Implementation of an Innovative Learning Experience to Address Vaccine Hesitancy.

ABSTRACT: The COVID-19 pandemic and subsequent vaccine hesitancy highlighted the need for additional learning experiences for nursing students to address person-centered care and communication. This project aimed to employ a three-step service-learning experience consisting of town hall meetings, motivational interviewing training, and rural health fairs to address vaccine hesitancy in communities surrounding the college. Evaluation of the project revealed satisfaction and increased confidence among participating nursing students.

Adrenal venous sampling for lateralization of cortisol hypersecretion in patients with bilateral adrenal masses.

OBJECTIVE: The objective of this study was to evaluate the role of adrenal venous sampling (AVS) in guiding the management of patients with corticotropin (ACTH)-independent glucocorticoid secretory autonomy and bilateral adrenal masses. DESIGN AND PATIENTS: A cohort with 25 patients underwent AVS and surgical management. MEASUREMENTS: Cortisol was measured from the adrenal veins (AVs) and inferior vena cava (IVC). AV/IVC cortisol ratio and cortisol lateralization ratio (CLR) (dominant AV cortisol concentration divided by the nondominant AV cortisol concentration) were calculated. Posthoc receiver-operating characteristic curves were generated to determine the specificity of revised AV/IVC cortisol ratio and CLR in differentiating unilateral from bilateral disease. RESULTS: Patients underwent unilateral (n = 21) or bilateral (n = 4) adrenalectomy. The mean AV/IVC cortisol ratio for unilateral adrenalectomy was 12.1 ± 9.6 (dominant) and 4.7 ± 3.8 (contralateral) with a mean CLR of 3.6 ± 3.5. The mean AV/IVC cortisol ratio for bilateral adrenalectomy was 7.5 ± 2.1, with a mean CLR of 1.1 ± 0.6. At a mean follow-up of 22 months, one patient who underwent unilateral adrenalectomy for the predicted bilateral disease developed recurrent mild autonomous cortisol secretion. Posthoc analyses demonstrated a specificity of 95%-100% for unilateral disease with AV/IVC cortisol ratio >9 for one side, <2.0 for the opposite side and a CLR > 2.3. The specificity was 80%-90% for bilateral disease with AV/IVC cortisol ratio >5.1 bilaterally and a CLR < 1.1. CONCLUSIONS: Among patients with bilateral adrenal masses and ACTH-independent autonomous cortisol secretion, AVS can distinguish between unilateral and bilateral disease with high specificity and may guide surgical management.

The Self-Determination Inventory: Student Report American Sign Language Translation.

Research literature and community narratives both emphasize the importance of self-determination in the lives of deaf youth. This paper describes the development, initial validation, and potential applications of a translated measure of self-determination for deaf youth, the SDI:SR ASL Translation (SDI:SR ASL). A sample of 3,309 young people who completed the SDI:SR, of whom 392 were deaf, was used in this validation study. Results provide preliminary support for the use of SDI:SR ASL with deaf youth. Findings also indicate that deaf youth who take the SDI:SR ASL score more similarly to youth without disabilities taking the SDI:SR than youth with disabilities. The SDI:SR ASL can be an important tool for researchers and practitioners to better understand self-determination among deaf youth and facilitate continued development of self-determination skills.

Peace, Love, Field Day: An Innovative Approach to Cultivating Healthy Academic Communities.

The American Nurses Association declared 2017 the Year of the Healthy Nurse. In an effort to promote a healthy academic environment, faculty and staff in institutions of higher learning should serve as role models for healthy living for their students. This article describes an innovative approach to cultivating a healthy academic environment. Details about planning and implementation are provided along with recommendations for future implementation.

Elevated Blood Pressure in Low-Income, Rural Preschool Children is Associated with Maternal Hypertension during Pregnancy.

Hypertension (HTN) is a significant public health problem in adults, and rates of HTN are rising in children as well. The purpose of this study was to determine blood pressure (BP) and body mass index (BMI) levels in low-income, rural preschool children and investigate the relationship between child and maternal factors that impact BP and BMI in these children. Results indicated high rates of overweight/obesity and elevated BP levels in this sample. Maternal hypertension during pregnancy also emerged as a predictor of elevated BP in their children.

Trauma and Resilience Among Deaf Individuals.

Resilience in the face of trauma is an important yet elusive construct in human development. While there are prevalent data suggesting high rates of trauma among deaf individuals, valuable insight on how resilience evolves among deaf individuals within the context of trauma has yet to be explored sufficiently. This study explored the concept of resilience through semi-structured interviews with a total of 19 experienced mental health providers. Using an applied thematic analysis approach, the following five themes were identified as crucial protective factors in resilience processes: individual assets, identity development, access to language and communication, access to information, and supportive networks. Findings both confirm previous findings about resilience as well as identify unique protective factors for deaf individuals with trauma. The discussion explores those protective factors and their role as resources for social services professionals and deaf individuals in efforts to support resilience.

Federal Food Assistance Programs and Cardiovascular Risk Factors in Low-Income Preschool Children.

Childhood obesity remains a significant public health concern. Children from lower income households have a greater risk of being obese. Low-income families generally have less access to healthy, affordable food choices and turn to federal food assistance programs. Few studies have examined the impact of food assistance programs on childhood obesity rates. This study explored the association between BMI, blood lipid levels, and three food assistance programs (WIC, reduced lunch, and food stamps) in a sample of predominantly low-income, minority preschool children enrolled in a city-wide preschool program. Screenings were performed at on-site health fairs conducted at nine schools in disadvantaged areas. Screenings included vital signs, a finger stick, head-to-toe exam, vision screening, dental screening, and hearing screening. Of the sample of 229 preschool children, 23.1 % were obese, almost three times the national rate in preschoolers. Children whose families received WIC benefits weighed significantly less than those who did not receive benefits. In addition, 20.6 % of the children screened had elevated systolic blood pressures. Of the sample, 33 % had unhealthy triglyceride levels and 46 % had unhealthy HDL levels with those that received WIC benefits having significantly lower levels of LDL cholesterol This study confirms that low-income, minority children in the South continue to be disproportionately affected by overweight and obesity. In addition, the results of this study indicate WIC as a potential public health initiative to combat the childhood obesity epidemic and reduce other cardiovascular risk factors, such as blood lipids and blood pressure.

Daily Spiritual Experiences of Nurse Educators and Relationship to Depression and Health.

This research describes the first reported assessment of spirituality in nurse educators. Faculty members at a public university in a southern U.S. state participated in a study to investigate the relationship between daily spiritual experiences (DSE), self-reported health, and depression. All participants viewed themselves as spiritual, had a religious affiliation, and recognized a difference between spirituality and religiosity. Many who reported spiritual experiences at least daily rated their health as good or excellent; those reporting less frequent DSE reported more depressive symptoms. Nurse educators' self-awareness of spirituality is important as they prepare future nursing professionals who will integrate spirituality into healthcare.

Differential TLR-ERK1/2 activity promotes viral ssRNA and dsRNA mimic-induced dysregulated immunity in macrophages.

RNA virus induced excessive inflammation and impaired antiviral interferon (IFN-I) responses are associated with severe disease. This innate immune response, also referred to as 'dysregulated immunity,' is caused by viral single-stranded RNA (ssRNA) and double-stranded-RNA (dsRNA) mediated exuberant inflammation and viral protein-induced IFN antagonism. However, key host factors and the underlying mechanism driving viral RNA-mediated dysregulated immunity are poorly defined. Here, using viral ssRNA and dsRNA mimics, which activate toll-like receptor 7 (TLR7) and TLR3, respectively, we evaluated the role of viral RNAs in causing dysregulated immunity. We show that murine bone marrow-derived macrophages (BMDMs) stimulated with TLR3 and TLR7 agonists induce differential inflammatory and antiviral cytokine response. TLR7 activation triggered a robust inflammatory cytokine/chemokine induction compared to TLR3 activation, whereas TLR3 stimulation induced significantly increased IFN/IFN stimulated gene (ISG) response relative to TLR7 activation. To define the mechanistic basis for dysregulated immunity, we examined cell-surface and endosomal TLR levels and downstream mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kB) activation. We identified a significantly higher cell-surface and endosomal TLR7 expression compared to TLR3, which further correlated with early and robust MAPK (pERK1/2 and p-P38) and NF-kB activation in TLR7-stimulated macrophages. Furthermore, blocking EKR1/2, p38, and NF-kB activity reduced TLR3/7-induced inflammatory cytokine/chemokine levels, whereas only ERK1/2 inhibition enhanced viral RNA-mimic-induced IFN/ISG responses. Collectively, our results illustrate that high cell surface and endosomal TLR7 expression and robust ERK1/2 activation drive viral ssRNA mimic-induced excessive inflammatory and reduced IFN/ISG responses, and blocking ERK1/2 activity would mitigate viral-RNA/TLR-induced dysregulated immunity.

Targeting of human cancer stem cells predicts efficacy and toxicity of FDA-approved oncology drugs.

Cancer remains the leading cause of death worldwide with approved oncology drugs continuing to have heterogenous patient responses and accompanied adverse effects (AEs) that limits effectiveness. Here, we examined >100 FDA-approved oncology drugs in the context of stemness using a surrogate model of transformed human pluripotent cancer stem cells (CSCs) vs. healthy stem cells (hSCs) capable of distinguishing abnormal self-renewal and differentiation. Although a proportion of these drugs had no effects (inactive), a larger portion affected CSCs (active), and a unique subset preferentially affected CSCs over hSCs (selective). Single cell gene expression and protein profiling of each drug's FDA recognized target provided a molecular correlation of responses in CSCs vs. hSCs. Uniquely, drugs selective for CSCs demonstrated clinical efficacy, measured by overall survival, and reduced AEs. Our findings reveal that while unintentional, half of anticancer drugs are active against CSCs and associated with improved clinical outcomes. Based on these findings, we suggest ability to target CSC targeting should be included as a property of early onco-therapeutic development.

Identification of cells of leukemic stem cell origin with non-canonical regenerative properties.

Despite most acute myeloid leukemia (AML) patients entering remission following chemotherapy, outcomes remain poor due to surviving leukemic cells that contribute to relapse. The nature of these enduring cells is poorly understood. Here, through temporal single-cell transcriptomic characterization of AML hierarchical regeneration in response to chemotherapy, we reveal a cell population: AML regeneration enriched cells (RECs). RECs are defined by CD74/CD68 expression, and although derived from leukemic stem cells (LSCs), are devoid of stem/progenitor capacity. Based on REC in situ proximity to CD34-expressing cells identified using spatial transcriptomics on AML patient bone marrow samples, RECs demonstrate the ability to augment or reduce leukemic regeneration in vivo based on transfusion or depletion, respectively. Furthermore, RECs are prognostic for patient survival as well as predictive of treatment failure in AML cohorts. Our study reveals RECs as a previously unknown functional catalyst of LSC-driven regeneration contributing to the non-canonical framework of AML regeneration.

Leukemic progenitor compartment serves as a prognostic measure of cancer stemness in patients with acute myeloid leukemia.

We systematically investigate functional and molecular measures of stemness in patients with acute myeloid leukemia (AML) using a cohort of 121 individuals. We confirm that the presence of leukemic stem cells (LSCs) detected through in vivo xenograft transplantation is associated with poor survival. However, the measurement of leukemic progenitor cells (LPCs) through in vitro colony-forming assays provides an even stronger predictor of overall and event-free survival. LPCs not only capture patient-specific mutations but also retain serial re-plating ability, demonstrating their biological relevance. Notably, LPC content represents an independent prognostic factor in multivariate analyses including clinical guidelines of risk stratification. Our findings suggest that LPCs provide a robust functional measure of AML, enabling quantitative and rapid assessment of a wide range of patients. This highlights the potential of LPCs as a valuable prognostic factor in AML management.

Hope on the horizon for healthcare professionals' mental health.

Healthcare professionals have battled physically, mentally, and emotionally overwhelming workforce pressures for years. The COVID-19 pandemic exacerbated this burnout substantially since its onset in 2020. Recently implemented federal initiatives aim to assist in the development of moral resiliency against a morally distressing workplace environment. But is this enough? Meeting the immediate need for substantial mental health resources in the healthcare field is essential and will be a long-lasting endeavor.

A Comparative Analysis of Rural versus Urban Preschool Children's Sugar-Sweetened Beverage Consumption, Body Mass Index and Parent's Weight Status.

Background: Childhood overweight and obesity continues to be a major public health concern, especially in minority, low-income, and rural populations. In order to develop health promotion interventions aimed at reducing obesity rates, there is a need to identify which populations have the highest rates of obesity and the risk factors associated with these high rates. Methods: Data collected from low-income, preschool children and their parents in an urban community and a rural community in Alabama were analyzed and compared. Body Mass Index (BMI) was collected during school based health screenings, and information regarding parent's BMI and child's consumption of sugar-sweetened beverages (SSBs) were collected by parent report. Results: Of the 363 children screened, 12.8% (15.2% rural and 11.9% urban) were considered overweight, and 15.8% (20.2% rural and 14.2% urban) of the sample was classified as obese. Rates of overweight and obesity for mothers were 27.6% (25.3% rural and 28.4% urban) and 48% (56.3% rural and 44.8% urban) respectively and 39.6% (53.3% rural and 34.4% urban) and 34.6% (28.3% rural and 36.9% urban) for fathers. Parents reported their child consumed 3.82 SSBs per day. Overall, mother's BMI, father's BMI and sugar-sweetened beverage consumption was positively associated with child's BMI. However, there were no significant interactions between the rural and urban groups. Conclusion: Rates of overweight and obesity remain high in low-income, predominantly minority preschool children and their parents in two communities in Alabama. Consumption of SSBs, mother's BMI, and father's BMI are three factors impacting the weight status of low-income preschool children. These factors are significant in both rural and urban children.

The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells.

Bitter taste receptors (T2Rs) localize to airway motile cilia and initiate innate immune responses in retaliation to bacterial quorum sensing molecules. Activation of cilia T2Rs leads to calcium-driven NO production that increases cilia beating and directly kills bacteria. Several diseases, including chronic rhinosinusitis, COPD, and cystic fibrosis, are characterized by loss of motile cilia and/or squamous metaplasia. To understand T2R function within the altered landscape of airway disease, we studied T2Rs in non-ciliated airway cell lines and primary cells. Several T2Rs localize to the nucleus in de-differentiated cells that typically localize to cilia in differentiated cells. As cilia and nuclear import utilize shared proteins, some T2Rs may target to the nucleus in the absence of motile cilia. T2R agonists selectively elevated nuclear and mitochondrial calcium through a G-protein-coupled receptor phospholipase C mechanism. Additionally, T2R agonists decreased nuclear cAMP, increased nitric oxide, and increased cGMP, consistent with T2R signaling. Furthermore, exposure to T2R agonists led to nuclear calcium-induced mitochondrial depolarization and caspase activation. T2R agonists induced apoptosis in primary bronchial and nasal cells differentiated at air-liquid interface but then induced to a squamous phenotype by apical submersion. Air-exposed well-differentiated cells did not die. This may be a last-resort defense against bacterial infection. However, it may also increase susceptibility of de-differentiated or remodeled epithelia to damage by bacterial metabolites. Moreover, the T2R-activated apoptosis pathway occurs in airway cancer cells. T2Rs may thus contribute to microbiome-tumor cell crosstalk in airway cancers. Targeting T2Rs may be useful for activating cancer cell apoptosis while sparing surrounding tissue.

Systematic Review of Beef Protein Effects on Gut Microbiota: Implications for Health.

The influence of diet on the gut microbiota is an emerging research area with significant impact on human health and disease. However, the effects of beef, the most consumed red meat in the United States, on gut microbial profile are not well studied. Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, the objective of this systematic review was to conduct a rigorous and thorough review of the current scientific literature regarding the effects of beef protein and the resulting bioactivity of beef protein and amino acids on the gut microbiota, with the goal of identifying gaps in the literature and guiding future research priorities. Utilizing MEDLINE Complete, PubMed, ScienceDirect, Scopus, and Google Scholar databases, we conducted searches including terms and combinations of the following: animal protein, amino acid, beef, bioactive compounds, diet, health, microbiome, peptide, processed beef, and protein. We identified 131 articles, from which 15 were included in our review. The effects of beef on mouse and rat models were mostly consistent for the bacterial phylum level. Short-term (1-4-wk) beef intakes had little to no effect on microbial profiles in humans. Most studies utilized high beef feeding (240-380 g/d), and no study examined recommended amounts of protein [∼3.71 oz/d (105 g/d) meats, poultry, and eggs, or ∼26 oz/week (737 g/wk) from these food sources] according to US dietary guidelines. Additionally, the majority of animal and human studies with adverse findings examined the impact of beef in the context of a diet high in fat or sugar. In conclusion, an extensive gap exists in the literature regarding beef and the microbiota. More studies are necessary to elucidate the role of the microbiota following the consumption of beef, especially in interaction with other dietary compounds, and how beef preparation, processing, and cooking methods differentially influence the biological effects of beef on human health.

Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria.

The tumor microenvironment is characterized by anomalous vascularization, hypoxia, and acidity at the core of solid tumors that culminates in concentrated necrosis and immune system dysregulation among other effects. While this environment presents several challenges for the development of oncotherapeutics that deliver their activity via the enhanced permeability and retention (EPR) effect of the leaky blood vessels around a tumor, oncolytic bacteria, or a class of bacteria with a noted capacity to lyse solid tumors, are attracted to the very environment found at the center of solid tumors that confounds other therapeutics. It is this capacity that allows for a potent, active penetration from the tumor margins into the core, and subsequent colonization to facilitate lysis and immune reactivation. Clostridium novyi in particular has recently shown great promise in preclinical and clinical trials when administered directly to the tumor. These studies indicate that C. novyi is uniquely poised to effectively accomplish the long sought after "holy grail" of oncotherapeutics: selective tumor localization via intravenous delivery. This study reports the development of efficient methods that facilitate experimental work and therapeutic translation of C. novyi including the ability to work with this obligate micro-anaerobe on the benchtop. Additionally, this study seeks to utilize this newfound experimental flexibility to address several gaps in the current knowledge regarding the efficacy of CRIPSR/Cas9-mediated gene insertion in this species to further develop this oncolytic bacteria and the genetic customization of bacteria in general.

The next frontier of oncotherapy: accomplishing clinical translation of oncolytic bacteria through genetic engineering.

The development of a 'smart' drug capable of distinguishing tumor from host cells has been sought for centuries, but the microenvironment of solid tumors continues to confound therapeutics. Solid tumors present several challenges for current oncotherapeutics, including aberrant vascularization, hypoxia, necrosis, abnormally high pH and local immune suppression. While traditional chemotherapeutics are limited by such an environment, oncolytic microbes are drawn to it - having an innate ability to selectively infect, colonize and eradicate solid tumors. Development of an oncolytic species would represent a shift in the cancer therapeutic paradigm, with ramifications reaching from the medical into the socio-economic. Modern genetic engineering techniques could be implemented to customize 'Frankenstein' bacteria with advantageous characteristics from several species.

Lay abstract Side effects of chemotherapeutics are thought to often be a reflection of our inability to target these toxic substances to only cancer cells; hence, scientists have spent centuries searching for alternative treatments that would confine their actions to tumor cells, sparing healthy tissue. Unfortunately, the dense nature of tumor tissue along with altered blood vessels, that lead to diminished tumor tissue oxygenation, altered tissue pH and cellular metabolic inactivity or even cell death have proven challenging. Importantly, these barriers have contributed to local and even sometimes systemic suppression of the patient's immune system that can allow the tumor to grow and progress unchecked. While most non-cancer cells are inhibited by the local tumor environment, certain microbes, including some bacteria and viruses, are drawn to it, possessing a natural ability to selectively infect, colonize and eradicate solid tumors. These microbes may also restore the patient's immune balance. However, use of these microbes is not without its own problems; nevertheless, modern genetic engineering techniques could be implemented to develop customized, safe, effective bacteria with advantageous characteristics. The development and clinical translation of cancer-fighting bacteria would represent a shift in cancer therapeutics and would have ramifications that reach beyond medical efficacy into the realm of socioeconomics. This review seeks to marry the current field of oncolytic bacteria with the expanding field of modern bacterial genetic engineering techniques in prospect of such a therapeutic.