Inflammatory mechanisms in ischemic stroke: therapeutic approaches

Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA) for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its use is limited by its short therapeutic window (three hours), complications derived essentially from the risk of hemorrhage, and the potential damage from reperfusion/ischemic injury. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. This review will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke and potential therapeutic strategies that target neuroinflammation and the innate immune system. Currently, little is known about endogenous counterregulatory immune mechanisms. However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies

Developing a Prediction Model for Real-Time Incident Detection Leveraging User-Oriented Participatory Sensing Data

Effective incident detection is essential for emergency response and transportation management. Traditional methods relying on stationary technologies are often costly and provide limited coverage, prompting the exploration of crowdsourced data such as Waze. While Waze offers extensive coverage, its data can be unverified and unreliable. This study aims to identify factors affecting the reliability of Waze alerts and develop a predictive model to distinguish true incidents from false alerts using real-time Waze data, thereby improving emergency response times. Real crash data from the New Jersey Department of Transportation (NJDOT) and crowdsourced data from Waze were matched using the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm to differentiate true and false alerts. A binary logit model was constructed to reveal significant predictors such as time categories around peak hours, road type, report ratings, and crash type. Findings indicate that the likelihood of accurate Waze alerts increases during peak hours, on streets, and with higher report ratings and major crashes. Additionally, multiple machine learning-based predictive models were developed and evaluated to forecast in real time whether Waze alerts correspond to actual incidents. Among those models, the Random Forest model achieved the highest overall accuracy (82.5%) and F1-score (82.8%), and an Area Under the Receiver Operating Characteristic Curve (AUC-ROC) of 0.90, demonstrating its robustness and reliability for real-time incident detection. Gradient Boosting, with an AUC-ROC of 0.90 and Area Under the Precision–Recall Curve (AUC-PR) of 0.90, also performed strongly, particularly excelling at predicting true alerts. The analysis further emphasized the importance of key predictors such as time of day, report ratings, and road type. These findings provide actionable insights for enhancing the accuracy of incident detection and improving the reliability of crowdsourced traffic alerts, supporting more effective traffic management and emergency response systems

A Unified Approach to Facial Contours and Volume Correction: The Role of the Cheek and the Chin

Background:. Facial proportions and contours influence perceptions of beauty and youthfulness. In particular, the shape and definition of the midface and lower face impact the overall appearance of the face. Methods:. This review provides anatomical evidence to support a holistic approach to facial analysis and rejuvenation that starts with assessment and treatment of the midface and lower face to create an aesthetically desirable facial balance. Results:. The cheek and chin can be considered “anchors” or starting points within full-face treatment because of the noticeable impact of their treatment on the definition and contour of the entire face. Age-related changes in the cheek and chin affect overall facial appearance and can produce unintended facial emotional attributes such as looking tired, angry, or sad. Patients seek facial aesthetic treatment typically for a global improvement such as revitalization or genderization of facial features. Best practices in aesthetics have evolved from treatment of individual areas to a holistic paradigm that uses multimodal therapy to improve overall facial emotional attributes. Hyaluronic acid fillers are useful for volume replacement and smoothing abrupt transitions that develop with age throughout the midface, chin, and jaw. A combination of hyaluronic acid filler for volume restoration and sodium deoxycholate and/or onabotulinumtoxinA for volume reduction where appropriate may optimize lower facial contour. Conclusions:. This review highlights the importance of facial angles and contours as well as the significance of panfacial assessments and treatment, focusing on the relationships within areas of the face, specifically the midface and lower face, to optimize results

Platysma Prominence: Review and Expert Analysis of Clinical Presentation, Burden, and Treatment Considerations

Background:. Platysma prominence (PP) is a sign of aging in the lower face and neck characterized primarily by a blunting of the jawline and the presence of vertical banding along the anterior and posterior margins of the muscle on one or both sides of the neck. The aim of this review was to combine findings from the literature on topics relevant to PP with expert perspective to help guide clinical decision-making in assessment and treatment. Methods:. A review of the literature focusing on platysma muscle anatomy and function; PP signs, characteristics, causes, clinical severity, and aesthetic and psychosocial effects; and treatment options for PP was performed and summarized. Expert clinical perspectives of these findings elucidated from the authors’ experience were used to develop considerations for the evaluation and treatment of PP. Results:. PP is an aesthetically undesirable condition that is bothersome to affected individuals and has negative effects on quality of life and psychological and emotional well-being. Knowledge of platysma muscle anatomy, proper patient assessment, and considerations in the use of onabotulinumtoxinA for the treatment of PP, including selection of the appropriate candidates and careful dosing and injection techniques, can produce consistent results with limited adverse events, potentially enhancing the patient’s quality of life. Conclusions:. PP is a bothersome condition with a detrimental impact on patient quality of life and psychological and emotional well-being. OnabotulinumtoxinA is a nonsurgical treatment option with a record of safe, consistent results in treating PP

Auditory cortical activity to different voice onset times in cochlear implant users.

OBJECTIVE: Voice onset time (VOT) is a critical temporal cue for perception of speech in cochlear implant (CI) users. We assessed the cortical auditory evoked potentials (CAEPs) to consonant vowels (CVs) with varying VOTs and related these potentials to various speech perception measures. METHODS: CAEPs were recorded from 64 scalp electrodes during passive listening in CI and normal-hearing (NH) groups. Speech stimuli were synthesized CVs from a 6-step VOT /ba/-/pa/ continuum ranging from 0 to 50 ms VOT in 10-ms steps. Behavioral measures included the 50% boundary point for categorical perception ( ba to pa ) from an active condition task. RESULTS: Behavioral measures: CI users with poor speech perception performance had prolonged 50% VOT boundary points compared to NH subjects. The 50% boundary point was also significantly correlated to the ability to discriminate consonants in quiet and noise masking. Electrophysiology: The most striking difference between the NH and CI subjects was that the P2 response was significantly reduced in amplitude in the CI group compared to NH. N1 amplitude did not differ between NH and CI groups. P2 latency increased with increases in VOT for both NH and CI groups. P2 was delayed more in CI users with poor speech perception compared to NH subjects. N1 amplitude was significantly related to consonant perception in noise while P2 latency was significantly related to vowel perception in noise. When dipole source modelling in auditory cortex was used to characterize N1/P2, more significant relationships were observed with speech perception measures compared to the same N1/P2 activity when measured at the scalp. N1 dipole amplitude measures were significantly correlated with consonants in noise discrimination. Like N1, the P2 dipole amplitude was correlated with consonant discrimination, but additional significant relationships were observed such as sentence and word identification. CONCLUSIONS: P2 responses to a VOT continuum stimulus were different between NH subjects and CI users. P2 responses show more significant relationships with speech perception than N1 responses. SIGNIFICANCE: The current findings indicate that N1/P2 measures during a passive listening task relate to speech perception outcomes after cochlear implantation

End-point effector stress mediators in neuroimmune interactions: their role in immune system homeostasis and autoimmune pathology

Much evidence has identified a direct anatomical and functional link between the brain and the immune system, with glucocorticoids (GCs), catecholamines (CAs), and neuropeptide Y (NPY) as its end-point mediators. This suggests the important role of these mediators in immune system homeostasis and the pathogenesis of inflammatory autoimmune diseases. However, although it is clear that these mediators can modulate lymphocyte maturation and the activity of distinct immune cell types, their putative role in the pathogenesis of autoimmune disease is not yet completely understood. We have contributed to this field by discovering the influence of CAs and GCs on fine-tuning thymocyte negative selection and, in particular, by pointing to the putative CA-mediated mechanisms underlying this influence. Furthermore, we have shown that CAs are implicated in the regulation of regulatory T-cell development in the thymus. Moreover, our investigations related to macrophage biology emphasize the complex interaction between GCs, CAs and NPY in the modulation of macrophage functions and their putative significance for the pathogenesis of autoimmune inflammatory diseases