National Institutes of Health–Funded Cardiac Arrest Research: A 10‐Year Trend Analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142427/1/jah32314.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142427/2/jah32314_am.pd

The International Liaison Committee for Resuscitation-Review of the last 25 years and vision for the future

Peer reviewe

Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunit

Alterations in the expression, molecular composition, and localization of voltage-gated sodium channels play major roles in a broad range of neurological disorders. Recent evidence identifies sodium channel proteolysis as a key early event after ischemia and traumatic brain injury, further expanding the role of the sodium channel in neurological diseases. In this study, we investigate the protease responsible for proteolytic cleavage of voltage-gated sodium channels (NaChs). NaCh proteolysis occurs after protease activation in rat brain homogenates, pharmacological disruption of ionic homeostasis in cortical cultures, and mechanical injury using an in vitro model of traumatic brain injury. Proteolysis requires Ca2+ and calpain activation but is not influenced by caspase-3 or cathepsin inhibition. Proteolysis results in loss of the full-length {alpha}-subunits, and the creation of fragments comprising all domains of the channel that retain interaction even after proteolysis. Cell surface biotinylation after mechanical injury indicates that proteolyzed NaChs remain in the membrane before noticeable evidence of neuronal death, providing a mechanism for altered action potential initiation, propagation, and downstream signaling events after Ca2+ elevation

“All citizens of the world can save a life” — The World Restart a Heart (WRAH) initiative starts in 2018

“All citizens of the world can save a life”. With these words, the International Liaison Committee on Resuscitation (ILCOR) is launching the first global initiative – World Restart a Heart (WRAH) – to increase public awareness and therefore the rates of bystander cardiopulmonary resuscitation (CPR) for victims of cardiac arrest. In most of the cases, it takes too long for the emergency services to arrive on scene after the victim's collapse. Thus, the most effective way to increase survival and favourable outcome in cardiac arrest by two- to fourfold is early CPR by lay bystanders and by “first responders”. Lay bystander resuscitation rates, however, differ significantly across the world, ranging from 5 to 80%. If all countries could have high lay bystander resuscitation rates, this would help to save hundreds of thousands of lives every year. In order to achieve this goal, all seven ILCOR councils have agreed to participate in WRAH 2018. Besides schoolchildren education in CPR (“KIDS SAVE LIVES”), many other initiatives have already been developed in different parts of the world. ILCOR is keen for the WRAH initiative to be as inclusive as possible, and that it should happen every year on 16 October or as close to that day as possible. Besides recommending CPR training for children and adults, it is hoped that a unified global message will enable our policy makers to take action to address the inequalities in patient survival around the world.Revisión por pare

Administration of Intranasal Insulin During Cardiopulmonary Resuscitation Improves Neurological Outcomes After Cardiac Arrest

INTRODUCTION: Over 325,000 people die from cardiac arrest each year. Prognosis is poor and survivors typically experience persistent neurologic deficits. Currently, neuroprotective treatments to reduce brain injury in cardiac arrest survivors are limited and ineffective. This study evaluates the potential neuroprotection induced by high dose intranasal insulin (HD-IN-I) in a rodent model of asphyxial cardiac arrest. METHODS: Male Long Evans rats were block randomized to sham-operated controls or 8-minute asphyxial cardiac arrest treated with placebo or HD-IN-I at the onset of CPR. To investigate mechanism of action, hippocampi were collected 30 minutes post-ROSC and analyzed by Western blot for phosphorylation of Akt. To assess long-term functional outcomes, neurobehavioral evaluation was conducted using neurologic function scores daily and Barnes maze, Rotarod, and passive avoidance on days 7-10 post-ROSC. Histologic quantification of surviving hippocampal CA1 pyramidal neurons was also conducted. RESULTS: Hippocampal phospho-Akt/total Akt ratio increased 2-fold in the placebo group and 5.7-fold in HD-IN-I group relative to shams (p \u3c 0.05). Rats treated with HD-IN-I had significantly improved performance on Rotarod, Barnes maze, and passive avoidance (p \u3c 0.05). HD-IN-I had no significant effect on ROSC rate, 10-day survival, systemic glycemic response, or on the number of surviving CA1 pyramidal neurons compared to placebo treatment. DISCUSSION: This study is the first to demonstrate that HD-IN-I administered at the onset of CPR, causes phosphorylation of brain Akt and results in significant neuroprotection. This primary work strongly suggests that intranasal insulin could be the first highly effective neuroprotective treatment for cardiac arrest patients

Over 675,000 lay people trained in cardiopulmonary resuscitation worldwide - The "World Restart a Heart (WRAH)" initiative 2018

Non peer reviewe

Silver nanowire networks: Physical properties and potential integration in solar cells

peer reviewedWith the growing interest in flexible electronics and the increased utilization of Indium Tin Oxide electrodes for display and photovoltaic applications the need for new materials is emerging. In this work we present the electro-optical properties of Ag nanowire networks as an alternative transparent conductive material. A comparison of different film deposition techniques is made and indicates that the properties of the network are independent of the fabrication method. Analysis of the electrical behavior as a function of nanowire density is made and compared with theoretical results as well as Monte Carlo simulations. Thermal annealing is shown to reduce the sheet resistance from 1000 Ω/sq to 8 Ω/sq; this reduction is achieved by local sintering of the nanowire junctions. Experimental optimization of Ag nanowire electrodes was undertaken and a peak in the electro-optical properties is observed at approximately 100 mg/m². Finally a discussion of the potential integration of Ag nanowire networks into solar cells is undertaken; we observe that these electrodes show promise as an emerging transparent conductive material, especially for flexible applications

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla

Background: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. Methods: We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. Results: In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037). Conclusion: The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study. Keywords: Calpain, Calpastatin, Pancreas, Ampulla, Bile duct, Cance

Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12

Disturbance of calcium homeostasis and accumulation of misfolded proteins in the endoplasmic reticulum (ER) are considered contributory components of cell death after ischemia. However, the signal-transducing events that are activated by ER stress after cerebral ischemia are incompletely understood. In this study, we show that caspase-12 and the PERK and IRE pathways are activated following oxygen-glucose deprivation (OGD) of mixed cortical cultures or neonatal hypoxia–ischemia (HI). Activation of PERK led to a transient phosphorylation of eIF2α, an increase in ATF4 levels and the induction of gadd34 (a subunit of an eIF2α-directed phosphatase). Interestingly, the upregulation of ATF4 did not lead to an increase in the levels of CHOP. Additionally, IRE1 activation was mediated by the increase in the processed form of xbp1, which would be responsible for the observed expression of edem2 and the increased levels of the chaperones GRP78 and GRP94. We were also able to detect caspase-12 proteolysis after HI or OGD. Processing of procaspase-12 was mediated by NMDA receptor and calpain activation. Moreover, our data suggest that caspase-12 activation is independent of the unfolded protein response activated by ER stress