Long-term low-dose lamotrigine for paroxysmal kinesigenic dyskinesia: a two-year investigation of cognitive function in children.

Objective: While low-dose lamotrigine has shown effectiveness in managing paroxysmal kinesigenic dyskinesia (PKD) in pediatric populations, the cognitive consequences of extended use are yet to be fully elucidated. This study seeks to assess the evolution of cognitive functions and the amelioration of attention deficit and hyperactivity disorder (ADHD) symptoms following a two-year lamotrigine treatment in children. Methods: This investigation employed an open-label, uncontrolled trial design. Between January 2008 and December 2021, thirty-one participants, ranging in age from 6.5 to 14.1 years, were enrolled upon receiving a new diagnosis of PKD, as defined by the clinical diagnostic criteria set by Bruno in 2004. Comprehensive evaluation of PRRT2 variants and 16p11.2 microdeletion was achieved using whole-exome sequencing (WES) and bioinformatics analysis of copy number variant (CNV) for all subjects. Immediately after diagnosis, participants commenced treatment with low-dose lamotrigine. Cognitive function was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR) at baseline and after 2 years, with ADHD diagnoses and symptom severity simultaneously assessed by experts in accordance with the DSM-IV diagnostic criteria for ADHD and the ADHD Rating Scale-IV (ADHD-RS-IV). Results: Initially, twelve out of 31 patients (38.7%) presented with comorbid ADHD. The latency to treatment initiation was notably longer in PKD patients with ADHD (30.75 ± 12.88 months) than in those without ADHD (11.66 ± 9.08 months), t = 4.856, p<0.001. Notably, patients with a latency exceeding 2 years exhibited a heightened risk for comorbid ADHD (OR = 4.671, P=0.015) in comparison to those with shorter latency. Out of the cohort, twenty-five patients saw the clinical trial to its completion. These individuals demonstrated a marked elevation in WISC-CR scores at the 2-year mark relative to the outset across FSIQ (baseline mean: 108.72 ± 10.45 vs 24 months: 110.56 ± 10.03, p=0.001), VIQ (baseline mean: 109.44 ± 11.15 vs 24 months: 110.80 ± 10.44, p=0.028), and PIQ domains (baseline mean: 106.52 ± 9.74 vs 24 months: 108.24 ± 9.38, p=0.012). Concurrently, a substantial mitigation was observed in ADHD inattention at 2 years compared to baseline (p<0.001), with an average total subscale scores decrement from 9.04 ± 4.99 to 6.24 ± 4.05. Conclusion: Prolonged duration of untreated PKD in children may elevate the risk of ADHD comorbidity. Notably, following a 2-year lamotrigine regimen, enhancements were observed in both cognitive test outcomes and ADHD symptomatology.

Mechanisms underlying palmitic acid-induced disruption of locomotor activity and sleep behavior in Drosophila.

The globally prevalent of sleep disorders is partly attributed to unhealthy dietary habits. This study investigated the underlying mechanisms of elevated palmitic acid (PA) intake on locomotor activity and sleep behavior in Drosophila. Our results indicate that exposure to PA significantly elevated Drosophila's daytime and nighttime locomotor activity while concurrently reducing overall sleep duration. Utilizing 16S rRNA sequencing, we observed substantial alterations in the composition of the gut microbiota induced by PA, notably, characterized by a significant reduction in Lactobacillus plantarum. Furthermore, PA significantly increased the levels of inflammatory factors Upd3 and Eiger in Drosophila intestines, and downregulated the expression of Gad and Tph, as well as 5-HT1A. Conversely, Gdh and Hdc were significantly upregulated in the PA group. Supplementation with L. plantarum or lactic acid significantly ameliorated PA-induced disruptions in both locomotor activity and sleep behavior. This supplementation also suppressed the expression of intestinal inflammatory factors, thus restoring impaired neurotransmitter-mediated sleep-wake regulation. Moreover, specific knockdown of intestinal epithelial Upd3 or Eiger similarly restored disrupted neurotransmitter expression, ultimately improving PA-induced disturbances in Drosophila locomotor activity and sleep behavior. These findings provide important insights into the intricate interplay between dietary components and essential behaviors, highlighting potential avenues for addressing health challenges associated with modern dietary habits.

Cytoophidia safeguard binucleation of Drosophila male accessory gland cells.

Although most cells are mononuclear, the nucleus can exist in the form of binucleate or even multinucleate to respond to different physiological processes. The male accessory gland of Drosophila is the organ that produces semen, and its main cells are binucleate. Here we observe that CTP synthase (CTPS) forms filamentous cytoophidia in binuclear main cells, primarily located at the cell boundary. In CTPSH355A, a point mutation that destroys the formation of cytoophidia, we find that the nucleation mode of the main cells changes, including mononucleates and vertical distribution of binucleates. Although the overexpression of CTPSH355A can restore the level of CTPS protein, it will neither form cytoophidia nor eliminate the abnormal nucleation pattern. Therefore, our data indicate that there is an unexpected functional link between the formation of cytoophidia and the maintenance of binucleation in Drosophila main cells.

Cytoophidia Maintain the Integrity of Drosophila Follicle Epithelium.

CTP synthase (CTPS) forms a filamentous structure termed the cytoophidium in all three domains of life. The female reproductive system of Drosophila is an excellent model for studying the physiological function of cytoophidia. Here, we use CTPSH355A, a point mutation that destroys the cytoophidium-forming ability of CTPS, to explore the in vivo function of cytoophidia. In CTPSH355A egg chambers, we observe the ingression and increased heterogeneity of follicle cells. In addition, we find that the cytoophidium-forming ability of CTPS, rather than the protein level, is the cause of the defects observed in CTPSH355A mutants. To sum up, our data indicate that cytoophidia play an important role in maintaining the integrity of follicle epithelium.

Novel fabrication and biological characterizations of AgNPs-decorated PEEK with gelatin functional nanocomposite to improve superior biomedical applications.

There is an increasing interest in the use of polyether ether ketone (PEEK) for biomedical applications. Herein, we have developed silver nanoparticles (AgNPs) decorated PEEK with gelatin (GEL) nanocomposite hydrogel with enhanced antibacterial and biocompatibility through the blending method. The prepared highly porous PEEK/GEL/AgNPs nanocomposite hydrogel was characterized using SEM, TEM, FTIR, and XRD analysis. The SEM image showed that AgNPs were encapsulated in the porous PEEK/GEL hydrogel; within this porous hydrogel, the AgNPs were homogeneously dispersed. Furthermore, the tensile strength, flexural strength, and Young's modulus were 99 ± 2.4 MPa, 154 ± 7.7 MPa, and 2.3 ± 0.1 GPa, respectively, when AgNPs were added to PEEK/GEL hydrogels it exhibited the mechanical performances. The antibacterial assays demonstrate that the AgNPs-decorated PEEK/GEL nanocomposite hydrogel effectively inhibits the antibacterial effect against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, respectively. Then, MC3T3-E1 cells demonstrated that the AgNPs-decorated PEEK/GEL nanocomposite hydrogel significantly enhanced cell viability and superior alkaline phosphatase (ALP) activity compared with PEEK/GEL hydrogel. This work opens a new avenue of the facile and effective modification of PEEK/GEL/AgNPs nanocomposite hydrogel has increased in vitro antibacterial and biocompatibility properties has great potential to be used as biomedical applications.

Effects of bone regeneration materials and tooth movement timing on canine experimental orthodontic treatment.

OBJECTIVES: To evaluate the effects of bone regeneration materials and orthodontic tooth movement (OTM) timing on tooth movement through alveolar bone defects treated with guided bone regeneration (GBR) utilizing xenografts (Bio-Oss) and alloplast (ß-TCP). MATERIALS AND METHODS: Twenty-four standard alveolar bone defects in six male beagle dogs were treated by GBR using either Bio-Oss or ß-TCP (experimental), whereas the control defects were left empty. The defects were further grouped into early or late subgroups, depending on OTM timing after GBR (ie 1 month or 2 months, respectively). Rates of OTM were measured intraorally, while computed tomography scan images were used to assess bone density, alveolar bone height, second premolar displacement, and tipping tendency. RESULTS: Generally, the Bio-Oss early and Bio-Oss late subgroups recorded the lowest amount of tooth movement compared with other modes of GBRs assessed. Before OTM, the control group registered significantly lower bone height compared with the Bio-Oss and ß-TCP groups ( P < .01). The control group was inferior on bone density and bone height compared with Bio-Oss and ß-TCP. CONCLUSIONS: The Bio-Oss group had favorable radiologic features (higher alveolar bone level and bone density with less premolar tipping) but showed slower OTM than the control group. The late OTM subgroup had favorable radiologic features and showed faster tooth movement than the early OTM in the ß -TCP group.

Temperature Uncertainty Analysis of Injection Mechanism Based on Kriging Modeling.

A kriging modeling method is proposed to conduct the temperature uncertainty analysis of an injection mechanism in squeeze casting. A mathematical model of temperature prediction with multi input and single output is employed to estimate the temperature spatiotemporal distributions of the injection mechanism. The kriging model applies different weights to the independent variables according to spatial location of sample points and their correlation, thus reducing the estimation variance. The predicted value of the kriging model is compared with the sample data at the corresponding position to investigate the influence of the temperature uncertainty of the injection mechanism on the injection process including friction. The results indicate that the significant error is observed at a few sample points in the early injection due to the impact of the uncertainty facts. The variance mean and standard deviation obtained by the model calibrated by experimental samples reduce largely in comparison to those obtained from the initial kriging model. This study indicates that model calibration produces more accurate prediction.

Effect of Fibronectin-Coated Micro-Grooved Titanium Surface on Alignment, Adhesion, and Proliferation of Human Gingival Fibroblasts.

BACKGROUND Surface characters of culture plates affect cellular behaviors such as cellular alignment and elongation. Microgrooves guide the cell growth along the grooves and spread. The aim of this study was to observe the effect of fibronectin (FN)-coated micro-grooved titanium plates on the alignment, spread, adhesion, and proliferation of human gingival fibroblasts (HGFs). MATERIAL AND METHODS Micro-grooved titanium plates were fabricated, and FN was immobilized onto the micro-grooved surfaces using silanization. HGFs were cultured on the smoothed or micro-grooved (with 35 µm width, 15 µm bridge, 10 µm depth) titanium plates, with or without the FN coating. We assessed the water contact angle and blood compatibility of the surfaces, and the earlier adhesion, adhesion strength, proliferation and morphology of the cells growing on the different titanium surfaces. RESULTS The results revealed that the blood hemolysis rates of different titanium surfaces were within the safety limits. HGFs aligned along the grooves, spread out more evidently, and showed significantly more adhesion in the FN-coated micro-grooved surface compared with other surfaces (p<0.05). CONCLUSIONS The micro-grooved surface coated with FN guides the HGFs to align along the grooves, and promotes cell spread, adhesion and proliferation, which might be used to improve the efficacy of dental implants.