Background/Aims: Chronic hepatitis C virus (HCV) infection is accompanied by persistent hepatic inflammation, progressive fibrogenesis and metabolic disturbance, of which insulin resistance (IR) is the most consistently reported. The neutrophil-to-lymphocyte ratio (NLR), derived from a routine complete blood count, has been proposed as an inexpensive index of systemic inflammatory activity, but its diagnostic accuracy for IR in fibrotic chronic hepatitis C has not been quantified in Iraqi patients. To quantify the cross-sectional diagnostic performance of NLR for the identification of insulin resistance in patients with fibrotic chronic hepatitis C, and to characterise its associations with metabolic, inflammatory and hepatic biochemical parameters. Methods: A case–control study was conducted at the Baghdad Hospital for Gastroenterology and Hepatology, Medical City, Baghdad, Iraq, between December 2021 and January 2022. One hundred and fifty participants were enrolled consecutively until each of three groups reached its a priori target of 50: patients with fibrotic chronic hepatitis C and insulin resistance (CHC+IR), patients with fibrotic chronic hepatitis C without insulin resistance (CHC−IR), and apparently healthy controls. Insulin resistance was defined a priori as a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) value ≥ 2.6. Hepatic fibrosis was recorded as present or absent from clinical, ultrasonographic and available histological records; stage-level fibrosis data were not available. Complete blood count, liver function tests including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), fasting glucose, fasting insulin, C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) were measured. Groups were compared by Welch analysis of variance with Games–Howell post hoc tests. Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis with DeLong confidence intervals and Youden-optimal cut-offs; associations were quantified by Pearson and Spearman correlation with 95 % confidence intervals, and independence was examined by multivariable linear regression and by Firth penalised logistic regression. A sensitivity analysis in which the HOMA-IR threshold of 2.6 was applied strictly, so that a single clinically allocated patient with a recalculated value of 2.59 was reassigned, was performed for all principal outcomes. Results: The three groups were comparable for age (p = 0.075) and sex (p = 0.593). NLR increased stepwise across controls, CHC−IR and CHC+IR (1.79 ± 0.02, 1.95 ± 0.13 and 2.53 ± 0.15, respectively; Welch F = 625.5, p < 0.001; all pairwise comparisons p < 0.001). Within the chronic hepatitis C cohort (n = 100), NLR separated insulin-resistant from non-insulin-resistant patients completely, giving an area under the curve (AUC) of 1.000 at an exploratory, cohort-derived Youden-optimal cut-off of 2.24, with sensitivity and specificity of 100 % (95 % CI 92.9–100 % for each). NLR discriminated fibrotic chronic hepatitis C from healthy controls with an AUC of 0.942 (95 % CI 0.885–0.972) at a cut-off of 1.85 (sensitivity 90.0 %, specificity 100 %), whereas the AST/ALT ratio was uninformative (AUC 0.528, p = 0.583). NLR correlated strongly with HOMA-IR (r = 0.898, 95 % CI 0.852–0.930), fasting insulin (r = 0.903), CRP (r = 0.913), TNF-α (r = 0.906) and IL-6 (r = 0.798) (all p < 0.001). NLR remained independently associated with HOMA-IR after adjustment for age and sex (B = 2.31, 95 % CI 2.08–2.54, p < 0.001) and after further adjustment for hepatic biochemical markers (B = 1.55, 95 % CI 1.16–1.94, p < 0.001). Under strict application of the HOMA-IR threshold, which reassigned that patient and gave strata of 49 and 51 patients, the AUC for NLR was 0.9994 (95 % CI 0.9932–0.9999), the Youden-optimal threshold was recovered unchanged at 2.24, sensitivity remained 100 % and specificity fell to 98.0 % (95 % CI 89.7–99.7 %), and the regression estimates were essentially unaltered (B = 2.31, 95 % CI 2.08–2.54; odds ratio 12.04 per 0.1-unit increment in NLR); the direction, magnitude and statistical significance of every principal result were unchanged. Conclusion: In this cohort, NLR was strongly and independently associated with insulin resistance and discriminated insulin-resistant from non-insulin-resistant patients with fibrotic chronic hepatitis C with high accuracy. Because the groups were completely separated on NLR and the threshold was derived in the same sample, the cut-off of 2.24 is an exploratory, cohort-derived threshold rather than an established clinical cut-off, and the accuracy estimates are optimistic and require independent external validation. As all patients had fibrosis and no fibrosis staging was available, the present data support a diagnostic association with the presence of disease rather than prediction of fibrosis severity.
Background/Aims: The use of tetrabromobisphenol A (TBBPA) as a brominated flame retardant has raised growing concerns of its potential toxicity due to its widespread use and persistence. The present study compares the threshold-like mechanism of hemolysis induced by TBBPA with that of its sulfone analog, tetrabromobisphenol S (TBBPS), using an in vitro model of human erythrocytes. Methods: Isolated red blood cells (5% hematocrit) obtained from healthy donors were exposed to TBBPA (10–50 µg/mL) or TBBPS (10–100 µg/mL) for 24 hours at 37°C. Hemolysis, methemoglobin formation, lipid peroxidation, glutathione levels, ATPase activity, membrane protein integrity, and interactions with human serum albumin were evaluated using spectrophotometric, fluorometric, flow cytometric, and electrophoretic (SDS-PAGE) analyses. Interactions of both compounds with human serum albumin (HSA) were investigated by fluorescence quenching and fluorescence lifetime measurements. Results: TBBPA induced a distinct threshold-like hemolytic response, with hemolysis increasing sharply above 12.5 µg/mL and reaching approximately 43.7% at 30 µg/mL, whereas TBBPS did not induce hemolysis within the tested concentration range. TBBPA-induced hemolysis was preceded by increased MetHb formation and accompanied by depletion of glutathione, impaired ATPase activity, and alterations in membrane proteins, including aggregation and loss of cytoskeletal components, but not by detectable lipid peroxidation. TBBPS produced substantially weaker effects on erythrocyte membrane integrity and antioxidant status. Fluorescence studies demonstrated that both TBBPs interacted with HSA, with predominantly static quenching accompanied by a contribution from dynamic quenching. The two compounds exhibited similar effects on HSA fluorescence under the experimental conditions used. Conclusion: TBBPA and TBBPS exhibit markedly different effects on erythrocytes despite their structural similarity, with TBBPA showing a distinct threshold-like hemolytic response associated with protein and antioxidant system damage rather than lipid peroxidation. The results suggest that differences in the chemical structure of TBBPs influence their interactions with proteins and may contribute to their distinct biological effects.
Background/Aims: Allergic rhinitis is a common chronic inflammatory disease affecting millions of people worldwide and substantially impairing quality of life. This study aimed to investigate the association of the IL-4 rs2243250 polymorphism with allergic rhinitis, inflammatory markers, and leukocyte profiles. Methods: A total of 182 participants were included, comprising 91 patients with allergic rhinitis and 91 healthy controls. Peripheral blood samples were collected for complete blood count, DNA extraction, and measurement of IL-4, IL-13, and IgE levels using enzyme-linked immunosorbent assays. Skin prick testing for weed, grass, tree, and mite allergens was performed to confirm IgE-mediated sensitization. The IL-4 rs2243250 polymorphism was detected by polymerase chain reaction followed by restriction fragment length polymorphism analysis using the AvaII restriction enzyme. Results: Significant differences (P < 0.001) between patients and controls were observed for all investigated immunological markers and differential white blood cell counts. For rs2243250, the CC genotype was associated with a reduced likelihood of allergic rhinitis (OR = 0.25; 95% CI: 0.11–0.55), whereas the TT genotype was associated with an increased likelihood (OR = 3.8; 95% CI: 1.82–8.17). Similarly, the C allele was associated with reduced disease likelihood (OR = 0.35; 95% CI: 0.23–0.53), while the T allele was associated with increased likelihood (OR = 2.88; 95% CI: 1.88–4.41; P < 0.001). Significant positive correlations among several white blood cell types were also observed. Conclusion: The findings demonstrate an association between the IL-4 rs2243250 polymorphism and allergic rhinitis. The C allele and CC genotype were associated with reduced disease likelihood, whereas the T allele and TT genotype were associated with increased likelihood. These genetic associations, together with alterations in inflammatory markers and leukocyte profiles, may contribute to understanding susceptibility to allergic rhinitis.
Background/Aims: DNA methylation is a critical epigenetic mechanism involved in the regulation of gene expression, including genes implicated in glucose metabolism. Despite growing evidence indicating that epigenetic mechanisms are involved in the pathogenesis and progression of type 2 diabetes mellitus (T2DM), available data remain limited. This study analyzed the genetic association of two single-nucleotide polymorphisms (SNPs) in the DNA methyltransferase 3A (DNMT3A) gene, rs11683424 and rs1550117, with T2DM susceptibility and investigated their potential associations with global DNA methylation. Methods: Total antioxidant status (TAS) and total oxidant status (TOS) were evaluated, the oxidative stress index (OSI) was calculated, and diabetes-related parameters were assessed in T2DM patients and healthy controls, including HbA1c, fasting blood glucose (FBG), insulin, insulin sensitivity (IS), and insulin resistance (IR). Global DNA methylation was determined, and rs11683424 and rs1550117 were genotyped. Associations between metabolic and oxidative stress parameters, global DNA methylation, DNMT3A genotypes, and T2DM status were statistically analyzed. Results: T2DM patients exhibited significantly higher HbA1c, FBG, insulin, and IR levels than healthy controls (p=0.001), whereas IS was significantly lower (p=0.001). TAS, TOS, and OSI were significantly increased in T2DM patients compared with controls (p=0.001), as was global DNA methylation (p=0.001). In patients, a weak but statistically significant inverse correlation was observed between 5mC levels and BMI. Global methylation showed weak inverse associations with TAS and TOS; however, these associations did not reach statistical significance. No significant associations (p>0.05) were observed between 5mC levels and the other studied biomarkers. Neither regression model for predictors of global DNA methylation was statistically significant in T2DM patients (F(5,94)=0.852, p=0.516) or healthy controls (F(4,95)=0.592, p=0.669), and all variance inflation factor (VIF) values were <2.0. For rs11683424, the CT genotype was detected in 15.6% of T2DM patients compared with 2.6% of controls (OR=6.81, 95% CI=1.50–31.25, χ²=7.902, p=0.005). The T allele was present at frequencies of 7.8% and 1.3%, respectively (χ²=7.502, p=0.006). In contrast, rs1550117 was not significantly associated with T2DM. Linkage disequilibrium analysis indicated incomplete or moderate linkage disequilibrium between the two SNPs. The CG haplotype was the most common in both groups, whereas the TG and TA haplotypes were enriched among patients and showed increased disease odds, particularly TG (OR=7.89); however, neither association reached statistical significance. Genotype–phenotype analyses revealed only limited differences in global DNA methylation among the investigated genotypes. Conclusion: T2DM was associated with altered oxidative stress parameters and increased global DNA methylation. The findings further indicate a potential association between DNMT3A rs11683424 and T2DM susceptibility, whereas rs1550117 was not significantly associated with disease status. However, the data do not establish a direct relationship between the investigated DNMT3A variants, oxidative stress, and global DNA methylation. These findings warrant validation in larger, multi-ethnic cohorts.
BACKGROUND/AIMS:This study aimed to evaluate the clinical efficacy, procedural metrics, and safety outcomes of radiofrequency catheter ablation (RFCA) for typical Wolff - Parkinson - White (WPW) syndrome utilizing a pre-procedural 12-lead surface electrocardiogram (ECG) schematic for accessory pathway (AP) localization in a Vietnamese cohort. METHODS:A prospective, descriptive study was performed on 109 consecutive patients with typical WPW syndrome undergoing electrophysiological study (EPS) and RFCA. A stepwise 12-lead ECG algorithm (the new schematic) was applied to predict the AP anatomical site prior to ablation, which was validated against intraprocedural electroanatomical mapping endpoints. Diagnostic performance (concordance between predicted and electrophysiologically confirmed AP locations) was evaluated. Operational metrics were compared with a historical control cohort (n=189) managed without the algorithm. RESULTS:All 109 patients (51.4% male, mean age 43.6 ± 14.9 years) presented with a single manifest AP (52 right-sided, 47.7%; 57 left-sided, 52.3%). The overall diagnostic accuracy of the ECG schematic for predicting the correct AP anatomical zone was 92.7% (101/109 cases). The acute procedural success rate was 100%. Right-sided AP ablations showed longer total procedure duration (52.9 ± 21.5 min vs. 44.9 ± 14.5 min, p < 0.05) higher total radiofrequency delivery time (368.1 ± 202.5 sec vs. 261.6 ± 110.6 sec, p < 0.01), and more RF applications (10.9 ± 8.3 vs. 5.7 ± 3.7, p < 0.001) than left-sided APs. Fluoroscopy time did not differ significantly between right- and left-sided groups (7.3 ± 4.2 min vs. 7.0 ± 3.8 min, p > 0.05). Compared with the historical control group (n=189), implementation of the ECG schematic was associated with reductions in total procedure duration (48.7 ± 18.5 min vs. 55.0 ± 29.7 min, p < 0.05) and fluoroscopy exposure (7.2 ± 4.0 min vs. 9.0 ± 5.0 min, p < 0.001). No major adverse cardiovascular events or permanent AV blocks occurred; one minor transient phrenic nerve response (0.9%) resolved spontaneously. CONCLUSION:The pre-procedural surface ECG prediction schematic provides reliable anatomical localization of APs in typical WPW syndrome. Its clinical application was associated with reduced total procedure duration and fluoroscopy exposure time, while maintaining a high acute success rate and a favorable safety profile.
