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.

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.

The multiplicity of caregiving burden: a qualitative analysis of families with prolonged disorders of consciousness.

Objective: To understand the multiple and sometimes conflicting roles substitute decision makers (SDMs) of individuals in a vegetative state (VS), minimally conscious state (MCS), or with locked-in syndrome (LIS) perform while caring for a loved one and the competing priorities derived from these roles.Methods: We conducted semi-structured qualitative interviews using a constructive-grounded theory design. Twelve SDMs, who were also family members for 11 patients, were interviewed at two time points (except one) for a total of 21 in-depth interviews.Results: Participants described that caregiving is often the central role which they identify as their top priority and around which they coordinate and to some extent subordinate their other roles. In addition to caregiving, they participated in a wide variety of roles, which were sometimes in conflict, as they became caregivers for a loved one with chronic and complex needs. SDMs described the caregiver role as complex and intense that lead to physical, emotional, social, and economic burdens.Conclusion: SDMs report high levels of burdens in caring for a person with a prolonged disorder of consciousness. Lack of health system support that recognized the broader context of SDMs lives, including their multiple competing priorities, was a major contributing factor.

Experiences of family of individuals in a locked in, minimally conscious state, or vegetative state with the health care system.

Primary Objective: To understand the experiences of family members of individuals in a locked-in state (LIS), minimally conscious state (MCS), or vegetative state (VS) with the health-care system when caring for their family member.Research Design: The study adopted a qualitative descriptive approach drawing on central tenets of constructivist grounded theory described by Charmaz. Our analysis drew on emphasizing connections between theory, concepts, and empirical data using a constant comparative method.Methods and Procedures: Semi-structured interviews were conducted with family members of individuals in a LIS, MCS, or VS. Participants were recruited between June 2014 and December 2016.Main Outcomes and Results: 22 interviews were conducted, which comprised interviews with 12 family members. The following themes were identified: care coordination challenges, lack of flexibility in health-care policies, and inappropriate care settings.Conclusions: Family members of individuals in a LIS, MCS, or VS described playing a significant role in the lives of their family member. Based on the results of this study, flexibility in health-care policies and/or programming should be adopted in the face of the challenges identified. Implementation of interventions to support caregivers and transitions is increasingly important.

[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.

Towards the assessment of quality of life in patients with disorders of consciousness.

PURPOSE: To generate foundational knowledge in the creation of a quality-of-life instrument for patients who are clinically diagnosed as being in a vegetative or minimally conscious state but are able to communicate by modulating their brain activity (i.e., behaviourally nonresponsive and covertly aware). The study aimed to identify a short list of key domains that could be used to formulate questions for an instrument that determines their self-reported quality of life. METHODS: A novel two-pronged strategy was employed: (i) a scoping review of quality-of-life instruments created for patient populations sharing some characteristics with patients who are behaviourally nonresponsive and covertly aware was done to compile a set of potentially relevant domains of quality of life; and (ii) a three-round Delphi consensus process with a multidisciplinary panel of experts was done to determine which of the identified domains of quality of life are most important to those who are behaviourally nonresponsive and covertly aware. Five expert groups were recruited for this study including healthcare workers, neuroscientists, bioethicists, quality-of-life methodologists, and patient advocates. RESULTS: Thirty-five individuals participated in the study with an average response rate of 95% per round. Over the three rounds, experts reached consensus on 34 of 44 domains (42 domains were identified in the scoping review and two new domains were added based on suggestions by experts). 22 domains were rated as being important for inclusion in a quality-of-life instrument and 12 domains were deemed to be of less importance. Participants agreed that domains related to physical pain, communication, and personal relationships were of primary importance. Based on subgroup analyses, there was a high degree of consistency among expert groups. CONCLUSIONS: Quality of life should be a central patient-reported outcome in all patient populations regardless of patients' ability to communicate. It remains to be determined how covertly aware patients perceive their circumstances and quality of life after suffering a life-altering injury. Nonetheless, it is important that any further dialogue on what constitutes a life worth living should not occur without direct patient input.

Isolation and Identification of Two Brucella Species from a Volcanic Lake in Mexico.

Brucellosis is a zoonosis caused by bacteria of the Brucella genus. Any source of contamination that could be infectious must be monitored to reduce the risk of exposure to brucellosis, so the purpose of this work was to determine the presence of Brucella spp. on surface water and tilapia (Oreochromis niloticus) skin from a volcanic lake in Mexico. A seasonal sampling during 2016-2017 was carried out at fifteen specific sites for water sampling and five sites for the collection of tilapia fish. From all water and fish samples tested, we found only three isolates of Brucella species. We isolated and identified B. abortus from surface water through bacteriological and molecular techniques, and B. abortus and B. suis from the same tilapia skin sample. The isolated strains likely came from breeding animals that are common to the region, such as infected pigs or cattle with Brucella abortus or B. suis, respectively. A similar finding has not been reported in a water from volcanic lake or tilapia fish in Mexico. We concluded that B. abortus and B. suis are present on the surface water of the volcanic lake and tilapia skin as possible contaminants derived from biological material from cows and pigs carrying this bacterium.

From Elemental Sulfur to Hydrogen Sulfide in Agricultural Soils and Plants.

Sulfur is an essential element in determining the productivity and quality of agricultural products. It is also an element associated with tolerance to biotic and abiotic stress in plants. In agricultural practice, sulfur has broad use in the form of sulfate fertilizers and, to a lesser extent, as sulfite biostimulants. When used in the form of bulk elemental sulfur, or micro- or nano-sulfur, applied both to the soil and to the canopy, the element undergoes a series of changes in its oxidation state, produced by various intermediaries that apparently act as biostimulants and promoters of stress tolerance. The final result is sulfate S+6, which is the source of sulfur that all soil organisms assimilate and that plants absorb by their root cells. The changes in the oxidation states of sulfur S0 to S+6 depend on the action of specific groups of edaphic bacteria. In plant cells, S+6 sulfate is reduced to S-2 and incorporated into biological molecules. S-2 is also absorbed by stomata from H2S, COS, and other atmospheric sources. S-2 is the precursor of inorganic polysulfides, organic polysulfanes, and H2S, the action of which has been described in cell signaling and biostimulation in plants. S-2 is also the basis of essential biological molecules in signaling, metabolism, and stress tolerance, such as reactive sulfur species (RSS), SAM, glutathione, and phytochelatins. The present review describes the dynamics of sulfur in soil and plants, considering elemental sulfur as the starting point, and, as a final point, the sulfur accumulated as S-2 in biological structures. The factors that modify the behavior of the different components of the sulfur cycle in the soil-plant-atmosphere system, and how these influences the productivity, quality, and stress tolerance of crops, are described. The internal and external factors that influence the cellular production of S-2 and polysulfides vs. other S species are also described. The impact of elemental sulfur is compared with that of sulfates, in the context of proper soil management. The conclusion is that the use of elemental sulfur is recommended over that of sulfates, since it is beneficial for the soil microbiome, for productivity and nutritional quality of crops, and also allows the increased tolerance of plants to environmental stresses.

Assessment of the Hospital Anxiety and Depression Scale for cancer patients.

BACKGROUND: Depression and anxiety are common in patients with cancer. AIM: To adapt and validate the Hospital Anxiety and Depression Scale (HADS) for adult Chilean cancer patients, and to provide information about their prevalence of anxiety and depression. MATERIAL AND METHODS: Two hundred fifteen patients with cancer answered an adapted version of HADS for Chilean population. The language adjustment of the scale was carried out with the opinions of 10 expert linguists and with a pilot study on 17 cancer patients. The Depression and Anxiety subscales of the DASS-21 were also applied to verify the convergent validity of HADS: Results: The confirmatory factor analysis indicated that the data fits the model of two correlated factors (anxiety and depression), χ2 = 98.608; df = 76;p < 0.05; χ2/df= 1.23, RMSEA = 0.037; CFI = 0.99; TLI = .98. Reliability analysis showed an adequate internal consistency of both subscales (.76 for anxiety and .84 for depression) and the general scale (.87). Correlations between HADS and DASS-21 scores were significant for both anxiety (r =.514, p < 0.001) and depression (r = 0.600, p < 0.001). Prevalence rates were approximately 30% for depression (actual = 12%, possible = 22.8%) and approximately 20% for anxiety (actual = 7%, possible = 8.4%). CONCLUSIONS: We conclude that HADS is a reliable and valid instrument for screening clinically relevant anxiety and depression symptoms in Chilean cancer patients.

Acknowledging awareness: informing families of individual research results for patients in the vegetative state.

Recent findings in cognitive neuroscience have revealed that some patients previously diagnosed as being in a vegetative state may retain some degree of covert awareness. However, it is unclear whether such findings should be disclosed to the families of these patients. Concerns about the preservation of scientific validity, reliability of results and potential harms associated with disclosure suggest that individual research results should be disclosed only under certain conditions. In the following paper, we offer four criteria for the disclosure of individual research results. Because the results of functional neuroimaging studies to detect covert awareness in vegetative patients are scientifically valid, informative and reasonably reliable and have considerable potential benefit for the patient, researchers have an obligation to disclose such results to family members. Further work is needed to develop educational materials for families and to systematically study the impact of disclosure on the families themselves.

Ethics of neuroimaging after serious brain injury.

BACKGROUND: Patient outcome after serious brain injury is highly variable. Following a period of coma, some patients recover while others progress into a vegetative state (unresponsive wakefulness syndrome) or minimally conscious state. In both cases, assessment is difficult and misdiagnosis may be as high as 43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic resonance imaging and electroencephalography have been used to detect residual cognitive function in vegetative and minimally conscious patients. Neuroimaging may improve diagnosis and prognostication. These techniques are beginning to be applied to comatose patients soon after injury. Evidence of preserved cognitive function may predict recovery, and this information would help families and health providers. Complex ethical issues arise due to the vulnerability of patients and families, difficulties interpreting negative results, restriction of communication to "yes" or "no" answers, and cost. We seek to investigate ethical issues in the use of neuroimaging in behaviorally nonresponsive patients who have suffered serious brain injury. The objectives of this research are to: (1) create an approach to capacity assessment using neuroimaging; (2) develop an ethics of welfare framework to guide considerations of quality of life; (3) explore the impact of neuroimaging on families; and, (4) analyze the ethics of the use of neuroimaging in comatose patients. METHODS/DESIGN: Our research program encompasses four projects and uses a mixed methods approach. Project 1 asks whether decision making capacity can be assessed in behaviorally nonresponsive patients. We will specify cognitive functions required for capacity and detail their assessment. Further, we will develop and pilot a series of scenarios and questions suitable for assessing capacity. Project 2 examines the ethics of welfare as a guide for neuroimaging. It grounds an obligation to explore patients' interests, and we explore conceptual issues in the development of a quality of life instrument adapted for neuroimaging. Project 3 will use grounded theory interviews to document families' understanding of the patient's condition, expectations of neuroimaging, and the impact of the results of neuroimaging. Project 4 will provide an ethical analysis of neuroimaging to investigate residual cognitive function in comatose patients within days of serious brain injury.

MRI tracking of transplanted iron-labeled mesenchymal stromal cells in an immune-compromised mouse model of critical limb ischemia.

Peripheral arterial disease is a clinical problem in which mesenchymal stromal cell (MSC) transplantation may offer substantial benefit by promoting the generation of new blood vessels and improving limb ischemia and wound healing via their potent paracrine activities. MRI allows for the noninvasive tracking of cells over time using iron oxide contrast agents to label cells before they are injected or transplanted. However, a major limitation of the tracking of iron oxide-labeled cells with MRI is the possibility that dead or dying cells will transfer the iron oxide label to local bystander macrophages, making it very difficult to distinguish between viable transplanted cells and endogenous macrophages in the images. In this study, a severely immune-compromised mouse, with limited macrophage activity, was investigated to examine cell tracking in a system in which bystander cell uptake of dead, iron-labeled cells or free iron particles was minimized. MRI was used to track the fate of MSCs over 21 days after their intramuscular transplantation in mice with a femoral artery ligation. In all mice, a region of signal loss was observed at the injection site and the volume of signal hypointensity diminished over time. Fluorescence and light microscopy showed that iron-positive MSCs persisted at the transplant site and often appeared to be integrated in perivascular niches. This was compared with MSC transplantation in immune-competent mice with femoral artery ligation. In these mice, the regions of signal loss caused by iron-labeled MSC cleared more slowly, and histology revealed iron particles trapped at the site of cell transplantation and associated with areas of inflammation.

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.].

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.

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.

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.

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.

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.