Introduction: Chronic kidney disease (CKD) involves a progressive loss of renal function and is characterized by chronic oxidative stress and kidney fibrosis. Tetrahydrocurcumin (THCu), a metabolite of curcumin, may possess antioxidant benefits in CKD. This study evaluated the transcriptomic changes and therapeutic potential of THCu against kidney damage and fibrosis in the 5/6 nephrectomy rat CKD model. Methods: Adult female Sprague–Dawley rats were randomized into CKD groups and three THCu doses were tested (100, 300 and 500 mg/kg). A liposomal formulation of THCu was given twice daily via oral gavage for 4 weeks. Serum creatinine and proteinuria were measured, and kidney fibrosis was assessed on histology. Kidney lysates were processed for total RNA sequencing to analyze differential gene expression in the experimental groups. The data were screened for outliers prior to ANOVA and correlation analyses. Results: In the untreated CKD group, serum creatinine and proteinuria were increased compared to control animals. Transcriptomic profiling revealed that untreated CKD animals exhibited marked upregulation across three key gene categories: immune cell activation, kidney injury and fibrosis, and inflammation and oxidative stress. THCu treatment mitigated these pathways by which there was downregulation of markers of immune cell activation as well as the kidney injury marker Kim1, while the fibrosis markers Col1a1 and Col3a1 were decreased to expression levels similar to non-CKD control animals. Furthermore, the highest dose of THCu at 500 mg/kg triggered a cellular detoxification and metabolic clearance response, with highly significant upregulation of Abcb11 and Gls2. Antioxidant benefit was evidenced by upregulation of Gpx1 in the high-dose THCu group compared to the untreated CKD group. Pathway enrichment analysis demonstrated that the high-dose THCu group restored key metabolic and signaling pathways disrupted in renal fibrosis, including small and organic solute metabolism, fatty acid oxidation, lipid biosynthesis, and peptide hormone response. Furthermore, the treatment upregulated essential anion and organic solute transport functions. Proteinuria was reduced with THCu therapy; however, serum creatinine and urine creatinine clearance were not significantly modified in comparison to untreated CKD rats. Conclusions: Oral THCu therapy demonstrated promising transcriptional changes in antioxidant and anti-fibrotic pathways in a rat CKD model. Confirmatory protein-level studies are needed to clarify benefits on kidney function.
BACKGROUND:Although simulation-based education is integral to emergency procedure training, computer monitor screen-based simulation (SBS) alone cannot develop the requisite feel and psychomotor skills. Haptic training simulations providing force feedback via a multi-degree-of-freedom stylus may improve this issue, offering tactile realism without the resource burdens of high-fidelity mannequins and consumable task trainers. This study compared user experience and skill acquisition between traditional task-trainer-based simulation and SBS with haptic feedback. METHODS:We conducted a crossover study with 22 emergency medicine learners (residents and medical students) to compare haptic-augmented SBS (3D Systems Touch™ with custom Unity™ software; 3D Systems, Inc., Rock Hill, SC, USA; Unity Technologies, San Francisco, CA, USA) versus traditional physical task trainers for lateral canthotomy (LC) and needle decompression (ND) procedures. Participants completed pre- and post-knowledge tests (five multiple-choice items per procedure) and post-simulation Likert surveys (1-5 scale) assessing realism, usability, and educational value. Knowledge changes were analyzed using the paired-samples proportion, Newcombe's method, and McNemar's test; Likert responses were summarized using median and interquartile range. RESULTS:Mean knowledge scores for LC increased by 20.9% (p < 0.001), and haptic simulation achieved median Likert ratings of 4-5 for realism, ease of use, and desirability. ND knowledge improved in certain topics (needle gauge choice, p = 0.007) with median Likert ratings of 4-5 for utility and integration potential. CONCLUSIONS:Haptic simulation represents a feasible and effective adjunct for procedural training in emergency medicine. For complex, dexterity-intensive tasks, such as LC, haptic augmented simulators offer educational outcomes comparable to those of traditional physical models while providing significant logistical and cost advantages. Conversely, traditional trainers remain at least as effective for less complex procedures such as ND. These preliminary findings support the integration of haptics into medical curricula, although future research must focus on long-term skill retention and the optimization of simulator design across a broader range of clinical interventions.
Background and Aims:Safety concerns have been raised regarding the glucagon-like peptide-1 receptor agonist (GLP-1RA) use in patients undergoing procedural sedation and anesthesia. The objective of this study is to assess the association between GLP-1RA use and postprocedural risk of pneumonia and all causes of urgent care (UC), emergency department, and hospitalization. Methods:Using a propensity-matched retrospective cohort design, we matched patients with active GLP-1RA at the time of gastrointestinal endoscopic procedure between January 2008 and June 2023 to non-GLP-1RA-exposed controls (1:4) using propensity scores generated by logistic regression. The primary outcome was risk of postprocedural pneumonia and all-cause hospitalization further adjusted for type sedation (conscious sedation vs monitored anesthesia care) as well as study year. We further assessed association between pre-endoscopic GLP-1RA exposure and subsequent UC, emergency department visits, and 30-day mortality. Results:The propensity-matched cohort comprised 63% colonoscopy, 25% esophagogastroduodenoscopy and 12% bidirectional endoscopy among 3825 patients with active GLP-1RA matched to 14,920 controls. There was no significant association between active GLP-1RA use and postprocedure pneumonia (0.13% vs 0.25%, odds ratio 0.56 (95% confidence interval: 0.22, 1.45)) or 30-day postprocedural hospitalization (1.9% vs 2.6%, 0.76 (95% confidence interval: 0.59, 0.98)) compared to nonusers. No significant association was observed for UC, emergency department visits or mortality at 7- or 30-days postprocedure. Conclusion:Uninterrupted use of GLP-1RA was not associated with major adverse events among patients undergoing gastrointestinal endoscopy with sedation.
ImportanceMaternal labor epidural analgesia (LEA) and oxytocin use for labor and delivery have been reported to be associated with child autism spectrum disorders (ASD). However, it remains unclear whether these 2 common medications used during labor and delivery have synergistic associations with ASD risk in children.ObjectiveTo assess the independent associations of LEA and oxytocin during labor and delivery with ASD, as well as outcome modification associated with the concurrent use of both interventions.Design, Setting, and ParticipantsData for this cohort study included 205 994 singleton births with vaginal deliveries in a single integrated health care system in Southern California from calendar years 2008 to 2017. Children were followed up to December 31, 2021. Data on use of LEA and oxytocin, covariates, and ASD outcome in children were obtained from electronic medical records. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) adjusting for covariates.ExposuresLabor epidural analgesia and/or oxytocin use during labor and delivery.Main Outcomes and MeasuresA child’s clinical diagnosis of ASD during follow-up and at age of diagnosis.ResultsAmong the cohort, 153 880 children (74.7%) were exposed to maternal LEA and 117 808 children (57.2%) were exposed to oxytocin during labor and delivery. The population of children was approximately half boys and half girls. The median (IQR) age of the mothers was 30.8 (26.8-34.5) years for those not exposed to LEA, 30.0 (25.9-33.8) years for those exposed to LEA, 30.4 (26.5-34.1) years for those unexposed to oxytocin, and 30.0 (25.9-33.9) years for those exposed to oxytocin during labor and delivery. A total of 5146 children (2.5%) had ASD diagnosed during follow-up. Oxytocin exposure was higher among LEA-exposed (67.7%) than -unexposed (26.1%) children. The ASD risk associated with LEA was independent of oxytocin exposure (HR, 1.28; 95% CI, 1.18-1.38); however, the ASD risk associated with oxytocin was not significant after adjusting for LEA exposure (HR, 1.05; 95% CI, 0.99-1.12). A significant interaction of LEA and oxytocin on child ASD risk was found (P = .02 for interaction). Compared with no exposure, HRs were 1.20 (95% CI, 1.09-1.32) for LEA alone, 1.30 (95% CI, 1.20-1.42) for both LEA and oxytocin, and 0.90 (95% CI, 0.78-1.04) for oxytocin alone.Conclusions and RelevanceThe findings of this cohort study suggest an association between maternal LEA and ASD risk in children, and the risk appeared to be further increased if oxytocin was also administered. Oxytocin exposure without LEA exposure was not associated with ASD risk in children. These findings must be interpreted with caution. Further studies are needed to replicate or refute the study results and examine biological plausibility.
Atopic dermatitis (AD) is a common inflammatory skin disorder induced by dysfunction of immune suppression sharing similar pathogenesis to autoimmune diseases. To explore the association between autoimmune diseases and AD in children, we linked the birth data from National Birth Registry with National Health Insurance Research Database. There were 1,174,941 children obtained from 2006 to 2012 birth cohort. A total of 312,329 children diagnosed with AD before 5 years old were compared to 862,612 children without AD in the control group. Conditional logistic regression was utilized to calculate adjusted odds ratio (OR) and Bonferroni-corrected confidence interval (CI) for overall significance level of 0.05. In 2006-2012 birth cohort, the prevalence rate of AD was 26.6% (95% CI 26.5, 26.7) before 5 years of age. Having parental autoimmune disease (including rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, ankylosing spondylitis, and psoriasis) was associated with a significant higher risk of children AD development. The other associated factors were maternal obstetric complications (including gestational diabetes mellitus and cervical incompetence), parental systemic diseases (including anemia, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, hyperthyroidism, and obstructive sleep apnea), and parental allergic disease (including asthma and AD). The subgroup analysis showed similar results between children's sexes. Moreover, maternal autoimmune disease had higher impact on the risk of developing AD in the child compared with paternal autoimmune disease. In conclusion, parental autoimmune diseases were found to be related to their children's AD before 5 years old.
