The role of globins in cardiovascular physiology.

Globin proteins exist in every cell type of the vasculature, from erythrocytes to endothelial cells, vascular smooth muscle cells, and peripheral nerve cells. Many globin subtypes are also expressed in muscle tissues (including cardiac and skeletal muscle), in other organ-specific cell types, and in cells of the central nervous system (CNS). The ability of each of these globins to interact with molecular oxygen (O2) and nitric oxide (NO) is preserved across these contexts. Endothelial α-globin is an example of extraerythrocytic globin expression. Other globins, including myoglobin, cytoglobin, and neuroglobin, are observed in other vascular tissues. Myoglobin is observed primarily in skeletal muscle and smooth muscle cells surrounding the aorta or other large arteries. Cytoglobin is found in vascular smooth muscle but can also be expressed in nonvascular cell types, especially in oxidative stress conditions after ischemic insult. Neuroglobin was first observed in neuronal cells, and its expression appears to be restricted mainly to the CNS and the peripheral nervous system. Brain and CNS neurons expressing neuroglobin are positioned close to many arteries within the brain parenchyma and can control smooth muscle contraction and thus tissue perfusion and vascular reactivity. Overall, reactions between NO and globin heme iron contribute to vascular homeostasis by regulating vasodilatory NO signals and scavenging reactive species in cells of the mammalian vascular system. Here, we discuss how globin proteins affect vascular physiology, with a focus on NO biology, and offer perspectives for future study of these functions.

The American Heart Association Emergency Cardiovascular Care 2030 Impact Goals and Call to Action to Improve Cardiac Arrest Outcomes: A Scientific Statement From the American Heart Association.

Every 10 years, the American Heart Association (AHA) Emergency Cardiovascular Care Committee establishes goals to improve survival from cardiac arrest. These goals align with broader AHA Impact Goals and support the AHA's advocacy efforts and strategic investments in research, education, clinical care, and quality improvement programs. This scientific statement focuses on 2030 AHA emergency cardiovascular care priorities, with a specific focus on bystander cardiopulmonary resuscitation, early defibrillation, and neurologically intact survival. This scientific statement also includes aspirational goals, such as establishing cardiac arrest as a reportable disease and mandating reporting of standardized outcomes from different sources; advancing recognition of and knowledge about cardiac arrest; improving dispatch system response, availability, and access to resuscitation training in multiple settings and at multiple time points; improving availability, access, and affordability of defibrillators; providing a focus on early defibrillation, in-hospital programs, and establishing champions for debriefing and review of cardiac arrest events; and expanding measures to track outcomes beyond survival. The ability to track and report data from these broader aspirational targets will potentially require expansion of existing data sets, development of new data sets, and enhanced integration of technology to collect process and outcome data, as well as partnerships of the AHA with national, state, and local organizations. The COVID-19 (coronavirus disease 2019) pandemic, disparities in COVID-19 outcomes for historically excluded racial and ethnic groups, and the longstanding disparities in cardiac arrest treatment and outcomes for Black and Hispanic or Latino populations also contributed to an explicit focus and target on equity for the AHA Emergency Cardiovascular Care 2030 Impact Goals.

Chondroitin sulfate enhances the barrier function of basement membrane assembled by heparan sulfate.

Glycosaminoglycans are ubiquitously expressed polysaccharides that are attached to proteoglycans. Here, we showed that ablation of the heparan sulfate (HS) polymerase Ext1 in retinal progenitor cells did not affect initial progression of retinal angiogenesis, but it disrupted the pruning of blood vessels and establishment of arterioles and venules. In the absence of retinal HS, blood vessels were also vulnerable to high oxygen tension in early postnatal stages, which could be rescued by exogenous vascular endothelial growth factor (VEGF), consistent with the role of retinal HS in the fine-tuning of VEGF signaling. Furthermore, we observed that the retinal inner limiting membrane (ILM) was disrupted by deletion of Ext1 in a timing-specific manner, suggesting that retinal HS is required for the assembly but not the maintenance of the basement membrane. Lastly, we showed that further deletion of C4st1, a chondroitin sulfate (CS) sulfation enzyme, did not affect the assembly of the ILM but, when combined with Ext1 deletion, it aggravated the retinal permeability by disrupting the retinal glycocalyx. These results demonstrate an important role of CS and HS in establishing the barrier function of the extracellular matrix.

Organ Donation After Out-of-Hospital Cardiac Arrest: A Scientific Statement From the International Liaison Committee on Resuscitation.

AIM OF THE REVIEW: Improving rates of organ donation among patients with out-of-hospital cardiac arrest who do not survive is an opportunity to save countless lives. The objectives of this scientific statement were to do the following: define the opportunity for organ donation among patients with out-of-hospital cardiac arrest; identify challenges and opportunities associated with organ donation by patients with cardiac arrest; identify strategies, including a generic protocol for organ donation after cardiac arrest, to increase the rate and consistency of organ donation from this population; and provide rationale for including organ donation as a key clinical outcome for all future cardiac arrest clinical trials and registries. METHODS: The scope of this International Liaison Committee on Resuscitation scientific statement was approved by the International Liaison Committee on Resuscitation board and the American Heart Association, posted on ILCOR.org for public comment, and then assigned by section to primary and secondary authors. A unique literature search was completed and updated for each section. RESULTS: There are a number of defining pathways for patients with out-of-hospital cardiac arrest to become organ donors; however, modifications in the Maastricht classification system need to be made to correctly identify these donors and to report outcomes with consistency. Suggested modifications to the minimum data set for reporting cardiac arrests will increase reporting of organ donation as an important resuscitation outcome. There are a number of challenges with implementing uncontrolled donation after cardiac death protocols, and the greatest impediment is the lack of legislation in most countries to mandate organ donation as the default option. Extracorporeal cardiopulmonary resuscitation has the potential to increase organ donation rates, but more research is needed to derive neuroprognostication rules to guide clinical decision-making about when to stop extracorporeal cardiopulmonary resuscitation and to evaluate cost-effectiveness. CONCLUSIONS: All health systems should develop, implement, and evaluate protocols designed to optimize organ donation opportunities for patients who have an out-of-hospital cardiac arrest and failed attempts at resuscitation.

An ecotoxicological assessment of a strigolactone mimic used as the active ingredient in a plant biostimulant formulation.

A risk assessment on the aquatic toxicity of the plant biostimulant strigolactone mimic (2-(4-methyl-5-oxo-2,5-dihydro-furan-2-yloxy)-benzo[de]isoquinoline-1,3-dione (SL-6) was performed using a suite of standardised bioassays representing different trophic groups and acute and chronic endpoints. In freshwater, three trophic groups of algae, crustacea and fish were used. Whilst in seawater, algae (unicellular and macroalgae), Crustacea and Mollusca were employed. In addition, the genotoxicity of SL-6 was determined with the comet assessment performed on unicellular marine algae, oysters, and fish embryos. This was the first time ecotoxicity tests have been performed on SL-6. In freshwater, the lowest LOEC was measured in the unicellular algae at 0.31 mg/L SL-6. Although, similar LOEC values were found for embryo malformations and impacts on hatching rate in zebrafish (LOEC 0.31-0.33 mg/L). Consistent malformations of pericardial and yolk sac oedemas were identified in the zebrafish embryos at 0.31 mg/L. In marine species, the lowest LOEC was found for both Tisbe battagliai mortality and microalgae growth at an SL-6 concentration of 1.0 mg/L. Significant genotoxicity was observed above control levels at 0.0031 mg/L SL-6 in the unicellular algae and 0.001 mg/L SL-6 in the oyster and zebrafish larvae. When applying the simple risk assessment, based on the lowest NOECs and appropriate assessment factors, the calculated predicted no effect concentration (PNEC), for the ecotoxicity and the genotoxicity tests were 1.0 µg/L and 0.01 µg/L respectively.

Novel salivary antihemostatic activities of long-form D7 proteins from the malaria vector Anopheles gambiae facilitate hematophagy.

To successfully feed on blood, hematophagous arthropods must combat the host's natural hemostatic and inflammatory responses. Salivary proteins of blood-feeding insects such as mosquitoes contain compounds that inhibit these common host defenses against blood loss, including vasoconstriction, platelet aggregation, blood clotting, pain, and itching. The D7 proteins are some of the most abundantly expressed proteins in female mosquito salivary glands and have been implicated in inhibiting host hemostatic and inflammatory responses. Anopheles gambiae, the primary vector of malaria, expresses three D7 long-form and five D7 short-form proteins. Previous studies have characterized the AngaD7 short-forms, but the D7 long-form proteins have not yet been characterized in detail. Here, we characterized the A. gambiae D7 long-forms by first determining their binding kinetics to hemostatic agonists such as leukotrienes and serotonin, which are potent activators of vasoconstriction, edema formation, and postcapillary venule leakage, followed by ex vivo functional assays. We found that AngaD7L1 binds leukotriene C4 and thromboxane A2 analog U-46619; AngaD7L2 weakly binds leukotrienes B4 and D4; and AngaD7L3 binds serotonin. Subsequent functional assays confirmed AngaD7L1 inhibits U-46619-induced platelet aggregation and vasoconstriction, and AngaD7L3 inhibits serotonin-induced platelet aggregation and vasoconstriction. It is therefore possible that AngaD7L proteins counteract host hemostasis by scavenging these mediators. Finally, we demonstrate that AngaD7L2 had a dose-dependent anticoagulant effect via the intrinsic coagulation pathway by interacting with factors XII, XIIa, and XI. The uncovering of these interactions in the present study will be essential for comprehensive understanding of the vector-host biochemical interface.

Optimizing Outcomes After Out-of-Hospital Cardiac Arrest With Innovative Approaches to Public-Access Defibrillation: A Scientific Statement From the International Liaison Committee on Resuscitation.

Out-of-hospital cardiac arrest is a global public health issue experienced by ≈3.8 million people annually. Only 8% to 12% survive to hospital discharge. Early defibrillation of shockable rhythms is associated with improved survival, but ensuring timely access to defibrillators has been a significant challenge. To date, the development of public-access defibrillation programs, involving the deployment of automated external defibrillators into the public space, has been the main strategy to address this challenge. Public-access defibrillator programs have been associated with improved outcomes for out-of-hospital cardiac arrest; however, the devices are used in <3% of episodes of out-of-hospital cardiac arrest. This scientific statement was commissioned by the International Liaison Committee on Resuscitation with 3 objectives: (1) identify known barriers to public-access defibrillator use and early defibrillation, (2) discuss established and novel strategies to address those barriers, and (3) identify high-priority knowledge gaps for future research to address. The writing group undertook systematic searches of the literature to inform this statement. Innovative strategies were identified that relate to enhanced public outreach, behavior change approaches, optimization of static public-access defibrillator deployment and housing, evolved automated external defibrillator technology and functionality, improved integration of public-access defibrillation with existing emergency dispatch protocols, and exploration of novel automated external defibrillator delivery vectors. We provide evidence- and consensus-based policy suggestions to enhance public-access defibrillation and guidance for future research in this area.

Community Interventions for Out-of-Hospital Cardiac Arrest in Resource-Limited Settings: A Scoping Review Across Low, Middle, and High-Income Countries.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a major global health challenge, characterized by poor survival outcomes worldwide. Resource-limited settings are burdened with suboptimal emergency response and worse outcomes than high-resource areas. Engaging the community in the response to OHCA has the potential to improve outcomes, although an overview of community interventions in resource-limited settings has not been provided. OBJECTIVE: This review evaluated the scope of community-based OHCA interventions in resource-limited settings. METHODS: Literature searches in electronic databases (MEDLINE, EMBASE, Global Health, CINAHL, Cochrane Central Register of Controlled Clinical Trials) and grey literature sources were performed. Abstract screening, full-text review, and data extraction of eligible studies were conducted independently by two reviewers. The PCC (Population, Concept, and Context) framework was used to assess study eligibility. Studies that evaluated community-based interventions for laypeople (Population), targeting emergency response activation, cardiopulmonary resuscitation (CPR), or automated external defibrillator (AED) use (Concept) in resource-limited settings (Context) were included. Resource-limited settings were identified by financial pressures (low-income or lower-middle-income country, according to World Bank data on year of publication) or geographical factors (setting described using keywords indicative of geographical remoteness in upper-middle-income or high-income country). RESULTS: Among 14,810 records identified from literature searches, 60 studies from 28 unique countries were included in this review. Studies were conducted in high-income (n = 35), upper-middle-income (n = 2), lower-middle-income (n = 22), and low-income countries (n = 1). Community interventions included bystander CPR and/or AED training (n = 34), community responder programs (n = 8), drone-delivered AED networks (n = 6), dispatcher-assisted CPR programs (n = 4), regional resuscitation campaigns (n = 3), public access defibrillation programs (n = 3), and crowdsourcing technologies (n = 2). CPR and/or AED training were the only interventions evaluated in low-income, lower-middle-income, and upper-middle-income countries. CONCLUSIONS: Interventions aimed at improving the community response to OHCA in resource-limited settings differ globally. There is a lack of reported studies from low-income countries and certain continental regions, including South America, Africa, and Oceania. Evaluation of interventions other than CPR and/or AED training in low- and middle-income countries is needed to guide community emergency planning and health policies.

The development of peripheral microvasculopathy with chronic metabolic disease in obese Zucker rats: a retrograde emergence?

The study of peripheral vasculopathy with chronic metabolic disease is challenged by divergent contributions from spatial (the level of resolution or specific tissue being studied) and temporal origins (evolution of the developing impairments in time). Over many years of studying the development of skeletal muscle vasculopathy and its functional implications, we may be at the point of presenting an integrated conceptual model that addresses these challenges within the obese Zucker rat (OZR) model. At the early stages of metabolic disease, where systemic markers of elevated cardiovascular disease risk are present, the only evidence of vascular dysfunction is at postcapillary and collecting venules, where leukocyte adhesion/rolling is elevated with impaired venular endothelial function. As metabolic disease severity and duration increases, reduced microvessel density becomes evident as well as increased variability in microvascular hematocrit. Subsequently, hemodynamic impairments to distal arteriolar networks emerge, manifesting as increasing perfusion heterogeneity and impaired arteriolar reactivity. This retrograde "wave of dysfunction" continues, creating a condition wherein deficiencies to the distal arteriolar, capillary, and venular microcirculation stabilize and impairments to proximal arteriolar reactivity, wall mechanics, and perfusion distribution evolve. This proximal arteriolar dysfunction parallels increasing failure in fatigue resistance, hyperemic responses, and O2 uptake within self-perfused skeletal muscle. Taken together, these results present a conceptual model for the retrograde development of peripheral vasculopathy with chronic metabolic disease and provide insight into the timing and targeting of interventional strategies to improve health outcomes.NEW & NOTEWORTHY Working from an established database spanning multiple scales and times, we studied progression of peripheral microvascular dysfunction in chronic metabolic disease. The data implicate the postcapillary venular endothelium as the initiating site for vasculopathy. Indicators of dysfunction, spanning network structures, hemodynamics, vascular reactivity, and perfusion progress in an insidious retrograde manner to present as functional impairments to muscle blood flow and performance much later. The silent vasculopathy progression may provide insight into clinical treatment challenges.

Monitoring ocean water quality by deployment of lumpfish (Cyclopterus lumpus) eggs: In situ bioaccumulation and toxicity in embryos.

Fish embryos can bioaccumulate and are particularly sensitive to a wide range of contaminants, which makes them suitable sentinels for environmental biomonitoring. However, fish embryos are very rarely utilized in environmental monitoring surveys, possibly due to their fragility and seasonality. In the present work, we assessed the applicability of caged lumpfish (Cyclopterus lumpus) eggs for in situ biomonitoring of exposure and effects of organic contaminants focusing on polyaromatic hydrocarbons and phenolic compounds. Fertilized eggs (1 dpf) were transplanted for 17-19 days at different locations that differed in terms of contaminant load, depths and weather conditions, namely at three stations close to the city of Trondheim (two harbour areas and a one in the Fjord) and three stations at a coastal aquaculture facility. High survival upon retrieval after deployment showed that lumpfish eggs are relatively robust and survive encaging in different environments. Bioaccumulation of organic contaminants (PAHs and phenolic compounds) was measured and potential effects on hatching, development, survival and larvae morphometry were determined. Chemical analyses showed that especially PAHs were effectively accumulated in eggs in contaminated sites, with concentrations of Æ©PAHs being 15 - 25 times higher in harbour areas compared to those at the aquaculture facility. A higher incidence of embryonic deformations was observed in the most polluted deployment location, but larvae morphometry revealed no evidence of toxicity related to pollutant body burden. In conclusion, the in-situ exposure method was proven to work well, making it attractive for implementations in environmental monitoring programs.

Adult Basic Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science With Treatment Recommendations on basic life support summarizes evidence evaluations performed for 22 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 5 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.

Experimental Babesia rossi infection induces hemolytic, metabolic, and viral response pathways in the canine host.

BACKGROUND: Babesia rossi is a leading cause of morbidity and mortality among the canine population of sub-Saharan Africa, but pathogenesis remains poorly understood. Previous studies of B. rossi infection were derived from clinical cases, in which neither the onset of infection nor the infectious inoculum was known. Here, we performed controlled B. rossi inoculations in canines and evaluated disease progression through clinical tests and whole blood transcriptomic profiling. RESULTS: Two subjects were administered a low inoculum (104 parasites) while three received a high (108 parasites). Subjects were monitored for 8 consecutive days; anti-parasite treatment with diminazene aceturate was administered on day 4. Blood was drawn prior to inoculation as well as every experimental day for assessment of clinical parameters and transcriptomic profiles. The model recapitulated natural disease manifestations including anemia, acidosis, inflammation and behavioral changes. Rate of disease onset and clinical severity were proportional to the inoculum. To analyze the temporal dynamics of the transcriptomic host response, we sequenced mRNA extracted from whole blood drawn on days 0, 1, 3, 4, 6, and 8. Differential gene expression, hierarchical clustering, and pathway enrichment analyses identified genes and pathways involved in response to hemolysis, metabolic changes, and several arms of the immune response including innate immunity, adaptive immunity, and response to viral infection. CONCLUSIONS: This work comprehensively characterizes the clinical and transcriptomic progression of B. rossi infection in canines, thus establishing a large mammalian model of severe hemoprotozoal disease to facilitate the study of host-parasite biology and in which to test novel anti-disease therapeutics. The knowledge gained from the study of B. rossi in canines will not only improve our understanding of this emerging infectious disease threat in domestic dogs, but also provide insight into the pathobiology of human diseases caused by Babesia and Plasmodium species.

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.

Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis.

The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element conserved in terrestrial but not aquatic animals, underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse. These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in the neural crest for lacrimal gland development.

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the US Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials.

Management of Patients with Candida auris Fungemia at Community Hospital, Brooklyn, New York, USA, 2016-20181.

Candida auris is an emerging fungus that can cause invasive infections. It is associated with high mortality rates and resistance to multiple classes of antifungal drugs and is difficult to identify with standard laboratory methods. We describe the management and outcomes of 9 patients with C. auris fungemia in Brooklyn, New York, USA.

Ranking Businesses and Municipal Locations by Spatiotemporal Cardiac Arrest Risk to Guide Public Defibrillator Placement.

BACKGROUND: Efforts to guide automated external defibrillator placement for out-of-hospital cardiac arrest (OHCA) treatment have focused on identifying broadly defined location categories without considering hours of operation. Broad location categories may be composed of many businesses with varying accessibility. Identifying specific locations for automated external defibrillator deployment incorporating operating hours and time of OHCA occurrence may improve automated external defibrillator accessibility. We aim to identify specific businesses and municipal locations that maximize OHCA coverage on the basis of spatiotemporal assessment of OHCA risk in the immediate vicinity of franchise locations. METHODS: This study was a retrospective population-based cohort study using data from the Toronto Regional RescuNET Epistry cardiac arrest database. We identified all nontraumatic public OHCAs occurring in Toronto, ON, Canada, from January 2007 through December 2015. We identified 41 unique businesses and municipal location types with ≥20 locations in Toronto from the YellowPages, Canadian Franchise Association, and the City of Toronto Open Data Portal. We obtained their geographic coordinates and hours of operation from Web sites, by phone, or in person. We determined the number of OHCAs that occurred within 100 m of each location when it was open (spatiotemporal coverage) for Toronto overall and downtown. The businesses and municipal locations were then ranked by spatiotemporal OHCA coverage. To evaluate temporal stability of the rankings, we calculated intraclass correlation of the annual coverage values. RESULTS: There were 2654 nontraumatic public OHCAs. Tim Hortons ranked first in Toronto, covering 286 OHCAs. Starbucks ranked first in downtown, covering 110 OHCAs. Coffee shops and bank machines from the 5 largest Canadian banks occupied 8 of the top 10 spots in both Toronto and downtown. The rankings exhibited high temporal stability with intraclass correlation values of 0.88 (95% confidence interval, 0.83-0.93) in Toronto and 0.79 (95% confidence interval, 0.71-0.86) in downtown. CONCLUSIONS: We identified and ranked businesses and municipal locations by spatiotemporal OHCA risk in their immediate vicinity. This approach may help policy makers and funders to identify and prioritize potential partnerships for automated external defibrillator deployment in public-access defibrillator programs.

Optimizing a Drone Network to Deliver Automated External Defibrillators.

BACKGROUND: Public access defibrillation programs can improve survival after out-of-hospital cardiac arrest, but automated external defibrillators (AEDs) are rarely available for bystander use at the scene. Drones are an emerging technology that can deliver an AED to the scene of an out-of-hospital cardiac arrest for bystander use. We hypothesize that a drone network designed with the aid of a mathematical model combining both optimization and queuing can reduce the time to AED arrival. METHODS: We applied our model to 53 702 out-of-hospital cardiac arrests that occurred in the 8 regions of the Toronto Regional RescuNET between January 1, 2006, and December 31, 2014. Our primary analysis quantified the drone network size required to deliver an AED 1, 2, or 3 minutes faster than historical median 911 response times for each region independently. A secondary analysis quantified the reduction in drone resources required if RescuNET was treated as a large coordinated region. RESULTS: The region-specific analysis determined that 81 bases and 100 drones would be required to deliver an AED ahead of median 911 response times by 3 minutes. In the most urban region, the 90th percentile of the AED arrival time was reduced by 6 minutes and 43 seconds relative to historical 911 response times in the region. In the most rural region, the 90th percentile was reduced by 10 minutes and 34 seconds. A single coordinated drone network across all regions required 39.5% fewer bases and 30.0% fewer drones to achieve similar AED delivery times. CONCLUSIONS: An optimized drone network designed with the aid of a novel mathematical model can substantially reduce the AED delivery time to an out-of-hospital cardiac arrest event.

2017 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary.

The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 pediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have prioritized and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question.

Protection from chronic stress- and depressive symptom-induced vascular endothelial dysfunction in female rats is abolished by preexisting metabolic disease.

While it is known that chronic stress and clinical depression are powerful predictors of poor cardiovascular outcomes, recent clinical evidence has identified correlations between the development of metabolic disease and depressive symptoms, creating a combined condition of severely elevated cardiovascular disease risk. In this study, we used the obese Zucker rat (OZRs) and the unpredictable chronic mild stress (UCMS) model to determine the impact of preexisting metabolic disease on the relationship between chronic stress/depressive symptoms and vascular function. Additionally, we determined the impact of metabolic syndrome on sex-based protection from chronic stress/depressive effects on vascular function in female lean Zucker rats (LZRs). In general, vasodilator reactivity was attenuated under control conditions in OZRs compared with LZRs. Although still impaired, conduit arterial and resistance arteriolar dilator reactivity under control conditions in female OZRs was superior to that in male or ovariectomized (OVX) female OZRs, largely because of better maintenance of vascular nitric oxide and prostacyclin levels. However, imposition of metabolic syndrome in combination with UCMS in OZRs further impaired dilator reactivity in both vessel subtypes to a similarly severe extent and abolished any protective effect in female rats compared with male or OVX female rats. The loss of vascular protection in female OZRs with UCMS was reflected in vasodilator metabolite levels, which closely matched those in male and OVX female OZRs subjected to UCMS. These results suggest that presentation of metabolic disease in combination with depressive symptoms can overwhelm the vasoprotection identified in female rats and, thereby, may reflect a severe impairment to normal endothelial function. NEW & NOTEWORTHY This study addresses the protection from chronic stress- and depression-induced vascular dysfunction identified in female compared with male or ovariectomized female rats. We determined the impact of preexisting metabolic disease, a frequent comorbidity of clinical depression in humans, on that vascular protection. With preexisting metabolic syndrome, female rats lost all protection from chronic stress/depressive symptoms and became phenotypically similar to male and ovariectomized female rats, with comparably poor vasoactive dilator metabolite profiles.