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Trunk rotation, spinal deformity and appearance, health-related quality of life, and treatment adherence: Secondary outcomes in a randomized controlled trial on conservative treatment for adolescent idiopathic scoliosis
Objective To explore secondary outcomes at endpoint comparing treatments with adequate self-mediated physical activity combined with either night-time brace (NB), scoliosis-specific exercise (SSE), or adequate self-mediated physical activity alone (PA) in Adolescent Idiopathic Scoliosis (AIS). Methods A longitudinal, prospective, multicenter RCT was conducted including 135 girls/boys, Cobb angle 25–40°, 9–17 years, and ≥1-year remaining growth were randomly allocated into NB, SSE, or PA group. Endpoint was curve progression of ≤6° (success) at skeletal maturity or >6° (failure). Outcomes included angle of trunk rotation (ATR), major curve Cobb angle, Spinal Appearance Questionnaire (pSAQ), Scoliosis Research Society-22r (SRS-22r), EQ-5Dimensions Youth 3Levels (EQ-5D-Y-3L), and EQ-Visual-Analogue-Scale (EQ-VAS), adherence to treatment and International Physical Activity Questionnaire (IPAQ-SF). Results At endpoint, 122 patients were analyzed per protocol, mean age 12.7 (±1.4) years, and mean Cobb angle 31° (±4.3). A significant difference in change for ATR favored NB group compared to SSE group -2.0º (95% CI -3.7 to -0.3). EQ-5D-Y-3L dimensions showed a significant difference in change with decrease in mobility (p=0.031), and usual activities (p=0.003) for SSE compared to NB and PA groups. Treatment adherence was adequate but slightly better in NB and PA groups compared to SSE on self-report (p=0.012), and health care provider (HCP) report was better in PA compared to SSE group (p=0.013). Higher motivation and capability explained 53% of the variability and gave better odds for higher adherence (OR = 11.12, 95% CI = 1.5 to 34.4; OR = 7.23, 95% CI = 2.9 to 43.3), respectively. Conclusions Night-time brace, scoliosis-specific exercise or physical activity interventions for adolescents with idiopathic scoliosis showed small differences between groups in trunk rotation, spinal deformity and appearance, health-related quality of life, and treatment adherence but not likely reaching clinical relevance.
Comprehensive analysis of TRIM56’s prognostic value and immune infiltration in Pan-Cancer
Elucidating the structural dynamics induced by active site mutations in 3C protease of foot-and-mouth disease virus
The viral replication of foot-and-mouth disease virus (FMDV) and other picornaviruses primarily depends on the successful processing of a polyprotein precursor by the enzyme 3C protease (3Cpro) at specific sites. The crucial role of 3Cpro in viral replication and pathogenesis makes it a potential target for developing novel therapeutics against foot-and-mouth disease. The β-ribbon region (residues 138–150) containing the active site residues (C142) in 3Cpro is found to be conserved and contributes significantly to substrate specificity. Moreover, experimental reports suggest that mutations at position 142, particularly C142S and C142L, exhibit different functional activities. However, the intrinsic dynamics and conformational changes induced by active-site mutations of 3Cpro remain unclear, limiting the development of novel inhibitors of 3C protease. Accordingly, we carried out molecular dynamics (MD) simulations with multiple replicates for both the WT and mutants of 3Cpro. The observed results suggest that the C142S mutant induces substantial structural transitions compared to the WT and C142L. In contrast, the essential dynamics of the mutants significantly varied from those of the WT 3Cpro. Moreover, cross-correlation analysis revealed a similar pattern of anti-correlation between the amino acid residues of the WT and C142L mutant complexes. Analysis of the betweenness centrality of the WT and the mutants from the residue interaction networks revealed common residues for intra-residual signal propagation. The results from our study suggest that the active site mutant C142S may induce conformational changes, which can cause the β-ribbon region to bend towards the catalytic pocket and inhibit the enzymatic activity. C142L substitution may also alter the β-ribbon region conformation, which may impact the substrate binding process during proteolysis, as reported in previous studies. These results can provide a better understanding of the conformational dynamic behavior of 3Cpro active-site mutants and may assist in developing potential inhibitors against foot-and-mouth disease.
Potential non-invasive biomarkers of chronic sleep disorders identified by salivary metabolomic profiling among middle-aged Japanese men
Cost-utility analysis of botulinum toxin type A versus oral drug treatment in patients with severe blepharospasm in Thailand
Background Blepharospasm is a chronic facial movement disorder affecting a person’s ability to work, causing depression, pain, and a reduced quality of life (QoL). Botulinum toxin type A (BoNT-A) treatment can improve these conditions; however, its cost remains a significant barrier for inclusion of this indication into the Thai National List of Essential Medicine. Objectives This study aimed to assess the cost-effectiveness of onabotulinumtoxinA (onaBoNT-A) and abobotulinumtoxinA (aboBoNT-A) treatment compared to oral medication treatment in patients with severe blepharospasm from a societal perspective. Methods A cost-utility analysis using a two-part model was conducted to analyze lifetime costs and quality-adjusted life-years (QALYs). Inputs were mainly obtained from real-world evidence of 159 Thai patients with blepharospasm. Costs and outcomes were discounted at 3% annually and presented as 2023 value. Incremental cost-effectiveness ratios (ICERs) were estimated. Deterministic and probabilistic sensitivity analyses were also conducted. Results In comparison to standard oral medication, both onaBoNT-A and aboBoNT-A incurred greater lifetime cost (3,055 USD, 2,889 USD vs 1,926 USD) while gaining additional QALYs (6.94 years, 6.94 years vs 6.53 years). The estimated ICERs were 2,722 USD/QALY for onaBoNT-A and 2,323 USD/QALY for aboBoNT-A. Utility and cost of BoNT-A were important determinants in the sensitivity analysis. Conclusion Among patients with severe blepharospasm, both onaBoNT-A and aboBoNT-A were considered a cost-effective strategy under the Thai willingness to pay threshold of 4,613 USD/QALY. Having aboBoNT-A was slightly more favorable due to lower cost, using a conversion ratio of 1U of onaBoNT-A: 3U of aboBoNT-A.
Exploration and future prospects of intelligent supervision technology and system development in biological laboratories
Dynamical analysis of scabies delayed epidemic model with second-order global stability
Scabies is a highly transmitted skin disease that can affect people of all ages, especially children. According to the World Health Organization (WHO), South Asia and sub-Saharan Africa are the regions most affected. For the study of the dynamics of scabies in the population, the mathematical model is designed with delay differential equations (DDEs) for four subpopulations: unvaccinated individuals, vaccinated individuals, infected individuals, and recovered individuals. The fundamental properties of the model, such as positivity, boundedness, existence, and uniqueness, are proved. The equilibria, reproduction number, sensitivity analysis, and (Local and Global) stabilities for the second order are studied rigorously. The numerical simulations were performed to confirm the validity of their theoretical results. The study’s findings suggest delay-based modeling of scabies and the advanced stability analysis provides a better understanding of epidemic management and disease dynamics over time.
Tumor associated chromosomal instability drives colorectal adenoma to adenocarcinoma progression based on 17 year follow up evidence
TGF-β expressed by M2 macrophages promotes wound healing by inhibiting TSG-6 expression by mesenchymal stem cells
Wound healing involves the collaboration of multiple cells, including macrophages and fibroblasts, and requires the coordination of cytokines, growth factors, and matrix proteins to regulate the repair response. In this study, we investigated how M2 macrophages regulate expression of the anti-fibrotic and anti-inflammatory regulator tumor necrosis factor-α (TNF-α)-stimulated gene 6 (TSG-6) secreted by adipose tissue-derived stem cells (ASCs) during wound healing. Interleukin (IL)-4/IL-13, which is used to differentiate macrophage M2 phenotypes, increases TSG-6 in ASCs; however, M2 macrophages significantly decrease TSG-6 in ASCs. Transforming growth factor (TGF)-β expression was increased, and TNF-α expression was decreased in M2 macrophages. TGF-β inhibited IL-4/IL-13-induced ASC TSG-6 expression. In addition, TSG-6 suppressed TGF-β-triggered wound closure and fibrogenic responses in LX-2 cells. Collectively, TSG-6 inhibited wound healing, but M2 macrophage-expressed TGF-β prevented TSG-6 production from ASCs, which ultimately helped wound healing. Our results indicate that the balance of TNF-α and TGF-β levels during wound healing regulates TSG-6 production from ASCs, which may ultimately modulate the healing process. Our study findings could contribute to novel therapeutic strategies that manipulate the delicate balance between TNF-α and TGF-β to enhance wound repair and mitigate fibrosis.
Enhanced peri-implantitis management through purple-LED irradiation coupled with silver ion application and calcium phosphate gene transfection carrier coating
Abstract The aim of this study was to investigate the bactericidal effect and recovery of biocompatibility of contaminated titanium surfaces using a combination treatment involving silver, copper, or iron ion application along with 400 nm purple-LED light irradiation. Additionally, the study sought to develop a functional calcium phosphate (CaP) coating treatment on titanium surfaces following disinfection, to promote re-osseointegration. A purple-LED emitting light at 400 nm was utilized to irradiate Staphylococcus aureus suspensions and biofilms in the presence of various concentrations of silver, copper, and iron solutions for 1 min. The bactericidal effect and electron spin resonance (ESR) spectrum were subsequently evaluated. Additionally, the hydrophilicity of the titanium surface and cell viability of MC3T3-E1 cells after combination treatment with silver ion was evaluated. Furthermore, a titanium surface coating with CaP gene transfection carrier containing plasmid DNA was developed using an electric current. The activity of hard tissue formation was then evaluated both in vitro and in vivo post-treatment. The bactericidal effect of the combination treatment with silver ions was attributed to the generation of hydroxyl radicals, whereas the effects from iron and copper treatments were not radical-mediated. The silver treatment significantly restored the hydrophilicity and cell affinity of the titanium surface. Moreover, CaP coating applied via an electric current (30 µA for 5 min) enhanced hard tissue formation activity on the titanium surface in both in vitro and in vivo settings. The combination treatment utilizing silver ions and purple-LED irradiation significantly enhanced bactericidal effects by generating high levels of hydroxyl radicals. Additionally, coating the titanium surface with functionalized CaP promoted early osseointegration, suggesting a promising strategy for improving implant outcomes.
Management of acute kidney disease as part of routine clinical care in low-resource settings: The International Society of Nephrology Kidney Care Network Project
Acute Kidney Disease (AKD) commonly affects disadvantaged populations in low-resourced areas with poor access to kidney care. Here, barriers to management include a lack of AKD education alongside an inability to measure serum creatinine (SCr) to identify kidney disease. The Kidney Care Network (KCN) is a service improvement initiative which aims to implement a novel strategy for the management of AKD into routine clinical care in low- and low-middle income countries (LLMICs). The strategy includes the development of a scoring system to screen patients for risk of AKD and the use of a device to measure SCr at the point-of-care (POC). This approach is underpinned by dedicated AKD training activities for healthcare workers providing front line clinical care. We report feasibility in the implementation of the KCN approach in adults in 4 LLMICs. Between 2018–2020, 4311 patients at project sites in Bolivia, Brazil, Nepal, and South Africa were deemed at risk of kidney disease and underwent SCr testing, predominantly with the POC device. AKD was identified in 2922 (67.8%) patients. AKD was most commonly due to infections and hypovolemia, and as such was treatable by relatively simple means. Most patients with AKD were treated at the site of patient presentation, including rural primary healthcare facilities, and with early AKD identification the need for kidney replacement therapy was low. In-hospital mortality was only 2.9% and follow-up occurred at 3 months in 1865 (62.3%) patients discharged post AKD diagnosis. Hence, we show the KCN approach is a feasible and effective mechanism for improving AKD management in LLMICs.
Sensitization of common allergens and co-sensitization patterns in the Korean population
The effects and post-exercise energy metabolism characteristics of different high-intensity interval training in obese adults
Phytochemical analysis and biological study on Sinapis alba L. seeds extract incorporated with metal nanoparticles, in vitro approach
Abstract White mustard (Sinapis alba L.) seeds are the most commonly used mustard species in herbal medicine to treat a wide range of inflammatory disorders. Due to its increased bioavailability and lower toxicity, the green biosynthesis of metal nanoparticles (M-NPs) utilizing plant extract as a capping agent has been demonstrated over a number of years. Thus, the current study sought to examine the in vitro biological activity of copper oxide nanoparticles (CuO-NPs) and selenium nanoparticles (Se-NPs) that were biosynthesized using aqueous, methanolic, and petroleum ether extracts from S. alba seeds. Phytochemical and in vitro biological activities (antioxidant, scavenging, anti-diabetic, anti-acetylcholinesterase, anti-arthritic, anti-inflammatory, and cytotoxic activities) were assayed in all prepared extracts before and after being used for the biosynthesis of the M-NPs. It was found that the total methanolic extract possessed the highest biological activities compared to other native extracts. The LC-ESI-MS/MS analysis of secondary metabolites showed that the total methanolic extract contained 7 phenolic acids and 9 flavonoid aglycones. This helped find the active ingredients. We characterized 8 phenolic acid derivatives, 7 flavonoid glycosides, 4 aliphatic glucosinolates, and 3 aromatic aryl glucosinolates in the aqueous extract. Furthermore, the methanolic extract contains the highest concentrations of total polyphenols, condensed tannins, and total flavonoid compounds. The biosynthesized Se-NPs using methanolic extract showed higher in vitro biological activities compared to those of the biosynthesized CuO-NPs. The median lethal dose (LD50) showed that the biosynthesized Se-NPs using the studied extracts appeared safer compared to those of the biosynthesized CuO-NPs. The findings of this study concluded that the total methanolic extract is the most suitable bioresource for biosynthesizing Se-NPs through green nanotechnology, with higher biological efficiency in relation to its metabolite fingerprint.
Comparative statistical evaluation of greenness, blueness, and whiteness spectrophotometric methods for dexamethasone and chloramphenicol estimation
Abstract Five sustainable and validated UV spectrophotometric methods were developed for analyzing chloramphenicol (CHL) and dexamethasone sodium phosphate (DSP) in pure and ophthalmic dosage forms. CHL was detected by zero order spectra method at 292.0 nm in the range 2.00–32.00 µg/mL with limits of detection (LOD) and quantification (LOQ) of 0.96 and 2.88, respectively. DSP was analyzed using the following four techniques: Induce dual wavelength (IDW), fourier self-deconvolution (FSD), ratio difference (RD), and derivative ratio (DD1). The IDW method used at 239.0 and 254.0 nm with a linearity range of 4.00–40.00 µg/mL with LOD and LOQ values were 0.93 and 2.79, respectively. The FSD approach used at 242.0 nm, with a linearity range of 2.00–32.00 µg/mL and 0.65, 1.95 as values of LOD and LOQ, respectively. In the linearity range of 4.00–32.00 µg/mL, RD and DD1 are applied. RD is utilized at 225.0–240.0 nm, while DD1 is carried out at 249.0 nm. Values of LOD and LOQ for RD were 0.70 and 2.10 while for DD1 were 0.80 and 2.40, respectively. These methods were evaluated for their environmental sustainability and validated according to ICH guidelines, overcoming challenges like spectral overlap and collinearity. Statistical comparisons with published methods revealed no significant differences.
Remimazolam attenuated lipopolysaccharide-induced behavioral deficits and neuronal injury via activation of the Nrf2 pathway
A combined approach of evolutionary game and system dynamics for user privacy protection in human intelligence interaction
Abstract The rapid development of generative artificial intelligence (GenAI) has generated significant economic and social value, alongside risks to user privacy. For this purpose, this study investigates privacy protection in human-AI interaction by employing a combined approach of evolutionary game and system dynamics. A three-party game model was developed to analyze the interactive effects and evolution of privacy protection strategies among the government, GenAI company, and users. Sensitivity analysis through system dynamics simulations was conducted on four kinds of factors—government, company, users, and incentive mechanisms, to reveal how these factors influence the strategy choices of the three parties. The results suggest that the government’s reputation, subsidies, free-riding benefits, fines, rewards from GenAI company to users, and the cost–benefit considerations of all three parties are key factors affecting strategic decisions. Moderate fine and subsidy policies can effectively promote privacy protection, with subsidy policies proving to be more effective than penalty policies. This paper provides theoretical support and decision-making guidance for balancing technological development and privacy protection in human–AI interaction, contributing to the regulated and orderly development of Generative Artificial Intelligence.