An Exploratory Approach of Clinically Useful Biomarkers of Cvid by Logistic Regression.

Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel.

Distinct SIV-specific CD8+ T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence.

Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8+ T cell functions, which requires a deeper understanding of CD8+ T cells promoting HIV control. Here we identifiy an antigen-responsive TOXhiTCF1+CD39+CD8+ T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8+ T cells and proteomic analysis of purified CD8+ T cell subsets identified TOXhiTCF1+CD39+CD8+ T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOXhiTCF1+CD39+CD8+ T cells were found at higher frequency than TCF1-CD39+CD8+ T cells in follicular microenvironments and were preferentially located in proximity of SIV-RNA+ cells. Their frequency was associated with reduced plasma viremia and lower SIV reservoir size. Highly similar TOXhiTCF1+CD39+CD8+ T cells were detected in lymph nodes from antiretroviral therapy-naive and antiretroviral therapy-suppressed people living with HIV, suggesting this population of CD8+ T cells contributes to limiting SIV and HIV persistence.

Local adaptation of Pinus leiophylla under climate and land use change models in the Avocado Belt of Michoacán.

Climate change and land use change are two main drivers of global biodiversity decline, decreasing the genetic diversity that populations harbour and altering patterns of local adaptation. Landscape genomics allows measuring the effect of these anthropogenic disturbances on the adaptation of populations. However, both factors have rarely been considered simultaneously. Based on a set of 3660 SNPs from which 130 were identified as outliers by a genome-environment association analysis (LFMM), we modelled the spatial turnover of allele frequencies in 19 localities of Pinus leiophylla across the Avocado Belt in Michoacán state, Mexico. Then, we evaluated the effect of climate change and land use change scenarios, in addition to evaluating assisted gene flow strategies and connectivity metrics across the landscape to identify priority conservation areas for the species. We found that localities in the centre-east of the Avocado Belt would be more vulnerable to climate change, while localities in the western area are more threatened by land conversion to avocado orchards. Assisted gene flow actions could aid in mitigating both threats. Connectivity patterns among forest patches will also be modified by future habitat loss, with central and eastern parts of the Avocado Belt maintaining the highest connectivity. These results suggest that areas with the highest priority for conservation are in the eastern part of the Avocado Belt, including the Monarch Butterfly Biosphere Reserve. This work is useful as a framework that incorporates distinct layers of information to provide a more robust representation of the response of tree populations to anthropogenic disturbances.

Eosinophilic esophagitis: Does age matter?

OBJECTIVES: Eosinophilic esophagitis (EoE) is often diagnosed in school-age children between 6- and 9-year-old. There is less known about those who are diagnosed with EoE that are younger than 6 years old. The objective of this study is to compare clinical presentation, comorbidities, and outcomes based on age at diagnosis of EoE. METHODS: Single-center retrospective chart review of children (<18 years) diagnosed with EoE between 2005 and 2020. We recorded demographics, clinical presentation, family history, past medical history, treatment, and endoscopic findings. Children in this cohort were classified based on age into three age groups: <2 years, 2-<6 years, and 6-<18 years. RESULTS: We identified 256 children with EoE, the mean age (SD) at the time of diagnosis was 9 (5.2) years and 184 (72%) were male. We had 164 (64%) patients with available follow-up esophagogastroduodenoscopies (EGDs) data (495 EGDs in total) of those 99/164 (60%) reached mucosal remission. In the very young children (<2 years) vomiting was the most common presentation, while poor weight gain was seen more in the 2-<6-year group in comparison to the >6-years. Food impaction and abdominal pain were most likely to present in older children 6-18 years. Combination therapy, as opposed to a single therapy, induced remission at a higher frequency in the <6-year group in comparison to the 6-<18-year group (85% vs. 66%). CONCLUSION: EoE should be considered in younger children presenting with feeding difficulty and poor weight gain. Combination therapy seems to be more effective in younger children with EoE, but further studies with bigger sample size are needed to study the efficacy of the different combination therapies.

Genomic and global gene expression profiling in pediatric and young adult acute leukemia with PICALM::MLLT10 Fusion.

PICALM: MLLT10 fusion is a rare but recurrent genetic driver in acute leukemias. To better understand the genomic landscape of PICALM::MLLT10 (PM) positive acute leukemia, we performed genomic profiling and gene expression profiling in twenty PM-positive patients, including AML (n = 10), T-ALL/LLy (n = 8), Mixed-phenotype acute leukemia (MPAL), T/B (n = 1) and acute undifferentiated leukemia (AUL) (n = 1). Besides confirming the known activation of HOXA, differential gene expression analysis compared to hematopoietic stem cells demonstrated the enrichment of genes associated with cell proliferation-related pathways and relatively high expression of XPO1 in PM-AML and PM-T-ALL/LLy. Our study also suggested PHF6 disruption as a key cooperating event in PICALM::MLLT10-positive leukemias. In addition, we demonstrated differences in gene expression profiles as well as remarkably different spectra of co-occurring mutations between PM-AML and PM-T-ALL/LLy. Alterations affecting TP53 and NF1, hallmarks of PM-AML, are strongly associated with disease progression and relapse, whereas EZH2 alterations are highly enriched in PM-T-ALL/LLy. This comprehensive genomic and transcriptomic profiling provides insights into the pathogenesis and development of PICALM::MLLT10 positive acute leukemia.

Radiation and anti-PD-L1 synergize by stimulating a stem-like T cell population in the tumor-draining lymph node.

Radiotherapy (RT) and anti-PD-L1 synergize to enhance local and distant (abscopal) tumor control. However, clinical results in humans have been variable. With the goal of improving clinical outcomes, we investigated the underlying synergistic mechanism focusing on a CD8+ PD-1+ Tcf-1+ stem-like T cell subset in the tumor-draining lymph node (TdLN). Using murine melanoma models, we found that RT + anti-PD-L1 induces a novel differentiation program in the TdLN stem-like population which leads to their expansion and differentiation into effector cells within the tumor. Our data indicate that optimal synergy between RT + anti-PD-L1 is dependent on the TdLN stem-like T cell population as either blockade of TdLN egress or specific stem-like T cell depletion reduced tumor control. Together, these data demonstrate a multistep stimulation of stem-like T cells following combination therapy which is initiated in the TdLN and completed in the tumor.

Novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and aggressive presentation.

Childhood melanoma is a rare and biologically heterogeneous pediatric malignancy. The differential diagnosis of pediatric melanoma is usually broad, including a wide variety of spindle cell or epithelioid neoplasms. Different molecular alterations affecting the MAPK and PI3K/AKT/mTOR pathways, tumor suppressor genes, and telomerase reactivation have been implicated in melanoma tumorigenesis and progression. Here, we report a novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and an aggressive clinical course.

Armodafinil as a Potential Pharmacological Treatment for Attention Deficit Hyperactivity Disorder in Adults: A Review.

INTRODUCTION: Armodafinil is a psychostimulant that promotes alertness, and it has been shown to improve attention, memory, and fatigue in healthy adults and adults with neurodevelopmental conditions that share symptoms with Attention Deficit Hyperactivity Disorder (ADHD). It is generally well tolerated and safe, and most of the adverse events reported are considered not serious. However, the available evidence on the efficacy of armodafinil for the treatment of ADHD in adults is scarce. OBJECTIVE: The present review aims to perform a systematized search of the available evidence on the possible therapeutic benefit of armodafinil treatment in adult patients with ADHD. METHODS: A literature review using PubMed was conducted to compile and summarize the available clinical and scientific evidence on the possible use of armodafinil as a pharmacological treatment in adult patients with ADHD. RESULTS: From the 86 articles reviewed, the available evidence showed that both acute and chronic treatment with armodafinil can improve wakefulness, memory, impulse control, and executive functions in adults with sleep disorders and other conditions. In addition, evidence of improvement in cognitive functions and mood alterations in other neuropsychiatric conditions was shown. CONCLUSION: Armodafinil could be useful for the treatment of ADHD in adults, according to the review of the literature from both pre-clinical and clinical studies.

Co-creation process of an intervention to implement a multiparameter point-of-care testing device in a primary healthcare setting for non-communicable diseases in Peru.

BACKGROUND: Point-of-care testing (POCT) devices are diagnostic tools that can provide quick and accurate results within minutes, making them suitable for diagnosing non-communicable diseases (NCDs). However, these devices are not widely implemented in healthcare systems and for this reason is relevant to understand the implementation process. AIM: To describe the process and define a strategy to implement a multiparameter POCT device for diagnosing and managing NCDs in one region of Peru. METHODS: A descriptive and non-experimental study, using the participatory methodologies of co-creation process. It was conducted in one region of Peru (Tumbes) to design an intervention for implementing a multiparameter POCT device. Two co-creation sessions were conducted involving five groups: community members, primary healthcare workers, these groups in both rural and urban settings, and regional decision-makers. These sessions included activities to understand patient journeys in receiving care for NCDs, identify facilitators and barriers to POCT devices usage, and define an implementation strategy for POCT devices in both rural and urban settings of Tumbes. The research team analysed the data and summarized key topics for discussion after each session. RESULTS: A total of 78 participants were enrolled across the five groups. Among community members: 22.2% had only diabetes, 24.1% had only hypertension, and 18.5% had both diagnoses. In the patient journey, community members mentioned that it took at least three days to receive a diagnosis and treatment for an NCD. Most of the participants agreed that the POCT devices would be beneficial for their communities, but they also identified some concerns. The strategy for POCT devices implementation included healthcare workers training, POCT devices must be placed in the laboratory area and must be able to perform tests for glucose, glycated haemoglobin, cholesterol, and creatinine. Advertising about POCT devices should be displayed at the healthcare centres and the municipality using billboards and flyers. CONCLUSIONS: The co-creation process was useful to develop strategies for the implementation of multiparameter POCT devices for NCDs, involving the participation of different groups of stakeholders guided by moderators in both, rural and urban, settings in Peru.

Maternal SARS-CoV-2 infection in pregnancy disrupts gene expression in Hofbauer cells with limited impact on cytotrophoblasts.

BACKGROUND: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these cells that are not directly infected has not been extensively studied. Herein, we profiled gene expression in HBCs and CTBs isolated from placentae of recovered pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy, placentae from subjects with active infection, SARS-CoV-2 vaccinated subjects, and those who were unexposed to the virus. METHODS: Placentae were collected within 4 h post-delivery and membrane-free tissues were enzymatically digested for the isolation of HBCs and CTBs. RNA extracted from HBCs and CTBs were sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) were identified by DESeq2 package in R and enriched in GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Gene Sets, and Canonical Pathways. Protein-protein interactions among the DEGs were modelled using STRING and BioGrid. RESULTS: Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 in i) the first (1T, n = 4), ii) second (2T, n = 5), iii) third (3T, n = 5) trimester, iv) tested positive at delivery (Delivery, n = 5), v) never infected (Control, n = 6), and vi) fully mRNA-vaccinated by delivery (Vaccinated, n = 5). Compared to the Control group, gene expression analysis showed that HBCs from infected subjects had significantly altered gene expression profiles, with the 2T group having the highest number of DEGs (1,696), followed by 3T and 1T groups (1,656 and 958 DEGs, respectively). These DEGs were enriched for pathways involved in immune regulation for host defense, including production of cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, and cell migration/adhesion. Protein-protein interaction analysis mapped these DEGs with oxidative phosphorylation, translation, extracellular matrix organization, and type I interferon signaling. Only 95, 23, and 8 DEGs were identified in CTBs of 1T, 2T, and 3T groups, respectively. Similarly, 11 and 3 DEGs were identified in CTBs and HBCs of vaccinated subjects, respectively. Reassuringly, mRNA vaccination did not induce an inflammatory response in placental cells. CONCLUSIONS: Our studies demonstrate a significant impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal HBCs, with limited effect on lining CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways associated with these DEGs identify potential targets for therapeutic intervention.

Early generation of a precursor CD8 T cell that can adapt to acute or chronic viral infection.

Virus specific PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells are essential for maintaining T cell responses during chronic infection and are also critical for PD-1 directed immunotherapy. In this study we have used the mouse model of chronic LCMV infection to examine when these virus specific stem-like CD8+ T cells are generated during the course of chronic infection and what is the role of antigen in maintaining the stem-like program. We found that these stem-like CD8+ T cells are generated early (day 5) during chronic infection and that antigen is essential for maintaining their stem-like program. This early generation of stem-like CD8+ T cells suggested that the fate commitment to this cell population was agnostic to the eventual outcome of infection and the immune system prepares a priori for a potential chronic infection. Indeed, we found that an identical virus specific stem-cell like CD8+ T cell population was also generated during acute LCMV infection but these cells were lost once the virus was cleared. To determine the fate of these early PD-1+TCF-1+TOX+ stem-like CD8+ T cells that are generated during both acute and chronic LCMV infection we set up two reciprocal adoptive transfer experiments. In the first experiment we transferred day 5 stem-like CD8+ T cells from chronically infected into acutely infected mice and examined their differentiation after viral clearance. We found that these early stem-like CD8+ T cells downregulated canonical markers of the chronic stem-like CD8+ T cells and expressed markers (CD127 and CD62L) associated with central memory CD8+ T cells. In the second experiment, we transferred day 5 stem-like cells from acutely infected mice into chronically infected mice and found that these CD8+ T cells could function like resource cells after transfer into a chronic environment by generating effector CD8+ T cells in both lymphoid and non-lymphoid tissues while also maintaining the number of stem-like CD8+ T cells. These findings provide insight into the generation and maintenance of virus specific stem-like CD8+ T cells that play a critical role in chronic viral infection. In particular, our study highlights the early generation of stem-like CD8+ T cells and their ability to adapt to either an acute or chronic infection. These findings are of broad significance since these novel stem-like CD8+ T cells play an important role in not only viral infections but also in cancer and autoimmunity.

A data-driven approach to complement the A/T/(N) classification system using CSF biomarkers.

AIMS: The AT(N) classification system not only improved the biological characterization of Alzheimer's disease (AD) but also raised challenges for its clinical application. Unbiased, data-driven techniques such as clustering may help optimize it, rendering informative categories on biomarkers' values. METHODS: We compared the diagnostic and prognostic abilities of CSF biomarkers clustering results against their AT(N) classification. We studied clinical (patients from our center) and research (Alzheimer's Disease Neuroimaging Initiative) cohorts. The studied CSF biomarkers included Aß(1-42), Aß(1-42)/Aß(1-40) ratio, tTau, and pTau. RESULTS: The optimal solution yielded three clusters in both cohorts, significantly different in diagnosis, AT(N) classification, values distribution, and survival. We defined these three CSF groups as (i) non-defined or unrelated to AD, (ii) early stages and/or more delayed risk of conversion to dementia, and (iii) more severe cognitive impairment subjects with faster progression to dementia. CONCLUSION: We propose this data-driven three-group classification as a meaningful and straightforward approach to evaluating the risk of conversion to dementia, complementary to the AT(N) system classification.

Actividades enzimáticas séricas de la ceruplasmina y la mieloperoxidasa en diabéticos tipo 2

Introducción: La diabetes mellitus tipo 2 se caracteriza por la hiperglucemia debido a la insuficiente producción de insulina de las células β. La mieloperoxidasa promueve el estrés oxidativo durante la inflamación y la ceruloplasmina se considera su inhibidor endógeno. Objetivo: Evaluar la relación entre la ceruloplasmina y la mieloperoxidasa, determinadas simultáneamente en el suero de pacientes diabéticos tipo 2. Métodos: Se estudiaron 362 pacientes diabéticos tipo 2 y 110 sujetos sanos. La actividad sérica de la ceruloplasmina se determinó por el método de Siotto; y el de la mieloperoxidasa, por el de Kraeisz. Resultados: El 72 % de los pacientes diabéticos tenían hiperglucemia y el 77 % presentaba obesidad abdominal. Las actividades de ambas enzimas se incrementaron significativamente en relación con el grupo control. El coeficiente de correlación de la actividad enzimática resultó bajo. El cociente RMPO/CP de los pacientes diabéticos superó el de los controles. La ceruloplasmina no inhibió la mieloperoxidasa. Conclusiones: Predominó la mieloperoxidasa, por tanto, no se manifestó el efecto inhibitorio de la ceruloplasmina. La elevada actividad de la mieloperoxidasa se asocia con un agravamiento del cuadro clínico del paciente diabético.

Introduction: Type 2 diabetes mellitus is characterized by hyperglycemia due to insufficient insulin production by β cells. Myeloperoxidase promotes oxidative stress during inflammation and ceruloplasmin is considered its endogenous inhibitor. Objective: To evaluate the relationship between ceruloplasmin and myeloperoxidase, determined simultaneously in the serum of type 2 diabetic patients. Methods: A total of 362 type 2 diabetic patients and 110 healthy subjects were studied. Serum ceruloplasmin activity was determined by the Siotto KM method and myeloperoxidase by the Kraeisz JE method. Results: 72% of diabetic patients had hyperglycemia and 77% had abdominal obesity. The activities of both enzymes were significantly increased relative to the control group. The correlation coefficient of enzyme activity was low. The ORMO/CP ratio of diabetic patients exceeded that of controls. Ceruloplasmin did not inhibit myeloperoxidase. Conclusions: Myeloperoxidase predominated, therefore, the inhibitory effect of ceruloplasmin was not manifested. The high activity of myeloperoxidase was associated with a worsening of the clinical picture of the diabetic patient.

Effect of light stress on lutein production with associated phosphorus removal from a secondary effluent by the autoflocculating microalgae consortium BR-UANL-01.

Microalgae have become promising microorganisms for generating high-value commercial products and removing pollutants in aquatic systems. This research evaluated the impact of sunlight intensity on intracellular pigment generation and phosphorus removal from secondary effluents by autoflocculating microalgae consortium BR-UANL-01 in photobioreactor culture. Microalgae were grown in a secondary effluent from a wastewater treatment plant, using a combination of low and high light conditions (photon irradiance; 44 µmol m-2 s-1 and ≈ 1270 µmol m-2 s-1, respectively) and 16:8 h light:dark and 24:0 h light:dark (subdivided into 18:6 LED:sunlight) photoperiods. The autoflocculant rate by consortium BR-UANL-01 was not affected by light intensity and achieved 98% in both treatments. Microalgae produced significantly more lutein, (2.91 mg g-1) under low light conditions. Phosphate removal by microalgae resulted above 85% from the secondary effluent, due to the fact that phosphorus is directly associated with metabolic and replication processes and the highest antioxidant activity was obtained in ABTS•+ assay by the biomass under low light condition (51.71% µmol ET g-1). In conclusion, the results showed that the autoflocculating microalgae consortium BR-UANL-01 is capable of synthesizing intracellular lutein, which presents antioxidant activity, using secondary effluents as a growth medium, without losing its autoflocculating activity and assimilating phosphorus.

Adicción a los teléfonos inteligentes en adolescentes tras la pandemia por la COVID-19

Introducción: La pandemia por la COVID-19 trajo consigo cambios en el comportamiento humano y afecciones psíquicas que afectan la salud mental. Objetivo: Estimar la adicción a los teléfonos inteligentes en adolescentes mujeres tras la pandemia por la COVID-19. Métodos: Estudio transversal realizado en noviembre y diciembre del 2022, en una institución educativa pública de Ica, Perú. Participaron 581 adolescentes que respondieron a un cuestionario con variables generales y la Escala de Adicción a los Teléfonos Inteligentes. Se aplicó un análisis estadístico descriptivo y multivariado mediante modelos lineales generalizados de la familia Poisson para evaluar la asociación entre las variables. Resultados: De las participantes, el 21,7 % reveló adicción a los teléfonos inteligentes y el 48,7 % se encuentra en riesgo alto de dependencia. Los conflictos familiares en el hogar (razón de prevalencia ajustada - RPa= 1,41; intervalo de confianza -IC 95 %: 1,00-1,99) y los sentimientos de vergüenza (RPa= 1,44; IC 95 %: 1,01-2,03), se asociaron a mayor adicción a los teléfonos inteligentes. No obstante, el sentimiento de tristeza, ansiedad o depresión y el hecho de sentirse rechazado por la sociedad presentaron asociación, no ajustada. Conclusiones: La adición a los teléfonos inteligentes y el riesgo de padecer este trastorno es alto en las adolescentes; existen variables generales susceptibles de ser modificadas que podrían mermar dicha afección comportamental inducida o potenciada por la pandemia de la COVID-19.

Introduction: The COVID-19 pandemic brought with it changes in human behavior and psychic conditions that affect mental health. Objective: Estimate smartphone addiction in female adolescents after COVID-19 pandemic. Methods: Cross-sectional study, conducted during November to December 2022, in a public educational institution in Ica, Peru. A total of 581 adolescents participated and answered a questionnaire with general variables and the Smartphone Addiction Scale. A descriptive and multivariate statistical analysis was applied using Poisson family generalized linear models to evaluate the association between variables. Results: Of the participants, 21.7% revealed addiction to smartphones and 48.7% were at high risk of dependence on these devices. Family conflicts at home (adjusted prevalence ratio-RPa = 1.41; 95% confidence interval-CI: 1.00-1.99) and feelings of shame (RPa = 1.44; 95% CI: 1.01-2.03), were associated with higher smartphone addiction. However, feelings of sadness, anxiety or depression and feeling rejected by society showed an unadjusted association. Conclusions: Smartphone addiction and risk for this disorder is high in adolescent girls; there are general variables amenable to modification that could diminish such a behavioral condition induced or potentiated by the COVID-19 pandemic.

Dificultades y vulnerabilidades de la niñez migrante durante la pandemia por covid-19 / Difficulties and vulnerabilities for migrant children in Chile during the COVID-19 pandemic / Perspectivas das crianças migrantes no Chile durante a pandemia da Covid-19

(analítico) Considerando la necesidad de escuchar a niños y niñas migrantes, examinamos desde su mirada las dificultades y vulnerabilidades a las que ellos, ellas y sus familias se enfrentaron durante las cuarentenas, en la pandemia por covid-19 en Chile; durante ellas mantuvieron clases a distancia, en línea o por guías de trabajo. Hicimos entrevistas semiestructuradas con guión temático -utilizando técnicas gráficas- a 37 niños y niñas migrantes de Latinoamérica, y realizamos análisis de contenido. Evidenciamos que las familias migrantes, desde la mirada de los niños y niñas, se han visto expuestas a dificultades y preocupaciones (dada la distancia física entre familiares), vulnerabilidades económicas, falta de redes familiares y dificultades en la organización del trabajo productivo y reproductivo; en cada caso desde los puntos de vista objetivo y subjetivo.

(analytical) After identifying the need to listen to migrant children regarding the vulnerability they and their families faced during the COVID-19 pandemic in Chile, we sought to examine the difficulties and vulnerabilities faced by their families from their point of view. Semistructured interviews with thematic scripts and graphic support were conducted with 37 children whose families had migrated from other countries in Latin America. Content analysis was carried out using the data collected during these interviews. According to these children, it was evident that migrant families faced a number of difficulties and vulnerabilities during the pandemic that included: physical distance between family members; economic vulnerabilities; lack of family support networks; and difficulties with accessing work. These vulnerabilities were evidenced using both objective and subjective points of view.

(analítico) Considerando a necessidade de ouvir a voz das crianças migrantes a respeito das vulnerabilidades enfrentadas por suas famílias durante o período de aulas online durante a pandemia da Covid-19 no Chile, procuramos examinar as dificuldades e vulnerabilidades enfrentadas por suas famílias a partir de seu ponto de vista. Foram realizadas entrevistas semi-estruturadas com roteiros temáticos, utilizando técnicas gráficas, com 37 crianças migrantes latino-americanas, e foi realizada uma análise de conteúdo. Tornou-se evidente que as famílias migrantes, do ponto de vista das crianças, foram expostas a dificuldades e preocupações, dada a distância física entre os membros da família; vulnerabilidades econômicas e falta de redes familiares; e dificuldades na organização do trabalho produtivo e reprodutivo. As vulnerabilidades são evidentes de um ponto de vista objetivo e subjetivo.

Platinum-based chemotherapy attenuates the effector response of CD8 T cells to concomitant PD-1 blockade.

PURPOSE: Combination of chemotherapy (CT) with programmed cell death (PD)-1 blockade is a front-line treatment for lung cancer. However, it remains unknown whether and how CT affects the response of exhausted CD8 T cells to PD-1 blockade. EXPERIMENTAL DESIGN: We used the well-established mouse model of T cell exhaustion with chronic lymphocytic choriomeningitis virus (LCMV) infection to assess the effect of CT (cisplatin+pemetrexed) on T cell response to PD-1 blockade, in the absence of the impact of CT on antigen release and presentation observed in tumor models. RESULTS: When concomitantly administered with PD-1 blockade, CT affected the differentiation path of LCMV-specific CD8 T cells from stem-like to transitory effector cells, thereby reducing their expansion and production of interferon (IFN)-γ. After combination treatment, these restrained effector responses resulted in impaired viral control, compared to PD-1 blockade alone. The sequential combination strategy, where PD-1 blockade followed CT, proved to be superior to the concomitant combination, preserving the proliferative response of exhausted CD8 T cells to PD-1 blockade. Our findings suggest that the stem-like CD8 T cells themselves are relatively unaffected by CT partly because they are quiescent and maintained by slow self-renewal at the steady state. However, upon the proliferative burst mediated by PD-1 blockade, the accelerated differentiation and self-renewal of stem-like cells may be curbed by concomitant CT, ultimately resulting in impaired overall CD8 T cell effector functions. CONCLUSIONS: In a translational context, we provide a proof-of-concept to consider optimizing the timing of chemo-immunotherapy strategies for improved CD8 T cell functions.

Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach.

Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children's blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell type abundance, gene and protein expression and secretion as well as cell-cell communications point towards increased immune cell migration and inflammation in SD progressors. Concurrently, antigen-presenting cells from SD progressors demonstrate intact uptake yet impaired interferon response and antigen processing and presentation signatures, which are partly modulated by DENV. Increased activation, regulation and exhaustion of effector responses and expansion of HLA-DR-expressing adaptive-like NK cells also characterize SD progressors. These findings reveal DENV target cells in human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.

Calidad de la alimentación en preescolares y escolares en Chile durante la pandemia de COVID-19 / Food quality in pre-school and school children in Chile during the COVID-19 pandemic

Introducción: la pandemia por COVID-19 puede afectar en la calidad de la alimentación y la nutrición de preescolares y escolares a través deun incremento de la inseguridad alimentaria de las familias, por medidas como el confinamiento y cierre de establecimientos educacionales, loque afecta la estructura diaria, horarios de alimentación y calidad de la alimentación.Objetivo: analizar la calidad global de la alimentación de preescolares y escolares en Chile durante la pandemia de COVID-19.Métodos: en un muestreo por conveniencia participaron 551 escolares (22,5 % niños y 77,5 % niñas) de cinco ciudades de Chile distribuidas enmacrozonas norte, centro y sur. Se aplicó el índice de calidad global de la alimentación. Los datos fueron analizados en el programa estadísticoIBM SPSSV24. Se analizaron diferencias de proporciones a través de tablas cruzadas.Resultados: escolares de zonas rurales presentaron menor calidad de la alimentación que pares de zonas urbanas (p = ,005). Escolares quecomen con toda la familia presentan mejores indicadores de calidad de la alimentación que aquellos que lo hacen solos (p = ,002). En nueve de12 componentes de la alimentación evaluados, las mujeres presentan mayor cumplimiento de recomendaciones alimentarias.Conclusiones: se requieren más investigaciones sobre los cambios de ingesta dietética y calidad de la alimentación de los niños y niñas ysus familias durante la pandemia. Esto permitirá analizar el impacto de la pandemia en la conducta alimentaria y sus posibles consecuencias. (AU)

Introduction: the COVID-19 pandemic can affect the quality of food and nutrition of preschoolers and schoolchildren through an increase in foodinsecurity of families, by measures such as confinement and closure of educational establishments, which affects the daily structure, feedingschedules, and quality of food.Objectives: analyze the overall food quality of preschool and school children in Chile during the COVID-19 pandemic.Methods: five hundred and fifty-one schoolchildren (22.5 % boys and 77.5 % girls) from five Chilean cities distributed in northern, central, andsouthern macro zones participated in a convenience sampling. The Global Food Quality Index was applied. The data were analyzed in the IBMSPSSV24 statistical program. Differences in proportions were analyzed employing crossed tables.Results: schoolchildren from rural areas presented lower eating quality than their urban peers (p = .005). Schoolchildren who eat with thewhole family had better indicators of eating quality than those who ate alone (p = .002). In nine out of 12 dietary components, evaluated femalespresent higher compliance with dietary recommendations.Conclusions: further research is needed on changes in dietary intake and dietary quality of children and their families during the pandemic. Thiswill allow us to analyze the impact of the pandemic on eating behavior and its possible consequences. (AU)

Effect of a Multi-Ingredient Coriolus-versicolor-Based Vaginal Gel in Women with HPV-Dependent Cervical Lesions: The Papilobs Real-Life Prospective Study.

Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare®) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women ≥ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study's duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild-moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare® vaginal gel than spontaneous regression rates reported in the literature.