Models, theoretical design and formal evaluation of integrated specialist community health service provision for the first 2000 days: a scoping review.

OBJECTIVE: This scoping review identifies evidence for design, models and evaluation of integrated care service provision for families and children in the first 2000 days, in the context of community-based specialised health, education and welfare services. DESIGN: Scoping review following the Joanna Briggs scoping review method. DATA SOURCES: Medline, CINAHL, Cochrane and PsycINFO. Grey literature used a manual search of original articles, and snowball technique to identify government and policy documents relevant to Australia. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Inclusion criteria were 'population' of prebirth to age 5; 'concept' of design, models and delivery of integrated specialist care for children and families; and 'context' of community-based specialised health, education and welfare services. Medical Subject Heading (MeSH) and free text searches were conducted in electronic database sources. Limits January 2010 to October 2022, full text, English language, human. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by two authors using a piloted data extraction table and presented in table and narrative form. RESULTS: Full text of 11 articles were reviewed, domains were coded using four domains of a framework identified in one reviewed article to maintain consistency of reporting; 'governance,' 'leadership,' 'organisational culture and ethos,' and 'front-line interdisciplinary practice.' A fifth domain was identified, 'access.' CONCLUSIONS: Services providing integrated care for families in the early years will ideally be based on values generated through codesign with families and the community. Considerations include sound governance and leadership, shared vision, and commitment to providing accessible and culturally safe family-centred care.

Identification of models, theoretical design and formal evaluation of integrated specialist community health service provision for the first 2000 days: a protocol for a scoping review.

INTRODUCTION: The first 2000 days of a child's life (during pregnancy up to age 5 years) represent a critical period, in which early interventions reduce risk associated with developmental delay, disability and intergenerational disadvantage. The risk is exacerbated by barriers to specialised early intervention for children and families. This scoping review seeks to contribute to the evidence for sustaining integrated community-based specialist care in these earliest years of a child's life. METHODS AND ANALYSIS: The Joanna Briggs Institute scoping review framework will be followed. Inclusion and exclusion criteria for screening of literature is predefined, guided by the criteria of population, concept and context. The review will identify models of care delivery, and will identify quality of care outcomes that have been measured, including evidence of reliability and validity. Sources of evidence will include CINAHL, Cochrane databases, Medline, PsycINFO and Scopus. ETHICS AND DISSEMINATION: In a three-part study, evidence synthesis from the scoping review of the literature; mapping of existing specialist early years services in one community and a consumer consultation (Curtin University Human Research Ethics approval HRE2021-0546) in the same community will inform a model of integrated care that accounts for the context of the community it seeks to serve. Results will be disseminated by peer-reviewed publications and conference presentations, contributing to the evidence base for delivering sustainable community-based integrated care in the context of the first 2000 days. This protocol is specific to the scoping review.

TDP-43 mediates SREBF2-regulated gene expression required for oligodendrocyte myelination.

Cholesterol metabolism operates autonomously within the central nervous system (CNS), where the majority of cholesterol resides in myelin. We demonstrate that TDP-43, the pathological signature protein for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), influences cholesterol metabolism in oligodendrocytes. TDP-43 binds directly to mRNA of SREBF2, the master transcription regulator for cholesterol metabolism, and multiple mRNAs encoding proteins responsible for cholesterol biosynthesis and uptake, including HMGCR, HMGCS1, and LDLR. TDP-43 depletion leads to reduced SREBF2 and LDLR expression, and cholesterol levels in vitro and in vivo. TDP-43-mediated changes in cholesterol levels can be restored by reintroducing SREBF2 or LDLR. Additionally, cholesterol supplementation rescues demyelination caused by TDP-43 deletion. Furthermore, oligodendrocytes harboring TDP-43 pathology from FTD patients show reduced HMGCR and HMGCS1, and coaggregation of LDLR and TDP-43. Collectively, our results indicate that TDP-43 plays a role in cholesterol homeostasis in oligodendrocytes, and cholesterol dysmetabolism may be implicated in TDP-43 proteinopathies-related diseases.

Understanding nurse preceptors' experiences in a primary health care setting: A descriptive qualitative study.

AIM: This study sought to understand primary health care nurse preceptors' experiences of precepting junior nurses. BACKGROUND: Nurse preceptors provide clinical teaching to nurses and pre-registration nurses and play a supervisory role in their work. The demand for preceptors in the primary health care setting is on the rise, and there is a huge responsibility placed on them on top of their routine workload. METHODS: A descriptive qualitative approach was adopted, and purposive sampling was used to select the participants. 14 nursing preceptors across six polyclinics were interviewed. Thematic analysis was used to analyse the data. RESULTS: The analysis revealed three themes: (1) a vessel for transferring knowledge; (2) building a therapeutic relationship; and (3) overcoming organisational barriers. CONCLUSION: In light of the study's findings, strategies to address the insufficient knowledge of nurse preceptors, lack of recognition and preceptorship opportunities must be developed. IMPLICATIONS FOR NURSING MANAGEMENT: More attention and opportunities for nurse preceptors' professional development such as courses to enhance their knowledge on educational and research developments as well as teaching seminars to maintain and build effective relationships with their preceptees. In addition, recognizing the role of nurse preceptors as a pillar of guiding the future generation of nurses and research to support nurse preceptors in their training cannot be undermined.

Extensive Inhibitory Gating of Viscerosensory Signals by a Sparse Network of Somatostatin Neurons.

Integration and modulation of primary afferent sensory information begins at the first terminating sites within the CNS, where central inhibitory circuits play an integral role. Viscerosensory information is conveyed to the nucleus of the solitary tract (NTS) where it initiates neuroendocrine, behavioral, and autonomic reflex responses that ensure optimal internal organ function. This excitatory input is modulated by diverse, local inhibitory interneurons, whose functions are not clearly understood. Here we show that, in male rats, 65% of somatostatin-expressing (SST) NTS neurons also express GAD67, supporting their likely role as inhibitory interneurons. Using whole-cell recordings of NTS neurons, from horizontal brainstem slices of male and female SST-yellow fluorescent protein (YFP) and SST-channelrhodopsin 2 (ChR2)-YFP mice, we quantified the impact of SST-NTS neurons on viscerosensory processing. Light-evoked excitatory photocurrents were reliably obtained from SST-ChR2-YFP neurons (n = 16) and the stimulation-response characteristics determined. Most SST neurons (57%) received direct input from solitary tract (ST) afferents, indicating that they form part of a feedforward circuit. All recorded SST-negative NTS neurons (n = 72) received SST-ChR2 input. ChR2-evoked PSCs were largely inhibitory and, in contrast to previous reports, were mediated by both GABA and glycine. When timed to coincide, the ChR2-activated SST input suppressed ST-evoked action potentials at second-order NTS neurons, demonstrating strong modulation of primary viscerosensory input. These data indicate that the SST inhibitory network innervates broadly within the NTS, with the potential to gate viscerosensory input to powerfully alter autonomic reflex function and other behaviors.SIGNIFICANCE STATEMENT Sensory afferent input is modulated according to state. For example the baroreflex is altered during a stress response or exercise, but the basic mechanisms underpinning this sensory modulation are not fully understood in any sensory system. Here we demonstrate that the neuronal processing of viscerosensory information begins with synaptic gating at the first central synapse with second-order neurons in the NTS. These data reveal that the somatostatin subclass of inhibitory interneurons are driven by visceral sensory input to play a major role in gating viscerosensory signals, placing them within a feedforward circuit within the NTS.

How shall we manage the incidentally found thyroid nodule?

Thyroid incidentalomas are commonly found on cross-sectional imaging of the neck and they are equally likely to be malignant as palpable thyroid nodules. Guidelines on their management are conflicting. Ultrasonography cannot accurately differentiate benign from malignant thyroid nodules and fine needle aspiration biopsy should be used selectively to avoid over-diagnosis and over-treatment. If the clinician follows current guidelines for the investigation of thyroid incidentalomas a proportion of malignant incidentalomas will inevitably be missed. Whether this is clinically important is controversial as it is generally agreed that the natural history of small incidental thyroid cancers is indolent. However a subset may have a more aggressive behaviour and it is not currently possible to predict whether a malignant incidentaloma will progress to clinical disease or remain latent. In this article we review the evidence-base around the current guidelines for investigating thyroid incidentalomas and suggest a practical approach to their management.

Squamous cell carcinoma antigen 1-mediated binding of hepatitis B virus to hepatocytes does not involve the hepatic serpin clearance system.

The cellular receptor for hepatitis B virus (HBV) has not yet been identified. A recent candidate is a homologue of squamous cell carcinoma antigen 1 (SCCA1), a serpin. This study confirms that transfection of SCCA1 into mammalian cells (both hepatocyte-derived and of non-hepatocyte origin) results in increased HBV binding. Furthermore, virus bound to transfected cells is protected significantly from degradation by trypsin (75% compared with 30% in untransfected cells). The possibility that HBV enters cells via the hepatic clearance system for serpin-enzyme complexes was investigated by analysis of the reactive site loop of SCCA1. Functional and deletion mutants of SCCA1 were constructed by site-directed mutagenesis and compared with the wild type construct. In no case was virus binding reduced by functional alterations or deletions within the reactive site loop. A possible role for the low density lipoprotein receptor-related protein (LRP) in binding virus was investigated. SCCA1 transfection of Huh7 cells was shown to result in up-regulation of LRP expression, reaching levels observed in total liver. However, the use of receptor-associated protein (RAP), a competitive ligand for LRP, suggests than LRP up-regulation is not responsible for enhanced virus binding to SCCA1-transfected cells.