AIM OF THE STUDY: This study aimed to investigate the detoxification effects and potential mechanism of action of spironolactone on triptolide-induced hepatotoxicity to provide a potential detoxifying strategy for triptolide, thereby promoting the safe applications of T. wilfordii preparations in clinical settings.
MATERIALS AND METHODS: Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and crystal violet staining. Nuclear fragmentation was visualized using 4',6-diamidino-2-phenylindole (DAPI) staining, and protein expression was analyzed by Western blotting. The inhibitory effect of spironolactone on triptolide-induced hepatotoxicity was evaluated by examining the effects of spironolactone on serum alanine aminotransferase and aspartate aminotransferase levels, as well as liver pathology in a mouse model of triptolide-induced acute hepatotoxicity. Furthermore, a survival assay was performed to investigate the effects of spironolactone on the survival rate of mice exposed to a lethal dose of triptolide. The effect of spironolactone on triptolide-induced global transcriptional repression was assessed through 5-ethynyl uridine staining.
RESULTS: Triptolide treatment decreased the cell viability, increased the nuclear fragmentation and the cleaved caspase-3 levels in both hepatoma cells and hepatocytes. It also increased the alanine aminotransferase and aspartate aminotransferase levels, induced the hepatocyte swelling and necrosis, and led to seven deaths out of 11 mice. The above effects could be mitigated by pretreatment with spironolactone. Additionally, molecular mechanism exploration unveiled that spironolactone inhibited triptolide-induced DNA-directed RNA polymerase II subunit RPB1 degradation, consequently increased the fluorescence intensity of 5-ethynyl uridine staining for nascent RNA.
CONCLUSIONS: This study shows that spironolactone exhibits a potent detoxification role against triptolide hepatotoxicity, through inhibition of RPB1 degradation induced by triptolide and, in turn, retardation of global transcriptional inhibition in affected cells. These findings suggest a potential detoxification strategy for triptolide that may contribute to the safe use of T. wilfordii preparations.
METHODS: In this phase 3a trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we randomly assigned children (6 to <12 years of age) with obesity, in a 2:1 ratio, to receive either once-daily subcutaneous liraglutide at a dose of 3.0 mg (or the maximum tolerated dose) or placebo, plus lifestyle interventions. The primary end point was the percentage change in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters). The confirmatory secondary end points were the percentage change in body weight and a reduction in BMI of at least 5%.
RESULTS: A total of 82 participants underwent randomization; 56 were assigned to the liraglutide group and 26 to the placebo group. At week 56, the mean percentage change from baseline in BMI was -5.8% with liraglutide and 1.6% with placebo, representing an estimated difference of -7.4 percentage points (95% confidence interval [CI], -11.6 to -3.2; P<0.001). The mean percentage change in body weight was 1.6% with liraglutide and 10.0% with placebo, representing an estimated difference of -8.4 percentage points (95% CI, -13.4 to -3.3; P = 0.001), and a reduction in BMI of at least 5% occurred in 46% of participants in the liraglutide group and in 9% of participants in the placebo group (adjusted odds ratio, 6.3 [95% CI, 1.4 to 28.8]; P = 0.02). Adverse events occurred in 89% and 88% of participants in the liraglutide and placebo groups, respectively. Gastrointestinal adverse events were more common in the liraglutide group (80% vs. 54%); serious adverse events were reported in 12% and 8% of participants in the liraglutide and placebo groups, respectively.
CONCLUSIONS: Among children (6 to <12 years of age) with obesity, treatment with liraglutide for 56 weeks plus lifestyle interventions resulted in a greater reduction in BMI than placebo plus lifestyle interventions. (Funded by Novo Nordisk; SCALE Kids ClinicalTrials.gov number, NCT04775082.).
METHODS: This randomized controlled trial was conducted at Montaserieh Hospital, Mashhad, Iran, involving 72 patients undergoing hemodialysis. Participants were randomly assigned to either the intervention group, receiving a custom-designed recreational therapy mobile app (including music, comedy, exercise, and educational content), or the control group, receiving standard care. The trial was registered with the Iranian Registry of Clinical Trials (IRCT20220803055608N1). Outcome assessors and statisticians were blinded to minimize bias. Sample size was calculated for an expected effect size of 0.90 with 80% power, resulting in 36 participants per group, adjusted for a 6% attrition rate. Depression levels were assessed using the Beck Depression Inventory-II (BDI-II) at baseline and after a 30-day intervention.
RESULTS: A total of 72 patients (36 per group) completed the analysis. The intervention group showed a significant decrease in depression scores compared to the control group (mean BDI-II score reduction: intervention group = 10.3 ± 4.1, control group = 4.6 ± 3.8; p
DISCUSSION: Creating an inclusive assessment culture is important for equitable education, even if priorities for inclusion might differ between contexts. We recognise challenges in the enactment of inclusive assessment, namely, the notion of lowering standards, harming reliability and robustness of assessment design and inclusion as a poorly defined and catchall term. Importantly, the lack of awareness that inclusion means recognising intersectionality is a barrier for well-designed inclusive assessments. This is why we offer considerations for HPE practitioners that can guide towards a unified direction of travel for inclusive assessments. This article highlights the importance of contextual prioritisation and initiatives to be considered at the global level to national, institutional, programme and the individual level. Utilising experience and literature from undergraduate, higher education contexts, we offer considerations with applicability across the assessment continuum.
CONTEXT: In this state of science paper, we were set the challenge of providing cross-cultural viewpoints on inclusive assessment. In this discursive article, we focus on inclusive assessment within undergraduate health professions education whilst looking to the wider higher education literature, since institutional policies and procedures frequently drive assessment decisions and influence the environment in which they occur. We explore our experiences of working in inclusive assessment, with the aim of bridging and enhancing practices of inclusive assessments for HPE. Unlike other articles that juxtapose views, we all come from the perspective of supporting inclusive assessment. We begin with a discussion on what inclusive assessment is and then describe our contexts as a basis for understanding differences and broadening conversations. We work in the United Kingdom, Australia and Malaysia, having undertaken research, facilitated workshops and seminars on inclusive assessment nationally and internationally. We recognise our perspectives will differ as a consequence of our global context, institutional culture, individual characteristics and educational experiences. (Note that individual characteristics are also known as protected characteristics in some countries). Then, we outline challenges and opportunities associated with inclusive assessment, drawing on evidence within our contexts, acknowledging that our understanding of inclusive assessment research is limited to publications in English and currently tilted to publications from the Global North. In the final section, we then offer recommendations for championing inclusion, focussing firstly on assessment designs, and then broader considerations to organise collective action. Our article is unapologetically practical; the deliberate divergence from a theoretical piece is with the intent that anyone who reads this paper might enact even one small change progressing towards more inclusive assessment practices within their context.
RESULTS: Lipase CN-TL (from Thermomyces lanuginosus) was selected through glycerolysis reaction and molecular docking to catalyze the glycerolysis reaction. Optimizing the immobilization method by covalently binding CN-TL to poly(ethylene glycol) diglycidyl ether (PEGDGE)-preactivated resin LX-201A resulted in the preparation of the immobilized enzyme TL-PEGDGE-LX. The immobilized enzyme retained over 90% of its initial activity after five consecutive reactions, demonstrating excellent reusability. The DAG content in the product remained at 84.8% of its initial level, further highlighting the enzyme's potential for reusability and its promising applications in the food and oil industries.
CONCLUSIONS: The immobilized lipase TL-PEGDGE-LX, created by covalently immobilizing lipase CN-TL on PEGDGE-preactivated carriers, demonstrated broad applicability and excellent reusability. This approach offers an economical and convenient immobilization strategy for the enzymatic glycerolysis production of DAG. © 2024 Society of Chemical Industry.
METHODS: This cross-sectional study on children aged 12-14 years collected data on the exposure (decayed tooth index), outcome (school examination results), and mediator (school absence due to toothache, and oral health impact on sleep and study performances using the Child-Oral Impact on Daily Performance instrument) variables. It used mediation analysis to examine the indirect effects of a single and two serial mediators using model 4 (caries → mediator → AP) and model 6 (caries → mediator 1 → mediator 2 → AP), respectively, in PROCESS macro add-on software in IBM SPSS v24. Analyses were carried out separately for boys and girls at a 5% significance level.
RESULTS: In model 4, school absence due to toothache (boys: 95% CI: 0.42, 1.01; girls: 95% CI: 0.58, 0.98), and impacted sleep (95% CI: 0.13, 0.41; 95% CI: 2.17, 13.03), and study (95% CI: 0.05, 0.42; 95% CI: 0.54, 0.94) performance were significant single mediators in both sexes. In model 6, school absence due to toothache and impacted sleep activity (boys: 95% CI: 0.02, 0.29 and girls: 95% CI: 1.37, 12.81), and school absence due to toothache and impacted study activity (girls: 95% CI: 1.37, 12.81) were significant two serial-mediators.
CONCLUSION: This study provides empirical evidence showing that dental caries and toothache can impact academic performance as they disrupt sleep and study performances to influence the learning and cognition process. The finding bridges the understanding of the mechanism underpinning the relationship and thus, further emphasizes the importance of caries prevention in children with high caries risk for improving their health outcomes and educational experience.
RESULTS: Scoby from black, green and oolong tea kombucha fermentation was assessed for its hydrocolloid effects in mango jam-making through evaluation of physicochemical, textural and sensory characteristics. Quality of jam was significantly improved with water activity reduction up to 22.22% to 0.679, moisture content reduction up to 37.06% to 19.92%, and a pH drop up to 5.9% to 3.19 with the use of 20 to 100 g kg-1 scoby. In colour analysis, presence of scoby led to a brighter jam due to higher L * values from 30.98 to a range of 31.82 to 40.83. Texture of jam with scoby gave higher gel strength and adhesiveness, with the most prominent effects from the black tea kombucha. Overall acceptability in sensory test scoring was above 70% on a nine-point hedonic scale with the 40 g kg-1 green tea kombucha scoby jam chosen as the most preferred.
CONCLUSION: Scoby gave significant contributions to jam stability, appearance and texture, showing potential as a clean-label food ingredient. © 2024 Society of Chemical Industry.
METHODS: We critically review the arguments proposed by proponents of antidepressant deprescribing in the context of the evidence-base for the treatment of depression.
RESULTS: Proponents of deprescribing do not address the substantive issues of whether inappropriate prescribing has been demonstrated, and when prescribing is needed. Their arguments for deprescribing are rebutted in this context.
CONCLUSIONS: Whether or not to deprescribe antidepressant medication needs to take into consideration the risk-benefit profile of the decision, the responsibility for which needs to be shared and based on the context of the patient's depression, their preferences, experiences and perspectives.
PURPOSE: This work aimed to ensure brain availability of nalbuphine via the nasal route.
METHOD: Chitosan based nanoparticles loaded with nalbuphine were successfully prepared using ionic gelation method and characterised.
RESULT: SEM results revealed that the nanoparticles were spherical in shape, with an average size of 192.4 ± 11.6 nm. Zeta potential and entrapment efficiency was found 32.8 mV and 88.43 ± 7.75%, respectively. The X-ray diffractometry and DSC results unravel a profound understanding on the physical and thermal characteristics. The in-vitro release of nalbuphine from the nanoparticles was biphasic, with an initial burst release followed by a slow-release profile. In-vitro cell study on HEK-293 cells and microscopic images of brain tissue confirmed the safety profile of formulation. In-vivo efficacy studies on animal confirmed the effectiveness of developed intranasal formulation as compared to the standard therapy. The in-vivo pharmacokinetic studies showed that the prepared nanoparticles were able to efficiently deliver nalbuphine to the brain in comparison to the other body organs. Gamma scintigraphy images showed retention of the drug in the brain. Furthermore, the efficacy studies confirmed that the nanoparticles were found significantly more effective than the marketed formulation in pain management.
METHODS: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). We assessed the associations of FOXO1 transcript expression levels in peripheral blood mononuclear cells (PBMC) with AR phenotype, total nasal symptom score (TNSS), and SNP genotype in a sub-cohort of n = 658 individuals from the SMCSGES population. Associations of FOXO1 SNPs with AR were assessed in a cohort of n = 5,072 individuals from the SMCSGES population. In vitro promoter luciferase assay was used to evaluate the effect of AR-associated SNPs on FOXO1 promoter activity.
RESULTS: FOXO1 transcript expression in PBMC was significantly associated with the risk of AR (p < 0.05) and TNSS among AR patients (p < 0.0001). We identified a significant association between tag-SNPs rs9549246 and FOXO1 transcript expression in PBMC from the SMCSGES sub-cohort and the multiethnic eQTLGen consortium (false discovery rate-adjusted p < 0.05). The minor allele "A" of tag-SNP rs9549246 was significantly associated with a higher risk of AR (p = 0.04422, odds ratio = 1.21, 95% confidence interval = 1.01-1.45) in the SMCSGES genotyping cohort (n = 5,072). In vitro luciferase assay showed the minor allele "A" of rs35594717 (tagged by rs9549246) was significantly associated with a higher FOXO1 promoter activity (p < 0.05).
CONCLUSION: FOXO1 transcript expression in PBMC has a strong association with the risk and symptom severity of AR. Genetic variants tagged by rs9549246 were shown to affect the expression of FOXO1 and contribute to the development of AR in the SMCSGES population.
METHODS: A total of 30 Longissimus thoracis samples from three sows were stored under vacuum conditions at 4°C±2°C for 27 days to acquire data. The freshness prediction model for pork loin employed partial least squares regression (PLSR) with Monte Carlo data augmentation. Total bacterial count (TBC) and volatile basic nitrogen (VBN), which exhibited increases correlating with metabolite changes during storage, were designated as freshness indicators. Metabolic contents of the sample were quantified using nuclear magnetic resonance.
RESULTS: A total of 64 metabolites were identified, with 34 and 35 showing high correlations with TBC and VBN, respectively. Lysine and malate for TBC (R2 = 0.886) and methionine and niacinamide for VBN (R2 = 0.909) were identified as the main metabolites in each indicator by Model 1. Model 2 predicted main metabolites using HSI spectral data. Model 3, which predicted freshness indicators with HSI spectral data, demonstrated high prediction coefficients; TBC R2p = 0.7220 and VBN R2p = 0.8392. Furthermore, the combination model (Model 4), utilizing HSI spectral data and predicted metabolites from Model 2 to predict freshness indicators, improved the prediction coefficients compared to Model 3; TBC R2p = 0.7583 and VBN R2p = 0.8441.
CONCLUSION: Combining HSI spectral data with metabolites correlated to the meat freshness may elucidate why certain HSI spectra indicate meat freshness and prove to be more effective in predicting the freshness state of pork loin compared to using only HSI spectral data.
METHODS: The model used the best available data inputs, with uncertainty considered using probabilistic sensitivity analysis. We additionally assessed the impact of neonatal jaundice (NNJ) on the economic benefits of increasing exclusive breastfeeding rates.
RESULTS: During 2010-2019, five admissions for GE and three admissions for LRTI per 1000 births would have been prevented in the first year of life if the exclusive breastfeeding rate at 4 months increased from the actual levels (~15-30%) to 50%, resulting in annual healthcare cost savings of USD1.05 (95% CI 1.03-1.07) million/year. The cost saving would reach USD1.89 (95% CI 1.86-1.92) million/year if the exclusive breastfeeding rate at 4 months increase to 70%. However, if higher NNJ admissions during 7-90 days related to more exclusive breastfeeding are considered, the cost saving would reduce by 60%.
CONCLUSION: Our findings can guide policymakers in allocating budget and resources for breastfeeding promotion in Hong Kong. The prevention of unnecessary NNJ admissions would maximise the economic benefits of exclusive breastfeeding at 4 months.