Single cell RNA analysis of the left-right organizer transcriptome reveals potential novel heterotaxy genes.

The establishment of left-right patterning in mice occurs at a transient structure called the embryonic node or left-right organizer (LRO). Previous analysis of the LRO has proven challenging due to the small cell number and transient nature of this structure. Here, we seek to overcome these difficulties to define the transcriptome of the LRO.

Congenital heart defects caused by FOXJ1.

FOXJ1 is expressed in ciliated cells of the airways, testis, oviduct, central nervous system and the embryonic left-right organizer. Ablation or targeted mutation of Foxj1 in mice, zebrafish and frogs results in loss of ciliary motility and/or reduced length and number of motile cilia, affecting the establishment of the left-right axis. In humans, heterozygous pathogenic variants in FOXJ1 cause ciliopathy leading to situs inversus, obstructive hydrocephalus and chronic airway disease.

SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification.

The mechanisms of neural crest cell induction and specification are highly conserved among vertebrate model organisms, but how similar these mechanisms are in mammalian neural crest cell formation remains open to question. The zinc finger of the cerebellum 1 (ZIC1) transcription factor is considered a core component of the vertebrate gene regulatory network that specifies neural crest fate at the neural plate border. In mouse embryos, however, mutation does not cause neural crest defects.

Loss of Zic3 impairs planar cell polarity leading to abnormal left-right signaling, heart defects and neural tube defects.

Loss of function of ZIC3 causes heterotaxy (OMIM #306955), a disorder characterized by organ laterality defects including complex heart defects. Studies using Zic3 mutant mice have demonstrated that loss of Zic3 causes heterotaxy due to defects in establishment of left-right (LR) signaling, but the mechanistic basis for these defects remains unknown. Here, we demonstrate Zic3 null mice undergo cilia positioning defects at the embryonic node consistent with impaired planar cell polarity (PCP).

WNT-responsive SUMOylation of ZIC5 promotes murine neural crest cell development, having multiple effects on transcription.

Zinc finger of the cerebellum (Zic) proteins act as classic transcription factors to promote transcription of the Foxd3 gene during neural crest cell specification. Additionally, they can act as co-factors that bind proteins from the T-cell factor/lymphoid enhancing factor (TCF/LEF) family (TCFs) to repress WNT-β-catenin-dependent transcription without contacting DNA. Here, we show that ZIC activity at the neural plate border is influenced by WNT-dependent SUMOylation.

Systematized reporter assays reveal ZIC protein regulatory abilities are Subclass-specific and dependent upon transcription factor binding site context.

The ZIC proteins are a family of transcription regulators with a well-defined zinc finger DNA-binding domain and there is evidence that they elicit functional DNA binding at a ZIC DNA binding site. Little is known, however, regarding domains within ZIC proteins that confer trans-activation or -repression. To address this question, a new cell-based trans-activation assay system suitable for ZIC proteins in HEK293T cells was constructed.

ZIC3 in Heterotaxy.

Mutation of ZIC3 causes X-linked heterotaxy, a syndrome in which the laterality of internal organs is disrupted. Analysis of model organisms and gene expression during early development suggests ZIC3-related heterotaxy occurs due to defects at the earliest stage of left-right axis formation. Although there are data to support abnormalities of the node and cilia as underlying causes, it is unclear at the molecular level why loss of ZIC3 function causes such these defects.

Home care packages: insights into the experiences of older people leading up to the introduction of consumer directed care in Australia.

This paper reports phase one, conducted from March to June 2015, of a two-phase, qualitative descriptive study designed to explore the perceptions and experiences of older people before and after the introduction of consumer directed care (CDC) to home care packages (HCP) in Australia. Eligible consumers with a local HCP provider were mailed information about the study. Data collection occurred before the introduction of CDC and included face-to-face, in-depth interviews, summaries of interviews, field notes and reflective journaling.

Socially disadvantaged women's views of barriers to feeling safe to engage in decision-making in maternity care.

Background: Although midwifery literature suggests that woman-centred care can improve the birthing experiences of women and birth outcomes for women and babies, recent research has identified challenges in supporting socially disadvantaged women to engage in decision-making regarding care options in order to attain a sense of control within their maternity care encounters.

Objective: The objective of this paper is to provide an understanding of the issues that affect the socially disadvantaged woman's ability to actively engage in decision-making processes relevant to her care.

Research Design: The qualitative approach known as Interpretative Phenomenological Analysis was used to gain an understanding of maternity care encounters as experienced by each of the following cohorts: socially disadvantaged women, registered midwives and student midwives.

A murine Zic3 transcript with a premature termination codon evades nonsense-mediated decay during axis formation.

The ZIC transcription factors are key mediators of embryonic development and ZIC3 is the gene most commonly associated with situs defects (heterotaxy) in humans. Half of patient ZIC3 mutations introduce a premature termination codon (PTC). In vivo, PTC-containing transcripts might be targeted for nonsense-mediated decay (NMD).

Zinc fingers of the cerebellum (Zic): transcription factors and co-factors.

The Zic genes encode zinc finger containing proteins that can bind proteins and DNA. The understanding of Zic molecular networks has been hampered by functional redundancy amongst family members, and because their loss-of-function phenotypes are indicative of a role in many signalling pathways. Recently molecular evidence has emerged confirming the pleiotropic nature of these proteins: they act both as classical transcription factors and as co-factors to directly and indirectly influence gene expression.

Efficacy of the use of evidence-based algorithmic guidelines in the acute care setting for pain assessment and management in older people: a critical review of the literature.

Aim: The aim of the literature review was to identify all examples of primary research using an algorithmic approach for the implementation of a clinical practice guideline relating to pain assessment and/or management within acute care, with a specific focus on older people.

Design: Critical literature review.

Data Sources: Inclusion criteria were; English language publications within the past 13 years; peer reviewed; research conducted within a hospital; about adult inpatients.

Examination of the utility of the promoting action on research implementation in health services framework for implementation of evidence based practice in residential aged care settings.

Aim: This study examined the relevance and fit of the PARiHS framework (Promoting Action on Research Implementation in Health Services) as an explanatory model for practice change in residential aged care.

Background: Translation of research knowledge into routine practice is a complex matter in health and social care environments. Examination of the environment may identify factors likely to support and hinder practice change, inform strategy development, predict and explain successful uptake of new ways of working.

The effectiveness of using human patient simulation manikins in the teaching of clinical reasoning skills to undergraduate nursing students: a systematic review.

Background: Human patient simulation manikins are being used extensively both nationally (in Australia) and internationally in the education of health professionals. There is evidence suggesting that these types of technologies are effective in teaching psychomotor skills. Furthermore student satisfaction with simulation approaches is generally high.

The critical elements within a journey towards the achievement of quality use of medicines.

In Australia, as in much of the rest of the Western world, the changing demographics of the population has resulted ina need for the aged care industry and the nursing profession tomodify their traditional skill mix in order to better respond to changes in the needs of older Australians. In particular, the role of the Enrolled Nurse (EN) in New South Wales (NSW) Australia has been under considerable scrutiny for the last decade resulting in a number of changes in the EN's scope of practice; notably the 2004 amendment to legislation and education that enabled ENs to administer medication. This changed scope of EN practice has resulted in a need to reconsider the role of all members of the aged care medication team.

Communication: principal barrier to nurse-consumer partnerships.

An 8-month pilot study conducted in urban, rural and remote areas of Australia sought to identify barriers to nurse-consumer partnerships, as well as strategies to overcome these barriers. One hundred and ninety-nine Registered Nurses (RNs) and 36 consumers participated across 14 workshops to collect data for the pilot study. Analysis of these data found that nurses' perceptions of partnership with consumers were diverse.

The manifestation and nursing management of agitation in institutionalised residents with dementia.

This participatory action research study is the first formal research study undertaken by nurses in a nursing development unit. The study emerged as the result of nurses brainstorming issues that they perceived to be problematic in their nursing practice and their unit environment. The nurses of the psycho-geriatric nursing development unit, Wallsend Aged Care Facility, New South Wales, Australia identified that the management of agitated behaviour manifested by their severely demented clients was a major challenge in their practice.