Examining factors associated with self-reported cognitive functioning in elite military settings: considerations of combat experiences and post-traumatic stress symptomology.

Exposure to traumatic events is associated with post-traumatic stress symptomology (PTSS) in a variety of populations. PTSS is also associated with self-reported everyday cognitive failures, which are acknowledged attentional lapses experienced in one's naturalistic everyday environment. While a growing literature suggests that PTSS is associated with both traumatic events and attentional functions, little is known regarding similar associations in elite military cohorts, such as Special Operations Forces (SOF) personnel. Herein, we investigate if prior combat experience is associated with everyday cognitive failures, while considering the possible mediating role of PTSS. SOF personnel (N = 119) completed self-report questionnaires assessing prior combat experience, PTSS, and everyday cognitive failures. Direct and indirect associations between these metrics were examined using structural equation modeling. Mediation analyses revealed that the correspondence between combat experiences and everyday cognitive failures is mediated by the severity of subclinical levels of PTSS. Such findings suggest that greater attention to subclinical PTSS is warranted due to its significant association with everyday cognitive failures that may contribute to deleterious mission-related failures in high-demand tactical professionals, such as SOF.

Paying attention to attention: a program evaluation of faculty-delivered mindfulness-based attention training to optimize wellness and professionalism in medical students.

BACKGROUND: As physician distress rises, medical schools must provide programs to counter such distress at the earliest stages of training. Mindfulness training (MT) is one intervention that can alleviate stress during medical school. However, framing MT around wellness alone misses the opportunity to connect core cognitive and psychological capacities strengthened by MT to professional goals and skill acquisition inherent to successful medical training. Here, we highlight how the attentional components of MT align with students' goals of becoming attending physicians while promoting academic, psychological, and interpersonal flourishing. MT courses that focus on strengthening attentional capacities can intuitively link academic and professional development with wellness, appealing to a wide array of students. METHODS: We iteratively recontextualized an existing short-form mindfulness training program for high-stress pre-professionals, known as Mindfulness Based Attention Training (MBAT), to the medical school context (MBAT-Rx). MBAT-Rx was offered by physician trainers to first-year medical students at Warren Alpert Medical School of Brown University as a tool for improving study habits and focus in addition to the development of both self-care and patient care strategies. MBAT-Rx consists of weekly, two-hour sessions over four weeks, with 10-15 min of daily mindfulness practice between sessions. At the end of the four weeks, students submitted voluntary program evaluation responses detailing their experience of the program. RESULTS: Optional program evaluation responses (n = 67) highlight that students found the program to be useful for their academic success and ability to pay attention, their interpersonal relationships, and their psychological health. By framing MT as an opportunity to boost core attentional capacities and connecting this to professional and academic goals in addition to wellness, MBAT-Rx appealed to a wide variety of students. CONCLUSIONS: Our ongoing work suggests that framing MT as both a professional development and wellness promotion tool, taught by physicians themselves, and structured around students' time demands, may be a successful model for medical schools looking to increase the impact of their mindfulness offerings. Such programs are needed to equip medical students to navigate the demands of a challenging healthcare training landscape.

Divergent androgenic modulation of SARS-CoV-2 infection cooperates with dysregulated immune response to dictate worse COVID-19 outcomes in men.

BACKGROUND: Sex-determined differences are rarely addressed in the management of diseases, despite well-known contrasting outcomes between female and male patients. In COVID-19 there is a remarkable disparity, with higher rates of mortality and more severe acute disease in men compared to women, who are mostly affected by long COVID-19. Furthermore, whether androgens play a protective or detrimental role in COVID-19 is still a matter of debate. Hence, the adequate management of the disease, especially regarding men presenting acute disease aggravation, still needs important data to elucidate the interplay between sex hormones and host immune responses that drive the worse evolution in male patients. METHODS: A cohort of 92 controls and 198 non-severe and severe COVID-19 patients, from both sexes, was assessed for clinical outcomes, plasma steroids, gonadotropins, sex hormone binding globulin (SHBG) and immune mediators, before vaccination. These data were correlated with the global gene expression of blood leukocytes. The androgen receptor (AR) signaling pathway was investigated by transcriptomics and tracheal aspirate was obtained from severe patients for SARS-COV-2 quantification in the respiratory tract. The interplay among clinical, endocrine and immunological data deciphered the sex differences in COVID-19. Importantly, statistical analyses, using 95% confidence interval, considered confounding factors such as age and comorbidities, to definitely parse the role of androgens in the disease outcome. RESULTS: There were notable contrasting levels of testosterone and dihydrotestosterone (DHT) throughout the disease course in male but not female patients. Inflammatory mediators presented significant negative correlations with testosterone, which was partially dependent on age and diabetes in men. Male subjects with severe COVID-19 had a significant up regulation of the AR signaling pathway, including modulation of TMPRSS2 and SRD5A1 genes, which are related to the viral infection and DHT production. Indeed, men had a higher viral load in the tracheal aspirate and levels of DHT were associated with increased relative risk of death. In contrast, the testosterone hormone, which was notably reduced in severe disease, was significantly related with susceptibility to COVID-19 worsening in male patients. Secondary hypogonadism was ruled out in the male severe COVID-19 subjects, as FSH, LH, and SHBG levels were not significantly altered. Instead, these subjects tended to have increased gonadotropin levels. Most interestingly, in this study we identified, for the first time, combined sets of clinical and immunoendocrine parameters that together predicted progression from non-severe to severe COVID-19 in men. One of the limitations of our study was the low or undetectable levels of DHT in many patients. Then, the evaluation of enzymes related to biosynthesis and signaling by androgens was mandatory and reiterated our findings. CONCLUSIONS: These original results unraveled the disease immunoendocrine regulation, despite vaccination or comorbidities and pointed to the fundamental divergent role of the androgens testosterone and DHT in the determination of COVID-19 outcomes in men. Therefore, sex-specific management of the dysregulated responses, treatments or public health measures should be considered for the control of COVID-19 pandemic.

Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19.

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients (n = 200) and healthy controls (n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course.

The turning point of COVID-19 severity is associated with a unique circulating neutrophil gene signature.

COVID-19 has a broad spectrum of clinical manifestations associated with the host immune response heterogeneity. Despite the advances in COVID-19 research, it is still crucial to seek a panel of molecular markers that enable accurate stratification of COVID-19 patients. Here, we performed a study that combined analysis of blood transcriptome, demographic data, clinical aspects and laboratory findings from 66 participants classified into different degrees of COVID-19 severity and healthy subjects. We identified a perturbation in blood-leukocyte transcriptional profile associated with COVID-19 aggravation, which was mainly related to processes that disfavoured lymphocyte activation and favoured neutrophil activation. This transcriptional profile stratified patients according to COVID-19 severity. Hence, it enabled identification of a turning point in transcriptional dynamics that distinguished disease outcomes and non-hospitalized from hospitalized moderate patients. Central genes of this unique neutrophil signature were S100A9, ANXA3, CEACAM6, VNN1, OLFM4, IL1R2, TCN1 and CD177. Our study indicates the molecular changes that are linked with the differing clinical aspects presented by humans when suffering from COVID-19, which involve neutrophil activation.

TRPV1 modulation of contextual fear memory depends on stimulus intensity and endocannabinoid signalling in the dorsal hippocampus.

The transient receptor potential vanilloid type-1 (TRPV1) channels have been implicated in the modulation of aversive responses. The endocannabinoid anandamide acts as an endogenous TRPV1 agonist, exerting opposite functions at TRPV1 and type-1 cannabinoid receptors (CB1R). Here we tested the hypothesis that hippocampal TRPV1 modulates contextual fear memory retrieval and investigated the influence of the aversive stimulus intensity as well as the role of endocannabinoid signaling. Male C57BL/6J mice were tested for contextual fear memory after low-, moderate-, or high-intensity shock protocols. The selective TRPV1 blockers SB366791 (1-10 nmol) and 6-I-NC (2 nmol) were infused via intra-dorsal hippocampus before the retrieval test session. The local levels of endocannabinoids and Arc and Zif268 mRNAs, involved in synaptic plasticity and memory, were quantified. First, both TRPV1 blockers reduced memory retrieval in animals exposed to moderate or high (but not low) intensity training protocols. In the second series of results, the magnitude of the freezing responses positively correlated with the hippocampal anandamide levels; TRPV1 and CB1R were found co-localized in this brain region; and the CB1R antagonist, AM251, prevented the effects of SB366791. Thus, endocannabinoid signaling possibly mediates the effects of TRPV1 blockers. Finally, inhibition of memory retrieval by TRPV1 blockers increased Arc and Zif268 mRNAs and impaired fear memory reinstatement. In conclusion, the modulation of fear memories by dorsal hippocampal TRPV1 channels may depend on the aversive stimulus intensity and occur via anandamide/CB1 signaling. Moreover, TRPV1 blockers promote Arc and Zif268 transcription, with subsequent attenuation of aversive memory reinstatement.

Investigating the protective effects of mindfulness-based attention training on mind wandering in applied settings.

Introduction: Mind wandering, a phenomenon in which attention drifts away from the task-at-hand, is associated with deleterious effects on performance and well-being. As such, efforts to curb mind wandering are warranted. Recently, mindfulness training (MT) has been found to protect against mind wandering. Yet, many MT programs are at risk of falling off the implementation cliff due to challenges implementing these programs in applied settings. To mitigate against this, early-stage research in small convenience samples may be necessary to spur stakeholder engagement and collaboration. Herein, the effects of MT on mind wandering were examined via an internal meta-analysis of early-stage studies of a manualized, context-adaptable short-form MT program, referred to as Mindfulness-Based Attention Training (MBAT). Methods: Five longitudinal studies (N = 304) were conducted in a variety of organizational cohorts. Self-reported mind wandering and meta-awareness, as well as accuracy (A') and response time variability (intra-individual coefficient of variation, ICV) during performance of the sustained attention to response task (SART) were assessed at baseline (T1) and 4 weeks later (T2) in MBAT and no-training participants. Results: Standardized mean change (SMC) from T1 to T2 significantly differed between MBAT and no-training groups for mind wandering (ΔSMC = -0.387, p < 0.001), meta-awareness (ΔSMC = -0.374, p < 0.001), and ICV (ΔSMC = -0.376, p = 0.043), suggesting potential protective effects in self-reported and performance-based metrics of mind wandering. Discussion: These results serve as preliminary proof-of-concept support for MBAT's protective effects on mind wandering. Further, they suggest that MBAT is amenable to implementation across a variety of applied and organizational settings and warrants additional research employing larger sample sizes in randomized controlled designs.

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule.

The non-classical histocompatibility antigen G (HLA-G) is an immune checkpoint molecule that has been implicated in viral disorders. We evaluated the plasma soluble HLA-G (sHLA-G) in 239 individuals, arranged in COVID-19 patients (n = 189) followed up at home or in a hospital, and in healthy controls (n = 50). Increased levels of sHLA-G were observed in COVID-19 patients irrespective of the facility care, gender, age, and the presence of comorbidities. Compared with controls, the sHLA-G levels increased as far as disease severity progressed; however, the levels decreased in critically ill patients, suggesting an immune exhaustion phenomenon. Notably, sHLA-G exhibited a positive correlation with other mediators currently observed in the acute phase of the disease, including IL-6, IL-8 and IL-10. Although sHLA-G levels may be associated with an acute biomarker of COVID-19, the increased levels alone were not associated with disease severity or mortality due to COVID-19. Whether the SARS-CoV-2 per se or the innate/adaptive immune response against the virus is responsible for the increased levels of sHLA-G are questions that need to be further addressed.

Acetylcholine, Fatty Acids, and Lipid Mediators Are Linked to COVID-19 Severity.

Lipid and cholinergic mediators are inflammatory regulators, but their role in the immunopathology of COVID-19 is still unclear. Here, we used human blood and tracheal aspirate (TA) to investigate whether acetylcholine (Ach), fatty acids (FAs), and their derived lipid mediators (LMs) are associated with COVID-19 severity. First, we analyzed the perturbation profile induced by SARS-CoV-2 infection in the transcriptional profile of genes related to the ACh and FA/LM pathways. Blood and TA were used for metabolomic and lipidomic analyses and for quantification of leukocytes, cytokines, and ACh. Differential expression and coexpression gene network data revealed a unique transcriptional profile associated with ACh and FA/LM production, release, and cellular signaling. Transcriptomic data were corroborated by laboratory findings: SARS-CoV-2 infection increased plasma and TA levels of arachidonic acid, 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid, 11-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid, and ACh. TA samples also exhibited high levels of PGE2, thromboxane B2, 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid, and 6-trans-leukotriene B4 Bioinformatics and experimental approaches demonstrated robust correlation between transcriptional profile in Ach and FA/LM pathways and parameters of severe COVID-19. As expected, the increased neutrophil-to-lymphocyte ratio, neutrophil counts, and cytokine levels (IL-6, IL-10, IL-1ß, and IL-8) correlated with worse clinical scores. Glucocorticoids protected severe and critical patients and correlated with reduced Ach levels in plasma and TA samples. We demonstrated that pulmonary and systemic hyperinflammation in severe COVID-19 are associated with high levels of Ach and FA/LM. Glucocorticoids favored the survival of patients with severe/critical disease, and this effect was associated with a reduction in ACh levels.

Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress.

Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.

sTREM-1 Predicts Disease Severity and Mortality in COVID-19 Patients: Involvement of Peripheral Blood Leukocytes and MMP-8 Activity.

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.

Lemongrass and cinnamon oil nanoemulsions: Formulation and study of their physical stability and activity against Zygosaccharomyces bailii.

The optimal conditions for elaborating oil/water nanoemulsions of lemongrass (LG), cinnamon bark (CB) and cinnamon leaves (CL) essential oils and their antimicrobial activity against Zygosaccharomyces bailii at pH 4.00 were studied. The effect of the emulsification methodology on the physical stability and antimicrobial activity of the nanoemulsions were also evaluated. Furthermore, the sensory impact of nanoemulsions added to an apple juice was tested. LG and CL nanoemulsions were elaborated by ultrasonication and CB nanoemulsion, by high-speed homogenization. They were stable for at least 120 days at 25 °C. They exhibited antimicrobial activity against Z. bailii being CB the most effective since it showed the smallest MIC value (156.3 mg/l), followed by LG (468.8 mg/l) and CL (1250.0 mg/l). A slight increase in growth rate was observed due to ultrasonication. An additive interaction in relation to the inhibitory effect between LG and CB nanoemulsions against Z. bailii was observed. While nanoemulsions obtained would be used as natural antimicrobial agents in food and beverage products, only LG nanoemulsion at MIC concentration diluted was acceptable in juice showing the sensory impact of essential oils on foods.

Cholinergic and lipid mediators crosstalk in Covid-19 and the impact of glucocorticoid therapy

Cytokine storms and hyperinflammation, potentially controlled by glucocorticoids, occur in COVID-19; the roles of lipid mediators and acetylcholine (ACh) and how glucocorticoid therapy affects their release in Covid-19 remain unclear. Blood and bronchoalveolar lavage (BAL) samples from SARS-CoV-2- and non-SARS-CoV-2-infected subjects were collected for metabolomic/lipidomic, cytokines, soluble CD14 (sCD14), and ACh, and CD14 and CD36-expressing monocyte/macrophage subpopulation analyses. Transcriptome reanalysis of pulmonary biopsies was performed by assessing coexpression, differential expression, and biological networks. Correlations of lipid mediators, sCD14, and ACh with glucocorticoid treatment were evaluated. This study enrolled 190 participants with Covid-19 at different disease stages, 13 hospitalized non-Covid-19 patients, and 39 healthy-participants. SARS-CoV-2 infection increased blood levels of arachidonic acid (AA), 5-HETE, 11-HETE, sCD14, and ACh but decreased monocyte CD14 and CD36 expression. 5-HETE, 11-HETE, cytokines, ACh, and neutrophils were higher in BAL than in circulation (fold-change for 5-HETE 389.0; 11-HETE 13.6; ACh 18.7, neutrophil 177.5, respectively). Only AA was higher in circulation than in BAL samples (fold-change 7.7). Results were considered significant at P<0.05, 95%CI. Transcriptome data revealed a unique gene expression profile associated with AA, 5-HETE, 11-HETE, ACh, and their receptors in Covid-19. Glucocorticoid treatment in severe/critical cases lowered ACh without impacting disease outcome. We first report that pulmonary inflammation and the worst outcomes in Covid-19 are associated with high levels of ACh and lipid mediators. Glucocorticoid therapy only reduced ACh, and we suggest that treatment may be started early, in combination with AA metabolism inhibitors, to better benefit severe/critical patients.

Voicing Jordanian Adolescents' Suicide.

BACKGROUND: Studies focusing on adolescent suicide in Arab countries are particularly scarce, with the few available undertaken from within an epidemiological paradigm. OBJECTIVE: This study aimed to understand Jordanian adolescents' perceptions, beliefs, and attitudes toward suicide. METHODS: A qualitative design using 12 dual-moderator focus group discussions was conducted in public schools. Participants were selected from the three main regions of the country (rural southern, urban central, and suburban northern). Participants included Jordanian adolescent boys and girls, aged 14-17 years, who reported experiencing mild to moderate depressive symptoms. A relational content analysis approach was used for coding data, and a content analysis was used to identify salient thematic categories. Data were analyzed using NVivo software. RESULTS: Four themes emerged, including perceived risk factors, perceived protective factors, active and passive suicidal ideations, and e-games and Internet influences. Main risk factors were depression; anxiety; stigma, shame, and isolation; family issues; life pressures; and guilt. Conversely, religiosity, perceived positive family functioning, and availability of long-term goals seemed to confer resilience to adolescents' suicidal ideation and behavior. Passive suicidality (having death wishes without any plans to complete suicide) was noticed most among participants who feared jeopardizing the family's reputation if they committed suicide. Several boys with active suicidal ideations used the Blue Whale Challenge e-game to learn how to complete suicide and relinquish their problems. DISCUSSION: Suicide is a multifactorial problem requiring multimodal strategies. Evidence from this research suggests that those most passionate about the outcome of interest are encouraged to redouble efforts to reduce modifiable risk factors, enrich protective factors, target the underlying psychiatric illness that informs suicidal ideations and behavior, and research the effect of social media and Internet activity more deeply. Parents are advised to monitor the online activities of their children and familiarize themselves with the digital applications they use.

Prognostic value of sTREM-1 in COVID-19 patients: a biomarker for disease severity and mortality

Background: The uncontrolled inflammatory response plays a critical role in the novel coronavirus disease (COVID-19) and triggering receptor expressed on myeloid cells-1 (TREM-1) is thought to be intricate to inflammatory signal amplification. This study aims to investigate the association between soluble TREM-1 (sTREM-1) and COVID-19 as a prognostic biomarker to predict the disease severity, lethality and clinical management.Methods: We enrolled 91 patients with COVID-19 in domiciliary care (44 patients) or in hospital care (47 patients), who were classified after admission into mild, moderate, severe and critical groups according to their clinical scores. As non-COVID-19 control, 30 healthy volunteers were included. Data on demographic, comorbidities and baseline clinical characteristics were obtained from their medical and nurse records. Peripheral blood samples were collected at admission and after hospitalization outcome to assess cytokine profile and sTREM-1 level by specific immunoassays Results: Within COVID-19 patients, the highest severity was associated with the most significant elevated plasma levels sTREM-1. Using receiver operating curve analysis (ROC), sTREM-1 was found to be predictive of disease severity (AUC= 0.988) and the best cut-off value for predicting in-hospital severity was [≥] 116.5 pg/mL with the sensitivity for 93.3% and specificity for 95.8%. We also described the clinical characteristics of these patients and explored the correlation with markers of the disease aggravation. The levels of sTREM-1 were positively correlated with IL-6, IL-10, blood neutrophils counts, and critical disease scoring (r= 0.68, p<0.0001). On the other hand, sTREM-1 level was significantly negative correlated with lymphocytes counting, and mild disease (r= -0.42, p<0.0001). Higher levels of sTREM-1 were related to poor outcome and death, patients who received dexamethasone tended to have lower sTREM-1 levels. Conclusion: Our results indicated that sTREM-1 in COVID-19 is associated with severe disease development and a prognostic marker for mortality. The use of severity biomarkers such as sTREM-1 together with patients clinical scores could improve the early recognition and monitoring of COVID-19 cases with higher risk of disease worsening. Key words: COVID-19; sTREM-1; Inflammation; Biomarker; Severity; Mortality.

NOD2 Deficiency Promotes Intestinal CD4+ T Lymphocyte Imbalance, Metainflammation, and Aggravates Type 2 Diabetes in Murine Model.

Type 2 diabetes (T2D) is a metabolic disease characterized by increased inflammation, NOD-like receptors (NLRs) activation and gut dysbiosis. Our research group has recently reported that intestinal Th17 response limits gut dysbiosis and LPS translocation to visceral adipose tissue (VAT), protecting against metabolic syndrome. However, whether NOD2 receptor contributes intestinal Th17 immunity, modulates dysbiosis-driven metabolic tissue inflammation, and obesity-induced T2D remain poorly understood. In this context, we observed that mice lacking NOD2 fed a high-fat diet (HFD) display severe obesity, exhibit greater adiposity, and more hepatic steatosis compared to HFD-fed wild-type (WT) mice. In addition, they develop increased hyperglycemia, worsening of glucose intolerance, and insulin resistance. Notably, the deficiency of NOD2 causes a deviation from M2 macrophage and regulatory T cells (Treg) to M1 macrophage and mast cells into VAT compared to WT mice fed HFD. An imbalance was also observed in Th17/Th1 cell populations, with reduced IL-17 and IL-22 gene expression in the mesenteric lymph nodes (MLNs) and ileum, respectively, of NOD2-deficient mice fed HFD. 16S rRNA sequencing indicates lower richness, alpha diversity, and a depletion of Allobaculum, Lactobacillus, and enrichment with Bacteroides genera in these mice compared to HFD-fed WT mice. These alterations were associated with disrupted tight-junctions expression, augmented serum LPS, and bacterial translocation into VAT. Overall, NOD2 activation is required for a protective Th17 over Th1 immunity in the gut, which seems to decrease gram-negative bacteria outgrowth in gut microbiota, attenuating the endotoxemia, metainflammation, and protecting against obesity-induced T2D.

Social Determinants of Resilience Among Syrian Refugees in Jordan.

The current study explores the level and social determinants of resilience among Syrian refugees residing in Jordan. Having high levels of resilience can help refugees positively adapt to challenges and cope with the burden of stressors associated with warfare, turmoil, and displacement. A sample of 151 Syrian refugees ages 18 to 69 residing in Jordan completed the Arabic version of the Connor-Davidson Resilience Scale. Resilience scores among Syrian refugees in Jordan were generally low. Refugees' place of residence, educational level, employment status, and monthly income were significantly associated with lower resilience scores and together explain approximately 37% of variance in resilience scores. Tailored resilience-building and educational programs are needed to help Syrian refugees develop the ability to withstand, adapt to, and recover from stress and adversity, and maintain or return to healthy mental states. Future research involving longitudinal assessment of resilience is needed to fully understand the role and determinants of resilience in this population. [Journal of Psychosocial Nursing and Mental Health Services, 58(8), 31-38.].

Interleukin-17/interleukin-17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high-fat diet-induced metabolic syndrome model.

Sound evidence supports a role for interleukin-17 (IL-17) -producing γδ T cells and IL-17-producing helper T (Th17) cells in intestinal homeostasis, especially in intestinal barrier integrity. In the present study, we aimed to evaluate the role of IL-17 cytokine in the regulation of intestinal immunity and obesity-induced metabolic syndrome (MetS) in an experimental murine model. C57BL/6 wild-type (WT) mice and mice lacking the IL-17 cytokine receptor (IL-17RA-/- ) were fed either a control diet (CD) or a high-fat diet (HFD) for 9 weeks. Our data demonstrate that IL-17RA-/- mice are protected against obesity, but develop hyperglycemia, hyperinsulinemia and insulin resistance. In parallel, HFD-fed IL-17RA-/- mice display intense inflammation in the ileum compared with WT mice on the HFD. IL-17RA-/- mice fed the HFD exhibit impaired neutrophil migration to the intestinal mucosa and reduced gene expression of the CXCL-1 chemokine and CXCR-2 receptor in the ileum. Interestingly, the populations of neutrophils (CD11b+  Ly6G+ ) and anti-inflammatory macrophages (CD11b+  CX3CR1+ ) are increased in the mesenteric lymph nodes of these mice. IL-17RA-/- mice on the HFD also display increased commensal bacterial translocation into the bloodstream and elevated lipopolysaccharide (LPS) levels in the visceral adipose tissue (VAT). Metagenomic analysis of bacterial 16S gene revealed increased Proteobacteria and Bacteroidetes phyla, the main representatives of Gram-negative bacteria, and reduced Akkermansia muciniphila in the fecal samples of IL-17RA-/- mice fed the HFD. Together, these data indicate that the IL-17/IL-17R axis drives intestinal neutrophil migration, limits gut dysbiosis and attenuates LPS translocation to VAT, resulting in protection to MetS.