Subclinical Inflammation Research Articles

Gestational diabetes mellitus may predispose to metabolic dysfunction-associated steatotic liver disease.

The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease (MASLD). Insulin resistance, subclinical inflammation, dyslipidemia, obesity, and hypertension are all factors in this reciprocal interaction that contribute to the development of MASLD, which includes hepatocellular carcinoma, advanced fibrosis/cirrhosis, and non-alcoholic steatohepatitis (NASH). A new risk factor for MASLD/NASH that affects the course of the disease independently throughout life is gestational diabetes mellitus (GDM). Women with a history of GDM had a higher chance of developing NASH, according to a recent study that used a large-scale database. Although the precise etiology is yet unknown, temporary disruption of pancreatic beta cell activity during pregnancy may set off systemic inflammation, affecting distant organs including the liver. Early screening and management strategies are crucial in mitigating MASLD progression and preventing adverse cardiovascular events in affected individuals.

Methamphetamine Use Disorder and Inflammation: A Case-Control Study

Objective Methamphetamine use disorder (MUD) is a global health condition that impairs a person’s health which may result in morbidity and mortality. Inflammation is a crucial process playing a vital role in MUD. For this reason, it is necessary to examine biochemical parameters for follow-up and treatment alternatives.Methods We aimed to reveal the relationship between inflammatory response and MUD by evaluating peripheral hemogram parameters, leukocyte count, subtypes, and their ratios to each other, systemic immune inflammation index (SII), monocyte/high-density lipoprotein (HDL) ratio, and human C-reactive protein (CRP) in adult men with MUD. We included 76 adult male participants in the patient group and 70 adult male participants in the control group. We calculated the neutrophil/lymphocyte rate (NLR), monocyte/lymphocyte rate (MLR), platelet/lymphocyte rate (PLR), and basophil/lymphocyte rate (BLR). In addition, we obtained the SII and the monocyte/HDL rate.Results The patients’ leukocyte (p<0.001), platelet (p<0.001), plateletcrit (PCT) (p=0.002), neutrophil (p<0.001), monocyte (p=0.002), CRP (p<0.001), NLR (p=0.001), PLR (p=0.004), MLR (p=0.009), SII (p<0.001) and monocyte/HDL ratio (p<0.001) were higher than the control group. We observed a significant and positive relationship between the daily methamphetamine intake, and methamphetamine use duration (p=0.002), PCT (p=0.044), neutrophil (p=0.021), NLR (p=0.001), PLR (p=0.004), MLR (p=0.029), and SII (p<0.001). Daily methamphetamine intake had a significant and positive effect on SII. A one-unit increase in daily methamphetamine intake elevated SII by 165.53 units.Conclusion The results confirm the presence of peripheral subclinical inflammation and systemic immune inflammation in adult men with MUD.

Dysbiosis in inflammatory bowel diseases: egg, not chicken

There is agreement that inflammatory bowel diseases are, both in terms of species composition and function, associated with an altered intestinal microbiome. This is usually described by the term “dysbiosis,” but this is a vague definition lacking quantitative precision. In this brief narrative review, the evidence concerning the primary or secondary role of this dysbiotic state is critically evaluated. Among others, the following facts argue against a primary etiological impact: 1) There is no specific dysbiotic microbiome in IBD, 2) the presence or absence of mucosal inflammation has a profound impact on the composition of the microbiome, 3) dysbiosis is not specific for IBD but linked to many unrelated diseases, 4) antibiotics, probiotics, and microbiome transfer have a very limited therapeutic effect, 5) the microbiome in concordant twins is similar to disease-discordant twins, and 6) the microbiome in relatives of IBD patients later developing IBD is altered, but these individuals already display subclinical inflammation.

#2684 Free light chains levels in ANCA associated vasculitis: a new potential inflammatory biomarker

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic disease characterized by an immune-mediated process where inflammation plays a central role. The widely available serum biomarkers of inflammation are not always able to detect ongoing disease activity in ANCA-associated vasculitis (AAV) patients. Free light chains (FLCs) expression levels have been proposed as new promising biomarker in some immune-mediated and inflammatory diseases. The aim of this study is to evaluate the expression levels of FLCs in patients affected by AAV and investigate the potential effect of rituximab treatment on FLCs levels. Method We conducted a retrospective multicenter study enrolling AAV patients in complete remission of AAV (defined as BVAS/GPA = 0); those with clinical suspicion of underlying hematologic malignancy were excluded. We analyzed κ and λ FLCs serum concentrations and evaluated their correlation with biomarkers of immune system activation, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum immunoglobulin (Ig) levels, serum C3 and C4 complement and albumin levels (which has a negative correlation with acute inflammatory phase). We assessed impact of rituximab (RTX) therapy within the last 6 months on the same laboratory parameters. Results A total of 137 patients with AAV were recruited, who were gender balanced, had an average age of 68 years and an estimated glomerular filtration rate of 68 (43-89) mL/min/1.73 m2. Fifty-one patients received rituximab treatment (RTX group), while 86 patients were on other immunosuppressive maintenance therapies (non-RTX group). In comparison to non-RTX group, patients treated with RTX experienced higher complement C3 levels, lower ESR levels and lower FLCs κ (p = 0.063) and λ (p = 0.013) levels. The differences between RTX and non-RTX groups in terms of FLCs were even more prominent after correction to total Ig concentration (p = 0.004 for κ /Ig and p = 0.003 for λ /Ig, respectively). Both, serum free κ and λ levels were found to correlate significantly with ESR (R = 0.55 and p < 0.001 for κ; R = 0.53 and p < 0.001 for λ) and albumin (R = ‒0.38 and p < 0.001 for κ; R = ‒0.33 and p < 0.001 for λ). Additionally, serum free κ levels showed an inverse association with C3 (R = ‒0.18 and p = 0.041). Conclusion In subjects with AAV, FLC levels were found to be associated with markers of inflammation and complement activation; hence FLCs levels may represent a promising biomarker for detection of subclinical inflammation in AAV patients on maintenance therapy. Rituximab therapy showed a potential to reduce the levels of markers of subclinical inflammation, including FLCs.

Investigation of subclinical ocular inflammation in the aqueous humor of patients with myopia following bilateral sequential collamer lens implantation

BackgroundThe aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. MethodsAqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. ResultsCompared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. ConclusionFollowing sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.

Indirect Markers of Intestinal Damage in IgA Nephropathy

Introduction: Presence of subclinical intestinal inflammation has repeatedly been shown in IgA nephropathy (IgAN) and the degree of histological inflammation has correlated with abnormal urinary findings. There is lack of noninvasive biomarkers evaluating the presence of subclinical intestinal damage in IgAN. We conducted this study hypothesizing that selected biomarkers regarded as indirect markers of intestinal damage could be elevated in IgAN. Methods: Eighty-five primary IgAN patients (median age 55 years, 54% men) participated in this single-center study in Tampere, Finland. None had end-stage kidney disease or previously diagnosed enteropathies. Celiac disease was excluded with serum transglutaminase 2 antibody (TG2Ab) and endomysial antibody tests and inflammatory bowel disease with fecal calprotectin. Intestinal damage was evaluated from sera with analyses of intestinal fatty-acid binding protein (I-FABP), soluble cluster of differentiation molecule 14 (sCD14), and lipopolysaccharide binding protein. Fourteen people suffering from dyspepsia and 15 healthy people served as controls. Results: I-FABP levels among IgAN patients were higher than in the healthy controls (median 830 pg/mL vs. 289 pg/mL, p < 0.001). Also, sCD14 was increased in IgAN patients compared to dyspepsia controls. Although TG2Ab levels were within the normal range among IgAN patients, they were higher than in the healthy controls (median 1.3 U/mL vs. 0.6 U/mL, p < 0.001). Conclusions: Elevated serum levels of I-FABP were present in primary IgAN patients without known enteropathies. Serum I-FABP may indicate the presence of subclinical intestinal damage. These findings encourage further investigation into the role of the intestine in the pathophysiology of IgAN.

High prevalence of dermatophytosis of the feet in acral melanoma of the foot.

The clinical characteristics and pathogenesis of acral melanoma of the foot (AMF) have not been sufficiently elucidated. Clinical or subclinical persistent inflammation of the feet is caused by dermatophytosis of the feet (DPF). Persistent inflammation is potentially associated with oncogenesis. Moreover, diabetes has been reported to be associated with the development of dermatophytosis and cancer. The present study aimed to elucidate the clinical association between DPF and AMF, with consideration of diabetes. The medical records of 114 Japanese patients were retrospectively examined and divided into an AMF group (n = 30) and a control group consisting of patients with foot diseases other than melanoma (n = 84). Microscopic DPF screening was performed on all patients who reported symptoms in the foot, with or without AMF. Patients underwent a microscopic test to detect the presence of dermatophytes, and the diagnosis of DPF was made based on a positive result. In the AMF group, 18 (60.0%) and eight (26.7%) patients had DPF and diabetes, respectively. Four patients (13.3%) had both DPF and diabetes. In the control group, 25 (29.8%) and 11 (13.1%) patients had DPF and diabetes, respectively. Five patients (6.0%) had both DPF and diabetes. Univariate analyses showed a significantly higher prevalence of DPF in the AMF group than in the control group (odds ratio, 3.540; p = 0.003, Pearson χ2 test). Furthermore, multivariate analyses of sex, body mass index, DPF, and diabetes revealed DPF as a significant factor associated with AMF (odds ratio, 4.285; p = 0.002, logistic regression analysis). The hyperkeratotic type of DPF was more frequently observed in patients with AMF than in control patients (odds ratio, 11.083; p < 0.001, Pearson χ2 test). In conclusion, the present study found a significantly higher prevalence of DPF, especially its hyperkeratotic type, in patients with AMF. DPF may be associated with AMF pathogenesis.

Greater methylation of the IL-6 promoter region is associated with decreased integrity of the corpus callosum in schizophrenia

BackgroundSchizophrenia is associated with chronic subclinical inflammation and decreased integrity of the corpus callosum (CC). Our previous study showed associations between peripheral IL-6 levels and the integrity of the CC. Epigenetic studies show associations between methylation of the genes related to immunological processes and integrity of the CC. AimTo investigate correlations between methylation status of IL-6 promotor and peripheral IL-6 levels and the integrity of the CC in schizophrenia. Material and methodsThe participants were 29 chronic schizophrenia patients (SCH) and 29 controls. Decreased integrity of the CC was understood as increased mean diffusivity (MD) and/or decreased fractional anisotropy (FA) in diffusion tensor imaging. Peripheral IL-6 concentrations were measured in serum samples and IL-6 promoter methylation status of 6 CpG sites was analyzed in peripheral leukocytes by pyrosequencing. ResultsModerate positive correlations were found between CpG1 methylation and the MD of proximal regions of the CC (CCR1–CCR3) and between CpGmean and MD of CCR1 in SCH. Weaker positive correlations were found for CpGmean with CCR2 and CCR3 and negative correlations were found for CpG1 and FA of CCR3 in SCH. Multivariate regression showed that methylation of CpG1, type of antipsychotic treatment, and their interaction were significant independent predictors of MD of CCR1 in SCH. Methylation of CpG2 was negatively correlated with serum IL-6 in SCH. ConclusionsThe methylation level of the IL-6 promotor region in peripheral leukocytes is associated with the integrity of the CC in schizophrenia and this association may depend on the type of antipsychotic treatment. Further studies are necessary to explain the mechanisms of the observed associations.

Subclinical joint inflammation in rheumatoid arthritis: comparing thermal and ultrasound imaging at the metacarpophalangeal joint

BackgroundWhile ultrasound and MRI are both superior to clinical examination in the detection of joint inflammation, there is presently a lack of data whether thermography may be similarly useful in the assessment of joint inflammation in patients with RA. Our study aims to evaluate the use of thermography in detecting subclinical joint inflammation at clinically quiescent (non-tender and non-swollen) metacarpophalangeal joints (MCPJs) in patients with rheumatoid arthritis (RA). The outcomes from thermography in our study will be compared with ultrasonography (which is a more established imaging tool used for joint inflammation assessment in RA).MethodsThe minimum (Tmin), average (Tavg) and maximum (Tmax) temperatures at the 10 MCPJs of each patient were summed to obtain the Total Tmin, Total Tavg and Total Tmax, respectively. Ultrasound grey-scale (GS) and power Doppler (PD) joint inflammation (scored semi-quantitatively, 0–3) at the 10 MCPJs were summed up to derive the respective TGS and TPD scores per patient. Pearson’s correlation and simple linear regression were respectively used to assess correlation and characterize relationships between thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TGS, TPD and the number of joint(s) with PD ≥ 1 or GS ≥ 2).ResultsIn this cross-sectional study, 420 clinically non-swollen and non-tender MCPJs from 42 RA patients were examined. All thermographic parameters (Total Tmin, Total Tavg and Total Tmax) correlated significantly (P-values ranging from 0.001 to 0.0012) with TGS score (correlation coefficient ranging from 0.421 to 0.430), TPD score (correlation coefficient ranging from 0.383 to 0.424), and the number of joint(s) with PD ≥ 1 or GS ≥ 2 (correlation coefficient ranging from 0.447 to 0.465). Similarly, simple linear regression demonstrated a statistically significant relationship (P-values ranging from 0.001 to 0.005) between all thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TPD and TGS).ConclusionFor the first time, thermographic temperatures were shown to correlate with ultrasound-detected joint inflammation at clinically quiescent MCPJs. The use of thermography in the detection of subclinical joint inflammation in RA appears promising and warrants further investigation.

Plasma Levels of Estradiol and Progesterone are Positively Associated with IL-1α and IL-1Ra in Young Women with PTSD

Introduction: Post-traumatic stress disorder (PTSD) is independently associated with greater cardiovascular disease (CVD) risk. Prior studies have reported higher inflammation as a possible underlying mechanism. Premenopausal females are typically thought to be protected from CVD due to estradiol (E2) and available data supports growing CVD risk in females before menopause by virtue of having PTSD. Given that E2 and progesterone (P4) have been shown to have a broad range of both pro- and anti-inflammatory effects, the purpose of our study was to investigate whether plasma levels of E2 and P4 are associated with subclinical inflammation in young women with PTSD. We hypothesized that E2 and P4 will be negatively associated with IL-1α, IL-1Ra, and IL-6. Methods: Seventy-five otherwise healthy young women (age, 28±7 years; BMI, 26.7±6 kg/m2) with a prior clinical diagnosis of PTSD (PTSD+, n=39) and without a PTSD diagnosis (PTSD-, n=36) were included in this study. We collected blood plasma samples to quantify E2 and P4 and inflammatory biomarkers Interleukin-1α (IL-1α), Interleukin-1 receptor antagonist (IL-1Ra) and Interleukin-6 (IL-6). Total plasma levels of E2 and P4 were measured using the quantitative sandwich enzyme immunoassay technique (ELISA). The inflammatory biomarkers were quantified using a Luminex assay. Participants were also asked to complete a self-administered PTSD checklist for DSM-5 (PCL5) to assess the severity of PTSD symptoms. We ran Pearson correlations between the sex hormones and the inflammatory biomarkers stratified by PTSD diagnosis. Results: We found a positive correlation between E2 levels and IL-1α (r=0.39, p=0.018), E2 and IL-1Ra (r=0.35, p=0.030), P4 and IL-1α (r=0.45, p=0.005), and P4 and IL-1Ra (r=0.27, p=0.101) in the PTSD+ group. In contrast, in the PTSD- group, there was no correlation between E2 and IL-1α (r=0.05, p=0.77), E2 and IL-1Ra (r=-0.06, p=0.73), P4 and IL-1α (r=-0.04, p=0.83) and P4 and IL-1Ra (r=0.07, p=0.68). Conclusion: Our analysis revealed that in young women with a clinical diagnosis of PTSD, E2 and P4 levels in the blood are positively associated with an increased IL-1α and IL-1Ra but not in young trauma-exposed women without PTSD. These findings suggest that in young women with PTSD, E2 and P4 might have a paradoxical effect on inflammation such that E2 and P4 promote the release of both pro-inflammatory (i.e. IL-1α) and anti-inflammatory (i.e. IL-1Ra) cytokines. Conversely, an increase in subclinical inflammation could lead to an increase in E2 and P4 levels, which in turn would promote the release of anti-inflammatory cytokines in order to inhibit the inflammatory response. K01HL161027 and UMN CTSI UL1TR002494 No Disclosure. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

THE SUBCLINICAL INFLAMMATION IN PEDIATRIC PATIENTS WITH PRIMARY HYPERTENSION AND WHITE COAT HYPERTENSION

Objective: Adult and experimental data indicate the vital role of inflammation in the pathogenesis of primary hypertension. The study aimed to evaluate subclinical inflammation in patients with primary hypertension (PH) and white coat hypertension (WCH). Design and method: In 56 untreated pediatric patients with PH, 40 with WCH, and 30 healthy individuals (CG – control group), we evaluated high sensitivity C-reactive protein (hsCRP), interleukin 18 (IL18) concentrations, complete blood count-derived markers of inflammation, office and ambulatory blood pressure, and selected clinical and biochemical parameters. Results: hsCRP was significantly higher in PH patients compared to CG (PH vs. CG: 4.9±5.2 vs. 2.8±5.4 [mg/dL], p=0.002), and neutrophil and monocyte counts were significantly higher in PH and WCH patients compared to CG (PH vs. WCH vs. CG, neutrophils: 3.89±1.44 vs. 3.40±1.75 vs. 2.63±0.96 [∗10^3/μL], p=0.001, monocytes: 0.56±0.17 vs. 0.53±0.18 vs. 0.46±0.14 [∗10^3/μL], p=0.026). Receiver operating characteristic analysis revealed good prognostic profiles for hsCRP (area under curve [AUC]=0.668, p=0.0005), neutrophil (AUC=0.691, p=0.0001), lymphocyte (AUC=0.615, p=0.0230), monocyte (AUC=0.622, p=0.0148), and platelet counts (AUC=0.606, p=0.0364), as well as the neutrophil-to-lymphocyte ratio (AUC=0.619, p=0.0181), monocyte-to-neutrophil ratio (MNR) (AUC=0.617, p=0.0204), and platelet-to-mean platelet volume ratio (AUC=0.606, p=0.0370) as predictors of the presence of primary hypertension. In multivariate analysis monocyte-to-lymphocyte ratio (MLR) and platelet count (beta=0.217, p=0.011; beta=0.191, p=0.036) were significant predictors of office diastolic blood pressure Z-score, neutrophil count predicted 24h systolic blood pressure Z-score (beta=0.365, p=0.005); MLR, lymphocyte count, IL-18, and MNR predicted 24 h diastolic blood pressure Z-score (beta=0.305, p=0.002; beta=0.253, p=0.010; beta=-0.197, p=0.019; beta=-0.189, p=0.029), and neutrophil count together with IL-18 predicted 24h mean arterial pressure Z-score (beta=0.210, p=0.027; beta=-0.209, p=0.012). Conclusions: 1.Patients with primary hypertension and white coat hypertension are characterized by similar levels of subclinical inflammation, significantly higher compared to healthy peers. 2. Complete blood count-derived indices, especially neutrophil count and MLR, can be an important adjunct to the clinical evaluation of pediatric patients with primary hypertension.

ASSOCIATION OF SUBCLINICAL INFLAMMATION MARKERS WITH PRIMARY HYPERTENSION IN CHILDREN - A SYSTEMATIC REVIEW WITH META-ANALYSIS

Objective: Primary hypertension (PH) is a growing threat to children's health. The pathogenesis of this phenomenon is not fully known, and subclinical inflammation and activation of the immune system are potential explanations. This systematic review and meta-analysis aimed to systematically determine whether there is an association between low–grade inflammation markers and PH in children. Design and method: The MEDLINE, EMBASE, and Cochrane databases were searched up to March 2023, with no language restrictions, for cohort, cross-sectional, and case-control studies; additional references were obtained from reviewed articles. The included studies needed to investigate an association between any inflammation markers and PH defined by the authors. Participants of the study were children (&lt;18 years old) with PH and healthy controls. The main outcome measured was the concentration of any subclinical inflammation markers in children with PH and in healthy controls. This meta-analysis included 12 studies published between 2005 and 2022, enrolling 1220 patients (689 with PH and 531 healthy controls). The data were analyzed using Review Manager. Pooled mean difference (MD) with 95% confidence interval (95% CI) was used to assess the differences in inflammation markers levels. All analyses were based on the random-effect model. The risk of bias was assessed using the Newcastle-Ottawa Scale. Results: There was a significant difference between hypertensive and control groups in high-sensitivity C-reactive protein (hsRCP) concentration (MD: 0.07 95%CI [0.04,0.09]), intercellular adhesion molecule 1 (ICAM-1) (MD: 85.28 95%CI: [50.57-119.99]), vascular cell adhesion molecule 1 (VCAM-1) (MD: 259.78 95%CI: [22.65-496.91]), neutrophil count (MD: 0.80 95%CI [0.53-1.07]), monocyte count (MD: 0.07 95%CI: [0.02-0.12]), and neutrophil-to-lymphocyte ratio (NLR) (MD: 0.49 95%CI: [0.32-0.65]). There was no difference in terms of interleukin 6 (IL-6), lymphocyte count, platelet count, mean platelet volume (MPV), as well as in platelet-to-lymphocyte (PLR) and monocyte-to-lymphocyte (MLR) ratios. Conclusions: Some easily accessible markers of low-grade inflammation might be used as an additional tool for diagnosis and screening for hypertension in pediatric patients. These promising results should be validated in large and well-conducted studies.

Environmental Factors Associated With Risk of Crohn’s Disease Development in the Crohn’s and Colitis Canada - Genetic, Environmental, Microbial Project

To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers. We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR); gut inflammation via fecal calprotectin (FCP) levels; and fecal microbiome composition through 16S rRNA sequencing. Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5 and 15 (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40-0.96; P= .034), and living with a large family size in the first year of life (HR, 0.43; 95% CI, 0.21-0.85; P= .016) were associated with decreased CD risk, whereas having a bird at the time of recruitment (HR, 2.78; 95% CI, 1.36-5.68; P= .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity, whereas bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR. This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis.

A systems biology-based mathematical model demonstrates the potential anti-stress effectiveness of a multi-nutrient botanical formulation

Stress is an adaptive response to the stressors that adversely affects physiological and psychological health. Stress elicits HPA axis activation, resulting in cortisol release, ultimately contributing to oxidative, inflammatory, physiological and mental stress. Nutritional supplementations with antioxidant, anti-inflammatory, and stress-relieving properties are among widely preferred complementary approaches for the stress management. However, there is limited research on the potential combined impact of vitamins, minerals and natural ingredients on stress. In the present study, we have investigated the effect of a multi-nutrient botanical formulation, Nutrilite® Daily Plus, on clinical stress parameters. The stress-modulatory effects were quantified at population level using a customized sub-clinical inflammation mathematical model. The model suggested that combined intervention of botanical and micronutrients lead to significant decline in physical stress (75% decline), mental stress (70% decline), oxidative stress (55% decline) and inflammatory stress (75% decline) as evident from reduction in key stress parameters such as ROS, TNF-α, blood pressure, cortisol levels and PSS scores at both individual and population levels. Further, at the population level, the intervention relieved stress in 85% of individuals who moved towards a healthy state. The in silico studies strongly predicts the use of Gotukola based Nutrilite® Daily Plus as promising anti-stress formulation.

CELIAC DISEASE AND CARDIOVASCULAR DISEASES

Background: Celiac disease, an immune-mediated enteropathy that occurs in susceptible individuals after gluten ingestion, has clinical manifestations that go beyond the classical malabsorption syndrome and can affect other systems. Objective: To review the current literature for cardiovascular changes described in patients with celiac disease. Method: We conducted a search in the PubMed database and selected articles based on their relevance to the objective. Results: Celiac patients have a 1.2 times higher risk of cardiovascular events compared to non-celiac patients. The most common cardiovascular manifestations include atherosclerosis, cardiac arrhythmias (especially atrial fibrillation), myocarditis, coronary artery disease, dilated cardiomyopathy, impaired aortic function, and cerebrovascular diseases. There are several possible explanations for this relationship, including: prothrombotic changes, accelerated atherosclerosis compared to patients without celiac disease, associated comorbidities, such as antiphospholipid syndrome and Type 1 Diabetes mellitus, subclinical chronic inflammation and genetic factors. Celiac disease patients have a 38% higher risk of developing atrial fibrillation and a 19% higher risk of coronary artery disease. Furthermore, celiac patients have a 22% higher risk of coronary artery disease-related death, regardless of small intestine histopathology. Patients with celiac disease also show an increased prevalence of dilated cardiomyopathy (5.7%) and a 73% higher risk of developing dilated cardiomyopathy, particularly within the first year of celiac disease diagnosis. Conclusion: Celiac disease may be associated with cardiovascular changes, especially in newly diagnosed patients who have not adhered to a gluten-free diet. Therefore, cardiovascular assessment should be considered as part of the initial assessment and follow-up of individuals with celiac disease.

Obesity and polycystic ovary syndrome influence on intestinal permeability at fasting, and modify the effect of diverse macronutrients on the gut barrier

Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.

Urinary Biomarkers for Lupus Nephritis: A Systems Biology Approach.

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder. Kidney involvement, termed lupus nephritis (LN), is seen in 40-60% of patients with systemic lupus erythematosus (SLE). After the diagnosis, serial measurement of proteinuria is the most common method of monitoring treatment response and progression. However, present treatments for LN-corticosteroids and immunosuppressants-target inflammation, not proteinuria. Furthermore, subclinical renal inflammation can persist despite improving proteinuria. Serial kidney biopsies-the gold standard for disease monitoring-are also not feasible due to their inherent risk of complications. Biomarkers that reflect the underlying renal inflammatory process and better predict LN progression and treatment response are urgently needed. Urinary biomarkers are particularly relevant as they can be measured non-invasively and may better reflect the compartmentalized renal response in LN, unlike serum studies that are non-specific to the kidney. The past decade has overseen a boom in applying cutting-edge technologies to dissect the pathogenesis of diseases at the molecular and cellular levels. Using these technologies in LN is beginning to reveal novel disease biomarkers and therapeutic targets for LN, potentially improving patient outcomes if successfully translated to clinical practice.

Effect of a 12-Week Walking Program Monitored by Global Physical Capacity Score (GPCS) on Circulating Cell-Free mtDNA and DNase Activity in Patients with Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.

Vitreous hyper-reflective dots and the macular thickness after cataract surgery.

To assess the association between vitreous hyper-reflective dots (VHD) and the macular thickness changes following uneventful phacoemulsification. In this prospective cohort study optical coherence tomography (OCT) examinations were performed preoperatively and 1 week, 1 month and 3 months postoperatively in patients undergoing cataract surgery. OCT images were analyzed for retinal central subfield thickness (CST) and preretinal VHDs. Surgeries were recorded for the assessment of lens fragments in the space of Berger. 111 eyes of 97 patient were enrolled of whom 69 (62.2%) were female. VHDs were seen in 25 eyes (22.5%) at week 1; in 21 eyes (18.9%) at month 1 and in 3 eyes (2.7%) at month 3. In all eyes with VHDs retro-capsular lens fragments were visible immediately after phacoemulsification. The number of VHDs significantly decreased over the postoperative period. There was a moderate correlation between the number of VHDs and CST at 1 month (r = 0.426, p<0.001). In eyes with VHD the CST averaged 238.8±17.6 μm (214-266) at 1 week; 276.1±63.5 μm (231-481) at 1 month and 285.1±122.3 μm (227-785) at 3 months. In eyes with no detectable VHDs CST averaged 235.9±23.3 μm (192-311) at 1 week; 240.1±21.6 μm (200-288) at 1 month and 242.2±21.3 μm (205-289) at 3 months. Although the differences among the assessment points were relatively low, there was a significant difference in general (p<0.001, Friedman test). In conclusion, VHDs seem to cause macular thickening throughout the postoperative course. The origin of VHDs is still unknown; however, they presumably represent lens fragments that provoke subclinical inflammation.

Interleukin-6 as a Milk Marker of Clinical and Subclinical Intramammary Infections (IMI) in Cows Caused by Streptococcus spp.

The aim of the study was to evaluate the concentrations of Interleukin-6 (IL-6) in milk and serum of healthy cows (HE) and cows with mastitis caused by Streptococcus spp. The blood and milk samples were obtained from Holstein-Friesian cows (Lublin region, Poland). A total of 43 milk and serum samples from 28 cows with mastitis and 15 healthy cows were selected for study. IL-6 levels in milk from HE cows ranged from 6.09-80.24 pg/mL (median 26.6 pg/mL) and were significantly lower than in milk from both cows with clinical and subclinical mastitis (487.09 pg/mL vs. 26.6 pg/mL in CM, p < 0.001; and 165.31 pg/mL vs. 26.6 pg/mL in SCM, p < 0.001). The IL-6 concentration in the serum of HE was not significantly different from the serum IL-6 of the entire group of mastitis cows, regardless of whether the inflammation proceeded in a clinical or subclinical form (44.37 pg/mL vs. 78.09 pg/mL; 128.29 pg/mL vs. 78.09 pg/mL, respectively). The present study indicates that cows with mastitis caused by Streptococcus spp. develop a local immune response in the mammary gland in response to the pathogen. Monitoring of IL-6 levels in milk can allow early detection of mastitis, which is especially important in cases of subclinical inflammation.