The response readiness tool: An instrument to measure knowledge, skills, and attitude after taking a stop the Bleed® course.

Stop the Bleed® is an emergency response course that offers a certificate of completion but no ending assessment. The purpose of this educational study was to develop and test the Response Readiness Tool (RRT) that measures learning of participants after taking Stop the Bleed®. The study used a pre-/post-test design to measure knowledge and attitudes, and a post-test only for skills. Participants were recruited from existing Stop the Bleed® courses. Knowledge was measured with a 10-item questionnaire, attitude was measured with five Likert-style questions, and skills were measured by observing simulated tourniquet placement. Ninety-five participants were recruited over two semesters. There was a significant difference in the knowledge and attitude scores indicating participants' improvement in learning and attitude toward responding. Internal consistency reliability of scores showed moderate reliability with Cronbach's Alpha of 0.73 and McDonald's Omega of 0.75. A positive correlation was found between expected proficiency and pre-test indicating the tool had construct validity. RRT provides Stop the Bleed® instructors with an instrument to measure knowledge, skills, and attitude of participants after taking Stop the Bleed®. Statistics show moderate reliability and validity; however, larger samples are needed for full psychometric testing. This publication presents the revised tool after the completion of this study.

Taking High-Fidelity Simulation to the Next Level: Nursing in Nontraditional Environments.

ABSTRACT: Nurse educators must prepare nursing students to be competent first responders and providers in nontraditional situations. We developed a course that provides in-depth experiential instruction in disaster nursing, remote/austere nursing, and global health. The Nursing in Nontraditional Environments course provides nursing students with the knowledge and skills to provide quality care to patients in environments outside traditional hospitals and clinics. The course merges survival skills with austere care using evidence-based practice derived from the US Military and the Wilderness Medical Society.

Implementing an approach to prevent life-threatening bleeding: Guidance on forming a campus initiative.

A community that is trained to respond to life-threatening bleeding can reduce the risk of death from trauma and violence. Stop The Bleed is a nationally recognized, free, 1-hour bleeding control training designed for laypersons. Implementing a campuswide Stop the Bleed initiative can be daunting, yet vital to creating a safe, prepared campus. Guidance is offered by faculty, staff, and students from a Stop the Bleed initiative at a public university in the southern United States. This guide provides real-life examples and recommendations based on experience. Utilization of population health nursing students is a fundamental component of success.

Cardiovascular involvement among collegiate athletes following COVID-19 infection.

BACKGROUND: Recent studies suggest that the prevalence of cardiac involvement in young competitive athletes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears to be low. AIM: This study aimed to determine the prevalence of cardiovascular involvement in young competitive athletes. METHODS: In this single-center retrospective cohort study from one Division I university; we assessed the prevalence of cardiovascular involvement among collegiate athletes who tested positive for SARS-CoV-2 by polymerase chain reaction testing. Data were collected from June 25, 2020, to May 15, 2021. The primary outcome was the prevalence of cardiac involvement based on a comparison of pre- and post-infection electrocardiogram (ECGs). The secondary outcome was to evaluate for any association between ethnicity and the presence or absence of symptoms. RESULTS: Among 99 athletes who tested positive for the SARS-CoV-2 virus (mean age 19.9 years [standard deviation 1.7 years]; 31% female), baseline ECG changes suggestive of cardiovascular involvement post-infection were detected in two athletes (2/99; 2%). There was a statistically significant association between ethnicity and the presence or absence of symptoms, χ 2 (3, n = 99) = 10.61, P = 0.01. CONCLUSIONS: The prevalence of cardiovascular involvement among collegiate athletes following SARS-CoV-2 infection in this cohort is low. Afro-American and Caucasian athletes are more likely to experience symptoms following SARS-CoV-2 infection in comparison to Hispanic and Pacific Islander athletes; however, there is no association between ethnicity and symptom severity. RELEVANCE FOR PATIENTS: These data add to the growing body of the literature and agree with larger cohorts that the risk of cardiac involvement post-infection appears to be low among elite athletic and semi-professional athletic populations.

Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model.

Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder caused by GAA repeat expansion within the FXN gene, leading to epigenetic changes and heterochromatin-mediated gene silencing that result in a frataxin protein deficit. Histone deacetylase (HDAC) inhibitors, including pimelic o-aminobenzamide compounds 106, 109 and 136, have previously been shown to reverse FXN gene silencing in short-term studies of FRDA patient cells and a knock-in mouse model, but the functional consequences of such therapeutic intervention have thus far not been described. We have now investigated the long-term therapeutic effects of 106, 109 and 136 in our GAA repeat expansion mutation-containing YG8R FRDA mouse model. We show that there is no overt toxicity up to 5 months of treatment and there is amelioration of the FRDA-like disease phenotype. Thus, while the neurological deficits of this model are mild, 109 and 106 both produced an improvement of motor coordination, whereas 109 and 136 produced increased locomotor activity. All three compounds increased global histone H3 and H4 acetylation of brain tissue, but only 109 significantly increased acetylation of specific histone residues at the FXN locus. Effects on FXN mRNA expression in CNS tissues were modest, but 109 significantly increased frataxin protein expression in brain tissue. 109 also produced significant increases in brain aconitase enzyme activity, together with reduction of neuronal pathology of the dorsal root ganglia (DRG). Overall, these results support further assessment of HDAC inhibitors for treatment of Friedreich ataxia.

Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model.

BACKGROUND: Friedreich's ataxia (FRDA), the most common recessive ataxia in Caucasians, is due to severely reduced levels of frataxin, a highly conserved protein, that result from a large GAA triplet repeat expansion within the first intron of the frataxin gene (FXN). Typical marks of heterochromatin are found near the expanded GAA repeat in FRDA patient cells and mouse models. Histone deacetylase inhibitors (HDACIs) with a pimelic diphenylamide structure and HDAC3 specificity can decondense the chromatin structure at the FXN gene and restore frataxin levels in cells from FRDA patients and in a GAA repeat based FRDA mouse model, KIKI, providing an appealing approach for FRDA therapeutics. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to further improve the pharmacological profile of pimelic diphenylamide HDACIs as potential therapeutics for FRDA, we synthesized additional compounds with this basic structure and screened them for HDAC3 specificity. We characterized two of these compounds, 136 and 109, in FRDA patients' peripheral blood lymphocytes and in the KIKI mouse model. We tested their ability to upregulate frataxin at a range of concentrations in order to determine a minimal effective dose. We then determined in both systems the duration of effect of these drugs on frataxin mRNA and protein, and on total and local histone acetylation. The effects of these compounds exceeded the time of direct exposure in both systems. CONCLUSIONS/SIGNIFICANCE: Our results support the pre-clinical development of a therapeutic approach based on pimelic diphenylamide HDACIs for FRDA and provide information for the design of future human trials of these drugs, suggesting an intermittent administration of the drug.

Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.

Insulin resistance arises from the inability of insulin to act normally in regulating nutrient metabolism in peripheral tissues. Increasing evidence from human population studies and animal research has established correlative as well as causative links between chronic inflammation and insulin resistance. However, the underlying molecular pathways are largely unknown. In this report, we show that many inflammation and macrophage-specific genes are dramatically upregulated in white adipose tissue (WAT) in mouse models of genetic and high-fat diet-induced obesity (DIO). The upregulation is progressively increased in WAT of mice with DIO and precedes a dramatic increase in circulating-insulin level. Upon treatment with rosiglitazone, an insulin-sensitizing drug, these macrophage-originated genes are downregulated. Histologically, there is evidence of significant infiltration of macrophages, but not neutrophils and lymphocytes, into WAT of obese mice, with signs of adipocyte lipolysis and formation of multinucleate giant cells. These data suggest that macrophages in WAT play an active role in morbid obesity and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance. We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue.

Structure and expression of the Huntington's disease gene: evidence against simple inactivation due to an expanded CAG repeat.

Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expanded, unstable trinucleotide repeat in a novel 4p16.3 gene. To lay the foundation for exploring the pathogenic mechanism in HD, we have determined the structure of the disease gene and examined its expression. The HD locus spans 180 kb and consists of 67 exons ranging in size from 48 bp to 341 bp with an average of 138 bp. Scanning of the HD transcript failed to reveal any additional sequence alterations characteristic of HD chromosomes. A codon loss polymorphism in linkage disequilibrium with the disorder revealed that both normal and HD alleles are represented in the mRNA population in HD heterozygotes, indicating that the defect does not eliminate transcription. The gene is ubiquitously expressed as two alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues, suggesting the operation of interacting factors in determining specificity of cell loss. The HD gene was disrupted in a female carrying a balanced translocation with a breakpoint between exons 40 and 41. The absence of any abnormal phenotype in this individual argues against simple inactivation of the gene as the mechanism by which the expanded trinucleotide repeat causes HD. Taken together, these observations suggest that the dominant HD mutation either confers a new property on the mRNA or, more likely, alters an interaction at the protein level.