Comparison of trauma-dosed tranexamic acid versus aminocaproic acid in cardiac surgery in the setting of drug shortage.

Background: Antifibrinolytic agents, tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA), are often used during cardiac surgery to decrease the number of allogenic blood transfusions and to prevent perioperative bleeding. Weight-based TXA dosing regimens have been compared to fixed-dose regimens of EACA with variable outcomes in perioperative blood product transfusions and chest tube output. Serious adverse events, including seizures, have been reported with higher doses of TXA.

Evaluation of Prescribing Practices and Outcomes Using Direct-acting Oral Anticoagulants After Cardiac Surgery.

Purpose: Cardiac surgery patients frequently require anticoagulation. Warfarin remains the preferred agent, and a few trials have reported negative outcomes with the use of direct-acting oral anticoagulants (DOACs) in these patients. Therefore, limited literature exists that supports the dosing, safety, and efficacy of DOACs within the cardiac surgery population.

Evaluation of safety of switching between oral P2Y12 inhibitors: a descriptive study.

Purpose: Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is recommended for patients with acute coronary syndrome and after percutaneous coronary intervention with stenting in stable coronary artery disease to help prevent further thromboembolic events. However, there is limited guidance on appropriate strategies for switching between oral P2Y12 inhibitors. The aim of this study was to evaluate safety of switching modalities at our institution and compare them to the recently published expert consensus recommendations.

Virtual optimization of guideline-directed medical therapy in hospitalized patients with heart failure with reduced ejection fraction: the IMPLEMENT-HF pilot study.

Aims: Implementation of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains incomplete. Non-cardiovascular hospitalization may present opportunities for GDMT optimization. We assessed the efficacy and durability of a virtual, multidisciplinary 'GDMT Team' on medical therapy prescription for HFrEF.

lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation.

Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein BRD3. BRD3 forms phase-separated condensates of which the formation is promoted by DIGIT, occupies enhancers of endoderm transcription factors and is required for endoderm differentiation.

Differential Morphological and Biochemical Recovery from Chemotherapy-Induced Peripheral Neuropathy Following Paclitaxel, Ixabepilone, or Eribulin Treatment in Mouse Sciatic Nerves.

The reversibility of chemotherapy-induced peripheral neuropathy (CIPN), a disabling and potentially permanent side effect of microtubule-targeting agents (MTAs), is becoming an increasingly important issue as treatment outcomes improve. The molecular mechanisms regulating the variability in time to onset, severity, and time to recovery from CIPN between the common MTAs paclitaxel and eribulin are unknown. Previously (Benbow et al.

Peripheral Neuropathy Induced by Microtubule-Targeted Chemotherapies: Insights into Acute Injury and Long-term Recovery.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of disability in cancer survivors. CIPN investigations in preclinical model systems have focused on either behaviors or acute changes in nerve conduction velocity (NCV) and amplitude, but greater understanding of the underlying nature of axonal injury and its long-term processes is needed as cancer patients live longer. In this study, we used multiple independent endpoints to systematically characterize CIPN recovery in mice exposed to the antitubulin cancer drugs eribulin, ixabepilone, paclitaxel, or vinorelbine at MTDs.

Potassium Chloride Sustained Release Dosing Pathway in an Academic Medical Center.

Potassium supplementation can be administered intravenously or orally with either immediate release or sustained release formulations. Sustained release potassium chloride allows for delayed absorption and peak effects. In the inpatient setting, it is important to monitor and prevent both hypokalemia and hyperkalemia.

Safety and Tolerability of Transitioning from Cangrelor to Ticagrelor in Patients Who Underwent Percutaneous Coronary Intervention.

The 3 phase 3 CHAMPION (Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials collectively demonstrated the safety of transitioning from cangrelor, a potent, parenteral rapidly-acting P2Y inhibitor, to clopidogrel in patients who underwent percutaneous coronary intervention (PCI). However, variation in timing of therapy, site-specific binding, and drug half-lives may theoretically complicate switching to other oral P2Y inhibitors. Since regulatory approval, limited data are available regarding the "real-world" safety and tolerability of transitioning to these more potent oral P2Y antagonists.

Effects of Paclitaxel and Eribulin in Mouse Sciatic Nerve: A Microtubule-Based Rationale for the Differential Induction of Chemotherapy-Induced Peripheral Neuropathy.

Microtubule targeting agents (MTAs) often lead to treatment limiting and life threatening side effects, including chemotherapy-induced peripheral neuropathy (CIPN). The frequency of severe CIPN varies among different MTAs. Since the microtubule binding interactions and mechanisms of action also vary among MTAs, we hypothesized that these distinct mechanisms may underlie the variability in frequency of severe CIPN.

Synthetic garments enhance comfort, thermoregulatory response, and athletic performance compared with traditional cotton garments.

The ability of a fabric to transfer moisture is referred to as "wicking," and an increase in this property may have benefits in terms of comfort and thermoregulation. However, this phenomenon has not been studied in the context of sporting-type activities. Therefore, the purpose of this study is to assess whether comfort, thermal physiological parameters, and physical performance can be affected by the garment that is used.

Implementation of an Automated Dispensing Cabinet Stewardship Program at a Tertiary Academic Medical Center.

Automated dispensing cabinet (ADC) use within hospitals is designed to replace or partially replace medication cabinets or carts to allow for a more decentralized model of medication distribution. This project was designed to improve medication delivery by decreasing the burden of dispensing patient-specific medications from a centralized inpatient pharmacy while decreasing overall inventory cost. This single-center pilot analysis evaluated ADC inventory optimization in a mixed medical population.

Solution phase conformation and proteolytic stability of amide-linked neuraminic acid analogues.

Amide-linked homopolymers of sialic acid offer the advantages of stable secondary structure and increased bioavailability making them useful constructs for pharmaceutical design and drug delivery. Defining the structural characteristics that give rise to secondary structure in aqueous solution is challenging in homopolymeric material due to spectral overlap in NMR spectra. Having previously developed computational tools for heteroologomers with resolved spectra, we now report that application of these methods in combination with circular dichroism, NH/ND NMR exchange rates and nOe data has enabled the structural determination of a neutral, δ-amide-linked homopolymer of a sialic acid analogue called Neu2en.

Multivalency amplifies the selection and affinity of bradykinin-derived peptides for lipid nanovesicles.

The trimer of a bradykinin derivative displayed a more than five-fold increase in binding affinity for phosphatidylserine-enriched nanovesicles as compared to its monomeric precursor. The nanovesicle selection is directly correlated with multivalency, which amplifies the electrostatic attraction. This strategy may lead to the development of novel molecular probes for detecting highly curved membrane bilayers.

Adaptation to altitude as a vehicle for experiential learning of physiology by university undergraduates.

In this article, an experiential learning activity is described in which 19 university undergraduates made experimental observations on each other to explore physiological adaptations to high altitude. Following 2 wk of didactic sessions and baseline data collection at sea level, the group ascended to a research station at 12,500-ft elevation. Here, teams of three to four students measured the maximal rate of oxygen uptake, cognitive function, hand and foot volume changes, reticulocyte count and hematocrit, urinary pH and 24-h urine volume, athletic performance, and nocturnal blood oxygen saturation.

Interleukin-1beta increases binding of the iron regulatory protein and the synthesis of ferritin by increasing the labile iron pool.

This study was undertaken to begin to elucidate the mechanisms by which cytokines influence intracellular iron homeostasis. Intracellular iron homeostasis is maintained by the coordinated regulation of ferritin and transferrin receptor synthesis. The synthesis of these proteins is coordinated by cytoplasmic iron regulatory proteins (IRP), which bind to iron responsive elements (IRE) on their mRNAs.

Transferrin is required for normal distribution of 59Fe and 54Mn in mouse brain.

Hypotransferrinemia (hpx/hpx) is a genetic defect in mice resulting in <1% of normal plasma transferrin (Tf) concentrations; heterozygotes for this mutation (+/hpx) have low circulating Tf concentrations. These mice provide a unique opportunity to examine the role of Tf in Fe and Mn transport in the brain. Twenty weanling wild-type BALB/cJ mice, 15 +/hpx mice, and 12 hpx/hpx mice of both sexes were injected i.