The impact of glucagon to support postabsorptive glucose flux and glycemia in healthy rats and its attenuation in male Zucker diabetic fatty rats.

Hyperglucagonemia is a hallmark of type 2 diabetes (T2DM), yet the role of elevated plasma glucagon (P-GCG) to promote excessive postabsorptive glucose production and contribute to hyperglycemia in patients with this disease remains debatable. We investigated the acute action of P-GCG to safeguard/support postabsorptive endogenous glucose production (EGP) and euglycemia in healthy Zucker control lean (ZCL) rats. Using male Zucker diabetic fatty (ZDF) rats that exhibit the typical metabolic disorders of human T2DM, such as excessive EGP, hyperglycemia, hyperinsulinemia, and hyperglucagonemia, we examined the ability of hyperglucagonemia to promote greater rates of postabsorptive EGP and hyperglycemia. Euglycemic or hyperglycemic basal insulin (INS-BC) and glucagon (GCG-BC) clamps were performed in the absence or during an acute setting of glucagon deficiency (GCG-DF, ∼10% of basal), either alone or in combination with insulin deficiency (INS-DF, ∼10% of basal). Glucose appearance, disappearance, and cycling rates were measured using [2-3H] and [3-3H]-glucose. In ZCL rats, GCG-DF reduced the levels of hepatic cyclic AMP, EGP, and plasma glucose (PG) by 50%, 32%, and 50%, respectively. EGP fell in the presence GCG-DF and INS-BC, but under GCG-DF and INS-DF, EGP and PG increased two- and threefold, respectively. GCG-DF revealed the hyperglucagonemia present in ZDF rats lacked the ability to regulate hepatic intracellular cyclic AMP levels and glucose flux, since EGP and PG levels fell by only 10%. We conclude that the liver in T2DM suffers from resistance to all three major regulatory factors, glucagon, insulin, and glucose, thus leading to a loss of metabolic flexibility.NEW & NOTEWORTHY In postabsorptive state, basal plasma insulin (P-INS) and plasma glucose (PG) act dominantly to increase hepatic glucose cycling and reduce endogenous glucose production (EGP) and PG in healthy rats, which is only counteracted by the acute action of basal plasma glucagon (P-GCG) to support EGP and euglycemia. Hyperglucagonemia, a hallmark of type 2 diabetes (T2DM) present in Zucker diabetic fatty (ZDF) rats, is not the primary mediator of hyperglycemia and high EGP as commonly thought; instead, the liver is resistant to glucagon as well as insulin and glucose.

Investigating Gene-Diet Interactions Impacting the Association Between Macronutrient Intake and Glycemic Traits.

Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate for fat, and its interactions with common and rare variants genome-wide. In main effect meta-analyses, participants consuming more carbohydrate had modestly lower glycemic trait values (e.g., for glycated hemoglobin [HbA1c], -0.013% HbA1c/250 kcal substitution). In GDI meta-analyses, a common African ancestry-enriched variant (rs79762542) reached study-wide significance and replicated in the UK Biobank cohort, indicating a negative carbohydrate-HbA1c association among major allele homozygotes only. Simulations revealed that >150,000 samples may be necessary to identify similar macronutrient GDIs under realistic assumptions about effect size and measurement error. These results generate hypotheses for further exploration of modifiable metabolic disease risk in additional cohorts with African ancestry. ARTICLE HIGHLIGHTS: We aimed to identify genetic modifiers of the dietary macronutrient-glycemia relationship using whole-genome sequence data from 10 Trans-Omics for Precision Medicine program cohorts. Substitution models indicated a modest reduction in glycemia associated with an increase in dietary carbohydrate at the expense of fat. Genome-wide interaction analysis identified one African ancestry-enriched variant near the FRAS1 gene that may interact with macronutrient intake to influence hemoglobin A1c. Simulation-based power calculations accounting for measurement error suggested that substantially larger sample sizes may be necessary to discover further gene-macronutrient interactions.

Evaluation of a media literacy education program for sexual health promotion in older adolescents implemented in Southern universities.

OBJECTIVE: This study evaluated a media literacy education program designed for sexual health promotion, Media Aware, in southeastern universities. PARTICIPANTS: Participants included college students from four universities in the southeastern United States (n = 457). METHODS: Media Aware was implemented on college campuses either in a group setting, one-on-one setting, at a student event, or online only. Media Aware contains four sections on sexual health promotion including on how media messages influence sexual health, gender stereotypes and representations of romantic relationships, sexual violence, substance use, consent, sexual risk behaviors, contraception, STIs, and partner communication. RESULTS: Results indicated significant changes in intention to visit a healthcare provider for sexual health services, intention to use condoms and other forms of birth control, and awareness of Long Acting Reversible Contraceptives after participation in Media Aware. CONCLUSION: Future research should explore how to extend program impacts and use an experimental study design to assess between group differences.

Knowledge and perceptions of adverse childhood experiences (ACEs) among prelicensure nursing students.

OBJECTIVES: Adverse childhood experiences (ACEs) impact health outcomes in adulthood. Positive childhood experiences (PCEs) are associated with resiliency and improved mental and physical health outcomes. There is often a lack of content on ACEs in nursing education. The purpose of this project was to determine the knowledge and perceptions of ACEs and PCEs among prelicensure nursing students. METHODS: A mixed-method pilot study was implanted. Prelicensure nursing students received didactic instruction on ACEs and PCEs and completed online, anonymous ten-item pre- and post-surveys about knowledge on ACEs and PCEs. RESULTS: A positive percent change was observed with all ten statements from pre- to post-surveys. Six themes emerged from qualitative analysis, revealing the importance and benefits of education on ACEs and PCEs. CONCLUSIONS: This study shows that nursing students valued education regarding ACEs, were willing to incorporate their knowledge of ACEs into their practice, and discovered they might have been exposed to ACEs themselves. Implications for International Audience: All nursing programs must include content on ACEs and PCEs to prepare better nurses to care for patients.

Resilience and GRIT among undergraduate nursing students during the COVID 19 pandemic.

OBJECTIVES: Grit and resilience are related but separate concepts. Grit is a long-term commitment toward goals, and it impacts student success and academic achievement. Resilience is the ability of students to recover from stress. Both are important factors in nursing students. METHODS: This descriptive study included surveys measuring demographics, grit, and resilience among two cohorts of senior nursing students in their last semester and explored challenges and difficulties experienced during the COVID-19 pandemic. RESULTS: The mean grit score for all students was 4.0 (0.52) and the mean resilience score was 3.63 (0.73). Directed content analysis of the ten open-ended survey questions revealed three themes: Impact on Education, Personal Impact, and Coping Mechanisms. CONCLUSIONS: Grit and resilience are important factors that can contribute to success in nursing programs and as graduate nurses in the healthcare settings.

Assessing the Impact of Unfolding Case Study Scenarios during High-Fidelity Pediatric Simulation among Undergraduate Nursing Students.

Simulation helps to prepare prelicensure nursing students for practice by providing opportunities to perform clinical skills and make decisions in a safe environment. The integration of nursing knowledge, skills, and decision-making abilities during simulated unfolding case-study scenarios may enhance student self-confidence and foster clinical judgement skills. The purpose of this study was to assess the impact of simulation using unfolding case-study scenarios on undergraduate nursing students' self-confidence in pediatric nursing knowledge, skills, and clinical judgment/decision-making abilities. This mixed methods study included a pre- and post-survey design to evaluate undergraduate nursing students' confidence in pediatric nursing knowledge, skills, and decision-making abilities after participation in both an instructor-led (guided) and a student-led (decision-making) simulation involving unfolding case-study scenarios. Friedman's ANOVA analyses revealed that all 16-items demonstrated statistically significant differences between the three measured responses (pre-simulation and both post-simulation surveys). Post-hoc Wilcoxon signed-rank tests revealed statistically significant differences in student ratings pre-simulation and post-instructor-led (guided) experience for all 16-scored items. The qualitative themes identified were perception of experience, pediatric nursing care, assimilation of knowledge, and critical thinking. Unfolding case-study simulation experiences positively impact the learning, self-confidence, and clinical judgement of undergraduate nursing students.

The impact of telehealth objective structured clinical evaluations in intraprofessional nursing education: A mixed methods study.

BACKGROUND: Telehealth is an expanding modality of providing care. In 2018, the National Organization of Nurse Practitioner Faculties (NONPF) released a white paper encouraging the inclusion of telehealth into nurse practitioner education. It is important for nursing students to gain experience with telehealth so that they are prepared to provide care via telehealth. OBJECTIVES: The purpose of this project was to evaluate the impact of incorporating telehealth simulation into objective structured clinical examinations (OSCEs) in the family nurse practitioner (FNP) and bachelor of science in nursing (BSN) programs. SETTING: This study was conducted at a public, liberal arts university in a rural area of the Southeast United States. PARTICIPANTS: The FNP and BSN students participated in this study. The FNP program is a hybrid master's degree program, which has a two-year plan of study. The BSN program is a traditional campus-based program, which includes two years of upper-division nursing courses. METHODS: This mixed-methods study included a pre- and post-survey design utilizing both quantitative and qualitative measures to evaluate undergraduate and graduate nursing students understanding of and comfort with telehealth and their perceptions of a simulated intradisciplinary telehealth OCSE experience. RESULTS: Students' telehealth knowledge, skills, and confidence were improved after the telehealth OSCE experience. Directed content analysis of the responses revealed three themes: increased knowledge of telehealth, technical difficulties, and teamwork/communication. CONCLUSIONS: It is beneficial for both undergraduate and family nurse practitioner students to have exposure to telehealth in their respective curriculums.

The Use of Debates in an Online Nursing Course.

BACKGROUND: It is important to foster active participation in online graduate nursing courses through creative teaching strategies, such as virtual synchronous debates. METHOD: A free videoconferencing system was used to complete the virtual synchronous debates. Demographic information and survey data were obtained to assess the impact of an online debate on critical thinking and presentation skills. RESULTS: Seven of the 10 scored survey items had statistically significant differences in preimplementation and postimplementation ranked scores. Five qualitative themes were revealed: predebate anxiety/nervousness, technical issues/online format, learning experience, improved presentation skills, and group work. CONCLUSION: Through virtual synchronous debates, graduate nursing students can gain a stronger appreciation for ethical issues in health care, learn to succinctly convey their views, and increase their confidence in presenting a professional argument.

Assessing the Impact of a Preclinical Immersion on Nurse Practitioner Student Confidence for the Initial Clinical Experience.

BACKGROUND: It is important for faculty to prepare nurse practitioner students for their first clinical experiences to ensure student success. PURPOSE: The purpose of this project was to implement a preclinical immersion and determine student perceptions about this experience. METHODS: A half-day preclinical immersion was instituted at the beginning of the family nurse practitioner students' first clinical course. Demographic information and survey data were obtained before the preclinical immersion experience, after completion of the immersion experience, and during the last 2 weeks of the first clinical course. RESULTS: Students' ratings of their clinical skills and knowledge improved during the duration of the semester for 5 of the 7 items. Directed content analysis revealed 3 themes: understanding of clinical expectations, face-to-face interactions with faculty, and cognitive/emotional clinical perceptions. CONCLUSION: The use of preclinical immersion experiences may both practically and emotionally prepare students for graduate nursing clinical experiences.

Toxicant-Induced Metabolic Alterations in Lipid and Amino Acid Pathways Are Predictive of Acute Liver Toxicity in Rats.

Liver disease and disorders associated with aberrant hepatocyte metabolism can be initiated via drug and environmental toxicant exposures. In this study, we tested the hypothesis that gene and metabolic profiling can reveal commonalities in liver response to different toxicants and provide the capability to identify early signatures of acute liver toxicity. We used Sprague Dawley rats and three classical hepatotoxicants: acetaminophen (2 g/kg), bromobenzene (0.4 g/kg), and carbon tetrachloride (0.3 g/kg), to identify early perturbations in liver metabolism after a single acute exposure dose. We measured changes in liver genes and plasma metabolites at two time points (5 and 10 h) and used genome-scale metabolic models to identify commonalities in liver responses across the three toxicants. We found strong correlations for gene and metabolic profiles between the toxicants, indicative of similarities in the liver response to toxicity. We identified several injury-specific pathways in lipid and amino acid metabolism that changed similarly across the three toxicants. Our findings suggest that several plasma metabolites in lipid and amino acid metabolism are strongly associated with the progression of liver toxicity, and as such, could be targeted and clinically assessed for their potential as early predictors of acute liver toxicity.

Virtual Collaboration in Academia.

More nurses and nurse educators today are working distantly in different geographic locations from others, and this includes working from home or satellite locations (Poulsen & Ipsen, 2017). Can we work collaboratively in a purely distance relationship? In academia, collaboration between colleagues is common and often mandated. Being able to engage with others in a collegial manner is necessary, and in some instances the relationship may be purely virtual. This revolution in cognitive capability uses long-distance interactive technology and the structure of professional learning communities. Successful group collaboration is driven by high expectations, shared goals, professionalism, and peer accountability. Such collaboration may be viewed as involving a nonlinear theory of change, with multiple factors influencing processes and outcomes. Factors impacting success include academic considerations (professional goals, disciplinary expertise), nonacademic issues (personal preferences, financial factors), and the development of a culture of trust and collective leadership. Practical strategies to implement such virtual collaboration are discussed.

Mechanism-based identification of plasma metabolites associated with liver toxicity.

Early diagnosis of liver injuries caused by drugs or occupational exposures is necessary to enable effective treatments and prevent liver failure. Whereas histopathology remains the gold standard for assessing hepatotoxicity in animals, plasma aminotransferase levels are the primary measures for monitoring liver dysfunction in humans. In this study, using Sprague Dawley rats, we investigated whether integrated analyses of transcriptomic and metabolomic data with genome-scale metabolic models (GSMs) could identify early indicators of injury and provide new insights into the mechanisms of hepatotoxicity. We obtained concurrent measurements of gene-expression changes in the liver and kidneys, and expression changes along with metabolic profiles in the plasma and urine, from rats 5 or 10 h after exposing them to one of two classical hepatotoxicants, acetaminophen (2 g/kg) or bromobenzene (0.4 g/kg). Global multivariate analyses revealed that gene-expression changes in the liver and metabolic profiles in the plasma and urine of toxicant-treated animals differed from those of controls, even at time points much earlier than changes detected by conventional markers of liver injury. Furthermore, clustering analysis revealed that both the gene-expression changes in the liver and the metabolic profiles in the plasma induced by the two hepatotoxicants were highly correlated, indicating commonalities in the liver toxicity response. Systematic GSM-based analyses yielded metabolites associated with the mechanisms of toxicity and identified several lipid and amino acid metabolism pathways that were activated by both toxicants and those uniquely activated by each. Our findings suggest that several metabolite alterations, which are strongly associated with the mechanisms of toxicity and occur within injury-specific pathways (e.g., of bile acid and fatty acid metabolism), could be targeted and clinically assessed for their potential as early indicators of liver damage.

Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data.

The immense resources required and the ethical concerns for animal-based toxicological studies have driven the development of in vitro and in silico approaches. Recently, we validated our approach in which the expression of a set of genes is uniquely associated with an organ-injury phenotype (injury module), by using thioacetamide, a known liver toxicant. Here, we sought to explore whether RNA-seq data obtained from human cells (in vitro) treated with thioacetamide-S-oxide (a toxic intermediate metabolite) would correlate across species with the injury responses found in rat cells (in vitro) after exposure to this metabolite as well as in rats exposed to thioacetamide (in vivo). We treated two human cell types with thioacetamide-S-oxide (primary hepatocytes with 0 (vehicle), 0.125 (low dose), or 0.25 (high dose) mM, and renal tubular epithelial cells with 0 (vehicle), 0.25 (low dose), or 1.00 (high dose) mM) and collected RNA-seq data 9 or 24 h after treatment. We found that the liver-injury modules significantly altered in human hepatocytes 24 h after high-dose treatment involved cellular infiltration and bile duct proliferation, which are linked to fibrosis. For high-dose treatments, our modular approach predicted the rat in vivo and in vitro results from human in vitro RNA-seq data with Pearson correlation coefficients of 0.60 and 0.63, respectively, which was not observed for individual genes or KEGG pathways.