Direct Causal Relationship Research Articles

Vitamin D Level and Immune Modulation in Children with Recurrent Wheezing.

A direct causal relationship between vitamin D (vit D) deficiency and recurrent wheezing has not been proven. The present study investigated the role of vit D in enhancing the risk of asthma or recurrent wheezing by modifying the intensity of the inflammatory process. Forty children with wheezing presenting at the emergency service and sixteen healthy control subjects were included in the study. Children with wheezing were either in the first episode (20) or with recurrent wheezing (20). Children with chronic diseases, and other conditions that present with acute wheezing or that might influence the vit D level, were excluded. Blood samples were taken at presentation and 3-6 months later, to evaluate the serum levels of total IgE, vit D, IL-10 and IL-31. Statistical analysis was performed using the SPSS 25 program, with a significance level of p < 0.05. The vit D level was lower in patients with recurrent wheezing compared with those with a single episode and with the control group, and this increased with time. IL-10 was significantly higher in children with wheezing than in the control group, with the highest values in those with an acute episode of wheezing. IL-31 was higher in children with recurrent wheezing than in those with a first episode only at the initial point, while at the final time point it was lower. Low levels of vit D appear to be detected more frequently in recurrent wheezing than in simple wheezing. Immune modulation, as measured by Th2 status reflected by IL-10 and IL-31 levels, appears to depend on the wheezing phenotype and on the general health status.

The Urinary Microbiome in Health and Disease: Relevance for Bladder Cancer.

Bladder cancer (BC) constitutes one of the most diagnosed types of cancer worldwide. Advancements in and new methodologies for DNA sequencing, leading to high-throughput microbiota testing, have pinpointed discrepancies in urinary microbial fingerprints between healthy individuals and patients with BC. Although several studies suggest an involvement of microbiota dysbiosis in the pathogenesis, progression, and therapeutic response to bladder cancer, an established direct causal relationship remains to be elucidated due to the lack of standardized methodologies associated with such studies. This review compiles an overview of the microbiota of the human urinary tract in healthy and diseased individuals and discusses the evidence to date on microbiome involvement and potential mechanisms by which the microbiota may contribute to the development of BC. We also explore the potential profiling of urinary microbiota as a biomarker for risk stratification, as well as the prediction of the response to intravesical therapies and immunotherapy in BC patients. Further investigation into the urinary microbiome of BC patients is imperative to unravel the complexities of the role played by host-microbe interactions in shaping wellness or disease and yield valuable insights into and strategies for the prevention and personalized treatment of BC.

The Influence of Strength and Sport Exposure on Psychological Readiness After ACL Reconstruction.

Among young athletes returning to sport after anterior cruciate ligament reconstruction (ACLR), the extent to which psychological readiness is influenced by factors beyond the psychological domain is largely unknown. Young athletes with recent sport exposure and higher quadriceps strength will demonstrate higher psychological readiness within 8 weeks of medical clearance to return to sport (RTS) after ACLR. Cross-sectional study. Level 3. A total of 38 young athletes after primary ACLR completed testing within 8 weeks of medical clearance to RTS. All participants completed isometric knee extension strength testing, in addition to the ACL Return to Sport after Injury (ACL-RSI) questionnaire. Athletes who participated in sport between time of medical clearance to RTS and date of study enrollment were categorized as SPORT-YES. Those who had not yet participated in sports were categorized as SPORT-NO. Multiple linear regression analyses were used to determine differences in ACL-RSI scores based on quadriceps strength and sport exposure status, while adjusting for age and sex. Of the 38 participants, 20 (52.6%) were categorized as SPORT-YES. The regression model estimating overall ACL-RSI score (P < 0.01, adjusted R2 = 0.389) included significant independent contributions from age, sex, and sport exposure variables (age: P = 0.01, β [95% CI] = -2.01 [-3.54, -0.48]; sex (male): P = 0.02, β [95% CI] = 12.50 [2.36, 22.64]; strength: P = 0.51, β [95% CI] = -2.47 [-10.07,5.13]; sport exposure: P < 0.01, β [95% CI] = 12.89 [3.58, 22.19]). In partial accordance with our hypothesis, recent sport exposure was significantly associated with higher ACL-RSI scores among young athletes in the weeks after medical clearance to RTS after ACLR, while quadriceps strength was not. Future prospective work is needed to determine the existence and direction of causal relationships between exposure to sport environment and psychological readiness among young athletes after ACLR.

Mental health and lower urinary tract symptoms: Results from the NHANES and Mendelian randomization study

BackgroundThe clinical observations suggest a correlation between lower urinary tract symptoms (LUTSs) and mental health problems. Nonetheless, establishing a direct causal relationship between them remains challenging. MethodsWe initially conducted a cross-sectional study using 2005–2018 the National Health and Nutrition Examination Survey (NHANES) data. Multivariable-adjusted logistic regression was the primary statistical approach. Additionally, we employed Mendelian randomization (MR) to reducing confounding and reverse causation. Genetic instruments were obtained from publicly available genome-wide association study (GWAS) databases. Inverse Variance Weighted was the primary statistical method. ResultsThe cross-sectional study involved 29,439 participants. Individuals with mental health problems had a higher risk of urinary incontinence (OR:4.38; 95%CI:3.32–5.76; P < 0.01) and overactive bladder (OR:2.31; 95%CI:2.02–2.63; P < 0.01). MR analysis then indicated a potential causal relationship between mental health problems and LUTSs. Depression symptoms was linked with urinary tract infection (UTI) (OR:1.005; 95%CI:1.003–1.008; PFDR < 0.01). Anxiety symptoms was related to the occurrence of UTI (OR:1.024; 95%CI:1.011–1.037; PFDR < 0.01) and bladder calcified/ contracted/ overactive (OR:1.017; 95%CI:1.007–1.027; PFDR < 0.01). The personality trait of neuroticism was related to the occurrence of cystitis (OR:1.072; 95%CI:1.022–1.125; PFDR = 0.02), extravasation of urine and difficulties with micturition (OR:1.001; 95%CI:1.001–1.002; PFDR < 0.01), and urinary frequency and incontinence (OR: 1.001; 95%CI:1.000–1.001; PFDR < 0.01). ConclusionsOur study provides various evidence for the correlation between mental health and LUTSs, emphasizing the significance of adopting a holistic approach to LUTSs management that incorporates both physical and psychological factors.

Dietary factors and hypertension: A Mendelian randomization analysis.

This research explores the causal link between dietary habits and hypertension through Mendelian randomization, providing distinct perspectives on the role of diet in addressing this worldwide health issue. Utilizing instrumental variables, we applied advanced statistical methods, including the weighted median, inverse variance weighted, and MR-Egger, to evaluate the impact of 17 dietary elements on hypertension. These elements ranged across various food groups, such as fruits, meats, vegetables, and beverages, both alcoholic and nonalcoholic. Our results identified a significant positive association of hypertension with weekly alcohol consumption (OR 1.340 [95%CI 1.0001 to 1.794], p = .0499) and poultry intake (OR 2.569 [95%CI 1.305 to 5.057], p = .00631). Conversely, a negative association was observed with lamb/mutton (OR 0.550 [95%CI 0.343 to 0.881], p = .0129), cheese (OR 0.650 [95%CI 0.519 to 0.813], p = .000159), tea (OR 0.797 [95%CI 0.640 to 0.993], p = .0433), cereal (OR 0.684 [95%CI 0.494 to 0.948], p = .0227), and dried fruit consumption (OR 0.492 [95%CI 0.343 to 0.707], p = .000127). These findings suggest that dietary modifications, such as increasing consumption of specific foods like cheese, lamb/mutton, tea, cereals, and dried fruits, could potentially reduce hypertension risk while reducing intake of alcoholic beverages and poultry might mitigate its increase. No direct causal relationships were established between other dietary factors and hypertension. The study highlights the importance of specific dietary modifications for the prevention and control of hypertension, making a substantial contribution to public health tactics and recommendations.

SELF-EFFICACY, JOB PERFORMANCE, AND TRANSFORMATIONAL LEADERSHIP: A STRUCTURAL EQUATION MODEL ON ORGANIZATIONAL COMMITMENT AMONG PUBLIC SCHOOL TEACHERS

&lt;p&gt;The study aimed to investigate the influence of self-efficacy, job performance, and transformational leadership style on organizational commitment using Structural Equation Modelling (SEM) to 400 public school teachers in Region XI, Philippines. Findings revealed a high level of self-efficacy, a very high level of job performance, and high levels of transformational leadership and organizational commitment. There is a strong, positive, and significant correlation between self-efficacy and organizational commitment; job performance and organizational commitment; and transformational leadership and organizational commitment. Further results showed that the best-fit model was model 3 showing the direct causal relationships of Self-Efficacy, Job Performance, and Transformational Leadership Style on Organizational Commitment. Moreover, the Organizational Commitment of the respondents was defined by the retained indicators, namely: Affective Commitment and Individual Performance. Self-efficacy was described with the following retained indicators: Disciplinary Self-efficacy, and Creative Positive School Climate. On the other hand, Job performance was described in terms of the indicators Workload and Working Environment. Finally, Transformational Leadership retained the following indicators: Political Skill Inventory, and Perception of Relational Uncertainty. Findings suggest that the policy-making body of the Department of Education should look into the provision of professional development, workload allocations, and benefits of the teachers to further improve their organizational commitment.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt; Article visualizations:&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;img src="/-counters-/soc/0517/a.php" alt="Hit counter" /&gt;&lt;/p&gt;

Absence of a causal link between COVID-19 and deep vein thrombosis: Insights from a bi-directional Mendelian randomisation study.

Several large-scale observational studies have found deep vein thrombosis (DVT) to be related with coronavirus disease 2019 (COVID-19). However, whether there is a clear causal connection between the two is unknown. Our primary analytical method was the inverse variance-weighted (IVW) approach, complemented by the Mendelian randomisation-Egger (MR-Egger) and weighted median methods. We also used MR-Egger to examine the presence of pleiotropy and the Mendelian randomisation pleiotropy residual sum and outlier (MR-PRESSO) approach to analyse for heterogeneity in the data. We did not observe a direct causal relationship between COVID-19 susceptibility (odds ratio (OR) = 1.023; 95% confidence interval (CI) = 0.828-1.264, standard error (SE) = 0.108, P = 0.833), hospitalisation (OR = 1.030; 95% CI = 0.943-1.125, SE = 0.374, P = 0.720), severity (OR = 0.994; 95% CI = 0.923-1.071, SE = 0.038, P = 0.877), and DVT. The results of the reverse Mendelian randomisation (MR) for DVT and COVID-19 susceptibility exhibited heterogeneity and horizontal pleiotropy. Even after removing outliers, we detected no direct causal relationship between the two (OR = 1.015; 95% CI = 0.954-1.080, SE = 0.032, P = 0.630). Similarly, we found no direct causal relationship between DVT and COVID-19 hospitalisation (OR = 0.999; 95% CI = 0.907-1.102, SE = 0.050, P = 0.999) or severity (OR = 1.014; 95% CI = 0.893-1.153, SE = 0.065, P = 0.826). In this MR study, we identified no direct causal impact in a European population between DVT and the COVID-19 susceptibility, severity, or hospitalisation.

Factoren geassocieerd aan agressiviteit en verwante gedragsproblemen bij kinderen en adolescenten met ASS: een grondige review

Factors associated with externalizing challenging behaviour in children and adolescents with ASD: a systematic review Autism spectrum disorder (ASD) is a neurodevelopmental syndrome with a high prevalence of comorbid challenging behaviours. Externalizing challenging behaviours are known to have a negative prognostic impact on children with ASD and their caregivers. Studies have shown several risk factors for externalizing challenging behaviours in the typically developing population. Less is known about the risk factors for children with ASD. The databases PubMed, Embase and Web of Science Core Collection were systematically searched. A systematic analysis of the selected articles was performed. A total of 95 studies were found. Despite the multitude of withheld articles, only a few factors showed to be clearly associated with externalizing challenging behaviour in children with ASD. The studies in this review mainly investigate cross-sectional and some prognostic associations, and often find conflicting results. Consequently, the authors cannot make strong statements about possible direct causal relationships of the studied factors with externalising behavioural problems. Nevertheless, they emphasize some possible implications for clinical practice. First, more attention should be paid to the adaptive skills of children with ASD. In addition, they underline the importance of systematic screening regarding the severity of the rigidity, encouraging flexibility and learning to cope with change. Furthermore, it is crucial to diagnose and treat ADHD and sleep disorders. Finally, the results mark the importance of early detection and intervention of contextual factors.

Causal relationship between periodontal disease-related phenotype and knee osteoarthritis: A two-sample mendelian randomization analysis.

This study aimed to explore the bidirectional causal relationship between periodontal disease-related phenotype (PDRP) and knee osteoarthritis (KOA) in a European population using a two-sample Mendelian Randomization (MR) approach. We leveraged publicly available GWAS summary statistics for PDRP (n = 975) and KOA (n = 403,124), assessing their roles as both exposures and outcomes. Our comprehensive MR analysis employed various methods, including inverse variance weighting (IVW), weighted median, Egger regression, simple mode, and weighted mode, to enhance the robustness of our findings. To ensure the reliability of our instrumental variables, we implemented a rigorous screening process based on p-values and F-values, utilized Phenoscanner to investigate potential confounders, and conducted sensitivity analyses. Our analysis identified five SNPs associated with PDRP and three SNPs with KOA, all surpassing the genome-wide significance threshold, as instrumental variables. The IVW method demonstrated a significant causal relationship from PDRP to KOA (beta = 0.013, SE = 0.007, P = 0.035), without evidence of directional pleiotropy (MR-Egger regression intercept = 0.021, P = 0.706). No support was found for reverse causality from KOA to PDRP, as further MR analyses yielded non-significant P-values. Additionally, funnel plots and Cochran's Q test detected no significant heterogeneity or directional pleiotropy, confirming the robustness of our results. In multivariate analysis, when considering smoking, alcohol consumption, BMI collectively no direct causal relationship between KOA and PDRP. Conversely, smoking and higher BMI were independently associated with an increased risk of KOA. In conclusion, our analysis revealed no direct causal relationship from KOA to PDRP. However, a causal relationship from PDRP to KOA was observed. Notably, when adjusting for potential confounders like smoking, alcohol intake, and BMI, both the causal connection from PDRP to KOA and the inverse relationship were not substantiated.

The use of intravascular contrast media in patients with impaired kidney function - joint clinical practice position statement of the Polish Society of Nephrology and the Polish Medical Society of Radiology.

Radiological procedures utilising intravascular contrast media (ICM) are fundamental to modern medicine, enhancing diagnostics and treatment in diverse medical fields. However, the application of ICM has been constrained in patients with compromised kidney function due to perceived nephrotoxic risks, called contrast-induced nephropathy or contrastinduced acute kidney injury. Historical evidence marked ICM as a possible contributor to kidney damage. This led to restrictive guidelines advocating limited ICM use in patients with impaired renal function, preventing crucial radiographic interventions in patients with acute kidney injury (AKI) and chronic kidney disease. Recent advances challenge these traditional views. In particular, no direct causal relationship has been confirmed between contrast admi-nistration and elevated serum creatinine concentrations in humans. Furthermore, contemporary research models and meta-analyses do not associate AKI with contrast usage. This paper, prepared by a cross-disciplinary team of nephrologists and radiologists, presents updated guidelines for ICM application amid renal function impairments, emphasising the reduced nephrotoxic risks currently understood and loosening the previous restrictive approach in patients with renal dysfunction.

The emerging role of neutrophil extracellular traps in the progression of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex etiology. Neutrophil extracellular traps (NETs are NETwork protein structures activated by neutrophils to induce the cleavage and release of DNA-protein complexes). Current studies have shown the critical involvement of NETs in the progression of autoimmune diseases, Neutrophils mostly gather in the inflammatory sites of patients and participate in the pathogenesis of autoimmune diseases in various ways. NETs, as the activated state of neutrophils, have attracted much attention in immune diseases. Many molecules released in NETs are targeted autoantigens in autoimmune diseases, such as histones, citrulline peptides, and myeloperoxidase. All of these suggest that NETs have a direct causal relationship between the production of autoantigens and autoimmune diseases. For RA in particular, as a disorder of the innate and adaptive immune response, the pathogenesis of RA is inseparable from the generation of RA. In this article, we investigate the emerging role of NETs in the pathogenesis of RA and suggest that NETs may be an important target for the treatment of inflammatory autoimmune diseases.

Causal associations of gut microbiota and pulmonary tuberculosis: a two-sample Mendelian randomization study.

The prevalence of pulmonary tuberculosis (PTB) as an infectious disease continues to contribute significantly to global mortality. According to recent studies, the gut microbiota of PTB patients and healthy controls (HCs) show significant disparities. However, the causal relationship between them has yet to be elucidated. We conducted a study using Mendelian Randomization (MR) to explore the potential causal link between gut microbiota and pulmonary tuberculosis (PTB). The summary statistics of the gut microbiota were acquired from the MiBioGen consortium, while data on PTB were sourced from pheweb.jp. A range of statistical methodologies were employed to evaluate causality, encompassing inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted model, and simple model. We utilized instrumental variables (IVs) that have a direct causal relationship with PTB to annotate SNPs, aiming to discover the genes harboring these genetic variants and uncover potential associations between host genes and the microbiome in patients with PTB. Among the 196 bacterial traits in the gut microbiome, we have identified a total of three microbiomes that exhibit a significant association with PTB. The occurrence of Dorea (P = 0.0458, FDR-adjusted P = 0.0458) and Parasutterella (P = 0.0056, FDR-adjusted P = 0.0168) was linked to an elevated risk of PTB, while the presence of Lachnoclostridium (P = 0.0347, FDR-adjusted P = 0.0520) demonstrated a protective effect against PTB. Our reverse Two-Sample Mendelian Randomization (TSMR) analysis did not yield any evidence supporting the hypothesis of reverse causality from PTB to alterations in the intestinal flora. We have established a connection between the gut microbiota and PTB through gene prediction analysis, supporting the use of gut microecological therapy in managing PTB and paving the way for further understanding of how gut microbiota contributes to PTB's development.

Causal associations of white blood cell count and sudden sensorineural hearing loss: a bidirectional and multivariable Mendelian randomization study.

Numerous compelling observational studies have demonstrated a plausible correlation between the white blood cell count and the susceptibility to sudden sensorineural hearing loss (SSNHL). Nevertheless, the exact causal relationship between these two factors remains ambiguous. The objective of our study was to assess the causal impact of white blood cell count on sudden sensorineural hearing loss through the implementation of a bidirectional and multivariable Mendelian randomization (MR) methodology. Genetic data pertaining to white blood cell count were acquired from the Blood Cell Consortium, encompassing a total of 563,946 subjects. Concurrently, summary data on sudden sensorineural hearing loss were sourced from a Genome-Wide Association Study (GWAS), involving 196,592 participants, comprising 1,491 cases and 195,101 controls. The primary method employed for MR analysis was the Inverse Variance Weighted method (IVW), while sensitivity analysis utilized the Weighted Median method, MR-Egger method, and MR-PRESSO method. In IVW method, genetically predicted elevated lymphocyte cell count demonstrates an effective reduction in the risk of sudden sensorineural hearing loss (odds ratio = 0.747, 95% CI = 0.565-0.987, p = 0.04). These findings remain consistent in multivariate MR analysis, even after adjusting for monocyte cell count and neutrophil cell count levels (odds ratio = 0.929, 95% CI = 0.867-0.995, p = 0.036). However, there is no discernible evidence supporting a direct causal relationship between monocyte cell count and neutrophil cell count levels and the occurrence of SSNHL. Within the normal range, higher lymphocyte cell count levels exhibit a potential protective effect against SSNHL. Meanwhile, no direct causal relationship are identified between monocyte cell count and neutrophil cell count levels and the risk of SSNHL.

Association of coagulation markers with the severity of white matter hyperintensities in cerebral small vessel disease.

This study aimed to explore the correlation and causal relationship between fibrinogen, D-dimer, and the severity of cerebral white matter hyperintensity (MMH). A retrospective analysis of 120 patients with cerebral small vessel disease (CSVD) confirmed by head MRI attending the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine from August 2021 to February 2023 was performed. According to the Fazekas scale score, the patients were divided into 42 cases in the mild group, 44 cases in the moderate group, and 34 cases in the severe group. The levels of fibrinogen and D-dimer were compared among the three groups; the correlations between fibrinogen, D-dimer, and WMH severity were further analyzed; and independent risk factors for WMH severity were explored using the multivariate ordered logistic regression analysis. Furthermore, a two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of fibrinogen and D-dimer on WMH. As the severity of WMH increased, the levels of D-dimer and fibrinogen also gradually increased, and the results showed a positive correlational association, with significant differences within the groups (all p < 0.05); the multivariate ordered logistic regression model showed that after adjusting for the relevant covariates, D-dimer (OR = 5.998, 95% CI 2.213-16.252, p < 0.001) and fibrinogen (OR = 9.074, 95% CI 4.054-20.311, p < 0.001) remained independent risk factors for the severity of WMH. In the MR study, the random-effect inverse variance weighted (IVW) model showed that increased levels of genetically predicted D-dimer (OR, 1.01; 95% confidence interval 0.95-1.06; p = 0.81) and fibrinogen (OR, 1.91; 95% confidence interval 0.97-3.78; p = 0.06) were not associated with increased risk of WMH. The authors did not obtain strong evidence of a direct causal relationship between D-dimer, fibrinogen, and WMH. In this retrospective-based study, the authors found possible associations between D-dimer, fibrinogen, and WMH, but there was no obvious causal evidence. Further efforts are still needed to investigate the pathophysiology between D-dimer, fibrinogen, and WMH.

Association of toxin-producing Clostridioides difficile with piglet diarrhea and potential transmission to humans.

The pathogenicity of Clostridioides difficile in piglets remains controversial. It is unknown whether C. difficile control helps protect piglet health. To clarify the association between C. difficile presence and piglet diarrhea, isolates were obtained from piglets with and without diarrhea. In addition, to determine the genetic relationship of C. difficile from pigs and humans, we performed whole-genome sequencing (WGS) of C. difficile isolates. Diarrheal and non-diarrheal stool samples were collected from neonatal piglets from five farms in Japan in 2021. To clarify the relationship between C. difficile derived from pigs and those from human clinical cases, WGS of C. difficile isolates was performed. Toxin-positive C. difficile were significantly more prevalent in piglets with diarrhea, although the overall frequency of C. difficile did not differ between piglets with and without diarrhea. This observation indicates an association between toxin-positive C. difficile and diarrhea in piglets. However, further studies are needed to establish a direct causal relationship and to explore other contributing factors to diarrhea in piglets. WGS results showed that C. difficile sequence type (ST) 11 including the hypervirulent PCR ribotype 078 isolates derived from Japanese pigs were closely related to ST11 of overseas strains (human clinical and animal-derived) and a Japanese human clinical strain. Toxin-positive C. difficile may cause diarrhea in piglets and hypervirulent C. difficile are spreading among pigs and human populations worldwide.

Altered Gut Microbiota as a Potential Risk Factor for Coronary Artery Disease in Diabetes: A Two-Sample Bi-Directional Mendelian Randomization Study.

The current body of research points to a notable correlation between an imbalance in gut microbiota and the development of type 2 diabetes mellitus (T2D) as well as its consequential ailment, coronary artery disease (CAD). The complexities underlying the association, especially in the context of diabetic coronary artery disease (DCAD), are not yet fully understood, and the causal links require further clarification. In this study, a bidirectional Mendelian randomization (MR) methodology was utilized to explore the causal relationships between gut microbiota, T2D, and CAD. By analyzing data from the DIAGRAM, GERA, UKB, FHS, and mibioGen cohorts and examining GWAS databases, we sought to uncover genetic variants linked to T2D, CAD, and variations in gut microbiota and metabolites, aiming to shed light on the potential mechanisms connecting gut microbiota with DCAD. Our investigation uncovered a marked causal link between the presence of Oxalobacter formigenes and an increased incidence of both T2D and CAD. Specifically, a ten-unit genetic predisposition towards T2D was found to be associated with a 6.1% higher probability of an increase in the Oxalobacteraceae family's presence (β = 0.061, 95% CI = 0.002-0.119). In a parallel finding, an augmented presence of Oxalobacter was related to an 8.2% heightened genetic likelihood of CAD (β = 0.082, 95% CI = 0.026-0.137). This evidence indicates a critical pathway by which T2D can potentially raise the risk of CAD via alterations in gut microbiota. Additionally, our analyses reveal a connection between CAD risk and Methanobacteria, thus providing fresh perspectives on the roles of TMAO and carnitine in the etiology of CAD. The data also suggest a direct causal relationship between increased levels of certain metabolites - proline, lysophosphatidylcholine, asparagine, and salicylurate - and the prevalence of both T2D and CAD. Sensitivity assessments reinforce the notion that changes in Oxalobacter formigenes could pose a risk for DCAD. There is also evidence to suggest that DCAD may, in turn, affect the gut microbiota's makeup. Notably, a surge in serum TMAO levels in individuals with CAD, coinciding with a reduced presence of methanogens, has been identified as a potentially significant factor for future examination.

The relationship between metabolite mediated immune regulatory imbalance and the occurrence of malignant tumors of bone and articular cartilage: a Mendelian randomization study.

This study aims to assess the causal relationship between immune cell characteristics and malignant tumors of bone and articular cartilage, focusing on the mediating role of metabolites. Using Mendelian randomization, we evaluated these relationships based on genetic variations to identify potential biomarkers and therapeutic targets. A two-sample Mendelian randomization analysis was conducted using GWAS data for immune cell features and 1,400 metabolites to investigate direct and mediating effects. Effective instrumental variables (IVs) were selected, and statistical analyses-including inverse variance weighting (IVW), weighted median, and mode-based methods-were performed using R software. This approach enabled the assessment of direct causal relationships as well as the potential mediating role of metabolites in the association between immune cell features and malignancies. Significant causal relationships were identified between 26 immune phenotypes and the risk of malignant tumors of bone and articular cartilage. Notably, the HLA DR+ NK cell phenotype SSC-A showed a positive correlation with the risk of these malignancies. Further analysis revealed causal relationships with 67 metabolites, 38 of which were positively correlated and 29 negatively correlated. Mediation analysis highlighted the role of immune surveillance and metabolic dysregulation in tumor development, as evidenced by the association between the immune phenotype SSC-A on HLA DR+ NK cells and the metabolite 5-hydroxyhexanoate. The findings suggest significant causal relationships between immune phenotypes and malignant tumors of bone and articular cartilage, with metabolites potentially mediating these relationships. These insights lay the groundwork for further research and could contribute to the development of new biomarkers and treatment strategies.

Instructional Leadership, work Engagement, Self-Efficacy of School Heads: A Structural Equation Model

This study aimed to determine the best-fit model of school effectiveness as influenced by instructional leadership, work engagement, self-efficacy of school heads among 400 public elementary school teachers in Davao Region, Philippines. With the used of Structural Equation Model Analysis, results gained a very high levels for Instructional Leadership and work engagement, a high level of self-efficacy of school heads and school effectiveness. Moreover, there was a strong, positive, and significant correlation between instructional leadership and school effectiveness, work engagement and school effectiveness. However, result for self- efficacy and school effectiveness is not correlated. Further, findings revealed that the influence of the exogenous variables indicates that the overall regression model is statistically significant. Furthermore, results showed that the best-fit model was model 3 showing the direct causal relationships of Instructional Leadership and self- efficacy on school effectiveness. Meanwhile, School effectiveness was defined by the retained indicators namely; Effectiveness of the School Climate, Effectiveness of the Relationship with Local Community, Effectiveness of Using Enrichment Activities in School and Student’s Sense of Belonging the Surrounding Environment. On the other hand, instructional leadership style was described with the following retained indicators: Framing the Goals, Supervise and Evaluate Instructions, Provide Incentives for Teachers and Promote Professional Development. While Self efficacy of school heads was described in terms of the retained indicators namely; Efficacy for Instructional Leadership and Efficacy for Moral Leadership. Findings suggest that the policy making body of the Department of Education may look into provision of benefits of the teachers and the school heads to further increase the school effectiveness.

PSYCHOLOGICAL CAPITAL, ACADEMIC JOB SATISFACTION AND EMOTIONAL INTELLIGENCE: A STRUCTURAL EQUATION MODEL ON WORK ENGAGEMENT AMONG PUBLIC SCHOOL TEACHERS

The study attempted to find the best-fit model on work engagement as influenced by psychological capital, academic job satisfaction, and emotional intelligence in public schools using Structural Equation Modeling (SEM) to 402 teachers in Davao Region, Philippines. Findings revealed very high levels of psychological capital and a high level of academic job satisfaction, emotional intelligence, and work engagement. There were significant correlations between psychological capital, academic job satisfaction, emotional intelligence, and work engagement. Further, results showed that the best-fit model was model 3 showing the direct causal relationships of psychological capital, academic job satisfaction, and emotional intelligence on work engagement. Furthermore, structure modifications revealed that psychological capital was described by its domains: hope and optimism while academic job satisfaction was determined by its retained indicators, namely: my work itself and interpersonal relationships. On the other hand, emotional intelligence was measured by its domains: empathy and motivating oneself. Finally, work engagement was defined by its retained indicators, namely: absorption and dedication. The study's findings could serve as an essential basis for teacher advancement programs, policies, and initiatives in educational organizations.&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt; Article visualizations:&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;img src="/-counters-/soc/0021/a.php" alt="Hit counter" /&gt;&lt;/p&gt;

Causal effects and immune cell mediators between prescription analgesic use and risk of infectious diseases: a Mendelian randomization study.

Clinical observations have found that prolonged use of analgesics increases the incidence of infection. However, the direct causal relationship between prescription analgesic use (PAU) and risk of infection (ROI) remains unclear. This study used Mendelian randomization (MR) design to estimate the causal effect of PAU on ROI, as well as their mediating factors. Genetic data on prescription analgesics use and immune cells were obtained from published GWAS. Additionally, data on ROI were extracted from the FinnGen database. Two-sample MR analysis and multivariate MR (MVMR) analysis were performed using inverse variance weighting (IVW) to ascertain the causal association between PAU and ROI. Finally, 731 immune cell phenotypes were analyzed for their mediating role between analgesics and infection. Using two-sample MR, IVW modeling showed that genetically predicted opioid use was associated with increased risk of pulmonary infection (PI) (OR = 1.13, 95% CI: 1.05-1.21, p< 0.001) and upper respiratory infection (URI) (OR = 1.18, 95% CI: 1.08-1.30, p< 0.001); non-steroidal anti-inflammatory drugs (NSAIDs) were related to increased risk of skin and subcutaneous tissue infection (OR = 1.21, 95% CI: 1.05-1.39, p = 0.007), and antimigraine preparations were linked to a reduced risk of virus hepatitis (OR = 0.79, 95% CI: 0.69-0.91, p< 0.001). In MVMR, the association of opioids with URI and PI remained after accounting for cancer conditions. Even with a stricter threshold (p< 0.05/30), we found a significant causal association between opioids and respiratory infections (URI/PI). Finally, mediation analyses found that analgesics influence the ROI through different phenotypes of immune cells as mediators. This MR study provides new genetic evidence for the causal relationship between PAU and ROI, and the mediating role of immune cells was demonstrated.