Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes.

New antibiotics are needed to combat rising levels of resistance, with new Mycobacterium tuberculosis (Mtb) drugs having the highest priority. However, conventional whole-cell and biochemical antibiotic screens have failed. Here we develop a strategy termed PROSPECT (primary screening of strains to prioritize expanded chemistry and targets), in which we screen compounds against pools of strains depleted of essential bacterial targets. We engineered strains that target 474 essential Mtb genes and screened pools of 100-150 strains against activity-enriched and unbiased compound libraries, probing more than 8.5 million chemical-genetic interactions. Primary screens identified over tenfold more hits than screening wild-type Mtb alone, with chemical-genetic interactions providing immediate, direct target insights. We identified over 40 compounds that target DNA gyrase, the cell wall, tryptophan, folate biosynthesis and RNA polymerase, as well as inhibitors that target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating the ability of PROSPECT to yield inhibitors against targets that would have eluded conventional drug discovery.

Guiding Elements for Success in the Nurse Educator Role.

ABSTRACT: As educators and administrators, we are challenged to find processes that support faculty entering educational roles whether in part-time, full-time, or tenured positions. This article focuses on guiding elements that bring about transition from the new or novice nurse instructor to the faculty role. Supporting elements for transition include mentoring, pedagogical instruction, and continued knowledge acquisition. Without formal role preparation, many nurse faculty experience conflict and ongoing deficits in the knowledge that is needed to be successful in an academic setting.

Predator odor evokes sex-independent stress responses in male and female Wistar rats and reduces phosphorylation of cyclic-adenosine monophosphate response element binding protein in the male, but not the female hippocampus.

Post-traumatic stress disorder (PTSD) is characterized by memory disturbances following trauma. Acute predator threat has emerged as an ethological model of PTSD, yet the effects of predator odor on signaling cascades associated with long-term memory remain poorly understood. In this study, we exposed male and female Wistar rats to the synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to assess behavioral and physiological responses as well as rapid modulation of signal transduction cascades associated with learning and memory in the male and female hippocampus. During exposure to TMT in the homecage, both male and female animals displayed robust immobility, avoidance, and altered activity as a function of time. Physiologically, TMT exposure increased circulating corticosterone and blood glucose in both male and female rodents, suggesting that TMT evokes sex-independent behavioral and physiological responses. With respect to signal transduction, TMT exposure rapidly reduced phosphorylation of cyclic-adenosine monophosphate response element binding protein (CREB) in the male, but not the female hippocampus. Furthermore, TMT exposure reduced phosphorylation of extracellular signal-regulated kinase 1/2 and increased nuclear expression of the synapto-nuclear messenger protein Jacob in the male hippocampus, consistent with activation of the CREB shut-off pathway. In a follow-up behavioral experiment, post-training exposure to TMT did not affect spatial water maze performance of male rats. However, male rats re-introduced to the context in which TMT had previously been presented displayed avoidance and hyperactivity, but not freezing behavior or elevated corticosterone responses, suggesting that TMT exposure supports a form of contextual conditioning which is not characterized by immobility. Taken together, our findings suggest that TMT evokes similar behavioral and physiological responses in male and female Wistar rats, but affects distinct signaling cascades in the male and female hippocampus which may contribute to behavioral disruptions associated with predator exposure.

A Paradigm Shift for the Nursing Education Model: A Scoping Review.

BACKGROUND: The Nursing Education Model (NEM) introduced a framework for education reform. This study examined the applications of NEM in education to determine whether modifications to NEM were warranted. METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews process for scoping reviews was used. Online databases and searches identified peer-reviewed articles published from 2010-to June 2023, and 71 articles were identified that met the inclusion and exclusion criteria. RESULTS: Six themes were derived from the findings: (1) learner-centered curricula; (2) instructional methods; (3) inclusive classrooms; (4) pedagogical creativity; (5) bridge theory-clinical divide; and (6) multiple units of analysis. CONCLUSION: The findings support the application of the NEM to promote a paradigm shift in instructional content, methods, and evaluation of outcomes. Based on use of the model identified in the literature, future modifications to NEM may be indicated, based on continued evidence. [J Nurs Educ. 2024;63(3):141-147.].

Moral Resilience and Race, Ethnicity, and Culture Within Healthcare Workers During the COVID-19 Pandemic in the USA: a Scoping Review.

The COVID-19 pandemic has and continues to impact the world affecting all aspects of life. Healthcare workers have been hit especially hard and, in many cases, experience negative impacts not only on their physical health but also on their mental and emotional well-being. Additionally, the COVID-19 pandemic has not affected populations equally and this is true in the USA, including healthcare workers. However, these workers have also persevered, drawing on moral resilience to push through challenging situations throughout this pandemic. In this scoping review, we analyzed studies to assess the role of race, ethnicity, and/or culture on the moral resilience of healthcare workers throughout the COVID-19 pandemic. Our aim was to understand the research that has assessed these potential connections and determine best practices for building moral resilience in the face of this global catastrophe. Fourteen articles met inclusion criteria and were analyzed in this review. Following a thematic analysis, several themes emerged including (1) moral resilience and the COVID-19 pandemic; (2) race, ethnicity, and culture among healthcare workers; and (3) building moral resilience. In sum, the findings from the literature indicate a paucity of studies that analyze the role played by race, ethnicity, and/or culture in connection to moral resilience during the COVID-19 pandemic.

Phone-delivered mindfulness training for patients with implantable cardioverter defibrillators: results of a pilot randomized controlled trial.

BACKGROUND: The reduction in adrenergic activity and anxiety associated with meditation may be beneficial for patients with implantable cardioverter defibrillators. PURPOSE: This study aims to determine the feasibility of a phone-delivered mindfulness intervention in patients with defibrillators and to obtain preliminary indications of efficacy on mindfulness and anxiety. METHODS: Clinically stable outpatients were randomized to a mindfulness intervention (eight weekly individual phone sessions) or to a scripted follow-up phone call. We used the Hospital Anxiety and Depression Scale and the Five Facets of Mindfulness to measure anxiety and mindfulness, and multivariate linear regression to estimate the intervention effect on pre-post-intervention changes in these variables. RESULTS: We enrolled 45 patients (23 mindfulness and 22 control; age, 43-83; 30 % women). Retention was 93 %; attendance was 94 %. Mindfulness (beta = 3.31; p = 0.04) and anxiety (beta = -1.15; p = 0.059) improved in the mindfulness group. CONCLUSIONS: Mindfulness training can be effectively phone-delivered and may improve mindfulness and anxiety in cardiac defibrillator outpatients.

Teaching about vulnerable populations: nursing students' experience in a homeless center.

Cultural competence is not limited to ethnicity, religion, or race but is inclusive of vulnerable groups, such as the homeless. The complex health and social issues related to homelessness requires educational instruction that supports students' ability to address and care for the multidimensional elements that surround this group. Exposure to homeless populations provides nursing students with increased awareness of the issues related to health disparities, while promoting introspective reflection on one's values and beliefs. To increase student exposure to working with homeless clients, a service-learning project using a critical social theory (CST) lens was offered at a homeless center. The students' response that clients were "just like" them, coupled with ambiguity regarding the complex social-economic-political issues surrounding the homeless, may indicate a need for further education regarding cultural understanding, sensitivity, and vulnerability. This project demonstrates the need for learning experiences that support advocacy and social responsibility for vulnerable groups.

Emergency Department Clinician Experience with Embedded Palliative Care.

Background: While the benefits of embedding palliative care (PC) clinicians into the emergency department (ED) are now more widely appreciated, only a handful of programs have been reported in the literature. None has previously evaluated the attitudes and experiences of the multidisciplinary ED team with such an intervention. Objectives: We evaluated the experience of ED attendings, residents, nurses, social workers, and chaplains with an embedded PC clinician in the ED. Design/Subjects: We embedded PC clinicians into an urban, academic ED in the United States and surveyed 142 ED clinicians about their experiences. We analyzed survey results using descriptive analysis for closed-ended responses and thematic analyses for open-ended responses. Measurements/Results: One hundred six of 141 clinicians responded (75% response rate). Quantitative analysis found that 99% of participants found the program valuable. Benefits of embedded PC included changing patients' management or care trajectory, freeing up ED providers for other tasks, contributing to provider education, helping providers feel more supported during their shifts, and adding to providers' skill sets and confidence in practicing primary PC. Most participants reported minimal barriers to engaging with PC. The qualitative analysis identified program approval, desire for expansion/continuation of the program, and ongoing education of ED staff. Important themes for future programs include staff education, PC proactivity, importance of adapting to the needs of the ED, and education regarding PC consultation criteria. Conclusions: ED clinicians' attitudes toward embedded PC reflected overall approval, with underlying themes of providers feeling more supported during their shifts, improved resource management, the perception of better patient care, and nursing empowerment.

Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility.

Candida auris is a fungal pathogen of high concern due to its ability to cause healthcare-associated infections and outbreaks, its resistance to antimicrobials and disinfectants and its persistence on human skin and in the inanimate environment. To inform surveillance and future mitigation strategies, we defined the extent of skin colonization and explored the microbiome associated with C. auris colonization. We collected swab specimens and clinical data at three times points between January and April 2019 from 57 residents (up to ten body sites each) of a ventilator-capable skilled nursing facility with endemic C. auris and routine chlorhexidine gluconate (CHG) bathing. Integrating microbial-genomic and epidemiologic data revealed occult C. auris colonization of multiple body sites not targeted commonly for screening. High concentrations of CHG were associated with suppression of C. auris growth but not with deleterious perturbation of commensal microbes. Modeling human mycobiome dynamics provided insight into underlying alterations to the skin fungal community as a possible modifiable risk factor for acquisition and persistence of C. auris. Failure to detect the extensive, disparate niches of C. auris colonization may reduce the effectiveness of infection-prevention measures that target colonized residents, highlighting the importance of universal strategies to reduce C. auris transmission.

A paradigm shift in nursing education: a new model.

Nurse educators are being inspired to rethink historically teacher-centered curriculum designs and to embrace new ideologies that have a stronger focus on student-centered learning. The paradigm shift is reflected in the National League for Nursing's call for nursing education to respond to the changing needs of our student population by providing an educational learning environment substantiated in evidence for both curriculum and pedagogical practice. To meet these expectations, education should provide active learning that promotes critical thinking and analysis and problem-solving skills. This article presents a model for higher education in nursing that takes into account the learner, the instructor, and the systems that influence their relationships, providing congruence for educational outcomes.

Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer.

BACKGROUND: Breast cancer invasion and metastasis involves both epithelial and stromal changes. Our objective was to delineate the pivotal role stroma plays in invasion by comparing transcriptomes among stromal and epithelial cells in normal tissue and invasive breast cancer. METHODS: Total RNA was isolated from epithelial and stromal cells that were laser captured from normal breast tissue (n = 5) and invasive breast cancer (n = 28). Gene expression was measured using Affymetrix U133A 2.0 GeneChips. Differential gene expression was evaluated and compared within a model that accounted for cell type (epithelial [E] versus stromal [S]), diagnosis (cancer [C] versus normal [N]) as well as cell type-diagnosis interactions. RESULTS: Compared to NE, the CE transcriptome was highly enriched with genes in proliferative, motility and ECM ontologies. Differences in CS and NS transcriptomes suggested that the ECM was being remodeled in invasive breast cancer, as genes were over-represented in ECM and proteolytic ontologies. Genes more highly expressed in CS compared to CE were primarily ECM components or were involved in the remodeling of ECM, suggesting that ECM biosynthesis and remodeling were initiated in the tumor stroma. CONCLUSION: Based on identified molecular cross-talk between the two contiguous cell populations, a mechanistic model that spurs invasion is proposed, that shows breast cancer invasion proceeds through the acquisition of a motile phenotype in tumor epithelial cells and a reactive phenotype in cancer associated fibroblasts.

Quality assessment of neoadjuvant therapy use in breast conservation: barriers to implementation.

Neoadjuvant systemic therapy (NST) for operable breast cancer can increase the options for conservative surgery in patients with breast cancer. We performed an analysis of a breast cancer outcomes database as a quality assessment of neoadjuvant therapy use in relation to breast conservative rate (BCR). Data were reviewed from a breast cancer database established to monitor outcomes of breast cancer surgery at a tertiary care breast cancer clinic. The frequency of NST-use was correlated to tumor size and BCR. Cause-specific factors for omitting NST in patients undergoing mastectomy for tumors 3 cm or greater were determined. NST was employed in 29 of 241 (12%) cases of invasive breast carcinoma treated surgically from 2003 to 2005. Although a significant decrease in BCR occurred in tumors >3 cm, NST was not frequently employed until tumors reached >5 cm. Defined contraindications to breast conservation (65%) and patient choice for mastectomy (30%) were the two most common reasons for omitting NST in tumors > or = 3 cm. Despite the initial appearance of NST under-utilization in tumors measuring between 3-5 cm, appropriate exclusion of patients not suitable for breast conservation and patient choice for mastectomy both emerged as leading factors for the omission of NST in this group. Use of NST is an important quality metric in optimizing breast conservation. Patient education and greater understanding of patient-related barriers to NST may help improve BCR.

Ductal lavage of cancerous and unaffected breasts: procedure success rate and cancer detection.

OBJECTIVE: To evaluate ductal lavage (DL) performance in women with known breast cancer and to assess cell yield from contralateral high-risk breasts. STUDY DESIGN: Women with newly diagnosed breast cancer were offered study participation. They underwent bilateral nipple aspiration, followed by DL of those ducts demonstrating nipple aspiration fluid (NAF) production. The procedures were conducted in the operating room prior to definitive surgery. Samples were interpreted masked as to which breast was malignant, and the interpretation used a 5-category scheme: insufficient, benign, mildly atypical, markedly atypical or malignant. RESULTS: A total of 23 women with 24 cancers were enrolled, ranging in age from 32 to 76. One had ductal carcinoma in situ; there were 13 T1, 6 T2 and 4 T3 lesions. NAF was identified in 72% of breasts, more commonly in cancerous than unaffected breasts. DL was performed on 33 breasts; of these, 55% were adequate. Only 16.6% of samples from malignant breasts contained abnormality, marked atypia in 1 and malignancy in 3. No samples from unaffected breasts demonstrated cellular abnormalities. CONCLUSION: The low sensitivity of DL performed on malignant breasts to identify abnormal cells adds to the growing body of evidence that this is not an effective tool in identifying existing breast cancer. Numbers are small, but the ability of DL to identify atypia in unaffected high-risk breasts may also be suboptimal. Future efforts should focus on molecular markers of risk and on alternate means of cell or tissue retrieval.

Simulation-Based Interprofessional Education: A Nursing and Social Work Collaboration.

BACKGROUND: Contemporary teaching and learning pedagogy commands interprofessional collaboration among allied professions such as nursing and social work, two professions that have a natural inclination to partner in the workforce. METHOD: Nursing and social work students participated in a structured simulated learning experience where they demonstrated their respective professional practice skills in a supported learning environment while working collaboratively to assess one of two patient types: high-fidelity or simulated. RESULTS: Both groups expressed initial worry during prebriefing but articulated their appreciation for and usefulness of working with the other profession. Future collaboration includes learning about respective professional roles, more direction regarding the professional handoff, and prior exposure to the appearance and functionality of high-fidelity patient types in an effort to establish best strategies for partnership. CONCLUSION: Interprofessional collaboration diverges from the silo effect, leading to collegiality among affiliated professionals, as well as increased patient safety and improved patient outcomes. [J Nurs Educ. 2019;58(2):110-113.].

Integrating Video Simulation Scenarios Into Online Nursing Instruction.

BACKGROUND: As nursing programs continue to expand online, innovative pedagogies that support online teaching and learning practices grounded in theoretical constructs are needed. METHOD: Video simulation scenarios and VoiceThread technology were used to create a model of online instruction that promotes active student participation and aligns with course objectives and content. Kolb's experiential learning theory serves as the framework for this project. RESULTS: The integration of multimedia in the course gave students a collaborative experience where they can apply their knowledge to the simulation scenarios. Inclusion of the vignettes was found to be effective in addressing specific areas of curriculum while stimulating student engagement. CONCLUSION: Increased use of online delivery for nursing education necessitates course designs that promote student interaction and foster community. Teaching and learning practices that include technologies and are supported by theoretical constructs promote best practices for online instruction. [J Nurs Educ. 2018;57(4):245-249.].

Teaching undergraduate nursing students about environmental health: addressing public health issues through simulation.

Schools of nursing are challenged to find clinical placements in public health settings. Use of simulation can address situations unique to public health, with attention to specific concerns, such as environmental health. Environmental health is an integral part of public health nursing and is a standard of professional practice. Current simulations focus on acute care situations, offering limited scenarios with a public health perspective and excluding environmental health. This study's simulation scenario was created to enhance nursing students' understanding of public health concepts within an environmental health context. Outcomes from the simulation include the need for integration of environmental issues in public health teaching. Students stated that this scenario provided a broader understanding of the environmental influences that can affect the client's and family's health. This scenario fills a void in simulation content, while providing an interactive teaching and learning strategy to help students to apply knowledge to practice.

Morphological parameters associated with ruptured posterior communicating aneurysms.

The rupture risk of unruptured intracranial aneurysms is known to be dependent on the size of the aneurysm. However, the association of morphological characteristics with ruptured aneurysms has not been established in a systematic and location specific manner for the most common aneurysm locations. We evaluated posterior communicating artery (PCoA) aneurysms for morphological parameters associated with aneurysm rupture in that location. CT angiograms were evaluated to generate 3-D models of the aneurysms and surrounding vasculature. Univariate and multivariate analyses were performed to evaluate morphological parameters including aneurysm volume, aspect ratio, size ratio, distance to ICA bifurcation, aneurysm angle, vessel angles, flow angles, and vessel-to-vessel angles. From 2005-2012, 148 PCoA aneurysms were treated in a single institution. Preoperative CTAs from 63 patients (40 ruptured, 23 unruptured) were available and analyzed. Multivariate logistic regression revealed that smaller volume (p = 0.011), larger aneurysm neck diameter (0.048), and shorter ICA bifurcation to aneurysm distance (p = 0.005) were the most strongly associated with aneurysm rupture after adjusting for all other clinical and morphological variables. Multivariate subgroup analysis for patients with visualized PCoA demonstrated that larger neck diameter (p = 0.018) and shorter ICA bifurcation to aneurysm distance (p = 0.011) were significantly associated with rupture. Intracerebral hemorrhage was associated with smaller volume, larger maximum height, and smaller aneurysm angle, in addition to lateral projection, male sex, and lack of hypertension. We found that shorter ICA bifurcation to aneurysm distance is significantly associated with PCoA aneurysm rupture. This is a new physically intuitive parameter that can be measured easily and therefore be readily applied in clinical practice to aid in the evaluation of patients with PCoA aneurysms.

Quality measures for breast cancer surgery: initial validation of feasibility and assessment of variation among surgeons.

OBJECTIVES: To identify and quantify surgical outcomes as possible quality measures of initial breast cancer surgery and to assess variation among surgeons. DESIGN: Descriptive analysis of concurrently collected outcome measures. SETTING: University hospital with a designated breast cancer center. PATIENTS: Patients with a preoperative diagnosis of invasive breast cancer or ductal carcinoma in situ undergoing their initial cancer surgery from April 1, 2003, to March 30, 2008. MAIN OUTCOME MEASURES: Eight measures were identified: (1) total mastectomy rate; (2) close (<1 mm) and positive margin rate following initial partial mastectomy; (3) number of operations required in breast conservation; (4) number of nodes obtained from sentinel lymph node biopsy; (5) number of nodes from axillary dissection; (6) proportion of patients with positive sentinel lymph node biopsy undergoing axillary dissection; (7) use of intraoperative lymph node assessment; and (8) time from diagnosis to surgery. RESULTS: Nine hundred ten operations (218 for ductal carcinoma in situ, 692 for invasive breast cancer) were performed by 6 surgeons. Variation existed among surgeons in the combined close and positive margin rate, number of nodes obtained from sentinel lymph node biopsy, and use of intraoperative lymph node assessment. No significant variation was seen for the overall mastectomy rate, mean number of operations, positive margin rate alone, and number of lymph nodes from axillary dissection. CONCLUSIONS: Quality indicators for breast cancer surgery can be identified and readily monitored. Outcome variation exists at a high-volume breast center. Further study into the causes and effects of this variation on short- and long-term patient outcomes as well as health care costs is needed.

Cytokeratin-positive cells in the bone marrow of breast cancer patients and noncancer donors.

Detection of disseminated tumor cells in the bone marrow may provide important prognostic information in breast cancer patients. With few exceptions the number of stained cells scored as cancer is very low; there may be only 1 cell per slide. This makes definitive interpretation of cancer in marrow challenging. False-positive staining of marrow cells with cytokeratin (CK) antibody is relatively common and makes interpretation more difficult. In this report we focus on false-positive staining of marrow specimens from breast cancer patients and noncancer controls and demonstrate that the frequency of false-positive events is common. Bone marrow was collected from 23 cancer-free donors and 60 breast cancer patients. Samples were processed by Ficoll density gradient centrifugation and slides were prepared for immunocytochemical staining with CK and irrelevant (IR) antibody. Slides were evaluated manually and positive cells were categorized as tumor cells, hematopoetic cells, or questionable cells. False-positive staining events were commonly observed in noncancer cases stained with CK or IR antibodies and in breast cancer cases stained with IR antibody. There was little difference in the number of breast cancer marrow specimens scored as tumor cells regardless of whether the antibody used was CK or IR. It is important to devise improved criteria and methods for accurate detection and interpretation of disseminated tumor cells in the marrow of breast cancer patients.