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Cervical cancer remains a major global health concern, with a specially alarming incidence in younger women. Traditional detection techniques such as the Pap smear and colposcopy often lack sensitivity and specificity and are highly dependent on the experience of the gynaecologist. In response, this study proposes the use of Hyperspectral Imaging, a pioneering technology that combines traditional imaging with spectroscopy to provide detailed spatial and spectral information. Over a period of six-months, our custom-designed hyperspectral colposcope was used on 62 patients. The gathered data underwent a specialized preprocessing workflow using a PCA-based strategy for unsupervised segmentation of the cervical region. This process extracted spectral signatures from various tissue types, and our subsequent statistical analysis highlighted its ability to detect differences and alterations in the cervical tissue. This offers a promising avenue for improving the precision of cervical lesion diagnosis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Despite high initial vaccination rates, Spain's current COVID-19 vaccination coverage in recommended groups does not meet WHO targets. For the upcoming season, challenges include revising vaccination age, updating risk groups, and unifying criteria with flu vaccine co-administration. European Commission's advance purchase agreements limit access to certain vaccines, and the need for vaccines effective against current variants adds administrative complexities. Spain's COVID-19 vaccination recommendations should adapt to these specific circumstances. Using vaccines effective against predominant variants with appropriate response duration is crucial to protect at-risk populations. Enhancing training and health education campaigns for health professionals and the general public, alongside utilizing tools to simplify vaccination recommendations, can promote higher vaccination rates in Spain. Addressing these challenges is essential to ensure adequate protection and improve vaccination coverage, ultimately achieving better public health outcomes in the face of evolving COVID-19 threats., (© 2024 Published by Elsevier España, S.L.U. on behalf of Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica.)

Despite high initial vaccination rates, Spain's current COVID-19 vaccination coverage in recommended groups does not meet WHO targets. For the upcoming season, challenges include revising vaccination age, updating risk groups, and unifying criteria with flu vaccine co-administration. European Commission's advance purchase agreements limit access to certain vaccines, and the need for vaccines effective against current variants adds administrative complexities. Spain's COVID-19 vaccination recommendations should adapt to these specific circumstances. Using vaccines effective against predominant variants with appropriate response duration is crucial to protect at-risk populations. Enhancing training and health education campaigns for health professionals and the general public, alongside utilizing tools to simplify vaccination recommendations, can promote higher vaccination rates in Spain. Addressing these challenges is essential to ensure adequate protection and improve vaccination coverage, ultimately achieving better public health outcomes in the face of evolving COVID-19 threats., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Background: Interferons (IFNs) represent a first-line defense against viruses and other pathogens. It has been shown that an impaired and uncontrolled release of these glycoproteins can result in tissue damage and explain severe progression of coronavirus disease 2019 (COVID-19). However, their potential role in Long-COVID syndrome (LC) remains debateable., Objectives: The objective of the present study is to shed further light on the possible role of IFNs (and related genes) gene expression patterns in the progression of COVID-19 and LC patients., Methods: We carried out a multi-cohort study by analyzing the IFN gene expression patterns (using different IFN gene signatures) in five cohorts of acute COVID-19 ( n  = 541 samples) and LC patients ( n  = 188), and compared them to patterns observed in three autoimmune diseases (systemic lupus erythematous [ n  = 242], systemic sclerosis [ n  = 91], and Sjögren's syndrome [ n  = 282])., Results: The data show that, while the interferon signatures are strongly upregulated in severe COVID-19 patients and autoimmune diseases, it decays with the time from symptoms onset and in LC patients. Differential pathway analysis of IFN-related terms indicates an over activation in autoimmune diseases (IFN-I/II) and severe COVID-19 (IFN-I/II/III), while these pathways are mostly inactivated or downregulated in LC (IFN-I/III). By analyzing six proteomic LC datasets, we did not find evidence of a role of IFNs in this condition., Conclusion: Our findings suggest a potential role of cytokine exhaustion mediated by IFN gene expression inactivation as a possible driver of LC.

Background: Oral food challenge (OFC) is the criterion standard for diagnosis of acute food protein-induced enterocolitis syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated., Objective: To assess clinical-hematological changes and predictors of severity of FPIES reactions at OFC., Methods: This was an observational multicenter prospective study. Children aged 0 to 18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centers in Spain and Italy. OFC outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed on the basis of published "2017 FPIES Consensus" criteria. Clinical characteristics were recorded, and full blood cell count was done at baseline, reaction onset, and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC., Results: A total of 81 children had positive OFC (mild in 11% [9 of 81], moderate in 61% [49 of 81], and severe in 28% [23 of 81]). Increase in neutrophils and reduction in eosinophils, basophils, and lymphocytes were observed (P < .05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed that a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not sex, age, culprit food, cumulative dose, and previous reaction severity) was associated with reduced odds of severe reaction compared with giving multiple doses in a single day., Conclusions: Distinct hematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may be associated with a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: GP trainees may not have experienced a systematic and comprehensive education in safe prescribing. Therefore, a self-assessment prescribing review was developed., Aim: To determine whether the assessment was feasible, had face validity, and did not disadvantage particular groups of participants., Design & Setting: An online survey that evaluates the opinions of GPs in training of a prescribing assessment in the UK. All full-time UK trainees who started their final year of GP training in August 2019 undertook the prescribing assessment along with their trainers, after which they completed an online anonymous feedback questionnaire., Method: The questionnaire completed by trainees sought their opinions of the assessment, and collected ethnicity and disability data. The trainer questionnaire was similar but did not include any demographic information., Results: The questionnaire was completed by 1741 trainees and 1576 trainers. There was no evidence that ethnic group and disability were related to aspects of the review. Most of the trainees (76.4%, n = 1330) and trainers (82.0%, n = 1293) agreed or strongly agreed that the prescribing review was helpful for assessing and learning about the trainee's prescribing. However, most participants (63.2%, n = 1092) took >4 hours to review their prescriptions. A majority of trainees (90.2%, n = 1571) reported that completing the assessment had resulted in a change in their prescribing practice., Conclusion: The majority of trainers and trainees reported that the prescribing assessment was helpful. The study was not able to assess whether there had been an actual change in practice that resulted in an error reduction., (Copyright © 2023, The Authors.)

Competing Interests: The authors declare that there are no competing interests.

RNA viruses have recently been detected in association with house dust mites, including laboratory cultures, dust samples, and mite-derived pharmaceuticals used for allergy diagnosis. This study aimed to assess the incidence of viral infection on Dermatophagoides pteronyssinus physiology and on the allergenic performance of extracts derived from its culture. Transcriptional changes between genetically identical control and virus-infected mite colonies were analysed by RNAseq with the support of a new D. pteronyssinus high-quality annotated genome (56.8 Mb, 108 scaffolds, N50 = 2.73 Mb, 96.7% BUSCO-completeness). Extracts of cultures and bodies from both colonies were compared by inspecting major allergen accumulation by enzyme-linked immunosorbent assay (ELISA), allergen-related enzymatic activities by specific assays, airway inflammation in a mouse model of allergic asthma, and binding to allergic patient's sera IgE by ImmunoCAP. Viral infection induced a significant transcriptional response, including several immunity and stress-response genes, and affected the expression of seven allergens, putative isoallergens and allergen orthologs. Major allergens were unaffected except for Der p 23 that was upregulated, increasing ELISA titers up to 29% in infected-mite extracts. By contrast, serine protease allergens Der p 3, 6 and 9 were downregulated, being trypsin and chymotrypsin enzymatic activities reduced up to 21% in extracts. None of the parameters analysed in our mouse model, nor binding to human IgE were significantly different when comparing control and infected-mite extracts. Despite the described physiological impact of viral infection on the mites, no significant consequences for the allergenicity of derived extracts or their practical use in allergy diagnosis have been detected., (© 2022 The Authors. Insect Molecular Biology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society.)

Background: Progressive osseous heteroplasia (POH) is an ultrarare genetic disorder characterized by an inactivating mutation in the GNAS gene that causes heterotopic ossification. Inhibition of the mammalian target of the rapamycin (mTOR) signalling pathway has been proposed as a therapy for progressive bone fibrodysplasia and non-genetic forms of bone heteroplasia. Herein, we describe the impact of using Everolimus as a rescue therapy for an identical twin girl exhibiting an aggressive clinical phenotype of POH., Methods: Clinical evaluation of the progression of the disease during Everolimus treatment was performed periodically. Cytokine markers involved in bone metabolism and protein markers related to bone activity were analyzed to explore bone turnover activity., Results: The patient received Everolimus therapy for 36 weeks. During treatment, no clinical improvement of the disease was perceived. Analysis of biochemical parameters, namely, β-CTX ( r 2  = -0.576, P -value = 0.016) and PNIP ( r 2  = -0.598, P -value = 0.011), indicated that bone turnover activity was significantly reduced. Additionally, bone metabolism-related biomarkers showed only a significant positive correlation with PTH levels., Conclusions: Everolimus treatment did not modify the clinical progression of the disease in an aggressive form of POH, although an impact on the protein markers studied was observed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Cebey-López, Currás-Tuala, Gómez-Rial, Rivero-Calle, Pardo-Seco, Mendez-Gallart, Pischedda, Gómez-Carballa, Barral-Arca, Justicia-Grande, Viz-Lasheras, Rodríguez-Tenreiro, Gómez, Salas and Martinón-Torres.)

Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. In this study, for the first time, we show how immunomodulatory treatments commonly administered to COVID-19 patients greatly alter the transcriptome. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response., (© 2022. The Author(s).)

Coronavirus Disease-19 (COVID-19) symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were present in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Co-expression network analysis adds further support to these findings, by detecting modules specifically correlated with severity involved in the abovementioned biological routes; this analysis also provides new candidate genes that might be tested as biomarkers in future studies. We also found tissue specific severity-related signatures mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Respiratory syncytial virus (RSV) infection has been associated with the subsequent development of recurrent wheezing and asthma, although the mechanisms involved are still unknown. We investigate the role of epigenetics in the respiratory morbidity after infection by comparing methylation patterns from children who develop recurrent wheezing (RW-RSV), subsequent asthma (AS-RVS), and those experiencing complete recovery (CR-RSV)., Methods: Prospective, observational study of infants aged < 2 years with RSV respiratory infection admitted to hospital and followed-up after discharge for at least three years. According to their clinical course, patients were categorized into subgroups: RW-RSV ( n = 36), AS-RSV ( n = 9), and CR-RSV ( n = 32). The DNA genome-wide methylation pattern was analyzed in whole blood samples, collected during the acute phase of the infection, using the Illumina Infinium Methylation EPIC BeadChip (850K CpG sites). Differences in methylation were determined through a linear regression model adjusted for age, gender and cell composition., Results: Patients who developed respiratory sequelae showed a statistically significant higher proportion of NK and CD8T cells (inferred through a deconvolution approach) than those with complete recovery. We identified 5,097 significant differentially methylated positions (DMPs) when comparing RW-RSV and AS-RVS together against CR-RSV. Methylation profiles affect several genes involved in airway inflammation processes. The most significant DMPs were found to be hypomethylated in cases and therefore generally leading to overexpression of affected genes. The lead CpG position (cg24509398) falls at the gene body of EYA3 ( P -value = 2.77×10 -10 ), a tyrosine phosphatase connected with pulmonary vascular remodeling, a key process in the asthma pathology. Logistic regression analysis resulted in a diagnostic epigenetic signature of 3-DMPs (involving genes ZNF2698 , LOC102723354 and RPL15 / NKIRAS1 ) that allows to efficiently differentiate sequelae cases from CR-RSV patients (AUC = 1.00). Enrichment pathway analysis reveals the role of the cell cycle checkpoint (FDR P -value = 4.71×10 -2 ), DNA damage (FD P -value = 2.53×10 -2 ), and DNA integrity checkpoint (FDR P -value = 2.56×10 -2 ) in differentiating sequelae from CR-RSV patients., Conclusions: Epigenetic mechanisms might play a fundamental role in the long-term sequelae after RSV infection, contributing to explain the different phenotypes observed., Competing Interests: IR-C has received honoraria from GSK, Pfizer, Sanofi Pasteur and MSD for taking part in advisory boards and expert meetings and for acting as a speaker in congresses outside the scope of the submitted work. IR-C has also acted as subinvestigator in randomized controlled trials of Ablynx, Abbot, Seqirus, Sanofi Pasteur MSD, Sanofi Pasteur, Cubist, Wyeth, Merck, Pfizer, Roche, Regeneron, Jansen, Medimmune, Novavax, Novartis and GSK. FM-T has received honoraria from GSK group of companies, Pfizer Inc, Sanofi Pasteur, MSD, Seqirus, Biofabri and Janssen for taking part in advisory boards and expert meetings and for acting as a speaker in congresses outside the scope of the submitted work. FM-T has also acted as principal investigator in randomized controlled trials of the above-mentioned companies as well as Ablynx, Gilead, Regeneron, Roche, Abbott, Novavax, and MedImmune, with honoraria paid to his institution. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pischedda, Rivero-Calle, Gómez-Carballa, Cebey-López, Barral-Arca, Gómez-Rial, Pardo-Seco, Curras-Tuala, Viz-Lasheras, Bello, Crujeiras, Diaz-Lagares, González-López, Martinón-Torres, Salas and GENDRES consortium.)

TIPiCO is an annual expert meeting and workshop on infectious diseases and vaccination. The edition of 2020 changed its name and format to aTIPiCO, the first series and podcasts on infectious diseases and vaccines. A total of 13 prestigious experts from different countries participated in this edition launched on the 26 November 2020. The state of the art of coronavirus disease-2019 (COVID-19) and the responsible pathogen, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the options to tackle the pandemic situation were discussed in light of the knowledge in November 2020. Despite COVID-19, the status of other infectious diseases, including influenza infections, respiratory syncytial virus disease, human papillomavirus infection, measles, pertussis, tuberculosis, meningococcal disease, and pneumococcal disease, were also addressed. The essential lessons that can be learned from these diseases and their vaccines to use in the COVID-19 pandemic were also commented with the experts.

Cylindrical magnetic nanowires are key elements of fast-recording and high-density 3D-storage devices. The accurate tuning of the magnetization processes at the nanoscale is crucial for the development of future nano-devices. Here, we analyzed the magnetization of Ni nanostructures with 15-100 nm in diameter and 12-230 nm in length and compared our results with experimental data for periodic arrays. Our modelling led to a phase diagram of the reversal modes where the presence of a critical diameter (d ≈ 30 nm) triggered the type of domain wall (DW) formed (transverse or vortex); while a critical length (L ≈ 100 nm) determined the number of DWs nucleated. Moreover, vortex-DWs originated from 3D skyrmion tubes, reported as one of the best configurations for storage devices. By increasing the diameter and aspect-ratio of nanowires with L > 100 nm, three reversal modes were observed: simultaneous propagation of two vortex-DWs; propagation of one vortex-DW; or spiral rotation of both DWs through "corkscrew" mechanism. Only for very low aspect-ratios (nanodisks), no skyrmion tubes were observed and reversal occurred by spiral rotation of one vortex-DW. The broad range of nanostructures studied allowed the creation of a complete phase diagram, highly important for future choice of nanoscaled dimensions in the development of novel nano-devices.

TIPICO is an expert meeting and workshop that aims to provide the most recent evidence in the field of infectious diseases and vaccination. The 10th Interactive Infectious Disease TIPICO workshop took place in Santiago de Compostela, Spain, on November 21-22, 2019. Cutting-edge advances in vaccination against respiratory syncytial virus, Streptococcus pneumoniae , rotavirus, human papillomavirus, Neisseria meningitidis , influenza virus, and Salmonella Typhi were discussed. Furthermore, heterologous vaccine effects were updated, including the use of Bacillus Calmette-Guérin (BCG) vaccine as potential treatment for type 1 diabetes. Finally, the workshop also included presentations and discussion on emergent virus and zoonoses, vaccine resilience, building and sustaining confidence in vaccination, approaches to vaccine decision-making, pros and cons of compulsory vaccination, the latest advances in decoding infectious diseases by RNA gene signatures, and the application of big data approaches.

Background: Rotavirus (RV) is an enteric pathogen that has devastating impact on childhood morbidity and mortality worldwide. The immunologic mechanism underlying the protection achieved after RV vaccination is not yet fully understood., Methods: We compared the transcriptome of children affected by community-acquired RV infection and children immunized with a live attenuated RV vaccine (RotaTeq ® )., Results: RV vaccination mimics the wild type infection causing similar changes in children's transcriptome, including transcripts associated with cell cycle, diarrhea, nausea, vomiting, intussusception, and abnormal morphology of midgut. A machine learning approach allowed to detect a combination of nine-transcripts that differentiates vaccinated from convalescent-naturally infected children (AUC: 90%; 95%CI: 70-100) and distinguishes between acute-infected and healthy control children (in both cases, AUC: 100%; 95%CI: 100-100). We identified a miRNA hsa-mir-149 that seems to play a role in the host defense against viral pathogens and may have an antiviral role., Discussion: Our findings might shed further light in the understanding of RV infection, its functional link to intussusception causes, as well as guide development of antiviral treatments and safer and more effective vaccines. The nine-transcript signature may constitute a marker of vaccine protection and helps to differentiate vaccinated from naturally infected or susceptible children., Competing Interests: FM-T has received honoraria from GSK, Pfizer, Sanofi Pasteur, MSD, Seqirus, and Janssen for taking part in advisory boards and expert meetings, and for acting as speaker in congresses outside the scope of the submitted work. JG-R has received honoraria from GSK, Pfizer, and MSD for taking part in advisory boards and expert meetings, and for acting as speaker in congresses outside the scope of the submitted work. FM-T has also acted as principal investigator in RCTs of the above-mentioned companies as well as Ablynx, Regeneron, Roche, Abbott, Novavax, and MedImmune, with honoraria paid to his institution. The remaining authors declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gómez-Carballa, Barral-Arca, Cebey-López, Currás-Tuala, Pischedda, Gómez-Rial, Habgood-Coote, Herberg, Kaforou, Martinón-Torres and Salas.)

A racetrack memory is a device where the information is stored as magnetic domains (bits) along a nanowire (track). To read and record the information, the bits are moved along the track by current pulses until they reach the reading/writing heads. In particular, 3D racetrack memory devices use arrays of vertically aligned wires (tracks), thus enhancing storage density. In this work, we propose a novel 3D racetrack memory configuration based on functional segments inside cylindrical nanowire arrays. The innovative idea is the integration of the writing element inside the racetrack itself, avoiding the need to implement external writing heads next to the track. The use of selective magnetic segments inside one nanowire allows the creation of writing and storage sections inside the same track, separated by chemical constraints identical to those separating the bits. Using micromagnetic simulations, our study reveals that if the writing section is composed of two segments with different coercivities, one can reverse its magnetization independently from the rest of the memory device by applying an external magnetic field. Spin-polarized current pulses then move the information bits along selected tracks, completing the writing process by pushing the new bit into the storage section of the wire. Finally, we have proven the efficacy of this system inside an array of 7 nanowires, opening the possibility to use this configuration in a 3D racetrack memory device composed of an array of thousands of nanowires produced by low-cost and high-yield template-electrodeposition methods.

Background: Emerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind., Methods: Fifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group., Results: sCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not., Conclusions: Monocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients., (Copyright © 2020 Gómez-Rial, Currás-Tuala, Rivero-Calle, Gómez-Carballa, Cebey-López, Rodríguez-Tenreiro, Dacosta-Urbieta, Rivero-Velasco, Rodríguez-Núñez, Trastoy-Pena, Rodríguez-García, Salas and Martinón-Torres.)

Spain is one of the countries most severely affected by the SARS-CoV-2 pandemic, with almost 190,000 cases as of April 18, 2020. As healthcare workers (HCW) are one of the groups hardest hit by the infection, it is important to know the seroprevalence of antibodies against SARS-CoV-2 in pediatric departments. We performed 175 immunoglobulin (Ig)M and IgG immunochromatographic rapid tests in the personnel working at the Pediatric Department of the Hospital Clínico Universitario of Santiago de Compostela (Spain), including pediatricians, residents, nurses, and other staff, on days 31-33 since the lockdown started. Seven out of the 175 tests were positive, including four for IgM and three for IgG, leading to a seroprevalence of 4.0% (95% CI: 1.1-6.9%). Only one of them had symptoms at the time of testing (sore throat). All seropositive cases yielded negative RT-PCR of the upper and lower respiratory tract. This is the first SARS-CoV-2 serological survey among HCWs reported in Spain. Notwithstanding the test limitations, our results reveal that personal protection policy and lockdown measures have been effective to limit population exposure. The low seroprevalence rate poses a significant challenge for the next strategic steps of pandemic control., (Copyright © 2020 Dacosta-Urbieta, Rivero-Calle, Pardo-Seco, Redondo-Collazo, Salas, Gómez-Rial and Martinón-Torres.)

Rotavirus, a major etiological agent of acute diarrhea in children worldwide, has historically been linked to autoimmunity. In the last few years, several physiopathological approaches have been proposed to explain the leading mechanism triggering autoimmunity, from the old concept of molecular mimicry to the emerging theory of bystander activation and break of tolerance. Epidemiological and immunological data indicate a strong link between rotavirus infection and two of the autoimmune pathologies with the highest incidence: celiac disease and diabetes. The role for current oral rotavirus vaccines is now being elucidated, with a so far positive protective association demonstrated., (Copyright © 2020. Published by Elsevier Ltd.)

Emerging studies from SARS-CoV-2-infected patients indicate a preponderant role of monocytes/macrophages in the pathogenesis of this viral infection, in a similar way to that previously observed in other coronavirus outbreaks (SARS and MERS). The clinical presentation of severe patients resembles viral-associated hemophagocytic syndrome, a rare condition previously seen during lethal influenza pandemics and during previous SARS and MERS coronavirus outbreaks. SARS-CoV-2 infection triggers an over-exuberant inflammatory response due to the development of a cytokine storm and the depletion of the adaptative immune compartment, which may prelude sepsis in many cases. The present review summarizes past evidence on the role of monocytes/macrophages in previous coronavirus outbreaks and the emerging knowledge on their role in COVID-19 pathogenesis. Treatment strategies incorporating the blockade of migration and differentiation of monocyte-macrophage, such as granulocyte macrophage-colony stimulating factor inhibitors, might enhance the promising results seen so far with selective cytokine blockade., Competing Interests: Jose Gomez-Rial reports personal fees from and being a speaker in scientific meetings and advisor for Merck Sharp and Dohme, GlaxoSmithkline, and Pfizer, outside the submitted work. Irene Rivero-Calle reports trials fees paid to the institution from Ablynx, Jansen, and Mediummune, grants, personal fees, other from GSK, grants and personal fees (research grants and honoraria as an advisor and speaker, and for attending conferences and practical courses; trials fees paid to the institution) from Pfizer, MSD, Sanofi Pasteur, outside the submitted work. Federico Martinón-Torres has received honoraria from GSK, Pfizer, Sanofi Pasteur, MSD, Seqirus, and Janssen for taking part in advisory boards and expert meetings, and for acting as speaker in congresses outside the scope of the submitted work. FM-T has also acted as principal investigator in RCTs of the above-mentioned companies as well as Ablynx, Regeneron, Roche, Abbott, Novavax, and MedImmune, with honoraria paid to his institution. The authors report no other possible conflicts of interest in this work., (© 2020 Gómez-Rial et al.)

Since the early 2000s, pneumococcal conjugate vaccines (PCVs) have been shown to be effective in the prevention of pneumonia and invasive pneumococcal diseases. In 2011, the Galician region incorporated PCV in the routine infant immunization, the very first stable program in Spain. We aim to assess direct and indirect benefits of PCV vaccination on all-cause pneumonia in the region across different age groups using an ecological study design. For this, we calculated the annual hospitalization rates using a hospital-based disease registry. We identified all-cause pneumonia, pneumococcal pneumonia and pneumococcal invasive diseases within the registry. Hospitalization rates were computed and compared across three study periods: pre-vaccination (1998-2003), early-vaccination (2005-2009) and routine-vaccination (2011-2015). Across Northern Spain, we identified 114,873 all-cause pneumonia hospitalizations, of which 24,808 were further diagnosed with pneumococcal pneumonia. The majority were elderly > 64 years (67.3%). Hospitalizations from all-cause pneumonia had a net increase from 20.6 (pre-PCV) and 21.4/10,000 (early) to 28.4/10,000 (routine) (+32.7%, p < .0001), this is attributed to the huge number of cases in the elderly age group. In contrast, a net reduction of incidence of hospitalized pneumococcal pneumonia was observed from 6.3/10,000 (pre-PCV) and 5.7/10,000 (early) to 2.4/10,000 (routine) cases (-57.9%, p < .0001). Thus, routine infant vaccination may have resulted to an overall decline of pneumococcal pneumonia in infants, as well as in elderly age groups. However, a paradoxical increase on all-cause pneumonia was observed in Galicia, mostly attributed to the growing number of cases in the elderly population.

Invasive meningococcal disease (IMD) is a major public health concern because of its high case fatality, long-term morbidity, and potential to course with outbreaks. IMD caused by Nesseira meningitidis serogroup B has been predominant in different regions of the world like Europe and only recently broadly protective vaccines against B serogroup have become available. Two protein-based vaccines, namely 4CMenB (Bexsero ® ) and rLP2086 (Trumenba ® ) are currently licensed for use in different countries against MenB disease. These vaccines came from a novel technology on vaccine design (or antigen selection) using highly specific antigen targets identified through whole-genome sequence analysis. Moreover, it has the potential to confer protection against non-B meningococcus and against other Neisserial species such as gonococcus. Real-world data on the vaccine-use are rapidly accumulating from the UK and other countries which used the vaccine for control of outbreak or as part of routine immunization program, reiterating its safety and efficacy. Additional data on real-life effectiveness, long-term immunity, and eventual herd effects, including estimates on vaccine impact for cost-effectiveness assessment are further needed. Given the predominance of MenB in Europe and other parts of the world, these new vaccines are crucial for the prevention and public health control of the disease, and should be considered., Competing Interests: FMT has received research grants and/or honoraria as a consultant/advisor and/or speaker and for conducting vaccine trials from GlaxoSmithKline, Sanofi Pasteur MSD, Merck, Sanofi Pasteur, Pfizer, Novartis, and MedImmune Inc. IRC has received research grants and honoraria as an advisor and speaker, and for attending conferences and practical courses from GlaxoSmithKline, Sanofi Pasteur MSD, Merck, Sanofi Pasteur, Novartis, and Pfizer. JGR has received honoraria as advisor and speaker from GlaxoSmithKline, Merck Sharp & Dohme and Pfizer. The authors report no other conflicts of interest in this work., (© 2019 Rivero-Calle et al.)

The diagnosis of bacterial infections in hospital settings is currently performed using bacterial culture from sterile site, but they are lengthy and limited. Transcriptomic biomarkers are becoming promising tools for diagnosis with potential applicability in clinical settings. We evaluated a RT-qPCR assay for a 2-transcript host expression signature (FAM89A and IFI44L genes) inferred from microarray data that allow to differentiate between viral and bacterial infection in febrile children. This assay was able to discriminate viral from bacterial infections (P-value = 1.04 × 10 -4 ; AUC = 92.2%; sensitivity = 90.9%; specificity = 85.7%) and showed very high reproducibility regardless of the reference gene(s) used to normalize the data. Unexpectedly, the monogenic IFI44L expression signature yielded better results than those obtained from the 2-transcript test (P-value = 3.59 × 10 -5 ; AUC = 94.1%; sensitivity = 90.9%; specificity = 92.8%). We validated this IFI44L signature in previously published microarray and whole-transcriptome data from patients affected by different types of viral and bacterial infections, confirming that this gene alone differentiates between both groups, thus saving time, effort, and costs. Herein, we demonstrate that host expression microarray data can be successfully translated into a fast, highly accurate and relatively inexpensive in vitro assay that could be implemented in the clinical routine.

Teenagers struggle to engage with healthcare providers. This article explores teenagers' perspectives of accessing healthcare needs and provides some suggestions for what practices could be doing to improve engagement with this group.

The comprehension of molecular recognition phenomena demands the understanding of the energetic and kinetic processes involved. General equations valid for the thermodynamic analysis of any observable that is assessed as a function of the concentration of the involved compounds are described, together with their implementation in the AFFINImeter software. Here, a maximum of three different molecular species that can interact with each other to form an enormous variety of supramolecular complexes are considered. The corrections currently employed to take into account the effects of dilution, volume displacement, concentration errors and those due to external factors, especially in the case of ITC measurements, are included. The methods used to fit the model parameters to the experimental data, and to generate the uncertainties are described in detail. A simulation tool and the so called kinITC analysis to get kinetic information from calorimetric experiments are also presented. An example of how to take advantage of the AFFINImeter software for the global multi-temperature analysis of a system exhibiting cooperative 1:2 interactions is presented and the results are compared with data previously published. Some useful recommendations for the analysis of experiments aimed at studying molecular interactions are provided., (Copyright © 2019. Published by Elsevier Inc.)

There is a growing interest in the possible relationship between rotavirus (RV) vaccine and hospitalizations due to childhood seizures. We explored variation in hospitalization rates after 9 years of vaccination against pre-vaccination period for children <5 years of age from Galicia (Northwest Spain) before and after the introduction of the RV vaccines. Hospitalization rates for childhood seizures in Galician children were compared before and after RV vaccine introduction (in 2007) using different statistical approaches, including time series analyses. Our study cohort totaled 7,712 children <5 years of age admitted to hospital between 2002 and 2015 for "all kind of childhood seizures". Hospitalization rates decreases steadily with reductions ranging from 22.3% (95% CI: 15.0-29.1) in 2008, to 50.9% (95% CI: 45.5-55.7) in 2014, and significant results were also observed for <1, 1, and 2-year-old children in comparison with pre-vaccination period hospitalization rate. Regression models indicate a negative association between RV vaccination and hospitalizations for all kind of seizures. In addition, time series analyses are consistent with this finding and predict that vaccination coverage will affect hospitalization rates for "all kind of seizures" after 9 months. The results strongly support that RV vaccination has significantly reduced hospitalization rates due to childhood seizures., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Competing Interests: JGR reports personal fees from Merck Sharp & Dohme, personal fees from Glaxo Smithkline (GSK), and personal fees from Pfizer. The authors report no other confilcts of interest in this communication.

The Ninth Interactive Infectious Disease workshop TIPICO was held on November 22-23, 2018, in Santiago de Compostela, Spain. This 2-day academic experience addressed current and topical issues in the field of infectious diseases and vaccination. Summary findings of the meeting include: cervical cancer elimination will be possible in the future, thanks to the implementation of global vaccination action plans in combination with appropriate screening interventions. The introduction of appropriate immunization programs is key to maintain the success of current effective vaccines such as those against meningococcal disease or rotavirus infection. Additionally, reduced dose schedules might improve the efficiency of some vaccines (i.e., PCV13). New vaccines to improve current preventive alternatives are under development (e.g., against tuberculosis or influenza virus), while others to protect against infectious diseases with no current available vaccines (e.g., enterovirus, parechovirus and flaviviruses) need to be developed. Vaccinomics will be fundamental in this process, while infectomics will allow the application of precision medicine. Further research is also required to understand the impact of heterologous vaccine effects. Finally, vaccination requires education at all levels (individuals, community, healthcare professionals) to ensure its success by helping to overcome major barriers such as vaccine hesitancy and false contraindications.

Background and Objective: Alcohol consumption is associated with enhanced TH2 immune responses. Objective: To investigate the frequency of false-positive results in serological tests for allergy in alcoholic patients., Methods: A total of 138 alcoholic patients consecutively admitted to hospital underwent a panel of allergy tests that included serum total IgE, a multiallergen IgE test (UniCAP Phadiatop), and skin prick tests to relevant aeroallergens in the area, which were considered the standard reference for atopy. In selected cases with positive specific IgE (sIgE) to cross-reactive carbohydrate determinants (CCDs) on ImmunoCAP, we determined sIgE to hymenoptera venom components (ADVIA Centaur) and a microarray of 103 allergen components (ISAC)., Results: Increased serum total IgE (>170 IU/mL) was observed in 59/110 (54%) of nonatopic (skin prick test-negative) patients. The result of the multiallergen IgE test was positive in 46 nonatopic patients (42%). This finding was closely associated with high serum concentrations of total IgE and sIgE to CCDs. The vast majority of patients with positive CCD-sIgE showed positivity to glycosylated plant and hymenoptera allergen components on ISAC and ADVIA Centaur. Only 1 out of 26 patients with positive sIgE to CCD and hymenoptera venom developed honeybee venom allergy after a median follow-up of 166 months. Correlations between measurements of sIgE to CCD markers on ImmunoCAP, ADVIA Centaur, and ISAC were imperfect., Conclusions: Serological tests for allergy should be interpreted with caution in alcoholic patients, who frequently have increased levels of total IgE and CCD-sIgE and subsequent positivity of sIgE to glycosylated allergen components, irrespective of the method used.

Standard molecular binding isothermal titration calorimetric (ITC) experiments are designed to get thermodynamic information: changes in Gibbs energy, enthalpy, and entropy associated to the studied process. Traditionally, the kinetic information contained in the ITC raw signal has been ignored. For a usual one-step process, this corresponds to the rate constants for the association and the dissociation of the complex (k on and k off ). The availability of highly sensitive ITC instruments with low response time, together with the development of theoretical methods and of public software for the proper analysis of the signal, cancels any reason for not retrieving this kinetic information. Here we describe how to further exploit ITC experiments of simple one-step interactions by using the software AFFINImeter.The method is exemplified using a standard reference system for thermodynamic and kinetic molecular binding analysis: the interaction of carbonic anhydrase (CA) with its inhibitor 4-carboxybenzenesulfonamide (4-CBS) at several temperatures. It is to be emphasized that old experiments initially designed and executed just for thermodynamic analysis can be readily recycled by using AFFINImeter to retrieve the previously ignored kinetic information.

The landscape of rotavirus (RV) infection has changed substantially in recent years. Autoimmune triggering has been added to clinical spectrum of this pathology, which is now known to be much broader than diarrhea. The impact of RV vaccines in these other conditions is becoming a growing field of research. The importance of host genetic background in RV susceptibility has been revealed, therefore increasing our understanding of vaccine effectiveness and giving some clues about the limited efficacy of RV vaccines in low-income settings. Also, interaction of RV with intestinal microbiota seems to play a key role in the process of infection vaccine effect. This article reviews current findings on the extraintestinal impact of RV infection and their widening clinical picture, and the recently described mechanisms of host susceptibility to infection and vaccine effectiveness. RV infection is a systemic disease with clinical and pathophysiological implications beyond the gut. We propose an "iceberg" model for this pathology with almost hidden clinical implications away from the gastrointestinal tract and eventually triggering the development of autoimmune diseases. Impact of current vaccines is being influenced by host genetics and gut microbiota interactions and these factors must be taken into account in the development of public health programs., Competing Interests: Disclosure This work was supported by grants from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): project GePEM ISCIII/PI16/01478/Cofinanciado FEDER (AS) and project ReSVinext ISCIII/PI16/01569/Cofinanciado FEDER (FMT); Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007-2012, PI16/01569), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del plan nacional de I + D + I (FMT), and 2016-PG071 Consolidación e Estructuración REDES 2016GI-1344 G3VIP (Grupo Gallego de Genética Vacunas Infecciones y Pediatría, ED341D R2016/021) (AS and FMT). FMT has received honoraria from GSK, Pfizer, Sanofi Pasteur, MSD, and Janssen for taking part in advisory boards and expert meetings, and for acting as speaker in congresses outside the scope of the submitted work. FMT has also acted as principal investigator in RCTs of the above-mentioned companies as well as Seqirus, Ablynx, Regeneron, Abbot, Novavax and Medimmune, with honorarium paid to his institution. The authors report no other conflicts of interest in this work.

With the increase in the number of routine vaccinations the development of pentavalent and hexavalent combination vaccines fitting the routine vaccination schedules became a necessity. In this respect, Europe has taken the lead in comparison with other world regions, and routine vaccination with pentavalent and hexavalent combinations including DTPa, Hib, HepB and IPV has been on European vaccination programs for >15years. Since the marketing authorization of Hexavac® and Infanrix Hexa® in 2000, immunization schedules in most European countries have included hexavalent vaccines. In the last years, two new hexavalent vaccines have been licensed and commercialized worldwide. This paper presents a review of the pharmaceutical profiles of the three hexavalent vaccines currently available. In addition, we aim to review safety, co-administration, tolerability and other practical concerns of their use., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Searching for high-performance permanent magnets components with no limitation in shape and dimensions is highly desired to overcome the present design and manufacturing restrictions, which affect the efficiency of the final devices in energy, automotive and aerospace sectors. Advanced 3D-printing of composite materials and related technologies is an incipient route to achieve functional structures avoiding the limitations of traditional manufacturing. Gas-atomized MnAlC particles combined with polymer have been used in this work for fabricating scalable rare earth-free permanent magnet composites and extruded flexible filaments with continuous length exceeding 10 m. Solution casting has been used to synthesize homogeneous composites with tuned particles content, made of a polyethylene (PE) matrix embedding quasi-spherical particles of the ferromagnetic τ -MnAlC phase. A maximum filling factor of 86.5 and 72.3% has been obtained for the composite and the filament after extrusion, respectively. The magnetic measurements reveal no deterioration of the properties of the MnAlC particles after the composite synthesis and filament extrusion. The produced MnAlC/PE materials will serve as precursors for an efficient and scalable design and fabrication of end-products by different processing techniques (polymerized cold-compacted magnets and 3D-printing, respectively) in view of technological applications (from micro electromechanical systems to energy and transport applications).

Pneumonia is the leading cause of death amongst infectious diseases. Streptococcus pneumoniae is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with complicated cases of pneumococcal pneumonia (empyema). An initial assessment of statistical association of WES variation with pneumonia was carried out using data from the 1000 Genomes Project (1000G) for the Iberian Peninsula (IBS) as reference controls. Pseudo-replication statistical analyses were carried out using different European control groups. Association tests pointed to single nucleotide polymorphism (SNP) rs201967957 (gene MEIS1 ; chromosome 2; p -value IBS = 3.71 × 10 -13 ) and rs576099063 (gene TSPAN15 ; chromosome 10; p -value IBS = 2.36 × 10 -8 ) as the best candidate variants associated to pneumococcal pneumonia. A burden gene test of pathogenicity signaled four genes, namely, OR9G9 , MUC6 , MUC3A and APOB , which carry significantly increased pathogenic variation when compared to controls. By analyzing various transcriptomic data repositories, we found strong supportive evidence for the role of MEIS1, TSPAN15 and APOBR (encoding the receptor of the APOB protein) in pneumonia in mouse and human models. Furthermore, the association of the olfactory receptor gene OR9G9 has recently been related to some viral infectious diseases, while the role of mucin genes ( MUC6 and MUC3A ), encoding mucin glycoproteins, are well-known factors related to chronic obstructive airway disease. WES emerges as a promising technique to disentangle the genetic basis of host genome susceptibility to infectious respiratory diseases.

Introduction: Salivary glands are known immune effector sites and considered to be part of the whole mucosal immune system. The aim of the present study was to assess the salivary immune response to rotavirus (RV) infection through the analysis of the cytokine immune profile in saliva., Material and Methods: A prospective comparative study of serial saliva samples from 27 RV-infected patients (sampled upon admission to the hospital during acute phase and at convalescence-i.e. at least three months after recovery) and 36 healthy controls was performed. Concentrations of 11 salivary cytokines (IFN-γ, IFN-α2, IL-1β, IL-6, IL-8, IL-10, IL-15, IL12p70, TNF-α, IFN-λ1, IL-22) were determined. Cytokine levels were compared between healthy controls acute infection and convalescence. The correlation between clinical data and salivary cytokine profile in infected children was assessed., Results: The salivary cytokine profile changes significantly in response to acute RV infection. In RV-infected patients, IL-22 levels were increased in the acute phase with respect to convalescence (P-value < 0.001). Comparisons between infected and control group showed significant differences in salivary IFN-α2, IL-1β, IL-6, IL-8, IL-10 and IL-22. Although acute-phase levels of IL-12, IL-10, IL-6 and IFN-γ showed nominal association with Vesikari's severity, this trend did not reach statistical significance after multiple test adjustment., Conclusions: RV infection induces a host salivary immune response, indicating that immune mucosal response to RV infection is not confined to the intestinal mucosa. Our data point to a whole mucosal implication in the RV infection as a result of the integrative mucosal immune response, and suggest the salivary gland as effector site for RV infection.

Respiratory syncytial virus (RSV) is an important cause of serious lower respiratory tract disease in infants. Several studies have shown evidence pointing to the genome of the host as an important factor determining susceptibility to respiratory disease caused by RSV. We sequenced the complete exomes of 54 patients infected by RSV that needed hospitalization due to development of severe bronchiolitis. The Iberian sample (IBS) from The 1000 Genomes Project (1000G) was used as control group; all the association results were pseudo-replicated using other 1000G-European controls and Spanish controls. The study points to SNP rs199665292 in the olfactory receptor (OR) gene OR13C5 as the best candidate variant (P-value = 1.16 × 10 -12 ; OR = 5.56). Genetic variants at HLA genes (HLA-DQA1, HLA-DPB1), and in the mucin 4 gene (MUC4) also emerge as susceptibility candidates. By collapsing rare variants in genes and weighing by pathogenicity, we obtained confirmatory signals of association in the OR gene OR8U1/OR8U8, the taste receptor TAS2R19, and another mucin gene (MUC6). Overall, we identified new predisposition variants and genes related to RSV infection. Of special interest is the association of RSV to olfactory and taste receptors; this finding is in line with recent evidence pointing to their role in viral infectious diseases.

Background: The IFI27 interferon gene expression has been found to be largely increased in rotavirus (RV)-infected patients. IFI27 gene encodes for a protein of unknown function, very recently linked to epidermal proliferation and related to the epidermal growth factor (EGF) protein. The EGF is a low-molecular-weight polypeptide that is mainly produced by submandibular and parotid glands, and it plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. Our aim was to determine salivary EGF levels in RV-infected patients in order to establish its potential relationship with IFI27 increased expression and EGF-mediated mucosal protection in RV infection., Methods: We conducted a prospective comparative study using saliva samples from 27 infants infected with RV (sampled at recruitment during hospital admission and at convalescence, i.e. at least 3 months after recovery) and from 36 healthy control children., Results: Median (SD) EGF salivary concentration was 777 (529) pg/ml in RV-infected group at acute phase and 356 (242) pg/m at convalescence, while it was 337 (119) pg/ml in the healthy control group. A significant association was found between EGF levels and hospitalization length of stay (P-value = 0.022; r 2  = -0.63)., Conclusions: The salivary levels of EGF are significantly increased during the acute phase of natural RV infection, and relate to length of hospitalization. Further assessment of this non-invasive biomarker in RV disease is warranted.

The mechanisms of rotavirus (RV) infection have been analyzed from different angles but the way in which RV modifies the transcriptome of the host is still unknown. Whole transcriptome shotgun sequencing of peripheral blood samples was used to reveal patterns of expression from the genome of RV-infected patients. RV provokes global changes in the transcriptome of infected cells, involving an over-expression of genes involved in cell cycle and chromatin condensation. While interferon IFI27 was hyper-activated, interferon type II was not suggesting that RV has developed mechanisms to evade the innate response by host cells after virus infection. Most interesting was the inhibition of genes of the glycophorins A and B (GYPA/B) family, which are the major sialoglycoproteins of the human erythrocyte membrane and receptor of several viruses for host invasion. RV infection induces a complex and global response in the host. The strong inhibition of glycophorins suggests a novel defense mechanism of the host to prevent viral infection, inhibiting the expression of receptors used by the virus for infection. The present results add further support to the systemic nature of RV infection., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A growing body of evidence warrants a revision of the received/conventional wisdom of rotavirus infection as synonymous with acute gastroenteritis. Rotavirus vaccines have boosted our interest and knowledge of this virus, but also importantly, they may have changed the landscape of the disease. Extraintestinal spread of rotavirus is well documented, and the clinical spectrum of the disease is widening. Furthermore, the positive impact of current rotavirus vaccines in reducing seizure hospitalization rates should prompt a reassessment of the actual burden of extraintestinal manifestations of rotavirus diseases. This article discusses current knowledge of the systemic extraintestinal manifestations of rotavirus infection and their underlying mechanisms, and aims to pave the way for future clinical, public health and research questions., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: A properly validated scoring system allowing objective categorization of infants with acute respiratory infections (ARIs), avoiding the need for in-person assessment and that could also be used by non-health professionals is currently not available. We aimed to develop a new clinical assessment scale meeting these specifications., Methods: We designed a clinical scale (ReSVinet scale) based on seven parameters (feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition, fever) that were assigned different values (from 0 to 3) for a total of 20 points.170 children under two years of age with ARI were assessed independently by three pediatricians using this scale. Parents also evaluated their offspring with an adapted version of the scale in a subset of 61 cases. The scale was tested for internal consistency (Cronbach's alpha), Pearson correlation coefficient for the items in the scale, inter-observer reliability (kappa index) and floor-ceiling effect., Results: Internal consistency was good for all the observers, with the lowest Cronbach's alpha being 0.72. There was a strong correlation between the investigators (r-value ranged 0.76-0.83) and also between the results obtained by the parents and the investigators(r = 0.73). Light's kappa for the observations of the three investigators was 0.74. Weighted kappa in the group evaluated by the parents was 0.73. The final score was correlated with length of hospital stay, PICU admission and Wood-Downes Score., Conclusions: The ReSVinet scale may be useful and reliable in the evaluation of infants with ARI, particularly acute bronchiolitis, even with data obtained from medical records and when employed by parents. Although further studies are necessary, ReSVinet scale already complies with more score validation criteria than the vast majority of the alternatives currently available and used in the clinical practice.

Isothermal titration calorimetry (ITC) has long been used for kinetic studies in chemistry, but this remained confined to enzymatic studies in the biological field. In fact, the biological community has long had the tendency of ignoring the kinetic possibilities of ITC considering it solely as a thermodynamic technique, whereas surface plasmon resonance is seen as the kinetic technique par excellence. However, the primary signal recorded by ITC is a heat power which is directly related to the kinetics of the reaction. Here, it is shown how this kinetic signal can be recovered by using kinITC, the kinetic extension of ITC. The theoretical basis of kinITC is detailed for the most common situation of a second-order reaction A+B Ω C characterized by kinetic parameters kon, koff. A simplified kinITC-ETC method based upon the determination of an "Equilibration Time Curve" (ETC) is presented. The ETC is obtained by automatic determination of the "effective end" of each injection. The method is illustrated with experimental results with a comparison to Surface Plasmon Resonance (SPR) data. kon values were obtained in a wide range, from 10(3) to 0.5×10(6) M(-1) s(-1). All procedures were implemented in the program AFFINImeter (https://www.affinimeter.com/)., (© 2016 Elsevier Inc. All rights reserved.)

Background: Rotavirus vaccine (RV) might reduce the risk of hospitalization due to childhood seizures (CS). We aimed to identify and assess variations in the incidence of hospitalizations for CS among children <5 years of age before and after RV introduction., Methods: Annual hospitalization rates for any kind of CS, before and after RV introduction in 2007, were calculated using the official surveillance system for hospitalization data., Results: Our study cohort totaled 6149 children <5 years of age admitted to the hospital between 2003 and 2013 with any kind of CS (780.3* + 779.0* + 333.2* + 345* ICD-9-CM code). The annual hospitalization rates for any kind of CS in children <5 years of age were correlated with RV coverage (r = -0.673; P = 0.033) and rotavirus acute gastroenteritis admission rates (ρ = 0.506; P = 0.001), with decrease rates ranging from 16.2% (95% confidence interval: 8.3-23.5%) in 2007 to 34.0% (27.3-40.1%) in 2010, as compared with the median rate of the pre-vaccination period (2003 to 2006). Similarly, for convulsions (780.3*ICD-9-CM code), the decrease seen in children <5 years of age was significantly correlated with the increase in RV coverage (r = -0.747; P = 0.013) and rotavirus acute gastroenteritis admission rates (ρ = 0.543; P < 0.001), with decrease rates ranging from 18.7% (9.6-26.8%) in 2007 to 42.5% (35.3-48.9%) in 2012. Significant results were also obtained for infants <12 months and infants 1-2 years of age. In the remaining age groups or diagnostic categories analyzed, changes were either not significant or not related to vaccination changes or rotavirus acute gastroenteritis admission rates., Conclusions: Our results show that rotavirus vaccination may have a significant impact in the decrease in seizure-related hospitalizations in childhood. This additional benefit of rotavirus vaccination seems more marked in the youngest infants.