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Mass gatherings include a diverse range of events such as sporting competitions, religious ceremonies, entertainment activities, political rallies and cultural celebrations, which have important implications for population well-being. However, if not managed properly, these events can amplify health risks including those related to communicable diseases, and place undue strain on health systems in host countries and potentially in attendees' home countries, upon their return. The coronavirus disease 2019 (COVID-19) pandemic has provided a unique opportunity to evaluate the risk factors associated with mass gatherings and the effectiveness of applying mitigation measures during infectious disease emergencies. The pandemic has also allowed event organizers and health officials to identify best practices for mass gathering planning in host countries. To guide decisions about whether to hold, postpone, modify or cancel a mass gathering during the COVID-19 pandemic, the World Health Organization and its partners developed normative guidance and derivative tools promoting a risk-based approach to mass gathering planning. This approach involves three steps to guide decision-making around mass gatherings: risk evaluation, risk mitigation and risk communication. The approach was applied in the planning and execution of several mass gathering events, including the Tokyo 2020 and Beijing 2022 Olympic and Paralympic Games. Lessons identified from these large-scale international events offer insights into the planning and implementation of mass gathering events during a pandemic, and the broader impacts of such events on society. These lessons may also further inform and refine planning for future mass gatherings. Les rassemblements de masse designent un large eventail d'evenements tels que des competitions sportives, ceremonies religieuses, activites de divertissement, manifestations politiques et fetes culturelles. Tous ont un impact considerable sur le bien-etre de la population. Toutefois, s'ils ne sont pas geres correctement, ils peuvent augmenter les risques sanitaires, notamment concernant les maladies transmissibles, et exercer une pression excessive sur les systemes de sante des pays hotes, voire sur ceux des pays d'origine des participants apres leur retour. La pandemie de maladie a coronavirus 2019 (COVID-19) a offert une occasion unique d'evaluer les facteurs de risque associes aux rassemblements de masse, ainsi que l'efficacite des mesures visant a limiter la propagation dans des situations d'urgence liees a des maladies infectieuses. Cette pandemie a egalement permis aux organisateurs d'evenements et responsables de sante d'identifier les bonnes pratiques a appliquer dans les pays hotes pendant les rassemblements de masse. Afin de guider les decisions relatives au maintien, au report, a la modification ou a l'annulation d'un rassemblement de masse durant la pandemie de COVID-19, l'Organisation mondiale de la Sante et ses partenaires ont mis au point des orientations normatives et des outils derives favorisant une approche tenant compte des risques au moment de la planification. Cette approche comprend trois etapes contribuant a la prise de decision: l'evaluation, la reduction et la communication des risques. Elle a ete deployee lors de la planification et de l'execution de nombreux rassemblements de masse, comme les Jeux olympiques et paralympiques de Tokyo 2020 et Beijing 2022. Les lecons tirees de ces evenements internationaux a grande echelle fournissent des informations sur leur organisation et leur mise en oeuvre en cas de pandemie, ainsi que les impacts de tels evenements sur la societe. Elles sont en outre susceptibles de faciliter et d'ameliorer la planification des futurs rassemblements de masse. Las concentraciones masivas Incluyen una gran variedad de eventos, como competiciones deportivas, ceremonias religiosas, actividades de entretenimiento, mitines politicos y celebraciones culturales, que tienen importantes implicaciones para el bienestar de la poblacion. Sin embargo, si no se gestionan adecuadamente, estos eventos pueden amplificar los riesgos para la salud, incluidos los relacionados con las enfermedades transmisibles, y suponer una carga excesiva para los sistemas sanitarios de los paises anfitriones y, potencialmente, de los paises de origen de los participantes a su regreso. La pandemia de la enfermedad por coronavirus de 2019 (COVID-19) ha brindado una oportunidad unica para evaluar los factores de riesgo asociados a las concentraciones masivas y la eficacia de aplicar medidas de mitigacion durante las emergencias por enfermedades infecciosas. La pandemia tambien ha permitido a los organizadores de eventos y a las autoridades sanitarias identificar las mejores practicas para la planificacion de concentraciones masivas en los paises anfitriones. Para orientar las decisiones sobre la celebracion, el aplazamiento, la modificacion o la cancelacion de una concentracion masiva durante la pandemia de la COVID-19, la Organizacion Mundial de la Salud y sus asociados elaboraron orientaciones normativas y herramientas derivadas que promueven un enfoque de la planificacion de concentraciones masivas basado en los riesgos. Este enfoque consta de tres pasos para orientar la toma de decisiones en torno a las concentraciones masivas: la evaluacion, la mitigacion y la comunicacion de riesgos. El enfoque se aplico en la planificacion y ejecucion de varias concentraciones masivas, incluidos los Juegos Olimpicos y Paralimpicos de Tokio 2020 y Pekin 2022. Las conclusiones extraidas de estos eventos internacionales a gran escala permiten comprender mejor la planificacion y ejecucion de concentraciones masivas durante una pandemia, asi como las repercusiones mas generales de estos eventos en la sociedad. Estas lecciones tambien pueden informar y perfeccionar la planificacion de futuras concentraciones masivas., Introduction Mass gatherings are characterized by the concentration of people at a specific location for a specific purpose over a set period. Such gatherings encompass a diverse range of events, [...]

Background Globally, since 1 January 2020 and as of 24 January 2023, there have been over 664 million cases of COVID-19 and over 6.7 million deaths reported to WHO. WHO developed an evidence-based alert system, assessing public health risk on a weekly basis in 237 countries, territories and areas from May 2021 to June 2022. This aimed to facilitate the early identification of situations where healthcare capacity may become overstretched.Methods The process involved a three-stage mixed methods approach. In the first stage, future deaths were predicted from the time series of reported cases and deaths to produce an initial alert level. In the second stage, this alert level was adjusted by incorporating a range of contextual indicators and accounting for the quality of information available using a Bayes classifier. In the third stage, countries with an alert level of ‘High’ or above were added to an operational watchlist and assistance was deployed as needed.Results Since June 2021, the system has supported the release of more than US$27 million from WHO emergency funding, over 450 000 rapid antigen diagnostic testing kits and over 6000 oxygen concentrators. Retrospective evaluation indicated that the first two stages were needed to maximise sensitivity, where 44% (IQR 29%–67%) of weekly watchlist alerts would not have been identified using only reported cases and deaths. The alerts were timely and valid in most cases; however, this could only be assessed on a non-representative sample of countries with hospitalisation data available.Conclusions The system provided a standardised approach to monitor the pandemic at the country level by incorporating all available data on epidemiological analytics and contextual assessments. While this system was developed for COVID-19, a similar system could be used for future outbreaks and emergencies, with necessary adjustments to parameters and indicators.

Background: Salvage radiotherapy (SRT) and androgen‐deprivation therapy (ADT) are widely used in routine clinical practice to treat patients with prostate cancer who develop biochemical recurrence (BCR) after radical prostatectomy (RP). However, there is no standard‐of‐care consensus on optimal duration ADT. Investigators propose three distinct risk groups in patients with prostate cancer treated with SRT in order to better define the indications and duration of ADT combined with SRT. Study design: The URONCOR 06‐24 trial (ClinicalTrials.gov identifier NCT05781217) is a prospective, multicentre, randomised, open‐label, phase III, clinical trial. The aim of the trial is to determine the impact of short‐term (6 months) vs long‐term (24 months) ADT in combination with SRT on distant metastasis‐free survival (MFS) in patients with prostate cancer with BCR after RP (intermediate and high risk). Endpoints: The primary endpoint is 5‐year MFS rates in patients with prostate cancer treated with long‐ vs short‐term ADT in combination with SRT. Secondary objectives are biochemical‐relapse free interval, pelvic progression‐free survival, time to start of systemic treatment, time to castration resistance, cancer‐specific survival, overall survival, acute and late toxicity, and quality of life. Methods and analysis: Total of 534 patients will be randomised 1:1 to ADT 6 months or ADT 24 months with a luteinizing hormone‐releasing hormone analogue in combination with SRT, stratified by risk group and pathological lymph node status. Ethics and dissemination: The study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer‐reviewed journals. Trial registration number: EudraCT number 2021‐006975‐41. [ABSTRACT FROM AUTHOR]

Background: Numerous scores are designed to predict outcomes of patients with liver cirrhosis. Our study aimed to evaluate the ability of the Liver Disease Undernutrition Screening Tool (LDUST) in predicting mortality and decompensation in outpatients with clinically significant portal hypertension (CSPH). We hypothesized that LDUST could help identify patients in need of nutritional supplementation and intervention. Methods: A prospective study of 57 CSPH patients (36.8% female, mean age: 63.5 ± 9.9 years) with a median follow-up of 41 months was conducted. Baseline liver function, nutrition, and sarcopenia were assessed, alongside LDUST. During follow-up, the occurrence of liver decompensation, hospital admission, need for emergency care, and mortality were evaluated. Results: A total of 56.1% of patients were Child A, and the most frequent etiology was alcohol (50.9%). Malnutrition risk according to LDUST raised mortality (HR: 25.96 (1.47–456.78)), decompensation (HR 9.78 (2.08–45.89)), and admission (HR 4.86 (1.09–21.61)) risks in multivariate Cox analysis. Combining LDUST with Child and MELD scores improved their decompensation prediction (0.936 vs. 0.811 and 0.866 vs. 0.700). Conclusions: The LDUST has a solid ability to predict complications in cirrhosis outpatients with CSPH, and its integration with Child and MELD models enhances their predictive power. LDUST implementation could identify individuals necessitating early nutritional support.

The advent of Indsutrial Internet of Things is one of the main drivers for the implementation of Industry 4.0 scenarios and applications, in which wireless communication systems play a key role in terms of flexibility, mobility and deployment capabilities. However, the integration of wireless communication systems poses challenges, owing to variable path loss conditions and interference impact. In this work, an Ultra-Wideband (UWB) system for indoor location in very large, complex industrial scenarios is presented. Precise wireless channel characterization for the complete volume of a logistical plant is performed, based on 3D hybrid ray launching approximation, in order to aid network node design process. Wireless characterization, implementation and measurement results are obtained for both 4 GHz and 6 GHz frequency bands, considering different densities of scatterers within the scenario under test. Time domain estimation results have been obtained and compared with time of flight measurement results, showing good agreement. The proposed methodology enables to perform system design and performance tasks, analyzing the impact of variable object density conditions in wireless channel response, providing accurate time of flight estimations without the need of complex channel sounder systems, aiding in optimal system planning and implementation.

Abstract A C9orf72 repeat expansion is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis. One of the suggested pathomechanisms is toxicity from dipeptide repeat proteins (DPRs), which are generated via unconventional translation of sense and antisense repeat transcripts with poly-GA, poly-GP and poly-GR being the most abundant dipeptide proteins. Animal and cellular studies highlight a neurotoxic role of poly-GR and poly-PR and to a lesser degree of poly-GA. Human post-mortem studies in contrast have been much less clear on a potential role of DPR toxicity but have largely focused on immunohistochemical methods to detect aggregated DPR inclusions. This study uses protein fractionation and sensitive immunoassays to quantify not only insoluble but also soluble poly-GA, poly-GP and poly-GR concentrations in brain homogenates of FTD patients with C9orf72 mutation across four brain regions. We show that soluble DPRs are less abundant in clinically affected areas (i.e. frontal and temporal cortices). In contrast, the cerebellum not only shows the largest DPR load but also the highest relative DPR solubility. Finally, poly-GR levels and poly-GP solubility correlate with clinical severity. These findings provide the first cross-comparison of soluble and insoluble forms of all sense DPRs and shed light on the distribution and role of soluble DPRs in the etiopathogenesis of human C9orf72-FTD.

Background: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. Methods: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. Results: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. Conclusion: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe.

Objective: provide new background in relation to the factor structure and reliability of the factors identified from the Utrecht Work Engagement Scale – Student (UWES-S) in students of health careers in Chile. Methods: A quantitative study with relational analytical scope was carried out, through a non-experimental cross-sectional design through a survey. 898 university students selected through non-probabilistic sampling by groups belonging to Medicine, Kinesiology, Pharmacy and Speech and language therapy. The students responded the UWES-S and a sociodemographic questionnaire. The total sample was randomly subdivided into two subsamples. With the first one, an Exploratory Factor Analysis was performed, using the method of extraction of the Main Axis Analysis. With the second one, a Confirmatory Factor Analysis was performed, using the maximum likelihood method and the following indices: Comparative Fit Index (CFI), Tucker-Lewis Index (TLI) and the Root Mean Square Error of Approximation (RMSEA). Also the Cronbach alpha reliability of each item was calculated. For data processing STATA 11 SE statistical package was used. Results: Kaiser-Guttman criterion and the Horn’s Parallel Analysis aimed to the existence of two factors called Involvement with studies and Enthusiasm for the career. CFI, TLI and RMSEA show that this is one of the solutions with best fit. Conclusion: Two factors were identified called Involvement with studies and Enthusiasm for the career. Neither the solution obtained nor the previous solutions showed an adequate adjustment to the data. The confirmatory factor analysis showed that this is one of the solutions with best fit. Continuous...

G4C2 repeat expansions within the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The repeats undergo repeat-associated non-ATG translation to generate toxic dipeptide repeat proteins. Here, we show that insulin/IGF signalling is reduced in fly models of C9orf72 repeat expansion using RNA sequencing of adult brain. We further demonstrate that activation of insulin/IGF signalling can mitigate multiple neurodegenerative phenotypes in flies expressing either expanded G4C2 repeats or the toxic dipeptide repeat protein poly-GR. Levels of poly-GR are reduced when components of the insulin/IGF signalling pathway are genetically activated in the diseased flies, suggesting a mechanism of rescue. Modulating insulin signalling in mammalian cells also lowers poly-GR levels. Remarkably, systemic injection of insulin improves the survival of flies expressing G4C2 repeats. Overall, our data suggest that modulation of insulin/IGF signalling could be an effective therapeutic approach against C9orf72 ALS/FTD.

Abstract Objective: Describing the results of a User-Centered Design workshop using Challenge Based Learning or CBL, where students from Chilean industrial design and health degrees, developed solutions to resolve health problems among the elderly. Method: It was a pre-experimental study; 45 university students took part in a workshop: 39 from Industrial Design, 3 from Speech Therapy, 2 from Medical Technology and 1 from Medicine. In this workshop, the students, using CBL in disciplinary heterogeneous groups, faced a 3-week challenge to develop products to overcome a health problem for an elderly person. Once the product was presented, the professors and students assessed the conceptual proposals, using a semantic differential. The students also evaluated the workshop with a perception survey. Results: Both the students and professors positively evaluated the usefulness and functionality of the conceptual proposals; although, the industrial design students were more critical about these aspects. The originality of proposals evaluated was the worst. Regarding the workshop, all students (100%) felt that instructions were clear as were the three moments of design, with problem definition stage best evaluated. Conclusions: The CBL is shown to be an educational tool that allows training professionals in product design and in developing health technology that is suitable for the users' needs. Regarding the process, heterogeneous make-up of the groups and clear external guide appear as essential for CBL to work well. Keywords: challenge-based learning, elderly, interdisciplinary, higher education. Continuous...

Small ruminant lentiviruses (SRLVs) are endemic in most areas of Europe, causing a chronic infection and a multisystemic disease affecting the udder, carpal joints, lungs, and central nervous system. Due to the lack of treatments and protective vaccination strategies, infection control is focused on the identification of infected animals through serological or molecular techniques. However, antigenic and genetic heterogeneity of SRLVs represent a clear drawback for diagnosis. Infected animals may present lower animal production parameters such as birth weight or milk production and quality, depending on productive systems considered and, likely, to the diagnostic method applied. In this study, four sheep flocks dedicated to dairy or meat production were evaluated using three different ELISA and two PCR strategies to classify animal population according to SRLV infection status. Productive parameters were recorded along one whole lactation or reproductive period and compared between positive and negative animals. SRLV was present in 19% of the total population, being unequally distributed in the different flocks. Less than half of the infected animals were detected by a single diagnostic method, highlighting the importance of combining different diagnostic techniques. Statistical analysis employing animal classification using all the diagnostic methods associated lambing size, lamb weight at birth, and daily weight gain with SRLV infection status in meat flocks. Milk production, somatic cell count, fat, and protein content in the milk were associated with SRLV infection in dairy flocks, to a greater extent in the flock showing higher seroprevalence. A multi-platform SRLV diagnostic strategy was useful for ensuring correct animal classification, thus validating downstream studies investigating production traits.

Objective: To conduct a literature review and present a case study of tubulopapillary cholangiocarcinoma. Material and Method: The clinical record and the clinical, radiological, and pathological characteristics of the tumor were reviewed, along with the scientific literature regarding tubulopapillary carcinoma. Case Report: Patient with progressive jaundice associated with weight loss. Imaging studies show amputation of the distal third of the common bile duct by soft tissue, suggestive of cholangiocarcinoma. Endosonography was performed, yielding “superficial fragments of tubulopapillary adenocarcinoma.” Subsequently, a cephalic duodenopancreatectomy is performed, followed by chemotherapy. Discussion: Cholangiocar)cinoma is a neoplasm of the biliary tract. There are different histological variants, including tubulopapillary cholangiocarcinoma. Its diagnosis is based on imaging and pathological studies. The main imaging finding will depend on the pattern of tumor growth: mass-forming, periductal, or intraductal. Among the intraductal types, a biliary carcinoma with tubulopapillary growth and an epithelial pancreatobiliary phenotype has been described. In recent years, they have been of interest due to their better prognosis. Conclusion: Tubulopapillary cholangiocarcinoma is a rare histological variant of cholangiocarcinoma that is associated with a better prognosis than other variants. [ABSTRACT FROM AUTHOR]

Macrophages exert potent effector functions against invading microorganisms but constitute, paradoxically, a preferential niche for many bacterial strains to replicate. Using a model of infection by Salmonella Typhimurium, we have identified a molecular mechanism regulated by the nuclear receptor LXR that limits infection of host macrophages through transcriptional activation of the multifunctional enzyme CD38. LXR agonists reduced the intracellular levels of NAD+ in a CD38-dependent manner, counteracting pathogen-induced changes in macrophage morphology and the distribution of the F-actin cytoskeleton and reducing the capability of non-opsonized Salmonella to infect macrophages. Remarkably, pharmacological treatment with an LXR agonist ameliorated clinical signs associated with Salmonella infection in vivo, and these effects were dependent on CD38 expression in bone-marrow-derived cells. Altogether, this work reveals an unappreciated role for CD38 in bacterial-host cell interaction that can be pharmacologically exploited by activation of the LXR pathway.

Small ruminant lentiviruses (SRLV) cause an incurable multiorganic disease widely spread in sheep and goats that disturbs animal welfare and production. In the absence of a vaccine, control measures have been traditionally based on early diagnosis and breeding with virus-inactivated colostrum with segregation of seropositive animals. However, antigenic heterogeneity, poor antibody production due to low viral load, and single strain design of most available ELISA, pose a threat to SRLV diagnosis. Genome-wide association studies have described TMEM154 E35K polymorphism as a good genetic marker for selection of resistant animals in some American and European breeds. In this study, a multitargeted serological and virological screening of more than 500 animals from four different breeds (latxa, raza Navarra, assaf, and churra) attending to SRLV infection status was performed. Then, animals were genotyped to characterize TMEM154 E35K polymorphism. ELISA procedures, individually considered, only identified a proportion of the seropositive animals, and PCR detected a fraction of seronegative animals, globally offering different animal classifications according to SRLV infection status. TMEM154 allele frequency differed substantially among breeds and a positive association between seroprevalence and TMEM154 genotype was found only in one breed. Selection based on TMEM154 may be suitable for specific ovine breeds or SRLV strains, however generalization to the whole SRLV genetic spectrum, ovine breeds, or epidemiological situation may need further validation.

The article titled "Theme 05 - Human Cell Biology and Pathology" is a comprehensive study conducted by multiple authors on the topic of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The study explores various aspects of these neurodegenerative diseases, including their underlying cellular and molecular mechanisms, genetic factors, and potential therapeutic targets. The research presented in the article provides valuable insights into the pathogenesis of ALS and FTD, which can be beneficial for further research and the development of effective treatments. [Extracted from the article]

Background: Numerous scores are designed to predict outcomes of patients with liver cirrhosis. Our study aimed to evaluate the ability of the Liver Disease Undernutrition Screening Tool (LDUST) in predicting mortality and decompensation in outpatients with clinically significant portal hypertension (CSPH). We hypothesized that LDUST could help identify patients in need of nutritional supplementation and intervention. Methods: A prospective study of 57 CSPH patients (36.8% female, mean age: 63.5 ± 9.9 years) with a median follow-up of 41 months was conducted. Baseline liver function, nutrition, and sarcopenia were assessed, alongside LDUST. During follow-up, the occurrence of liver decompensation, hospital admission, need for emergency care, and mortality were evaluated. Results: A total of 56.1% of patients were Child A, and the most frequent etiology was alcohol (50.9%). Malnutrition risk according to LDUST raised mortality (HR: 25.96 (1.47–456.78)), decompensation (HR 9.78 (2.08–45.89)), and admission (HR 4.86 (1.09–21.61)) risks in multivariate Cox analysis. Combining LDUST with Child and MELD scores improved their decompensation prediction (0.936 vs. 0.811 and 0.866 vs. 0.700). Conclusions: The LDUST has a solid ability to predict complications in cirrhosis outpatients with CSPH, and its integration with Child and MELD models enhances their predictive power. LDUST implementation could identify individuals necessitating early nutritional support. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5%) were discharged (109 (20.5%) died). A total of 319 (64.3%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9%) and GGT (47.3%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.

Direct comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce. To compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages. Cross-sectional analysis of the EoE CONNECT registry. The adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood‐onset cohort (patients diagnosed at <18 y), 254. Vomiting, nausea, chest and abdominal pain, weight loss, slow eating and food aversion were significantly more frequent in children; dysphagia, food bolus impaction and heartburn predominated in adults. A family history of EoE was present in 16% of pediatric and 8.2% of adult patients (p <0.001). Concomitant atopic diseases did not vary across ages. Median±IQR diagnostic delay (years) from symptom onset was higher in adults (2.7 ± 6.1) than in children (1 ± 2.1; p <0.001). Esophageal strictures and rings predominated in adults (p <0.001), who underwent esophageal dilation more commonly (p = 0.011). Inflammatory EoE phenotypes were more common in children (p = 0.001), who also presented higher eosinophil counts in biopsies (p = 0.015) and EREFS scores (p = 0.017). Despite PPI predominating as initial therapy in all cohorts, dietary therapy and swallowed topical corticosteroids were more frequently prescribed in children (p <0.001). Childhood‐onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment. [ABSTRACT FROM AUTHOR]

Intrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible to small ruminant lentivirus (SRLVs) infection and contain three APOBEC3 genes encoding four proteins (A3Z1, Z2, Z3 and Z2-Z3) with yet not deeply described antiviral properties. Using sheep blood monocytes and in vitro-derived macrophages, we found that A3Z1 expression is associated with lower viral replication in this cellular type. A3Z1 transcripts may also contain spliced variants (A3Z1Tr) lacking the cytidine deaminase motif. A3Z1 exogenous expression in fully permissive fibroblast-like cells restricted SRLVs infection while A3Z1Tr allowed infection. A3Z1Tr was induced after SRLVs infection or stimulation of blood-derived macrophages with interferon gamma (IFN-γ). Interaction between truncated isoform and native A3Z1 protein was detected as well as incorporation of both proteins into virions. A3Z1 and A3Z1Tr interacted with SRLVs Vif, but this interaction was not associated with degradative properties. Similar A3Z1 truncated isoforms were also present in human and monkey cells suggesting a conserved alternative splicing regulation in primates. A3Z1-mediated retroviral restriction could be constrained by different means, including gene expression and specific alternative splicing regulation, leading to truncated protein isoforms lacking a cytidine-deaminase motif.