A phenomenological exploration of the gender transition experience: findings to improve culturally competent nursing care and decrease health disparities.

BACKGROUND: Most recently, it has been reported that 1.4 million adults in the United States identify as transgender. This number is double what was reported just five years earlier. What little research has been completed on this vulnerable population indicates that people who identify as transgender experience higher rates of depression, suicide, and social stigmatization than the cisgender population. Stigmatization of transgender people and lack of access to quality care is often the root for these disparities. Very few studies have examined the experience of transition. OBJECTIVE: The purpose of this phenomenological study was to explore the experience of transitioning from one gender to another. METHODS: Non-structured, in-depth interviews were conducted via an online platform with 11 male-to-female transgender adults who gave their informed consent to participate. RESULTS: Through a process of group data analysis, four major themes emerged: (a) Everybody Saw the Mask; (b) A Turning Point; (c) Shedding My Skin; and (d) Navigating the Way. CONCLUSIONS: These findings can heighten healthcare personnel's sensitivity to this vulnerable population, as well as guide students and providers to provide culturally appropriate care, which can lead to a decrease in health disparities.

Crystal structure of a cap-independent translation enhancer RNA.

In eukaryotic messenger RNAs, the 5' cap structure binds to the translation initiation factor 4E to facilitate early stages of translation. Although many plant viruses lack the 5' cap structure, some contain cap-independent translation elements (CITEs) in their 3' untranslated region. The PTE (Panicum mosaic virus translation element) class of CITEs contains a G-rich asymmetric bulge and a C-rich helical junction that were proposed to interact via formation of a pseudoknot. SHAPE analysis of PTE homologs reveals a highly reactive guanosine residue within the G-rich region proposed to mediate eukaryotic initiation factor 4E (eIF4E) recognition. Here we have obtained the crystal structure of the PTE from Pea enation mosaic virus 2 (PEMV2) RNA in complex with our structural chaperone, Fab BL3-6. The structure reveals that the G-rich and C-rich regions interact through a complex network of interactions distinct from those expected for a pseudoknot. The motif, which contains a short parallel duplex, provides a structural mechanism for how the guanosine is extruded from the core stack to enable eIF4E recognition. Homologous PTE elements harbor a G-rich bulge and a three-way junction and exhibit covariation at crucial positions, suggesting that the PEMV2 tertiary architecture is conserved among these homologs.

Insights into Substrate Recognition by the Unusual Nitrating Enzyme RufO.

Nitration reactions are crucial for many industrial syntheses; however, current protocols lack site specificity and employ hazardous chemicals. The noncanonical cytochrome P450 enzymes RufO and TxtE catalyze the only known direct aromatic nitration reactions in nature, making them attractive model systems for the development of analogous biocatalytic and/or biomimetic reactions that proceed under mild conditions. While the associated mechanism has been well-characterized in TxtE, much less is known about RufO. Herein we present the first structure of RufO alongside a series of computational and biochemical studies investigating its unusual reactivity. We demonstrate that free l-tyrosine is not readily accepted as a substrate despite previous reports to the contrary. Instead, we propose that RufO natively modifies l-tyrosine tethered to the peptidyl carrier protein of a nonribosomal peptide synthetase encoded by the same biosynthetic gene cluster and present both docking and molecular dynamics simulations consistent with this hypothesis. Our results expand the scope of direct enzymatic nitration reactions and provide the first evidence for such a modification of a peptide synthetase-bound substrate. Both of these insights may aid in the downstream development of biocatalytic approaches to synthesize rufomycin analogues and related drug candidates.

Nurse Practitioner's Confidence and Competence of Advance Directives: The Benefits of an Educational Program.

The increase in the number of people developing dementia, the growing number of geriatric patients suffering and dying from serious chronic diseases, and the rising costs of health care as a result of an aging population have centered attention on advance care planning. Advance care planning is the recurrent conversation between competent patients, their families, and the health care provider about end of life care. Although vital, advance care planning discussions between providers and patients are not occurring regularly, and completion rates of advance directives are low. Barriers to health care providers discussing advance directives include lack of time, knowledge, and confidence. The purpose of this project was to evaluate the effectiveness of an educational program regarding advance directives on nurse practitioner's competency and confidence to start advance care planning discussions. Wilcoxon signed rank test indicated that post-education, confidence improved significantly for all items (average rank of 4.5 vs average rank of 10.65). The study showed that most of the nurse practitioners were knowledgeable about advance directives and the educational program increased their level of confidence about initiating advance directive discussions.

Explicating How Skill Determines the Qualities of User-Avatar Bonds.

Many frameworks exist that explain how people interact with avatars. Our core argument is that the primary theoretical mechanisms of a user-avatar bond (i.e., UAB) rest with the way people engage avatars and, thereby, the broader digital environment. To understand and predict such engagement, we identify a person's skill in handling/engaging the avatar in the digital environment as an ordering parameter (i.e., organizing predictor). Accordingly, we define skill as a person's ability to enact their agency successfully to achieve desired states. To explain how skill orders experience, we ground our theorizing in ecological perception and systems theory. In our explication, we describe how stable action coupling (i.e., the linking of action inputs to perceived outcomes) enables a state of embeddedness (i.e., when the environment facilitates and constrains behaviors) in the digital environment. Then, we explain how embeddedness promotes motivational attunement (i.e., orienting of motivational systems) and what the digital environment affords to users at different levels of skill. Throughout, we consider how our theoretical scaffolding generates tractable contentions regarding how skill influences UABs.

Nutritional interventions in older people with COVID-19: an overview of the evidence.

Older people are a high-risk group for coronavirus disease 2019 (COVID-19) because of a range of factors, including age-related changes in anatomical pulmonary and muscle function, decreased immunity and increased inflammation. These factors partly explain why older people with COVID-19 experience more severe symptoms and higher mortality than younger adults and are more likely to require nutritional support. Furthermore, there is an association between suboptimal nutritional status and poorer recovery from COVID-19. Therefore, nutritional interventions are an important aspect of care for older people with COVID-19. All members of the multidisciplinary team, including dietitians and nurses, need to assess, treat and prevent nutritional deficiencies in older people with COVID-19. This literature review provides an overview of the evidence regarding the role of nutritional interventions in the treatment of, and recovery from, COVID-19 in older people.

Transcriptome profiles of stem-like cells from primary breast cancers allow identification of ITGA7 as a predictive marker of chemotherapy response.

BACKGROUND: Breast cancer stem cells (BCSCs) are drivers of therapy-resistance, therefore are responsible for poor survival. Molecular signatures of BCSCs from primary cancers remain undefined. Here, we identify the consistent transcriptome of primary BCSCs shared across breast cancer subtypes, and we examine the clinical relevance of ITGA7, one of the genes differentially expressed in BCSCs. METHODS: Primary BCSCs were assessed using immunohistochemistry and fluorescently labelled using Aldefluor (n = 17). Transcriptomes of fluorescently sorted BCSCs and matched non-stem cancer cells were determined using RNA-seq (n = 6). ITGA7 expression was examined in breast cancers using immunohistochemistry (n = 305), and its functional role was tested using siRNA in breast cancer cells. RESULTS: Proportions of BCSCs varied from 0 to 9.4%. 38 genes were significantly differentially expressed in BCSCs; genes were enriched for functions in vessel morphogenesis, motility, and metabolism. ITGA7 was found to be significantly downregulated in BCSCs, and low expression significantly correlated with reduced survival in patients treated with chemotherapy, and with chemoresistance in breast cancer cells in vitro. CONCLUSIONS: This study is the first to define the molecular profile of BCSCs from a range of primary breast cancers. ITGA7 acts as a predictive marker for chemotherapy response, in accordance with its downregulation in BCSCs.

Factors affecting nurse practitioners' integration of evidence into practice.

BACKGROUND: Evidence-based clinical practice guidelines bridge the gap between clinical practice and research, improve patient outcomes, promote consistency of care, and enhance quality of care. However, guideline adherence varies widely among individual providers and organizations. PURPOSE: To identify factors that facilitate or impede nurse practitioners' integration of guideline recommendations into practice. METHODS: Every nurse practitioner in Alabama was invited to complete an online 45-question survey evaluating beliefs and attitudes regarding evidence-based guidelines, facilitators and barriers to implementation, and utilization of information resources in patient care. RESULTS: The five most commonly identified barriers to evidence-based guideline implementation in participants' current work settings are patients with multiple comorbidities, time constraints, pressure from patients to provide nonrecommended care, insufficient staffing, and inadequate financial resources. The five most commonly identified facilitators in participants' current work settings are easy access to guidelines, support from leadership, free access to guidelines, in-person education regarding a guideline, and clinical decision support software programs. Participants expressed a desire for free and easy access to evidence-based practice (EBP) guidelines and clinical decision support programs, as well as education regarding guidelines and opportunities to discuss evidence with colleagues. IMPLICATIONS FOR PRACTICE: The barriers and facilitators of guideline implementation that were identified in this study should be useful in the development and refinement of future studies and interventions to enhance guideline implementation among individuals and organizations.

Identification of factors that influence the decision to take chemoprevention in patients with a significant family history of breast cancer: results from a patient questionnaire survey.

PURPOSE: Chemoprevention reduces the risk of developing breast cancer in women with increased family history (FH) risk of breast cancer. However, chemoprevention uptake remains low and the reasons for this remain unclear. METHODS: Patients with moderate- or high-risk FH of breast cancer were counselled about chemoprevention (n = 1620; September 2015 to July 2018) in breast clinics. A postal questionnaire survey was subsequently sent to these patients in order to explore the potential factors influencing their decision on chemoprevention uptake. RESULTS: 518 patients (32%) completed the questionnaire survey; 75% were pre-menopausal and the majority had moderate as opposed to high-risk FH (87.5% vs. 12.5%). Breast cancer chemoprevention uptake rate was 10.8% (56/518). The identified incentives were more commonly stated for patients who took chemoprevention when compared to those who refused chemoprevention. The commonest incentives were breast cancer prevention (89.3% vs. 61.7%; p = 0.001), belief in the effectiveness of chemoprevention (76.8% vs. 63.4%; p = 0.048), and personal perception of breast cancer risk (67.9% vs. 45.5%; p = 0.002). Similarly, the identified barriers were more commonly stated for patients who refused chemoprevention when compared to those who took chemoprevention. The commonest barriers were side effects (79.4% vs. 55.4%; p = 0.001) and lack of information (53% vs. 28.6%; p = 0.001). CONCLUSION: Despite its proven efficacy, chemoprevention uptake in patients with a significant FH of breast cancer remains low. We have identified important factors which influence the patient's decision making. Future clinic consultations should focus on exploring these factors to aid patient decision making.

Inhibition of interferon-signalling halts cancer-associated fibroblast-dependent protection of breast cancer cells from chemotherapy.

BACKGROUND: Triple negative breast cancers (TNBC) have poor prognoses despite aggressive treatment with cytotoxic chemotherapy. Cancer-associated fibroblasts (CAFs) are prominent in tumour stroma. Our hypothesis was that CAFs modulate chemotherapy sensitivity. METHODS: TNBC cells and breast fibroblasts were cultured; survival after chemotherapeutics was assessed using luciferase or clonogenic assays. Signalling was investigated using transcriptomics, reporters, recombinant proteins and blocking antibodies. Clinical relevance was investigated using immunohistochemistry. RESULTS: Breast CAFs dose-dependently protected TNBC cell lines MDA-MB-231 and MDA-MB-157, but not MDA-MB-468s, from chemotherapy. CAF-induced protection was associated with interferon (IFN) activation. CAFs were induced to express IFNß1 by chemotherapy and TNBC co-culture, leading to paracrine activation in cancer cells. Recombinant IFNs were sufficient to protect MDA-MB-231 and MDA-MB-157 but not MDA-MB-468 cells. In TNBC patients, IFNß1 expression in CAFs correlated with cancer cell expression of MX1, a marker of activated IFN signalling. High expression of IFNß1 (CAFs) or MX1 (tumour cells) correlated with reduced survival after chemotherapy, especially in claudin-low tumours (which MDA-MB-231 and MDA-MB-157 cells represent). Antibodies that block IFN receptors reduced CAF-dependent chemoprotection. CONCLUSIONS: CAF-induced activation of IFN signalling in claudin-low TNBCs results in chemoresistance. Inhibition of this pathway represents a novel method to improve breast cancer outcomes.

Audit of routine preoperative blood test requests for patients undergoing elective breast surgery: Less is more.

In 2016, the National Institute for Health and Care Excellence updated guidelines on preoperative blood tests for elective surgery; with failure of adherence having implications for both patients and healthcare providers. A local audit was performed on 919 patients undergoing elective breast surgery that determined compliance and the financial implications of performing inappropriate preoperative blood tests against the National Institute for Health and Care Excellence guideline. Initial findings of an unacceptable quantity of inappropriate blood tests led to the education of the pre-assessment clinic staff regarding the guidelines along with the development of a poster to guide the ordering of appropriate tests. A re-audit of 451 patients assessed impact of interventions which resulted in a significant reduction in the number of blood tests requested with a 71% reduction in financial expenditure. The blood tests considered inappropriate in both the initial and re-audit did not add any relevant clinical information and abnormal results did not alter the clinical course of the patient.

Analysis of Secondary Surgeries after Immediate Breast Reconstruction for Cancer Compared with Risk Reduction.

This study sets out to compare reconstructive practice between patients undergoing immediate breast reconstruction (IBR) for cancer and those who opted for risk reduction (RR), with an emphasis on examining patterns of secondary surgery. METHODS: Data collection was performed for patients undergoing mastectomy and IBR at a teaching hospital breast unit (2013-2016). RESULTS: In total, 299 patients underwent IBR (76% cancer versus 24% RR). Implant-based IBR rate was similar in both groups (58% cancer versus 63% RR). Reconstruction loss (5.3% cancer versus 4.2% RR) and complication (16% cancer versus 12.9% RR) rates were similar. Cancer patients were more likely to undergo secondary surgery (68.4% versus 56.3%; P = 0.025), including contralateral symmetrization (22.8% versus 0%) and conversion to autologous reconstruction (5.7% versus 1.4%). Secondary surgeries were mostly planned for cancer patients (72% planned versus 28% unplanned), with rates unaffected by adjuvant therapies. This distribution was different in RR patients (51.3% planned versus 48.7% unplanned). The commonest secondary procedure was lipomodeling (19.7% cancer versus 23.9% RR). For cancer patients, complications resulted in a significantly higher unplanned secondary surgery rate (82.5% versus 38.8%; P = 0.001) than patients without complications. This was not evident in the RR patients, where complications did not lead to a significantly higher unplanned surgery rate (58.9% versus 35.2%; P = 0.086). CONCLUSIONS: Most of the secondary surgeries were planned for cancer patients. However, complications led to a significantly higher rate of unplanned secondary surgery. Approximately 1 in 4 RR patients received unplanned secondary surgery, which may be driven by the desire to achieve an optimal aesthetic outcome.

Enhancing the incorporation of lysine derivatives into proteins with methylester forms of unnatural amino acids.

We have improved the incorporation of l- and d-forms of unnatural amino acid (UAA) Nε-thiaprolyl-l-lysine (ThzK) into ubiquitin (UB) and green fluorescent protein (GFP) by 2-6 folds with the use of the methylester forms of the UAAs in E coli cell culture. We also improved the yields of UAA-incorporated UB and GFP with the methylester forms of Nε-Boc-l-Lysine (BocK) and Nε-propargyl-l-Lysine (PrK) by 2-5 folds compared to their free acid forms. Our work demonstrated that using methylester-capped UAAs for protein expression is a useful strategy to enhance the yields of UAA-incorporated proteins.

Genomic and Expression Analyses Define MUC17 and PCNX1 as Predictors of Chemotherapy Response in Breast Cancer.

Poor-prognosis breast cancers are treated with cytotoxic chemotherapy, but often without any guidance from therapy predictive markers because universally accepted markers are not currently available. Treatment failure, in the form of recurrences, is relatively common. We aimed to identify chemotherapy predictive markers and resistance pathways in breast cancer. Our hypothesis was that tumor cells remaining after neoadjuvant chemotherapy (NAC) contain somatic variants causing therapy resistance, while variants present pre-NAC but lost post-NAC cause sensitivity. Whole-exome sequencing was performed on matched pre- and post-NAC cancer cells, which were isolated by laser microdissection, from 6 cancer cases, and somatic variants selected for or against by NAC were identified. Somatic variant diversity was significantly reduced after therapy (P < 0.05). MUC17 variants were identified in 3 tumors and were selected against by NAC in each case, while PCNX1 variants were identified in 2 tumors and were selected for in both cases, implicating the function of these genes in defining chemoresponse. In vitro knockdown of MUC17 or PCNX1 was associated with significantly increased or decreased chemotherapy sensitivity, respectively (P < 0.05), further supporting their roles in chemotherapy response. Expression was tested for predictive value in two independent cohorts of chemotherapy-treated breast cancers (n = 53, n = 303). Kaplan-Meier analyses revealed that low MUC17 expression was significantly associated with longer survival after chemotherapy, whereas low PCNX1 was significantly associated with reduced survival. We concluded that therapy-driven selection of somatic variants allows identification of chemotherapy response genes. With respect to MUC17 and PCNX1, therapy-driven selection acting on somatic variants, in vitro knockdown data concerning drug sensitivity, and survival analysis of expression levels in patient cohorts all define the genes as mediators of and predictive markers for chemotherapy response in breast cancer.

Implementation of a Shared Medical Appointment as a Holistic Approach to CHF Management.

Congestive heart failure is a costly chronic disease within the United States. The purpose of this study was to examine the effect of a holistic shared medical appointment (SMA) approach to congestive heart failure. Findings suggest the SMA approach improves depression, quality of life (QOL), and health-promoting behaviors. This study implemented congestive heart failure self-management education in primary care using a holistic multidisciplinary approach with SMA to provide evidence-based interventions to improve depression, QOL, and health promotion outcomes. Patients participating in the holistic multidisciplinary SMA experienced improvement in depression, QOL, and health promotion behaviors. A comparison of the means between preintervention and postintervention showed an overall reduction in systolic blood pressure, weight, depression scores, QOL scores, and several indicators of health promotion lifestyle.

Nutritional interventions for preventing malnutrition in people with dementia.

Dementia is a progressive, chronic condition affecting cognitive functioning and is most prevalent in people aged over 65. Weight loss, malnutrition and dehydration are common in people living with dementia and can occur at any stage of the condition. Malnutrition can have devastating consequences on quality of life and clinical outcomes and significantly increases the risk of morbidity and mortality. Dementia affects a person's ability and desire to eat and drink to meet their nutritional requirements. This article identifies problems associated with nutritional status in people living with dementia and outlines the effectiveness of interventions to counteract the negative effects on nutritional status.

Hyperkalemia during general anesthesia in two Greyhounds.

CASE DESCRIPTION: A 36-kg (79-lb) castrated male Greyhound (dog 1) and a 25-kg (55 lb) spayed female Greyhound (dog 2) underwent general anesthesia for dental care with similar perianesthetic protocols on multiple occasions from 2013 to 2016. Both dogs had periodontal disease but were otherwise deemed healthy. Both dogs developed clinically relevant hyperkalemia, with signs including loss of P waves on ECG tracings, during multiple anesthetic events. CLINICAL FINDINGS: Dog 1 developed hyperkalemia during 2 of 2 anesthetic events, with ECG changes noted during the first event. Dog 2 developed hyperkalemia during 3 of 4 anesthetic events, with ECG changes identified during the second and third events. Serum potassium concentration for both dogs was within the reference range prior to and between anesthetic events. No underlying etiopathogenesis for hyperkalemia was identified for either dog. TREATMENT AND OUTCOME: In each hyperkalemic event, the clinician stopped the dental procedure and continued to provide supportive care and monitoring while the dog recovered from anesthesia. The ECG changes resolved, and serum potassium concentration returned to the reference range rapidly after inhalant anesthetic administration was discontinued. The dogs were discharged from the hospital without further complications. CLINICAL RELEVANCE: Hyperkalemia in anesthetized Greyhounds resulted in serious cardiac conduction abnormalities, which could be potentially fatal if not recognized and promptly treated. Further investigation into the etiopathogenesis, prevention and treatment strategies, and genetic or familial components of this condition is indicated.

Intrapartum Nurse Perception of Labor Support After Implementation of the Coping With Labor Algorithm.

The purpose of this research project was to determine if using the Coping with Labor Algorithm would lead to changes in the perception of the intrapartum (IP) nurses' beliefs toward birth practices and frequency of labor support interventions. Twenty-three participants completed the preintervention survey, which included the IP Nurses' Belief Toward Birth Practice Scale and the Labor Support Scale. Following completion of the preintervention survey, participants received a copy of the Coping with Labor Algorithm and Toolkit and then began implementation of the Coping with Labor Algorithm. After implementation, 13 IP nurses completed the postintervention survey. The surveyed IP nurses reported positive changes in their perceived frequency of labor support and a slight change in their birth beliefs.

Implementation of a Standardized Evaluation Tool to Improve Preceptor Confidence.

Preceptors guide the transition of new graduate nurses into practice. Having access to evidence-based tools for evaluation of new graduate nurses promotes preceptor confidence and consistent measures of performance. The Norwegian Nurse Competence Scale was implemented across three acute care organizations for evaluation of new graduate nurse performance. After implementing a standardized process to evaluate new graduate nurses, individual summary scores ranged from 17-25 (preintervention) to 20-25 (postintervention), indicating mid to high levels of preceptor confidence.

Discovery of a novel and potent class of anti-HIV-1 maturation inhibitors with improved virology profile against gag polymorphisms.

A new class of betulin-derived α-keto amides was identified as HIV-1 maturation inhibitors. Through lead optimization, GSK8999 was identified with IC50 values of 17nM, 23nM, 25nM, and 8nM for wild type, Q369H, V370A, and T371A respectively. When tested in a panel of 62 HIV-1 isolates covering a diversity of CA-SP1 genotypes including A, AE, B, C, and G using a PBMC based assay, GSK8999 was potent against 57 of 62 isolates demonstrating an improvement over the first generation maturation inhibitor BVM. The data disclosed here also demonstrated that the new α-keto amide GSK8999 has a mechanism of action consistent with inhibition of the proteolytic cleavage of CA-SP1.