Interaction Test Research Articles

Association between weight-adjusted-waist index and serum anti-aging protein α-Klotho in U.S. adults: Evidence from NHANES 2007-2016.

As unhealthy diets have proliferated, there has been an increasing trend in the prevalence of obesity along with socioeconomic progress. WWI, mainly representing weight-independent central obesity, is a more accurate indicator of obesity than BMI and WC. Klotho is known to be one of the root causes of several age-related illnesses. There has never been any prior evidence associating WWI and serum α-Klotho levels. The current cross-sectional investigation used data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. The calculation of each participant's WWI involved dividing their waist circumference in centimeters by the square root of their weight in kilograms. Using multivariable linear regression models, the association between serum Klotho concentrations and WWI was analyzed. Smoothed curve fitting was utilized to investigate the nonlinear connection. In addition, interaction tests and other subgroup analyses were carried out. With an average age of 57.57±10.81years, 13,172 participants were enrolled in this study, of whom 51.45% were female. After full adjustment, each unit increase in WWI was significantly associated with a decrease in Klotho by 23.18ng/ml [β(95%CI)=-23.18 (-31.34, -15.02)]. Moreover, we uncovered that WWI had a stronger negative correlation with Klotho than other obesity markers, such as WC, body mass index (BMI), and a body shape index (ABSI). To sum up, weight-adjusted-waist index levels were negatively associated with serum Klotho protein concentration and showed a stronger correlation than other obesity markers. Our findings indicated that WWI may be a predictor of reduced Klotho levels, and that controlling obesity in accordance with WWI may help lower the Klotho levels.

Utilisation of waste rock backfill materials in deep gobs for mitigating mining-induced water inrush risks: compression deformation and seepage characteristics

ABSTRACT In deep backfilling coal mines, granular waste rocks face complex stress and water environments after being backfilled in the goaf. To characterize the compression deformation and seepage of granular waste rock backfill materials in the deep goaf, a fluid-structure interaction (FSI) test system for granular waste rocks was developed. Influences of overburden stress on deformation and seepage characteristics of granular waste rocks were investigated. The research shows that the high overburden stress in deep underground coal mines can continuously change the structure of granular waste rocks. In the process of increasing overburden stress from 15 to 22.5 MPa, the porosity of granular waste rocks decreases rapidly and the permeability reduces fast accordingly. After the axial pressure exceeds 22.5 MPa, the porosity and permeability of granular waste rocks both tend to be stable. In the seepage process of confined groundwater under single overburden stress, the increase in water pressure can improve the porosity and permeability of granular waste rocks. Small waste rocks in samples play the leading role, they can achieve a waterproof state under relatively low overburden stress. The backfilling method that combines large and small particles can be considered, which can achieve rapid water proofing at a low cost.

Sex differences in the colorectal tumor immune microenvironment.

283 Background: Males have increased risk and mortality rates of colorectal cancer (CRC) compared to females, but the reasons for these disparities are not well understood. Immune responses differ by sex, and a robust T cell response is an important prognostic indicator in CRC. We hypothesized that females exhibit a stronger CRC-associated T cell response, contributing to reduced mortality in females compared to males. Methods: The study cohort included 2,751 incident CRC patients (1,337 female; 1,414 male) from a population-based case-control study. T cell receptor (TCR) abundance and clonality were quantified using immunoSEQ, and a gastrointestinal pathologist scored tumor-infiltrating lymphocyte counts per high-powered field (TILs/hpf). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between T cell metrics and sex, adjusting for age, anatomic site, and microsatellite instability (MSI) status. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals for the association between sex and 5-year all-cause and CRC-specific survival, adjusting for known prognostic indicators. We also conducted a formal test for interaction between sex and T cell features in relation to survival outcomes. Results: There were no associations between sex and TCR abundance (OR=1.05, 95% CI=0.98-1.13, p=0.14), TCR clonality (OR=0.99, 95% CI=0.91-1.06, p=0.72), or TILs/hpf (OR=1.05, 95% CI=0.88-1.25, p=0.60). We observed no differences in overall or disease-specific five-year survival between males and females. Further, the associations between T cell responses and survival did not significantly differ by sex. Conclusions: In a well-powered analysis, no robust sex differences were observed in the CRC immune microenvironment or in the relationship between T cell infiltration and CRC outcomes. The high burden of CRC and the emergence of immunotherapy as an important therapeutic approach suggest a need for further research investigating immunological sex differences in the setting of treatment response. Summary of associations between the colorectal tumor T cell response and sex. T cell Features Odds Ratio(Female vs. Male) Lower 95% CI Upper 95% CI P Value TCR Abundance 1.05 0.98 1.13 0.14 TCR Clonality 0.99 0.91 1.06 0.72 TILs/hpf* <2 1.05 0.88 1.25 0.60 *A total of 99 patients (45 female; 54 male) with missing TILs/hpf data were excluded from the regression analysis.

Impact of sirtuin genes expression on first-line treatment outcomes in patients (pts) with metastatic colorectal cancer (mCRC) enrolled in CALGB/SWOG 80405 (Alliance).

269 Background: Sirtuins (SIRT1-7) are class III histone deacetylases with different roles in CRC as tumor suppressive and oncogenic, mainly influencing proliferation, migration, invasion, DNA damage and chemoresistance. In the present study, we explored the association between tumor gene expression of sirtuins and first-line treatment outcomes in mCRC pts. Methods: We evaluated the impact of the tumor gene expression of sirtuin genes ( SIRT1 -7) on treatment outcomes (overall survival: OS; progression free survival: PFS) in 433 pts enrolled in the randomized, phase III CALGB/SWOG 80405 (NCT00265850) trial. RNA extracted from FFPE tumor samples was sequenced using the HiSeq 2500 (Illumina). Subgroup analyses were based on treatment (bevacizumab [bev] (N = 226) vs. cetuximab [cet] (N = 207)). For each gene, expression was divided into tertiles of high, medium and low. The associations between tumor gene expression and outcomes (PFS and OS) were assessed using log-rank test in univariate analysis. Multivariable Cox proportional hazards regression model was used to compute hazard ratios (HR) and 95% confidence intervals while adjusting for baseline characteristics. Treatment-gene interactions were analyzed using the likelihood ratio test. Results: Of the seven genes analyzed, SIRT3 high was associated with both longer PFS (HR: 0.59 [95% CI: 0.46-0.74], P < 0.001) and OS (HR:0.64 [95% CI: 0.50-0.83], P = 0.002) overall. Treatment-gene interaction testing found significant interactions for SIRT1 and SIRT5 with PFS ( P values: 0.021 and 0.016, respectively) and OS ( P values: 0.038 and 0.014, respectively) with targeted therapies (bev vs. cet). Multivariate analysis showed SIRT1 high associated with longer PFS (HR: 0.62 [95% CI: 0.42-0.89], P = 0.014) and OS (HR: 0.59 [95% CI: 0.40-0.89], P = 0.036) in cet-treated pts; in contrast with shorter observed PFS (HR: 1.38 [95% CI: 0.96-1.99], P = 0.22) and OS (HR: 1.31 [95% CI: 0.90-1.93], P = 0.23) in bev-treated pts. SIRT5 high showed similar results and associated with longer PFS (HR: 0.64 [95% CI: 0.45-0.91], P = 0.039) and OS (HR: 0.57 [95% CI: 0.39-0.83], P = 0.013) in cet-treated pts, with no similar associations in bev-treated pts. Conclusions: Our results highlight a potential role for SIRT3 as prognostic and, SIRT1 and SIRT5 as predictive biomarkers for first-line treatment in mCRC, with differential effects based on targeted agents. Significant interaction favored cet treatment in SIRT1 high and SIRT5 high tumors. However, previous reports suggest an opposite role of SIRT5 that has been linked to chemotherapy and/or cet resistance in CRC via the inactivation of succinate dehydrogenase complex subunit A. Therefore, further studies are warranted to dissect the mechanism behind the interaction of SIRT5 with cetuximab activity and establish the potential of targeting SIRT1/5 in CRC.

Abstract TMP113: Sex differences in the effects of social isolation on behavioral and metabolic parameters in a model of cerebral amyloid angiopathy

Introduction: The prevalence of social isolation (SI) increases with aging and contributes to poor health outcomes and increased risk of cognitive impairment, especially in Aβ-related diseases. Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) deposition in the cortical and leptomeningeal vessels, and is a leading cause of hemorrhagic stroke and age-related cognitive impairment. How social isolation affects vascular amyloid deposition, cognitive decline and social behavior in CAA is unknown. Methods: TgSwDI mice carrying Swedish, Dutch, and Iowa mutations of human amyloid precursor protein were used as a CAA model. Male and female C57BL/6 wildtype (WT) and CAA mice were randomly assigned to pair housing (PH) or SI at 3 months of age. Affective and social behaviors were assessed at baseline and every 3 months thereafter using the tail suspension test (TST) and three-chamber social interaction test. At 9 months post-SI, cognitive behaviors and general well-being were measured using fear conditioning (FC) and the nesting test, respectively. Body weights were recorded, and white adipocyte size was measured using immunostaining. Results: SI led to increased immobility in the TST at 3- and 6-months post-SI in both male and female WT and CAA mice, suggesting depressive-like behavior (n=5-8/grp, p<0.05). Isolated CAA mice displayed greater cognitive deficits in FC, while only male WT SI mice showed impaired cognition (n=5-12/grp, p<0.005). Sex differences in social behavior were observed in isolated CAA mice. Specifically, at 6 months post-SI, female CAA mice displayed deficits in sociability and social novelty (n=4-9/grp, p<0.05), which was not seen in male CAA mice. SI negatively impacts the general well-being in both male WT and CAA SI animals (n=5-12/grp, p<0.005). Preliminary findings showed increased white adipocyte size in male WT SI mice with a similar trend in male CAA SI animals, pointing to potential metabolic effects of isolation. Conclusion: SI induced cognitive decline in both male and female CAA mice. Behavioral differences between sexes were noted in CAA mice including nesting ability, sociability, and depressive-like behaviors. Further research is needed to determine the cellular and molecular mechanism underlying SI-induced metabolic changes in CAA.

Abstract TP384: The secretome of intestinal epithelial stem cells attenuates acute and chronic stroke impairment

Background: We showed that intestinal epithelial stem cells (IESCs) obtained from healthy young donor rats and transplanted to aging animals after stroke reduced infarct volume and sensorimotor impairment in the acute phase and mitigated cognitive impairment in the chronic phase. In most cases, stem cell transplants do not engraft or differentiate in vivo and their beneficial effects are proposed to occur through their secretions. Here we tested the hypothesis that IESC conditioned media (CM) would be similarly effective in improving acute and chronic stroke outcomes. Methods: IESCs from young animals were cultured as organoids using our published protocol (PMID:36328163). Conditioned media was collected from these cultures and tested for treatment efficacy in middle-aged male and female rats assigned to the following groups: Control (sham), stroke+vehicle injection, or stroke+ IESC-CM treatment. Two treatment regimens were performed for IESC-CM treatments: 4h/24h/48h or 4h/12h/36h/48h after stroke. Stroke was induced by middle cerebral artery occlusion (MCAo) via Endothelin-1 (vasoconstrictor) followed by intraperitoneal injection (ip) of IESC-CM. Infarct volume and sensorimotor function were assessed on 4d post stroke and at 30 days post stroke, animals were tested on the Social Interaction test (depressive-like behavior) and, Novel object Recognition test and Barnes maze test respectively (cognitive assessment). Serum levels of the gut permeability markers and cytokines level were measured at both time points. Results: IP treatment with IESC-CM significantly improved acute stroke outcomes and reduced gut permeability in middle-aged females. In chronic phase, vehicle-treated MCAo animals showed depressive-like behaviors compared to their pre-stroke behavior. In contrast, stroke animals that received IESCs-CM were no different from their pre stroke performance and were similar sham (no-stroke) animals. When assessing cognition, the MCAo+ vehicle animals showed poor discrimination abilities and impaired learning and retrieval memory. MCAo+IESCs-CM animals showed some improvement in episodic memory and spatial learning and retrieval with the 3 dose treatment, and significant improvement in both tests with the 4 dose treatment. Conclusion: These data indicate that the secretome of IESCs is sufficient to promote stroke recovery and suggests a strategy to increase the translational potential of this therapy.

Juvenile chronic social defeat stress reduces prosocial behavior in adult male mice

Exposure to stress in early life can have a significant impact on individuals. However, the effects of early-life stress (ELS) on prosocial behavior remain unclear, as do the underlying mechanisms. In this study, ICR juvenile mice were subjected to juvenile chronic social defeat stress (jCSDS) between postnatal days 32 and 41, during which body weight changes were continuously monitored. The behaviors of adult mice were evaluated using the open field test (OFT), the social interaction test (SIT), and the prosocial choice task (PCT). ELISA was used to quantify serum levels of oxytocin, serotonin, and dopamine. The density of dendritic spines in the basolateral amygdala was evaluated by Golgi staining. Behavioral test results showed that jCSDS induced anxiety-like behavior and decreased prosocial selection tendency in mice. Additionally, exposure to jCSDS increased the serum levels of oxytocin, decreased those of serotonin, and increased the density of dendritic spines in the basolateral amygdala. Correlation analysis indicated that prosocial behavior was negatively correlated with serum oxytocin levels and dendritic spine density in the basolateral amygdala. These results suggested that jCSDS reduced prosocial behavior, possibly due to changes in serum oxytocin contents and adaptive changes in amygdaloid neurons.

Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice.

Reports indicate that depression is a common mental health issue following traumatic brain injury (TBI). Our prior research suggests that Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-related neuroinflammation, modulated by glial cells such as astrocytes, is likely to play a crucial role in the progression of anxiety and cognitive dysfunction. However, there is limited understanding of the potential of astrocytic NLRP3 in treating depression under mild TBI condition. This study aimed to determine whether astrocytic NLRP3 knockout (KO) could mitigate depressive-like behaviors following mild TBI and explore potential variations in such behaviors between genders post-mild TBI. Mild TBI was induced in mice using Feeney's weight-drop method. Behavioral assessments included neurological severity scores (NSS), social interaction test (SI), tail suspension test (TST), and forced swimming test (FST). Pathological changes were evaluated through immunofluorescence and local field potential (LFP) recordings at various time points post-injury. Our findings indicated that astrocyte-specific NLRP3 KO decreased cleaved caspase-1 colocalized with astrocytes, decreased pathogenic astrocytes and increased Postsynaptic density protein 95 (PSD95) intensity, and significantly alleviated mild TBI-induced depression-like behaviors. It also led to the upregulation of protective astrocytes and apoptosis-associated factors, including cleaved caspase-3 post-mild TBI. Additionally, astrocyte-specific NLRP3 deletion resulting in improved θ and γ power and θ-γ phase coupling in the social interaction test (SI). Notably, under mild TBI conditions, astrocyte-specific NLRP3 exhibited greater neuroprotective effects in female knockout mice compared to males. Astrocyte NLRP3 knockout demonstrated a protective mechanism in mice subjected to mild TBI, possibly attributed to the inhibition of pyroptosis through the NLRP3 signaling pathway in astrocytes.

Dietary phytoestrogens recalibrate socioemotional behavior in C57Bl/6J mice in a sex- and timing-dependent manner.

Estrogens are potent regulators of socioemotional behavior across species. Ubiquitous in human and animal diets, plant-derived phytoestrogens (PE) bind estrogen receptors. While prior work has examined the impact of PE exposure on socioemotional behavior, findings are inconsistent across studies. To investigate whether the timing of PE diet initiation may govern differential behavioral effects, we compared the impacts of PE-free (<20mg/kg) versus PE-rich (810mg/kg) diet exposure across the lifetime versus acutely in adulthood. Reproductive physiology was assessed through age at puberty onset and gonadal size. In adulthood, all mice underwent a behavioral battery consisting of the open field, elevated plus maze, and social interaction tests, followed by assessment of emotional memory dynamics with cued threat conditioning, extinction, recall, and renewal. Lifetime PE exposure delayed puberty onset and increased adult gonadal size selectively in males, whereas both lifetime and adult-only PE exposure decreased adult body weight in both sexes. In males, adult-only exposure increased open-arm avoidance in the elevated plus maze but enhanced threat memory extinction. In females, lifetime PE exposure increased open-arm avoidance, reduced sociability, and impaired threat memory extinction. Interestingly, lifetime PE exposure increased the context-dependent renewal of threat memory in both sexes. These findings demonstrate sex- and timing-dependent effects of PE exposure. Male lifetime PE exposure impacts reproductive measures with limited behavioral effects, whereas female lifetime exposure broadly impairs socioemotional behavior. Conversely, adult-only PE exposure altered behavior in males with limited impact in females. This study highlights the importance of diet composition, exposure period, and sex in rodent behavioral studies.

Clinical and molecular characterization of FAP and SPP1 in colorectal cancer (CRC), CALGB (Alliance)/SWOG 80405 and real-world data.

276 Background: FAP and SPP1 contribute to immune modulation in the CRC tumor microenvironment (TME). FAP is expressed by cancer associated fibroblasts, aiding in tissue remodeling and tumor invasion. SPP1 is an integrin-binding protein expressed by tumor associated macrophages that promotes tumor growth, adhesion, and metastasis. We present a clinical and molecular characterization of FAP and SPP1 in CRC. Methods: We analyzed 24,257 CRC samples tested at Caris Life Sciences (Phoenix, AZ) with WTS (Illumina NovaSeq), NextGen DNA sequencing (NextSeq), and PD-L1 expression (SP142, positive ≥ 2+, 5%). RNA deconvolution analysis estimated cell infiltration in the TME. Data from the phase 3 CALGB/SWOG 80405 trial (NCT00265850) on 433 metastatic CRC patients treated with bevacizumab (Bev, n = 226) or cetuximab (Cet, n = 207) in combination with first-line chemotherapy were also evaluated. RNA isolated from FFPE tumor samples were sequenced with HiSeq 2500 (Illumina). Overall survival (OS) and progression-free survival (PFS) were compared using Cox regression in categorical gene expression tertiles (high (T3), medium (T2), and low (T1)) for FAP and SPP1 . Results: FAP -T3 and SPP1 -T3 had increased PD-L1 positivity (q&lt;0.05), while SPP1 -T3 also demonstrated increased MSI-H (8.4% vs 5.3%) and TMB-H(&gt;10 mt/mb, 15.0% vs 10.1%) status relative SPP1 -T1 (all q&lt;0.001). T3 of both genes of correlated with increased M1/M2 macrophages, NK cells and T cell inflamed score (q&lt;0.001); dendritic cells and neutrophils were increased in SPP1 -T3 and FAP -T1 tumors (q&lt;0.05). FAP -T3 and SPP1 -T3 had increased pathway activation of epithelial-mesenchymal transition (EMT), inflammatory response, TNF-a signaling, angiogenesis and KRAS signaling (all q &lt; .005). In Caris cohorts, FAP -T3 demonstrated worse OS in Cet/panitumumab treated CRC (T3: 23.6 vs T1: 21.0 months [mo], P = .005; HR 0.85, 95% CI [0.77-0.95]), but SPP1 did not correlate with OS. In 80405, FAP -T3 showed shorter PFS (T3: 9.5 vs T2: 11.5 vs T1: 12.6 mo, T3 vs T1 (reference) adjusted HR 1.27 [1.07-1.51]) and OS (25.2 vs 29.4 vs 35.5 mo, adjusted HR 1.31 [1.10-1.57]). Similarly, SPP1 -T3 demonstrated worse PFS (9.0 vs 12.7 vs 14.0 mo, adjusted HR 1.29 [1.12-1.48]) and OS (20.9 vs 34.0 vs 36.3 mo, HR 1.24 [1.07-1.44], P &lt; 0.001). Treatment interaction tests noted FAP -T1 CRC benefited from Cet over Bev with respect to PFS ( P = 0.003) and OS ( P = 0.044), while SPP1-T1 tumors demonstrated a PFS benefit with Cet ( P = 0.009). Conclusions: Our results indicate that increased FAP and SPP1 expression is associated with immune cell infiltration, EMT, and inflammatory signaling. Additionally, their expression may be prognostic and predictive of targeted therapy. These data support the evaluation of FAP and SPP1 as predictive markers and therapeutic targets in CRC.

Association of oxidative balance score with the risk of all-cause and CVD mortality in younger US adults with diabetes

Oxidative balance score (OBS) is a composite measures that assess the balance between pro-oxidant and antioxidant factors in an individual’s diet and lifestyle, with higher scores indicating greater antioxidant exposure. Despite its potential significance, there is a limited body of research exploring the relationship between OBS and all-cause and cardiovascular disease (CVD) mortality specifically in younger patients with diabetes. We aimed to investigate the possible relationship between OBS and all-cause and CVD mortality in younger patients with diabetes. Data for this study were obtained from the 2003–2018 NHANES. This study enrolled 3501 participants. The endpoints were all-cause and CVD mortality, determined by the National Death Index (NDI). OBS, which consists of 16 dietary factors and 4 lifestyle factors, is categorized into pro-oxidants and antioxidants. The OBS was categorized into four quartiles (Q1-Q4). We used multivariable Cox proportional hazards regression models to examine the association between continuous and quartile measures of OBS, lifestyle OBS (lifestyle antioxidants such as physical activity, etc., and lifestyle pro-oxidants such as alcohol, smoking, etc.), and dietary OBS (dietary antioxidants such as fiber, β-carotene, riboflavin, etc., and dietary pro-oxidants, such as total fat, etc.) with all-cause and CVD mortality. Additionally, we explored restricted cubic spline (RCS) analysis and also performed subgroup analyses and interaction tests. The occurrence of 409 all-cause deaths (11.7%) and 108 CVD-related deaths (3.1%) was recorded during the follow-up period. Our results found that OBS, lifestyle OBS, and dietary OBS were negatively associated with patients’ all-cause and CVD mortality. The RCS analysis further validated the association of a linear negative correlation between OBS and all-cause and CVD mortality. The results of our subgroup analyses revealed that the negative association between OBS and CVD mortality may be influenced by alcohol use. In conclusion, results from a nationally representative study of younger American patients with diabetes suggest a negative association between OBS, lifestyle OBS, and dietary OBS and all-cause and CVD mortality. Antioxidant-rich diets and lifestyle improvements are essential for reducing all-cause and CVD mortality in patients.

Association of systemic immune-inflammation index (SII) with risk of psoriasis: a cross-sectional analysis of National Health and Nutrition Examination Survey 2011–2014

BackgroundThe systemic immune-inflammation index (SII) is an emerging marker of inflammation, and the onset of psoriasis is associated with inflammation. The aim of our study was to investigate the potential impact of SII on the incidence rate of adult psoriasis.MethodsWe conducted a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES) 2011–2014 data sets. Multiple logistic regression analyses with appropriate covariates adjustment were the major methods in this study. Subgroup analyses were conducted by age, gender, race, smoking status, alcohol consumption, history of heart attack, stroke, coronary heart disease and diabetes. Interactions among these variables were also detected. We further utilized smooth curve fitting to explore potential nonlinear associations between SII and psoriasis across different subgroups. The receiver operating characteristic curve analysis was used to assess the diagnostic value of SII for psoriasis in the general population and diabetic individuals. Multiple imputation was adopted as sensitivity analysis to address potential bias due to missing data.Results9314 participants (≥ 20 years) were included. A significant positive association was observed between SII and psoriasis (OR = 1.56; P = 0.0069). Subgroup analysis revealed significant positive association in males (OR = 1.52; P = 0.0288), females (OR = 1.61; P = 0.0322), Non-Hispanic Whites (OR = 1.55; P = 0.0190), people aged 40–59 years (OR = 1.98; P = 0.0386), diabetics (OR = 3.40; P = 0.0088), and overweight participants (OR = 1.80; P = 0.0034). SII had a higher predictive value for psoriasis in diabetic patients (AUC = 0.62; 95% CI [0.55, 0.70]). In stroke patients, SII was negatively correlated with the occurrence of psoriasis, and interaction test suggested the effect of SII on psoriasis was significantly modified by stroke (P = 0.0003). Nonlinear relationships between SII and psoriasis were observed in participants aged 20 to 39, former smokers, current drinkers, individuals with or without heart attack, those without coronary heart disease, and overweight participants.ConclusionsSII was positively associated with psoriasis. Testing for SII levels may help to identify the onset of psoriasis early.

Evaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on Aging

High intraocular pressure (IOP) is an important risk factor for glaucoma, which is influenced by genetic and environmental factors. However, the etiology of high IOP remains uncertain. Metabolites are compounds involved in metabolism which provide a link between the internal (genetic) and external environments. O-methylascorbate has been reported to be associated with IOP. In addition, researchers have identified several genetic variants which are associated with metabolite concentrations, including O-methylascorbate and another vitamin C related metabolite, ascorbic acid 2-sulfate. We aimed to understand how O-methylascorbate and ascorbic acid 2-sulfate, or genetic variants associated with these metabolites, modify the associations between dietary environmental variables and IOP. We used data from 8060 participants of the Canadian Longitudinal Study on Aging. Using linear models adjusted for relevant covariates, we tested for interactions between six genetic variants previously found to be associated with O-methylascorbate and ascorbic acid 2-sulfate and four environmental variables related to diet (alcohol consumption frequency, smoking status, fruit consumption, and vegetable consumption). We also tested for interactions between serum concentrations of O-methylascorbate and ascorbic acid 2-sulfate and these environmental factors. We used a False Discovery Rate approach to correct for the 32 interaction tests performed. One interaction was suggestively significant after multiple testing correction (adjusted P-value < 0.1): rs8050812 and alcohol consumption frequency. Understanding how genetic variants and metabolites interact with the environment could shed light on biological pathways controlling IOP and lead to improved prevention and treatment of glaucoma.

Metabolically healthy overweight/obesity with no metabolic abnormalities and incident hyperglycaemia in Chinese adults: analysis of a retrospective cohort study

ObjectivesTo explore whether metabolically healthy overweight (MHOW) and/or metabolically healthy obesity (MHO) increase hyperglycaemia risk in a Chinese population with a broad age range.DesignRetrospective cohort study.SettingSecondary analysis of data from...

The Effect of Motivation, Competence, Compensation on Employee Performance with Organizational Culture as A Moderating Variable

Motivation, Competence, Compensation, and Organizational Culture have a great influence on the Employee Performance of PT. Adi Dharma Abadi. These four variables prove that this study aims to analyze the influence of motivation, competence, and compensation on employee performance with organizational culture as moderating variables in PT. Adi Dharma Abadi Bogor Regency. The study was conducted at PT. Adi Dharma Abadi Bogor Regency took 35 employees as the research sample, which was calculated using an equation formula through an interaction test often referred to as Moderated Regression Analysis (MRA) with a total population of 35 employees at an error margin of 2.5 %, for the data collection techniques, questionnaires, interviews, and observations. The data is processed using the SPSS version 26 application. The test data used in this research are reliability tests, validity tests, statistical tests, and classical assumption tests. The results of this study show that Motivation, Competence, Compensation, and Organizational Culture have a positive and significant influence on Performance.

Association between lipid accumulation product and the risk of colon cancer in adults: A population-based study.

The purpose of this study was to look into any potential connections between the occurrence of colon cancer and the condition of the body of lipid accumulation product (LAP) index. Using data from the 2009-2018 National Health and Nutrition Examination Survey (NHANES), we performed a cross-sectional analysis with 24,592 individuals. Utilizing multivariate logistic regression modelling, the relationship between LAP levels and colon cancer risk was investigated. Subgroup analysis, trend test, interaction test, and stratified smoothed curve were also carried out. LAP levels and colon cancer risk were positively correlated after controlling for potential covariates (OR = 10.56, 95% CI: 2.40-46.53), the findings of trend tests are statistically significant. In particular groups, subgroup analysis revealed a positive connection between LAP levels and the risk of colon cancer. The association between LAP levels and colon cancer risk was shown to be M-shaped in the group under 60 years old, inverted V-shaped in the female and no-diabetes groups, and inverted L-shaped in the smoking and no-hypertensive groups, according to stratified smoothed curve fitting. According to our findings, there is a strong correlation between LAP levels and the risk of colon cancer.

Association Between Riboflavin Intake and Suicidal Ideation: A Nationwide Study in Korea

Background/Objectives: In recent years, there has been an increased interest in reducing suicide rates through dietary modification; however, the relationship between riboflavin intake and suicide risk remains unclear. This study aims to examine the association between dietary riboflavin and suicidal ideation. Methods: A total of 17,320 participants from the Korean National Health and Nutrition Examination Survey (KNHANES) 2014–2020 were included. Suicidal ideation was assessed using the ninth item of the Patient Health Questionnaire-9 (PHQ-9). Riboflavin intake was evaluated through dietary assessments. Multivariate logistic regression, restricted cubic spline (RCS) regression analysis, subgroup analysis, and interaction tests were conducted to explore the relationship between riboflavin intake and suicidal ideation. Results: There was a statistically significant association between riboflavin intake and suicidal ideation [OR (95%CI): 0.83 (0.77, 0.91), p &lt; 0.001], after full adjustment for covariates. The linear trend test, using Q1 as the reference, showed ORs (95% CI) for Q2 and Q3 of 0.96 (0.81, 1.15) and 1.06 (0.80, 1.42), respectively. The RCS analysis revealed a non-linear pattern in the relationship between riboflavin intake and suicidal thoughts. This association was particularly significant among women and individuals younger than 60 years. Subgroup analyses and interaction tests indicated that the associations remained consistent across subgroups and were not influenced by factors other than anaerobic exercise. Conclusions: Our findings suggest a non-linear inverse relationship between riboflavin intake and suicidal ideation, with notable variations by sex and age. Modifying dietary riboflavin intake may be a crucial strategy for reducing suicide risk.

A Behavioral Screening Method for Predicting PTSD-like Phenotypes: Novel Application to Female Rats.

Only a small percentage of trauma-exposed subjects develop PTSD, with females being twice as likely. Most rodent models focus on males and fail to account for inter-individual variability in females. We tested a behavioral PTSD model in female rats to distinguish between susceptible and resilient individuals. In Experiment 1, female rats underwent footshocks paired with social isolation, a PTSD risk factor. They were re-exposed to the conditioned context to test memory retention, and assessed in the Elevated Plus Maze (EPM) and Social Interaction (SI) tests for anxiety and social behavior. Footshock-exposed rats showed fear memory retention up to 16 days, indicated by elevated freezing behavior during re-exposure. They also exhibited reduced exploration in the EPM and less SI time compared to controls. In Experiment 2, we classified rats into normal responders, susceptible, and resilient groups based on locomotor activity after trauma, correlating with memory retention and anxiety. Unlike existing models focused on males and lacking predictive variables before trauma, our method identifies PTSD-like susceptibility and resilience in female rats by using exploratory behavior as a predictor before trauma exposure. Exploratory activity in a novel environment after trauma and before extinction is a reliable predictor of PTSD-like phenotypes and differentiates between susceptible and resilient female rats.

Association between the hemoglobin A1c/High-density lipoprotein cholesterol ratio and stroke incidence: a prospective nationwide cohort study in China

BackgroundStroke has emerged as an escalating public health challenge among middle-aged and older individuals in China, closely linked to glycolipid metabolic abnormalities. The Hemoglobin A1c/High-Density Lipoprotein Cholesterol (HbA1c/HDL-C) ratio, an integrated marker of glycolipid homeostasis, may serve as a novel predictor of stroke risk.MethodsOur investigation utilized data from the China Health and Retirement Longitudinal Study cohort (2011–2018). Stroke cases were identified based on self-reported, physician-confirmed diagnoses. Logistic regression models were established to determine the correlation between HbA1c/HDL-C and stroke prevalence (2011) as well as between cumulative mean HbA1c/HDL-C (2011–2015) and new stroke incidence (2015–2018). Additionally, smoothed curve fitting, subgroup analyses, and interaction tests were conducted to ensure the robustness of the findings.ResultsIn the cross-sectional analysis, 8,502 participants were enrolled, of whom 189 had a history of stroke. Our findings revealed a significant positive linear relationship between HbA1c/HDL-C and stroke prevalence after adjusting for covariates (OR: 1.26, 95% CI: 1.09–1.45). When HbA1c/HDL-C was categorized into tertiles, only the highest tertile (T3) showed a significant correlation with stroke prevalence compared to the lowest tertile (T1) (OR:1.71, 95% CI: 1.05–2.77). In the longitudinal analysis of 5,165 participants, 336 cases of new-onset stroke were identified over a follow-up period of 7 years. Adjusting for confounders, individuals with higher cumulative mean HbA1c/HDL-C exhibited an increased likelihood of new stroke incidence (OR: 1.14, 95% CI: 1.01–1.29). Using the T1 of cumulative mean HbA1c/HDL-C as a reference, the fully adjusted OR for stroke was 1.65 (95% CI: 1.21–2.24) in T2 and 1.54 (95% CI: 1.08–2.19) in T3. The predictive value of the HbA1c/HDL-C in stroke risk assessment have been significantly improved compared to the traditional HDL-C and HbA1c. Consistent associations were observed across most stratified subgroups.ConclusionsElevated baseline and cumulative mean HbA1c/HDL-C levels are significantly associated with an increased risk of stroke among middle-aged and older individuals in China, underscoring the potential of HbA1c/HDL-C as a clinical marker for long-term stroke risk assessment and prevention strategies.

School performance gap between non-immigrant and second-generation immigrant children in Sweden—time trends and contributing factors

We aimed to investigate the school performance gap and its potential trend from 2010 to 2020 in non-immigrant and second-generation immigrant children in Sweden, whether parental mental disorders and low socioeconomic status contribute to this gap and its trends, and whether the effects of these factors differ by immigration status. We used multiple Swedish population registers, including 829,787 children born 1994–2004. We examined the school performance gap and its trends by the interaction between immigration status and year with linear mixed models. We assessed whether parental mental disorders and socioeconomic status contributed to this gap and its trends, and whether their effects on school performance differ by immigration status. The existing gap was explained by parental mental disorders in addition to parental education and neighborhood socioeconomic status for both males and females. The unadjusted model suggested an increasing trend of the existing gap in school performance by immigration status for both males and females. In the adjusted model, the increasing trend of the gap remained among males and was partially attributed to parental education and neighborhood socioeconomic status. The interaction tests showed that the potential effects of these factors on school performance were smaller among second-generation immigrant children. Efforts to reduce the effects of socioeconomic inequalities and parental mental disorders are warranted in addition to extra support for second-generation immigrant children at schools.