Modulation of mitochondrial function with near-infrared light reduces brain injury in a translational model of cardiac arrest.

BACKGROUND: Brain injury is a leading cause of morbidity and mortality in patients resuscitated from cardiac arrest. Mitochondrial dysfunction contributes to brain injury following cardiac arrest; therefore, therapies that limit mitochondrial dysfunction have the potential to improve neurological outcomes. Generation of reactive oxygen species (ROS) during ischemia-reperfusion injury in the brain is a critical component of mitochondrial injury and is dependent on hyperactivation of mitochondria following resuscitation. Our previous studies have provided evidence that modulating mitochondrial function with specific near-infrared light (NIR) wavelengths can reduce post-ischemic mitochondrial hyperactivity, thereby reducing brain injury during reperfusion in multiple small animal models. METHODS: Isolated porcine brain cytochrome c oxidase (COX) was used to investigate the mechanism of NIR-induced mitochondrial modulation. Cultured primary neurons from mice expressing mitoQC were utilized to explore the mitochondrial mechanisms related to protection with NIR following ischemia-reperfusion. Anesthetized pigs were used to optimize the delivery of NIR to the brain by measuring the penetration depth of NIR to deep brain structures and tissue heating. Finally, a model of out-of-hospital cardiac arrest with CPR in adult pigs was used to evaluate the translational potential of NIR as a noninvasive therapeutic approach to protect the brain after resuscitation. RESULTS: Molecular evaluation of enzyme activity during NIR irradiation demonstrated COX function was reduced in an intensity-dependent manner with a threshold of enzyme inhibition leading to a moderate reduction in activity without complete inhibition. Mechanistic interrogation in neurons demonstrated that mitochondrial swelling and upregulation of mitophagy were reduced with NIR treatment. NIR therapy in large animals is feasible, as NIR penetrates deep into the brain without substantial tissue heating. In a translational porcine model of CA/CPR, transcranial NIR treatment for two hours at the onset of return of spontaneous circulation (ROSC) demonstrated significantly improved neurological deficit scores and reduced histologic evidence of brain injury after resuscitation from cardiac arrest. CONCLUSIONS: NIR modulates mitochondrial function which improves mitochondrial dynamics and quality control following ischemia/reperfusion. Noninvasive modulation of mitochondria, achieved by transcranial treatment of the brain with NIR, mitigates post-cardiac arrest brain injury and improves neurologic functional outcomes.

COVID-19 Vaccine Discourse on Twitter: A Content Analysis of Persuasion Techniques, Sentiment and Mis/Disinformation.

This research aims to understand the persuasion techniques used in Twitter posts about COVID-19 vaccines by the different vaccine sentiments (i.e., Pro-Vaccine, Anti-Vaccine, and Neutral) using the Elaboration Likelihood Model, Social judgment Theory, and the Extended Parallel Process Model as theoretical frameworks. A content analysis was conducted on a data set of 1,000 Twitter posts. The corpus of Tweets was examined using the persuasion frameworks; tweets that were identified as emanating from bots were further examined. Results found Anti-Vaccine messages predominantly used Anecdotal stories, Humor/Sarcasm, and Celebrity figures as persuasion techniques, while Pro-Vaccine messages primarily used Information, Celebrity figures, and Participation. Results also showed the Anti-Vaccine messages primarily focused on values related to the categories of Safety, Political/Conspiracy Theories, and Choice. Finally, results revealed Anti-Vaccine messages primarily used Perceived Severity and Perceived Susceptibility, which are fear appeal elements. The findings for messages by bots were comparable to the messages in the larger corpus of tweets. Based on the findings, a response framework-Health Information Persuasion Exploration (HIPE)-is proposed to address mis/disinformation and Anti-Vaccine messaging. The results of this study and the HIPE framework can inform a national COVID-19 vaccine health campaign to increase vaccine adoption.

Rapid Treatment with Intramuscular Magnesium Sulfate During Cardiopulmonary Resuscitation Does Not Provide Neuroprotection Following Cardiac Arrest.

Brain injury is the most common cause of death for patients resuscitated from cardiac arrest. Magnesium is an attractive neuroprotective compound which protects neurons from ischemic injury by reducing neuronal calcium overload via NMDA receptor modulation and preventing calcium-induced mitochondrial permeability transition. Intramuscular (IM) delivery of MgSO4 during CPR has the potential to target these mechanisms within an early therapeutic window. We hypothesize that IM MgSO4 administrated during CPR could achieve therapeutic serum magnesium levels within 15 min after ROSC and improve neurologic outcomes in a rat model of asphyxial cardiac arrest. Male Long Evans rats were subjected to 8-min asphyxial cardiac arrest and block randomized to receive placebo, 107 mg/kg, 215 mg/kg, or 430 mg/kg MgSO4 IM at the onset of CPR. Serum magnesium concentrations increased rapidly with IM delivery during CPR, achieving twofold to fourfold increase by 15 min after ROSC in all magnesium dose groups. Rats subjected to cardiac arrest or sham surgery were block randomized to treatment groups for assessment of neurological outcomes. We found that IM MgSO4 during CPR had no effect on ROSC rate (p > 0.05). IM MgSO4 treatment had no statistically significant effect on 10-day survival with good neurologic function or hippocampal CA1 pyramidal neuron survival compared to placebo treatment. In conclusion, a single dose IM MgSO4 during CPR achieves up to fourfold baseline serum magnesium levels within 15 min after ROSC; however, this treatment strategy did not improve survival, recovery of neurologic function, or neuron survival. Future studies with repeated dosing or in combination with hypothermic targeted temperature management may be indicated.

Temporal and Geographic Patterns of Social Media Posts About an Emerging Suicide Game.

PURPOSE: Rates of suicide are increasing rapidly among youth. Social media messages and online games promoting suicide are a concern for parents and clinicians. We examined the timing and location of social media posts about one alleged youth suicide game to better understand the degree to which social media data can provide earlier public health awareness. METHODS: We conducted a search of all public social media posts and news articles on the Blue Whale Challenge (BWC), an alleged suicide game, from January 1, 2013, through June 30, 2017. Data were retrieved through multiple keyword search; sources included social media platforms Twitter, YouTube, Reddit, Tumblr, as well as blogs, forums, and news articles. Posts were classified into three categories: individual "pro"-BWC posts (support for game), individual "anti"-BWC posts (opposition to game), and media reports. Timing and location of posts were assessed. RESULTS: Overall, 95,555 social media posts and articles about the BWC were collected. In total, over one-quarter (28.3%) were "pro"-BWC. The first U.S. news article related to the BWC was published approximately 4 months after the first English language U.S. social media post about the BWC and 9 months after the first U.S. social media post in any language. By the close of the study period, "pro"-BWC posts had spread to 127 countries. CONCLUSIONS: Novel online risks to mental health, such as prosuicide games or messages, can spread rapidly and globally. Better understanding social media and Web data may allow for detection of such threats earlier than is currently possible.

A model-based tool to predict the propagation of infectious disease via airports.

Epidemics of novel or re-emerging infectious diseases have quickly spread globally via air travel, as highlighted by pandemic H1N1 influenza in 2009 (pH1N1). Federal, state, and local public health responders must be able to plan for and respond to these events at aviation points of entry. The emergence of a novel influenza virus and its spread to the United States were simulated for February 2009 from 55 international metropolitan areas using three basic reproduction numbers (R(0)): 1.53, 1.70, and 1.90. Empirical data from the pH1N1 virus were used to validate our SEIR model. Time to entry to the U.S. during the early stages of a prototypical novel communicable disease was predicted based on the aviation network patterns and the epidemiology of the disease. For example, approximately 96% of origins (R(0) of 1.53) propagated a disease into the U.S. in under 75 days, 90% of these origins propagated a disease in under 50 days. An R(0) of 1.53 reproduced the pH1NI observations. The ability to anticipate the rate and location of disease introduction into the U.S. provides greater opportunity to plan responses based on the scenario as it is unfolding. This simulation tool can aid public health officials to assess risk and leverage resources efficiently.