Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues.

Women acquire HIV through sexual transmission, with increasing incidence in women >50 years old. Identifying protective mechanisms in the female genital tract (FGT) is important to prevent HIV-acquisition in women as they age. Human genital and blood neutrophils inactivate HIV by releasing neutrophil extracellular traps (NETs), an innate protective mechanism against HIV-infection. However, how NET formation is triggered by HIV in different tissues and whether this mechanism is affected by aging remain unknown. We demonstrate that the mechanisms that trigger NET release in response to HIV are different in blood and genital tissues, and that NET release decreases with aging. In blood neutrophils, HIV stimulation independently activated calcium pathways and endosomal TLR8, but aging reduced calcium responses, resulting in delayed NET release. In contrast, calcium responses were absent in genital neutrophils and NET release was triggered preferentially through TLR8 activation, but aging impaired this pathway. HIV induced NET formation through non-lytic pathways in blood and FGT neutrophils, except for a small subset of NETs that incorporated annexin V and lactoferrin predominantly in blood, suggesting proinflammatory and lytic NET release. Our findings demonstrate that blood neutrophils cannot model genital neutrophil responses which has important implications to understanding protection against HIV acquisition.

Novel genetic resources associated with sucrose and stachyose content through genome-wide association study in soybean (Glycine max (L.) Merr.).

The nutritional value of soybean [Glycine max (L.) Merr.] for animals is influenced by soluble carbohydrates, such as sucrose and stachyose. Although sucrose is nutritionally desirable, stachyose is an antinutrient causing diarrhea and flatulence in non-ruminant animals. We conducted a genome-wide association study of 220 soybean accessions using 21,317 single nucleotide polymorphisms (SNPs) from the SoySNP50K iSelect Beadchip data to identify significant SNPs associated with sucrose and stachyose content. Seven significant SNPs were identified for sucrose content across chromosomes (Chrs.) 2, 8, 12, 17, and 20, while thirteen significant SNPs were identified for stachyose content across Chrs. 2, 5, 8, 9, 10, 13, 14, and 15. Among those significant SNPs, three sucrose-related SNPs on Chrs. 8 and 17 were novel, while twelve stachyose-related SNPs on Chrs. 2, 5, 8, 9, 10, 13, 14, and 15 were novel. Based on Phytozome, STRING, and GO annotation, 17 and 24 candidate genes for sucrose and stachyose content, respectively, were highly associated with the carbohydrate metabolic pathway. Among these, the publicly available RNA-seq Atlas database highlighted four candidate genes associated with sucrose (Glyma.08g361200 and Glyma.17g258100) and stachyose (Glyma.05g025300 and Glyma.13g077900) content, which had higher gene expression levels in developing seed and multiple parts of the soybean plant. The results of this study will extend knowledge of the molecular mechanism and genetic basis underlying sucrose and stachyose content in soybean seed. Furthermore, the novel candidate genes and SNPs can be valuable genetic resources that soybean breeders may utilize to modify carbohydrate profiles for animal and human usage.

Corrigendum: Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study.

[This corrects the article DOI: 10.3389/fimmu.2022.976564.].

Translating the observed differences in interleukin-6 levels between some antiretroviral regimens into potential long-term risk of serious non-AIDS events: A modeling study.

Introduction: Variable levels of systemic inflammation are observed in people with HIV (PWH), but the clinical significance of differences among antiretroviral therapy (ART) regimens on associated levels of inflammatory markers is unclear. Based on data from previous epidemiologic studies that defined the predicted change in risk of serious non-AIDS events (SNAEs)/death by changes in interleukin-6 (IL-6) and D-dimer, we modeled the effects of differences in these markers between specific ART regimens on the long-term risk of clinical outcomes. Methods: We used a Markov model to compare the risk of SNAEs/death with differences in IL-6 and D-dimer levels associated with remaining on specific three-drug regimens versus switching to specific two-drug ART regimens over 5 years of treatment. We used IL-6 and D-dimer data based on trajectories over time from the randomized TANGO and observational AIR studies. Age at model entry was set at 39 years. The primary endpoint was the number needed to treat for one additional SNAE/death. Results: Over 144 weeks, PWH on one of the three-drug regimens studied were predicted to spend 22% more time in the low IL-6 quartile and 13% less time in the high IL-6 quartile compared with those on one of the two-drug regimens. Over 144 weeks, the predicted mean number of SNAEs/deaths per 100 PWH was 5.6 for a three-drug regimen associated with lower IL-6 levels versus 6.8 for a two-drug regimen associated with higher IL-6 levels. The number needed to treat for one additional SNAE/death among PWH receiving a two-drug versus three-drug regimen for 240 weeks was 43. Approximately 2,900 participants would be required for a 240-week clinical study to evaluate the accuracy of the model. Conclusions: Our Markov model suggests that higher IL-6 levels associated with switching from specific three- to two- drug ART regimens may be associated with an increase in the risk of SNAEs/death. Clinical studies are warranted to confirm or refute these results.

Implementation of a web-based system to measure, monitor, and promote school engagement strategies. A Chilean experience.

This paper presents the implementation and usability of a technology-based web system and the available evidence on educational engagement's predictive capacity to influence students' educational trajectories in Chilean schools. The web-based system was developed through collaborative work between universities, the information technology team, school communities, and stakeholders (government institutions). It is an online system composed of six steps whose axis is centered on a decision-making space between teachers-students-parents (School Engagement Board) tasked with applying online and scientifically validated school engagement and contextual factors measurement instruments, checking specific report results for each actor involved in the system (teacher, School Engagement Board coordinator, school) as well as reviewing promotion strategies relevant to the school context and managing the implementation of strategies supported by the management datasheets that the model offers to schools. The objective of this paper is to present the usability of the system through a case study of the implementation in Chilean public schools. In order to discuss about what elements should be incorporated to adjust and improve the usability of the system and to guarantee its effective implementation, the paper describes those aspects that have favored and/or hindered the use of this educational technological platform in the Chilean case. The results show that there have been more difficulties related to management aspects than IT aspects, which indicates that these conditions are critical for implementation, even when system for evaluation, monitoring and strategies for the promotion of student engagement and contextual factors (SIESE) is designed for stand-alone use. Although there are aspects to be improved, such as extending its use to other browsers, improving the intervention guidelines and other systems functionalities, this web-based system has been considered by the educational communities as a simple, useful, and intuitive platform. The paper concludes on the importance of having this type of platform in Chile and other Latin American countries, for its contribution to school management -being helpful for day-to-day educational practice- due to the different technical facilitators.

Adaptation and psychometric properties of the school engagement and contextual factors questionnaires for Covid-19 and post Covid-19 context.

School engagement has been demonstrated to be a relevant aspect in promoting students' successful trajectories, a commitment that in its turn is influenced by contextual factors (family, teachers, and peers). Having instruments to measure these constructs allows decisions to be made to improve student retention, especially relevant in the context of uncertainty caused by covid-19. The aim of the study was to adapt and analyze the psychometric properties of questionnaires used to measure school engagement and contextual factors in the context of the pandemic with elementary school students in Chile. After adaptation of the instruments, through expert evaluation and focus groups with students, they were administered to 579 students in seventh and eighth grade (mean age = 12.79, 52% were boys), and to 334 students in fifth and sixth grade (mean age = 11.35, 38% were boys) in Chile. Confirmatory factor analyses showed that the two versions of the school engagement measurement instrument had an adequate fit with the original model of three correlated factors, cognitive, affective, and behavioral commitment. Similarly, these two versions of the instrument measuring the contextual factors had a good fit with the original model of three correlated factors, family, teachers, and peers. In addition, both versions of both questionnaires presented appropriate levels of internal consistency.

Short-Chain Fatty Acids Impair Neutrophil Antiviral Function in an Age-Dependent Manner.

Half of the people living with HIV are women. Younger women remain disproportionally affected in endemic areas, but infection rates in older women are rising worldwide. The vaginal microbiome influences genital inflammation and HIV infection risk. Multiple factors, including age, induce vaginal microbial alterations, characterized by high microbial diversity that generate high concentrations of short-chain fatty acids (SCFAs), known to modulate neutrophil function. However, how SCFAs may modulate innate anti-HIV protection by neutrophils is unknown. To investigate SCFA-mediated alterations of neutrophil function, blood neutrophils from younger and older women were treated with SCFAs (acetate, butyrate and propionate) at concentrations within the range reported during bacterial vaginosis, and phenotype, migration and anti-HIV responses were evaluated. SCFA induced phenotypical changes preferentially in neutrophils from older women. Butyrate decreased CD66b and increased CD16 and CD62L expression, indicating low activation and prolonged survival, while propionate increased CD54 and CXCR4 expression, indicating a mature aged phenotype. Furthermore, acetate and butyrate significantly inhibited neutrophil migration in vitro and specifically reduced α-defensin release in older women, molecules with anti-HIV activity. Following HIV stimulation, SCFA treatment delayed NET release and dampened chemokine secretion compared to untreated neutrophils in younger and older women. Our results demonstrate that SCFAs can impair neutrophil-mediated anti-HIV responses.

SLAMF8 Downregulates Mouse Macrophage Microbicidal Mechanisms via PI3K Pathways.

Signaling lymphocytic activation molecule family 8 (SLAMF8) is involved in the negative modulation of NADPH oxidase activation. However, the impact of SLAMF8 downregulation on macrophage functionality and the microbicide mechanism remains elusive. To study this in depth, we first analyzed NADPH oxidase activation pathways in wild-type and SLAMF8-deficient macrophages upon different stimulus. Herein, we describe increased phosphorylation of the Erk1/2 and p38 MAP kinases, as well as increased phosphorylation of NADPH oxidase subunits in SLAMF8-deficient macrophages. Furthermore, using specific inhibitors, we observed that specific PI3K inhibition decreased the differences observed between wild-type and SLAMF8-deficient macrophages, stimulated with either PMA, LPS, or Salmonella typhimurium infection. Consequently, SLAMF8-deficient macrophages also showed increased recruitment of small GTPases such as Rab5 and Rab7, and the p47phox subunit to cytoplasmic Salmonella, suggesting an impairment of Salmonella-containing vacuole (SCV) progression in SLAMF8-deficient macrophages. Enhanced iNOS activation, NO production, and IL-6 expression were also observed in the absence of SLAMF8 upon Salmonella infection, either in vivo or in vitro, while overexpression of SLAMF8 in RAW264.7 macrophages showed the opposite phenotype. In addition, SLAMF8-deficient macrophages showed increased activation of Src kinases and reduced SHP-1 phosphate levels upon IFNγ and Salmonella stimuli in comparison to wild-type macrophages. In agreement with in vitro results, Salmonella clearance was augmented in SLAMF8-deficient mice compared to that in wild-type mice. Therefore, in conclusion, SLAMF8 intervention upon bacterial infection downregulates mouse macrophage activation, and confirmed that SLAMF8 receptor could be a potential therapeutic target for the treatment of severe or unresolved inflammatory conditions.

Definitions of Bronchopulmonary Dysplasia: Which One Should We Use?

OBJECTIVE: To assess the clinical applicability of the current definitions of bronchopulmonary dysplasia (BPD) and their ability to predict subsequent respiratory outcomes. STUDY DESIGN: In this retrospective cohort study, data were collected from 104 preterm infants (mean gestational age, 25.8 weeks) diagnosed with BPD between 2010 and 2018 at a single tertiary care center. The infants were classified according to the following definitions: 2001 National Institute of Child Health and Human Development (NICHD), 2017 Canadian Neonatal Network (CNN), 2018 NICHD, and 2019 Neonatal Research Network (NRN). Logistic regression and the area under the receiver operating characteristic curve (AUC) were used to assess the predictive ability of each definition on mortality or severe respiratory morbidity at 18-24 months of age. RESULTS: All patients could be adequately classified by each definition, except for the 2001 NICHD definition, in which 11.4% were unclassifiable. The prevalence of BPD was 49% by the 2017 CNN definition and 70% by the 2018 NICHD and 2019 NRN definitions. The best regression model was the one that included the 2018 NICHD definition, which had an accuracy of 85.6% and a significantly higher AUC compared with the 2001 NICHD (0.891 vs 0.824; P = .015) and 2017 CNN (0.891 vs 0.811; P = .036) definitions, but not compared with the 2019 NRN definition (0.891 vs 0.833; P = .09). CONCLUSIONS: The current definitions of BPD showed a good predictive ability for mid-term respiratory outcomes, with the highest ability for the 2018 NICHD definition. Further studies are needed to establish the most appropriate definition of BPD.

School engagement profiles in Chilean secondary students.

School engagement is considered a key variable in promoting educational trajectories. Previous research shows that maintaining high levels of school engagement is fundamental, given its association with multiple academic results and lower-risk behaviors. This article aims to show how school engagement profiles (based on the behavioral, affective, and cognitive subdimensions) relate to academic achievement (math and language), contextual factors (family, teachers, and peer support), and gender. This study involved 527 students enrolled in the 1st year of secondary education in public schools in Chile. All students came from vulnerable schools. Our study used cluster analysis to identify students' profiles. We identified the existence of three different profiles of school engagement (high, medium, and low) considering the three subdimensions of school engagement (behavioral, affective and cognitive). Secondly, ANOVA analysis showed differences in language and math academic achievement scores between the profiles, where higher engagement students showed higher academic performance in language and math. These findings are consistent with previous studies showing that contextual factors strongly influence school engagement and better behavioral engagement in female than male students. It will discuss the pertinence of person-centered approaches focusing on combinations of variables within students rather than taking each variable as the focal point when analyzing goals. These techniques are a favorable methodological alternative to investigate why some students have better results than others instead of just ranking students by their performance. It will conclude with some future lines of research and practical implications.

Adaptation of practical classes of clinical subjects in the COVID-19 era

Abstract Pharmaceutical Care is a subject within the Pharmacy Degree that is taught using theoretical and practical classes. When COVID-19 appeared, Faculty of Pharmacy had to change its way of teaching and learning to online classes. Our aim is to assess the impact of COVID-19 situation on practical classes in Pharmaceutical Care. A prospective study was performed by undergraduate students from Pharmaceutical Care subject. Students attended to 2-day practical classes and were assessed through an evaluative workbook. Undergraduate students (n=390) obtained a score of 8.4±0.8 in practical classes, being higher in face-to-face sessions than online sessions, but not significant differences among both methodologies. The higher score was for the session of minor ailment services (9.3±1.3) and the lower for Personalized Medication Dosage (7.0±1.6) and similar in both scenarios. 59% of students obtained more than 8 score in the global punctuation, being higher in in-face-to-face practical classes. This study showed that learning in health care can be guided and evaluated through an online method. Adapt to new technologies, prevent vulnerable students from being left behind, as well as working on cross-cutting skills at a distance, are some of the challenges of higher education in times of COVID-19.

[Frequency of depression and anxiety in a group of 623 patients with cancer]. / Estado emocional de pacientes oncológicos: evaluación de la ansiedad y la depresión en función de variables clínicas y sociodemográficas.

BACKGROUND: Patients with life threatening diseases may experience anxiety and depression. AIM: To analyze anxiety and depression in Chilean patients with cancer. MATERIAL AND METHODS: The Hospital Anxiety and Depression Scale (HADS) was applied to 623 ambulatory and hospitalized patients with cancer (70% women). RESULTS: A low frequency of clinical anxiety (11,7%) and depression (5,3%) was observed. Depression was more common in women, in patients with mid-level education, in unemployed patients and in older people. Anxiety was more common in young and unemployed patients. CONCLUSIONS: The frequency of depression and anxiety was low in this group of cancer patients. Women, educated, uneomployed, and older subjects are risk groups for depression. Young and unemployed subjects experience more anxiety.

Caregiver reactions to neuroimaging evidence of covert consciousness in patients with severe brain injury: a qualitative interview study.

BACKGROUND: Severe brain injury is a leading cause of death and disability. Diagnosis and prognostication are difficult, and errors occur often. Novel neuroimaging methods can improve diagnostic and prognostic accuracy, especially in patients with prolonged disorders of consciousness (PDoC). Yet it is currently unknown how family caregivers understand this information, raising ethical concerns that disclosure of neuroimaging results could result in therapeutic misconception or false hope. METHODS: To examine these ethical concerns, we conducted semi-structured interviews with caregivers of patients with PDoC who were enrolled in a concurrent neuroimaging research program designed to detect covert consciousness following severe brain injury. Caregivers held surrogate decision-making status for a patient. Interviews were conducted at two time points for each caregiver. The first interview occurred before the disclosure of neuroimaging results. The second occurred after disclosure. Descriptive analysis was applied to the data of four interview topics: (1) expectations for neuroimaging; (2) reactions to evidence of preserved cognition; (3) reactions to null results; and (4) understanding of the results and study. RESULTS: Twelve caregivers participated in the study; two caregivers shared surrogate decision-making status for one patient with PDoC. Twenty-one interviews were completed; one caregiver declined to participate in the post-disclosure interview. Three patients with PDoC associated with the study displayed evidence of covert consciousness. Overall, caregivers understood the neuroimaging research and results. Caregivers who received results of covert consciousness were generally pleased. However, there was some variation in expectations and reactions to these data and null results. CONCLUSION: This study, for the first time, reveals caregiver expectations for and reactions to neuroimaging evidence of covert consciousness in patients with PDoC. Caregivers understood the neuroimaging research and results, casting doubt on speculative ethical concerns regarding therapeutic misconception and false hope. However, disclosure of neuroimaging result could be improved. Pre-disclosure consultations might assist professionals in shaping caregiver expectations. Standardization of disclosure might also improve comprehension of the results.

Prospective multicenter evaluation of real time PCR Kit prototype for early diagnosis of congenital Chagas disease.

BACKGROUND: Current algorithm for Congenital Chagas Disease (cCD) diagnosis is unsatisfactory due to low sensitivity of the parasitological methods. Moreover, loss to follow-up precludes final serodiagnosis after nine months of life in many cases. A duplex TaqMan qPCR kit for Trypanosoma cruzi DNA amplification was prospectively evaluated in umbilical cord (UCB) and peripheral venous blood (PVB) of infants born to CD mothers at endemic and non-endemic sites of Argentina. METHODS: We enrolled and followed-up 370 infants; qPCR was compared to gold-standard cCD diagnosis following studies of diagnostic accuracy guidelines. FINDINGS: Fourteen infants (3·78%) had cCD. The qPCR sensitivity and specificity were higher in PVB (72·73%, 99·15% respectively) than in UCB (66·67%, 96·3%). Positive and negative predictive values were 80 and 98·73% and 50 and 98·11% for PVB and UCB, respectively. The Areas under the Curve (AUC) of ROC analysis for qPCR and micromethod (MM) were 0·81 and 0·67 in UCB and 0·86 and 0·68 in PVB, respectively. Parasitic loads ranged from 37·5 to 23,709 parasite equivalents/mL. Discrete typing Unit Tc V was identified in five cCD patients and in six other cCD cases no distinction among Tc II, Tc V or Tc VI was achieved. INTERPRETATION: This first prospective field study demonstrated that qPCR was more sensitive than MM for early cCD detection and more accurate in PVB than in UCB. Its use, as an auxiliary diagnostic tool to MM will provide more accurate records on cCD incidence. FUNDING: FITS SALUD 001-CHAGAS (FONARSEC, MINCyT, Argentina) to the Public-Private Consortium (INGEBI-CONICET, INP-ANLIS MALBRAN and Wiener Laboratories); ERANET-LAC-HD 328 to AGS and PICT 2015-0074 (FONCYT, MinCyT) to AGS and FA.

Estado emocional de pacientes oncológicos: evaluación de la ansiedad y la depresión en función de variables clínicas y sociodemográficas / Frequency of depression and anxiety in a group of 623 patients with cancer

Background: Patients with life threatening diseases may experience anxiety and depression. Aim: To analyze anxiety and depression in Chilean patients with cancer. Material and Methods: The Hospital Anxiety and Depression Scale (HADS) was applied to 623 ambulatory and hospitalized patients with cancer (70% women). Results: A low frequency of clinical anxiety (11,7%) and depression (5,3%) was observed. Depression was more common in women, in patients with mid-level education, in unemployed patients and in older people. Anxiety was more common in young and unemployed patients. Conclusions: The frequency of depression and anxiety was low in this group of cancer patients. Women, educated, uneomployed, and older subjects are risk groups for depression. Young and unemployed subjects experience more anxiety.

Protocolo de profilaxis antibiótica preoperatoria para pacientes ortopédicos del Hospital México: un análisis de cumplimiento / Hospital Mexico’s preoperative antibiotic prophylaxis protocol for orthopedic patients: a compliance analysis

Objetivo: Analizar el cumplimiento en la prescripción de la profilaxisantibiótica prequirúrgica, según el protocolo establecido por el Programade Optimización de Antibióticos y el Servicio de Ortopedia del HospitalMéxico, Caja Costarricense del Seguro Social, ubicado en San José,Costa Rica, de febrero a marzo de 2019. Desde la instauración del protocolo en 2018 no se ha realizado una evaluación de su cumplimiento nise ha determinado la tasa de infección del sitio quirúrgico.Método: Estudio observacional retrospectivo; se identificaron lospacientes hospitalizados en el Servicio de Ortopedia desde el 1 defebrero al 31 de marzo de 2019. Se accedió al expediente digitalde cada paciente, se caracterizó la profilaxis antibiótica prescrita y seanalizó el cumplimiento según el protocolo vigente. Se estimó la tasade infección de sitio quirúrgico. Se realizó un análisis descriptivo de lapoblación.Resultados: El estudio incluyó 110 expedientes clínicos. Los antibióticos más prescritos fueron clindamicina y gentamicina de manera concomitante. El cumplimiento de la prescripción de profilaxis antibiótica oscilóentre 89,1% y 100% para los criterios considerados en el protocolo,exceptuando dosis y antibiótico al alta (14,3 y 65,8%, respectivamente). (AU)

Objective: To analyze compliance with a prescribed pre-surgical antibiotic prophylaxis protocol established by the Antimicrobial StewardshipProgram team and the Orthopedics Department of Hospital Mexico, apublic hospital located in Costa Rica, from February to March 2019. Noassessments of compliance with the protocol had been conducted sinceits introduction in 2018, nor had variations in surgical site infection ratesbeen determined.Method: This is a retrospective observational study that extended fromFebruary 1st to March 31st, 2019. We identified patients hospitalizedduring the study period in the hospital’s Orthopedics Department. Wereviewed each patient’s medical record to record their prescribed antibiotic prophylaxis. Following an analysis of the overall compliance with theprotocol, we made an estimation of the surgical site infection rate as wellas a descriptive analysis of the studied population.Results: The study included 110 clinical records. The most frequentlyprescribed antibiotics were clindamycin and gentamicin. Compliancewith the protocol ranged between 89.1% and 100% across the differentcriteria, except for dosing appropriateness and prescription of antibioticsat discharge (14.3% and 65.8%, respectively). The most common noncompliance factor was gentamicin´s dosing. The surgical site infection ratewas 5%. (AU)