The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population.

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

Nutritional status affects immune function and exacerbates the severity of pulmonary tuberculosis.

Aim: To comprehensively evaluate the association and impact of nutritional status and immune function on the severity of pulmonary tuberculosis (PTB). Methods: This descriptive cross-sectional study involved 952 participants who were diagnosed with active PTB. Severe PTB involves three or more lung field infections based on chest radiography. Nutritional status was evaluated using various indicators, including body mass index (BMI), the nutritional risk screening score (NRS-2002), total protein (TP), prealbumin (PA), transferrin (TRF), and serum albumin (ALB) levels and the prognostic nutritional index (PNI). Immune dysfunction was defined as a CD4+ count <500 cells/µl or a CD4+/CD8+ ratio <1. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were also calculated. Multivariate logistic and generalized linear regression were used to assess the associations between nutritional status, immune function, the severity of PTB, and the number of infected lung fields, adjusting for age, sex, and diabetes. Mediation analysis was conducted to evaluate the extent to which immune function mediated the impact of nutritional status on the severity of PTB. Sensitivity analysis was performed to enhance the robustness of the results. Results: Compared to those in the general PTB group, patients in the severe PTB group tended to be older men with diabetes. Higher nutritional risk, higher proportion of immune dysfunction and lower lymphocyte counts were observed in the severe group. BMI and the PNI were found to be protective factors, while PLR was identified as a risk factor for disease severity. Immune dysfunction and the PLR are mediators of the relationship between nutritional status and PTB severity. When BMI, the PNI, and the PLR were combined with traditional clinical indicators, these parameters showed promising diagnostic value, and the AUC reached 0.701 (95% CI: 0.668-0.734). Conclusion: The findings suggest that nutritional status is significantly associated with the severity of PTB, and immune function mediates the effects of nutritional status on the severity of PTB. Maintaining adequate BMI, PNI levels, and immune function or reducing PLR levels helps reduce the risk of severe PTB.

Genetically predicted elevated circulating 3,4-dihydroxybutyrate levels mediate the association between family Christensenellaceae and osteoporosis risk: a Mendelian randomization study.

Objective: To investigate the impact of gut microbiota on osteoporosis and identify the mediating role of blood metabolites in this process. Methods: This two-sample Mendelian randomization (MR) study utilized summary level data from genome-wide association studies (GWAS). Gut microbiota GWAS data were obtained from the MiBio-Gen consortium meta-analysis (n=13,266), while osteoporosis summary statistics were sourced from the FinnGen consortium R9 release data (7300 cases and 358,014 controls). Metabolite data, including 1400 metabolites or metabolite ratios, were derived from a study involving 8,299 unrelated individuals. The primary MR method employed was the inverse variance weighted (IVW) method. Reverse MR analysis was conducted on bacteria causally associated with osteoporosis in forward MR. The gut microbiota with the smallest p-value was selected as the top influencing factor for subsequent mediation analysis. A two-step MR approach quantified the proportion of the blood metabolite effect on gut microbiota influencing osteoporosis. IVW and Egger methods were used to assess heterogeneity and horizontal pleiotropy. Results: IVW estimates indicated a suggestive effect of family Christensenellaceae on osteoporosis (odds ratio(OR) = 1.292, 95% confidence interval(CI): 1.110-1.503, P =9.198 × 10-4). Reverse MR analysis revealed no significant causal effect of osteoporosis on family Christensenellaceae (OR = 0.947, 95% CI: 0.836-1.072, P =0.386). The proportion of the effect of family Christensenellaceae on osteoporosis mediated by circulating levels of 3,4-dihydroxybutyrate was 9.727%. No significant heterogeneity or horizontal pleiotropy was detected in the instrumental variables used for MR analysis. Conclusion: This study establishes a causal link between family Christensenellaceae and osteoporosis, with a minor proportion of the effect mediated by elevated circulating levels of 3,4-dihydroxybutyrate. Further randomized controlled trials (RCTs) are warranted to validate this conclusion.

The Effect of Sodium Glucose Cotransporter-2 Inhibitors on Hemoglobin A1c Variability and Acute Kidney Injury: A Causal Mediation Analysis.

PURPOSE: The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c variability. METHODS: Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis. RESULTS: With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses. CONCLUSIONS: Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.

Study approaches mediate associations between learning environment and academic performance.

BACKGROUND: While study approaches have been directly associated with students' academic performance, learning environment factors may play a more indirect role. The aim of this study was (i) to assess learning environment factors as predictors of students' average exam grades, and (ii) whether study approaches mediated associations between learning environment factors and exam grades. METHODS: Three annual surveys (2017-2019) yielded data from a total of 263 Norwegian occupational therapy students. Learning environment factors were assessed with the Course Experience Questionnaire, and the Approaches and Study Skills Inventory for Students were used to assess study approaches. Linear regression analyses and mediation analyses were performed. RESULTS: Higher levels of 'student autonomy' were directly associated with lower averaged grades whereas higher levels of 'appropriate workload' were associated with higher averaged grades. There were statistically significant total indirect effects of 'clear goals' and 'appropriate workload' on grades; these effects occurred through the study approach variables. However, all learning environment variables showed one or more relationships with academic performance that was mediated by study approach variables. CONCLUSION: Learning environment variables appear to be complexly associated with academic performance, both directly and indirectly.

Sensory impairments and the risk of cognitive decline and dementia across sex, age, and regions: Longitudinal insights from Europe.

BACKGROUND: In aging populations, understanding predictors of cognitive decline is essential. We aimed to investigate the risk of cognitive decline and dementia by sensory impairments across sex, age, and European regions, and examined the mediating role of activities of daily living (ADL), physical activity, and depressive symptoms. METHODS: A cohort study of 72,287 Europeans aged 50+ participating in at least two waves of the Survey of Health, Ageing and Retirement in Europe. We employed mixed-effects and time-to-event models, incorporating sex interactions, and adjusting for socio-demographic factors and medical history. RESULTS: Compared to individuals with good vision and hearing, lower cognitive function was found for people with vision impairment (VI) (males: coef. -0.70, 95 % CI -0.95; -0.46; females: coef. -1.12, 95 % CI -1.33; -0.92), hearing impairment (HI) (males: coef. -0.64, 95 % CI -0.93; -0.35; females: coef. -0.96, 95 % CI -1.27; -0.65) and dual sensory impairment (DSI, i.e. VI and HI) (males: coef. -1.81, 95 % CI -2.16; -1.46; females: coef. -2.71, 95 % CI -3.05; -2.38), particularly among females. Moreover, higher dementia risk was observed among participants with VI (hazard ratio (HR) 1.29, 95 % CI 1.17; 1.43), HI (HR 1.18, 95 % CI 1.05; 1.34), and DSI (HR 1.62, 95 % CI 1.45; 1.81) with no sex-interactions. Findings were overall consistent across age and European regions. CONCLUSION: The results suggest the necessity of preventing sensory impairments to maintain good cognitive function. Mitigating depressive symptoms, ADL limitations, and physical inactivity could potentially reduce a significant portion of the total effect of sensory impairments on cognitive decline.

Self-Esteem and Anxiety as Mediators in the Relationship Between Emotional Intelligence and Eating Disorder Symptoms.

This study investigated the relationship between emotional intelligence (EI) and eating disorder symptoms (EDS) by testing the serial mediation model, with self-esteem and anxiety as mediators. A total of 923 participants (61.9% female) aged 15-60 years completed questionnaires assessing their EI, self-esteem, anxiety, and EDS. Correlational analyses were conducted to assess the relationship between the study variables, and a serial mediation analysis was conducted to test the possible mediating role of self-esteem and anxiety in the relationship between EI and EDS. Correlation analyses revealed significant bivariate relationships between EI, self-esteem, and anxiety, but no significant correlation between EI and EDS. The relationship between EI and EDS was serially mediated by self-esteem and anxiety. High levels of EI were associated with higher self-esteem, which, in turn, was associated with lower anxiety and less EDS. The results offer potential mechanisms that could explain the relationship between EI and EDS and highlight the importance of EI in regulating eating behavior through self-esteem and anxiety.

Serum uric acid, body mass index, and cardiovascular diseases: A multiple two-step Mendelian randomization study.

BACKGROUND AND AIMS: A number of health issues, including high serum uric acid (SUA) and cardiovascular disease (CVD), have been linked to obesity based on observational evidence, though it's currently unclear how these issues are causally related. In order to determine whether obesity mediates this association, we set out to investigate the causal relationship between SUA, obesity, and CVD. METHODS AND RESULTS: From publicly available genome-wide association studies, we acquired instrumental variables that had a strong correlation to SUA and body mass index (BMI). We employed multiple two-step Mendelian randomization (MR) analyses, using genetic and clinical data from various publicly available biological databases. The mediating role of BMI was examined through mediation analysis. SUA was genetically correlated with BMI [OR = 1.080, 95% CI: 1.024-1.139, P = 0.005]. There was a positive causal effect of SUA on AF [OR = 0.892, 95% CI: 0.804-0.990, P = 0.032], CAD [OR = 0.942, 95% CI: 0.890-0.997, P = 0.037], and EHT [OR = 1.080, 95% CI: 1.024-1.139, P = 0.005]. Among them, BMI mediated the effects of SUA on AF (42.2%; 95% CI, 35.3%-51.9%), CAD (76.3%; 95% CI, 63.4%-92.0%), and EHT (10.0%; 95% CI, 0%-20.0%). CONCLUSION: Our research revealed a causal relationship between high SUA exposure and an increased risk of obesity. Additionally, a high SUA level was linked to an increased risk of various CVDs. Given that individuals with high SUA are more likely to be susceptible to AF, CAD, and EHT, attention must be given to their weight status.

Causal mediation analyses for the natural course of hepatitis C: a prospective cohort study.

BackgroundHepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality.MethodsA community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants' serum samples. The cohort data were linked to Taiwan's National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases.ResultsIn 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose-response relationship of HCV viral load was further demonstrated for the mediation effect.ConclusionBoth intrahepatic and extrahepatic manifestations mediated approximately a half of HCV-induced mortality. The mediation mechanisms are supported by a dose-response relationship of HCV viral load.

Bisphenol mixtures, metal mixtures and type 2 diabetes mellitus: Insights from metabolite profiling.

BACKGROUND: Little is known about the combined effect of bisphenol mixtures and metal mixtures on type 2 diabetes mellitus (T2DM) risk, and the mediating roles of metabolites. METHODS: The study included 606 pairs of T2DM cases and controls matched by age and sex, and information of participants was collected through questionnaires and laboratory tests. Serum bisphenol and plasma metal concentrations were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. Widely targeted metabolomics was employed to obtain the serum metabolomic profiles. Conditional logistic regression models were used to assess the single associations of bisphenols and metals with T2DM risk after multivariable adjustment. Additionally, the joint effects of bisphenol mixtures and metal mixtures were examined using quantile-based g-computation (QG-C) models. Furthermore, differential metabolites associated with T2DM were identified, and mediation analyses were performed to explore the role of metabolites in the associations of bisphenols and metals with T2DM risk. RESULTS: The results showed bisphenol mixtures were associated with an increased T2DM risk, with bisphenol A (BPA) identified as the primary contributor. While the association between metal mixtures and T2DM remained inconclusive, cobalt (Co), iron (Fe), and zinc (Zn) showed the highest weight indices for T2DM risk. A total of 154 differential metabolites were screened between the T2DM cases and controls. Mediation analyses indicated that 9 metabolites mediated the association between BPA and T2DM, while L-valine mediated the association between Zn and T2DM risk. CONCLUSIONS: The study indicated that BPA, Co, Fe, and Zn were the primary contributors to increased T2DM risk, and metabolites played a mediating role in the associations of BPA and Zn with the risk of T2DM. Our findings contribute to a better understanding of the mechanisms underlying the associations of bisphenols and metals with T2DM.

The Impact of Stigma and Sexual Identity on PrEP Awareness and Use Among At-Risk Men Who Have Sex With Men in Four U.S. Cities (HPTN 078).

Persistent pre-exposure prophylaxis (PrEP) use reduces the risk of HIV infection, yet uptake lags among those with the greatest need. Sexual identity stigma may be a significant barrier to PrEP awareness and use among high-risk communities. The primary aim of this study was to determine whether sexual identity was related to PrEP awareness and use. This multi-site HIV Prevention Trials Network (HPTN) study (HPTN 078) focuses on men who have sex with men (MSM) (n=335) who were HIV-negative at screening. The majority of participants were non-white (62.1%), younger than 35 (57.9%), single (79.1%), and aware of PrEP, yet had never taken PrEP (52.5%). Participants completed questionnaires including sexual history and identity; lesbian, gay, bisexual, transgender, queer (LGBTQ) community engagement; PrEP awareness and use; and several measures of sexual identity stigma including family and friend stigma, general societal stigma, and anticipated healthcare stigma. Univariate and multinomial logistic regression models helped to determine factors associated with PrEP awareness and use. There were stark disparities in PrEP awareness comparing Black and White participants; 50% of Black participants reported being PrEP unaware vs 11.8% of White participants. In this sample, gay sexual identity (compared to bisexual identity) was associated with increased PrEP awareness (AOR 6.66) and use (AOR 16.9). Additionally, 29% of the association between sexual orientation and PrEP use was mediated through internalized stigma. Given low PrEP uptake among MSM, interventions that address sexual identity stigma may motivate greater PrEP uptake.

The mediating role of health behaviors in the relationship between internal locus of control and life satisfaction in public health students.

Well-being is a continuous process requiring decisions and actions to maintain or build health. This study examines the indirect effect of health locus of control on life satisfaction via healthy behaviors based on living systems theory. Participants were 730 students of various majors related to medicine and health, aged between 19 and 30 (M = 22.29, SD = 1.64), including 79.04% women. Self-report measures were used to assess life satisfaction, multidimensional health locus of control, and health behavior. Women scored higher than men on the total health behavior scale, especially in a healthy diet and preventive behavior. Men scored higher than women on internal health locus of control (HLC), while women scored higher than men on the powerful others HLC in making decisions about their health. The study confirmed the mediating effect of healthy behavior on the relationship between the internal HLC and life satisfaction. The present mechanism highlights the crucial role of internal motivation in increasing subjective well-being by maintaining health behaviors among young adults. The role of intervention programs focused on improving internal HLC and health behaviors is discussed.

Effects of Inappropriate Nurturing Experiences, Depressive Rumination, and Trait Anxiety on Depressive Symptoms.

Background: Prior research has shown that inappropriate childhood nurturing experiences (low care and high overprotection), trait anxiety, and depressive rumination are risk factors for depression. However, no studies to date have analyzed the overall association between these factors and depressive symptoms. In the present study, we hypothesized that depressive rumination mediates the impacts of inappropriate childhood nurturing experiences on depressive symptoms, and that these mediating effects are moderated by trait anxiety, and tested these hypotheses in adult volunteers. Methods: The subjects were adult volunteers who were investigated between April 2017 and April 2018. A self-report questionnaire on demographic data, childhood nurturing experiences, trait anxiety, depressive rumination, and depressive symptoms was distributed to conduct the survey, and written informed consent and valid responses were obtained from 585 subjects. Mediation and moderated-mediation analyses were performed by SPSS 28 and macro PROCESS 4.0 software. This study was approved by the Ethics Committee of Tokyo Medical University. Results: Parental care showed a significant negative indirect effect on depressive symptoms via its effect on depressive rumination (p < 0.01), whereas parental overprotection showed the opposite effect (p < 0.01). Furthermore, the mediation effect of depressive rumination on depressive symptoms was increased by trait anxiety (p < 0.05). Conclusion: Our present study demonstrated that the main factor affecting depressive symptoms is inappropriate childhood nurturing experiences, which indirectly enhance depression by intensifying depressive rumination, and that depressive rumination and trait anxiety mutually reinforce each other to enhance depressive symptoms. These findings may be useful for the prevention of depressive symptoms. Large-scale prospective studies are needed to confirm the causal associations among these factors in the future.

The impact of social media information exposure on appearance anxiety in young acne patients: a moderated chain mediation model.

Introduction: The boom of social media has provided a wider space for ordinary people to display themselves, but visual presentation has also intensified the focus on appearance, which in turn triggers anxiety about appearance. The study aims to investigate the impact of social media information exposure on appearance anxiety in young acne patients and the pathways and mechanisms that cause this effect. Methods: A moderated chain mediation model was constructed, and a questionnaire was used to collect information on social media information exposure, internalization of beauty ideals, fear of negative evaluation, self-esteem, and appearance anxiety in young acne patients (N = 382), and the relationships between the variables were explored through regression analysis. Results: The results show that there was a significant path of effect (t > 2.5, p < 0.05) between social media information exposure, internalization of beauty ideals, fear of negative evaluation, and appearance anxiety. Self-esteem significantly moderated the relationship between social media information exposure and internalization of beauty ideals (t < -2, p < 0.05). Discussion: In conclusion, in young acne patients, internalization of beauty ideals and fear of negative evaluation chain mediated the association between social media information exposure and appearance anxiety, and young acne patients' internalization of beauty ideals was inversely correlated with their level of self-esteem.

Contract governance to reduce antimicrobial overuse in hog farms in China.

Antimicrobial resistance caused by the overuse of antimicrobials by farmers is an essential health issue. Currently, signing contracts between farmers and cooperatives has become crucial for small farmers to integrate into the modern agricultural industry chain. Unlike vertical government governance, which aims to intervene in the overuse of antimicrobials by farmers through many mandatory or incentive measures, contract governance refers to the social governance model that clarifies rights and obligations between farmers and cooperatives to ensure the adequate performance of contracts, which is especially beneficial to regulate farmers' safe production behavior such as the standard use of antimicrobials. However, there is a research gap concerning the effectiveness of contract governance in inhibiting farmers' overuse of animal antimicrobials. This study applies propensity score matching and mediation analysis method to assess how contract governance affects the overuse of antimicrobials by hog farmers. The paper uses data from 498 hog farmers of China's Hebei, Henan, and Hubei provinces to explore the impact and underlying mechanisms of contract governance on antimicrobial overuse in agriculture. The results showed that contract governance was found to inhibit the overuse of antimicrobials, with the amount paid for antimicrobials reduced by 118 yuan/household. We found evidence that this effect is exerted through three mechanisms: cooperative supervision (CS), technical guidance (TG), and product premium perception (PP). The CS, TG, and PP mediation effects accounted for 19.94%, 27.90%, and 26.93% of the total impact, respectively. Therefore, policy implications of these results include strengthening the standard of contract signing procedures and the integrity of executing contracts, increasing the market premium for products that meet the antimicrobial residue standards, and enhancing farmers' knowledge and contracting ability.

Prognostic implications of thyroid hormones in acute aortic dissection: mediating roles of renal function and coagulation.

Background: Thyroid hormones significantly influence cardiovascular pathophysiology, yet their prognostic role in acute aortic dissection (AAD) remains inadequately explored. This study assesses the prognostic value of thyroid hormone levels in AAD, focusing on the mediating roles of renal function and coagulation. Methods: We included 964 AAD patients in this retrospective cohort study. Utilizing logistic regression, restricted cubic splines, and causal mediation analysis, we investigated the association between thyroid hormones and in-hospital mortality and major adverse cardiovascular events (MACEs). Results: In AAD patients overall, an increase of one standard deviation in FT4 levels was associated with a 31.9% increased risk of MACEs (OR 1.319; 95% CI 1.098-1.584) and a 36.1% increase in in-hospital mortality (OR 1.361; 95% CI 1.095-1.690). Conversely, a higher FT3/FT4 ratio was correlated with a 20.2% reduction in risk of MACEs (OR 0.798; 95% CI 0.637-0.999). This correlation was statistically significant predominantly in Type A AAD, while it did not hold statistical significance in Type B AAD. Key renal and coagulation biomarkers, including blood urea nitrogen, creatinine, cystatin C, prothrombin time ratio, prothrombin time, and prothrombin time international normalized ratio, were identified as significant mediators in the interplay between thyroid hormones and MACEs. The FT3/FT4 ratio exerted its prognostic influence primarily through the mediation of renal functions and coagulation, while FT4 levels predominantly impacted outcomes via a partial mediation effect on coagulation. Conclusion: FT4 levels and the FT3/FT4 ratio are crucial prognostic biomarkers in AAD patients. Renal function and coagulation mediate the association between the thyroid hormones and MACEs.

Causal effect of obesity and adiposity distribution on the risk of pressure ulcers and potential mediation by type 2 diabetes mellitus: insights from multivariable mendelian randomization and mediation analysis.

Previous observational studies have identified a link between obesity, adiposity distribution, type 1 Diabetes Mellitus (T1DM), type 2 Diabetes Mellitus (T2DM), and the risk of pressure ulcers (PUs). However, the definitive causality between obesity and PUs, and potential DM mediators remains unclear. Univariable, multivariable, and mediation Mendelian randomization (MR) analyses were conducted to explore the mediating role of T1DM or T2DM in the association between obesity, adiposity distribution, and PUs. Instrumental variables for obesity and adiposity distribution, including Body Mass Index (BMI), waist circumference, hip circumference, trunk fat mass, whole body fat mass, trunk fat percentage, and body fat percentage, were selected from two genome-wide association studies (GWAS). In univariable MR analysis, BMI, hip circumference, and obesity were associated with PUs using inverse variance weighted (IVW) regression. These findings were further corroborated by the replication cohorts and meta-analysis (BMI: OR = 1.537, 95% CI = 1.294-1.824, p < 0.001; Hip circumference: OR = 1.369, 95% CI = 1.147-1.635, p < 0.001; Obesity: OR = 1.235, 95% CI = 1.067-1.431, p = 0.005), respectively. Even after adjusting for confounding factors such as T1DM and T2DM, BMI and hip circumference remained statistically significant in multivariable MR analyses. T2DM may mediate the pathogenesis of BMI-related (OR = 1.106, 95% CI = 1.054-1.160, p = 0.037) and obesity-related PUs (OR = 1.053, 95% CI = 1.034-1.973, p = 0.004). These findings provide insights for the prevention and treatment of PUs, particularly in patients with obesity or DM.

Impact of a change from A-F grading to honors/pass/fail grading on academic performance at Yonsei University College of Medicine in Korea: a cross-sectional serial mediation analysis.

PURPOSE: This study aimed to explore how the grading system affected medical students' academic performance based on their perceptions of the learning environment and intrinsic motivation in the context of changing from norm-referenced A-F grading to criterion-referenced honors/pass/fail grading. METHODS: The study involved 238 second-year medical students from 2014 (n=127, A-F grading) and 2015 (n=111, honors/pass/fail grading) at Yonsei University College of Medicine in Korea. Scores on the Dundee Ready Educational Environment Measure, the Academic Motivation Scale, and the Basic Medical Science Examination were used to measure overall learning environment perceptions, intrinsic motivation, and academic performance, respectively. Serial mediation analysis was conducted to examine the pathways between the grading system and academic performance, focusing on the mediating roles of student perceptions and intrinsic motivation. RESULTS: The honors/pass/fail grading class students reported more positive perceptions of the learning environment, higher intrinsic motivation, and better academic performance than the A-F grading class students. Mediation analysis demonstrated a serial mediation effect between the grading system and academic performance through learning environment perceptions and intrinsic motivation. Student perceptions and intrinsic motivation did not independently mediate the relationship between the grading system and performance. CONCLUSION: Reducing the number of grades and eliminating rank-based grading might have created an affirming learning environment that fulfills basic psychological needs and reinforces the intrinsic motivation linked to academic performance. The cumulative effect of these 2 mediators suggests that a comprehensive approach should be used to understand student performance.