Enhancement or suppression: a double-edged sword? Differential association of digital literacy with subjective health of older adult-evidence from China.

Background: The emergence of an aging society and the digital age makes healthy aging a hot topic in Chinese society. This paper explores the associations between digital literacy and the subjective health of older adult individuals in PR China, offering insights that May assist policymakers and service providers in developing strategies and interventions suited to the digital era, potentially enhancing the healthy aging process for this demographic in China. Methods: This study utilized data from the China Longitudinal Aging Social Survey. Initially, demographic variables of 2086 individuals in the sample were analyzed. Subjective health differences among different populations and correlations between core variables were examined. Subsequently, multivariate linear regression and chain mediation methods were utilized to examine the relationships and potential pathways among the three dimensions of digital literacy and the subjective health of older adult individuals. Results: (1) The subjective health status of older adult individuals in China was generally favorable, with an average score of 3.406 ± 0.764. (2) There was no direct correlation observed between the frequency of digital information use and the subjective health of the older adult (b = -0.032, p > 0.1). Digital entertainment information (b = 0.294, p > 0.1) did not show a significant effect, whereas life management information (b = 0.437, p < 0.01) demonstrated a positive association. Similarly, the use of smart healthcare devices (b = 0.842, p < 0.001) indicated a positive association (3) The frequency of digital information use indirectly enhanced the subjective health of the older adult through life management digital information and the use of smart healthcare devices, but had no indirect effect through entertainment and leisure digital information. Conclusion: Digital literacy is significantly correlated with the subjective health of the older adult, especially when they acquire life management information and utilize smart healthcare devices. However, a potential negative relationship is suggested between digital entertainment information and the subjective health of older adult individuals. Therefore, digital infrastructure should have prioritized the provision of high-quality, age-friendly digital applications for the older adult. This approach could have better harnessed the potential of digitalization to enhance health and well-being in older adults.

MultiSC: a deep learning pipeline for analyzing multiomics single-cell data.

Single-cell technologies enable researchers to investigate cell functions at an individual cell level and study cellular processes with higher resolution. Several multi-omics single-cell sequencing techniques have been developed to explore various aspects of cellular behavior. Using NEAT-seq as an example, this method simultaneously obtains three kinds of omics data for each cell: gene expression, chromatin accessibility, and protein expression of transcription factors (TFs). Consequently, NEAT-seq offers a more comprehensive understanding of cellular activities in multiple modalities. However, there is a lack of tools available for effectively integrating the three types of omics data. To address this gap, we propose a novel pipeline called MultiSC for the analysis of MULTIomic Single-Cell data. Our pipeline leverages a multimodal constraint autoencoder (single-cell hierarchical constraint autoencoder) to integrate the multi-omics data during the clustering process and a matrix factorization-based model (scMF) to predict target genes regulated by a TF. Moreover, we utilize multivariate linear regression models to predict gene regulatory networks from the multi-omics data. Additional functionalities, including differential expression, mediation analysis, and causal inference, are also incorporated into the MultiSC pipeline. Extensive experiments were conducted to evaluate the performance of MultiSC. The results demonstrate that our pipeline enables researchers to gain a comprehensive view of cell activities and gene regulatory networks by fully leveraging the potential of multiomics single-cell data. By employing MultiSC, researchers can effectively integrate and analyze diverse omics data types, enhancing their understanding of cellular processes.

Medical Maximizing Orientation and the Desire for Low-Value Screening: An Examination of Mediating Mechanisms.

BACKGROUND: Medical maximizing orientation is a stable, traitlike inclination to actively use health care, often associated with pursuing low-value care. Despite attempts to reduce the overuse of low-value care by targeting this orientation directly, such interventions have not always been effective. To design effective interventions to reduce the overuse of low-value care, it is critical to understand the underlying mechanisms that govern the impact of medical maximizing orientation. OBJECTIVE: To examine whether risk perception (deliberative, affective, and experiential) and knowledge of the benefits and harms of low-value screening mediate the potential impact of medical maximizing orientation on attitudes toward screening uptake and screening decisions. METHODS: A secondary analysis was conducted on data from a Web-based experiment examining various communication tactics in an information booklet regarding low-value thyroid ultrasonography among South Korean women (N = 492). Multiple linear, zero-inflated negative binomial and multinomial logistic regressions were used to examine the relationships between medical maximizing orientation and other study variables. A mediation analysis was performed to test mediating mechanisms. RESULTS: Medical maximizing orientation was associated with an increased positive attitude toward screening uptake and a lower likelihood of deciding not to get screened or being uncertain regarding screening decisions (relative to deciding to get screened). Knowledge and affective risk perception partially mediated the relationship between medical maximizing orientation and positive attitudes. Knowledge, deliberative, and affective risk perceptions partially mediated the relationship between medical maximizing orientation and the screening decision. CONCLUSIONS: Interventions should prioritize targeting more amenable factors arising from medical maximizing orientation, such as inflated risk perceptions, particularly affective risk perception, and limited comprehension or acceptance of information about the benefits and risks associated with low-value care. HIGHLIGHTS: This study demonstrated that people's medical maximizing orientation can increase their positive attitudes toward the uptake of low-value screening and make them more likely to undergo it. This can happen both directly and indirectly by decreasing their understanding of the benefits and risks of screening and increasing their perception of disease risk.The study suggests that to effectively mitigate the excessive utilization of low-value care through patient-centered interventions, it is crucial to tackle 2 key issues associated with a medical maximizing mindset: inflated risk perceptions (specifically affective risk perception) and limited comprehension or acceptance of information about the benefits and risks of low-value care.This study contributes to developing a theoretical framework for interventions to improve evidence-based medical decision making by uncovering one mechanism by which medical maximizing orientation may affect the propensity to seek low-value care.

Corrigendum: Serum TRPA1 mediates the association between olfactory function and cognitive function.

[This corrects the article DOI: 10.3389/fnagi.2024.1411031.].

Loneliness, Internalizing and Externalizing Problems, and Suicidal Ideation Among Chinese Adolescents: A Longitudinal Mediation Analysis.

PURPOSE: Research indicates that loneliness and emotional and behavioral problems increase the risk of suicidal ideation in adolescents, but less is known about the distinct contributions of these problems. This study aimed to distinguish the pathways through which loneliness, internalizing problems, and externalizing problems contribute to suicidal ideation in Chinese adolescents. METHODS: We did a longitudinal mediation analysis with data collected at 3 time points (2021.05, 2021.10, and 2022.05) from 28 Taizhou high schools. Loneliness and suicidal ideation were assessed using the UCLA 3-Item Loneliness Scale and one suicide item from the Children's Depression Inventory, respectively. The Strength and Difficulties Questionnaire assessed internalizing (emotional and peer problems) and externalizing problems (conduct and hyperactivity problems). Structural equation modeling was used to construct complete longitudinal path models. RESULTS: Using data from 2,190 adolescents in junior and senior high schools, we found that loneliness, internalizing problems, and externalizing problems separately contributed to subsequent higher levels of suicidal ideation. Most notably, loneliness predicted worse subsequent internalizing problems (ß = 0.279, p < .001) and externalizing problems (ß = 0.159, p < .001), which in turn predicted more severe suicidal ideation (ß = 0.019, p < .001; ß = 0.018, p < .001). Loneliness also partially mediated the association between internalizing or externalizing problems and suicidal ideation. DISCUSSION: Loneliness, internalizing problems, and externalizing problems were strongly intertwined with suicidal ideation in adolescents. Public health initiatives could reduce loneliness and emotional and behavioral problems by implementing multifaceted interventions, thereby breaking the vicious circle and protecting against the development of suicidal ideation.

Circulating immune cells and apolipoprotein A mediation: a Mendelian randomization study on hypertensive disorder of pregnancy.

Background: Studies using observational epidemiology have indicated that inflammation and immunological dysregulation are important contributors to placental and renal failure, which ultimately results in maternal hypertension. The potential causal relationships between the immunophenotypes and hypertensive disorder of pregnancy (HDP) are yet unclear. Methods: We conducted two-sample Mendelian randomization (MR) analyses to thoroughly examine the relationship between immunophenotypes and HDP. The GWAS data on immunological traits was taken from public catalog for 731 immunophenotypes and the summarized GWAS data in 4 types of HDP were retrieved from FinnGen database. The link between immune cell traits and HDP was examined through our study methodology, taking into account both direct relationships and mediation effects of apolipoprotein A (apoA). The inverse variance weighted (IVW) method served as the main analysis, while sensitivity analysis was carried out as a supplement. Results: We identified 14 highly correlative immunophenotypes and 104 suggestive possible factors after investigating genetically predicted immunophenotype biomarkers. According to the IVW analysis, there was a strong correlation between HDP and HLA DR on DC and plasmacytoid DC. Reverse MR analysis showed that there was no statistically significant effect of HDP on immune cells in our investigation. Mediation analysis confirmed that apoA mediates the interaction between HLA DR on DC and HDP. Conclusion: Our results highlight the complex interplay of immunophenotypes, apoA, and HDP. Moreover, the pathophysiological link between HLA DR on DC and HDP was mediated by the level of apoA.

The impact of negative COVID-19 experiences on cancer survivors' health-related quality of life and psychological distress: a moderated mediation model.

Introduction: Cancer survivors experienced poorer health-related quality of life (HRQoL) and greater psychological distress during the COVID-19 pandemic than those without cancer. However, the underlying mechanisms that may explain how negative experiences during the pandemic are associated with distress and HRQoL remain unknown. We examined whether psychosocial risk factors (i.e., healthcare disruption, disruption to daily activities and social interaction [DDASI], and financial hardship) mediated the relationship between negative COVID-19-related experiences and cancer survivors' HRQoL and psychological distress (i.e., depressive symptoms, and anxiety) and whether the mediating effects were moderated by psychosocial protective factors (i.e., stress management ability and social support). Methods: A total of 9,651 cancer survivors completed a questionnaire assessing negative COVID-19-related experiences, psychosocial and practical experiences, and HRQoL. Conditional process analysis was used to evaluate the proposed moderated mediation models. Results: Participants had a mean age of 63.8 years (SD = 12.3) and were mostly non-Hispanic White (82.3%). DDASI and financial hardship mediated the relationship between negative COVID-19-related experiences and cancer survivor's HRQoL and psychological distress. Stress management ability buffered the indirect effect of DDASI on cancer survivors' HRQoL and psychological distress. Social support buffered the indirect effect of financial hardship on HRQoL and depressive symptoms. Conclusion: Financial resources and social interactions may buffer negative effects of major disruptions such as the COVID-19 pandemic. Future studies should assess the longitudinal impact of these associations.

Effect of inflammatory cytokines and plasma metabolome on OSA: a bidirectional two- sample Mendelian randomization study and mediation analysis.

Background: Obstructive sleep apnea (OSA) is a common sleep disorder. Inflammatory factors and plasma metabolites are important in assessing its progression. However, the causal relationship between them and OSA remains unclear, hampering early clinical diagnosis and treatment decisions. Methods: We conducted a large-scale study using data from the FinnGen database, with 43,901 cases and 366,484 controls for our discovery MR analysis. We employed 91 plasma proteins from 11 cohorts (totaling 14,824 participants of European descent) as instrumental variables (IVs). Additionally, we conducted a GWAS involving 13,818 cases and 463,035 controls to replicate the MR analysis. We primarily used the IVW method, supplemented by MR Egger, weighted median, simple mode, and weighted mode methods. Meta-analysis was used to synthesize MR findings, followed by tests for heterogeneity, pleiotropy, and sensitivity analysis (LOO). Reverse MR analysis was also performed to explore causal relationships. Results: The meta-analysis showed a correlation between elevated Eotaxin levels and an increased risk of OSA (OR=1.050, 95% CI: 1.008-1.096; p < 0.05). Furthermore, we found that the increased risk of OSA could be attributed to reduced levels of X-11849 and X-24978 (decreases of 7.1% and 8.4%, respectively). Sensitivity analysis results supported the reliability of these findings. Conclusions: In this study, we uncovered a novel biomarker and identified two previously unknown metabolites strongly linked to OSA. These findings underscore the potential significance of inflammatory factors and metabolites in the genetic underpinnings of OSA development and prognosis.

Gut microbiota and autoimmune thyroid disease: a bidirectional Mendelian randomization study and mediation analysis.

Background: The gut microbiota (GM) plays a pivotal role in influencing various health outcomes, including immune-mediated conditions, but its potential association with autoimmune thyroid disease (AITD) remains underexplored. We aimed to investigate the potentially pathogenic or protective causal impacts of specific GM on two types of AITD, namely Graves' disease and Hashimoto's thyroiditis, and analyzed the mediating effect of 731 immune cell phenotypes. Methods: Leveraging pooled genome-wide association study (GWAS) data of 211 gut microbiota traits, 731 immune cell phenotypes, and two types of AITD (Hashimoto's thyroiditis and Graves' disease), we performed bidirectional Mendelian randomization (MR) analyses to explore the causal relationships between the GM and AITD. Subsequently, we employed a multivariable MR analysis to discover potential mediating immune cell traits. Additionally, sensitivity analyses were utilized to ensure the reliability of the outcomes. Results: Our analysis revealed that a total of 7 GM taxa were positively associated with AITD, and other 14 taxa showed a negative correlation with AITD. Furthermore, we identified several immune cell traits that mediated the effects of GM on AITD. Most notably, Actinobacteria (p) presented protective effects on Hashimoto's thyroiditis via CCR2 on myeloid Dendritic Cell (5.0%), and Bifidobacterium (g) showed facilitating effects on Graves' disease through CD39+ CD4+ T cell %CD4+ T cell (5.0%) and CD14 on CD33+ HLA DR+ CD14dim (12.2%). Conclusion: The current MR study provides evidence supporting the causal relationships between several specific GM taxa and AITD, and further identified potential mediating immunophenotypes.

A longitudinal examination of the effect of physical exercise on the emotional states of college students: exploring the sense of coherence as a mediator through a cross-lagged panel analysis.

Purpose: This longitudinal study aimed to investigate the causal relationship between physical exercise and emotional states among university students, focusing on the mediating role of sense of coherence. Method: A total of 1,215 university students (aged 18-25 years) were recruited and completed questionnaires assessing physical activity (International Physical Activity Questionnaire-Short Form), emotional states (Positive and Negative Affect Schedule), and sense of coherence (Sense of Coherence Scale-13) at three time points over a three-month period. Preliminary analyses included independent samples t-tests, chi-square tests, and Pearson correlations. Cross-lagged panel mediation analysis was conducted using Mplus 8.3, with bootstrapping employed to test indirect effects. Results: Results indicated that sense of coherence significantly predicted positive affect (ß = 0.259-0.369, p < 0.001). Positive affect, in turn, predicted physical exercise (ß = 0.083-0.182, p < 0.05), while negative affect also influenced physical exercise (ß = -0.096-0.203, p < 0.05). Physical exercise indirectly influenced positive affect through sense of coherence (ß = 0.037, p = 0.045), and positive affect indirectly influenced physical exercise through sense of coherence (ß = 0.029, p = 0.028). Other indirect effects involving physical exercise, sense of coherence, and negative affect were non-significant. Conclusion: This study underscores the importance of sense of coherence in promoting emotional well-being among university students and in the reciprocal relationship between physical exercise and positive emotional states. Findings suggest that interventions targeting sense of coherence may enhance the emotional benefits of physical exercise. Future research should explore other potential mediators and moderators of the relationship between physical exercise and emotions and examine the effectiveness of sense of coherence-based interventions on well-being in this population.

Mediation Analysis with Multiple Exposures and Multiple Mediators.

A mediation analysis approach is proposed for multiple exposures, multiple mediators, and a continuous scalar outcome under the linear structural equation modeling framework. It assumes that there exist orthogonal components that demonstrate parallel mediation mechanisms on the outcome, and thus is named principal component mediation analysis (PCMA). Likelihood-based estimators are introduced for simultaneous estimation of the component projections and effect parameters. The asymptotic distribution of the estimators is derived for low-dimensional data. A bootstrap procedure is introduced for inference. Simulation studies illustrate the superior performance of the proposed approach. Applied to a proteomics-imaging dataset from the Alzheimer's disease neuroimaging initiative (ADNI), the proposed framework identifies protein deposition - brain atrophy - memory deficit mechanisms consistent with existing knowledge and suggests potential AD pathology by integrating data collected from different modalities.

Effort-reward imbalance and well-being among psychiatric nurses: the mediating role of burnout and decent work.

BACKGROUND: Psychiatric nurses face additional challenges due to negative perceptions, workplace violence, and a lack of respect, impacting their well-being and job satisfaction, which are crucial for improving psychiatric care and patient outcomes. OBJECTIVES: This study aims to examine the relationship between effort-reward imbalance, well-being, burnout, and decent work among psychiatric nurses. METHODS: This study used a cross-sectional design. Data were collected using a convenience sampling method in February 2024 from 397 psychiatric nurses at two psychiatric hospitals in Hangzhou and Huzhou, Zhejiang Province. The Effort-Reward Imbalance Scale, Decent Work Perception Scale, Maslach Burnout Inventory-General Survey, and General Well-Being Schedule Scale were used for data collection. Data analysis was conducted using SPSS 26.0 and the PROCESS macro. RESULTS: The study found that effort-reward imbalance among psychiatric nurses was negatively correlated with decent work (r = -0.564, p < 0.001) and well-being (r = -0.541, p < 0.001), and positively correlated with burnout (r = 0.603, p < 0.001). Burnout mediated the relationship between effort-reward imbalance and well-being (95% CI [-0.386, -0.257]), while decent work also served as a mediator (95% CI [-0.100, -0.012]). Additionally, burnout and decent work were found to mediate the relationship between effort-reward imbalance and well-being (95% CI [-0.050, -0.006]). CONCLUSION: This study highlights the impact of effort-reward imbalance on well-being, confirming that burnout and decent work serve as mediators. Enhancing support, fair compensation, reasonable work schedules, and professional development can promote psychiatric nurses' perception of decent work and improve their well-being.

Predictive value analysis of albumin-related inflammatory markers for short-term outcomes in patients with In-hospital cardiac arrest.

OBJECTIVE: This study investigated the predictive value of albumin-related inflammatory markers for short-term outcomes in in-hospital cardiac arrest (IHCA) patients. METHODS: A linear mixed model investigated the dynamic changes of markers within 72 hours after return of spontaneous circulation (ROSC). Time-Dependent COX regression explored the predictive value. Mediation analysis quantified the association of markers with organ dysfunctions and adverse outcomes. RESULTS: Prognostic Nutritional Index (PNI) and RDW-Albumin Ratio (RAR) slightly changed (p > 0.05). Procalcitonin-Albumin Ratio (PAR1) initially increased and then slowly decreased. Neutrophil-Albumin Ratio (NAR) and Platelet-Albumin Ratio (PAR2) decreased slightly during 24-48 hours (all p<0.05). PNI (HR = 1.646, 95%CI (1.033,2.623)), PAR1 (HR = 1.69, 95%CI (1.057,2.701)), RAR (HR = 1.752,95%CI (1.103,2.783)) and NAR (HR = 1.724,95%CI (1.078,2.759)) were independently associated with in-hospital mortality. PNI (PM = 45.64%, 95%CI (17.05%,87.02%)), RAR (PM = 45.07%,95%CI (14.59%,93.70%)) and NAR (PM = 46.23%,95%CI (14.59%,93.70%)) indirectly influenced in-hospital mortality by increasing SOFA (central) scores. PNI (PM = 21.75%, 95%CI(0.67%,67.75%)) may also indirectly influenced outcome by increasing SOFA (renal) scores (all p < 0.05). CONCLUSIONS: Within 72 hours after ROSC, albumin-related inflammatory markers (PNI, PAR1, RAR, and NAR) were identified as potential predictors of short-term prognosis in IHCA patients. They may mediate the adverse outcomes of patients by causing damages to the central nervous system and renal function.

Dietary Carbohydrates, Genetic Susceptibility, and Gout Risk: A Prospective Cohort Study in the UK.

This study aimed to investigate the associations between carbohydrate intake and gout risk, along with interactions between genetic susceptibility and carbohydrates, and the mediating roles of biomarkers. We included 187,387 participants who were free of gout at baseline and completed at least one dietary assessment in the UK Biobank. Cox proportional hazard models were used to estimate the associations between carbohydrate intake and gout risk. Over a median follow-up of 11.69 years, 2548 incident cases of gout were recorded. Total carbohydrate intake was associated with a reduced gout risk (Q4 vs. Q1: HR 0.67, 95% CI 0.60-0.74), as were total sugars (0.89, 0.80-0.99), non-free sugars (0.70, 0.63-0.78), total starch (0.70, 0.63-0.78), refined grain starch (0.85, 0.76-0.95), wholegrain starch (0.73, 0.65-0.82), and fiber (0.72, 0.64-0.80), whereas free sugars (1.15, 1.04-1.28) were associated with an increased risk. Significant additive interactions were found between total carbohydrates and genetic risk, as well as between total starch and genetic risk. Serum urate was identified as a significant mediator in all associations between carbohydrate intake (total, different types, and sources) and gout risk. In conclusion, total carbohydrate and different types and sources of carbohydrate (excluding free sugars) intake were associated with a reduced risk of gout.

Exploring causal effects and potential mediating mechanisms of genetically linked environmental senses with intracerebral hemorrhage.

The occurrence mechanism of intracerebral hemorrhage remains unclear. Several recent studies have highlighted the close relationship between environmental senses and intracerebral hemorrhage, but the mechanisms of causal mediation are inconclusive. We aimed to investigate the causal relationships and potential mechanisms between environmental senses and intracerebral hemorrhage. Multiple Mendelian randomization methods were used to identify a causal relationship between environmental senses and intracerebral hemorrhage. Gut microbiota and brain imaging phenotypes were used to find possible mediators. Enrichment and molecular interaction analyses were used to identify potential mediators and molecular targets. No causal relationship between temperature and visual perception with intracerebral hemorrhage was found, whereas long-term noise was identified as a risk factor for intracerebral hemorrhage (OR 2.95, 95% CI: 1.25 to 6.93, PIVW = 0.01). The gut microbiota belonging to the class Negativicutes and the order Selenomonadales and the brain image-derived phenotypes ICA100 node 54, edge 803, edge 1149, and edge 1323 played mediating roles. "Regulation of signaling and function in synaptic organization" is the primary biological pathway of noise-induced intracerebral hemorrhage, and ARHGAP22 may be the critical gene. This study emphasized the importance of environmental noise in the prevention, disease management, and underlying biological mechanisms of intracerebral hemorrhage.

Effects of Income on Subjective Well-Being in the Elderly: Complete Mediation Roles of Self-Rated Health and Psychological Capital.

Although income and living conditions of residents have greatly improved in recent years, people's subjective well-being does not seem to increase daily. This study aimed to explore income, self-rated health, and psychological capital on subjective well-being, using data from the China General Social Survey conducted in 2017. A total of 1136 elderly as subsamples data were selected from 12 582 participants, involving general sociodemographic characteristics, income, self-rated health, psychological capital, and subjective well-being. SPSS v26.0 macro was used for descriptive statistics, ANOVA and correlation analysis. PROCESS v3.4 macro was performed to examine multiple mediating effects of self-rated health and psychological capital. The elderly residing in urban (P = .016) and having completed 9-year compulsory education (P = .016) reported higher subjective well-being scores. The findings revealed that subjective well-being was positively associated with income, health, and psychological capital among the aged adults (all P < .001). Self-rated health and psychological capital played complete mediation roles between income and subjective well-being (Effect indirect = 0.040, 95% bootstrap CI [0.022, 0.060]; Effect indirect = 0.027, 95% bootstrap CI [0.013, 0.044], respectively). Collectively, our findings indicate that residing in rural and having lower education levels serve as negative predictors of subjective well-being among the elderly. Although income still affects the elderly's subjective well-being, self-rated health and psychological capital may be the crucial mediating factors. Therefore, it is of utmost importance to improve health conditions and positive psychological capital for subjective well-being of the older people.

Effect of adequacy of empirical antibiotic therapy for hospital-acquired bloodstream infections on ICU patient prognosis: a causal inference approach using data from the Eurobact2 study.

OBJECTIVES: Hospital-acquired bloodstream infections (HA-BSI) in the intensive care unit (ICU) are common life-threatening events. We wanted to investigate the association between early adequate antibiotic therapy and 28-day mortality in ICU patients surviving for at least 1 day after the onset of HA-BSI. METHODS: We used individual data from a prospective, observational, multicenter, intercontinental cohort study (Eurobact2). We included patients followed for ≥1 day for whom time-to-appropriate treatment was available. We used an adjusted frailty-Cox proportional hazard model to assess the effect of time-to-treatment-adequacy on 28-day mortality. Infection- and patient-related variables identified as confounders by the Directed Acyclic Graph were used for adjustment. Adequate therapy within 24 hours was used for primary analysis. Secondary analyses were performed for adequate therapy within 48 and 72 hours and for identified patient subgroups. RESULTS: Among the 2,418 patients included in 330 centers worldwide, 28-day mortality was 32.8% (n=402/1226) in patients who were adequately treated within 24 hours after HA-BSI onset and 40% (n=477/1192) in inadequately treated patients (p<0.01). Adequacy within 24 hours was more common in young, immunosuppressed patients, and with HA-BSI due to Gram-negative pathogens. Antimicrobial adequacy was significantly associated with 28-day survival (aHR 0.83, 95% CI 0.72-0.96, p=0.01). The estimated population attributable fraction (PAF) of 28-day mortality of inadequate therapy was 9.15% (95% CI 1.9%-16.2%). CONCLUSIONS: In patients with HA-BSI admitted in ICU, the PAF of 28-day mortality of inadequate therapy within 24 hours was 9.15%. This estimate should be used when hypothesizing the possible benefit of any intervention aiming at reducing the time-to-appropriate antimicrobial therapy in HA-BSI.

Dexmedetomidine administration is associated with improved outcomes in critically ill patients with acute myocardial infarction partly through its anti-inflammatory activity.

Background: Dexmedetomidine (DEX) is a commonly used sedative in the intensive care unit and has demonstrated cardioprotective properties against ischemia-reperfusion injury in preclinical studies. However, the protective effects of early treatment of DEX in patients with acute myocardial infarction (AMI) and its underlying mechanism are still not fully understood. This study aims to investigate the association between early DEX treatment and in-hospital mortality in patients with AMI, and to explore the potential mediating role of white blood cell (WBC) reduction in this relationship. Methods: A retrospective cohort analysis was conducted using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients with AMI were divided into the DEX and non-DEX group, based on whether they received DEX treatment in the early stage of hospitalization. The primary outcome measured was in-hospital mortality. The study evaluated the association between DEX use and in-hospital mortality using the Kaplan-Meier (KM) method and Cox proportional hazards model. Additionally, 1:1 propensity score matching (PSM) was conducted to validate the results. Furthermore, causal mediation analysis (CMA) was utilized to explore potential causal pathways mediated by WBC reduction between early DEX use and the primary outcome. Results: This study analyzed data from 2,781 patients, with 355 in the DEX group and 2,426 in the non-DEX group. KM survival analysis revealed a significantly lower in-hospital mortality rate in the DEX group compared to the non-DEX group. After adjusting for multiple confounding factors, the Cox regression model demonstrated a significant positive impact of DEX on the risk of in-hospital mortality in patients with AMI, with hazard ratios (HR) of 0.50 (95% confidence interval (CI): 0.35-0.71, p < 0.0001). PSM analysis confirmed these results, showing HR of 0.49 (95% CI: 0.31-0.77, p = 0.0022). Additionally, CMA indicated that 13.7% (95% CI: 1.8%-46.9%, p = 0.022) of the beneficial effect of DEX on reducing in-hospital mortality in patients with AMI was mediated by the reduction in WBC. Conclusion: The treatment of DEX was associated with a lower risk of in-hospital mortality in patients with AMI, potentially due to its anti-inflammatory properties.

The Role of Platelet Distribution Width in the Association Between Blood Glucose and Neurological Impairment Severity in Acute Ischemic Stroke: A Moderated Mediation Model.

Objective: Fasting blood glucose (FBG) is a recognized risk factor for Ischemic Stroke, but little research has examined the interaction among FBG, Platelet Distribution Width (PDW) and the severity of neuronal damage. Thus, the present study constructs a moderated mediation model aimed to elucidate the relationships among FBG, PDW, and NIHSS scores in patients with acute ischemic stroke (AIS). Methods: We conducted a cross-sectional study on 431 AIS patients. Upon hospital admission, we assessed the patients' NIHSS scores and collected blood samples to measure FBG and PDW levels. The relationship between FBG and NIHSS scores moderated by PDW was analyzed by linear curve fitting analysis, multiple linear regression analysis, and moderated mediation analysis respectively. Results: In the tertile grouping based on FBG, both PDW and NIHSS scores of AIS patients demonstrated an increase corresponding with rising levels of FBG (p<0.001 for both). Multiple linear regression analysis revealed that, the ß coefficients (95% CI) for the relationship between FBG and NIHSS scores were 1.49 (1.27-1.71, p<0.01) post-adjustment for potential confounders. The ß coefficients (95% CI) for the relationship between FBG and PDW were 0.02 (0.01-0.04, p<0.01) post-adjustment. Likewise, for the relationship between PDW and NIHSS scores, the ß coefficients (95% CI) were 4.33 (3.07-5.59, p<0.01) after adjustment. These positive association remained consistent in sensitivity analysis and hierarchical analysis. Smoothed plots suggested that there are linear relationships between FBG and PDW and NIHSS scores respectively. Further mediation analysis indicated that increased PDW significantly (p<0.01) mediated 5.91% of FBG-associated increased NIHSS scores. Conclusion: This study suggested that FBG levels were associated with NIHSS scores, and the FBG-associated neurological impairment may be partially mediated by PDW. These findings underscore the importance of monitoring FBG and PDW levels in AIS patients, potentially guiding risk intervention strategies.

Causal relationship between key genes and metabolic dysfunction-associated fatty liver disease risk mediated by immune cells: A Mendelian randomization and mediation analysis.

AIM: Non-invasive diagnostics for metabolic dysfunction-associated fatty liver disease (MAFLD) remain challenging. We aimed to identify novel key genes as non-invasive biomarkers for MAFLD, elucidate causal relationships between biomarkers and MAFLD and determine the role of immune cells as potential mediators. MATERIALS AND METHODS: Utilizing published transcriptome data of patients with biopsy-proven MAFLD, we applied linear models for microarray data, least absolute shrinkage and selector operation (LASSO) regressions and receiver operating characteristic (ROC) curve analyses to identify and validate biomarkers for MAFLD. Using the expression quantitative trait loci database and a cohort of 778 614 Europeans, we used Mendelian randomization to analyse the causal relationships between key biomarkers and MAFLD. Additionally, mediation analysis was performed to examine the involvement of 731 immunophenotypes in these relationships. RESULTS: We identified 31 differentially expressed genes, and LASSO regression showed three hub genes, IGFBP2, PEG10, and P4HA1, with area under the receiver operating characteristic (AUROC) curve of 0.807, 0.772 and 0.791, respectively, for identifying MAFLD. The model of these three genes had an AUROC of 0.959 and 0.800 in the development and validation data sets, respectively. This model was also validated using serum-based enzyme-linked immunosorbent assay data from MAFLD patients and control subjects (AUROC: 0.819, 95% confidence interval: 0.736-0.902). PEG10 was associated with an increased MAFLD risk (odds ratio = 1.106, p = 0.032) via inverse variance-weighted analysis, and about 30% of this risk was mediated by the percentage of CD11c + CD62L- monocytes. CONCLUSIONS: The MAFLD panels have good diagnostic accuracy, and the causal link between PEG10 and MAFLD was mediated by the percentage of CD11c + CD62L- monocytes.