Nursing leaders' perceptions of the impact of the Strengths-Based Nursing and Healthcare Leadership program three months post training.

Background: Development of nursing leadership is necessary to ensure that nurse leaders of the future are well-equipped to tackle the challenges of a burdened healthcare system. In this context, the Strengths-Based Nursing and Healthcare Leadership program was delivered to 121 participants from 5 organizations in Canada in 2021 and 2022. To date, no study used a qualitative approach to explore nursing leaders' perceptions of a leadership Strengths-Based Nursing and Healthcare Leadership program three months post training.

Evaluation of the effectiveness of a Strengths-Based Nursing and Healthcare Leadership program aimed at building leadership capacity: A concurrent mixed-methods study.

Background: Targeted interventions have been found effective for developing leadership practices in nurses. However, to date, no leadership training program based on the Strengths-Based Nursing and Healthcare Leadership approach exists.

Objectives: Demonstrate the effectiveness of a Strengths-Based Nursing and Healthcare Leadership 6-month program designed for nurse and healthcare leaders on leadership capacity and psychological outcomes.

Creating Empowering Conditions for Nurses with Workplace Autonomy and Agency: How Healthcare Leaders Could Be Guided by Strengths-Based Nursing and Healthcare Leadership (SBNH-L).

The COVID-19 pandemic had the unintended consequence of placing nurses in the spotlight because their knowledge and skills were in desperate need. While it will be years until we fully understand the impact that this pandemic has exacted on the nursing workforce, early studies have found that nurses have been traumatized by this event and many intend to leave the profession This seismic event only further exacerbated an already vulnerable and strained nursing workforce that pre-existed worldwide prior to COVID-19. The pandemic also highlighted the many challenges facing nursing leadership, in particular, how to create conditions to maintain and sustain a healthy nursing workforce.

Why Tumor Genetic Heterogeneity May Require Rethinking Cancer Genesis and Treatment.

Tumor genetic heterogeneity, in which individual tumors contain both multiple variant cancer-associated and normal genes, has been widely reported, although its significance has yet to be fully understood. We propose a genetic heterogeneity-based selection-centric hypothesis in which genetic heterogeneity, caused by the temporary reduction of DNA repair efficiency, occurs very early in human development, resulting in a small minority of cells in normal tissues acquiring cancer-associated genes that remain dormant. Cancer develops when precancer cells are selected for by altered tissue microenvironments; similar scenarios occur with development of metastases and therapeutic resistance in established cancer.

Strengths-Based Nursing: A Process for Implementing a Philosophy Into Practice.

Strengths-Based Nursing (SBN) is both a philosophy and value-driven approach that can guide clinicians, educators, manager/leaders, and researchers. SBN is rooted in principles of person/family centered care, empowerment, relational care, and innate health and healing. SBN is family nursing yet not all family nursing models are strengths-based.

Characterization of the NPC1L1 gene and proteome from an exceptional responder to ezetimibe.

Background: Strategies to reduce LDL-cholesterol involve reductions in cholesterol synthesis or absorption. We identified a familial hypercholesterolemia patient with an exceptional response to the cholesterol absorption inhibitor, ezetimibe. Niemann-Pick C 1-like 1 (NPC1L1) is the molecular target of ezetimibe.

Changing genetic paradigms: creating next-generation genetic databases as tools to understand the emerging complexities of genotype/phenotype relationships.

Understanding genotype/phenotype relationships has become more complicated as increasing amounts of inter- and intra-tissue genetic heterogeneity have been revealed through next-generation sequencing and evidence showing that factors such as epigenetic modifications, non-coding RNAs and RNA editing can play an important role in determining phenotype. Such findings have challenged a number of classic genetic assumptions including (i) analysis of genomic sequence obtained from blood is an accurate reflection of the genotype responsible for phenotype expression in an individual; (ii) that significant genetic alterations will be found only in diseased individuals, in germline tissues in inherited diseases, or in specific diseased tissues in somatic diseases such as cancer; and (iii) that mutation rates in putative disease-associated genes solely determine disease phenotypes. With the breakdown of our traditional understanding of genotype to phenotype relationships, it is becoming increasingly apparent that new analytical tools will be required to determine the relationship between genotype and phenotypic expression.

Making sense of intratumor genetic heterogeneity: altered frequency of androgen receptor CAG repeat length variants in breast cancer tissues.

To examine the significance of intratumor genetic heterogeneity (ITGH) of the androgen receptor (AR) gene in breast cancer, patient-matched samples of laser capture microdissected breast tumor cells, adjacent normal breast epithelia cells, and peripheral blood leukocytes were sequenced using a novel next generation sequencing protocol. This protocol measured the frequency of distribution of a variable AR CAG repeat length, a functional polymorphism associated with breast cancer risk. All samples exhibited some degree of ITGH with up to 30 CAG repeat length variants identified.

Principles of strengths-based nursing leadership for strengths-based nursing care: a new paradigm for nursing and healthcare for the 21st century.

The current healthcare system is slowly evolving into a new system built on a vision of health promotion, primary care and community-based home care, with hospitals still being a core pillar of the healthcare system but not its primary service. This transformation requires a new approach to practice, namely, Strengths-Based Nursing Care (SBC). SBC is about mobilizing, capitalizing and developing a person's strengths to promote health and facilitate healing.

The androgen receptor gene mutations database: 2012 update.

The current version of the androgen receptor gene (AR) mutations database is described. A major change to the database is that the nomenclature and numbering scheme now conforms to all Human Genome Variation Society norms. The total number of reported mutations has risen from 605 to 1,029 since 2004.

Selection and mutation in the "new" genetics: an emerging hypothesis.

It has been anticipated that new, much more sensitive, next generation sequencing (NGS) techniques, using massively parallel sequencing, will likely provide radical insights into the genetics of multifactorial diseases. While NGS has been used initially to analyze individual human genomes, and has revealed considerable differences between healthy individuals, we have used NGS to examine genetic variation within individuals, by sequencing tissues "in depth", i.e.

BAK1 gene variation and abdominal aortic aneurysms.

We sought to examine the role of genetics in the multifactorial disease, abdominal aortic aneurysm (AAA), by studying sequence variation in the BAK1 gene (BAK1) that codes for an apoptotic-promoting protein, as chronic apoptosis activation has been linked to AAA development and progression. BAK1 abdominal aorta cDNA from AAA patients and nondiseased individuals were compared with each other, as well as to the BAK1 genomic sequence obtained from matching blood samples. We found specific BAK1 single nucleotide polymorphism (SNP) containing alleles in both aneurysmic (31 cases) and healthy aortic tissue (5 cases) without seeing them in the matching blood samples.

Isolation of human proteasomes and putative proteasome-interacting proteins using a novel affinity chromatography method.

The proteasome is the primary subcellular organelle responsible for protein degradation. It is a dynamic assemblage of 34 core subunits and many differentially expressed, transiently interacting, modulatory proteins. This paper describes a novel affinity chromatography method for the purification of functional human holoproteasome complexes using mild conditions.

An investigation into CAG repeat length variation and N/C terminal interactions in the T877A mutant androgen receptor found in prostate cancer.

Prostate cancer may progress by circumventing ablation therapy due to mutations in the androgen receptor (AR) gene. The most intensively studied is the T877A mutation in the ligand binding domain (LBD), which causes the AR to become promiscuous, i.e.

Human genome variation and pharmacogenetics.

A recent HGVS-sponsored symposium has examined, for the first time, the possible effects of the discovery of very large and widespread amounts of human genome variation on the emerging fields of pharmacogenetics and pharmacogenomics. This article discusses the effects of the resultant paradigm shifts and raises a number of important questions that need to be considered in order to truly advance the field in a meaningful and significant way.

Will knowledge of human genome variation result in changing cancer paradigms?

Our incomplete understanding of carcinogenesis may be a significant reason why some cancer mortality rates are still increasing. This lack of understanding is likely due to a research approach that relies heavily on genetic comparison between cancerous and non-cancerous tissues and cells, which has led to the identification of genes of cancer proliferation rather than differentiation. Recent observations showing that a tremendous degree of natural human genetic variation occurs are likely to lead to a shift in the basic paradigms of cancer genetics, in that there is a need to consider both the nature of the genes involved, and the idea that not every genetic variation identified in these genes may be associated with carcinogenesis.

PhenCode: connecting ENCODE data with mutations and phenotype.

PhenCode (Phenotypes for ENCODE; http://www.bx.psu.

The Developmental/Health Framework within the McGill Model of Nursing: "laws of nature" guiding whole person care.

The Developmental/Health Framework (DHFW) within the McGill Model of Nursing (MMN) provides the foundational knowledge consistent with Nightingale's vision of working with the "laws of nature" to promote health and healing. The DHFW describes the processes, principles, and mechanisms rooted in the biological, developmental, and nursing sciences that are required to provide "whole person" care. The MMN provides a model of nursing based on a strengths-based approach within a collaborative partnership relationship.

Somatic mosaicism and cancer: a micro-genetic examination into the role of the androgen receptor gene in prostate cancer.

Recent evidence has shown that the androgen receptor (AR) plays a major role in all prostate cancer stages, including both androgen-dependent and -independent tumors. A large number of studies have examined the possible effects of a functional polymorphism in the AR gene, a variable-length CAG repeat, on the development of prostate cancer, but the results to date have been inconclusive. We have considered the fact that the tissue heterogeneity present in almost all prostate cancer tumors has rarely been regarded as an indicator of AR genetic heterogeneity.

Molecular pathology of the androgen receptor in male (in)fertility.

Idiopathic male infertility, accounting for 40% of all male infertility cases, is postulated to have a genetic basis. The androgen receptor (AR) plays a crucial post-meiotic role during male germ cell differentiation, which includes terminal differentiation of spermatids and their release from the seminiferous epithelium. Mutations in the AR gene result in a condition known as androgen insensitivity syndrome (AIS) affecting normal male morphogenesis.

Nuclear receptors and disease: androgen receptor.

The death of cells by apoptosis is a fundamental event in development and the maintenance of cell homoeostasis. The other side of the coin, however, is that excessive cell death by apoptosis or the lack of apoptosis is often the driving force of many diseases. Whereas reduced apoptosis sensitivity is a basic characteristic of many tumour cells, accelerated tissue cell death and loss of tissue functions is the underlying cause of many auto-immune and inflammatory diseases.

The androgen receptor gene mutations database (ARDB): 2004 update.

The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 374 to 605, and the number of AR-interacting proteins described has increased from 23 to 70, both over the past 3 years. A 3D model of the AR ligand-binding domain (AR LBD) has been added to give a better understanding of gene structure-function relationships.

An examination of how different mutations at arginine 855 of the androgen receptor result in different androgen insensitivity phenotypes.

Two substitutions at an identical location in the ligand-binding domain (LBD) of the human androgen receptor (AR), R855C and R855H, are associated with complete androgen insensitivity syndrome (AIS) and partial AIS, respectively. Kinetic analysis of the mutant receptors in genital skin fibroblasts and in transfected cells revealed very low total binding (Bmax) and increased rate constants of dissociation (k) for the R855C mutant; and normal Bmax and k, with slightly elevated equilibrium affinity constants (Kd), but decreased transactivational capacity for the R855H mutant. Further analysis of the R855H mutant revealed both thermolability and decreased N/C-terminal inter-actions in the presence and absence of the co-activator transcriptional intermediary factor 2.