Pediatric Emergency Cases in the First Year of the COVID-19 Pandemic in a Tertiary-Level Emergency Setting

Aim: Emergency cases are uncommon events in the pediatric emergency setting. This study aimed to evaluate the effect of the Coronavirus disease 2019 (COVID-19) pandemic by describing the number and type of pediatric emergency cases that arrived at the pediatric emergency department (PED) of a tertiary-level children's hospital in Italy. Methods: We performed a retrospective study, collecting the main features of pediatric emergency patients who arrived during the first year of the COVID-19 pandemic (March 2020-February 2021) compared to the pre-pandemic period (March 2016-February 2020). Results: During the study period, 112,168 patients were visited at the PED, and 237 (0.21%) were emergency cases, median age of 4 years (IQR: 1-12). In the first year of the pandemic, 42 children were coded as emergency cases compared to 195 (49/year) during the pre-pandemic period. The proportion of emergency cases was stable (0.27% during the COVID-19 period versus 0.20% during the pre-COVID-19 period, p = 0.19). No differences were found regarding the age, gender, hour of arrival, and outcome of patients. We found a significant decrease in the proportion of emergency cases related to respiratory diseases (9/42, 21.4% during the COVID-19 period versus 83/195 during the pre-COVID-19 period (42.6%), p = 0.01). Conclusion: In conclusion, our data suggest that the pandemic had a more significant impact on respiratory emergency cases than on pediatric emergencies in general

Nanoscale Operando Characterization of Electrolyte-Gated Organic Field-Effect Transistors Reveals Charge Transport Bottlenecks

Charge transport in electrolyte-gated organic field-effect transistors (EGOFETs) is governed by the microstructural property of the semiconducting thin film that is in direct contact with the electrolyte. Therefore, a comprehensive nanoscale operando characterization of the active channel is crucial to pinpoint various charge transport bottlenecks for rational and targeted optimization of the devices. Here, the local electrical properties of EGOFETs are systematically probed by in-liquid scanning dielectric microscopy (in-liquid SDM) and a direct picture of their functional mechanism at the nanoscale is provided across all operational regimes, starting from subthreshold, linear to saturation, until the onset of pinch-off. To this end, a robust interpretation framework of in-liquid SDM is introduced that enables quantitative local electric potential mapping directly from raw experimental data without requiring calibration or numerical simulations. Based on this development, a straightforward nanoscale assessment of various charge transport bottlenecks is performed, like contact access resistances, inter- and intradomain charge transport, microstructural inhomogeneities, and conduction anisotropy, which have been inaccessible earlier. Present results contribute to the fundamental understanding of charge transport in electrolyte-gated transistors and promote the development of direct structure–property–function relationships to guide future design rules

Analysis of the Vehicle-Bicycles Interaction on Two-Lane Rural Roads Using a Driving Simulator Based on Field Data

[EN] The presence of cyclists on Spanish two-lane rural roads is common, so they have to interact with motor vehicles. Due to the speed differential and vulnerability of cyclists, overtaking is one of the most dangerous and frequent interactions. Therefore, a minimum distance of 1.5 m must be observed. The overtaking maneuver depends on road section and cyclist group distribution. Interaction between cyclists and vehicles has been characterized in the past but overtaking to cyclist groups has barely been studied. This study uses a driving simulator to analyze how the presence of cyclists and their group configuration affect traffic operation and safety on two-lane rural roads. A fixed driving simulator has been adapted to incorporate cyclists, using speed and lateral position obtained from field studies. Based on field data, a physical scenario and different traffic scenarios have been recreated, so volunteers can drive the simulator ¿ emulating a motor vehicle ¿ tracking their speed, lateral position, and other variables. These results can be compared to those observed for checking the validity of this methodology. The driving simulator offers some results which are difficult to obtain through other methodologies, enabling a better analysis of the phenomenon. By sorting different bicycle patterns and including several volunteers, the impact of bicycle pelotons on traffic performance and safety can be characterized. This will help in offering recommendations to integrate cyclists and motor vehicles in a safer way.This study was part of a research project titled Improvement of safety and operation of twolane rural roads with cyclists (Bike2Lane) (TRA 2016-8089-R) subsidized by Spanish Ministry of Science and Innovation. In addition, the authors would like to thank the Road Department of the Valencian Provincial Council, and General Directorate of Traffic of Spain, for their cooperation in field data gathering.Dols Ruiz, JF.; Molina, J.; Moll Montaner, S.; López-Maldonado, G.; Camacho-Torregrosa, FJ.; García García, A. (2021). Analysis of the Vehicle-Bicycles Interaction on Two-Lane Rural Roads Using a Driving Simulator Based on Field Data. Universidad de Burgos. 1363-1376. https://doi.org/10.36443/97884184651231363137

Analysis of the vehicle-bicycles interaction on two-lane rural roads using a driving simulator based on field data

[EN] The presence of cyclists on Spanish two-lane rural roads is common, so they have to interact with motor vehicles. Due to the speed differential and vulnerability of cyclists, overtaking is one of the most dangerous and frequent interactions. Therefore, a minimum distance of 1.5 m must be observed. The overtaking manoeuvre depends on road section and cyclist group distribution. Interaction between cyclists and vehicles has been characterized in the past but overtaking to cyclist groups has barely been studied. This study uses a driving simulator to analyse how the presence of cyclists and their group configuration affect traffic operation and safety on two-lane rural roads. A fixed driving simulator has been adapted to incorporate cyclists, using speed and lateral position obtained from field studies. Based on field data, a physical scenario and different traffic scenarios have been recreated, so volunteers can drive the simulator ¿ emulating a motor vehicle ¿ tracking their speed, lateral position, and other variables. These results can be compared to those observed for checking the validity of this methodology. The driving simulator offers some results which are difficult to obtain through other methodologies, enabling a better analysis of the phenomenon. By sorting different bicycle patterns and including several volunteers, the impact of bicycle pelotons on traffic performance and safety can be characterized. This will help in offering recommendations to integrate cyclists and motor vehicles in a safer way.This study was part of a research project entitled Improvement of safety and operation of two-lane rural roads with cyclists (Bike2Lane) (TRA 2016-8089-R) subsidized by Spanish Ministry of Science and Innovation. In addition, the authors would like to thank the Road Department of the Valencian Provincial Council, and General Directorate of Traffic of Spain, for their cooperation in field data gathering.Dols Ruiz, JF.; Molina, J.; Moll Montaner, S.; López-Maldonado, G.; Camacho-Torregrosa, FJ.; García García, A. (2021). Analysis of the vehicle-bicycles interaction on two-lane rural roads using a driving simulator based on field data. Transportation Research Procedia. (58):543-550. https://doi.org/10.1016/j.trpro.2021.11.0725435505

PKM2 subcellular localization is involved in oxaliplatin resistance acquisition in HT29 human colorectal cancer cell lines

Ajuts: Beca bianual de la Fundació Olga Torres 2008-2009Chemoresistance is the main cause of treatment failure in advanced colorectal cancer (CRC). However, molecular mechanisms underlying this phenomenon remain to be elucidated. In a previous work we identified low levels of PKM2 as a putative oxaliplatin-resistance marker in HT29 CRC cell lines and also in patients. In order to assess how PKM2 influences oxaliplatin response in CRC cells, we silenced PKM2 using specific siRNAs in HT29, SW480 and HCT116 cells. MTT test demonstrated that PKM2 silencing induced resistance in HT29 and SW480 cells and sensitivity in HCT116 cells. Same experiments in isogenic HCT116 p53 null cells and double silencing of p53 and PKM2 in HT29 cells failed to show an influence of p53. By using trypan blue stain and FITC-Annexin V/PI tests we detected that PKM2 knockdown was associated with an increase in cell viability but not with a decrease in apoptosis activation in HT29 cells. Fluorescence microscopy revealed PKM2 nuclear translocation in response to oxaliplatin in HCT116 and HT29 cells but not in OXA-resistant HTOXAR3 cells. Finally, by using a qPCR Array we demonstrated that oxaliplatin and PKM2 silencing altered cell death gene expression patterns including those of BMF, which was significantly increased in HT29 cells in response to oxaliplatin, in a dose and time-dependent manner, but not in siPKM2-HT29 and HTOXAR3 cells. BMF gene silencing in HT29 cells lead to a decrease in oxaliplatin-induced cell death. In conclusion, our data report new non-glycolytic roles of PKM2 in response to genotoxic damage and proposes BMF as a possible target gene of PKM2 to be involved in oxaliplatin response and resistance in CRC cells

Model simulation of heavy metals in river systems: case study the Negro river basin

This work describes a water quality model for heavy metals simulation in river systems. The proposed strategy comprises an 1D modeling approach with an ADZ-QUASAR extension to represent the behavior of heavy metals. This methodology seeks to strengthen their predictive capability based on the integration of variables which play an important role in the adsorption and desorption of these particles. The methodology was implemented in a reach of the Negro river (eastern side of Antioquia, Colombia), using Chromium, Copper and Nickel as heavy metals, because these are the heavy metals representative of the currents in the study area. Results are showing, with some degree of uncertainty, the capacity of the methodology to predict the behavior of environmental interesting substances, which makes it an important management tool

Madness at the Hospital of Innocents of Seville (1436-1840)

En el presente trabajo se estudia el funcionamiento y desarrollo histórico del Hospital de San Cosme y San Damián, la primera y más antigua de las instituciones existentes en Sevilla cuya función principal era la de «curar a los pobres enfermos faltos de juicio». Concretamente se estudia el origen, la evolución y significación del hospital a lo largo de los siglos, así como la información disponible acerca de los ingresos, patologías y tratamientos que constan en la documentación. También se exploran las competencias y funciones de las diferentes figuras que formaban parte del servicio a los enfermos.This article studies the functioning and the historical development of the Hospital de San Cosme y San Damián, the first and oldest institution of Seville which main function was «healing the insane without sense». Specifically, we study the origin, evolution and significance of the hospital through the centuries, as well as the available information regarding admissions, pathologies and treatment contained in the documentation. Moreover we explore the responsibilities and roles of the people who were part of the assistance to the insane

A New Set of in Silico Tools to Support the Interpretation of ATM Missense Variants Using Graphical Analysis

Establishing the pathogenic nature of variants in ATM, a gene associated with breast cancer and other hereditary cancers, is crucial for providing patients with adequate care. Unfortunately, achieving good variant classification is still difficult. To address this challenge, we extended the range of in silico tools with a series of graphical tools devised for the analysis of computational evidence by health care professionals. We propose a family of fast and easy-to-use graphical representations in which the impact of a variant is considered relative to other pathogenic and benign variants. To illustrate their value, the representations are applied to three problems in variant interpretation. The assessment of computational pathogenicity predictions showed that the graphics provide an intuitive view of pre-diction reliability, complementing and extending conventional numerical reliability indexes. When applied to variant of unknown significance populations, the representations shed light on the nature of these variants and can be used to prioritize variants of unknown significance for further studies. In a third application, the graphics were used to compare the two versions of the ATM-adapted American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines, obtaining valuable information on their relative virtues and weaknesses. Finally, a server [ATMision (ATM missense in silico interpretation online)] was generated for users to apply these representations in their variant interpretation problems, to check the ATM-adapted guidelines' criteria for computational evidence on their variant(s) and access different sources of information. (J Mol Diagn 2024, 26: 17-28; https://doi.org/10.1016/j.jmoldx.2023.09.009

Immune Correlates of Natural HIV Elite Control and Simultaneous HCV Clearance—Supercontrollers

HIV-elite controllers are a minority group of HIV-infected patients with the ability to maintain undetectable HIV viremia for long time periods without antiretroviral treatment. A small group of HIV-controllers are also able to spontaneously clear the hepatitis C virus (HCV) whom we can refer to as “supercontrollers.” There are no studies that explore immune correlates looking for the mechanisms implicated in this extraordinary phenomenon. Herein, we have analyzed HCV- and HIV-specific T-cell responses, as well as T, dendritic and NK cell phenotypes. The higher HCV-specific CD4 T-cell polyfunctionality, together with a low activation and exhaustion T-cell phenotype was found in supercontrollers. In addition, the frequency of CD8 CD161high T-cells was related with HIV- and HCV-specific T-cells polyfunctionality. Interesting features regarding NK and plasmacytoid dendritic cells (pDCs) were found. The study of the supercontroller's immune response, subjects that spontaneously controls both chronic viral infections, could provide further insights into virus-specific responses needed to develop immunotherapeutic strategies in the setting of HIV cure or HCV vaccination

A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients

Background Gene panel testing by massive parallel sequencing has increased the diagnostic yield but also the number of variants of uncertain significance. Clinical interpretation of genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic variants increase the risk of cancer, particularly breast cancer. For this reason, ATM is included in most hereditary cancer panels. It is a large gene, showing a high number of variants, most of them of uncertain significance. Hence, we initiated a collaborative effort to improve and standardize variant classification for the ATM gene. Methods Six independent laboratories collected information from 766 ATM variant carriers harboring 283 different variants. Data were submitted in a consensus template form, variant nomenclature and clinical information were curated, and monthly team conferences were established to review and adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria to ATM, which were used to classify 50 representative variants. Results Amid 283 different variants, 99 appeared more than once, 35 had differences in classification among laboratories. Refinement of ACMG/AMP criteria to ATM involved specification for twenty-one criteria and adjustment of strength for fourteen others. Afterwards, 50 variants carried by 254 index cases were classified with the established framework resulting in a consensus classification for all of them and a reduction in the number of variants of uncertain significance from 58% to 42%. Conclusions Our results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management.FEDER funds-a way to build Europe PI19/00553 PI16/00563 PI16/01898 SAF2015-68016-RGeneralitat de Catalunya 2017SGR1282 2017SGR496CERCA Program: Government of CataloniaXunta de GaliciaInstituto de Salud Carlos III. AES PI19/00340Spanish Government SAF2016-80255-REuropean Commission EFA086/15Instituto de Salud Carlos III European Commissio