Annexin A1 based inflammation resolving mediators and nanomedicines for inflammatory bowel disease therapy.

Inflammatory bowel diseases (IBD) such as Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic, progressive, and relapsing disorders of the gastrointestinal tract (GIT), characterised by intestinal epithelial injury and inflammation. Current research shows that in addition to traditional anti-inflammatory therapy, resolution of inflammation and repair of the epithelial barrier are key biological requirements in combating IBD. Resolution mediators include endogenous lipids that are generated during inflammation, e.g., lipoxins, resolvins, protectins, maresins; and proteins such as Annexin A1 (ANXA1). Nanoparticles can specifically deliver these potent inflammation resolving mediators in a spatiotemporal manner to IBD lesions, effectively resolve inflammation, and promote a return to homoeostasis with minimal collateral damage. We discuss these exciting and timely concepts in this review.

Salivary C-reactive protein exhibits a diurnal pattern and relates to biobehavioral health in military men.

C-reactive protein is a systemic inflammatory biomarker that is positively associated with the development of disease. Salivary C-reactive protein (sCRP) has previously been reported to have a diurnal rhythm with higher levels upon awakening and lower levels thereafter. The aims of this study were to evaluate the stability of sCRP across two days, characterize the daily sCRP pattern, compute morning sCRP parameters, and evaluate associations with biobehavioral health in US Navy Explosive Ordnance Disposal (EOD) technicians. Seventy male EOD technicians (age = 34.9 ±â€¯6.5 years) participated in this study, which included a tablet-based survey, measures of health and fitness, and saliva collection. In a free-living setting, participants self-collected saliva on 2 consecutive days at WAKE, WAKE+30, WAKE+60, 4p.m., and 9p.m., for a total of 10 samples. Parameters (e.g., area under the curve) were computed to characterize the morning sCRP magnitude and pattern. Pearson product-moment correlation analyses were used to assess the stability of sCRP samples and parameters across the study period and to examine associations with biobehavioral health. Average sCRP concentrations for the 2-day period were evaluated using an analysis of variance with repeated measures. The stabilities between corresponding time points on Days 1 and 2 were very high (rs = 0.87-.94, all ps ≤ 0.001). sCRP concentrations were highest at WAKE, decreased by 73.6 % at WAKE+30, and then plateaued for the rest of the day. Parameters stabilities were good to excellent (rs = 0.77-.98, all ps ≤ 0.001). We also observed associations between sCRP parameters, self-reported health behaviors, and objective measures of health and fitness. In this study of a military population, we characterized sCRP as diurnal with robust stability across 2 consecutive days, which demonstrates the feasibility of sCRP as a biomarker. These results have significant implications for study methodology and for using sCRP as a marker of dysfunction or disease.

Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties.

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial-mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient's age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences.

Mediators of Periodontitis complementing the development of Neural Disorders.

As a common oral health concern, periodontitis has been a source of attention for the global health community because of its linkage with systemic and neurological diseases. The purpose of the present study is to reveal the mediating role of specific cytokines, neuropeptides, and pathogens in the association of chronic periodontitis and neural disorders. To find the related literature different search engines namely PMC, Science Direct, PubMed, Research Gate, and Google Scholar were explored for a study period of five months from October 2022 to February 2023. This review offers a summary of those neuronal diseases that were more related to human behaviors in association with chronic periodontitis. Those neuronal pathologies mainly included Alzheimer's disease, psychosis, stress, anxiety, dementia, Alzheimer's, major depressive disorder, and diabetic peripheral neuropathy, which may otherwise remain subside or even control in the absence of chronic periodontitis and its mediators. Specifically, periodontitis related specific cytokines i.e. IL-6, IL-1, Tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and alpha1-antichymotrypsin, neuropeptides such as insulin-like growth factor-2 (IGF-2), neuropeptide Y, substance P, neurokinin A, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP), and a polybacterial pathogenic consortium of porphyromonas gingivalis, tannerella forsythia, and treponema denticola, were involved in the mediation and exacerbation of the associated neuronal cognitive pathologies.

Disrupted Resolution Mechanisms Favor Altered Phagocyte Responses in COVID-19.

[Figure: see text].

Association of dietary and blood inflammatory indicators with depression, anxiety, and stress in adults with vitamin D deficiency.

BACKGROUND: There is growing evidence that vitamin D may be related to mental health. The aim of the current study was to investigate the association of dietary and blood inflammatory factors with mental health disorders in subjects with vitamin D deficiency, shedding further light on the complex interplay of these conditions. METHOD: In this cross-sectional study, 306 subjects completed the validated Depression, Anxiety, and Stress Scale questionnaire to evaluate their depression, anxiety, and stress scores. Dietary inflammatory index (DII) and healthy eating index (HEI) were calculated using a validated 65-item food frequency questionnaire. Blood samples were taken and vitamin D, cytokine, and hs-CRP levels were measured using enzyme-linked immunosorbent assay kits. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) were calculated using standard laboratory methods. RESULTS: The subjects were divided into two groups based on their vitamin D levels: a vitamin D < 20 µg/dl group (N = 257) and a vitamin D ≥ 20  µg/dl group (N = 49). Between group analysis revealed that only DII (p = 0.015), platelet (p = 0.04), and hs-CRP (p = 0.015) were significantly different. In adults with vitamin D levels below 20 µg/dl, NLR and DII were significantly higher in subjects with anxiety (p < 0.05), and this relationship remained significant only for NLR after adjusting for age and sex. Additionally, PLR and HEI were significantly different in depressed compared to non-depressed subjects, and this association remained significant only for HEI after adjusting for age and sex. CONCLUSION: In subjects with vitamin D deficiency, increased levels of PLR, NLR, and DII were associated with depression and anxiety, while HEI was negatively associated with depression. These associations were not found in subjects with vitamin D levels ≥20 µg/dl.

Development of Acute Transverse Myelitis following COVID-19 Infection: A Review on the Potential Pathways.

BACKGROUND: Acute transverse myelitis (ATM) is a rare neurological disorder in adults characterized by localized inflammation of gray and white matter in one or more contiguous spinal cord segments in the absence of a compressive injury. Several reports have connected the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the pathophysiology of ATM. SUMMARY: Direct invasion of the spinal cord, cytokine storm, or an autoimmune response are the possible pathways by which the SARS-CoV-2 virus can affect the spinal cord and lead to ATM. Direct invasion is facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) receptors on the membranes of the spinal cord neurons. Cytokine storm syndrome could be derived from elevated levels of several immunological factors following severe involvement with coronavirus disease 2019 (COVID-19). Finally, autoimmune responses can cause post-infectious ATM through several hypothesized processes, including molecular mimicry, epitope spreading, bystander activation, and polyclonal B-cell activation. KEY MESSAGES: COVID-19-induced ATM is mostly a longitudinally-extensive ATM (LEATM), in which more spinal cord segments are damaged, which results in a worse sequel compared to short-segment ATM. Therefore, it is suggested that COVID-19 patients, particularly severe cases, be followed up for a probable incidence of ATM, even long after recovery from the disease and elimination of the virus from the host, because an early diagnosis and effective therapy may stop the spread of inflammation to adjacent segments.

Results and insights from a phase I clinical trial of Lomecel-B for Alzheimer's disease.

HYPOTHESIS: We hypothesized that Lomecel-B, an allogeneic medicinal signaling cell (MSC) therapeutic candidate for Alzheimer's disease (AD), is safe and potentially disease-modifying via pleiotropic mechanisms of action. KEY PREDICTIONS: We prospectively tested the predictions that Lomecel-B administration to mild AD patients is safe (primary endpoint) and would provide multiple exploratory indications of potential efficacy in clinical and biomarker domains (prespecified secondary/exploratory endpoints). STRATEGY AND KEY RESULTS: Mild AD patient received a single infusion of low- or high-dose Lomecel-B, or placebo, in a double-blind, randomized, phase I trial. The primary safety endpoint was met. Fluid-based and imaging biomarkers indicated significant improvement in the Lomecel-B arms versus placebo. The low-dose Lomecel-B arm showed significant improvements versus placebo on neurocognitive and other assessments. INTERPRETATION: Our results support the safety of Lomecel-B for AD, suggest clinical potential, and provide mechanistic insights. This early-stage study provides important exploratory information for larger efficacy-powered clinical trials.

The Influence of Fixed Dental Prostheses on the Expression of Inflammatory Markers and Periodontal Status-Narrative Review.

A dental prosthesis will only be successful if the restoration lasts for a long period and does not cause any illness. The presence of permanent prosthetic restorations has been linked to an increased risk of periodontal infections, according to a large body of research that has been gathered. When chronic inflammation is brought on by fixed prosthetic constructions, both cellular and noncellular immunity are activated as adaptive immune mechanisms. It has previously been stated that both clinically adequate and inadequate restorations might cause gingival inflammation. Areas surrounding the abutment teeth presented periodontal pockets, attachment loss, congestion, bleeding on probing, and gingival hyperplasia after fixed restorations were removed. The depth of pockets, bleeding on probing, and bone loss are all closely correlated with disease's severity and IL-1ß concentration in gingival crevicular fluid; IL-1ß shows higher values in disease sites than in healthy ones. hs-CRP and TNF-α blood levels showed a considerable reduction one day after fixed restorations were applied, in comparison with the pre-treatment values. Collaboration between prosthodontists and periodontists is essential for a good treatment outcome since it will increase the restoration's lifespan, enhance periodontal health, and improve the quality of life for dental patients.

Polymorphisms in immune-mediator genes and the risk of dengue virus infection: Lights from a systematic revaluation by Bayesian approaches.

Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.

Intracerebral Proinflammatory Cytokine Increase in Surgically Evacuated Intracerebral Hemorrhage: A Microdialysis Study.

BACKGROUND: Treatment options for spontaneous intracerebral hemorrhage (ICH) are limited. A possible inflammatory response in the brain tissue surrounding an ICH may exacerbate the initial injury and could be a target for treatment of subsequent secondary brain injury. The study objective was to compare levels of inflammatory mediators in the interstitial fluid of the perihemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) in the acute phase after surgical evacuation of ICH, with the hypothesis being that a difference could be demonstrated between the PHZ and the SNX. METHODS: In this observational study, ten patients needing surgical evacuation of supratentorial ICH received two cerebral microdialysis catheters: one in the PHZ and one in the SNX that is remote from the ICH. The microdialysate was analyzed for energy metabolites (including lactate pyruvate ratio and glucose) and for inflammatory mediators by using a multiplex immunoassay of 27 cytokines and chemokines at 6-10 h, 20-26 h, and 44-50 h after surgery. RESULTS: A metabolic crisis, indicated by altered energy metabolic markers, that persisted throughout the observation period was observed in the PHZ when compared with the SNX. Proinflammatory cytokines interleukin (IL) 8, tumor necrosis factor α, IL-2, IL-1ß, IL-6 and interferon γ, anti-inflammatory cytokine IL-13, IL-4, and vascular endothelial growth factor A were significantly higher in PHZ compared with SNX and were most prominent at 20-26 h following ICH evacuation. CONCLUSIONS: Higher levels of both proinflammatory and anti-inflammatory cytokines in the perihemorrhagic brain tissue implies a complex role for inflammatory mediators in the secondary injury cascades following ICH surgery, suggesting a need for targeted pharmacological interventions.

High-frequency near-infrared diode laser irradiation suppresses IL-1ß-induced inflammatory cytokine expression and NF-κB signaling pathways in human primary chondrocytes.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are common inflammation-associated cartilage degenerative diseases. Recent studies have shown that low-level diode laser treatment can reduce inflammatory cytokine expressions in cartilage. We recently reported that high-frequency low-level diode laser irradiation attenuates matrix metalloproteinases (MMPs) expression in human primary chondrocytes. However, the molecular mechanism underlying the effect of high-frequency low-level diode laser on chondrocytes remains unclear. Therefore, we aimed to elucidate the effect of high-frequency low-level diode laser irradiation on inflammatory cytokine expression in human primary chondrocytes. Normal human articular chondrocytes were treated with recombinant interleukin-1 beta (IL-1ß) for 30 min or 24 h and irradiated with a high-frequency NIR diode laser at 8 J/cm2. The expression of IL-1ß, interleukin-6, and tumor necrosis factor-alpha was assessed using western blot analysis. To evaluate the nuclear factor-kappa B (NF-κB) signaling pathway, the phosphorylation, translocation, and DNA-binding activity of NF-κB were detected using western blot analysis, immunofluorescence analysis, electrophoretic mobility shift assay, and enzyme-linked immunosorbent assay analysis. High-frequency low-level diode laser irradiation decreased inflammatory cytokine expression in IL-1ß-treated chondrocytes. Moreover, high-frequency low-level diode laser irradiation decreased the phosphorylation, nuclear translocation, and DNA-binding activity of NF-κB in the IL-1ß-treated state. However, irradiation alone did not affect NF-κB activity. Thus, high-frequency low-level diode laser irradiation at 8 J/cm2 can reduce inflammatory cytokine expressions in normal human articular chondrocytes through NF-κB regulation. These findings indicate that high-frequency low-level diode laser irradiation may reduce the expression of inflammatory cytokines in OA and RA.

Proof-of-Principle Study Suggesting Potential Anti-Inflammatory Activity of Butyrate and Propionate in Periodontal Cells.

Short-chain fatty acids (SCFAs) are potent immune modulators present in the gingival crevicular fluid. It is therefore likely that SCFAs exert a role in periodontal health and disease. To better understand how SCFAs can module inflammation, we screened acetic acid, propionic acid, and butyric acid for their potential ability to lower the inflammatory response of macrophages, gingival fibroblasts, and oral epithelial cells in vitro. To this end, RAW 264.7 and primary macrophages were exposed to LPSs from Porphyromonas gingivalis (P. gingivalis) with and without the SCFAs. Moreover, gingival fibroblasts and HSC2 oral epithelial cells were exposed to IL1ß and TNFα with and without the SCFAs. We report here that butyrate was effective in reducing the lipopolysaccharide (LPS)-induced expression of IL6 and chemokine (C-X-C motif) ligand 2 (CXCL2) in the RAW 264.7 and primary macrophages. Butyrate also reduced the IL1ß and TNFα-induced expression of IL8, chemokine (C-X-C motif) ligand 1 (CXCL1), and CXCL2 in gingival fibroblasts. Likewise, butyrate lowered the induced expression of CXCL1 and CXCL2, but not IL8, in HSC2 cells. Butyrate further caused a reduction of p65 nuclear translocation in RAW 264.7 macrophages, gingival fibroblasts, and HSC2 cells. Propionate and acetate partially lowered the inflammatory response in vitro but did not reach the level of significance. These findings suggest that not only macrophages, but also gingival fibroblasts and oral epithelial cells are susceptive to the anti-inflammatory activity of butyrate.

Nutraceutic Potential of Bioactive Compounds of Eugenia dysenterica DC in Metabolic Alterations.

The fruit and leaves of Eugenia dysenterica DC., locally known as cagaita, are rich in antioxidant glycosylated quercetin derivatives and phenolic compounds that have beneficial effects on diabetes mellitus, hypertension and general inflammation. We conducted a literature search to investigate the nutraceutical potentials of these phenolic compounds for treating obesity, diabetes mellitus and intestinal inflammatory disease. The phenolic compounds in E. dysenterica have demonstrated effects on carbohydrate metabolism, which can prevent the development of these chronic diseases and reduce LDL (low-density lipoprotein) cholesterol and hypertension. E. dysenterica also improves intestinal motility and microbiota and protects gastric mucosa, thereby preventing inflammation. However, studies are necessary to identify the mechanism by which E. dysenterica nutraceutical compounds act on such pathological processes to support future research.

Association between chemosensory dysfunctions and inflammatory biomarkers in patients with SARS-CoV-2 infection: a systematic review and meta-analysis.

BACKGROUND: There is evidence that chemosensory dysfunctions, including smell and taste disorders, are common findings in patients with SARS-CoV-2 infection. However, the underlying biological mechanisms and the role of inflammatory markers are still poorly understood. AIM: To investigate the inflammatory biomarkers levels in patients with COVID-19 presenting chemosensory dysfunctions. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A systematic literature search was performed from January 1, 2020, to May 12, 2022. Observational studies that provided data on hematological, biochemical, infection-related indices and cellular immunity, and coagulation function in patients with COVID-19 experiencing smell and/or taste disorders were considered eligible. Effect sizes were reported as standardized mean difference (SMD) with 95% confidence intervals (CI). A negative effect size indicated that the inflammatory biomarker levels were lower among patients with chemosensory dysfunctions. RESULTS: Eleven studies were included. Patients with chemosensory disturbances had lower levels of leukocytes (SMD - 0.18, 95% CI - 0.35 to - 0.01, p = 0.04), lactate dehydrogenase (SMD - 0.45, 95% CI - 0.82 to - 0.09, p = 0.01), IL-6 (SMD - 0.25, 95% CI - 0.44 to - 0.06, p < 0.01), and C-reactive protein (SMD - 0.33, 95% CI - 0.58 to - 0.08, p < 0.01) than patients without chemosensory disturbances. CONCLUSION: Patients with SARS-CoV-2 infection who have olfactory and gustatory disorders have a lower inflammatory response than patients who do not have chemosensory alterations. The presence of these symptoms may indicate a more favorable clinical course for COVID-19.

[How T lymphocytes coordinate rheumatic inflammation]. / Wie T-Lymphozyten rheumatische Entzündung koordinieren.

Helper T (Th) cells play a decisive role in triggering and maintaining chronic rheumatic inflammation. Via secretion of proinflammatory cytokines and expression of costimulatory cell surface molecules, Th lymphocytes coordinate the recruitment and activation of effector cells, which are ultimately responsible for the immunopathology and tissue destruction. However, therapeutic approaches aimed at eliminating Th cells were unsuccessful due to their lack of selectivity. At the German Rheumatism Research Center (Deutsches Rheuma-Forschungszentrum, DRFZ), we are working to improve the understanding of the Th cells involved in chronic inflammatory reactions. Based on this understanding, our aim is to develop novel treatment strategies that selectively target the pathogenic Th lymphocytes causing rheumatic inflammation. The current article summarizes the DRFZ's research activities on this subject.

Different expression patterns of inflammatory cytokines induced by lipopolysaccharides from Escherichia coli or Porphyromonas gingivalis in human dental pulp stem cells.

BACKGROUND: Lipopolysaccharide (LPS) is one of the leading causes of pulpitis. The differences in establishing an in vitro pulpitis model by using different lipopolysaccharides (LPSs) are unknown. This study aimed to determine the discrepancy in the ability to induce the expression of inflammatory cytokines and the underlying mechanism between Escherichia coli (E. coli) and Porphyromonas gingivalis (P. gingivalis) LPSs in human dental pulp stem cells (hDPSCs). MATERIAL AND METHODS: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to evaluate the mRNA levels of inflammatory cytokines including IL-6, IL-8, COX-2, IL-1ß, and TNF-α expressed by hDPSCs at each time point. ELISA was used to assess the interleukin-6 (IL-6) protein level. The role of toll-like receptors (TLR)2 and TLR4 in the inflammatory response in hDPSCs initiated by LPSs was assessed by QRT-PCR and flow cytometry. RESULTS: The E. coli LPS significantly enhanced the mRNA expression of inflammatory cytokines and the production of the IL-6 protein (p < 0.05) in hDPSCs. The peaks of all observed inflammation mediators' expression in hDPSCs were reached 3-12 h after stimulation by 1 µg/mL E. coli LPS. E. coli LPS enhanced the TLR4 expression (p < 0.05) but not TLR2 in hDPSCs, whereas P. gingivalis LPS did not affect TLR2 or TLR4 expression in hDPSCs. The TLR4 inhibitor pretreatment significantly inhibited the gene expression of inflammatory cytokines upregulated by E. coli LPS (p < 0.05). CONCLUSION: Under the condition of this study, E. coli LPS but not P. gingivalis LPS is effective in promoting the expression of inflammatory cytokines by hDPSCs. E. coli LPS increases the TLR4 expression in hDPSCs. P. gingivalis LPS has no effect on TLR2 or TLR4 expression in hDPSCs.

Dysregulation of immune response in otitis media.

OBJECTIVE: Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We evaluate the evidence of a dysregulated immune response in the pathogenesis of OM. METHODS: A comprehensive systematic review of the literature using search terms [otitis media OR glue ear OR AOM OR OME] OR [middle ear AND (infection OR inflammation)] which were run through Medline and Embase via Ovid, including both human and animal studies. In total, 82 955 studies underwent automated filtering followed by manual screening. One hundred studies were included in the review. RESULTS: Most studies were based on in vitro or animal work. Abnormalities in pathogen detection pathways, such as Toll-like receptors, have confirmed roles in OM. The aetiology of OM, its chronic subgroups (chronic OM, persistent OM with effusion) and recurrent acute OM is complex; however, inflammatory signalling mechanisms are frequently implicated. Host epithelium likely plays a crucial role, but the characterisation of human middle ear tissue lags behind that of other anatomical subsites. CONCLUSIONS: Translational research for OM presently falls far behind its clinical importance. This has likely hindered the development of new diagnostic and treatment modalities. Further work is urgently required; particularly to disentangle the respective immune pathologies in the clinically observed phenotypes and thereby work towards more personalised treatments.

Systemic circulating inflammatory burden and periodontitis in adolescents.

OBJECTIVES: To analyze the association between systemic inflammatory burden of cardiovascular disease (CVD) risk and periodontitis in adolescents, including mediating pathways triggered by their common risk factors. MATERIALS AND METHODS: Using a population-based sample study (n = 405) of Brazilian adolescents (17-18 years old), direct and mediation pathways triggered by "Socioeconomic Status," "Adiposity," Smoking, and "Blood Pressure" were modelled for the association between the "Systemic Circulating Inflammatory Burden of CVD Risk" (IL-1ß, IL-6, IL-8, TNF-α) and the "Initial Periodontitis" (bleeding on probing (BoP), probing depth (PD) ≥ 4 mm, clinical attachment loss (CAL) ≥ 4 mm), both as continuous latent variables, using structural equation modeling. Sensitivity analysis was performed for the outcomes "Gingivitis" (visible plaque; BoP); "Moderate Periodontitis" (PD ≥ 5 mm and CAL ≥ 5 mm) and periodontitis (CDC-AAP case definition). RESULTS: Higher "Systemic Circulating Inflammatory Burden of CVD Risk" was directly associated with higher "Initial Periodontitis" (standardized coefficient [SC] = 0.178, P value < 0.001). Lower "Socioeconomic Status" (SC = - 0.022, P value = 0.015) and Smoking (SC = 0.030, P value = 0.021) triggered the "Initial Periodontitis", mediated by "Systemic Circulating Inflammatory Burden of CVD Risk". Sensitivity analysis showed a dose-response relationship between "Systemic Circulating Inflammatory Burden of CVD Risk" and "Moderate Periodontitis" (SC = 0.323, P value = 0.021). CONCLUSIONS: "Systemic Circulating Inflammatory Burden of CVD Risk" appeared as an underlying mechanism of early periodontal breakdown in adolescents, also triggered by social vulnerability and smoking. CLINICAL RELEVANCE: The association between periodontitis and CVD in adulthood seems to establish much earlier in life than had been previously studied, giving impetus to preventive approaches focused on their common risk factors.

IL-6 Predicts Poor Early Post-Natal Growth in Very Low-Birth-Weight Infants in a Low-Middle Income Setting.

BACKGROUND: Extra-uterine growth restriction (EUGR) is common in preterms and may be associated with elevated pro-inflammatory cytokines. OBJECTIVE: Describe postnatal growth in a cohort of very low-birth-weight (VLBW) infants and determine the association of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) in umbilical cord blood with growth at 40 weeks and 12 months postmenstrual age (PMA). METHODS: Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019 with follow-up to 31 March 2020. Infants <1500 g at birth were enrolled, cord blood collected for IL-6 and TNF-α assays and postnatal care, including anthropometry, provided to 12 months PMA. Informed consent and ethics approval were obtained. RESULTS: In total, 279 patients were enrolled; 84 (30.1%) died before 12 months and 91 (32.6%) lost to follow-up. Anthropometry was available for 151 infants at 40 weeks and 105 at 12 months. Z-Scores at 40 weeks for males and females combined were -2.5, -2.1 and -1.2 for weight, length and head circumference. EUGR occurred in 103/113 (91.2%), 98/107 (91.6%) and 70/109 (64.2%) participants for weight, length and head circumference. Elevated IL-6 was associated with restricted weight (56.0 vs. 14.5 pg/ml, p = 0.02) and length (60.4 vs. 7.3 pg/ml, p = 0.01) at 40 weeks. There was no difference in IL-6 at 12 months and no difference in TNF-α at 40 weeks or 12 months. CONCLUSION: The study reports significant EUGR. Elevated IL-6 was associated with growth restriction at 40 weeks but not 12 months PMA.