Perivascular adipose tissue (PVAT) negatively regulates vascular muscle contraction. However, in the context of obesity, the PVAT releases vasoconstrictor substances that detrimentally affect vascular function. A pivotal player in this scenario is the peptide endothelin-1 (ET-1), which induces oxidative stress and disrupts vascular function. The present study postulates that obesity augments ET-1 production in the PVAT, decreases the function of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, further increasing reactive oxygen species (ROS) generation, culminating in PVAT dysfunction. Male C57BL/6 mice were fed either a standard or a high-fat diet for 16 weeks. Mice were also treated with saline or a daily dose of 100 mg·kg-1 of the ETA and ETB receptor antagonist Bosentan, for 7 days. Vascular function was evaluated in thoracic aortic rings, with and without PVAT. Mechanistic studies utilized PVAT from all groups and cultured WT-1 mouse brown adipocytes. PVAT from obese mice exhibited increased ET-1 production, increased ECE1 and ETA gene expression, loss of the anticontractile effect, as well as increased ROS production, decreased Nrf2 activity, and downregulated expression of Nrf2-targeted antioxidant genes. PVAT of obese mice also exhibited increased expression of Tyr216-phosphorylated-GSK3β and KEAP1, but not BACH1 - negative Nrf2 regulators. Bosentan treatment reversed all these effects. Similarly, ET-1 increased ROS generation and decreased Nrf2 activity in brown adipocytes, events mitigated by BQ123 (ETA receptor antagonist). These findings place ET-1 as a major contributor to PVAT dysfunction in obesity and highlight that pharmacological control of ET-1 effects restores PVAT's cardiovascular protective role.

Background: Augmentative and alternative communication (AAC) is the approach that enhances communication competence in individuals with complex communication needs. With the advancement of technology, there are varieties of AAC applications with colored-graphic symbols and speech output, improving communication’s intelligibility compared to low-tech AAC systems. However, those AAC applications had some features that were not entirely suitable for Thai users, such as symbol appearance, speech intonation, etc. Objective: This study aimed to develop the first version of the Thai AAC application, A-Speak, based on Thai culture, lexicon, and intonation and remove other constraints that other AAC applications had, such as variation in voice-output age and gender. The proficiency of A-Speak regarding communication functions was also examined. Materials and methods: The participants comprised 15 individuals with cerebral palsy and complex communication needs. The participants were trained to use the A-Speak application, installed on a tablet, to communicate. The training procedures consisted of 3 phases: Phase 1: Train to select icons; Phase 2: Shift to different categories; and Phase 3: Use A-Speak to communicate. The researchers trained the participants to achieve adequate operational skills (i.e., Phases 1 and 2) before beginning Phase 3. In Phases 1 and 2, switches were employed to facilitate participants with limited mobility to operate A-Speak by finger. The researchers also taught the participants’ caregivers to continue training them at home. The researchers collected the participants’ communication abilities regarding communication functions in the recorded form. The data was reported into code numbers according to communication proficiency. Results: After receiving A-Speak training, all participants showed improvement in their communication abilities across a variety of communication functions. Participants showed significant progress in 10 out of 12 communication functions. The communication function in which participants exhibited the most improvement was explaining skills, whereas the communication function that showed the least development was storytelling skills. Conclusion: A-Speak AAC application reduced the constraints that possibly influenced communication intelligibility in the Thai language. Nevertheless, A-Speak still had a few drawbacks that required to be corrected to increase the productivity of this program. The findings indicated that participants gained communication skills through A-Speak as a means of communication. Keywords: A-Speak, augmentative and alternative communication, application, High-tech AAC

This study sought to answer the following questions: (1) Are there differences in knowledge on time to treatment (TTT) between stroke, myocardial infarction (MI), and hip fractures in the general population? (2) Are there differences in condition-specific knowledge across these conditions? (3) Are there underlying demographic factors that may contribute to differences in hip fracture-specific knowledge? This was a cross-sectional cohort analysis. Participants were acquired using an online survey distribution platform, Amazon Mechanical Turk (MTurk). Individuals older than 18 years with English fluency and literacy were included. A total of 913 participants who completed a survey with questions on TTT knowledge, condition-specific knowledge, history of hip fracture, and demographics were recruited. On comparing TTT knowledge, the MI mean score was 36.92% higher than that of hip fractures (P<.0001). On comparing condition-specific knowledge, the MI-specific mean score was 8.24% higher than that of hip fractures (P<.0001). Hip fracture knowledge was associated with demographic factors. Asian and Black participants and participants with Medicaid or Medicare as their primary insurance type were associated with significantly lower hip fracture knowledge. Hip fracture knowledge was significantly lower than MI knowledge in the study population. Just as professional societies have invested resources in public education campaigns on the importance of TTT for stroke and MI, public education campaigns on the importance of TTT for hip fractures may support earlier TTT for populations vulnerable to delays (Asian and Black). [Orthopedics. 20XX;4X(X):XXX-XXX.].