Development and Validation of a Nomogram for Predicting Obstructive Sleep Apnea Severity in Children.

Purpose: The clinical presentation of Obstructive Sleep Apnea (OSA) in children is insidious and harmful. Early identification of children with OSA, particularly those at a higher risk for severe symptoms, is essential for making informed clinical decisions and improving long-term outcomes. Therefore, we developed and validated a risk prediction model for severity in Chinese children with OSA to effectively identify children with moderate-to-severe OSA in a clinical setting. Patients and Methods: From June 2023 to September 2023, we retrospectively analyzed the medical records of 367 Children diagnosed with OSA through portable bedside polysomnography (PSG). Predictor variables were screened using the least absolute shrinkage and selection operator (LASSO) and logistic regression techniques to construct nomogram to predict the severity of OSA. Receiver operating characteristic curve (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to determine the discrimination, calibration, and clinical usefulness of the nomogram. Results: A total of 367 children with a median age of 84 months were included in this study. Neck circumference, ANB, gender, learning problem, and level of obstruction were identified as independent risk factors for moderate-severe OSA. The consistency indices of the nomogram in the training and validation cohorts were 0.841 and 0.75, respectively. The nomogram demonstrated a strong concordance between the predicted probabilities and the observed probabilities for children diagnosed with moderate-severe OSA. With threshold probabilities ranging from 0.1 to 1.0, the predictive model demonstrated strong predictive efficacy and yielded improved net benefit for clinical decision-making. ROC analysis was employed to classify the children into high and low-risk groups, utilizing the Optimal Cutoff value of 0.39. Conclusion: A predictive model using LASSO regression was developed and validated for children with varying levels of OSA. This model identifies children at risk of developing OSA at an early stage.

The Effects of Orofacial Myofunctional Therapy on Children with OSAHS's Craniomaxillofacial Growth: A Systematic Review.

Orofacial myofunctional therapy (OMT) is one of the therapeutic methods for neuromuscular re-education and has been considered as one of the auxiliary methods for obstructive sleep apnea hypopnea syndrome (OSAHS) and orthodontic treatment. There is a dearth of comprehensive analysis of OMT's effects on muscle morphology and function. This systematic review examines the literature on the craniomaxillofacial effects of OMT in children with OSAHS. This systematic analysis was carried out using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards, and the research was scanned using PICO principles. A total of 1776 articles were retrieved within a limited time, with 146 papers accepted for full-text perusing following preliminary inspection and 9 of those ultimately included in the qualitative analysis. Three studies were rated as having a severe bias risk, and five studies were rated as having a moderate bias risk. Improvement in craniofacial function or morphology was observed in most of the 693 children. OMT can improve the function or morphology of the craniofacial surface of children with OSAHS, and its effect becomes more significant as the duration of the intervention increases and compliance improves. In the majority of the 693 infants, improvements in craniofacial function or morphology were seen. The function or morphology of a kid's craniofacial surface can be improved with OMT, and as the duration of the intervention lengthens and compliance rises, the impact becomes more pronounced.

Apicidin attenuates memory deficits by reducing the Aß load in APP/PS1 mice.

AIMS: Amyloid beta (Aß) is an important pathological feature of Alzheimer's disease (AD). A disintegrin and metalloproteinase 10 (ADAM10) can reduce the production of toxic Aß by activating the nonamyloidogenic pathway of amyloid precursor protein (APP). We previously found that apicidin, which is a histone deacetylase (HDAC) inhibitor, can promote the expression of ADAM10 and reduce the production of Aß in vitro. This study was designed to determine the potential of apicidin treatment to reverse learning and memory impairments in an AD mouse model and the possible correlation of these effects with ADAM10. METHODS: Nine-month-old APP/PS1 mice and C57 mice received intraperitoneal injections of apicidin or vehicle for 2 months. At 11 months of age, we evaluated the memory performance of mice with Morris water maze (MWM) and context fear conditioning tests. The Aß levels were assessed in mouse brain using the immunohistochemical method and ELISA. The expression of corresponding protein involved in proteolytic processing of APP and the phosphorylation of tau were assessed by Western blotting. RESULTS: Apicidin reversed the deficits of spatial reference memory and contextual fear memory, attenuated the formation of Aß-enriched plaques, and decreased the levels of soluble and insoluble Aß40/42 in APP/PS1 mice. Moreover, apicidin significantly increased the expression of ADAM10, improved the level of sAPPα, and reduced the production of sAPPß, but did not affect the levels of phosphorylated tau in APP/PS1 mice. CONCLUSION: Apicidin significantly improves the AD symptoms of APP/PS1 mice by regulating the expression of ADAM10, which may contribute to decreasing the levels of Aß rather than decreasing the phosphorylation of tau.

AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.

AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer disease (AD) by generating the toxic ß-amyloid peptide (Aß). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aß in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aß, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.

Synergistic effect of combination chemotherapy with praziquantel and DW-3-15 for Schistosoma japonicum in vitro and in vivo.

BACKGROUND: Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. In our previous studies, we found that the patented compound DW-3-15 (patent no. ZL201110142538.2) displayed significant and stabilized antiparasitic activity through a mechanism that might be distinct from PZQ. Here, we investigated the antischistosomal efficacy of PZQ combined with DW-3-15 against schistosomula and adult worms of Schistosoma japonicum in vitro and in vivo, to verify whether there was a synergistic effect of the two compounds. METHODS: The antischistosomal efficacy of PZQ combined with DW-3-15 in comparison with an untreated control and monotherapy group against schistosomula and adult worms was assessed both in vitro and in vivo. Parasitological studies, scanning electron microscopy, combination index, and histopathological analysis were used for the assessment. RESULTS: The results showed significantly reduced viability of schistosomes, achieving 100% viability reduction for juveniles and males by combination chemotherapy using PZQ together with DW-3-15 in vitro. The combination index was 0.28, 0.27, and 0.53 at the higher concentration of PZQ combined with DW-3-15 against juveniles, males, and females, respectively, indicating that the two compounds display strong synergism. Scanning electron microscopy observations also demonstrated that the compound combination induced more severe and extensive alterations to the tegument and subtegument of S. japonicum than those with each compound alone. In vivo, compared with the single-compound-treated group, the group treated with the higher-dose combination demonstrated the best schistosomicidal efficacy, with significantly reduced worm burden, egg burden, and granuloma count and area, which was evident against schistosomula and adult worms. CONCLUSIONS: Our study provides a potential novel chemotherapy for schistosomiasis caused by S. japonicum. It would improve the antischistosomal effect on schistosomula and adult worms of S. japonicum, and decrease individual dosages.