Carbon dots as dual inhibitors of tau and amyloid-beta aggregation for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of senile dementia, presenting a significant challenge for the development of effective treatments. AD is characterized by extracellular amyloid plaques and intraneuronal neurofibrillary tangles. Therefore, targeting both hallmarks through inhibition of amyloid beta (Aß) and tau aggregation presents a promising approach for drug development. Carbon dots (CD), with their high biocompatibility, minimal cytotoxicity, and blood-brain barrier (BBB) permeability, have emerged as promising drug nanocarriers. Congo red, an azo dye, has gathered significant attention for inhibiting amyloid-beta and tau aggregation. However, Congo red's inability to cross the BBB limits its potential to be used as a drug candidate for central nervous system (CNS) diseases. Furthermore, current studies only focus on using Congo red to target single disease hallmarks, without investigating dual inhibition capabilities. In this study, we synthesized Congo red-derived CD (CRCD) by using Congo red and citric acid as precursors, resulting in three variants, CRCD1, CRCD2 and CRCD3, based on different mass ratios of precursors. CRCD2 and CRCD3 exhibited sustained low cytotoxicity, and CRCD3 demonstrated the ability to traverse the BBB in a zebrafish model. Moreover, thioflavin T (ThT) aggregation assays and AFM imaging revealed CRCD as potent inhibitors against both tau and Aß aggregation. Notably, CRCD1 emerged as the most robust inhibitor, displaying IC50 values of 0.2 ± 0.1 and 2.1 ± 0.5 µg/mL against tau and Aß aggregation, respectively. Our findings underscore the dual inhibitory role of CRCD against tau and Aß aggregation, showcasing effective BBB penetration and positioning CRCD as potential nanodrugs and nanocarriers for the CNS. Hence, CRCD-based compounds represent a promising candidate in the realm of multi-functional AD therapeutics, offering an innovative formulation component for future developments in this area. STATEMENT OF SIGNIFICANCE: This article reports Congo red-derived carbon dots (CRCD) as dual inhibitors of tau and amyloid-beta (Aß) aggregation for the treatment of Alzheimer's disease (AD). The CRCD are biocompatible and show strong fluorescence, high stability, the ability to cross the blood-brain barrier, and the function of addressing two major pathological features of AD.

Nano-carrier for gene delivery and bioimaging based on pentaetheylenehexamine modified carbon dots.

Carbon dots (CDs) have attracted much attention due to their excellent properties and applications, especially the use for gene delivery. Considering the risks and concerns involved in the use of viral vectors for gene delivery in vivo, non-viral vectors such as CDs have gradually become an ideal alternative due to their biocompatibility and low toxicity. Therefore, in this study, the potential to apply CDs as a non-viral vector for gene delivery was investigated. The CDs were prepared using citric acid and pentaethylenehexamine (PEHA) as precursors via a one-step microwave-mediated approach. The optical, structural, and morphological properties of PEHA-derived CDs (PCDs) were characterized by ultra-violet spectroscopy (UV-vis), photoluminescence (PL), Fourier Transform Infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), zeta potential, circular dichroism spectrometry, atomic force (AFM) and transmission electron microscopies (TEM). The analysis demonstrated that the as-prepared PCDs were rich in amine groups and were positively charged. Subsequently, gel retardation assay showed that PCDs could non-covalently bind with DNA at a mass ratio of 2:1 (PCDs: DNA). Additionally, PCDs possessed a tremendously lower cytotoxicity compared with polyethylenimine (PEI), a popular precursor/dopant for many CDs preparations, and their plasmid composite showed a high transfection efficiency. Meanwhile, PCDs were also observed to cross the blood-brain barrier (BBB) by using a zebrafish model. In conclusion, these results significantly indicate that PCDs are a potential non-viral nucleic acid/gene vector to gene therapy. Also, PCDs can be utilized in drug delivery for treating brain diseases, such as Alzheimer's disease and brain tumors.

"Help Me Sleep": A Quality Initiative to Reduce Overnight Vital Signs.

BACKGROUND AND OBJECTIVES: Sleep is an essential part of the recovery process, yet inpatient sleep quality is poor. Patients and families report that vital signs are the most bothersome overnight disruption. Obtaining vital signs every 4 hours (Q4H) is not evidence-based and is frequently ordered indiscriminately. We aimed to decrease the percentage of patient nights with vital sign checks between 12 am and 6 am in a low-risk population from 98% to 70% within 12 months to minimize overnight sleep disruptions and improve inpatient sleep. METHODS: We conducted a quality improvement project on 3 pediatric hospital medicine teams at a large free-standing children's hospital. Our multidisciplinary team defined low-risk patients as those admitted for hyperbilirubinemia and failure to thrive. Interventions were focused around education, electronic health record decision support, and patient safety. The outcome measure was the percentage of patient nights without a vital sign measurement between 12 am and 6 am and was analyzed by using statistical process control charts. Our process measure was the use of an appropriate vital sign order. Balancing measures included adverse patient events, specifically code blues outside the ICU and emergent transfers. RESULTS: From March 2020 to April 2021, our pediatric hospital medicine (PHM) services admitted 449 low-risk patients for a total of 1550 inpatient nights. The percentage of patient nights with overnight vital signs decreased from 98% to 38%. There were no code blues or emergent transfers. CONCLUSION: Our improvement interventions reduced the frequency of overnight vital sign monitoring in 2 low-risk groups without any adverse events.

More Than a Game: Musculoskeletal Injuries and a Key Role for the Physical Therapist in Esports.

SYNOPSIS: The esports industry is growing exponentially: more viewers, more support, more money, and more players. Esports competitors require high-level cognitive function and dexterity. There is an increasing demand for physical therapists to manage esports-related musculoskeletal injuries across all levels of play (amateur, semi-professional, professional). Clinicians have relied on general musculoskeletal principles and extrapolating research findings from other populations, including athletes, office workers, air traffic controllers, and musicians, to inform an evidence-based practice approach to assessing and managing injury in esports competitors. The physical demands of esports competitors are triple those of office workers, varying across esports games, platforms (computer, console, mobile), and levels of performance. We highlight the role of physical therapy in esports, the need for best-practice guidelines for musculoskeletal health care, the current research evidence, and the large research gaps in the field. J Orthop Sports Phys Ther 2021;51(9):415-417. doi:10.2519/jospt.2021.0109.