Initiating your coronation.

Earning an advanced degree in biomedical sciences can be a challenging experience, and recent data indicate high levels of stress and anxiety among the current generation of learners. We propose here a new illustration for all graduate students to visualize their didactic journey as a coronation process. Before their coronation, trainees must undergo rigorous preparation. During the training, four key attributes, best described by the acronym COST (Credibility, Opportunity, Strength, and Tenacity), are cultivated. Throughout their academic journey, which is a critical period of intellectual and personal growth, the trainees will enhance their understanding of the responsibility of wearing a CROWN, which requires accepting the Cost of earning a diadem, Revolutionizing their thought construct, being Open to innovation and research, acknowledging that Wealth is intrinsically connected to their health, and Never forsaking their aspiration and pursuits. Executing these principles daily will provide a mechanism on which to rise to the stature of achieving individual career goals (i.e., being a Regent of your life). Actualization of this process requires sacrifice, maturity, and a sense of fearlessness. The results of taking this approach will lead to an educational legacy that establishes a pattern of academic success that can be emulated by future learners.

Thoracic aortic syndromes in the emergency department: recognition and management.

Acute aortic syndromes include aortic dissection, penetrating atherosclerotic ulcer, and intramural hematomas, but aortic dissection is the most common and the deadliest. This review summarizes the latest evidence on developing a differential for aortic dissection when common complaints, such as chest pain, abdominal pain, and syncope are also present. Recent evidence on the optimal uses of emergency department imaging studies and risk stratification tools are reviewed, along with special considerations in the management of penetrating atherosclerotic ulcer and intramural hematoma. Pharmacologic therapies for managing hemodynamic parameters and shock, and indications for operative intervention are also reviewed, along with cutting-edge diagnostic and treatment options on the horizon.

Case Series on 2g Tranexamic Acid Flush From the 75th Ranger Regiment Casualty Database.

Early tranexamic acid (TXA) administration for resuscitation of critically injured warfighters provides a mortality benefit. The 2019 Tactical Combat Casualty Care (TCCC) recommendations of a 1g drip over 10 minutes, followed by 1g drip over 8 hours, is intended to limit potential TXA side effects, including hypotension, seizures, and anaphylaxis. However, this slow and cumbersome TXA infusion protocol is difficult to execute in the tactical care environment. Additionally, the side effect cautions derive from studies of elderly or cardiothoracic surgery patients, not young healthy warfighters. Therefore, the 75th Ranger Regiment developed and implemented a 2g intravenous or intraosseous (IV/IO) TXA flush protocol. We report on the first six cases of this protocol in the history of the Regiment. After-action reports (AARs) revealed no incidences of post-TXA hypotension, seizures, or anaphylaxis. Combined, the results of this case series are encouraging and provide a foundation for larger studies to fully determine the safety of the novel 2g IV/IO TXA flush protocol toward preserving the lives of traumatically injured warfighters.

Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (-)-pentazocine.

The mixed-action κ-opioid receptor (KOR) agonist, pentazocine, binds to both KOR and the µ-opioid receptor (MOR). Racemic (±)-pentazocine and (-)-pentazocine, each administered systemically, have been shown to produce antinociception in various animal models. In contrast, racemic (±)-pentazocine failed to produce antinociception when administered intrathecally (i.t.). However, whether spinal activation of KOR and MOR by (-)-pentazocine produces antinociception and the relative contribution of KOR and MOR in mediating antinociception remain unknown. Hence, we investigated whether i.t. (-)-pentazocine produces dose-dependent modulation of acute thermal nociception. Drugs were administered intrathecally in Sprague-Dawley rats and tail flick latency was recorded. Pentazocine produced a significant antinociceptive effect that was mediated by KOR and/or MOR at differential doses. MOR blockade restored the antinociceptive effect of an ineffective dose and prolonged the duration of an effective dose of pentazocine. Hence, spinal KOR and MOR mediated the effect of pentazocine. This study provides evidence that spinal MOR negatively modulates the KOR-mediated antinociceptive effect of i.t. pentazocine.

Estrogen facilitates and the kappa and mu opioid receptors mediate antinociception produced by intrathecal (-)-pentazocine in female rats.

Pentazocine, a mixed-action kappa opioid receptor (KOR) agonist, has high affinity for both KOR and the mu opioid receptor (MOR), and has been shown clinically to alleviate pain with a pronounced effect in women. However, whether local application of pentazocine in the spinal cord produces antinociception and the contribution of spinal KOR and MOR in mediating the effect of pentazocine in female rats remain unknown. Also, it is not known whether pentazocine-induced antinociception in females is estrogen-dependent. Hence, we investigated whether intrathecal (i.t.) (-)-pentazocine produces thermal antinociception and whether estrogen modulates the drug effect in female rats. Only the highest dose of pentazocine (500 nmol) was effective in producing antinociception in ovariectomized (OVX) rats. In contrast, pentazocine produced antinociception in estradiol-treated ovariectomized females (OVX+E) rats with the lowest effective dose being 250nmol. KOR or MOR mediated the effect of the lowest effective dose in OVX+E rats; however, MOR blockade extended the KOR-mediated effect of 500nmol pentazocine in both groups. In normally cycling females, the 250nmol dose was effective in producing antinociception at the proestrous, but not at the diestrous stage of the estrous cycle. Thus, estrogen facilitates and KOR or MOR mediates. the antinociceptive effect of i.t. (-)-pentazocine in female rats. Selective doses of (-)-pentazocine, with or without MOR blockade, may have a therapeutic benefit.