virological characteristics, comorbidities, vaccination history, and antiviral treatment were collected and analysed. The crude odds ratio (OR) and adjusted OR (aOR) with the corresponding 95% confidence interval (CI) values were calculated. RESULTS: In total, 5080 patients hospitalized for severe influenza were included, 63.5% (3224/5080) of whom had pneumonia-mostly men (56.8%; 1830/3224) and mostly in the ≥75 age group (39.3%; 1267/3224)-and of whom 14.0% died (451/3224). Virus A and virus B accounted for 78.1% (2518/3224) and 21.9% (705/3224) of influenza types, respectively. Starting antiviral treatment ≤48 h after symptom onset (aOR = 0.69; 95%CI: 0.53-0.90) and a history of seasonal influenza vaccination (aOR = 0.85; 95%CI: 0.72-0.98) were protective factors in developing pneumonia. CONCLUSIONS: Adherence to seasonal influenza vaccination and starting antiviral treatment within 48 h of symptom onset can reduce pneumonia risk in severe influenza cases.

Health service and psychotropic medication use for mental health conditions among healthcare workers active during the Spain Covid-19 Pandemic - A prospective cohort study using web-based surveys.

Little is known about healthcare workers' (HCW) use of healthcare services for mental disorders. This study presents data from a 16-month prospective cohort study of Spanish HCW (n = 4,809), recruited shortly after the COVID-19 pandemic onset, and assessed at four timepoints using web-based surveys. Use of health services among HCW with mental health conditions (i.e., those having a positive screen for mental disorders and/or suicidal thoughts and behaviours [STB]) was initially low (i.e., 18.2 %) but increased to 29.6 % at 16-month follow-up. Service use was positively associated with pre-pandemic mental health treatment (OR=1.99), a positive screen for major depressive disorder (OR=1.50), panic attacks (OR=1.74), suicidal thoughts and behaviours (OR=1.22), and experiencing severe role impairment (OR=1.33), and negatively associated with being female (OR = 0.69) and a higher daily number of work hours (OR=0.95). Around 30 % of HCW with mental health conditions used anxiolytics (benzodiazepines), especially medical doctors. Four out of ten HCW (39.0 %) with mental health conditions indicated a need for (additional) help, with most important barriers for service use being too ashamed, long waiting lists, and professional treatment not being available. Our findings delineate a clear mental health treatment gap among Spanish HCW.

Epidemiological Characteristics and Factors Associated with Repeat Sexually Transmitted Infections in Barcelona, Spain Over a Decade.

In the last few years, the frequency of sexually transmitted infections (STI) has increased, as has the number of people with multiple infections. The aim of our study was to describe the epidemiological characteristics of persons with repeated bacterial STI and to determine the risk factors for these episodes in persons living in Barcelona during the period 2007-2018. We studied all cases of bacterial STI included in the STI registry of Barcelona. Repeated STI were defined as a diagnosis of gonorrhea, syphilis, or lymphogranuloma venereum (LGV) after a first episode of one of these infections. Analysis was stratified by sex and place of birth. The factors associated with time to reinfection were determined by Kaplan-Meier estimates, while the factors associated with risk of infection were determined by a Cox proportional hazards model. Of 9927 persons with a diagnosis of bacterial STI, 1690 (17.0%) had at least two episodes of STI during the study period. On multivariate analysis, repeat STI were independently associated with male sex assigned at birth (HR: 3.45; 95%CI 2.22-5.36), age less than 34 years (HR: 1.22; 95%CI 1.10-1.35); gay, bisexual, and other men who have sex with men, and transgender o transsexual woman (GBSMS/Trans) (HR: 4.03; 95%CI 3.24-5.03), having gonorrhea as first diagnosis (HR:1.49, 95%CI 1.34-1.66) or LGV (HR:1.75; 95%CI 1.47-2.08) and coinfection with HIV (HR:1.98; 95%CI 1.78-2.21). Sexual health programs should be strengthened to prevent STI and reinfection in key populations.

The impact of COVID-19 pandemic on the incidence of acute gastroenteritis outbreaks in Catalonia (Spain).

We carried out a retrospective study of acute gastroenteritis (AGE) outbreaks reported between 1 January 2015 and 31 December 2021 in Catalonia (Spain) to compare the incidence from 2015 to 2019 with that observed from 2020 to 2021. We observed a higher incidence rate of outbreaks during the prepandemic period (16.89 outbreaks/1,000,000 person-years) than during the pandemic period (6.96 outbreaks/1,000,000 person-years) (rate ratio (RR) 0.41; 95% confidence interval (CI) 0.34 to 0.51). According to the aetiology of the outbreak, those of viral aetiology decreased from 7.82 to 3.38 outbreaks/1,000,000 person-years (RR 2.31; 95% CI 1.72 to 3.12), and those of bacterial aetiology decreased from 5.01 to 2.78 outbreaks/1,000,000 person-years (RR 1.80; 95% CI 1.29 to 2.52). There was a great reduction in AGE outbreaks in Catalonia. This reduction may have been due to the effect of the nonpharmaceutical measures applied to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the collapse of the healthcare system and epidemiological surveillance services may also have had a strong influence.

Hepatitis C antibody prevalence and active hepatitis C infection in HIV-negative gay, bisexual, and other men who have sex with men in Barcelona and Madrid, Spain (March 2018-March 2021).

Objectives: Hepatitis C virus (HCV) has been recognized as a sexually transmitted infection (STI) in HIV-positive men who have sex with men (MSM), with an increased notification in HIV-negative MSM. The aim of this study was to determine the prevalence of HCV antibody and active HCV infection in HIV-negative gay, bisexual, and other MSM (GBMSM), and their characteristics, in Barcelona and Madrid, from March 2018 to March 2021. Methods: Cross-sectional study conducted on 3548 HIV-undiagnosed GBMSM, across four HIV/STI testing centers. Respondents submitted an online, self-administered questionnaire after consultation, which collected information on sociodemographics, sexual health history, HCV knowledge, and substance consumption. Prevalence of HCV antibodies was determined by a reactive result in a rapid anti-HCV test or enzyme-linked immunosorbent assay (ELISA), while active HCV infection was determined by participants who were also positive on an HCV-RNA test. Crude and adjusted Poisson analyses with robust variance are presented for both prevalence and active infection. Results: In total, 97.6% of participants (n = 3463) were HIV-negative. Of those, 18 were found to have HCV antibodies (0.52%), of which nine (0.26%) were also HCV-RNA positive. Those with HCV antibodies were associated to have lived with an HCV (+) person (adjusted prevalence ratio [APR]: 7.84, [95% confidence interval: 2.50-24.53]), using injectable drugs for sex (APR: 6.92, [1.20-39.79]) and testing positive for an STI in the previous year (APR: 4.06, [1.09-15.12]). Presenting an active infection was strongly associated with a previous HCV diagnosis (APR: 100.82 [22.16-458.76]), sexualized injectable drug use (APR: 17.53 [2.70-113.76]), and sharing douching material (APR: 7.45, [2.12-25.95]). Conclusion: Sexual practices with a higher risk of bleeding and sexualized drug use, particularly sexualized injectable drug use, were associated with higher rates of HCV diagnosis in GBMSM. Identifying these practices during consultation, contact tracing new cases and regularly testing those with a previous history of HCV, will facilitate HCV eradication.

Traumatic stress symptoms among Spanish healthcare workers during the COVID-19 pandemic: a prospective study.

AIM: To investigate the occurrence of traumatic stress symptoms (TSS) among healthcare workers active during the COVID-19 pandemic and to obtain insight as to which pandemic-related stressful experiences are associated with onset and persistence of traumatic stress. METHODS: This is a multicenter prospective cohort study. Spanish healthcare workers (N = 4,809) participated at an initial assessment (i.e., just after the first wave of the Spain COVID-19 pandemic) and at a 4-month follow-up assessment using web-based surveys. Logistic regression investigated associations of 19 pandemic-related stressful experiences across four domains (infection-related, work-related, health-related and financial) with TSS prevalence, incidence and persistence, including simulations of population attributable risk proportions (PARP). RESULTS: Thirty-day TSS prevalence at T1 was 22.1%. Four-month incidence and persistence were 11.6% and 54.2%, respectively. Auxiliary nurses had highest rates of TSS prevalence (35.1%) and incidence (16.1%). All 19 pandemic-related stressful experiences under study were associated with TSS prevalence or incidence, especially experiences from the domains of health-related (PARP range 88.4-95.6%) and work-related stressful experiences (PARP range 76.8-86.5%). Nine stressful experiences were also associated with TSS persistence, of which having patient(s) in care who died from COVID-19 had the strongest association. This association remained significant after adjusting for co-occurring depression and anxiety. CONCLUSIONS: TSSs among Spanish healthcare workers active during the COVID-19 pandemic are common and associated with various pandemic-related stressful experiences. Future research should investigate if these stressful experiences represent truly traumatic experiences and carry risk for the development of post-traumatic stress disorder.

Prepandemic personal concentrations of per- and polyfluoroalkyl substances (PFAS) and other pollutants: Specific and combined effects on the incidence of COVID-19 disease and SARS-CoV-2 infection.

OBJECTIVE: To investigate the specific and combined effects of personal concentrations of some per- and polyfluoroalkyl substances (PFAS), other persistent organic pollutants (POPs), and chemical elements -measured in individuals' blood several years before the pandemic- on the development of SARS-CoV-2 infection and COVID-19 disease in the general population. METHODS: We conducted a prospective cohort study in 240 individuals from the general population of Barcelona. PFAS, other POPs, and chemical elements were measured in plasma, serum, and whole blood samples, respectively, collected in 2016-2017. PFAS were analyzed by liquid chromatography-triple quadrupole mass spectrometry. SARS-CoV-2 infection was detected by rRT-PCR in nasopharyngeal swabs and/or antibody serology in blood samples collected in 2020-2021. RESULTS: No individual PFAS nor their mixtures were significantly associated with SARS-CoV-2 seropositivity or COVID-19 disease. Previously identified mixtures of POPs and elements (Porta et al., 2023) remained significantly associated with seropositivity and COVID-19 when adjusted for PFAS (all OR > 4 or p < 0.05). Nine chemicals comprised mixtures associated with COVID-19: thallium, ruthenium, lead, benzo[b]fluoranthene, DDD, other DDT-related compounds, manganese, tantalum, and aluminium. And nine chemicals comprised the mixtures more consistently associated with SARS-CoV-2 seropositivity: thallium, ruthenium, lead, benzo[b]fluoranthene, DDD, gold, and (protectively) selenium, indium, and iron. CONCLUSIONS: The PFAS studied were not associated with SARS-CoV-2 seropositivity or COVID-19. The results confirm the associations between personal blood concentrations of some POPs and chemical elements and the risk of COVID-19 and SARS-CoV-2 infection in what remains the only prospective and population-based cohort study on the topic. Mixtures of POPs and chemical elements may contribute to explain the heterogeneity in the risks of SARS-CoV-2 infection and COVID-19 in the general population.

Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy.

The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A∗02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such "multipronged" T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.

Socioeconomic inequalities in COVID-19 incidence during the first six waves in Barcelona.

BACKGROUND: The emergence of SARS-CoV-2 affected urban areas. In Barcelona, six waves of COVID-19 hit the city between March 2020 and March 2022. Inequalities in the incidence of COVID-19 have been described. However, no studies have examined the daily trends of socioeconomic inequalities and how they changed during the different phases of the pandemic. The aim of this study is to analyse the dynamic socioeconomic inequalities in the incidence of COVID-19 during the six waves in Barcelona. METHODS: We examined the proportion of daily cases observed in the census tracts in the lower income tercile compared with the proportion of daily cases observed in the sum of the lower and higher income terciles. Daily differences in these proportions were assessed as a function of the epidemic waves, sex, age group, daily incidence and daily change in the incidence. A logistic regression model with an autoregressive term was used for statistical analysis. RESULTS: A time-dynamic effect was found for socioeconomic inequalities in the incidence of COVID-19. In fact, belonging to a lower-income area changed from being a risk factor (Waves 1, 2, 4 and 5) to being a protective factor in the sixth wave of the pandemic. Age also had a significant effect on incidence, which also changed over the different waves of the pandemic. Finally, the lower-income areas showed a comparatively lower incidence during the ascending phase of the epidemic waves. CONCLUSION: Socioeconomic inequalities in COVID-19 changed by wave, age group and wave phase.

Community outbreak of COVID-19 among people who use drugs attending a harm reduction centre in Barcelona, Spain.

BACKGROUND: The COVID-19 pandemic particularly affected the health of vulnerable population, such as people who use drugs. Due to compromised baseline health status, certain drug uses and settings and socioeconomic deprivation related to poverty and homelessness, drug users faced higher risk of COVID-19 infection. They had difficulty in adhering to the public health measures (i.e. physical distancing, hand hygiene and mask use). Also, the struggle to implement non-pharmaceutical actions (i.e. test-trace-isolate-quarantine strategy) among SARS-COV-2-infected drug users and their close contacts challenged the public health response. Therefore, this study aimed to describe a community COVID-19 outbreak and its approach among drug users of a harm reduction programme in an outpatient drug treatment centre in Barcelona, Spain. METHODS: We conducted an observational descriptive study of an outbreak of COVID-19 among people who use drugs attending the harm reduction programme of an outpatient drug treatment centre in the city of Barcelona, between July and October 2021 (n = 440). A passive search for cases was carried out with rapid antigens tests targeting symptomatic users who attended the facilities. RESULTS: Nineteen positive COVID-19 cases were identified among symptomatic drug users, between July and October 2021, with an attack rate of 4.3%. Specific measures were taken to control the outbreak, such as offering accommodation to self-isolate in a low-threshold residential resource to homeless drug users who tested positive and intensifying the vaccination strategy. The management of the outbreak was carried out in close collaboration between the outpatient centre and the main public health stakeholders in the city of Barcelona. CONCLUSIONS: This study shows the complexity of managing and investigating COVID-19 outbreaks in vulnerable population groups. Epidemiological control measures, such as the test-trace-isolate-quarantine strategy, were challenging to implement due to technology-related barriers and socioeconomic vulnerabilities, especially homelessness. Community-based interventions, cooperation among stakeholders and housing-related policies were helpful in tackling outbreaks among people who use drugs. When addressing vulnerable and hidden populations, the perspective of inequalities should be included in epidemiological surveillance and outbreak control strategies.

Individual blood concentrations of persistent organic pollutants and chemical elements, and COVID-19: A prospective cohort study in Barcelona.

BACKGROUND: There is wide, largely unexplained heterogeneity in immunological and clinical responses to SARS-CoV-2 infection. Numerous environmental chemicals, such as persistent organic pollutants (POPs) and chemical elements (including some metals, essential trace elements, rare earth elements, and minority elements), are immunomodulatory and cause a range of adverse clinical events. There are no prospective studies on the effects of such substances on the incidence of SARS-CoV-2 infection and COVID-19. OBJECTIVE: To investigate the influence of blood concentrations of POPs and elements measured several years before the pandemic on the development of SARS-CoV-2 infection and COVID-19 in individuals from the general population. METHODS: We conducted a prospective cohort study in 154 individuals from the general population of Barcelona. POPs and elements were measured in blood samples collected in 2016-2017. SARS-CoV-2 infection was detected by rRT-PCR in nasopharyngeal swabs and/or by antibody serology using eighteen isotype-antigen combinations measured in blood samples collected in 2020-2021. We analyzed the associations between concentrations of the contaminants and SARS-CoV-2 infection and development of COVID-19, taking into account personal habits and living conditions during the pandemic. RESULTS: Several historically prevalent POPs, as well as arsenic, cadmium, mercury, and zinc, were not associated with COVID-19, nor with SARS-CoV-2 infection. However, DDE (adjusted OR = 5.0 [95% CI: 1.2-21]), lead (3.9 [1.0-15]), thallium (3.4 [1.0-11]), and ruthenium (5.0 [1.8-14]) were associated with COVID-19, as were tantalum, benzo(b)fluoranthene, DDD, and manganese. Thallium (3.8 [1.6-8.9]), and ruthenium (2.9 [1.3-6.7]) were associated with SARS-CoV-2 infection, and so were lead, gold, and (protectively) iron and selenium. We identified mixtures of up to five substances from several chemical groups, with all substances independently associated to the outcomes. CONCLUSIONS: Our results provide the first prospective and population-based evidence of an association between individual concentrations of some contaminants and COVID-19 and SARS-CoV-2 infection. POPs and elements may contribute to explain the heterogeneity in the development of SARS-CoV-2 infection and COVID-19 in the general population. If the associations are confirmed as causal, means are available to mitigate the corresponding risks.

A large outbreak of COVID-19 linked to an end of term trip to Menorca (Spain) by secondary school students in summer 2021.

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in young people from Catalonia (Spain) who travelled to Menorca (Spain) in summer 2021. This outbreak appeared when governments relaxed Covid-19 preventive measures: the mask usage and the opening of nightlife. It was related to a super-disseminating mass event: Sant Joan festivities in Ciutadella. The aim of this article is to describe an outbreak of COVID-19 in young people aged 17-19 years from Catalonia travelling to Menorca. METHODS: This is an observational study of a COVID-19 outbreak. The study population comprised Catalonian youth aged 17-19 years who travelled to Menorca from 15 June to 10 July. Epidemiological descriptive indicators were obtained. Descriptive and geographical statistics were carried out. Bivariate Moran's I test was used to identify spatial autocorrelation between the place of residence and deprivation. The outbreak control method was based on identifying and stopping chains of transmission by implementing the test-trace-isolate-quarantine (TTIQ) strategy. RESULTS: We identified 515 confirmed cases infected in Menorca, 296 (57.5%) in girls and 219 (42.5%) in boys, with a total of 2,280 close contacts. Of them, 245 (10.7%) were confirmed as cases. The cases were diagnosed between 15 June and 10 July. None of the persons with confirmed infection died or required hospitalisation. The attack rate was 27.2%. There was an inverse relationship between deprivation and number of confirmed cases (p<0.005), there were clusters of confirmed cases in the most socioeconomic favoured areas. DISCUSSION: The outbreak is related with young people from socioeconomic favoured areas who travelled to Menorca in summer 2021. Failure to comply with preventive measures in binge-drinking events and during holidays may have favoured SARS-CoV-2 transmission. The interauthority coordination and establishment of a clear line of leadership allowed continuous communication between institutions, which were key to managing this complex COVID-19 outbreak.

CD4 T-Cell Subsets and the Pathophysiology of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an umbrella term for the chronic immune-mediated idiopathic inflammation of the gastrointestinal tract, manifesting as Crohn's disease (CD) or ulcerative colitis (UC). IBD is characterized by exacerbated innate and adaptive immunity in the gut in association with microbiota dysbiosis and the disruption of the intestinal barrier, resulting in increased bacterial exposure. In response to signals from microorganisms and damaged tissue, innate immune cells produce inflammatory cytokines and factors that stimulate T and B cells of the adaptive immune system, and a prominent characteristic of IBD patients is the accumulation of inflammatory T-cells and their proinflammatory-associated cytokines in intestinal tissue. Upon antigen recognition and activation, CD4 T-cells differentiate towards a range of distinct phenotypes: T helper(h)1, Th2, Th9, Th17, Th22, T follicular helper (Tfh), and several types of T-regulatory cells (Treg). T-cells are generated according to and adapt to microenvironmental conditions and participate in a complex network of interactions among other immune cells that modulate the further progression of IBD. This review examines the role of the CD4 T-cells most relevant to IBD, highlighting how these cells adapt to the environment and interact with other cell populations to promote or inhibit the development of IBD.

Analysis of Monocyte Recruitment During Inflammation by Intravital Imaging.

Monocytes play essential roles in the inflammatory and anti-inflammatory processes that take place during an immune response, acting both within the vascular network and interstitially. Monocytes are activated, mobilized, and recruited in response to an inflammatory stimulus or different forms of tissue injury. The recruitment of circulating monocytes to the inflamed tissue is essential to resolving the injury.Monocyte recruitment is a multistep process that begins with a decrease in rolling velocity, is followed by adhesion to the endothelium and crawling over the luminal vessel surface, and culminates in monocyte transmigration into the surrounding tissue. Intravital microscopy is a powerful visualization tool for the study of leukocyte behavior and function, intercellular interactions, cell trafficking, and recruitment in pathological and physiological conditions. This modality is therefore widely used for the detailed analysis of the immune response to multiple insults and the molecular mechanisms underlying monocyte interactions within the vascular system in vivo. This chapter describes a protocol for the use of intravital microscopy to analyze monocyte recruitment from the blood vessel to the inflammatory site.