Short sleep duration is associated with worse quality of life in Parkinson's disease: A multicenter cross-sectional study.

OBJECTIVE: To characterize sleep duration and investigate its association with quality of life among Parkinson's Disease (PD) patients. METHODS: In this multicenter cross-sectional study, 970 PD patients were divided into five groups based on self-reported sleep duration: <5, ≥5 to <6, ≥6 to <7, ≥7 to ≤8, and >8 h. The quality of life was evaluated using the 39-Item Parkinson's Disease Questionnaire (PDQ-39). Multivariable linear regression analysis, subgroup analysis, and mediation analysis were conducted to examine the association between sleep duration and quality of life. RESULTS: In multivariable linear regression model, patients with sleep duration (<5 h) had significantly higher PDQ-39 scores (ß = 8.132, 95 % CI: 3.99 to 12.266), especially in mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort (p < 0.05). The association between sleep duration (<5 h) and worse quality of life was more pronounced in patients with higher HY stage, longer disease duration, and sleep disorders. Moreover, a significant indirect effect of sleep duration (<5 h) on quality of life was observed, with UPDRS I, UPDRS II, and UPDRS IV scores acting as mediators. CONCLUSIONS: Short sleep duration (<5 h) is associated with worse quality of life among PD patients. This association was stronger among patients with advanced PD and sleep disorders, while non-motor symptoms and motor complications were identified as significant mediators in this association. These findings highlight the significance of adequate sleep duration and suitable interventions for sleep may help improve quality of life.

Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) is a well-established and effective treatment for patients with advanced Parkinson's disease (PD), yet its underlying mechanisms remain enigmatic. Optogenetics, primarily conducted in animal models, provides a unique approach that allows cell type- and projection-specific modulation that mirrors the frequency-dependent stimulus effects of DBS. Opto-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD treatment. DBS-induced neuronal responses rely on a complex interplay between the distributions of presynaptic inputs, frequency-dependent synaptic depression, and the intrinsic excitability of postsynaptic neurons. This orchestration leads to conversion of firing patterns, enabling both antidromic and orthodromic modulation of neural circuits. Understanding these mechanisms is vital for decoding position- and programming-dependent effects of DBS. Furthermore, patterned stimulation is emerging as a promising strategy yielding long-lasting therapeutic benefits. Research on the neuronal and synaptic adaptations to DBS may pave the way for the development of more enduring and precise modulation patterns. Advanced technologies, such as adaptive DBS or directional electrodes, can also be integrated for circuit-specific neuromodulation. These insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels.

Emerging Role of Microglia-Mediated Neuroinflammation in Epilepsy after Subarachnoid Hemorrhage.

Epilepsy is a common and serious complication of subarachnoid hemorrhage (SAH), giving rise to increased morbidity and mortality. It's difficult to identify patients at high risk of epilepsy and the application of anti-epileptic drugs (AEDs) following SAH is a controversial topic. Therefore, it's pressingly needed to gain a better understanding of the risk factors, underlying mechanisms and the optimization of therapeutic strategies for epilepsy after SAH. Neuroinflammation, characterized by microglial activation and the release of inflammatory cytokines, has drawn growing attention due to its influence on patients with epilepsy after SAH. In this review, we discuss the risk factors for epilepsy after SAH and emphasize the critical role of microglia. Then we discuss how various molecules arising from pathophysiological changes after SAH activate specific receptors such as TLR4, NLRP3, RAGE, P2X7R and initiate the downstream inflammatory pathways. Additionally, we focus on the significant responses implicated in epilepsy including neuronal excitotoxicity, the disruption of blood-brain barrier (BBB) and the change of immune responses. As the application of AEDs for seizure prophylaxis after SAH remains controversial, the regulation of neuroinflammation targeting the key pathological molecules could be a promising therapeutic method. While neuroinflammation appears to contribute to epilepsy after SAH, more comprehensive experiments on their relationships are needed.

Aptamer-Conjugated Gold Nanoparticles Targeting Epidermal Growth Factor Receptor Variant III for the Treatment of Glioblastoma.

PURPOSE: In this study, we constructed novel brain-targeting complexes (U2-AuNP) by conjugating aptamer U2 to the gold nanoparticle (AuNPs) surface as a promising option for GBM therapy. MATERIALS AND METHODS: The properties of the U2-AuNP complexes were thoroughly characterized. Then, we detected the in vitro effects of U2-AuNP in U87-EGFRvIII cell lines and the in vivo antitumor effects of U2-AuNP in GBM-bearing mice. Furthermore, we explored the inhibition mechanism of U2-AuNP in U87-EGFRvIII cell lines. RESULTS: We found that U2-AuNP inhibits the proliferation and invasion of U87-EGFRvIII cell lines and prolongs the survival time of GBM-bearing mice. We found that U2-AuNP can inhibit the EGFR-related pathway and prevent DNA damage repair in GBM cells. CONCLUSION: These results reveal the promising potential of U2-AuNP as a drug candidate for targeted therapy in GBM.