METHODS: The effects of mitragynine on the P-gp regulation were investigated in human brain capillary endothelial cells (hCMEC/D3) using molecular docking and dynamic simulation and an optimized bidirectional transport assay, respectively. Repeated-dose treatment and neurotoxicity assessment were carried out using a blood-brain barrier model and polimerase chain reaction (PCR) array.
KEY FINDINGS: Mitragynine inhibits the P-gp transport activity via binding onto the nucleotide-binding domain site and forms a stable interaction with the P-gp protein complex. Nontoxic concentrations of mitragynine (<4 μM) and substrate drugs (0.001 μM) in the cells significantly enhanced endothelial cell permeability and elicited signs of neurotoxicity in PC-12 cells.
CONCLUSIONS: Mitragynine is likely a P-gp inhibitor, hence concurrent administration of kratom products with P-gp substrates may lead to clinically significant interactions and neurotoxicity.
METHODS: A retrospective review was conducted on 99 women who underwent Surelift System surgery for advanced POP Stage III and IV between July 2018 to January 2020. Objective evaluation included Pelvic Organ Prolapse Quantification (POP-Q), multichannel urodynamic (UDS), and introital 2D ultrasonographic measurement. Subjective evaluation uses validated questionnaires of Incontinence Impact Questionnaire-7(IIQ-7), Urogenital Distress Inventory-6(UDI-6), Pelvic Organ Prolapse Distress Inventory 6(POPDI-6), Colorectal Anal Distress Inventory-8(CRADI-8) and Pelvic organ prolapse/ Urinary Incontinence Sexual Questionnaire (PISQ-12). Outcomes were examined at 3 months, yearly and at 3 years postoperative. Secondary outcome included de novo or persistent urodynamic stress incontinence (USI) and surgical complications.
RESULTS: Eighty-five women were included in the final analysis. At 3 years postoperative, the objective cure rate was 94.1 % and subjective cure rate of 91.8 %. Ultrasonography revealed initial mesh elongation and thickening at first year, resolving by the third year, while the distance between the bladder neck and mesh remained stable. Significant improvement in POP-Q components (Aa,Ba,C,Ap,Bp and TVL of p
METHODS: We report on a series of 31 patients who underwent dry MT with artificial pneumothorax induction using Veress needle under thoracic ultrasonography (TUS) guidance. A procedure was considered technically successful if it met all the following criteria: successful pneumothorax induction, allowing smooth insertion of the semi-rigid thoracoscope; absence of immediate significant procedural-related complications; and no delayed complications such as persistent air leaks, defined as leakage lasting more than 5 days necessitating extended chest tube placement.
RESULTS: Complete pneumothorax induction was achieved in 25 cases, resulting in an 80.6% technical success rate; however, biopsies were successfully performed in all cases. The most frequent histopathological diagnoses were malignancy (n=9, 29.0%), followed by inflammatory pleuritis (n=8, 25.8%) and tuberculosis (n=8, 25.8%). No procedural complications were reported.
CONCLUSION: These results indicate that TUS-guided dry MT utilizing a Veress needle is technically feasible and secure when performed by experienced MT practitioners in TUS.
METHODS: Fifty-one (51) participants (36 males and 15 females, 38.84 ± 11.73 years) with overweight and obesity (BMI = 29.75 ± 5.04 kg/m2) were recruited and monitored before and at the end of the commencement of the four-week IF. Six healthy subjects with normal BMI (21.4 ± 2.20 kg/m2) were recruited only to standardize the reference for normal levels of gene expressions. At the two time points, anthropometric, biochemical, and dietary assessments were performed, and LAMP2, LC3B, ATG5, and ATG4D gene expressions were assessed using qRT-PCR on RNA extracted from whole blood samples.
RESULTS: At the end of IF, and compared to the pre-fasting levels, the relative gene expressions among participants with overweight/obesity were significantly increased for the three autophagy genes LAMP2, LC3B, and ATG5, with increments of about 4.2 folds, 1.9-fold, and 1.4-fold, respectively. In contrast, the increase in the ATG4D gene was not significant. Concomitantly, significant decreases were found in body weight, BMI, fat mass, body fat percent, hip and waist circumferences, LDL, IL-6, and TNF-a (P
AIM OF THE STUDY: To investigate the antineuropathic and antinociceptive activities of Trifolium resupinatum leaves essential oil (TREO) in male Wistar rats, as well as to explore the potential mechanisms of action.
MATERIALS AND METHODS: The antinociceptive activity of TREO and its main constituents, quercetin (Qc) was assessed using the formalin-induced paw licking test. Moreover, the potential mechanisms of antinociception were evaluated through various competitive and non-competitive antagonisms. Additionally, the antineuropathic potential was investigated using the cervical spinal cord hemi-contusion (CCS) model, and the role of phosphorylated Stat-3 was analyzed using Western blotting.
RESULTS: TREO exerted significant antinociceptive activity (P
AIMS: The PEACH in Asia pilot study aimed to test the feasibility of a standardized protocol for investigating SCEs in anesthesia practices across Asia, evaluate the data acquisition processes, and determine the sample size for a main study.
METHODS: This multicenter pilot study involved ten institutions across nine Asian countries, including children from birth to 15 years undergoing diagnostic or surgical procedures. Data on SCEs were collected using standardized definitions. The study assessed the feasibility and estimated the sample size needed for the main study.
RESULTS: The pilot study enrolled 330 patients, with a SCE incidence of 12.4% (95% CI: 9.2-16.4%). Respiratory events were observed in 7.0% of cases, cardiovascular instability in 4.9%, and drug errors in 0.6%. Based on the SCE incidence observed in the pilot study, the estimated sample size required for the main study is at least 10 958 patients. The pilot study demonstrated the feasibility of the study protocol but identified several challenges, particularly in resource-limited settings. These challenges included a significant burden associated with data collection, technical issues with electronic case report forms (e-CRFs), variability in patient enrollment across institutions (ranging from 4 to 86 patients per site), and incomplete data acquisition (24.8% of height data and 9.7% of disposition data were missing).
CONCLUSIONS: The PEACH in Asia pilot study successfully validated a protocol for investigating SCEs in pediatric anesthesia across Asia. Addressing the challenges identified in the pilot study will be crucial for generating robust data to improve pediatric anesthesia safety in the region. Key issues to address include improving data collection methods, resolving e-CRF technical difficulties, and ensuring consistent institutional support.
METHODS: This is a retrospective cohort study of 9-year-old Singaporean children. The primary outcome was the success of prophylactic management of asymptomatic DE premolars with a single session of tubercle grinding and composite overlay, as determined by the absence of clinical signs or symptoms. The factors associated with survival of DE premolars treated were evaluated using Cox proportional hazard regression.
RESULTS: The prevalence of DE among Singaporean children was 7.1% (12,677/178,801). DE premolars were more prevalent among females (56.1%) and those of Chinese ethnicity (87.1%). At the tooth level, 26,875 asymptomatic DE premolars were prophylactically managed with tubercle grinding and composite overlay and 2471 DE premolars did not receive any intervention. The mean review period was 46.2 ± 20.2 months. The success rate for DE premolars that received the intervention was significantly higher (p
METHODS: Data from the medical records of patients who were stepped up to FP/SAL PRD were extracted retrospectively at baseline and follow-up (between 3 and 6 months after stepping up to FP/SAL PRD). The primary endpoint was the percentage of patients with improvement in asthma control assessed via the Asthma Control Test (ACT). Secondary endpoints included safety and the percentage of patients with moderate and severe exacerbations. Additionally, patient-reported use of reliever medication, systemic corticosteroids, emergency department visits, or hospitalization was also analyzed.
RESULTS: One hundred twenty patients with uncontrolled asthma who were stepped up to FP/SAL PRD were enrolled in the study. Of these, 76 (63.3%) patients were on prior budesonide/formoterol PRN, and 44 (36.7%) were on prior ICS with SABA PRN treatment. After stepping up to FP/SAL PRD with a mean follow-up of 5.8 months, 110 (91.7%) patients achieved asthma control at the follow-up visit (p