Polymerase Chain Reaction (PCR) is a Useful and Low-Cost Tool for Molecular Sexing Psittaciformes under Human Care: An Example of a Collaborative Approach in Mexico.

Sex determination in monomorphic birds is a precondition for captive breeding programs and management and conservation strategies for threatened species. Most species of the order Psittaciformes often present complications since these birds lack external sexual phenotypic traits, making it impossible to differentiate males and females. In the present study, we used molecular techniques to determine the sex of 31 individuals belonging to nine species of the order Psittaciformes kept under human care at the Akumal Monkey Sanctuary & Rescued Animals in Quintana Roo, Mexico. This is a useful and low-cost methodology based on the analysis of the conserved region of the CHD1 gene, which was amplified by PCR with two sets of primers: P8/P2 and 2550F/2718 R. All individuals were successfully sexed with the first set of primers, while only 28 out of 31 samples (90%) could be amplified with the second set. Out of the 31 individuals analyzed, fifteen are female, and seventeen are male. This information represents a handy tool for adequately managing birds under human care, resulting in their reproduction and eventual reintegration into their natural habitat.

Anti-predator defences are linked with high levels of genetic differentiation in frogs.

Predator-prey interactions have been suggested as drivers of diversity in different lineages, and the presence of anti-predator defences in some clades is linked to higher rates of diversification. Warning signals are some of the most widespread defences in the animal world, and there is evidence of higher diversification rates in aposematic lineages. The mechanisms behind such species richness, however, are still unclear. Here, we test whether lineages that use aposematism as anti-predator defence exhibit higher levels of genetic differentiation between populations, leading to increased opportunities for divergence. We collated from the literature more than 3000 pairwise genetic differentiation values across more than 700 populations from over 60 amphibian species. We find evidence that over short geographical distances, populations of species of aposematic lineages exhibit greater genetic divergence relative to species that are not aposematic. Our results support a scenario where the use of warning signals could restrict gene flow, and suggest that anti-predator defences could impact divergence between populations and potentially have effects at a macro-evolutionary scale.

Influence of standard culture conditions and effect of oleoresin from the microalga Haematococcus pluvialis on splenic cells from healthy Balb/c mice - a pilot study.

In this work, we used splenocytes from healthy mice to study the effects of the two most commonly used cell culture media (A, B) with different compositions of redox reagents. The incubation of cells for 24 h resulted in a significant decrease in viability and metabolic activity of splenocytes, and the negative effects of incubation in medium B were more pronounced. In standard conditions, oxidative stress in cells was manifested by reduced mitochondrial potential, and this effect correlated with the transition of 58.3% of cells to the early stage of apoptosis under reducing conditions of medium A and up to 66.1% of cells under super-reducing conditions in medium B, suggesting altered cell physiology. High levels of ROS/RNS activated transcription factor Nrf2, superoxide dismutase 1, and catalase. The higher mRNA levels of these genes were under the conditions of medium B, whose super-reducing environment in combination with the environment of conventional incubators proved to be less suitable for the cells compared to medium A. Treatment of the cells with a lower concentration (10 µg/ml) of oleoresin obtained from the microalga H. pluvialis partially eliminated the negative effects of cultivation. Higher concentration of oleoresin (40 µg/ml) was slightly cytotoxic, due to the significant antioxidant effect of astaxanthin, the main bioactive component of the extract, which eliminated most of the ROS/RNS acting as signalling molecules. This study shows that the standard culture conditions do not reflect the physiological in vivo cell conditions; therefore, they are not generally suitable for incubation of all cell types.

Estigma en mujeres de peso alto a través de un análisis fenomenológico interpretativo

Tener peso alto es una característica que ha sido devaluada y denigrada socialmente, convirtiendo a las personas de cuerpos grandes en víctimas de estereotipos, prejuicios y discriminación, lo que se ha denominado estigmatización por el peso, fenómeno que ocurre especialmente en mujeres. El objetivo de este estudio fue describir las experiencias de estigma de peso de mujeres con obesidad que viven en el sur de Chile. Participaron seis mujeres entre 20 y 57 años a través de entrevistas semi-estructuradas realizadas de manera remota. Mediante Análisis Fenomenológico Interpretativo se identificaron cuatro supratemas y diversos subtemas, los supratemas son: 1. La obesidad como parte de la persona. 2. Las experiencias de sentirse discriminada. 3. Todo gira en función del peso. 4. Lo que la sociedad piensa de la obesidad, los que en su conjunto permiten caracterizar la experiencia de vivir con obesidad y sufrir el estigma asociado al peso en distintos ámbitos de sus vidas, incluso en contextos sanitarios. Las consecuencias de esta experiencia son diversas y negativas, destacando el impacto que tiene en su autoestima y las constantes emociones negativas que derivan de las situaciones de discriminación. Estos resultados ponen de manifiesto la importancia de avanzar hacia la diversidad y aceptación corporal, lo que supone un desafío a la sociedad en general y en particular a los proveedores de salud, ya que se requiere de intervenciones libres de prejuicios y orientadas a la salud y el bienestar de las personas.

Carrying a high weight is a characteristic that has been devalued and socially denigrated, turning people with large bodies into victims of stereotypes, prejudice, or discrimination, which has been called weight stigmatisation, a phenomenon that occurs especially in women. The aim of this study was to describe the weight stigma experiences of women with obesity who live in southern Chile. Six women between 20 and 57 years of age participated in semi-structured interviews conducted remotely. Through Interpretative Phenomenological Analysis four supra-themes and several sub-themes were identified, the supra-themes are: 1. Obesity as part of the person. 2. Experiences of feeling discriminated. 3. Everything is about weight. 4. what society thinks of obesity, which together allow characterising the experience of living with obesity and suffering the weight stigma in different areas of their lives, including in health contexts. The consequences of this experience are diverse and negative, highlighting the impact it has on their self-esteem and the constant negative emotions that derive from discrimination situations. These results highlight the importance of moving toward body diversity and acceptance, which is a challenge for society in general and health care providers in particular, as it requires interventions free from prejudice and orientated to the health and well-being of individuals.

Variation in nest-building behaviour in birds: a multi-species approach.

Researchers have long suggested that animals with greater behavioural flexibility will be more likely to survive in face of environmental changes. However, it is unknown how this varies across species. Nest building is a behaviour directly related to the reproduction and survival of species by conferring protection from external environmental conditions. The study of nests offers a window into the behaviour of birds, and variation in nest morphology is necessarily linked to variation in building behaviours. We test whether variation in nest morphology is phylogenetically conserved by using data on nest morphology from 55 passerine species (>700 specimens) and measuring intraspecific variability in nest structure. We found that species mean and within-species variation in nest morphology are phylogenetically conserved, and that species with domed nests presented higher levels of nest morphology variation than cup nest species. We also revealed that the capacity of species to present innovative behaviours is not linked with how they vary nest morphology. Moreover, we revealed that nests from species with larger variation in clutch size and that are built by single parents are more variable. Our results help in the understanding of how behaviour and extended phenotypes evolve, and highlight the importance of exploring the phylogenetic history of behavioural flexibility when trying to predict the capacity of species to respond to novel challenges. This article is part of the theme issue 'The evolutionary ecology of nests: a cross-taxon approach'.

Isolation of Mycosporine-like Amino Acids from Red Macroalgae and a Marine Lichen by High-Performance Countercurrent Chromatography: A Strategy to Obtain Biological UV-Filters.

Marine organisms have gained considerable biotechnological interest in recent years due to their wide variety of bioactive compounds with potential applications. Mycosporine-like amino acids (MAAs) are UV-absorbing secondary metabolites with antioxidant and photoprotective capacity, mainly found in organisms living under stress conditions (e.g., cyanobacteria, red algae, or lichens). In this work, five MAAs were isolated from two red macroalgae (Pyropia columbina and Gelidium corneum) and one marine lichen (Lichina pygmaea) by high-performance countercurrent chromatography (HPCCC). The selected biphasic solvent system consisted of ethanol, acetonitrile, saturated ammonium sulphate solution, and water (1:1:0.5:1; v:v:v:v). The HPCCC process for P. columbina and G. corneum consisted of eight separation cycles (1 g and 200 mg of extract per cycle, respectively), whereas three cycles were performed for of L. pygmaea (1.2 g extract per cycle). The separation process resulted in fractions enriched with palythine (2.3 mg), asterina-330 (3.3 mg), shinorine (14.8 mg), porphyra-334 (203.5 mg) and mycosporine-serinol (46.6 mg), which were subsequently desalted by using precipitation with methanol and permeation on a Sephadex G-10 column. Target molecules were identified by HPLC, MS, and NMR.

Astaxanthin Extract from Haematococcus pluvialis and Its Fractions of Astaxanthin Mono- and Diesters Obtained by CCC Show Differential Antioxidant and Cytoprotective Effects on Naïve-Mouse Spleen Cells.

Carotenoids are the most abundant lipid-soluble phytochemicals and are used as dietary supplements to protect against diseases caused by oxidative stress. Astaxanthin, a xanthophyll carotenoid, is a very potent antioxidant with numerous beneficial effects on cellular functions and signaling pathways. In this study, using spleen cells from healthy Balb/c mice, we report the bio-functional effects of an astaxanthin-rich extract (EXT) prepared from the microalga Haematococcus pluvialis and its astaxanthin monoesters-rich fraction (ME) and astaxanthin diesters-rich fraction (DE) obtained by fractionation of EXT using countercurrent chromatography (CCC). After incubation under standard culture conditions (humidity, 37 °C, 5% CO2, atmospheric oxygen), the viability of untreated splenocytes, as determined by the trypan blue exclusion assay, the MTT assay, and the neutral red assay, decreases to approximately 75% after 24 h compared with naïve splenocytes. This effect correlated with the decrease in mitochondrial membrane potential and the transition of ~59% of cells to the early stage of apoptosis, as well as with the decreased ROS production, indicating that hyperoxia in cell-culture deteriorates cell functions. They are restored or stimulated by co-cultivation with EXT, ME, and DE up to 10 µg/mL in the order EXT > DE > ME, suggesting that esterification increases bioavailability to cells in vitro. ROS and H2O2 concentrations reflect mRNA transcriptional activity of Nrf2, superoxide dismutase 1 (SOD1), catalase, and glutathione peroxidase 1, as well as SOD-mediated ROS conversion, whereas they inversely correlate with iNOS-mediated NO production. The highest-tested concentration of EXT, ME, and DE (40 µg/mL) is detrimental to cells, probably because of the overwhelming scavenging activity of astaxanthin and its esters for the reactive oxygen/nitrogen species required for cellular functions and signal transduction at low physiological concentrations. In this study, we demonstrate that differential activities of ME and DE contribute to the final antioxidant and cytoprotective effects of astaxanthin extract, which is beneficial in preventing a wide range of ROS-induced adverse effects, with DE being more effective. In addition, the selection of physioxia-like conditions for pharmacological research is highlighted.

Herramientas educativas audiovisuales inclusivas: diseño y aplicación

Fundamento: lograr que las personas con necesidades educativas especiales se formen sobre la base del mérito, las capacidades propias, el esfuerzo, la perseverancia y sobre todo que tomen en cuenta sus potencialidades, es un reto. Objetivo: diseñar videos accesibles para estudiantes, incluyendo aquellos con necesidades educativas especiales, así como evaluar su aplicabilidad. Métodos: se diseñaron videos y su aplicación en base al modelo teórico Technological Pedagogical and Content Knowledge: conocimiento curricular, conocimiento pedagógico y conocimiento tecnológico, con énfasis en la adaptación a necesidades educativas especiales para facilitar el aprendizaje. La evaluación consideró la aplicación del instrumento "Evaluación de herramientas educativas audiovisuales" desde los parámetros: atención, curiosidad, utilidad en repaso, estímulo a aprender, ayuda al entendimiento y el deseo de reutilizarlos. Resultados: se diseñaron tres videos con elementos de accesibilidad para estudiantes, incluyendo estudiantes con necesidades educativas especiales. En la evaluación se consiguió, de forma general, el aumento de la calificación en las pruebas parciales de la asignatura tras el empleo de los videos; la percepción de uso determinó la satisfacción como recurso de aprendizaje. Conclusiones: el diseño de recursos audiovisuales accesibles sin diferencia con estudiantes en condición de discapacidad beneficia a todo el grupo de estudiantes, en el marco de la igualdad.

Background: to achieve that people with special educational needs are trained on the basis of merit, their own abilities, effort, perseverance and above all that they take into account their potential, is a challenge. Objective: design accessible videos for students, including those with special educational needs, as well as evaluate their applicability. Methods: videos and their application were designed based on the Technological Pedagogical and Content Knowledge theoretical model: curricular knowledge, pedagogical knowledge and technological knowledge, with emphasis on adaptation to special educational needs to facilitate learning. The evaluation considered the application of the instrument "Evaluation of audiovisual educational tools" from the parameters: attention, curiosity, usefulness in review, stimulus to learn, help to understand and the desire to reuse them. Results: three videos were designed with accessibility elements for students, including students with special educational needs. In the evaluation, it was achieved, in a general way, the qualification increase in the partial tests of the subject after the use of the videos; the use's perception determined the satisfaction as a learning resource. Conclusions: the design of accessible audiovisual resources without difference with students with disabilities, benefits the entire group of students, within the equality framework.

Evaluation of counselling materials for hybrid cardiac rehabilitation in a low-resource setting: Perceptions of patients and providers.

OBJECTIVE: This study evaluated the usefulness of a booklet as support material for counseling focused on self-efficacy and therapist interaction in the course of counseling in a hybrid CR program (i.e., supervised and unsupervised sessions) developed for low-resource settings. METHODS: Counseling material was developed by a multidisciplinary team, with patient input. Using multi-methods, first input from patients from six centers in Chile was sought through a telephone survey (cross-sectional). Second, input from physiotherapists delivering the intervention at all centres was solicited qualitatively through a focus group on Zoom. Content analysis was performed using a deductive-thematic approach. RESULTS: Seventy-one patients were included. All (100 %) participants responded that the materials were easy to understand, contained suggestions applicable to daily life, captured their attention and was useful for future questions. The booklet overall was rated 6.7 ± 0.6/7 %, and 98.2 % were satisfied with the counselling. Overall themes from the six deliverers related to the CR intervention (e.g., well manualized protocols for counselling), the deliverer (e.g., expertise to deliver) and patients (e.g., found information useful). CONCLUSION: The usefulness of the counseling together with the supporting booklet was established by patients and delivering professionals. PRACTICE IMPLICATIONS: Thus, with some final refinement, this resource can be disseminated for use by other Spanish CR programs.

Research and Publication Trends in Pediatric Surgery in Latin America: A Bibliometric and Visual Analysis from 2012 to 2021.

INTRODUCTION: Pediatric surgery is a developing specialty with increasing volume in Latin America. However, the research and scientific activity trends carried out in this region in recent years are unknown. This study aimed to analyze and visualize Latin American research in pediatric surgery from 2012 to 2021. MATERIAL AND METHODS: Bibliometric cross-sectional study of scientific articles on pediatric surgery published by Latin American authors from 2012 to 2021 in Scopus was performed. Statistical and visual analysis was performed with R programming language and VOS viewer. RESULTS: 449 articles were found. Observational studies (44.7%; n = 201), case reports (20.4%; n = 92) and narrative reviews (11.4%; n = 51) were found to be the most common study designs. The published articles were predominantly monocentric (73.1%; n = 328), only 17% (n = 76) involved authors from 2 or more countries, and mostly there was no collaboration with high-income countries (80.6%; n = 362). The Journal of Pediatric Surgery was the journal with the highest volume of articles published (n = 37). The most used terms were Laparoscopy, Complications, and Liver Transplantation, and the countries with the highest number of articles published were Brazil and Argentina. CONCLUSIONS: This study found a progressive increase in the scientific activity of Latin authors in pediatric surgery from 2012 to 2021. The evidence produced was mainly from observational studies and case reports, predominantly conducted in Brazil. Multinational and international collaboration was low; the most frequent topics of interest were laparoscopy and minimally invasive surgery. LEVELS OF EVIDENCE: IV.

[Relation between weight stigma and emotional eating: an approach from structural equation modeling]. / Relación entre estigma de peso y alimentación emocional: una aproximación desde el modelo de ecuaciones estructurales.

Introduction: Introduction: dietary intake has been shown to be one of the main factors influencing weight gain, and weight stigma contributes to increased emotional eating. However, the factors that mediate this relationship have been less studied. Objective: the aim of this study was to identify the relationship between weight stigma and emotional eating, and whether this relationship is mediated by internalizing weight bias and psychological distress. Methods: a non-probabilistic sample of 332 people from the general population (192 women and 140 men) answered self-report psychological instruments and provided anthropometric measurements. Results: through structural equation analysis (SEM), direct relationships were identified, among which the relationship between weight stigma and emotional eating stands out (ß = 0.422, p < 0.001), in addition to the indirect relationship between these variables mediated by internalized weight bias and psychological distress (ßindirect = 0.016, p = < 0.05). The model had good indicators of goodness of fit and explained 85 % of the variance. Conclusion: the results show the importance of including psychological and behavioral variables in the treatment of emotional eating in people with overweight and obesity, as well as addressing these issues from public policies to reduce the associated stigma that still prevails in society.

Introducción: Introducción: se ha demostrado que la ingesta alimentaria es uno de los principales factores que influyen en el incremento del peso y que el estigma de peso contribuye a una mayor alimentación emocional. Sin embargo, los factores que median esta relación han sido menos estudiados. Objetivo: el objetivo de este estudio fue identificar la relación que existe entre estigma de peso y alimentación emocional, y si esta relación está mediada por la internalización del sesgo de peso y el malestar psicológico. Métodos: una muestra no probabilística de 332 personas de población general (192 mujeres y 140 hombres) respondió instrumentos psicológicos de autorreporte y proporcionó medidas antropométricas. Resultados: por medio de un análisis de ecuaciones estructurales (SEM), se identificaron relaciones directas, entre las que destaca la relación del estigma de peso y alimentación emocional (ß = 0,422, p < 0,001), además de la relación indirecta entre estas variables mediante la internalización del sesgo de peso y malestar psicológico (ßindirecto = 0,016, p = < 0,05). El modelo tuvo buenos indicadores de bondad de ajuste y explicó un 85 % de la varianza. Conclusión: los resultados muestran la importancia de incluir variables psicológicas y conductuales en el tratamiento de la alimentación emocional en personas con sobrepeso y obesidad, así como de abordar estos temas desde políticas públicas para disminuir el estigma asociado que aún impera en la sociedad.

Liver decompensation is a frequent cause of treatment discontinuation and prognostic factor in intermediate-advanced HCC.

INTRODUCTION AND OBJECTIVES: With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. PATIENTS AND METHODS: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. CONCLUSIONS: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists.

Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults.

BACKGROUND: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. METHODS: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. FINDINGS: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. INTERPRETATION: Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. FUNDING: The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.

Problemas de salud mental en universitarios durante la pandemia por COVID-19: ¿qué tipo de ayuda buscan? / Mental health problems in university students during the COVID-19 pandemic: What kind of help do they seek?

Introducción: La pandemia por COVID-19 ha tenido un impacto negativo en el bienestar psicológico de la población, siendo los jóvenes un grupo especialmente vulnerable. Objetivo: El presente estudio se propuso examinar los niveles de búsqueda de ayuda (formal e informal) para problemas en salud mental y sus variables asociadas en una muestra de estudiantes universitarios de la Región de La Araucanía, en el contexto de la pandemia por COVID-19. Método: A través de un muestreo no probabilístico por conveniencia, se reclutó a 500 estudiantes de entre 18 y 29 años. Se describió y comparó su nivel de búsqueda de ayuda, así como variables que podrían obstaculizarla o facilitarla, según género. Adicionalmente, se estimaron modelos de regresión lineal múltiple diferenciados por género, con la búsqueda de ayuda informal como variable criterio. Resultados: Se evidenció una renuencia general a buscar ayuda (formal e informal) tanto en hombres como mujeres, una mayor experimentación de malestar psicológico y mayor conocimiento sobre salud mental en mujeres. Finalmente, se observaron diferencias en los predictores de la búsqueda de ayuda informal entre hombres y mujeres, siendo el apoyo social y las emociones negativas en pandemia los únicos comunes entre géneros. Conclusión: Se discuten los bajos niveles de búsqueda de ayuda evidenciados, y las diferencias observadas en variables asociadas, en función de la brecha de género en salud mental.

Introduction: The COVID-19 pandemic has impacted the psychological well-being of the population, with young people being a particularly vulnerable group. Aim: The present study examines help-seeking intention for mental health problems and associated variables among male and female university students in La Araucanía Region during the COVI-19 pandemic. Method: A sample of 500 students aged 18 to 29 was recruited through non-probabilistic convenience sampling. Help-seeking levels and facilitating or hindering variables were compared by gender. Multiple linear regression models were estimated separately by gender to predict the criterion variable of informal help-seeking. Results: The results indicate that both men and women are reluctant to seek help (formal and informal). Women reported higher levels of psychological distress and greater knowledge about mental health than men. Differences in predictors of informal help-seeking between men and women are evidenced, with social support and negative emotions in pandemic being the only common predictors between genders. Conclusion: The low levels of help-seeking evidenced, and the differences observed in associated variables based on the gender gap in mental health, are discussed.

Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections.

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.

Role of Protein Kinase A Activation in the Immune System with an Emphasis on Lipopolysaccharide-Responsive and Beige-like Anchor Protein in B Cells.

Cyclic AMP-dependent protein kinase A (PKA) is a ubiquitous enzymatic complex that is involved in a broad spectrum of intracellular receptor signaling. The activity of PKA depends on A-kinase anchoring proteins (AKAPs) that attach to PKAs close to their substrates to control signaling. Although the relevance of PKA-AKAP signaling in the immune system is evident in T cells, its relevance in B and other immune cells remains relatively unclear. In the last decade, lipopolysaccharide-responsive and beige-like anchor protein (LRBA) has emerged as an AKAP that is ubiquitously expressed in B and T cells, specifically after activation. A deficiency of LRBA leads to immune dysregulation and immunodeficiency. The cellular mechanisms regulated by LRBA have not yet been investigated. Therefore, this review summarizes the functions of PKA in immunity and provides the most recent information regarding LRBA deficiency to deepen our understanding of immune regulation and immunological diseases.

Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children.

Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.

Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial.

Background: The development of vaccines to control the coronavirus disease 2019 (COVID-19) pandemic progression is a worldwide priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac separated by 2 (0-14 schedule) or 4 weeks (0-28 schedule); 2302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern (VOCs) between schedules. Stimulation of peripheral blood mononuclear cells (PBMCs) with Mega pools of Peptides (MPs) induced the secretion of interferon (IFN)-γ and the expression of activation induced markers in CD4+ T cells for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-γ secretion. Conclusions: Immunization with CoronaVac in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. Funding: Ministry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. Clinical trial number: NCT04651790.

Female offspring gestated in hypothyroxinemia and infected with human Metapneumovirus (hMPV) suffer a more severe infection and have a higher number of activated CD8+ T lymphocytes.

Maternal thyroid hormones (THs) are essential for the appropriate development of the fetus and especially for the brain. Recently, some studies have shown that THs deficiency can also alter the immune system development of the progeny and their ability to mount an appropriate response against infectious agents. In this study, we evaluated whether adult mice gestated under hypothyroxinemia (Hpx) showed an altered immune response against infection with human metapneumovirus (hMPV). We observed that female mice gestated under Hpx showed higher clinical scores after seven days of hMPV infection. Besides, males gestated under Hpx have higher lung viral loads at day seven post-infection. Furthermore, the female offspring gestated in Hpx have already reduced the viral load at day seven and accordingly showed an increased proportion of activated (CD71+ and FasL+) CD8+ T cells in the lungs, which correlated with a trend for a higher histopathological clinical score. These results support that T4 deficiency during gestation might condition the offspring differently in males and females, enhancing their ability to respond to hMPV.

Model to Predict Healthcare Behaviors: Comparison of a Chilean and Mexican Sample.

(1) Background: Adherence to treatment and medical check-ups are important for health outcomes, but low adherence to treatment is a common phenomenon. Thus, we aimed to examine the role of cultural beliefs about physicians, perceived mistreatment, and emotions associated with the experience of mistreatment as an antecedent of healthcare behavior among Chilean and Mexican primary care patients using Betancourt's model for the study of health behavior. (2) Methods: This is a multivariate cross-sectional study with a non-probabilistic sample of 326 Mexican and 337 Chilean participants. Multigroup structural equation modeling was used to test the structural relations among the cultural and psychological variables as determinants of healthcare avoidance behavior. (3) Results: The results revealed a pattern of associations that work in the same way for Chilean and Mexican samples. Negative cultural beliefs about physicians have a direct effect on avoidance behaviors in healthcare. In addition, this effect is mediated through psychological factors, such as perception of mistreatment and negative emotions associated with mistreatment. (4) Conclusions: A structural invariance test showed that the perception of mistreatment and negative emotions were less intense for Chileans than Mexicans. In contrast, the association between negative emotions and avoidance behaviors was less intense for Mexicans.