Outcomes and care priorities for older people living with frailty and advanced chronic kidney disease: a multi-professional scoping review.

The growing older population with advanced chronic kidney disease (ACKD stages 4-5) poses a challenge for healthcare worldwide. The high prevalence of frailty and associated adverse health outcomes highlights concerns for management and interventions specific to this population. The aim was to objectively review the evidence relating to older people (≥65 years) living with frailty and ACKD. More specifically how frailty is identified, what interventions have been studied and what outcomes have been reported including outcomes important to patients, families and carers. A scoping review was undertaken following the PRISMA-Scr guidelines. Nine databases were searched and a review team of five people followed a process using defined inclusion and exclusion criteria. Data were then analysed to answer the specific questions of the review. The World Health Organization's International Classification of Functioning Disability and Health was used to map outcomes across the domains. A total of 90 studies were included. The most reported frailty measure was the frailty phenotype. The most reported outcomes were mortality, hospitalisation and healthcare utilisation. Health-related quality of life was the most common patient-reported outcome measure. There were few intervention studies and limited evidence of patient and carer perspectives. This scoping review highlights important areas for further research in older people living with frailty and ACKD. This includes a 'gold standard' measure for identifying frailty, interventions and improvements in outcome measures that matter to patients (including studies that focus on carers and carer burden) and priority setting for future research.

Patient-reported outcome measures for life participation in peritoneal dialysis: a systematic review.

BACKGROUND: Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD. METHODS: We searched MEDLINE, Embase, PsychInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled Trials from inception to May 2020 for all studies that reported life participation in patients on PD. The characteristics, dimensions of life participation and psychometric properties of these measures were extracted and analyzed. RESULTS: Of the 301 studies included, 17 (6%) were randomized studies and 284 (94%) were nonrandomized studies. Forty-two different measures were used to assess life participation. Of these, 23 (55%) were used in only one study. Fifteen (36%) measures were specifically designed to assess life participation, while 27 (64%) measures assessed broader constructs, such as quality of life, but included questions on life participation. The 36-Item Short Form Health Survey and Kidney Disease Quality of Life Short Form were the most frequently used measures [122 (41%) and 86 (29%) studies, respectively]. Eight (19%) measures had validation data to support their use in patients on PD. CONCLUSIONS: The many measures currently used to assess life participation in patients receiving PD vary in their characteristics, content and validation. Further work to pilot and validate potential measures is required to establish a core patient-reported outcome measure to assess life participation in patients receiving PD.

A randomized controlled trial of different serum phosphate ranges in subjects on hemodialysis.

BACKGROUND: Hyperphosphataemia in dialysis subjects is associated with increased mortality. However cause and effect has not been proven, and the ideal phosphate target range is unknown despite KDOQI's call for studies over 12 years ago. The design and conduct of a randomized controlled trial is challenging because maintaining two groups within differing target ranges of serum phosphate has not been achieved over a long follow-up of 1 year, in a trial setting, before. The SPIRiT study examines the subject acceptance, recruitment and retention rates for such a study in which subjects were randomised to two distinct serum phosphate concentrations, then titrated and maintained over 12 months. METHODS: A two center trial of 104 hemodialysis subjects randomized to lower range LRG 0.8-1.4 mmol/L or 2.5-4.3 mg/dL) and higher range (HRG 1.8-2.4 mmol/L or 5.6-7.4 mg/dL) serum phosphate groups. Two months' titration and ten months' maintenance phase. Interventions were non-calcium phosphate binders, self-help questionnaires, with blood tests at specified time intervals. RESULTS: Thirteen percent of the eligible dialysis population were successfully recruited. A mean separation by serum phosphate of 1.1 mg/dL was achieved and maintained between the groups over 10 months. Drop-out rate was 27% with mortality 10%. Nine subjects in the HRG (17.6%) and two subjects in the LRG (3.8%) died during the study, however the study was not powered to detect significant differences in outcomes. CONCLUSION: Randomizing dialysis subjects to separate treatment targets for serum phosphate can achieve a clinically significant sustained separation over 12 months. A large scale longer term study is required to examine outcomes including mortality. TRIAL REGISTRATION: The trial registration number is ISRCTN24741445 - Date of registration 16th January, retrospectively registered.

A realist evaluation of the implementation of open visiting in an acute care setting for older people.

BACKGROUND: Open visiting refers to the principle of unrestricted visiting hours in the hospital setting to enable relatives, families and carers to visit at any time. There has been recognition that open visiting supports the principle of patient and family supported care and improves communication. Despite this there has been difficulty in implementing open visiting and barriers identified. The aims of this study were therefore to evaluate the implementation of open visiting, the barriers to implementation, sustainability and the impact of open visiting on communication between health care professionals, families and carers. METHODS: The study was conducted on two large acute wards for the older person. Realist evaluation methods were used to understand 'what works well, how, for whom and to what extent.' Mixed methods were employed including qualitative interviews and descriptive analyses of routine data sets. Following the methodology of realist evaluation, programme theories were identified a long with the context, mechanisms and outcomes of implementation, to better understand the implementation process. RESULTS: The results of this study identified some key findings, demonstrating that open visiting does improve communication and can help to build trusting relationships between families/carers and health care professionals (HCP). Barriers to implementation were based on the belief that it would impinge on routines within the ward setting. To achieve the principles of patient and family/carer centred care, the key mechanisms are the confidence and skills of individual nurses and health care assistants to engage with relatives/carers, whilst retaining a sense of control, particularly when care is being delivered to other patients. CONCLUSION: In summary, open visiting creates a positive culture which fosters better relationships between families/carers and HCPs. Involving families/carers as partners in care does not happen automatically in an environment where open visiting is the policy, but requires engagement with staff to encourage and support relatives/carers.

Rehabilitation interventions to modify physical frailty in adults before lung transplantation: a systematic review protocol.

INTRODUCTION: Lung transplantation is the gold-standard treatment for end-stage lung disease for a small group of patients meeting strict acceptance criteria after optimal medical management has failed. Physical frailty is prevalent in lung transplant candidates and has been linked to worse outcomes both on the waiting list and postoperatively. Exercise has been proven to be beneficial in optimising exercise capacity and quality of life in lung transplant candidates, but its impact on physical frailty is unknown. This review aims to assess the effectiveness of exercise interventions in modifying physical frailty for adults awaiting lung transplantation. METHODS AND ANALYSIS: This protocol was prospectively registered on the PROSPERO database. We will search four databases plus trial registries to identify primary studies of adult candidates for lung transplantation undertaking exercise interventions and assessing outcomes pertaining to physical frailty. Studies must include at least 10 participants. Article screening will be performed by two researchers independently at each stage. Extraction will be performed by one reviewer and checked by a second. The risk of bias in studies will be assessed by two independent reviewers using tools appropriate for the research design of each study; where appropriate, we will use Cochrane Risk of Bias 2 or ROBINS-I. At each stage of the review process, discrepancies will be resolved through a consensus or consultation with a third reviewer. Meta-analyses of frailty outcomes will be performed if possible and appropriate as will prespecified subgroup and sensitivity analyses. Where we are unable to perform meta-analysis, we will conduct narrative synthesis following Synthesis without Meta-analysis guidance. The review will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. ETHICS AND DISSEMINATION: No ethical issues are predicted due to the nature of this study. Dissemination will occur via conference abstracts, professional networks, peer-reviewed journals and patient support groups. PROSPERO REGISTRATION NUMBER: CRD42022363730.

Nursing management of catheter-related non-infectious complications of PD: Your questions answered.

A review from the last seven years (August 2016-July 2023) of questions posted to the International Society for Peritoneal Dialysis (ISPD) website "Questions about PD" by nurses and physicians from around the world revealed that 19 of the questions were associated with optimal approaches for preventing, assessing, and managing issues related to PD catheter non-infectious complications. Our review focused on responses to these questions whereby existing best practice recommendations were considered, if available, relevant literature was cited and differences in international practices discussed. We combined similar questions, revised both the original questions and responses for clarity, as well as updated the references to these questions. PD catheter non-infectious complications can often be prevented or, with early detection, the potential severity of the complication can be minimized. We suggest that the PD nurse is key to educating the patient on PD about PD catheter non-infectious complications, promptly recognize a specific complication and bring that complication to the attention of the Home Dialysis Team. The questions posted to the ISPD website highlight the need for more education and resources for PD nurses worldwide on the important topic of non-infectious complications related to PD catheters, thereby enabling us to prevent such complications as PD catheter malfunction, peri-catheter leakage and infusion or drain pain, as well as recognize and resolve these issues promptly when they do arise, thus allowing patients to extend their time on PD therapy and enhance their quality of life whilst on PD.

Development of a Resource for Health Professionals to Raise Advance Care Planning Topics During Kidney Care Consultations: A Multiple User-Centered Design.

Rationale & Objective: Planning and delivering treatment pathways that integrate end-of-life care, frailty assessment, and enhanced supportive care is a service priority. Despite this, people with kidney failure are less likely to have an advance care plan and receive hospice and palliative care compared with other chronic illness populations. This is linked to health professionals feeling unskilled initiating conversations around future treatment and care options. This article describes research underpinning the development of a guide for kidney health professionals discussing end-of-life and advance care planning options with people with kidney failure and family members. Study Design: The study comprised 2 parts: an initial cross-sectional qualitative approach using in-depth interviews with older adults with kidney failure and (bereaved) carers followed by resource development with input from multiple stakeholders. Setting & Participants: Older adults with kidney failure and (bereaved) carers recruited from 2 renal units in the North of England and by online advertisements with national United Kingdom-based kidney patient charities. Resource development included input from co-applicants, independent advisory committee, patient and public involvement team, multidisciplinary health professionals and academics in the United Kingdom and Denmark. Analytical Approach: Thematic analysis was used to analyze the data. Results: Twenty-seven people were interviewed: older adults with kidney failure (n = 18), carers (n = 5), bereaved carers (n = 4). Five themes are described: the context within which end-of-life conversations take place, preferences for end-of-life treatment and care, family members' role and needs in supporting people with kidney failure at the end-of-life, expectations and experience of dialysis treatment, and beliefs and experiences of death and dying. Limitations: Participants were mainly White, British, and receiving hemodialysis. Conclusions: People with (lived) experience of kidney failure informed a guide which aims to build on health professionals existing skills and improve confidence having conversations about future treatment and care. Kidney teams have expressed interest implementing the guide in practice and within their broader communications training packages.

Delivering treatment pathways integrating end-of-life care, frailty assessment, and enhanced supportive care is a service priority. Despite this, people with kidney failure are less likely to have an advance care plan and receive hospice and palliative care compared with other chronic illness populations. This article describes how people with (lived) experience of kidney failure informed a guide to build on health professionals existing skills and improve confidence having conversations about future treatment and care. The study comprised 2 parts: cross-sectional qualitative approach using in-depth interviews with older adults with kidney failure and (bereaved) carers followed by resource development with input from coapplicants, an independent advisory committee, a patient and public involvement team, multidisciplinary health professionals, and academics.

AP-2gamma promotes proliferation in breast tumour cells by direct repression of the CDKN1A gene.

Overexpression of the activator protein (AP)-2gamma transcription factor in breast tumours has been identified as an independent predictor of poor outcome and failure of hormone therapy. To understand further the function of AP-2gamma in breast carcinoma, we have used an RNA interference and gene expression profiling strategy with the MCF-7 cell line as a model. Gene expression changes between control and silenced cells implicate AP-2gamma in the control of cell cycle progression and developmental signalling. A function for AP-2gamma in cell cycle control was verified using flow cytometry: AP-2gamma silencing led to a partial G1/S arrest and induction of the cyclin-dependent kinase inhibitor, p21cip/CDKN1A. Reporter and chromatin immunoprecipitation assays demonstrated a direct, functional interaction by AP-2gamma at the CDKN1A proximal promoter. AP-2gamma silencing coincided with acquisition of an active chromatin conformation at the CDKN1A locus and increased gene expression. These data provide a mechanism whereby AP-2gamma overexpression can promote breast epithelial proliferation and, coupled with previously published data, suggest how loss of oestrogen regulation of AP-2gamma may contribute to the failure of hormone therapy in patients.

Delivering Personalized, Goal-Directed Care to Older Patients Receiving Peritoneal Dialysis.

Background: An aging population living with chronic kidney disease and progressing to kidney failure, subsequently receiving peritoneal dialysis (PD) is growing. A significant proportion of these patients are also living with multi-morbidities and some degree of frailty. Recent practice recommendations from the International Society of Peritoneal Dialysis advocate for high-quality, goal-directed PD prescription, and the Standardized Outcomes of Nephrology-PD initiative emphasized the need for an individualized, goal-based care approach in all patients receiving PD treatment. In older patients, this approach to PD care is even more important. A frailty screening assessment, followed by a comprehensive geriatric assessment (CGA) prior to PD initiation and when dictated by change in relevant circumstances is paramount in tailoring PD care and prescription according to the needs, life goals, as well as clinical status of older patients with kidney failure. Summary: Our review aimed to summarize the different dimensions to be taken into account when delivering PD care to the older patient - from frailty screening and CGA in older patients receiving PD to employing a personalized, goal-directed PD prescription strategy, to preserving residual kidney function, optimizing blood pressure (BP) control, and managing anemia, to addressing symptom burden, to managing nutritional intake and promoting physical exercise, and to explore telehealth opportunities for the older PD population. Key Messages: What matters most to older PD patients may not be simply extending survival, but more importantly, to be living comfortably on PD treatment with minimal symptom burden in a home environment and to minimize treatment complications.

PD effluent specimen collection: Your questions answered.

When a patient on peritoneal dialysis (PD) presents with suspected PD-related peritonitis (e.g. cloudy PD fluid and abdominal pain), one of the most important initial aspects of management is for the nephrology nurse/home dialysis nurse to collect PD effluent specimens for white blood cells count, Gram stain, culture and sensitivity for inspection and to send for laboratory testing before antibiotics are started. A review by seven members of the International Society for Peritoneal Dialysis (ISPD) Nursing Committee of all 133 questions posted to the ISPD website 'Questions about PD' over the last 4 years (January 2018-December 2021), revealed 97 posted by nephrology nurses from around the world. Of these 97 questions, 10 were noted to be related to best practices for PD effluent specimen collection. For our review, we focused on these 10 questions along with their responses by the members of the ISPD 'Ask The Experts Team', whereby existing best practice recommendations were considered, if available, relevant literature was cited and differences in international practice discussed. We revised the original responses for clarity and updated the references. We found that these 10 questions were quite varied but could be organised into four categories: how to collect PD effluent safely; how to proceed with PD effluent collection; how to collect PD effluent for assessment; and how to proceed with follow-up PD effluent collection after intraperitoneal antibiotics have been started. In general, we found that there was limited evidence in the PD literature to answer several of these 10 questions posted to the ISPD website 'Questions about PD' by nephrology nurses from around the world on this important clinical topic of best practices for PD effluent specimen collection. Some of these questions were also not addressed in the latest ISPD Peritonitis Guidelines. Moreover, when polling members of our ISPD Nursing Committee we found when answering a few of these questions, nursing practice varied within and among countries. We encourage PD nurses to conduct their own research on this important topic, focusing on areas where research evidence is lacking.

ISPD Catheter-related Infection Recommendations: 2023 Update.

Peritoneal dialysis (PD) catheter-related infections are important risk factors for catheter loss and peritonitis. The 2023 updated recommendations have revised and clarified definitions and classifications of exit site infection and tunnel infection. A new target for the overall exit site infection rate should be no more than 0.40 episodes per year at risk. The recommendation about topical antibiotic cream or ointment to catheter exit site has been downgraded. New recommendations include clarified suggestion of exit site dressing cover and updated antibiotic treatment duration with emphasis on early clinical monitoring to ascertain duration of therapy. In addition to catheter removal and reinsertion, other catheter interventions including external cuff removal or shaving, and exit site relocation are suggested.

Establishing a core outcome measure for life participation in patients receiving peritoneal dialysis: A Standardised Outcomes in Nephrology-Peritoneal Dialysis consensus workshop report.

BACKGROUND: Life participation is an outcome of critical importance to patients receiving peritoneal dialysis (PD). However, there is no widely accepted or validated tool for measuring life participation in patients receiving PD. METHODS: Online consensus workshop to identify the essential characteristics of life participation as a core outcome, with the goal of establishing a patient-reported outcome measure for use in all trials in patients receiving PD. Thematic analysis of transcripts was performed. RESULTS: Fifty-six participants, including 17 patients and caregivers, from 15 countries convened via online videoconference. Four themes were identified: reconfiguring expectations of daily living (accepting day-to-day fluctuation as the norm, shifting thresholds of acceptability, preserving gains in flexibility and freedom), ensuring broad applicability and interpretability (establishing cross-cultural relevance, incorporating valued activities, distinguishing unmodifiable barriers to life participation), capturing transitions between modalities and how they affect life participation (responsive to trajectory towards stable, reflecting changes with dialysis transitions) and maximising feasibility of implementation (reducing completion burden, administrable with ease and flexibility). CONCLUSIONS: There is a need for a validated, generalisable outcome measure for life participation in patients receiving PD. Feasibility, including length of time to complete and flexible mode of delivery, are important to allow implementation in all trials that include patients receiving PD.

Alternative TFAP2A isoforms have distinct activities in breast cancer.

INTRODUCTION: AP-2α is a transcription factor implicated in the regulation of differentiation and proliferation in certain tissues, including the mammary gland. In breast tumours, continued expression of AP-2α has been correlated with a better prognosis, but this is hard to reconcile with a reported role in the upregulation of the ERBB2 oncogene. The existence of TFAP2A isoforms, deriving from alternative first exons and differing in their N-terminal sequence, has been described in some mammals, but their relative abundance and activity has not been investigated in the human breast. METHODS: Expression levels of four TFAP2A isoforms were assayed at the level of RNA and protein (via the generation of isoform-specific antibodies) in a panel of breast tumour cell lines and in tissue from normal breast and primary tumour samples. Expression constructs for each isoform were used in reporter assays with synthetic and natural promoters (cyclin D3 and ERBB2) to compare the activation and repression activity of the isoforms. RESULTS: We demonstrate that the two isoforms AP-2α 1b and AP-2α 1c, in addition to the originally cloned, AP-2α 1a, are conserved throughout evolution in vertebrates. Moreover, we show that isoform 1c in particular is expressed at levels at least on a par with the 1a isoform in breast epithelial lines and tissues and may be more highly expressed in tamoxifen resistant tumours. The isoforms share a similar transactivation mechanism involving the recruitment of the adaptors CITED2 or 4 and the transactivators p300 or CBP. However, isoform 1b and 1c are stronger transactivators of the ERBB2 promoter than isoform 1a. In contrast, AP-2α 1a is the only isoform able to act as a repressor, an activity that requires an intact sumoylation motif present within the N-terminus of the protein, and which the other two isoforms lack. CONCLUSIONS: Our findings suggest that TFAP2A isoforms may be differentially regulated during breast tumourigenesis and this, coupled with differences in their transcriptional activity, may impact on tumour responses to tamoxifen therapy. These data also have implications for the interpretation of tumour studies that seek to correlate outcomes with TFAP2A expression level.

Outcomes and care priorities for older people living with frailty and advanced chronic kidney disease: a multiprofessional scoping review protocol.

INTRODUCTION: Reported outcomes for older people with advanced chronic kidney disease (CKD) often focus on survival and mortality and little attention is paid to symptom burden and health-related quality of life. Recognising frailty and providing interventions that may improve outcomes have been studied in the general population with a growing research interest within CKD. METHODS AND ANALYSIS: A scoping review will be undertaken following a recommended process to understand relevant research and priorities for older people living with frailty and advanced CKD. Databases will be searched and following a systematic process by a core team, a final list of included studies will be analysed. Focus groups will then be conducted with older people with advanced CKD to incorporate stakeholder views. ETHICS AND DISSEMINATION: Our scoping review will use robust methodology to identify relevant literature focused on outcomes and care priorities for older people with advanced CKD. Ethical approval will be sought to conduct the focus groups. The result of this review will be disseminated through patient networks and national conferences. The interdisciplinary team collaborating plan to continue work in this area to improve the care and management of older people with advanced CKD.

Delivering peritoneal dialysis for the multimorbid, frail and palliative patient.

Peritoneal dialysis (PD) is only one component of care for older multimorbid, frail and/or palliative patients. Goals of care should be determined for all patients by shared decision-making at the start of during time on PD. Burden of PD should be minimized by individualizing the prescription by allowing for residual renal function and tailored to what is acceptable to the patient. PD facilities should develop the care pathways needed for this group of patients including integration with local geriatric, palliative care and social services.

Prescribing high-quality peritoneal dialysis: Moving beyond urea clearance.

Urea removal in peritoneal dialysis (PD) has been a primary measure of dialysis adequacy, but its utility remains limited due to its poor correlation with the clearance of other important uraemic retention solutes and the low certainty of evidence relating peritoneal urea clearance and survival of individuals doing PD. Indeed, clearances of other uraemic solutes, electrolyte imbalances, hypoalbuminaemia and nutritional status, may provide a more holistic measure of dialysis adequacy when evaluating individuals on PD in addition to focusing on person-centred outcomes. Here, we review the history of the urea and creatinine-centric approach to dialysis adequacy and explore the potential importance of other uraemic retention solutes, electrolyte disturbances, phosphorus control, peritoneal protein losses and hypoalbuminaemia, as well as nutritional management to promote a broader multidimensional concept of clearance for PD.

The relationship among BSN students' employment, educational, and health-related characteristics and semester grades: A multi-site study.

BACKGROUND: While many nursing students work during clinical semesters, little is known about employment characteristics and relationships among employment, academic success and other variables. PURPOSE: To describe the demographic, educational, and health-related characteristics of clinical nursing students and the relationships among employment, semester grades and other characteristics. METHOD: Descriptive, correlational. RESULTS: Participants were BSN students (N = 1014) from four southern US universities who were 22.6 years old (SD = 4.6) and most likely to be Caucasian (N = 832, 82%) never married (N = 852, 84%) females (N = 886, 87%) with mean GPA of 2.97 (SD = 0.61). Most students (N = 670, 66%) reported semester employment averaging 16.7 (SD = 8.3) hours/week. Although no relationship was found between hours worked and semester GPA (r = -0.017, p = .588), race/ethnicity (F [2, 1003] = 19.87, p < .0001) and nighttime sleep hours (F [3, 997] = 7.841, p < .0001) had significant effects. Students working in healthcare had higher GPAs (M = 3.09, SD = 0.61, p < .0001) than non-healthcare workers. Students working daytime (M = 3.04, SD = 0.65, p = .031) or irregular shifts (M = 3.04, SD = 0.56, p = .036) had higher GPAs than students working evenings. CONCLUSION: While employment status did not influence GPA, race/ethnicity and amount of reported sleep did. Additional research is needed to provide evidence-based advisement recommendations for employed students.

Calcium and magnesium flux in automated peritoneal dialysis.

BACKGROUND: Calcium and magnesium balance in continuous ambulatory peritoneal dialysis (CAPD) has been extensively studied with several of the different formulations of fluid available. Calcium and magnesium balance in automated PD (APD) is less well studied and the effect on Ca and Mg flux is unknown. Data on glucose polymer solutions are also lacking. This prospective observational study was undertaken to examine mass transfer of Ca and Mg in APD patients. METHODS: 12 patients on APD were studied for two 24-hour periods using, alternately, 1.75 mmol/L and 1.25 mmol/L Ca (Dianeal PD1 and Dianeal PD4; Baxter Healthcare, Newbury, UK) 1.36% glucose-based dialysis fluid for the 9-hour overnight dialysis, followed by a 15-hour daytime dwell of glucose polymer-based fluid (icodextrin). Serum ionized Ca, serum Mg, and dialysate Ca and Mg concentrations were measured at the beginning and end of each period. Mass transfer was calculated as millimoles per exchange. RESULTS: During rapid overnight exchanges with Dianeal PD1 and PD4, mass transfer of Mg and Ca did not show significant correlations with serum levels when using PD1 fluid; however, mass transfer of Mg, but not Ca, was significantly correlated to serum levels when using PD4 fluid. During the long dwell with icodextrin, dialysate drain volume was the most significant factor determining the flux of both Ca and Mg. CONCLUSION: Mass transfer of Ca and Mg in APD patients using conventional dialysis fluid was not related to drain volume in this study, which differs to studies in CAPD. Flux of Ca and Mg during icodextrin use was found to be dependent on ultrafiltration rate and not dialysate or serum concentration.

The Teacher-Scholar Project: how to help faculty groups develop scholarly skills.

Nursing education's challenge in the new millennium is to prepare all nurses as scholars. With many nurse educators feeling like impostors when it comes to scholarship, this is no small task. Turning the millenial challenge into an opportunity, this article describes how a collaborative faculty development initiative is turning a National League for Nursing Center of Excellence school's "scholar-impostors" into teacher-scholars. This Teacher-Scholar Project will interest those in teaching intensive schools of nursing or in teaching tracks in research-intensive institutions.

Arylamine N-acetyltransferase 1 expression in breast cancer cell lines: a potential marker in estrogen receptor-positive tumors.

The prognosis for patients with estrogen receptor (ER)-positive breast cancer has improved significantly with the prescription of selective ER modulators (SERMs) for ER-positive breast cancer treatment. However, only a proportion of ER-positive tumors respond to SERMs, and resistance to hormonal therapies is still a major problem. Detailed analysis of published microarray studies revealed a positive correlation between overexpression of the drug metabolizing enzyme arylamine N-acetyltransferase type 1 (NAT1) and ER positivity, and increasing evidence supports a biological role for NAT1 in breast cancer progression. We have tested a range of ER-positive and ER-negative breast cancer cell lines for NAT1 enzyme activity, and monitored promoter and polyadenylation site usage. Amongst ER-positive lines, NAT1 activities ranged from 202 +/- 28 nmol/min/mg cellular protein (ZR-75-1) to 1.8 +/- 0.4 nmol/min/mg cellular protein (MCF-7). The highest levels of NAT1 activity could not be attributed to increased NAT1 gene copy number; however, we did detect differences in NAT1 promoter and polyadenylation site usage amongst the breast tumor-derived lines. Thus, whilst all cell lines tested accumulated transcripts derived from the proximal promoter, the line expressing NAT1 most highly additionally initiated transcripts initiating at a more distal, "tissue"-specific promoter. These data pave the way for investigating NAT1 transcripts as candidate prognostic markers in ER-positive breast cancer.