New Processes for Ionizing Nonvolatile Compounds in Mass Spectrometry: The Road of Discovery to Current State-of-the-Art.

This covers discovery and mechanistic aspects as well as initial applications of novel ionization processes for use in mass spectrometry that guided us in a series of subsequent discoveries, instrument developments, and commercialization. matrix-assisted ionization on an intermediate pressure matrix-assisted laser desorption/ionization source the use of a laser, high voltages, or any other added energy was simply unbelievable, at first. Individually and as a whole, the various discoveries and inventions started to paint, , an exciting new picture and outlook in mass spectrometry from which key developments grew that were at the time unimaginable, and continue to surprise us in its simplistic preeminence.

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.

Pediatric Resident Confidence in Assessing Neurological Cases: A Nationwide Survey.

Background: A relative shortage of pediatric neurologists in proportion to estimated neurological disorders often results in general pediatricians evaluating and treating children with complex neurological conditions. Dedicated rotations in pediatric neurology are not mandated during medical school or pediatric residency. We evaluated the perceptions of a large cohort of pediatric residents and program directors (PDs) regarding child neurology training.

Does Disruption of Optic Atrophy-1 (OPA1) Contribute to Cell Death in HL-1 Cardiomyocytes Subjected to Lethal Ischemia-Reperfusion Injury?

Disruption of mitochondrial structure/function is well-recognized to be a determinant of cell death in cardiomyocytes subjected to lethal episodes of ischemia-reperfusion (IR). However, the precise mitochondrial event(s) that precipitate lethal IR injury remain incompletely resolved. Using the in vitro HL-1 cardiomyocyte model, our aims were to establish whether: (1) proteolytic processing of optic atrophy protein-1 (OPA1), the inner mitochondrial membrane protein responsible for maintaining cristae junction integrity, plays a causal, mechanistic role in determining cardiomyocyte fate in cells subjected to lethal IR injury; and (2) preservation of OPA1 may contribute to the well-documented cardioprotection achieved with ischemic preconditioning (IPC) and remote ischemic conditioning.

Parathyroid Hormone-Related Peptide and Its Analog, Abaloparatide, Attenuate Lethal Myocardial Ischemia-Reperfusion Injury.

Parathyroid hormone-related peptide (PTHrP) is well-known to play a role in bone formation, and abaloparatide, an analog of PTHrP(1-34), is approved for the treatment of osteoporosis in post-menopausal women. PTHrP has also been reported to have cardiovascular effects, with recent data demonstrating that exogenously administered PTHrP can limit the death of isolated cardiomyocytes subjected to oxidative stress via upregulation of classic ‘survival kinase’ signaling. Our aim in the current study was to extend this concept and, employing both in vitro and in vivo models, establish whether PTHrP(1-36) and abaloparatide are cardioprotective in the setting of lethal myocardial ischemia-reperfusion injury.

Mitochondrial fission and mitophagy are independent mechanisms regulating ischemia/reperfusion injury in primary neurons.

Mitochondrial dynamics and mitophagy are constitutive and complex systems that ensure a healthy mitochondrial network through the segregation and subsequent degradation of damaged mitochondria. Disruption of these systems can lead to mitochondrial dysfunction and has been established as a central mechanism of ischemia/reperfusion (I/R) injury. Emerging evidence suggests that mitochondrial dynamics and mitophagy are integrated systems; however, the role of this relationship in the context of I/R injury remains unclear.

Machine learning-based classification of mitochondrial morphology in primary neurons and brain.

The mitochondrial network continually undergoes events of fission and fusion. Under physiologic conditions, the network is in equilibrium and is characterized by the presence of both elongated and punctate mitochondria. However, this balanced, homeostatic mitochondrial profile can change morphologic distribution in response to various stressors.

Mitochondrial Quality Control: Role in Cardiac Models of Lethal Ischemia-Reperfusion Injury.

The current standard of care for acute myocardial infarction or 'heart attack' is timely restoration of blood flow to the ischemic region of the heart. While reperfusion is essential for the salvage of ischemic myocardium, re-introduction of blood flow paradoxically (rather than rescues) a population of previously ischemic cardiomyocytes-a phenomenon referred to as 'lethal myocardial ischemia-reperfusion (IR) injury'. There is long-standing and exhaustive evidence that mitochondria are at the nexus of lethal IR injury.

Non-invasive treatment with near-infrared light: A novel mechanisms-based strategy that evokes sustained reduction in brain injury after stroke.

Ischemic stroke is a debilitating disease that causes significant brain injury. While restoration of blood flow is critical to salvage the ischemic brain, reperfusion can exacerbate damage by inducing generation of reactive oxygen species (ROS). Recent studies by our group found that non-invasive mitochondrial modulation with near-infrared (NIR) light limits ROS generation following global brain ischemia.

Ischaemic and hypoxic conditioning: potential for protection of vital organs.

New Findings: What is the topic of this review? Remote ischaemic preconditioning (RIPC) and hypoxic preconditioning as novel therapeutic approaches for cardiac and neuroprotection. What advances does it highlight? There is improved understanding of mechanisms and signalling pathways associated with ischaemic and hypoxic preconditioning, and potential pitfalls with application of these therapies to clinical trials have been identified. Novel adaptations of preconditioning paradigms have also been developed, including intermittent hypoxia training, RIPC training and RIPC-exercise, extending their utility to chronic settings.

Publisher Correction: GLS-409, an Antagonist of Both P2Y and P2Y, Potently Inhibits Canine Coronary Artery Thrombosis and Reversibly Inhibits Human Platelet Activation.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

GLS-409, an Antagonist of Both P2Y and P2Y, Potently Inhibits Canine Coronary Artery Thrombosis and Reversibly Inhibits Human Platelet Activation.

Dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) P2Y receptor antagonist reduces ischemic events in patients with acute coronary syndrome. Previous evidence from our group, obtained in a preclinical model of recurrent platelet-mediated thrombosis, demonstrated that GLS-409, a diadenosine tetraphosphate derivative that inhibits both P2Y and P2Y ADP receptors, may be a novel and promising antiplatelet drug candidate. However, the salutary antiplatelet effects of GLS-409 were accompanied by a trend toward an unfavorable increase in bleeding.

Publisher Correction: Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Remote ischemic preconditioning fails to reduce infarct size in the Zucker fatty rat model of type-2 diabetes: role of defective humoral communication.

Remote ischemic preconditioning (RIPC), the phenomenon whereby brief ischemic episodes in distant tissues or organs render the heart resistant to infarction, has been exhaustively demonstrated in preclinical models. Moreover, emerging evidence suggests that exosomes play a requisite role in conveying the cardioprotective signal from remote tissue to the myocardium. However, in cohorts displaying clinically common comorbidities-in particular, type-2 diabetes-the infarct-sparing effect of RIPC may be confounded for as-yet unknown reasons.

Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury.

The interaction of light with biological tissue has been successfully utilized for multiple therapeutic purposes. Previous studies have suggested that near infrared light (NIR) enhances the activity of mitochondria by increasing cytochrome c oxidase (COX) activity, which we confirmed for 810 nm NIR. In contrast, scanning the NIR spectrum between 700 nm and 1000 nm revealed two NIR wavelengths (750 nm and 950 nm) that reduced the activity of isolated COX.

Guidelines for experimental models of myocardial ischemia and infarction.

Myocardial infarction is a prevalent major cardiovascular event that arises from myocardial ischemia with or without reperfusion, and basic and translational research is needed to better understand its underlying mechanisms and consequences for cardiac structure and function. Ischemia underlies a broad range of clinical scenarios ranging from angina to hibernation to permanent occlusion, and while reperfusion is mandatory for salvage from ischemic injury, reperfusion also inflicts injury on its own. In this consensus statement, we present recommendations for animal models of myocardial ischemia and infarction.

Examining self-reported and biological stress and near misses among Emergency Medicine residents: a single-centre cross-sectional assessment in the USA.

Objectives: To examine the relationship between perceived and biological stress and near misses among Emergency Medicine residents.

Design: Self-rated stress and stress biomarkers were assessed in residents in Emergency Medicine before and after a day shift. The supervising physicians and residents reported numbers of near misses.

Ischemic Conditioning Attenuates Platelet-Mediated Thrombosis: A Tale of Reverse Translation.

Data obtained in both preclinical models and humans have revealed that the favorable cardiac consequences of ischemic conditioning extend beyond a direct effect on the cardiomyocyte. In the current review, we summarize our as-yet limited understanding of the complex relationships between ischemic conditioning, platelet activation-aggregation, and cardioprotection.

Parathyroid Hormone-Related Peptide: A Novel Endocrine Cardioprotective "Conditioning Mimetic".

An as-yet limited body of evidence suggests that calcium-regulating endocrine hormones-in particular, parathyroid hormone-related peptide (PTHrP)-may have unappreciated cardioprotective effects. The current review focuses on the concept that PTHrP may, via modulation of classic cardioprotective signaling pathways, provide a novel strategy to attenuate myocardial ischemia-reperfusion injury.

Mitochondrial Quality Control and Disease: Insights into Ischemia-Reperfusion Injury.

Mitochondria are key regulators of cell fate during disease. They control cell survival via the production of ATP that fuels cellular processes and, conversely, cell death via the induction of apoptosis through release of pro-apoptotic factors such as cytochrome C. Therefore, it is essential to have stringent quality control mechanisms to ensure a healthy mitochondrial network.

Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke.

Background: Rapid and accurate diagnosis of patients presenting with symptoms of stroke is needed to facilitate the timely delivery of proven effective treatment for patients with acute ischemic stroke (AIS). The aim of this study was to determine whether early assessment of platelet reactivity in patients presenting with symptoms of AIS was associated with a diagnosis of AIS, transient ischemic attack (TIA), or stroke mimic.

Methods: This prospective study included patients with symptoms of AIS treated at an inner-city emergency department (ED).

Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery.

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research.

Inhibition of mitochondrial fission as a molecular target for cardioprotection: critical importance of the timing of treatment.

Recent attention has focused on the concept that mitochondrial dynamics-that is, the balance between mitochondrial fusion and fission (fragmentation)-may play a pivotal role in determining cell fate in the setting of myocardial ischemia-reperfusion injury. In this regard, there is an emerging consensus that: (1) ischemia-reperfusion favors mitochondrial fragmentation and (2) strategies aimed at inhibiting the translocation of dynamin-related protein 1 (DRP1: the 'master regulator' of fission) from the cytosol to the mitochondria, when initiated as a pretreatment, are cardioprotective. However, direct molecular evidence of a cause-and-effect relationship between mitochondrial fission and cardiomyocyte death has not been established.