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Mayerlys Martínez, Hiltony S Villa-Dangond, Eva M López, Camilo Guzmán Department of Pharmacy, Faculty of Health Sciences, Universidad de Córdoba, Monteria, ColombiaCorrespondence: Camilo Guzmán, Email cantonioguzman@correo.unicordoba.edu.coPurpose: To analyze the adverse events reported in the pharmacovigilance of the health service provider institutions of the municipality of Monteria in the period 2018– 2021.Patients and Methods: Descriptive, cross-sectional, retrospective, and quantitative approach study, the information was analyzed by statistical analysis by multiple correspondence using Orange Data Mining software; the analysis consisted of visual programming to perform interactive data exploration, to identify and differentiate associations or oppositions between different categories in space.Results: The most frequently reported adverse events were allergic reactions, with 28.5%. Female sex and adult age are the groups most prone to present these events; antibiotics were the pharmacological group that produced the most adverse events with 18.3%; the main errors that produce these events are related to prescription.Conclusion: Age and sex increase the risk of adverse drug events; most of these events are the product of erroneous prescriptions. The findings presented in this article are useful for pharmacovigilance programs in health institutions.Keywords: adverse event, patient safety, drug, pharmacovigilance, public health

This study provides a gender-based analysis of the Food and Nutrition Education Program, developed in Spain over the last decades of the 20th century, to explore nutrition education messages and strategies aimed at improving the skills of housewives as guardians of family welfare and experts in all areas of household management. The Program's specific approach to housewives, and the assumptions on which it was based, further entrenched a social model of gender in which men were solely responsible for household income and women were family carers. [ABSTRACT FROM AUTHOR]

Objective: To determine the usefulness of perspective-filet view for polypoid lesions in paediatric patients in comparison with conventional virtual colonoscopy (VC) analysis and optical colonoscopy. Methods: Sixty-one patients (mean age 5 years old) with a previous episode of rectal bleeding were studied using a 16 slices CT scanner. All patients underwent a colonic preparation. Two acquisitions were done in supine and prone positions with slices of 2mm thickness; increment 1mm, 30-50mA; 90-120kV. In a workstation an experienced radiologist reviewed images twice. The first read was done using the conventional virtual colonoscopy technique with the evaluation of two-dimensional (2D), three-dimensional (3D) and endoscopical images. Later, in a second session, perspective-filet view was used. It shows a 360 degrees unrolled visualization of the inner colon. The presence, size and location of the lesions were determined. A record of the reading time was made. Results: At per patient evaluation the conventional virtual colonoscopy analysis obtained a sensitivity of 86% and a specificity of 98%. The perspective-filet view obtained a sensitivity of 91% and a specificity of 99%. In the evaluation on a per lesion basis the conventional analysis had a sensitivity of 81% and a specificity of 88%. Perspective-filet view, had a sensitivity of 82% and specificity of 90%. The average total reading time using conventional colonoscopy technique was 18+/-3min, versus 4+/-1min using the perspective-filet view. Conclusion: Virtual colon dissection with perspective-filet view is more time-efficient than conventional virtual colonoscopy evaluation with correct correlation in results. [ABSTRACT FROM AUTHOR]

Abstract Background Ebola viruses cause viral hemorrhagic fever in humans and non-human primates and are endemic in Africa. Reston ebolavirus (REBOV) has caused several epizootics in cynomolgus monkeys (Macaca fascicularis) but is not associated with any human disease. In late 2008, REBOV infections were identified in swine for the first time in the Philippines. Methods A total of 215 swine sera collected at two REBOV-affected farms in 2008, in Pangasinan and Bulacan, were tested for the presence of REBOV-specific antibodies using multiple serodiagnosis systems. A total of 98 swine sera collected in a non-epizootic region, Tarlac, were also tested to clarify the prevalence of REBOV infection in the general swine population in the Philippines. Results Some 70 % of swine sera at the affected farms were positive for REBOV antibodies in the multiple serodiagnosis systems. On the other hand, none of the swine sera collected in Tarlac showed positive reactions in any of the diagnosis systems. Conclusions The high prevalence of REBOV infection in swine in the affected farms in 2008 suggests that swine is susceptible for REBOV infection. The multiple serological assays used in the study are thought to be useful for future surveillance of REOBV infection in swine in the Philippines.

Gastric cancer ranks fifth in both world prevalence and lethality, with a 5-year survival of less than 30%. HLA-G, a non-classical class I HLA gene, has emerged as a potential marker for cancer susceptibility and prognosis due to its immunomodulatory properties. Its level of expression is regulated by polymorphisms in the 3' untranslated region (3'UTR) polymorphisms, which form various combined haplotypes (UTR-1 to -9). In this study, we examined HLA-G 3'UTR polymorphisms in paired tissue samples from 111 patients with gastric adenocarcinoma and 119 healthy controls. Polymorphism analysis was performed using PCR and Sanger sequencing, followed by statistical analysis using SNPStats software. Survival analysis was conducted using Kaplan-Meier curves and multivariate Cox regression models. High-expressor HLA-G 3'UTR haplotypes (UTR-1 and UTR-6) were significantly associated with gastric cancer susceptibility, indicating a potential role in tumor immune evasion. Additionally, the 14 base pair insertion/deletion polymorphism (14 bp I/D) emerged as a prognostic marker, with D/D genotype carriers showing lower survival rates compared to I/D and I/I genotype carriers. Our study highlights the clinical relevance of HLA-G polymorphisms in gastric cancer, suggesting their potential as prognostic markers and therapeutic targets. Further elucidation of HLA-G-related pathways could lead to personalized treatment strategies and improved patient outcomes in gastric cancer., Competing Interests: Declarations Conflict of interest 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. Human and animal rights The studies involving human participants were reviewed and approved by Comité ético de investigación clínica, Hospital Clínico San Carlos, Madrid, Spain. The patients/participants provided their written informed consent to participate in this study. Informed consent The study was performed in accordance with the ethical standards as laid down in the Declarations of Helsinki and approved by the local ethics committee. Written informed consent was obtained from all subjects., (© 2024. The Author(s).)

Purpose of Review: This review aims to provide an overview of the current understanding of eosinophilic gastrointestinal disorders (EGIDs) and the role of the epithelium in influencing disease pathogenesis to inform and devise future therapeutic strategies., Recent Findings: Changes in epithelial cell structure, functions, and integrity are observed in EGIDs. In eosinophilic esophagitis (EoE), the esophageal epithelium has been shown to play key roles in perpetuating the inflammatory response in EoE through the expression of pro-inflammatory cytokines and immunological cell-surface proteins. Similar mechanisms appear to exist in the other EGIDs, including eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Because of the increasing rarity of each non-EoE EGID, research focusing on how the epithelium is modulating disease in each lower gastrointestinal compartment is still in its rudimentary stages., Summary: While there has been significant progress in understanding the role of the epithelium in EoE, further research is needed to obtain a better understanding of the mechanisms mediating epithelial-immune crosstalk in non-EoE EGIDs. Using EoE-epithelial cell research to inform future EGID investigations could lead to the development of new therapeutic interventions, such as targeted therapies to restore epithelial barrier function and reduce inflammation, to improve rare disease-patient quality of life., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A non-randomized controlled trial, conducted from June 2018 to March 2019 in two rural communes in the health district of Mayahi in Niger, showed that including community health workers (CHWs) in the treatment of severe acute malnutrition (SAM) resulted in a better recovery rate (77.2% vs. 72.1%) compared with the standard treatment provided solely at the health centers. The present study aims to assess the cost and cost-effectiveness of the CHWs led treatment of uncomplicated SAM in children 6-59 months compared to the standard national protocol., Methods: To account for all relevant costs, the cost analysis included activity-based costing and bottom-up approaches from a societal perspective and on a within-trial time horizon. The cost-effectiveness analysis was conducted through a decision analysis network built with OpenMarkov and evaluated under two approaches: (1) with recovery rate and cost per child admitted for treatment as measures of effectiveness and cost, respectively; and (2) assessing the total number of children recovered and the total cost incurred. In addition, a multivariate probabilistic sensitivity analysis was carried out to evaluate the effect of uncertainty around the base case input data., Results: For the base case data, the average cost per child recovered was 116.52 USD in the standard treatment and 107.22 USD in the CHWs-led treatment. Based on the first approach, the CHWs-led treatment was more cost-effective than the standard treatment with an average cost per child admitted for treatment of 82.81 USD vs. 84.01 USD. Based on the second approach, the incremental cost-effectiveness ratio of the transition from the standard to the CHWs-led treatment amounted to 98.01 USD per additional SAM case recovered., Conclusions: In the district of Mayahi in Niger, the CHWs-led SAM treatment was found to be cost-effective when compared to the standard protocol and provided additional advantages such as the reduction of costs for households., Trial Registration: ISRCTN with ID 31143316. https://doi.org/10.1186/ISRCTN31143316., (© 2024. The Author(s).)

Recent research has shown that Massive Open Online Courses (MOOCs) create barriers for students with disabilities. Not taking into account their needs in the design, production or delivery of MOOCs may be one of the main causes behind this. It leads to poor compliance with suitable learning designs and web accessibility standards, as well as a lack of knowledge about the students' needs. The objective of our research is to analyze the learning performance of the students in MOOCs on topics related to Design for All, offered in an Open edX-based platform. Accessibility support was conceived from the outset, including compliance of both the platform and the learning resources with the WCAG 2.1 accessibility standard, and with a subset of the principles of Universal Design for Learning. Additionally, students were consulted on their accessibility needs and preferences, following publicly available modeling schemes and previous research. From a sample of 765 students, who completed at least one of the graded assessment activities of the course, a multilevel multiple logistic regression model was fitted. Based on that model, the results indicate that: a) users of screen readers and users of captions show a statistically significant positive association with a good performance when compared to students with no preferences, with an odds ratio of, respectively, OR = 13.482 and OR = 13.701; b) students who have low vision or very low vision show a significant negative association with a good performance when compared to users of screen readers and to users of captions, with OR = 26.817 and OR = 27.254, respectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rodriguez-Ascaso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clinical capacity for sustainability, or the clinical resources needed to sustain an evidence-based practice, represent proximal determinants that contribute to intervention sustainment. We examine the relationship between clinical capacity for sustainability and sustainment of PEWS, an evidence-based intervention to improve outcomes for pediatric oncology patients in resource-variable hospitals. We conducted a cross-sectional survey among Latin American pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), an improvement collaborative to implement Pediatric Early Warning Systems (PEWS). Hospitals were eligible if they had completed PEWS implementation. Clinicians were eligible to participate if they were involved in PEWS implementation or used PEWS in clinical work. The Spanish language survey consisted of 56 close and open-ended questions about the respondent, hospital, participants' assessment of clinical capacity to sustain PEWS using the clinical sustainability assessment tool (CSAT), and perceptions about PEWS and its use as an intervention. Results were analyzed using a multi-level modeling approach to examine the relationship between individual, hospital, intervention, and clinical capacity determinants to PEWS sustainment. A total of 797 responses from 37 centers in 13 countries were included in the analysis. Eighty-seven percent of participants reported PEWS sustainment. After controlling for individual, hospital, and intervention factors, clinical capacity was significantly associated with PEWS sustainment (OR 3.27, p < .01). Marginal effects from the final model indicate that an increasing capacity score has a positive influence (11% for every additional CSAT point) of predicting PEWS sustainment. PEWS is a sustainable intervention and clinical capacity to sustain PEWS contributes meaningfully to PEWS sustainment., Competing Interests: Conflict of interest We have no known conflict of interest to disclose.

Recently, the use of nanotechnology in food has gained great interest. Iron nanoparticles with unique chemical, physical and structural properties allow their potential use mainly as iron fortifiers, colorants and antimicrobial agents. However, in the market we can find only supplements and food colorants based on iron nanoparticles. Their use in food fortification has so far been focused only on in vitro and in vivo experimental studies, since the toxicological evaluation of these studies has so far been the basis for the proposals of laws and regulations, which are still in an early stage of development. Therefore, the aim of this work was to summarize the use of the different forms of iron nanoparticles (oxides, oxyhydroxides, phosphates, pyrophosphates and sulfates) as food additives and supplements and to resume the perspectives of legislation regarding the use of these types of nanoparticles in the food industry., Competing Interests: Competing interestsOn behalf of all authors, the corresponding author states that they have no competing interests., (© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Malnutrition is a recurring problem that has become more relevant in recent years. The aim of this study is to assess the risk of malnutrition and nutritional status on admission and its evolution until discharge in patients aged 65 and over admitted to medical and surgical hospitalization units in hospitals of the Spanish National Health System., Methods: Prospective observational study to be carried out in the medical-surgical hospitalization units of 9 public hospitals between 01/09/2022 and 31/12/2024. Using consecutive sampling, a total of 4077 patients will be included (453 in each hospital). Variables included are related to the care process, functionality, cognition and comorbidity, risk profile, nutritional status and dysphagia; as well as frailty, dietary quality and contextual variables. The incidence of risk of malnutrition, undernutrition and dysphagia during the care process and at discharge will be calculated. The association with risk factors will be studied with logistic regression models and multivariate Cox regression models. In addition, an analysis of participants' satisfaction with food services will be carried out. The study was approved by the Ethics and Research Committee on 30/09/2020, approved for funding on 02/12/2021 and with registration number RBR-5jnbyhk in the Brazilian clinical trials database (ReBEC) for observational studies., Discussion: Some studies address nutritional status or dysphagia in older people in various care settings. However, there is a lack of large sample studies including both processes of the impact of hospitalization. The results of the project will provide information on the incidence and prevalence of both pathologies in the study subjects, their associated factors and their relationship with the average length of stay, mortality and early readmission. In addition, early detection of a problem such as malnutrition related to the disease and/or dysphagia during a hospital stay will favor the action of professionals to resolve both pathologies and improve the health status of patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Carretero-Randez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Paediatric early warning systems (PEWS) aid in the early identification of clinical deterioration events in children admitted to hospital. We aimed to investigate the effect of PEWS implementation on mortality due to clinical deterioration in children with cancer in 32 resource-limited hospitals across Latin America., Methods: Proyecto Escala de Valoración de Alerta Temprana (Proyecto EVAT) is a quality improvement collaborative to implement PEWS in hospitals providing childhood cancer care. In this prospective, multicentre cohort study, centres joining Proyecto EVAT and completing PEWS implementation between April 1, 2017, and May 31, 2021, prospectively tracked clinical deterioration events and monthly inpatient-days in children admitted to hospital with cancer. De-identified registry data reported between April 17, 2017, and Nov 30, 2021, from all hospitals were included in analyses; children with limitations on escalation of care were excluded. The primary outcome was clinical deterioration event mortality. Incidence rate ratios (IRRs) were used to compare clinical deterioration event mortality before and after PEWS implementation; multivariable analyses assessed the correlation between clinical deterioration event mortality and centre characteristics., Findings: Between April 1, 2017, and May 31, 2021, 32 paediatric oncology centres from 11 countries in Latin America successfully implemented PEWS through Proyecto EVAT; these centres documented 2020 clinical deterioration events in 1651 patients over 556 400 inpatient-days. Overall clinical deterioration event mortality was 32·9% (664 of 2020 events). The median age of patients with clinical deterioration events was 8·5 years (IQR 3·9-13·2), and 1095 (54·2%) of 2020 clinical deterioration events were reported in male patients; data on race or ethnicity were not collected. Data were reported per centre for a median of 12 months (IQR 10-13) before PEWS implementation and 18 months (16-18) after PEWS implementation. The mortality rate due to a clinical deterioration event was 1·33 events per 1000 patient-days before PEWS implementation and 1·09 events per 1000 patient-days after PEWS implementation (IRR 0·82 [95% CI 0·69-0·97]; p=0·021). In the multivariable analysis of centre characteristics, higher clinical deterioration event mortality rates before PEWS implementation (IRR 1·32 [95% CI 1·22-1·43]; p<0·0001), being a teaching hospital (1·18 [1·09-1·27]; p<0·0001), not having a separate paediatric haematology-oncology unit (1·38 [1·21-1·57]; p<0·0001), and having fewer PEWS omissions (0·95 [0·92-0·99]; p=0·0091) were associated with a greater reduction in clinical deterioration event mortality after PEWS implementation; no association was found with country income level (IRR 0·86 [95% CI 0·68-1·09]; p=0·22) or clinical deterioration event rates before PEWS implementation (1·04 [0·97-1·12]; p=0·29)., Interpretation: PEWS implementation was associated with reduced clinical deterioration event mortality in paediatric patients with cancer across 32 resource-limited hospitals in Latin America. These data support the use of PEWS as an effective evidence-based intervention to reduce disparities in global survival for children with cancer., Funding: American Lebanese Syrian Associated Charities, US National Institutes of Health, and Conquer Cancer Foundation., Translations: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: It is known that SARS-CoV-2 antibodies from pregnant women with SARS-CoV-2 infection during pregnancy cross the placenta but the duration and the protective effect of these antibodies in infants is scarce., Methods: This prospective study included mothers with SARS-COV-2 infection during pregnancy and their infants from April 2020 to March 2021. IgG antibodies to SARS-CoV-2 spike protein were performed on women and infants at birth and at two and six months during follow-up. Anthropometrical measures and physical and neurological examinations and a clinical history of symptoms and COVID-19 diagnosis were collected. Simple linear regression was performed to compare categorical and continuous variables. To compare the mother's and infant's antibody titers evolution, a mixed linear regression model was used. A predictive model of newborn antibody titers at birth has been established by means of simple stepwise linear regression., Results: 51 mother-infant couples were included. 45 (90%) of the mothers and 44 (86.3%) of the newborns had a positive serology al birth. These antibodies were progressively decreasing and were positive in 34 (66.7%) and 7 (13.7%) of infants at 2 and 6 months, respectively. IgG titers of newborns at birth were related to mothers' titers, with a positive moderate correlation (Pearson's correlation coefficient: 0.82, p < 0,001). Fetal/maternal antibodies placental transference rate was 1.3 (IQR: 0.7-2.2). The maternal IgG titers at delivery and the type of maternal infection (acute, recent, or past infection) was significantly related with infants' antibody titers at birth. No other epidemiological or clinical factors were related to antibodies titers. Neurodevelopment, psychomotor development, and growth were normal in 94.2% of infants in the third follow-up visit. No infants had a COVID-19 diagnosis during the follow-up period., Conclusions: Transplacental transfer of maternal antibodies is high in newborns from mothers with recent or past infection at delivery, but these antibodies decrease after the first months of life. Infant's IgG titers were related to maternal IgG titers at delivery. Further studies are needed to learn about the protective role of maternal antibodies in infants., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Three coordination compounds from the reaction of copper(II) bromide with the flexible bis-tetrazole organosulfur ligand, 1,2-bis(1-methyl-1 H -tetrazole-5-ylthio)ethane (bmtte) have been isolated and characterised. The identification of polymeric 2∞Cu 2 Br 4 (bmtte) (1), trinuclear [Cu 3 Br 4 (bmtte) 2 ] (2) and tetranuclear [Cu 2 Br 2 (bmtte)] 2 (3) compounds shows that the reaction conditions have a significant influence on the structure of the complexes formed. Moreover, two polymorphs of the 2D Cu(II)-coordination polymer 1 have been isolated and these crystallise in the monoclinic C 2/ m (1m) and the triclinic P 1̄ (1t) space groups. The thermal stabilities and behaviour in aqueous media of compounds 1-3 were investigated along with the reactivity of compound 2 with CuBr 2 and KI. The solid-state reaction between mixed-valence compound 2 with KI or the direct reaction of CuI and bmtte under microwave irradiation allowed the preparation of the polymeric 2∞Cu 4 I 4 (bmtte) 2 (4). The redox behaviour of complexes 2 and 3 was analysed by cyclic voltammetry.

We describe the use of monoclonal antibodies for the treatment of persistent SARS-CoV-2 infection in a pediatric patient with severe combined immunodeficiency who required urgent stem cell transplantation to cure his disease., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Acute Epstein-Barr virus (aEBV) and cytomegalovirus (CMV) infections frequently have similar manifestations. We aim to evaluate the characteristics of aEBV infection, risk factors for hospitalisation and differences according to CMV IgM detection (EBV-CMV co-detection) in children., Methods: Retrospective, single-centre study including patients <16 years diagnosed with aEBV infection (positive anti-EBV IgM/Paul-Bunnell test and acute symptomatology). EBV-CMV co-detection was defined as positive CMV IgM. Factors associated with age, hospitalisation and EBV-CMV co-detection were analysed in a multivariate analysis., Results: A total of 149 patients were included (median age 4.6 years). Most frequent manifestations were fever (77%), cervical lymphadenopathy (64%) and elevated liver enzymes (54%). Younger children had lower rate of positive Paul-Bunnell test (35% vs. 87%; p < 0.01), but higher rate of EBV-CMV co-detection (54% vs. 29%; p = 0.03). These children tended to have less typical symptoms of infectious mononucleosis and higher hospitalisation rate. The overall antibiotic prescription was 49%. Hospitalisation (27 children; 18%) was independently associated with prior antibiotic therapy and anaemia. Sixty-two cases (42%) had EBV-CMV co-detection, which was independently associated with elevated liver enzymes and younger age., Conclusion: In this study, younger children with aEBV infection presented more frequently with atypical clinical symptoms, had higher EBV-CMV co-detection rates and were more often hospitalised. Hospitalisation was associated with prior antibiotic prescription., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient's characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance. The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends., (Copyright © 2023 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Invasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time., Methods: Retrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome., Results: Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, [IQR 4.9-15.1]), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment. Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p<0.001) and a 277% increase in the number of HSCT (p=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674)., Conclusions: In this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates., (© 2023. The Author(s).)

Nine potentially S,N,N py -tridentate thiosemicarbazones (HL) derived from pyridine-2-carbaldehyde or 1-(2-pyridyl)ethanone have been prepared and fully characterized. The X-ray crystal structures of six of them and two hydrochlorides were determined and analyzed. The reaction of the [ReX(CH 3 CN) 2 (CO) 3 ]/[ReX(CO) 5 ] (X = Cl and Br) precursors with these ligands yielded different kinds of compounds: the adducts [ReX(HL)(CO) 3 ], in which the ligands were S,N-bidentate; the trinuclear species [Re 3 Cl 2 (L 23 )(HL 23 )(CO) 9 ]; and the thiosemicarbazonate compounds [Re(L)(CO) 3 ], where the ligand is S,N,N py -tridentate. Besides, the reaction in methanol or ethanol of the thiosemicarbazones derived from aldehydes yielded S,N,N py -tridentate hemiaminal cationic [Re(HL OR )(CO) 3 ]X and neutral [Re(L OMe )(CO) 3 ] complexes after the coordinated ligand underwent addition of the alcohol group to the imine bond. The reactivity of the complex [ReX(HL)(CO) 3 ] in MeOH and NEt 3 led to the formation of dinuclear [Re 2 (L) 2 (CO) 6 ], where the thiosemicarbazonate is again S,N-bidentate. The influence that the substituents on the thiosemicarbazone ligands have on the stability of the complexes and the effect of the reaction medium on the resulting compounds have been analyzed.

The presence of cells with regulatory functions in patients with cancer is one of the mechanisms whereby the immune system cannot confront tumor growth. We sought to determine the prevalence of immunoregulatory T-cell subpopulations, expressing the latency TGFβ-associated peptide (LAP), in patients with gastric adenocarcinoma. T cells were enriched from blood or gastric tissue (tumoral, TT or tumor-free, TF) samples from 22 patients, 6 with early (EGC) and 16 with advanced gastric cancer (AGC). CD4, CD8, LAP, FoxP3 and IFN-γ were measured by cytometry. CD8 + LAP + cells were increased at tumoral sites, especially in early stages of the disease, as compared to tumor-free explants (EGC 5.28 % [4.67-6.64]*; AGC 2.90 % [1.37-4.44]; TF 3.14 % [2.33-4.16]; *p < 0.05 vs TF). Likewise, the LAP+/CD8 + LAP- ratio is increased in gastric samples from patients with early disease (EGC 0.38 [0.30-0.45]*, AGC 0.12 [0.07-0.14]; TF 0.12 [0.09-0.31]; *p < 0.05 vs AGC).Disease progression is accompanied by decreased LAP membrane expression and, probably, increased LAP secretion, therefore limiting the response to the tumor., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The reaction of [Ru 2 Cl 2 (μ-Cl) 2 (η 6 - p -cymene) 2 ] with two thiosemicarbazones obtained by the condensation of N-(4-methoxybenzyl) thiosemicarbazide and 1,4-hydroxy-3-methoxyphenyl)ethan-1-one ( HL 1 ) or 2-fluoro-4-hydroxybenzaldehyde ( HL 2 ) was studied. The cationic complexes of formula [RuCl(η 6 - p -cymene)(HL)] + were isolated as solid chloride and trifluoromethylsulfate (TfO) salts. A study of the solid state and NMR spectra suggests the presence in the material of two isomers that differ in the configuration in the iminic bond, C2=N3, of the coordinated thiosemicarbazone in the triflate salts and only the E isomer in the chloride. An X-ray study of single crystals of the complexes supports this hypothesis. The thiosemicarbazone ligand coordinates with the ruthenium center through the iminic and sulfur atoms to form a five-membered chelate ring. Furthermore, the isolation of single crystals containing the thiosemicarbazonate complex [Ru 2 (μ-L 2 ) 2 (η 6 - p -cymene) 2 ] 2+ suggests the easy labilization of the coordinated chloride in the complex. The redox behavior of the ligands and complexes was evaluated by cyclic voltammetry. It seems to be more difficult to oxidize the complex derived from HL 1 than HL 2 . The ability of the complexes to inhibit cell growth against the NCI-H460, A549 and MDA-MB-231 lines was evaluated. The complexes did not show greater potency than cisplatin, although they did have greater efficacy, especially for the complex derived from HL 1 .

Protein kinase C (PKC) comprises a family of highly related serine/threonine protein kinases involved in multiple signaling pathways, which control cell proliferation, survival, and differentiation. The role of PKCα in cancer has been studied for many years. However, it has been impossible to establish whether PKCα acts as an oncogene or a tumor suppressor. Here, we analyzed the importance of PKCα in cellular processes such as proliferation, migration, or apoptosis by inhibiting its gene expression in a luminal A breast cancer cell line (MCF-7). Differential expression analysis and phospho-kinase arrays of PKCα-KD vs. PKCα-WT MCF-7 cells identified an essential set of proteins and oncogenic kinases of the JAK/STAT and PI3K/AKT pathways that were down-regulated, whereas IGF1R, ERK1/2, and p53 were up-regulated. In addition, unexpected genes related to the interferon pathway appeared down-regulated, while PLC, ERBB4, or PDGFA displayed up-regulated. The integration of this information clearly showed us the usefulness of inhibiting a multifunctional kinase-like PKCα in the first step to control the tumor phenotype. Then allowing us to design a possible selection of specific inhibitors for the unexpected up-regulated pathways to further provide a second step of treatment to inhibit the proliferation and migration of MCF-7 cells. The results of this study suggest that PKCα plays an oncogenic role in this type of breast cancer model. In addition, it reveals the signaling mode of PKCα at both gene expression and kinase activation. In this way, a wide range of proteins can implement a new strategy to fine-tune the control of crucial functions in these cells and pave the way for designing targeted cancer therapies.

Introduction: The Mediterranean diet (MD) has been shown to be a good tool for the prevention of obesity and other chronic noncommunicable diseases (NCDs) and to have a low environmental impact. The aim of the present study was to evaluate the relationship between declared morbidity, lifestyles and other sociodemographic factors with high adherence to the MD (AMD) in an adult population in southeastern Spain., Material and Methods: We conducted a cross-sectional study of a sample ( n = 2728) representative of a non-institutionalized population ≥16 years. The data corresponded to the 2010-11 Nutrition Survey of the Valencian Community. The AMD was assessed using the Mediterranean Diet Adherence Screener questionnaire. The association of variables and high AMD was assessed by univariate and multivariate logistic regression determining crude and adjusted odds ratios., Results: Multivariate analysis showed that age 45 years or older, living with a partner, eating between meals, and not smoking were associated with high AMD. The age groups 45-64 years and 65 years or older showed the strongest association with high AMD in both sexes., Conclusion: The investigation showed a generational loss of AMD. People older than 45 years and living in company are more likely to adhere to DM, the risk group being young people living alone and smokers.

In the last few years, an increasing interest in the neuroprotective effect of cannabinoids has taken place. The aim of the present work was to study the effects of modulating cannabinoid receptor 1 (CB1) in the context of light induced retinal degeneration (LIRD), using an animal model that resembles many characteristics of human age-related macular degeneration (AMD) and other degenerative diseases of the outer retina. Sprague Dawley rats ( n = 28) were intravitreally injected in the right eye with either a CB1 agonist (ACEA), or an antagonist (AM251). Contralateral eyes were injected with respective vehicles as controls. Then, rats were subjected to continuous illumination (12,000 lux) for 24 h. Retinas from 28 animals were processed by GFAP-immunohistochemistry (IHC), TUNEL technique, Western blotting (WB), or qRT-PCR. ACEA-treated retinas showed a significantly lower number of apoptotic nuclei in the outer nuclear layer (ONL), lower levels of activated Caspase-3 by WB, and lower levels of glial reactivity by both GFAP-IHC and WB. qRT-PCR revealed that ACEA significantly decreased the expression of Bcl-2 and CYP1A1. Conversely, AM251-treated retinas showed a higher number of apoptotic nuclei in the ONL, higher levels of activated Caspase-3 by WB, and higher levels of glial reactivity as determined by GFAP-IHC and WB. AM251 increased the expression of Bcl-2, Bad, Bax, Aryl hydrocarbon Receptor (AhR), GFAP, and TNFα. In summary, the stimulation of the CB1 receptor, previous to the start of the pathogenic process, improved the survival of photoreceptors exposed to LIRD. The modulation of CB1 activity may be used as a neuroprotective strategy in retinal degeneration and deserves further studies., 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., (Copyright © 2022 Soliño, Larrayoz, López, Rey-Funes, Bareiro, Loidl, Girardi, Caltana, Brusco, Martínez and López-Costa.)

Purpose: The purpose of this study is to determine whether the use of a surgical navigation system in total knee replacement (TKR) enables beginner and intermediate surgeons to achieve clinical PROM outcomes as good as those conducted by expert surgeons in the long term., Methods: We enrolled 100 consecutive patients whose total navigated knee arthroplasty (TKA) was performed in our institution from 2008 to 2010. According to the principal surgeon's surgical experience, the patients were divided into three groups: (1) beginner surgeons, with no more than 30 previous knee replacement performances, (2) intermediate surgeons, with more than 30 but not more than 300, and (3) expert surgeons, with more than 300 knee replacements. Demographic data collected on the cohort included gender, laterality, age, and body mass index (BMI). The outcome measures assessed were Forgotten Joint Score (FJS), implant positioning, limb alignment, and prosthesis survival rate. A margin of equivalence of ± 18.5 points in the FJS scale was prespecified in terms of the minimal clinically important difference (MCID) to compare the FJS results obtained in the long period between the groups of interest., Results: The mean follow-up was 11.10 ± 0.78, 10.86 ± 0.66, and 11.30 ± 0.74 years, respectively, for each of the groups. The long-term FJS mean score was 80.86 ± 21.88, 81.36 ± 23.87, and 90.48 ± 14.65 for each group. The statistical analysis proved noninferiority and equivalence in terms of the FJS results reported in the long term by patients in Groups 1 or 2 compared to those in Group 3. More specifically, it has been proved that the mean difference between groups is within the interval of equivalence defined in terms of the MCID. The overall prostheses survival rate was 93.7%., Conclusion: Navigated assisted TKA, under expert guidance, can be as effective when performed by beginner or intermediate surgeons as performed by senior surgeons regarding the accuracy of implant positioning, limb alignment, and long-term clinical outcome., Competing Interests: Conflict of InterestThe author R. Larrainzar-Garijo is a paid consultant who receives royalties from B-Braun Aesculap. The other authors have no conflicts of interest to declare concerning this study., (© The Author(s) 2022.)

Severe bacterial infections (SBI) have become less frequent in children with sickle cell disease (SCD) in the last decades. However, because of their potential risk of SBI, they usually receive empirical therapy with broad-spectrum antibiotics when they develop fever and are hospitalized in many cases. We performed a prospective study including 79 SCD patients with fever [median age 4.1 (1.7-7.5) years, 78.5% males; 17 of the episodes were diagnosed with SBI and 4 of them were confirmed] and developed a risk score for the prediction of SBI. The optimal score included CRP > 3 mg/dl, IL-6 > 125 pg/ml and hypoxemia, with an AUC of 0.91 (0.83-0.96) for the prediction of confirmed SBI and 0.86 (0.77-0.93) for possible SBI. We classified the patients in 3 groups: low, intermediate and high risk of SBI. Our risk-score-based management proposal could help to safely minimize antibiotic treatments and hospital admissions in children with SCD at low risk of SBI., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Continuous illumination induces the degeneration of photoreceptors. This animal model of light-induced retinal degeneration resembles many characteristics of human degenerative diseases of the outer retina, such as age-related macular degeneration. This work aimed to evaluate the potential neuroprotective effect of the modulation of adenosine A2A receptor in the model of light-induced retinal degeneration. Sprague-Dawley rats were intravitreally injected in the right eye with either CGS 21680, an adenosine A2A receptor agonist, or SCH 58261, an adenosine A2A receptor antagonist. Contralateral eyes were injected with respective vehicles as control. Then, rats were subjected to continuous illumination (12,000 lux) for 24 h. Retinas were processed by glial fibrillary acidic protein (GFAP) immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technique, Western blotting (WB), and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Another group of rats was subjected to functional studies by electroretinography. Animals treated with CGS21680 showed a significant increase of apoptotic nuclei in the outer nuclear layer and a significant increase of GFAP immunoreactive area of the retinas but did not alter WB nor electroretinography results. qRT-PCR showed that CGS 21680 significantly increased the expression of interleukin-1β. On the opposite, SCH 58261 significantly decreased apoptotic nuclei in the outer nuclear layer and GFAP immunoreactive area of the retinas. It also significantly decreased GFAP and activated caspase-3 levels as measured by WB and preserved retinal function, as treated eyes showed significantly greater amplitudes of a- and b-waves and oscillatory potentials. qRT-PCR revealed that SCH 58261 significantly decreased the expression of tumor necrosis factor-α. These results show that the blockade of the A2A receptor before the start of the pathogenic process is neuroprotective, as it prevents light-induced retinal damage. The use of A2A receptor antagonists deserves to be evaluated in retinal degenerative diseases., 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., (Copyright © 2022 Soliño, Larrayoz, López, Rey-Funes, Bareiro, Loidl, Girardi, Martínez and López-Costa.)

Social determinants of health are a major contributing factor to health inequalities and have important effects on the health of the population. The aim of the study was to estimate the prevalence of overweight/obesity in native and immigrant children aged 2-14 years residing in Spain, and to explore its relationship with socioeconomic factors, habits, and living and health conditions. This study used data from the 2017 Spanish National Health Survey, which collects health information on the population residing in Spain. Multivariate logistic regression models were fitted to estimate the risk of overweight/obesity controlling for the variables of interest. The final sample consisted of 2351 households. Children of immigrant origin had a significantly higher overall prevalence of overweight and/or obesity than natives, both in boys (40.5% vs. 29.5%) and girls (44.8% vs. 30.3%), and a higher adjusted risk of overweight/obesity (OR = 1.67). In addition, it has been observed that children of immigrant origin were at higher risk of consuming sugary soft drinks, exercising less, and using screens more. In conclusion, the increased risk of having different habits that may contribute to developing excess weight and of having overweight/obesity in children with a migrant background should guide public health policies and interventions, emphasizing those groups at higher risk and incorporating considerations of socioeconomic inequalities.

This study aimed to clarify the relations between morphological awareness and literacy skills in Spanish and English in young simultaneous bilingual learners. Guided by theoretical perspectives on the associations between morphological awareness and word- versus sentence-level literacy skills, and their transfer between bilinguals' two languages, we asked bilingual children ( N = 90; M = 8.07 years old) to complete dual-language literacy assessments. First, we observed cross-linguistic differences in the associations between morphology and reading. In English, morphological awareness was directly related to word reading and reading comprehension, whereas in Spanish, the association with reading comprehension was fully mediated by vocabulary and single word reading. Second, we observed cross-linguistic associations from English word reading to Spanish reading comprehension, and from Spanish reading comprehension to English reading comprehension. Our findings inform bilingual literacy theory by revealing both cross-linguistic differences and bidirectional associations between literacy skills across typologically-distinct orthographies. In particular, children's word-level skills transferred from the language of schooling (English) into their heritage language (Spanish), and their broader reading comprehension skills transferred from the heritage language to support English. Taken together, these findings support the value of bilingual heritage language maintenance for reading achievement in children's dominant language of literacy instruction.

The food industry, in response to current consumer demand for natural and functional foods, is constantly evolving and reformulating traditional products formulations. Thus, during the last decades, multiple natural sources have been investigated to replace the need to add synthetic additives. In addition, the use of natural sources can also increase the nutritional quality of the food. With this in mind, elderberry is used in the food industry for certain purposes. However, its potential is much higher than the number of applications it currently has. Its high content of anthocyanins, as well as other polyphenols and vitamins, means that it can be used by the food industry both as a colorant and as an antioxidant. In addition, the incorporation of these bioactive compounds results in functional foods, with a high antioxidant capacity. Moreover, the inclusion of elderberry products in foods formulation increases their shelf-life, but the correct amount and strategy for adding elderberry to food should be studied to ensure a positive effect on nutritional and technological properties without affecting (or improving) the sensory quality of foods. Therefore, this manuscript aims to review the main bioactive compounds present in elderberries, as well as their potential uses in the food industry.

Background: Eosinophilic esophagitis (EoE) is a T-cell-mediated disease that is caused by specific foods and results in esophageal dysfunction. Existing allergy testing modalities are not helpful when attempting to identify EoE-causal foods necessitating empiric food elimination and recurrent endoscopy. The goal of this study was to identify and compare allergen-specific immune features that can be assayed in a minimally invasive manner to predict clinical food allergy in EoE., Methods: We obtained blood samples from control subjects (n = 17), subjects with clinical EoE milk allergy (n = 17), and subjects with immunoglobulin E-mediated milk allergy (n = 9). We measured total and milk-specific plasma immunoglobulin G (IgG)4 levels and peripheral memory CD4 + T helper (T H ) cell proliferation and cytokine production after stimulation with endotoxin-depleted milk proteins. Sensitivity and specificity for predicting clinical EoE milk allergy were calculated and compared between approaches., Results: Total and milk-specific IgG4 levels were not significantly different between control subjects and subjects with clinical EoE milk allergy. Stimulation with milk proteins caused T H lymphocytes from subjects with clinical EoE milk allergy to proliferate more (%P1 of 38.3 ± 4.6 vs. 12.7 ± 2.8, p < 0.0001), and produce more type 2 cytokines (%IL-4 + of 33.7 ± 2.8 vs. 6.9 ± 1.6, p < 0.0001) than cells from control subjects. Milk-dependent memory T H -cell proliferation (sensitivity and specificity of 88% and 82%, respectively) and interleukin 4 (IL-4) production (sensitivity and specificity of 100%) most strongly predicted clinical EoE milk allergy., Conclusions: Peripheral markers of allergen-specific immune activation may be useful in identifying EoE-causal foods. Assaying milk-dependent IL-4 production by circulating memory T H lymphocytes most accurately predicts clinical EoE milk allergy., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Cell death plays a critical role in inflammatory responses. During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores that mediate cell lysis and IL-1 cytokine release. Terminal cell lysis and IL-1β release following caspase activation can be uncoupled in certain cell types or in response to particular stimuli, a state termed hyperactivation. However, the factors and mechanisms that regulate terminal cell lysis downstream of GSDMD cleavage remain poorly understood. In the course of studies to define regulation of pyroptosis during Yersinia infection, we identified a line of Card19-deficient mice (Card19lxcn) whose macrophages were protected from cell lysis and showed reduced apoptosis and pyroptosis, yet had wild-type levels of caspase activation, IL-1 secretion, and GSDMD cleavage. Unexpectedly, CARD19, a mitochondrial CARD-containing protein, was not directly responsible for this, as an independently-generated CRISPR/Cas9 Card19 knockout mouse line (Card19Null) showed no defect in macrophage cell lysis. Notably, Card19 is located on chromosome 13, immediately adjacent to Ninj1, which was recently found to regulate cell lysis downstream of GSDMD activation. RNA-seq and western blotting revealed that Card19lxcn BMDMs have significantly reduced NINJ1 expression, and reconstitution of Ninj1 in Card19lxcn immortalized BMDMs restored their ability to undergo cell lysis in response to caspase-dependent cell death stimuli. Card19lxcn mice exhibited increased susceptibility to Yersinia infection, whereas independently-generated Card19Null mice did not, demonstrating that cell lysis itself plays a key role in protection against bacterial infection, and that the increased infection susceptibility of Card19lxcn mice is attributable to loss of NINJ1. Our findings identify genetic targeting of Card19 being responsible for off-target effects on the adjacent gene Ninj1, disrupting the ability of macrophages to undergo plasma membrane rupture downstream of gasdermin cleavage and impacting host survival and bacterial control during Yersinia infection., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Opher S. Kornfeld and Bettina L. Lee are employees of Genentech.

Background & Aims: In recent years, there has been an increased interest in analyzing the mathematical performance of students with learning difficulties in order to provide them with teaching methods adapted to their needs. In particular, the importance of studying the type of informal strategy that students use when solving problems has been highlighted. Observing how these strategies emerge and develop in children with learning difficulties is crucial, as it allows us to understand how they develop a subsequent understanding of arithmetic operations. In this paper we study the effect of explicit instruction in addition strategies, focusing on the minimum addend strategy, and analyze the difficulties that arise during this process., Methods: An adapted multiple-probe design across students with a microgenetic approach was employed to assess the effectiveness of the teaching instruction and the acquisition of the minimum addend strategy while solving addition word problems. The participants were three primary-school children (two boys and one girl) with learning difficulties, one of them diagnosed with autism spectrum disorder. The instruction on the minimum addend strategy was sequenced into levels of abstraction based on the addends represented with and without manipulatives., Results: The results show that the three participants were able to acquire the minimum addend strategy and transfer it to two-step problems. They all showed difficulties during the instructional process, with quantity comparison difficulties predominating. The instruction provided to address these and other difficulties is detailed for each participant., Conclusions: The teaching of the minimum addend strategy has proven effective, and all three students acquired it throughout the instruction. The results concerning the student diagnosed with autism spectrum disorder are especially interesting given the lack of studies that focus on the strategies employed by students with this disorder to solve arithmetic problems. In this sense, the use of the microgenetic approach was especially useful to observe the type of spontaneous strategies used by this participant, and how they varied in response to the instruction., Implications: Each study participant faced different difficulties and needed different periods of time to assimilate the new strategy. Conclusions are drawn for educators to help children with learning difficulties advance to more sophisticated strategies, so they can acquire these and subsequent mathematical concepts., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Sepsis management remains one of the most important challenges in modern clinical practice. Rapid progression from sepsis to septic shock is practically unpredictable, hence the critical need for sepsis biomarkers that can help clinicians in the management of patients to reduce the probability of a fatal outcome. Circulating nucleoproteins released during the inflammatory response to infection, including neutrophil extracellular traps, nucleosomes, and histones, and nuclear proteins like HMGB1, have been proposed as markers of disease progression since they are related to inflammation, oxidative stress, endothelial damage, and impairment of the coagulation response, among other pathological features. The aim of this work was to evaluate the actual potential for decision making/outcome prediction of the most commonly proposed chromatin-related biomarkers (i.e., nucleosomes, citrullinated H3, and HMGB1). To do this, we compared different ELISA measuring methods for quantifying plasma nucleoproteins in a cohort of critically ill patients diagnosed with sepsis or septic shock compared to nonseptic patients admitted to the intensive care unit (ICU), as well as to healthy subjects. Our results show that all studied biomarkers can be used to monitor sepsis progression, although they vary in their effectiveness to separate sepsis and septic shock patients. Our data suggest that HMGB1/citrullinated H3 determination in plasma is potentially the most promising clinical tool for the monitoring and stratification of septic patients.

HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo , tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches., 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., (Copyright © 2021 Vaquero-Yuste, Juarez, Molina-Alejandre, Molanes-López, López-Nares, Suárez-Trujillo, Gutiérrez-Calvo, López-García, Lasa, Gómez, Fernández-Cruz, Rodrígez-Sainz, Arnaiz-Villena and Martín-Villa.)

PKCε is highly expressed in mast cells and plays a fundamental role in the antigen-triggered activation of the allergic reaction. Although its regulation by diacylglycerols has been described, its regulation by acidic phospholipids and how this regulation leads to the control of downstream vesicle secretion is barely known. Here, we used structural and evolutionary studies to find the molecular mechanism that explains the selectivity of the C1B domain of PKCε by Phosphatidic Acid (PA). This resided in a collection of Arg residues that form a specific rim on the outer surface of the C1B domain, around the diacylglycerol binding cleft. In RBL-2H3 cells, this basic rim allowed the kinase to respond specifically to phosphatidic acid signals that induced its translocation to the plasma membrane and subsequent activation. Further experiments in cells that overexpress PKCε and a mutant of the PA binding site, showed that PA-dependent PKCε activation increased vesicle degranulation in RBL-2H3 cells, and this correlated with increased SNAP23 phosphorylation. Over-expression of PKCε in these cells also induced an increase in the number of docked vesicles containing SNAP23, when stimulated with PA. This accumulation could be attributed to the stabilizing effect of phosphorylation on the formation of the SNARE complex, which ultimately led to increased release of content in the presence of Ca 2+ during the fusion process. Therefore, these findings reinforce the importance of PA signaling in the activation of PKCε, which could be an important target to inhibit the exacerbated responses of these cells in the allergic reaction., (Copyright © 2021. Published by Elsevier B.V.)

Background: Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI)., Methods: A prospective, case-control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed., Results: A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence rate of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences rates, respectively)., Conclusion: We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management., (© 2021. The Author(s).)

We propose to investigate brain electrophysiological alterations associated with Parkinson's disease through a novel adaptive dynamical model of the network of the basal ganglia, the cortex and the thalamus. The model uniquely unifies the influence of dopamine in the regulation of the activity of all basal ganglia nuclei, the self-organised neuronal interdependent activity of basal ganglia-thalamo-cortical circuits and the generation of subcortical background oscillations. Variations in the amount of dopamine produced in the neurons of the substantia nigra pars compacta are key both in the onset of Parkinson's disease and in the basal ganglia action selection. We model these dopamine-induced relationships, and Parkinsonian states are interpreted as spontaneous emergent behaviours associated with different rhythms of oscillatory activity patterns of the basal ganglia-thalamo-cortical network. These results are significant because: (1) the neural populations are built upon single-neuron models that have been robustly designed to have eletrophysiologically-realistic responses, and (2) our model distinctively links changes in the oscillatory activity in subcortical structures, dopamine levels in the basal ganglia and pathological synchronisation neuronal patterns compatible with Parkinsonian states, this still remains an open problem and is crucial to better understand the progression of the disease., (© The Author(s) 2020.)

Introduction: Background: chronic non-communicable diseases represent a challenge for public health, and the Mediterranean diet (MD) has been identified as an alternative for their prevention. Aim: the study aimed to evaluate, in a sample of the adult population of the Comunitat Valenciana, the association between lifestyle and sociodemographic factors with high adherence to MD. Methods: a cross-sectional study of a sample (n = 2,728) representative of the population ≥ 16 years of age. The data were collected from the Comunitat Valenciana Nutrition Survey 2010-11. MD adherence was assessed using the Mediterranean Diet Adherence Screener questionnaire. The association of the variables with high MD adherence was tested using univariate and multivariate logistic regression, determining the crude and adjusted odds ratios. Results: a multivariate analysis showed that age, type of cohabitation, country of birth, eating between meals, and smoking were associated with high adherence to MD. The age groups of 45-64 years and 65 years or older showed the greatest association with high adherence to MD in both sexes. Living with a partner was positively associated with high adherence to MD in men, women, and the age group of 45-64 years. Conclusion: a generational loss of MD adherence was observed. Younger people and those who do not live with a partner showed the highest risk of not adhering to the Mediterranean dietary pattern.

To determine and compare the antimicrobial effect of Hibiscus sabdariffa calyx extracts, six types of commercial mouthwashes, and chlorhexidine on Streptococcus mutans , Streptococcus sanguinis , Capnocytophaga gingivalis , and Staphylococcus aureus . Two varieties of H. sabdariffa cultivated in Mexico were used. Aqueous, methanolic, ethanolic, acetonic, and ethyl acetate extracts were obtained from H. sabdariffa calyces. Six different types of mouthwash (Astringosol ® , Colgate plax-ice-infinity ® , Crest pro-health ® , Dental max ® , Equate ® , and Listerine zero ® ) and chlorhexidine (0.12%) were purchased at a pharmacy. The antimicrobial activity of the H. sabdariffa calyx extracts, mouthwashes, and chlorhexidine was determined by the agar disc diffusion technique. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of all solutions were determined by the broth dilution method and the pour plate technique, respectively. Also, the effect of H. sabdariffa extracts and chlorhexidine on permeability of the bacterial membrane was determined by the violet crystal assay. All H. sabdariffa calyx extracts and chlorhexidine showed antibacterial activity against all oral pathogenic bacteria. The mouthwashes showed lower antibacterial effect than H. sabdariffa extracts and chlorhexidine. Dental max showed no antibacterial effect. The MICs and MBCs, respectively, for H. sabdariffa extracts were between 5-20 and 10-20 mg/mL; and for chlorhexidine, between 3-4 and 3-5 mg/mL. For the Listerine ® , the MIC and MBC values were between 20-25 and 25-33 mg/mL, respectively. The results of the crystal violet test indicate that H. sabdariffa calyx extracts and chlorhexidine alter the permeability of the bacterial membrane. All H. sabdariffa extracts and chlorhexidine showed significantly greater antimicrobial effect than mouthwashes. This is the first report in which the antimicrobial effect of the H. sabdariffa calyx extracts, mouthwashes, and chlorhexidine is compared.

TGF-β1 is involved in tumour growth. Four TGFB1 SNPs and TGF-β1 production by stimulated PBMC were determined in seventy-eight gastric adenocarcinoma patients. In addition, TGF-β1 levels were measured in the plasma of further thirty patients. rs1800471-G/C genotype was prevalent in patients (20.7%) compared to controls (8.4%), as it also was the rs1800468 SNP-G/A genotype in stage IV patients (20.7%) compared to stage I, II and III patients, combined (10.3%). Conversely, the T/T rs1800469 SNP-T/T genotype was absent in the former group and present in 19.0% in the latter. Furthermore, the rs1800469-C/rs1800470-T (CT) haplotype was found in 15.0% of stage IV patients as compared to 3.0% of the remaining patients (3.0%) and also identifies patients with worse five-year life expectancy (P = .03). TGF-β1 synthesis by stimulated PBMCs was significantly lower in patients with the risk SNPs or haplotype, compared to the alternative genotype. Finally, TGF-β1 plasma levels were lower in patients with worse life expectancy. Analysis of TGFB1 SNPs and measurement of plasma TGF-β1 levels serves to identify patients at risk of developing a more aggressive disease., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Since the potential anticancer activity of auranofin was discovered, gold compounds have attracted interest with a view to developing anticancer agents that follow cytotoxic mechanisms other than cisplatin. Two benzimidazole gold(I) derivatives containing triphenylphosphine (Au(pben)(PPh 3 )) ( 1 ) or triethylphosphine (Au(pben)(PEt 3 )) ( 2 ) were prepared and characterized by standard techniques. X-ray crystal structures for 1 and 2 were solved. The cytotoxicity of 1 and 2 was tested in human neuroblastoma SH-SY5Y cells. Cells were incubated with compounds for 24 h with concentrations ranging from 10 µM to 1 nM, and the half-maximal inhibitory concentration (IC 50 ) was determined. 1 and 2 showed an IC 50 of 2.7 and 1.6 µM, respectively. In order to better understand the type of cell death induced by compounds, neuroblastoma cells were stained with Annexin-FITC and propidium iodide. The fluorescence analysis revealed that compounds were inducing apoptosis; however, pre-treatment with the caspase inhibitor Z-VAD did not reduce cell death. Analysis of compound effects on caspase-3 activity and reactive oxygen species (ROS) production in SH-SY5Y cells revealed an antiproliferative ability mediated through oxidative stress and both caspase-dependent and caspase-independent mechanisms.

A number of neoplasms of the central nervous system can demonstrate diffuse eosinophilic globules, known to be secretory products of the corresponding cell type, but they have not been a salient feature in descriptions of classic ependymoma. Here, we present a case of a posterior fossa ependymoma demonstrating glassy PAS-positive, diastase-resistant, eosinophilic globules with light microscopic and ultrastructural features resembling Reissner fiber, the secretory product of the subcommissural organ. While there has been a single published description of an ependymoma with intra- and extracellular granulofibrillary material suggested to be evidence of secretory differentiation, ours is the first case to demonstrate diffuse eosinophilic globules in an ependymoma. The extent of globules allowed full study by electron microscopy to provide new insight into the secretory material and the surrounding structures. Our findings suggest that neoplastic ependymal cells can recapitulate the secretory capacity of the subcommissural organ.