Timing of standard chow exposure determines the variability of mouse phenotypic outcomes and gut microbiota profile.

Standard chow diet contributes to reproducibility in animal model experiments since chows differ in nutrient composition, which can independently influence phenotypes. However, there is little evidence of the role of timing in the extent of variability caused by chow exposure. Here, we measured the impact of diet (5V5M, 5V0G, 2920X, and 5058) and timing of exposure (adult exposure (AE), lifetime exposure (LE), and developmental exposure (DE)) on growth & development, metabolic health indicators, and gut bacterial microbiota profiles across genetically identical C57BL6/J mice. Diet drove differences in macro- and micronutrient intake for all exposure models. AE had no effect on measured outcomes. However, LE mice exhibited significant sex-dependent diet effects on growth, body weight, and body composition. LE effects were mostly absent in the DE model, where mice were exposed to chow differences from conception to weaning. Both AE and LE models exhibited similar diet-driven beta diversity profiles for the gut bacterial microbiota, with 5058 diet driving the most distinct profile. Diet-induced beta diversity profiles were sex-dependent for LE mice. Compared to AE, LE drove 9X more diet-driven differentially abundant genera, majority of which were the result of inverse effects of 2920X and 5058. Our findings demonstrate that lifetime exposure to different chow diets has the greatest impact on reproducibility of experimental measures that are common components of preclinical mouse model studies. Importantly, weaning DE mice onto a uniform diet is likely an effective way to reduce unwanted phenotypic variability among experimental models.

Analysis of 26 STR loci (PowerPlex® Fusion 6C System) in a mestizo population from Mexico city.

BACKGROUND: Short tandem repeats (STRs) are the most widely used genetic markers in forensic genetics. Therefore, it is essential to document genetic population data of new kits designed for human identification purposes to enable laboratories to use these genetic systems to interpret and solve forensic casework. However, in Mexico, there are no studies with the PowerPlex Fusion 6C System, which includes 26 STRs (23 autosomal STRs and 3 Y-STRs). METHODS AND RESULTS: 600 DNA samples from Mexico City were subjected to genotyping using the PowerPlex Fusion 6C System. For autosomal STRs, 312 different alleles were observed. Combined PE and PD were 99.999999809866% and 99.99999999999999999999999818795%, respectively. Genetic distances and AMOVA test showed low but significant differentiation between Mexican populations. CONCLUSIONS: The results reported in this work demonstrate the efficacy of this system for human identification purposes in the population studied and justify its possible application in other Mexican Mestizo populations.

Forensic parameters and population structure based on 21 autosomal STRs with the investigator 24plex QS in mestizos from the Mexico City population.

Allele frequencies and forensic parameters for 21 STR autosomal markers (CSF1PO, D10S1248, D12S391, D13S317,D16S539, D18S51, D19S433, D1S1656,D21S11, D22S1045, D2S1338, D2S441, D3S1358, D5S818, D7S820, D8S1179, FGA, SE33, TH01, TPOX and vWA) were reported in 289 unrelated individuals from Mexico City, Mexico. In addition, an interpopulation analysis was performed including other world populations. In brief, the established population database of 21 autosomal STR markers in the present work is adequate for human identification purposes.

Reassessing the role of milrinone in the treatment of heart failure and pulmonary hypertension in neonates and children: a systematic review and meta-analysis.

To evaluate milrinone's impact on pediatric cardiac function, focusing on its specific role as an inotrope and lusitrope, while considering its systemic and pulmonary vasodilatory effects. Search of PubMed, EMBASE, and the Cochrane Library up to August 2023. We included all studies that evaluated milrinone in children under 18 years old in neonatal, pediatric, or cardiac intensive care units. We excluded case reports, studies that did not provide tabular information on milrinone's outcomes, and studies focused on non-intensive care populations. We extracted data on the research design, objectives, study sample, and results of each study, including the impact of milrinone and any associated factors. We screened a total of 9423 abstracts and 41 studies were ultimately included. Milrinone significantly improved left ventricular ejection fraction (WMD 3.41 [95% CI 0.61 - 6.21]), left ventricle shortening fraction (WMD 4.25 [95% CI 3.43 - 5.08]), cardiac index (WMD 0.50 [95% CI 0.32 to 0.68]), left ventricle output (WMD 55.81 [95% CI 4.91 to 106.72]), serum lactate (WMD -0.59 [95% CI -1.15 to -0.02]), and stroke volume index (WMD 2.95 [95% CI 0.09 - 5.82]). However, milrinone was not associated with improvements in ventricular myocardial performance index (WMD -0.01 [95% CI -0.06 to 0.04]) and ventricular longitudinal strain (WMD -2.14 [95% CI -4.56 to 0.28]). Furthermore, milrinone was not associated with isovolumetric relaxation time reduction (WMD -8.87 [95% CI -21.40 to 3.66]). CONCLUSION: Our meta-analysis suggests potential clinical benefits of milrinone by improving cardiac function, likely driven by its systemic vasodilatory effects. However, questions arise about its inotropic influence and the presence of a lusitropic effect. Moreover, milrinone's pulmonary vasodilatory effect appears relatively weaker compared to its systemic actions. Further research is needed to elucidate milrinone's precise mechanisms and refine its clinical applications in pediatric practice. WHAT IS KNOWN: • Milrinone is a phosphodiesterase III inhibitor that has been used to treat a variety of pediatric and neonatal conditions. • Milrinone is believed to exert its therapeutic effects by enhancing cardiac contractility and promoting vascular relaxation. WHAT IS NEW: • Milrinone may not have a significant inotropic effect. • Milrinone's pulmonary vasodilatory effect is less robust than its systemic vasodilatory effect.

Chronic Respiratory Diseases as a Risk Factor for Herpes Zoster Infection

Introduction: Herpes zoster (HZ) is a condition that results from the reactivation of the varicella zoster virus (VZV). Several diseases have been reported to increase the risk of developing HZ and postherpetic neuralgia (PHN). The objective of this study is to analyze the prevalence and risk factors for HZ and PHN in the most frequent chronic respiratory diseases, which are chronic obstructive pulmonary disease (COPD), asthma, lung cancer and obstructive sleep apnea (OSA). Methods: We conducted an observational, retrospective, non-interventional study between January 2012 and December 2020 based on data from the Castilla-La Mancha Regional Health System in Spain. We used the Savana Manager 3.0 artificial intelligence-enabled system to collect information from electronic medical records. Results: 31765 subjects presented a diagnosis of HZ. Mean age was 64.5 years (95%CI 64.3–64.7), and 58.2% were women. The prevalence of HZ showed an increasing trend in patients over the age of 50. A risk analysis adjusted for sex and comorbidities in COPD, asthma, lung cancer and OSA presented a higher risk of developing HZ in the first three (OR 1.16 [95%CI 1.13–1.19], 1.67 [1.63–1.71], 1.68 [1.60–1.76], respectively), which further increased in all three when associated with comorbidities. Regarding postherpetic neuralgia, an increased risk was only observed related to COPD and lung cancer (OR 1.24 [95%CI 1.23–1.25], 1.14 [1.13–1.16], respectively), further increasing when associated with comorbidities. Conclusions: In a standard clinical practice setting, the most prevalent respiratory diseases (asthma, COPD and lung cancer) are related to a higher risk of HZ and PHN. These data are fundamental to assess the potential impact of vaccination in this population. (AU)

Impact of the COVID-19 Pandemic on the Epidemiological Situation of Pulmonary Tuberculosis-Using Natural Language Processing.

BACKGROUND: We aimed to analyze the impact of the COVID-19 pandemic on pulmonary tuberculosis (TB) using artificial intelligence. To do so, we compared the real-life situation during the pandemic with the pre-2020 situation. METHODS: This non-interventional, retrospective, observational study applied natural language processing to the electronic health records of the Castilla-La Mancha region of Spain. The analysis was conducted from January 2015 to December 2020. RESULTS: A total of 2592 patients were diagnosed with pulmonary tuberculosis; 64.6% were males, and the mean age was 53.5 years (95%CI 53.0-54.0). In 2020, pulmonary tuberculosis diagnoses dropped by 28% compared to 2019. In total, 62 (14.2%) patients were diagnosed with COVID-19 and pulmonary tuberculosis coinfection in 2020, with a mean age of 52.3 years (95%CI 48.3-56.2). The main symptoms in these patients were dyspnea (27.4%) and cough (35.5%), although their comorbidities were no greater than patients with isolated TB. The female sex was more frequently affected, representing 53.4% of this patient subgroup. CONCLUSIONS: During the first year of the COVID-19 pandemic, a decrease was observed in the incidence of pulmonary tuberculosis. Women presented a significantly higher risk for pulmonary tuberculosis and COVID-19 coinfection, although the symptoms were not more severe than patients diagnosed with pulmonary tuberculosis alone.

In-Host HEV Quasispecies Evolution Shows the Limits of Mutagenic Antiviral Treatments.

Here, we report the in-host hepatitis E virus (HEV) quasispecies evolution in a chronically infected patient who was treated with three different regimens of ribavirin (RBV) for nearly 6 years. Sequential plasma samples were collected at different time points and subjected to RNA extraction and deep sequencing using the MiSeq Illumina platforms. Specifically, we RT-PCR amplified a single amplicon from the core region located in the open-reading frame 2 (ORF2). At the nucleotide level (genotype), our analysis showed an increase in the number of rare haplotypes and a drastic reduction in the frequency of the master (most represented) sequence during the period when the virus was found to be insensitive to RBV treatment. Contrarily, at the amino acid level (phenotype), our study revealed conservation of the amino acids, which is represented by a high prevalence of the master sequence. Our findings suggest that using mutagenic antivirals concomitant with high viral loads can lead to the selection and proliferation of a rich set of synonymous haplotypes that express the same phenotype. This can also lead to the selection and proliferation of conservative substitutions that express fitness-enhanced phenotypes. These results have important clinical implications, as they suggest that using mutagenic agents as a monotherapy treatment regimen in the absence of sufficiently effective viral inhibitors can result in diversification and proliferation of a highly diverse quasispecies resistant to further treatment. Therefore, such approaches should be avoided whenever possible.

Chronic Respiratory Diseases as a Risk Factor for Herpes Zoster Infection.

INTRODUCTION: Herpes zoster (HZ) is a condition that results from the reactivation of the varicella zoster virus (VZV). Several diseases have been reported to increase the risk of developing HZ and postherpetic neuralgia (PHN). The objective of this study is to analyze the prevalence and risk factors for HZ and PHN in the most frequent chronic respiratory diseases, which are chronic obstructive pulmonary disease (COPD), asthma, lung cancer and obstructive sleep apnea (OSA). METHODS: We conducted an observational, retrospective, non-interventional study between January 2012 and December 2020 based on data from the Castilla-La Mancha Regional Health System in Spain. We used the Savana Manager 3.0 artificial intelligence-enabled system to collect information from electronic medical records. RESULTS: 31765 subjects presented a diagnosis of HZ. Mean age was 64.5 years (95%CI 64.3-64.7), and 58.2% were women. The prevalence of HZ showed an increasing trend in patients over the age of 50. A risk analysis adjusted for sex and comorbidities in COPD, asthma, lung cancer and OSA presented a higher risk of developing HZ in the first three (OR 1.16 [95%CI 1.13-1.19], 1.67 [1.63-1.71], 1.68 [1.60-1.76], respectively), which further increased in all three when associated with comorbidities. Regarding postherpetic neuralgia, an increased risk was only observed related to COPD and lung cancer (OR 1.24 [95%CI 1.23-1.25], 1.14 [1.13-1.16], respectively), further increasing when associated with comorbidities. CONCLUSIONS: In a standard clinical practice setting, the most prevalent respiratory diseases (asthma, COPD and lung cancer) are related to a higher risk of HZ and PHN. These data are fundamental to assess the potential impact of vaccination in this population.

Post-natal prognostic factors in CDH: experience of 11 years in a referral center in Brazil.

OBJECTIVE: To describe post-natal risk factors associated with death in Newborns (NB) with Congenital Diaphragmatic Hernia (CDH) in a Brazilian reference center. METHODS: In this retrospective cohort study, post-natal clinical factors of all NB diagnosed with CDH were reviewed in an 11-year period (2007‒2018). The primary outcome was death. Secondary outcomes included clinical features, prognostic indexes, type of mechanical ventilation, complications during hospitalization and surgical repair. RESULTS: After applying the exclusion criteria, the authors analyzed 137 charts. Overall mortality was 59% (81/137), and the highest rates were observed for low-birth-weight NB (87%), syndromic phenotype (92%), and those with major malformations (100%). Prognostic indexes such as Apgar, SNAPPE-II and 24hOI (best oxygenation index in 24 hours) were all associated with poor evolution. In a multivariate analysis, only birth weight and 24hOI were statistically significant risk factors for mortality, with a reduction in mortality risk of 17.1% (OR = 0.829, 95% IC 0.72‒0.955, p = 0.009) for each additional 100g at birth and an increase by 26.5% (OR = 1.265, 95% IC 1.113‒1.436, p = 0.0003) for each unitary increase at the 24hOI. CONCLUSION: Prognostic indexes are an important tool for predicting outcomes and improving resource allocation. Post-natal risk factors may be more suitable for settings where antenatal diagnosis is not universal. Classical risk factors, such as prematurity, low birth weight, higher need for supportive care, and poorer prognostic indexes were associated with mortality in our CDH population.

Clinical Profile of Patients with Idiopathic Pulmonary Fibrosis in Real Life.

OBJECTIVE: The objective of this study is to define the real-life clinical profile and therapeutic management of patients with idiopathic pulmonary fibrosis using artificial intelligence. METHODS: We have conducted an observational, retrospective, non-interventional study using data from the Castilla-La Mancha Regional Healthcare Service (SESCAM) in Spain between January 2012 and December 2020. The Savana Manager 3.0 artificial intelligence platform was used to collect information from electronic medical records by applying natural language processing. RESULTS: Our study includes 897 subjects whose diagnosis was compatible with idiopathic pulmonary fibrosis; 64.8% were men, with a mean age of 72.9 years (95% CI 71.9-73.8), and 35.2% were women, with a mean age of 76.8 years (95% CI 75.5-78). Patients who had a family history of IPF (98 patients; 12%) were younger and predominantly female (53.1%). Regarding treatment, 45% of patients received antifibrotic therapy. Patients who had undergone lung biopsy, chest CT, or bronchoscopy were younger than the patient population in whom these studies were not completed. CONCLUSIONS: This study has used artificial intelligence techniques to analyze a large population over a 9-year period and determine the situation of IPF in standard clinical practice by identifying the patient clinical profile, use of diagnostic tests and therapeutic management.

Bioinformatic Tools for NGS-Based Metagenomics to Improve the Clinical Diagnosis of Emerging, Re-Emerging and New Viruses.

Epidemics and pandemics have occurred since the beginning of time, resulting in millions of deaths. Many such disease outbreaks are caused by viruses. Some viruses, particularly RNA viruses, are characterized by their high genetic variability, and this can affect certain phenotypic features: tropism, antigenicity, and susceptibility to antiviral drugs, vaccines, and the host immune response. The best strategy to face the emergence of new infectious genomes is prompt identification. However, currently available diagnostic tests are often limited for detecting new agents. High-throughput next-generation sequencing technologies based on metagenomics may be the solution to detect new infectious genomes and properly diagnose certain diseases. Metagenomic techniques enable the identification and characterization of disease-causing agents, but they require a large amount of genetic material and involve complex bioinformatic analyses. A wide variety of analytical tools can be used in the quality control and pre-processing of metagenomic data, filtering of untargeted sequences, assembly and quality control of reads, and taxonomic profiling of sequences to identify new viruses and ones that have been sequenced and uploaded to dedicated databases. Although there have been huge advances in the field of metagenomics, there is still a lack of consensus about which of the various approaches should be used for specific data analysis tasks. In this review, we provide some background on the study of viral infections, describe the contribution of metagenomics to this field, and place special emphasis on the bioinformatic tools (with their capabilities and limitations) available for use in metagenomic analyses of viral pathogens.

Analysis of a hypersaline drought-prone estuary reveals low density and diversity of fish eggs and larvae.

We analyzed fish eggs and larvae in an estuary under severe drought conditions. We detected an inverse salinity gradient, with values increasing from the mouth to the upper estuary. Egg densities decreased from the estuarine mouth to the upstream areas following the salinity increase for all three mesh net sizes. This pattern was also found for the density of larvae, which decreased in estuarine regions with hypersalinity (38 to 62). The low diversity constituted only nine fish species, which were classified as anadromous (Anchoa hepsetus), estuarine and marine (Bathygobius soporator, Hippocampus reidi, Eucinostomus sp., and Diapterus auratus), marine estuarine-opportunist (Caranx latus and Bardiella rochus), and marine stragglers (Echeneis naucrates and Haemulon sp.). In addition, we observed an oversimplification of the assemblage to include stress-tolerant estuarine and marine species. Our baseline results suggest that this hypersaline estuarine ecosystem has lower densities and diversity than a healthy mangrove system.

ERRATUM: Kidney decontamination during perfusion for transplantation procedure: In vitro and ex vivo viability analysis.

Organ transplantations have an increasing medical relevance. It is becoming a regular procedure with an increase in individuals waiting for organs. The increase in the number of discarded organs is mostly due to the donor's bacterial and/or viral infection. In this article, we are demonstrating the feasibility of reduction of the bacterial load in the kidney model by using Ultraviolet-C (UV-C) as a germicidal agent in circulating liquids. Using Staphylococcus aureus as a bacteria model, we were able to demonstrate that in less than 30 min of liquid circulation and associated to irradiation, the bacterial load of the perfusate Custodiol® HTK, histidine-tryptophan-ketoglutarate (solution with 5 log CFU ml-1 ), was fully eliminated. A modeling approach was created to verify the possibility of bacterial load decrease, when an organ (here, a renal experimental model) is present in the circuit, releasing a varied rate of microorganisms over time, while the solution is irradiated. Finally, we use an ex vivo model with a swine kidney, circulating in the preservation solution with a Lifeport® Kidney Transporter machine, to demonstrate that we can contaminate the organ and then promote the elimination of the microbiological load. The results show the feasibility of the technique.

Atualidades e perspectivas futuras da comissão consultiva em avaliação psicológica / Current affairs and future perspectives of the consultative commission on psychological assessment (CCAP) / Actualidades y perspectivas de futuro de la comisión consultiva en evaluación psicológica

A Comissão Consultiva em Avaliação Psicológica (CCAP), atrelada ao Sistema de Avaliação de Testes Psicológicos (SATEPSI) do Conselho Federal de Psicologia (CFP), tem como objetivos emitir pareceres acerca de solicitações advindas da avaliação psicológica(AP), elaborar e propor atualizações de documentos técnicos e normativos do CFP relativos à AP, elaborar e propor diretrizes para o ensino e formação continuada em AP, conduzir o processo de avaliação dos instrumentos submetidos ao SATEPSI e discutir temas e propor ações no âmbito da AP. Nos últimos 20 anos, a CCAP vem buscando atender a esses objetivos, indicando novos caminhos para a área. Nesse sentido, este artigo tem como objetivo apresentar as principais atualidades e movimentos da CCAP, indicando caminhos possíveis e perspectivas futuras para a área de AP. São discutidas as ações atuais que vêm sendo desenvolvidas pela CCAP, bem como as ações futuras delineadas que buscam promover uma AP cada vez mais democrática. Concluímos que a AP é uma prática do(a) psicólogo(a) que deve ser operacionalizada com compromisso ético, atrelada aos direitos humanos e à justiça, com embasamento científico e alinhada às mudanças sociais.(AU)

The Consultative Commission on Psychological Assessment (CCAP), affiliated with the Psychological Test Evaluation System under the Federal Council of Psychology (CFP), has the following objectives: to provide expert opinions on requests stemming from psychological assessments (PA), to draft and propose updates to the CFP technical and normative documents pertaining to PA, to formulate and recommend guidelines for education and ongoing professional development in PA, to oversee the evaluation process of instruments submitted to SATEPSI, and to engage in discussions and propose initiatives within the PA. Over the past two decades, CCAP has diligently worked to achieve these goals, charting new avenues in the field. In this context, this study aims to describe the most current developments and initiatives of CCAP and outline prospective directions and future outlooks for the PA. This study delves into the current initiatives undertaken by CCAP and the prospective actions delineated to foster a progressively more inclusive PA. Thus, we claim that PA is a practice inherent to psychologists that demands ethical commitment, alignment with human rights and justice, a solid scientific foundation, and adaptation to evolving social dynamics.(AU)

La Comisión Consultiva en Evaluación Psicológica (CCAP), vinculada al Sistema de Evaluación de Pruebas Psicológicas (SATEPSI) del Consejo Federal de Psicología (CFP), tiene como objetivo emitir opinión técnica sobre solicitudes derivadas de la evaluación psicológica (EP), elaborar y proponer actualizaciones de documentos técnicos y normativos del CFP relacionados con EP, desarrollar y proponer lineamientos para la enseñanza y la formación continua en EP, conducir el proceso de evaluación de los instrumentos presentados al SATEPSI y discutir temas y proponer acciones en el ámbito de EP. Durante los últimos veinte años, la CCAP ha buscado alcanzar estos objetivos indicando nuevos caminos para el área. En este sentido, este artículo tiene como objetivo presentar las principales actualidades y movimientos de la CCAP indicando posibles caminos y perspectivas de futuro para el área de EP. Se discuten las acciones actuales que ha desarrollado la CCAP, así como las acciones futuras perfiladas que buscan promover una EP cada vez más democrática. Se concluye que la EP es una práctica del psicólogo que debe ponerse en práctica con compromiso ético, vinculada a los derechos humanos y la justicia, con base científica y alineada con los cambios sociales.(AU)

Post-natal prognostic factors in CDH: experience of 11 years in a referral center in Brazil

Abstract Objective To describe post-natal risk factors associated with death in Newborns (NB) with Congenital Diaphragmatic Hernia (CDH) in a Brazilian reference center. Methods In this retrospective cohort study, post-natal clinical factors of all NB diagnosed with CDH were reviewed in an 11-year period (2007‒2018). The primary outcome was death. Secondary outcomes included clinical features, prognostic indexes, type of mechanical ventilation, complications during hospitalization and surgical repair. Results After applying the exclusion criteria, the authors analyzed 137 charts. Overall mortality was 59% (81/137), and the highest rates were observed for low-birth-weight NB (87%), syndromic phenotype (92%), and those with major malformations (100%). Prognostic indexes such as Apgar, SNAPPE-II and 24hOI (best oxygenation index in 24 hours) were all associated with poor evolution. In a multivariate analysis, only birth weight and 24hOI were statistically significant risk factors for mortality, with a reduction in mortality risk of 17.1% (OR = 0.829, 95% IC 0.72‒0.955, p = 0.009) for each additional 100g at birth and an increase by 26.5% (OR = 1.265, 95% IC 1.113‒1.436, p = 0.0003) for each unitary increase at the 24hOI. Conclusion Prognostic indexes are an important tool for predicting outcomes and improving resource allocation. Post-natal risk factors may be more suitable for settings where antenatal diagnosis is not universal. Classical risk factors, such as prematurity, low birth weight, higher need for supportive care, and poorer prognostic indexes were associated with mortality in our CDH population.

Quasispecies Fitness Partition to Characterize the Molecular Status of a Viral Population. Negative Effect of Early Ribavirin Discontinuation in a Chronically Infected HEV Patient.

The changes occurring in viral quasispecies populations during infection have been monitored using diversity indices, nucleotide diversity, and several other indices to summarize the quasispecies structure in a single value. In this study, we present a method to partition quasispecies haplotypes into four fractions according to their fitness: the master haplotype, rare haplotypes at two levels (those present at <0.1%, and those at 0.1−1%), and a fourth fraction that we term emerging haplotypes, present at frequencies >1%, but less than that of the master haplotype. We propose that by determining the changes occurring in the volume of the four quasispecies fitness fractions together with those of the Hill number profile we will be able to visualize and analyze the molecular changes in the composition of a quasispecies with time. To develop this concept, we used three data sets: a technical clone of the complete SARS-CoV-2 spike gene, a subset of data previously used in a study of rare haplotypes, and data from a clinical follow-up study of a patient chronically infected with HEV and treated with ribavirin. The viral response to ribavirin mutagenic treatment was selection of a rich set of synonymous haplotypes. The mutation spectrum was very complex at the nucleotide level, but at the protein (phenotypic/functional) level the pattern differed, showing a highly prevalent master phenotype. We discuss the putative implications of this observation in relation to mutagenic antiviral treatment.

The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants.

The SARS-CoV-2 Omicron variant emerged showing higher transmissibility and possibly higher resistance to current COVID-19 vaccines than other variants dominating the global pandemic. In March 2020 we performed a study in clinical samples, where we found that a portion of genomes in the SARS-CoV-2 viral population accumulated deletions immediately before the S1/S2 cleavage site (furin-like cleavage site, PRRAR/S) of the spike gene, generating a frameshift and appearance of a premature stop codon. The main aim of this study was to determine the frequency of defective deletions in prevalent variants from the first to sixth pandemic waves in our setting and discuss whether the differences observed might support epidemiological proposals. The complete SARS-CoV-2 spike gene was deeply studied by next-generation sequencing using the MiSeq platform. More than 90 million reads were obtained from respiratory swab specimens of 78 COVID-19 patients with mild infection caused by the predominant variants circulating in the Barcelona city area during the six pandemic waves: B.1.5, B.1.1, B.1.177, Alpha, Beta, Delta, and Omicron. The frequency of defective genomes found in variants dominating the first and second waves was similar to that seen in Omicron, but differed from the frequencies seen in the Alpha, Beta and Delta variants. The changing pattern of mutations seen in the various SARS-CoV-2 variants driving the pandemic waves over time can affect viral transmission and immune escape. Here we discuss the putative biological effects of defective deletions naturally occurring before the S1/S2 cleavage site during adaption of the virus to human infection.

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats.

Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during adult life. Persistent triacylglyceride (TAG) accumulation in the liver, in turn, is a feature of non-alcoholic fatty liver disease (NAFLD), which serves as a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In the present study, we demonstrate that the combination of IUGR and fructose treatment during adulthood also results in increased hepatic myeloperoxidase (MPO) activity, AKT phosphorylation and serum aspartate transaminase. Growth-restricted rats also presented reduced hepatic TRIB3 and GADD45a after fructose treatment. Other markers of cell proliferation, such as Cyclin D, PCNA, Hgf and Hspa4/Hsp70 expression and the number of Ki-67 positive cells, were all increased in the liver of growth- restricted rats treated with fructose. On the other hand, the combination of IUGR and fructose treatment during adult life reduced the levels of IGF-1. In conclusion, our data indicate that after exposure to fructose, adult rats subjected to dexamethasone-induced IUGR display exacerbated molecular changes in markers of NASH and HCC.

Characteristics of 24 SARS-CoV-2-Sequenced Reinfection Cases in a Tertiary Hospital in Spain.

Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the main concern is whether reinfections are possible, and which are the associated risk factors. This study aims to describe the clinical and molecular characteristics of 24 sequence-confirmed reinfection SARS-CoV-2 cases over 1 year in Barcelona (Catalonia, Spain). Methods: Patients with > 45 days between two positive PCR tests regardless of symptoms and negative tests between episodes were initially considered as suspected reinfection cases from November 2020 to May 2021. Whole-genome sequencing (WGS) was performed to confirm genetic differences between consensus sequences and for phylogenetic studies based on PANGOLIN nomenclature. Reinfections were confirmed by the number of mutations, change in lineage, or epidemiological criteria. Results: From 39 reported suspected reinfection cases, complete viral genomes could be sequenced from both episodes of 24 patients, all were confirmed as true reinfections. With a median age of 44 years (interquartile range [IQR] 32-65), 66% were women and 58% were healthcare workers (HCWs). The median days between episodes were 122 (IQR 72-199), occurring one-third within 3 months. Reinfection episodes were frequently asymptomatic and less severe than primary infections. The absence of seroconversion was associated with symptomatic reinfections. Only one case was reinfected with a variant of concern (VOC). Conclusion: Severe acute respiratory syndrome coronavirus 2 reinfections can occur in a shorter time than previously reported and are mainly found in immunocompetent patients. Surveillance through WGS is useful to identify viral mutations associated with immune evasion.

Normatização da Bateria de Provas de Raciocínio (BPR-5) usando a Teoria de Resposta ao Item / Standardization of the Reasoning Tests Battery (BPR-5) using Item Response Theory / Estandarización de la Batería de Pruebas de Razonamiento (BPR-5) usando la teoría de respuesta al ítem

A Bateria de Provas de Raciocínio (BPR-5) é um instrumento bastante utilizado para avaliação da inteligência no Brasil, possuindo três formas: infantil (1º ao 6º ano do Ensino Fundamental), Forma A (7º ao 9º ano do Ensino Fundamental) e Forma B (Ensino Médio e Superior). Visando a possibilidade de comparar os resultados entre sujeitos que respondem a formas diferentes, o presente estudo objetivou: (a) calibrar os itens das três formas pelo modelo de Rasch, realizando a equalização por itens comuns de modo a obter uma escala equiparável para as três formas, (b) atualizar as normas expandindo a representatividade das amostras e produzindo-se normas para diferentes combinações de idade, escolaridade e sexo, (c) descrever padrões de desenvolvimento da inteligência a partir da escala, comum, produzida entre 6 e 52 anos. Dois estudos foram relatados, o primeiro sobre a calibração dos parâmetros segundo o modelo de Rasch indicando um bom ajuste ao modelo. O segundo estudo exemplificou a utilização de regressão múltipla para criação de normas para testes psicológicos, considerando as variáveis idade, escolaridade e sexo como preditoras dos escores na BPR-5. Essas três variáveis tiveram efeitos significativos explicando 8% (Raciocínio Abstrato), 13% (Raciocínio Verbal), 12% (Raciocínio Espacial), 8% (Raciocínio Numérico) e 22% (Raciocínio Mecânico).(AU)

The Reasoning Tests Battery (BPR-5) is widely used in Brazil for the assessment of intelligence. It has three different forms: children (1st to 6th grade of elementary school), Form A (7th to 9th grade of elementary school) and Form B (high school and higher education). This study describes the steps followed to create a common metric across the forms. It aimed to: (a) calibrate the items of the three forms using Rasch model, link items and equate subjects' scores across forms using the anchoring of common items method, (b) update the norms by expanding the representativeness of the samples by producing norms for different combinations of age, education and sex, and (c) describe the developmental patterns of the BPR-5 subtests across a wide age range, from 6 to 52 years. We present two studies, the first reporting the calibration of item and person parameters with the Rasch model and a good fit to the model. The second illustrated the use of multiple regression analysis to create norms for the psychological tests considering the variables age, education and gender as predictors of the BPR-5 scores. These three variables had significant effects explaining 8% (Abstract Reasoning), 13% (Verbal Reasoning), 12% (Spatial Reasoning), 8% (Numerical Reasoning) and 22% (Mechanical Reasoning) of the variance. (AU)

La Batería de Pruebas de Razonamiento (BPR-5) es un instrumento muy utilizado para la evaluación de la inteligencia en Brasil, disponiendo de tres formas: infantil (1° al 6° año de la Enseñanza Fundamental), Forma A (7° al 9° año de la Enseñanza Fundamental) y Forma B (Bachillerato y Educación Superior). Teniendo como finalidad la posibilidad de comparar los resultados entre sujetos que responden a diferentes versiones, el presente estudio tuvo como objetivo: (a) calibrar los ítems de las tres formas por el modelo de Rasch, realizando la igualación por ítems comunes a fin de obtener una escala equiparable para las tres formas, (b) actualizar las normas ampliando la representatividad de las muestras y produciendo normas para diferentes combinaciones de edad, escolarización y sexo, (c) describir patrones de desarrollo de la inteligencia a partir de la escala, común, producida entre los 6 y los 52 años. Dos estudios fueron reportados, el primer sobre la calibración de los parámetros de acuerdo con el modelo de Rasch, indicando un buen ajuste al modelo. El segundo estudio ejemplificó la utilización de regresión múltiple para crear normas para tests psicológicos, considerando las variables edad, educación y sexo como predictivos de los escores en el BPR-5. Esas tres variables tuvieron efectos significativos explicando 8% (Razonamiento Abstracto), 13% (Razonamiento Verbal), 12% (Razonamiento Espacial), 8% (Razonamiento Numérico), y 22% (Razonamiento Mecánico).(AU)