To assess the associations between the Dietary Inflammatory Index (DII) and obesity and dietary intake in adults with type 2 diabetes (T2DM), and to compare the findings with those obtained using the modified Japanese Diet Index (mJDI). We conducted a cross-sectional study of 1,565 adults with T2DM in Japan between 2014 and 2019. Dietary intake was assessed using a validated food frequency questionnaire. The DII calculation was based on 25 nutrients. Participants were categorized into DII tertiles, and obesity was defined as BMI ≥ 25 kg/m2. Logistic regression models were used to estimate associations between the DII and obesity with sequential adjustment for demographic, dietary, and lifestyle factors. Subgroup and sensitivity analyses were performed, and correlations between the DII and food group intakes were examined. Participants in higher DII tertiles were younger, more often male, and had higher BMI, lower energy intake, lower protein intake per kg of body weight, and lower physical activity. Higher DII scores were associated with greater odds of obesity (OR 2.412, 95% CI 1.751-3.323; P-trend < 0.001). The association was consistent across sex, age, energy intake, and physical activity categories. The DII was inversely correlated with intakes of vegetables, fruits, fish/seafood, soy products, and other nutrient-dense foods. Sensitivity analyses using BMI ≥ 30 kg/m2 showed similar but weaker associations. Higher DII scores were associated with obesity and lower intake of nutrient-dense foods in Japanese adults with T2DM, whereas higher mJDI scores were inversely associated with obesity. Associations appeared stronger for the DII.
Sex hormones and HIV infection both influence cardiovascular health. However, the association between sex hormones and subclinical atherosclerosis is not fully understood, especially in the context of HIV. Among 321 men (65% with HIV) from the MACS/WIHS Combined Cohort Study, we measured 14 serum sex hormones and sex hormone-binding globulin (SHBG), assessed carotid artery plaque (IMT > 1.5 mm) using high-resolution B-mode ultrasound, and performed metagenomic sequencing on stool samples. In 312 men, we measured 986 plasma metabolites via liquid chromatography-tandem mass spectrometry and 2883 plasma proteins using the Olink Explore 3072 platform. In stratified analyses of men with (MWH) and without HIV (MWOH) and adjusting for covariates and multiple testing, we (1) examined associations of sex hormones with plaque; (2) characterized multi-omics profiles related to sex hormones; and (3) generated sex hormone-related omics scores via linear combination of related species, metabolites, and proteins, respectively, to explore whether these sex hormone-related multi-omics profiles were associated with plaque. Median age of participants was 62 years (interquartile range: 58-68), and 31.5% had carotid artery plaque. Sex hormones were differentially associated with plaque in MWH and MWOH. In MWH, an inverse association was observed between SHBG and plaque (OR = 0.60 per 1-SD increase, 95% CI: 0.41, 0.90). Furthermore, higher SHBG levels were associated with overall gut microbial composition, lower abundance of species from genera Prevotella, Fibrobacter and Coprococcus, higher levels of certain metabolites (primarily lipid and carnitine metabolites) and proteins enriched in the cell-cell adhesion pathway. Some SHBG-related species (e.g., Mediterranea massiliensis), metabolites (e.g., phosphatidylcholine-based lipids) and proteins (e.g., enriched in immune response pathway) were also associated with plaque in MWH. All three SHBG-related omics scores were inter-correlated and inversely associated with plaque in MWH. In MWOH, estrone-sulfate was positively associated with plaque (OR = 3.80, 95% CI: 1.41, 10.22) but not with any species, metabolites or proteins. Higher SHBG, and related microbial species, circulating metabolites, and proteins, were inversely associated with carotid artery plaque. These findings suggested that SHBG may play a protective role in subclinical atherosclerosis in MWH.
Adolescent screen exposure is increasing, yet clinically interpretable thresholds for cognitive risk are unclear. This study examined associations between daily screen time and cognitive screening performance and derived a screen-time cutoff associated with cognitive impairment. We conducted an observational cross-sectional study (March-April 2022) at a private junior high school in Indonesia during online learning. Students completed digital questionnaires reporting educational and recreational screen time and a directly reported overall estimate; a computed overall (educational + recreational) was generated to assess reporting consistency. Cognitive function was assessed using the MoCA-Ina, with < 24 as the primary impairment threshold based on recent psychometric evidence favoring lower cutoffs for improved classification accuracy. Sixty-seven adolescents were included (34 girls, 50.7%; 33 boys, 49.3%), with median age 13.0 years (12.0-16.0) and median MoCA-Ina 25.0 (19.0-31.0). MoCA-Ina did not differ by sex (girls 25.0 [19.0-31.0] vs. boys 26.0 [20.0-30.0]; p = 0.244). Recreational screen time correlated inversely with MoCA-Ina (ρ = -0.446, p < 0.001), as did overall screen time (ρ = -0.360, p = 0.003), whereas educational screen time was not associated (ρ = -0.061, p = 0.624). In adjusted regression, overall screen time remained negatively associated with MoCA-Ina (β = -0.24 per hour/day; 95% CI - 0.41 to - 0.07; p = 0.007), while age was positively associated (β = 0.96; 95% CI 0.07 to 1.85; p = 0.034). All variance inflation factors were below 2.5, indicating no substantial multicollinearity. ROC analysis showed fair discrimination (AUC 0.66; optimism-corrected AUC after bootstrap internal validation [1,000 resamples]: 0.63) with an optimal cutoff > 8.97 h/day (sensitivity 83.3%, specificity 48.8%, PPV 47.6%, NPV 84.0%); risk of impairment was higher above the cutoff (RR 2.98; 95% CI 1.15-7.72; p = 0.010; OR 4.77; 95% CI 1.40-16.31). High daily screen exposure was associated with poorer cognitive screening performance. The > 8.97-hour/day threshold represents a preliminary, hypothesis-generating cutoff that may help identify adolescents at elevated likelihood of cognitive impairment, pending external validation in larger, more diverse samples. 071/K-LKJ/ETIK/II/2022.
Central nervous system (CNS) relapse is a serious complication of diffuse large B-Cell lymphoma (DLBCL), often associated with poor clinical outcomes. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables detection of subtle blood-brain barrier (BBB) leakage. We assessed BBB permeability, using the Patlak model, in 63 patients with DLBCL without CNS involvement and 11 healthy controls using DCE-MRI, and investigated associations with established risk factors for CNS relapse. Patients with high risk of CNS relapse (CNS-IPI  ≥4) demonstrated near-significant increased BBB permeability in cortical gray matter (GM) compared with both low-risk patients (p = 0.053) and healthy controls (p = 0.02). BBB permeability in cortical GM and in cerebral white matter (WM) correlated positively with age (p < 0.001). After adjusting for age, patients with kidney and/or adrenal involvement exhibited significantly higher BBB permeability in cortical GM (p = 0.04). Furthermore, plasma albumin levels were inversely correlated with BBB permeability in both GM (p = 0.003) and WM (p = 0.005). These findings indicate that subclinical BBB dysfunction may contribute to CNS vulnerability in DLBCL, potentially predisposing patients to relapse even before CNS involvement occurs. The observed age-related increase in BBB permeability is consistent with previous reports and may represent an independent risk for CNS relapse. Collectively, these results suggest that BBB imaging could improve CNS risk stratification in DLBCL. Prospective studies are warranted to determine whether early BBB alterations can predict CNS relapse in individual patients.
Frailty is a common and clinically significant condition among older adults undergoing surgical procedures and is associated with adverse postoperative outcomes. In addition to biological vulnerability, psychosocial factors such as social support may influence recovery processes. However, studies examining the relationship between frailty and perceived social support in older orthopedic surgical patients remain limited. This study aimed to examine the relationship between frailty and perceived social support in older orthopedic surgical patients and to determine how these variables differ according to sociodemographic and clinical characteristics. This cross-sectional study was conducted with 241 older orthopedic surgical patients aged 65 years and older who underwent orthopedic surgical procedures. Data were collected using the Descriptive Characteristics Form, the Edmonton Frail Scale, and the Multidimensional Scale of Perceived Social Support. Descriptive statistics, independent samples t-tests, one-way ANOVA, and Spearman correlation analysis were used. A p value of < 0.05 was considered statistically significant. Participants showed clinically relevant levels of frailty, with many classified as mildly, moderately, or severely frail, and reported moderate to high levels of perceived social support. Social support was highest from family and lowest from a significant other. A substantial proportion of patients were identified as having mild, moderate, or severe frailty. No significant relationship was found between total perceived social support and frailty; however, family support was significantly and inversely associated with frailty (p < 0.05). Frailty levels were significantly higher among female participants and those with lower educational levels (p < 0.05). Frailty remains a prevalent condition among older orthopedic surgical patients, even in the presence of relatively high levels of perceived social support. Family-based support was significantly and inversely associated with frailty; however, this finding should be interpreted as an association rather than evidence of a protective or causal effect. Integrating frailty screening with the assessment of social support in perioperative care may support the development of individualized and patient-centered nursing interventions. Future studies should explore causal relationships using longitudinal designs and include detailed clinical variables such as surgical type.
The carbon-to-nitrogen (C:N) ratio constrains microbial metabolism, yet whether nutrient stoichiometry controls the differential fates of intracellular (iARGs) versus extracellular antibiotic resistance genes (eARGs) remains unknown. This study aimed to test whether C:N ratios approaching the bacterial threshold elemental ratio (TER) would maximize iARG enrichment through a dissolved organic matter (DOM)-extracellular polymeric substance (EPS)-mobile genetic element (MGE) cascade, while eARG dynamics would be governed by physicochemical processes. Cyanobacteria-bacteria co-cultures at four C:N ratios (5:1, 10:1, 20:1, 40:1) were analyzed using shotgun metagenomics, FTICR-MS, 3D-EEM, untargeted metabolomics, and EPS fractionation. C:N = 10:1 produced the highest iARG abundance (65.1 ± 17.4 TPM, mean ± SD) and a 17-fold iARG/eARG ratio, while eARG showed no significant treatment effect (Kruskal-Wallis p = 0.082, treating triplicate subsamples as observations). FTICR-MS revealed the lowest intensity-weighted O/C (0.334), most negative NOSC (-0.67), and highest molecular diversity (8029 formulas) at C:N = 10:1, indicating a uniquely reduced, aliphatic-enriched DOM pool. (Note: FTICR-MS samples were pooled from triplicate subsamples per treatment, yielding one composite per C:N level; these results are therefore descriptive and unreplicated.) EPS polysaccharide/protein ratios peaked at 2.8, correlating with iARG across treatments (ρ=0.91, p < 0.001) but inversely with eARG (ρ=-0.59, p = 0.044). Guanosine (ppGpp precursor) peaked at C:N = 10:1 (ρ=0.75 with iARG) while UDP-glucose was depleted, confirming active EPS biosynthesis. Piecewise structural equation modeling identified a pathway from C:N through DOM, EPS, and MGE to iARG (R²=0.78, Fisher's C p = 0.31), whereas eARG depended on eDNA physicochemical trapping (R²=0.41). These findings provide evidence that nutrient stoichiometry acts as a selective control on ARG partitioning, suggesting that C:N monitoring could be incorporated into eutrophic water ARG risk assessment.
Diet is recognized as both a determinant of health and a potential exposure source of environmental chemicals, but evidence linking comprehensive dietary indices to chemicals remains limited. We investigated the associations between diet quality, measured by the Healthy Eating Index 2020 (HEI-2020), and exposures to multiple environmental chemicals in a nationally representative U.S. NHANES 2017-2020 data (n = 4944) were used for the primary analysis, and NHANES 2013-2020 data (n = 11,739) were used for multi-cycle validation. Survey-weighted regression models assessed associations between HEI-2020 scores and chemical concentrations. Generalized additive models explored nonlinearity, and component-level analyses identified dietary components contributing to selected associations. Higher HEI-2020 scores were positively associated with urinary nitrate (β = 0.008), urinary arsenic (β = 0.002), and blood mercury (β = 0.005). Negative associations were observed for blood cadmium (β = -0.001) and perfluorononanoic acid (β = -0.002). Arsenic and mercury showed nonlinear patterns, and multi-cycle analyses supported the general stability of most associations. Component-level analyses suggested that vegetables and greens were major contributors to the nitrate association, seafood and plant proteins were related to mercury and arsenic, and fruit components were inversely associated with cadmium. Healthier diet patterns may accompany beneficial nutrients but also elevate certain contaminant exposures. These results support integrated nutrition and environmental health strategies to maximize dietary benefits while minimizing toxicant exposure.
The cardiovascular-kidney-metabolic (CKM) syndrome represents a continuum linking metabolic dysfunction, chronic kidney disease, and cardiovascular disease, in which chronic inflammation plays a central role. However, conventional inflammatory biomarkers may not fully capture local inflammatory processes involved in CKM stage transitions. Pentraxin 3 (PTX3), a long pentraxin produced locally at sites of inflammation, may provide complementary information, yet its association with CKM staging has not been systematically evaluated. In this cross-sectional study, circulating PTX3 levels were measured in 240 adults, including healthy controls (stage 0, S0; n = 60) and individuals with stage 2 (S2; n = 60), stage 3 (S3; n = 60), and stage 4 (S4; n = 60) CKM, classified according to the CKM staging framework. Associations between PTX3 and inflammatory, metabolic, cardiac, and renal biomarkers were assessed using Spearman correlation analysis. Multivariable logistic regression models were constructed within the CKM population (S2-S4) to distinguish early-stage CKM (S2) from mid-advanced-stage CKM (S3 + S4). Model discrimination and calibration were evaluated using receiver operating characteristic (ROC) analysis and the Hosmer-Lemeshow goodness-of-fit test. PTX3 levels were significantly elevated in early-stage CKM (S2) compared with healthy controls (p < 0.001) and showed further differentiation between S2 and S3 (p < 0.01). PTX3 showed moderate correlations with biomarkers reflecting inflammatory activation, metabolic dysregulation, myocardial injury, and renal dysfunction, including high-sensitivity C-reactive protein (hs-CRP; rs = 0.361, p < 0.001), glycated hemoglobin (HbA1c; rs = 0.434, p < 0.001), triglycerides (TG; rs = 0.296, p < 0.001), and high-sensitivity cardiac troponin T (hs-cTnT; rs = 0.411, p < 0.001), and was inversely correlated with estimated glomerular filtration rate (eGFR; rs = -0.419, p < 0.001). In multivariable logistic regression models adjusting for demographic factors, metabolic indices, and cardiorenal biomarkers, PTX3 remained independently associated with classification into mid-advanced-stage CKM (S3 + S4 vs S2; odds ratio [OR] per unit increase = 1.05, 95% confidence interval [CI]: 1.03-1.08; p < 0.001), whereas hs-CRP and procalcitonin (PCT) showed no independent associations. Compared with the clinical base model, addition of PTX3 improved model discrimination, increasing the AUC from 0.833 to 0.892 (ΔAUC = 0.059; DeLong p = 0.008), without evidence of impaired calibration. Circulating PTX3 is cross-sectionally associated with CKM stage classification and demonstrates incremental discriminative value beyond demographic, metabolic, and cardiorenal variables, as well as conventional inflammatory markers, in distinguishing early-stage from mid-advanced-stage CKM. These findings suggest that PTX3 may reflect inflammatory processes not fully captured by systemic markers, supporting its potential role in CKM risk stratification.
To synthesise evidence on (i) average emotional-intelligence (EI) levels in undergraduate dental students worldwide and (ii) the strength of association between EI, mental stress and educational performance. PubMed, Embase and Scopus were searched (1 Jan 2000-17 Apr 2025). Observational studies that used a validated EI instrument in undergraduate dental cohorts were eligible. Two reviewers independently screened, extracted data and applied the Joanna Briggs Institute risk-of-bias checklist. Random-effects meta-analyses are restricted to (a) mean Schutte EI scores and (b) Fisher-z-transformed correlations between EI and Perceived Stress Scale (PSS) scores, representing a subset of the overall evidence base, with other EI tools and performance outcomes synthesised narratively. Forty-seven cross-sectional studies (n = 10 233 students, 19 countries) met the criteria. The pooled mean EI from 19 cohorts (n = 3226) on the 33-item Schutte scale was 121.3 out of 165 (95% CI 119.5-123.1; I2 < 0.01%), indicating comparable EI across regions. Eleven cohorts (n = 1512) contributed to the EI-stress meta-analysis: higher EI correlated inversely with perceived stress (pooled r = -0.29; 95% CI -0.38 to -0.20; I2 = 14.6%). Qualitative mapping indicated that 21 of the 23 EI-performance comparisons, derived from 17 primary studies (n = 3186), demonstrated positive associations between EI scores and grades, clinical competence or patient-centred outcomes, whereas two comparisons found no relationship; no negative associations were observed. Although the direction of association was predominantly positive, these findings should be interpreted as a pattern across heterogeneous outcomes rather than a coherent quantitative effect. Undergraduate dental students from 19 different countries display similar mid-range EI scores. Higher EI is modestly associated against perceived stress and tends to link with better academic and clinical performance, suggesting potential educational value of nurturing emotional competencies in dental curricula. However, it is important to highlight that the effects are modest and evidence is entirely cross-sectional, supporting EI as a promising but not yet decisive predictor. Future research should standardise ability-based EI measures, link EI to objective performance metrics and employ longitudinal designs to clarify causality.
Physical activity may play a supportive role in cancer survivorship. However, evidence on the association between post-diagnosis physical activity and mortality among women with gynecological cancer remains limited and inconsistent. We conducted a systematic review of the literature published between 1949 and January 2026. Eligible observational studies were identified, and random-effects meta-analyses were performed to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnosis physical activity and all-cause mortality among women diagnosed with gynecological cancer. A total of ten eligible studies on endometrial, ovarian, and cervical cancer were included, collectively reporting 3,867 deaths. High levels of post-diagnosis physical activity, compared with low levels, were associated with lower mortality (HR: 0.65; 95% CI 0.54-0.78). This inverse relationship was evident in both endometrial and ovarian cancer survivors (endometrial cancer: HR: 0.60; 95% CI 0.43-0.83; ovarian cancer: HR: 0.71; 95% CI 0.58-0.86). Medium levels of physical activity tended to be inversely associated with mortality (HR: 0.88; 95% CI 0.76-1.02). Higher levels of physical activity after a gynecological cancer diagnosis were associated with improved survival. The results suggest that physical activity may represent a modifiable lifestyle factor with the potential to improve long-term outcomes among gynecological cancer survivors. This supports the potential value of integrating physical activity into survivorship care, although further high-quality prospective studies are needed to strengthen causal inference.
Despite widespread recognition of dermal exposure to hazardous compounds transferred from consumer products, limited information exists on the friction-mediated transfer of low molecular weight (LMW) chemicals. These chemicals, readily soluble in skin secretions, may pose prolonged dermal exposure risks. To address the knowledge gap, we investigated the frictional transfer of chemicals (formamide, benzothiazole, p-bis(2-hydroxyisopropyl)benzene (pHPB), and bis(2-ethylhexyl) terephthalate (DEHT)) from mats to rubbing fabrics under dry and skin-secretion conditions to simulate clothing-mediated dermal exposure. Gas-phase emissions were also measured. Under dry conditions, transfer efficiencies inversely correlated with molecular weights, namely, for formamide (0.072-0.4%), benzothiazole (0.047-0.072%), pHPB (0.0054-0.035%), and DEHT (0.00037-0.0083%). Skin secretions facilitated friction-mediated chemical transfer, with the extent of facilitation correlating with log Kow. Sweat increased formamide accumulation 5.6-9.0-fold, while sebum boosted DEHT transfer up to 110-fold. Chemical transfer was amplified under intensified mechanical conditions (duration, load, and sliding speed) and modulated by mat surface roughness. In 30 min exercise simulations, formamide (an LMW chemical) transfer efficiency through friction (0.16-1.6%) was comparable to that through gas-phase emission (0.026-0.23%). These findings indicate that frictional contact is a significant pathway for LMW chemical transfer from mats to clothing, providing critical insight for dermal exposure.
Inflammation is a key driver of age-related disease and has been associated with social conditions. We examined how cumulative community-level social and structural disadvantage is associated with inflammatory proteomic profiles in older Black adults. We employed data from the Minority Aging Research Study and the Rush Clinical Core, including the Social Vulnerability Index (SVI; global score and four domains) and 92 plasma inflammatory proteins (Olink® Target-96 Inflammation). Cross-sectional associations between each SVI metric and inflammatory proteins (principal component (PC)-derived global proteomic profile and protein-specific) were assessed using multivariable linear models (demographic, behavioral, and individual-level socioeconomic factors adjusted), with additional sex-by-SVI interaction terms. In a secondary analysis, we replaced SVI with the Index of Concentration at the Extremes (ICE) for household income (ICEincome). A total of 580 participants (mean (SD) age of 74.9 (6.50) years; 79.7% women) had global SVI and proteomics assessed. Lower household composition (SVIHHC) was associated with the primary global proteomic profile, represented by the 1st proteomic PC (beta = -0.429, p-value = 0.019). A secondary exploratory analysis using the first five proteomic PCs showed that higher minority status/language (SVIMSL) and socioeconomic status (SVISES) were associated with an inflammatory proteomic profile (SVIMSL-PC3: beta=0.160, p-value = 0.048; SVISES-PC2: beta = 0.286, p-value = 0.012). In protein-specific analyses, no SVI-protein associations were found. We found an SVIHHC-by-sex interaction for interleukin-10 receptor alpha (IL-10RA; beta = -0.258, p-value = 5.01×10-4), and among men, SVIMSL was associated with Sirtuin 2 (beta = -0.397, p-value = 8.51×10-04) and STAM binding protein (beta = -0.304, p-value = 9.87×10-04). ICEincome was inversely associated with the global proteomic profile (beta = -0.233, p-value = 0.051), and an ICEincome-by-sex interaction was found for IL-10RA (beta=0.279, p-value = 4.66×10-04). By analyzing associations between community-level factors and inflammation-related proteins, our study provides new molecular insights into how social context may relate to biological risk, identifies proteomic patterns that could inform the development of community-level interventions, and underscores the utility of integrating multi-omics approaches to investigate biological pathways relevant to health disparities research.
This study investigated the association between the fat infiltration rate (FIR) of lumbar paraspinal muscles-specifically the multifidus, erector spinae, and psoas major-and bone mineral density (BMD) in postmenopausal women. By examining muscular and segmental (L2-L4) adiposity variations, we aimed to identify imaging biomarkers for early osteoporosis detection and to inform integrated "bone-muscle" therapeutic strategies. A retrospective analysis was performed on 120 postmenopausal women who underwent dual-energy X-ray absorptiometry (DXA) and lumbar computed tomography (CT) between 2024 and 2025. Participants were categorized into three cohorts-normal bone mass, osteopenia, and osteoporosis-based on DXA T-scores. Demographic data, including BMI, were recorded and subsequently utilized as a covariate in the regression models to ensure robust statistical adjustment. The L2-L4 paraspinal musculature was automatically segmented in 3D using 3D Slicer software with the MuscleMap plug-in to determine the FIR for each muscle group. Data normality was assessed using Shapiro-Wilk tests, while inter-group differences were compared via one-way ANOVA or Kruskal-Wallis H tests. Correlations were quantified using Pearson or Spearman analyses. Age was comparable across groups ( P = 0. 160 ), but BMI and average BMD differed significantly. Multifidus FIR showed a significant inverse correlation with BMD ( P < 0. 001 ). After adjusting for BMI, multifidus fat infiltration remained an independent predictor of BMD. At the segmental level, the L3 multifidus displayed the greatest inter-group variance and the strongest negative correlation with BMD ( r = -0. 689, P < 0. 001 ). Lumbar paraspinal muscle adiposity, particularly in the L3 multifidus, is inversely associated with BMD in postmenopausal women. Consequently, L3 multifidus FIR is a statistically significant auxiliary imaging metric for proactive osteoporosis screening and the assessment of osteosarcopenia risk.
OBJECTIVES: Fibroblast growth factor 21 is a metabolic regulator involved in glucose and lipid homeostasis. However, its relationship with excessive intrapancreatic fat deposition in type 2 diabetes mellitus remains unclear. We aimed to evaluate the association between serum fibroblast growth factor 21 levels and excessive intrapancreatic fat deposition in patients with type 2 diabetes mellitus. METHODS: This prospective cross-sectional study included 101 participants who had previously undergone abdominal computed tomography. Group 1 consisted of patients with type 2 diabetes mellitus and excessive intrapancreatic fat deposition (n=31), Group 2 consisted of patients with type 2 diabetes mellitus without excessive intrapancreatic fat deposition (n=40), and Group 3 consisted of individuals without type 2 diabetes mellitus or excessive intrapancreatic fat deposition (n=30). Excessive intrapancreatic fat deposition was assessed on computed tomography by a blinded radiologist. Correlation, multivariable logistic regression, and receiver operating characteristic analyses were performed. RESULTS: Fibroblast growth factor 21 levels were higher in Group 1 than in Groups 2 and 3 (82.32 pg/mL vs. 48.36 pg/mL vs 48.36 pg/mL, respectively; p<0.001). Serum fibroblast growth factor 21 levels were inversely correlated with the pancreas-to-spleen ratio in the overall cohort (ρ=- 0.527, p<0.001) and in the type 2 diabetes mellitus subgroup (ρ=- 0.510, p<0.001). In multivariate analysis, higher serum fibroblast growth factor 21 levels were independently associated with excessive intrapancreatic fat deposition both in the subgroup with diabetes (odds ratio: 1.03, 95% confidence interval: 1.01-1.05; p=0.004) and in the overall study population (odds ratio: 1.03, 95% confidence interval: 1.01-1.05; p=0.003). Receiver operating characteristic analysis showed an area under the curve (AUC) of 0.796 for fibroblast growth factor 21 in predicting excessive intrapancreatic fat deposition. A fibroblast growth factor 21 cutoff value of>62.15 pg/mL yielded a sensitivity of 83.87% and a specificity of 67.14%. CONCLUSIONS: Serum fibroblast growth factor 21 levels were increased in patients with type 2 diabetes mellitus and excessive intrapancreatic fat deposition and were independently associated with excessive intrapancreatic fat deposition. Circulating fibroblast growth factor 21 may reflect pancreatic fat accumulation in the setting of metabolic dysfunction.
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may disrupt maternal fatty acid (FA) metabolism; however, compartment-specific responses, nonmonotonic dose-response relationships (NMDRs), and mixture effects remain insufficiently characterized. We quantified 14 plasma PFAS and comprehensively profiled FAs, FA-class distributions, health-related indices, and product-to-precursor ratios in plasma (n = 192) and red blood cells (RBCs; n = 119) from pregnant women in China. Associations were assessed using multiple linear regression (MLR), restricted cubic splines (RCS), and Bayesian kernel machine regression (BKMR). Perfluorooctane sulfonate (PFOS) was the predominant PFAS, with a median concentration of 3.90 ng/mL, accounting for 45.9% of the total PFAS burden. MLR revealed distinct compartment-specific patterns. In plasma, PFOS and PFOS-related metrics were inversely associated with long-chain n-3 polyunsaturated FAs (PUFAs), including EPA, DHA, Σn-3, and EPA + DHA (β = -0.83 to -0.44), and positively associated with saturation- and n-6-dominant ratios, including Σn-6/Σn-3, ARA/DHA, and ΣSFA/ΣPUFA (β = 0.35-0.78). In RBCs, associations were fewer and were mainly characterized by inverse relationships of total PFAS and long-chain PFAS with arachidonic acid and n-3 PUFA biomarkers (β = -0.75 to -0.65). RCS identified significant NMDRs only in plasma, primarily exhibiting inverted U-shaped or threshold-type patterns, with PFOS breakpoints of approximately 3.00-7.39 ng/mL, corresponding to the 30th-80th percentiles, within environmentally relevant exposure ranges; stronger disruptions were observed above these thresholds. BKMR supported compartment-specific mixture effects, showing nonlinear, PFOS-dominated associations in plasma, with posterior inclusion probabilities of 0.93-1.00, but largely linear and more distributed contributions in RBCs, where saturation ratios increased and n-6 PUFAs decreased with increasing co-exposure. Overall, real-world prenatal PFAS exposure was associated with PUFA depletion and a shift toward more saturated and potentiall pro-inflammatory FA profiles through compartment-specific and nonlinear pathways.
Mycobacterium tuberculosis (Mtb) survives within macrophages by adapting its metabolism to host-imposed constraints, yet how host species shape bacterial metabolic state remains poorly defined. Here, we directly compared the intracellular transcriptional and metabolic states of Mtb during infection of human and mouse macrophages. Cross-species transcriptomics revealed distinct host-imposed microenvironments that drive Mtb into separable metabolic programs, with mouse macrophages inducing stress-associated pathways and human macrophages promoting fatty acid import and catabolism. Strikingly, these differences manifested in a species-specific phenotype: Mtb formed intracellular lipid inclusions (ILIs) in murine macrophages but not in human macrophages, despite equivalent lipid availability. This divergence was independent of macrophage ontogeny, culture conditions, nitric oxide, or itaconate. Instead, bacterial lipid storage in ILIs was inversely correlated with host triacylglycerol synthesis. Pharmacologic inhibition of diacylglycerol acyltransferase 1 in human macrophages partially restored Mtb ILI formation, identifying host lipid sequestration as a metabolic gate that restricts bacterial lipid storage. Together, these findings establish host lipid metabolism as a key determinant of intracellular Mtb metabolic state and reveal a species-specific barrier that limits bacterial access to host lipid stores in human macrophages.IMPORTANCETuberculosis remains a leading cause of infectious death worldwide, yet much of what we know about how Mycobacterium tuberculosis survives inside immune cells comes from studies in animal models. This work shows that human and mouse macrophages impose fundamentally different metabolic constraints on the bacterium, leading to distinct survival strategies. In mouse cells, the pathogen adopts a stress-associated state and stores lipids, whereas in human cells, it does not. We identify host lipid metabolism as a key factor limiting bacterial access to these resources in human macrophages. These findings highlight an important species-specific difference that may influence how well animal models predict human infection and suggest that targeting host lipid pathways could offer new strategies to control tuberculosis.
Sepsis-induced cardiomyopathy (SCM) is one of the common complications caused by sepsis. Despite the higher mortality rate associated with SCM, the pathogenesis of SCM is poorly understood. The study of circular RNA (circRNA) in a variety of diseases has accelerated over recent decades. However, the function of circRNAs in SCM is rarely reported. Here, we found that the circRNA from the TTN gene (circTTN) was increased in the SCM mouse and cell models. Modulation of circTTN affected the characteristics of SCM both in mouse and cell models. The expression of ferroptosis regulators, GPX4 and SLC7A11, in SCM models changes inversely with the level of circTTN. Function analysis revealed that circTTN promotes ferroptosis through binding to heat shock protein family A (HSPA5) protein. This finding may promote knowledge about the pathogenesis of SCM and may be helpful for targeted therapy based on circTTN in the future.
To assess in neonates with hypoxic-ischemic encephalopathy (HIE) whether multimodal neuromonitoring, using near-infrared spectroscopy and amplitude-integrated electroencephalography (aEEG), correlates with cerebral injury observed on brain magnetic resonance imaging (MRI) as well as neurodevelopmental outcome. Neonates born at >35 weeks and >1800 gram undergoing therapeutic hypothermia were included in this prospective-retrospective, multicenter study. The aEEG pattern, cerebral tissue oxygenation (rScO2), burden of rScO2≥95%, arterial blood pressure, heart rate, and cerebrovascular autoregulation were monitored during therapeutic hypothermia and rewarming from 0-24, 24-48, 48-72, and 72-96 hours. Early cerebral MRI was assessed using a validated quali-quantitative score. Neurodevelopmental outcome was assessed using Bayley Scales of Infant Development (BSID-III) cognitive and motor scores at 24 months. In 128 neonates with a median Thompson score of 9, greater seizure burden (beta coefficient, B24-48h=3.21, 95% confidence interval limits, 95%CI [2.01, 4.41]), absent sleep-wake-cycling (B24-48h=-5.53, 95%CI [-8.29, -2.77]), and a higher burden of rScO2≥95% (B0-24h=0.34, 95%CI [0.07, 0.61]) were associated with worse cerebral injury on MRI. Cognitive and motor scores inversely correlated with aEEG abnormalities, rScO2, burden of rScO2≥95%, and absent sleep-wake-cycling, whereas higher arterial blood pressures between 0-24 hours were associated with higher neurodevelopmental outcome scores. Combined abnormal aEEG characteristics and rScO2, but not cerebrovascular autoregulation assessed as cerebral oximetry index or tissue oxygenation heart rate-reactivity index, correlated significantly with brain injury on MRI and neurodevelopmental outcome after HIE. These findings provide valuable clinical information and, in future studies, may support identification of infants who might benefit from adjuvant therapies.
Multiple VA-ECMO studies have recently reported that early hyperoxia is associated with increased mortality, yet the underlying mechanism is unclear. As prior analyses did not account for native cardiac output or fraction of delivered oxygen, it remains unknown whether hyperoxia is directly injurious or primarily a surrogate of poor intrinsic cardiac function and proximal mixing. This study aims to evaluate whether hyperoxia is an independent predictor of mortality in VA-ECMO patients or whether it primarily reflects impaired native cardiac function. We conducted a single-center retrospective cohort study of 227 VA-ECMO patients to evaluate the relationship between hyperoxia and ICU mortality, accounting for native cardiac index using multivariable regression and principal component analysis. Average PaO2 and cardiac index were analyzed as continuous variables. Decreased cardiac index was the strongest independent predictor of ICU mortality in a multivariable regression (OR 0.22; 95% CI 0.06-0.70; p = 0.018). After adjusting for native cardiac index and utilization of advanced therapies (i.e., heart transplant or LVAD), the association between hyperoxia and mortality became insignificant. Average PaO2 and cardiac index were strongly inversely collinear (Variance Inflation Factor (VIF) = 7.2 and 11.5, respectively), with their interaction term yielding a VIF of 20.3. Non-survivors and survivors who received advanced therapies share similar PC1 score distributions (a weighted composite of average PaO2 and cardiac index) and impaired hemodynamic profiles, including reduced ejection fraction, pulse pressures, and oxygen delivery indices. The association between early hyperoxia and mortality in VA-ECMO is primarily driven by underlying cardiac failure rather than direct oxygen toxicity. The availability of advanced therapies further modifies this relationship, underscoring the need to account for both native cardiac output and heart replacement strategies when evaluating optimal PaO2 targets and the independent effect of hyperoxia on VA-ECMO outcomes.
This study evaluated the association between midtrimester cervical length (CL) and pregnancy outcomes in low-risk nulliparous and multiparous singletons and assessed whether combining CL with obstetric and medical history improved the prediction of spontaneous preterm birth (sPTB). This multicenter prospective cohort study included singletons without prior sPTB < 34 weeks who had CL measured at 18-22 weeks GA. Outcomes were retrieved through linkage with the national perinatal registry. Primary outcome was sPTB < 37 weeks. Secondary outcomes included PTB rates, NICU admission and perinatal death. Sensitivity and specificity were calculated per CL group. GA at birth was analyzed using Kaplan-Meier curves, and predictors were assessed using multivariable Cox regression with hazard ratios (HR) and 95% confidence intervals (CI). Results are reported separately for nulliparous and multiparous singletons. We retrieved 15,524 pregnancy outcomes following a CL measurement between 2015-2022. In nulliparous singletons (N = 8,078), sPTB < 37 weeks occurred in 31.0%, 8.7%, 9.3%, and 3.5% for CL ≤ 25, 26-30, 31-35, and > 35 mm, respectively. CL ≤ 25 mm identified 7.8% of sPTB < 37 weeks and 31.3% of sPTB < 32 weeks. In multiparous singletons (N = 7,446), rates were 17.2%, 7.9%, 5.2%, and 2.3%, with CL ≤ 25 mm identifying 5.6% of sPTB < 37 weeks and 24.2% of sPTB < 32 weeks. Multivariable Cox regression showed that in nulliparous singletons, only CL categories were associated with sPTB < 37 weeks compared with the reference > 35 mm, with the highest hazard for CL ≤ 25 mm (HR 10.8, 95% CI 6.3-18.8; p < 0.0001). In multiparous singletons, CL ≤ 25, 26-30, and 31-35 mm (p < 0.0001, p = 0.001, p = 0.04), low SES (p = 0.03), smoking (p < 0.0001), and an interpregnancy interval < 6 months (p = 0.02) were significantly associated. This study confirmed the strong inverse correlation between midtrimester CL and sPTB risk, with multivariable regression analyses reinforcing CL as the dominant predictor. Given its ability in identifying those at highest risk, particularly for sPTB < 32 weeks, universal CL measurements should be central to PTB prevention strategies.