The effect of a dominant kinase-dead Csf1r mutation associated with adult-onset leukoencephalopathy on brain development and neuropathology.

Amino acid substitutions in the kinase domain of the human CSF1R protein are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-associated mutation (Glu631Lys; E631K) in the mouse Csf1r locus. Previous analysis demonstrated that heterozygous mutation (Csf1r) had a dominant inhibitory effect on CSF1R signaling in vitro and in vivo but did not recapitulate human disease pathology.

Palliative management of nausea and vomiting in advanced cancer.

Background: Patients with cancer often experience nausea. In some cases, a specific cause such as chemotherapeutic adverse effects, raised intracranial pressure or malignant bowel obstruction is identified. In other cases, no specific cause is apparent.

Community Palliative Care: What are the Best Models?

Palliative care seeks to address the physical, psychosocial and spiritual concerns of patients with a life limiting illness and their caregivers. Early referral to palliative care improves symptoms and is the standard of care. This paper evaluates the evidence for different models of community palliative care and looks at the effects of homecare, hospice programs and residential aged care facility (RACF) interventions on symptom management, home death rate and acute health service utilization.

Visualizing the spatial organization of monocytes, interstitial macrophages, and tissue-specific macrophages in situ.

Tissue-resident mononuclear phagocytes (MPs) are an abundant cell population whose localization in situ reflects their identity. To enable assessment of their heterogeneity, we developed the red/green/blue (RGB)-Mac mouse based upon combinations of Cx3cr1 and Csf1r reporter transgenes, providing a complete visualization of their spatial organization in situ. 3D-multi-photon imaging for spatial mapping and spectral cytometry employing the three markers in combination distinguished tissue-associated monocytes, tissue-specific macrophages, and three subsets of connective-tissue-associated MPs, including CCR2 monocyte-derived cell, CX3CR1, and FOLR2 interstitial subsets, associated with distinct sub-anatomic territories.

Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective.

Background: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD).

Top Ten Tips Palliative Care Clinicians Should Know About Designing a Clinical Trial in Palliative Care.

The palliative care field is experiencing substantive growth in clinical trial-based research. Randomized controlled trials provide the necessary rigor and conditions for assessing a treatment's efficacy in a controlled population. It is therefore important that a trial is meticulously designed from the outset to ensure the integrity of the ultimate results.

Two HUSH complexes connect a direct LINE to innate immunity.

In this issue of Molecular Cell, Danac et al. identify a second HUSH complex, HUSH2, that represses interferon-stimulated genes and, by competing for subunits with the canonical HUSH complex, couples LINE-1 (L1) retrotransposon transcription with immune activation.

An evaluation of education videos for women experiencing domestic and family violence in healthcare settings: protocol for a mixed methods systematic review.

Background: Domestic and family violence (DFV) is a significant public health issue that poses a high risk to women, globally. Women experiencing DFV have higher rates of healthcare utilisation than women not experiencing DFV. Healthcare services are therefore well placed to address DFV and deliver education and awareness interventions to women.

Top Ten Tips Palliative Care Clinicians Should Know About Interpreting a Clinical Trial.

Evidence-based practice is foundational to high-quality palliative care delivery. However, the clinical trials that compose the evidence base are often methodologically imperfect. Applying their conclusions without critical application to the clinical practice context can harm patients.

High level of genomic divergence in orf-I p12 and hbz genes of HTLV-1 subtype-C in Central Australia.

Background: Human T cell lymphotropic virus type 1 (HTLV-1) infection remains a largely neglected public health problem, particularly in resource-poor areas with high burden of communicable and non-communicable diseases, such as some remote populations in Central Australia where an estimated 37% of adults are infected with HTLV-1. Most of our understanding of HTLV-1 infection comes from studies of the globally spread subtype-A (HTLV-1a), with few molecular studies reported with the Austral-Melanesian subtype-C (HTLV-1c) predominant in the Indo-Pacific and Oceania regions.

Results: Using a primer walking strategy and direct sequencing, we constructed HTLV-1c genomic consensus sequences from 22 First Nations participants living with HTLV-1c in Central Australia.

Characteristics and outcomes of community-based perinatal peer support: Protocol for a systematic review.

Background: Mental health issues and parenting difficulties in the perinatal period are common, and have significant negative impacts on individuals, families, and broader society. Community-based peer support programs might be an effective adjunct to standard mental health interventions in perinatal mental health issues, specifically where low-cost interventions are required, or access to professional care is limited.

Methods: A systematic review will be undertaken.

Molecular genetic analysis of candidate genes for glutaric aciduria type II in a cohort of patients from Queensland, Australia.

Glutaric aciduria type II (GAII) is a heterogeneous genetic disorder affecting mitochondrial fatty acid, amino acid and choline oxidation. Clinical manifestations vary across the lifespan and onset may occur at any time from the early neonatal period to advanced adulthood. Historically, some patients, in particular those with late onset disease, have experienced significant benefit from riboflavin supplementation.

Does an allied health transdisciplinary stroke assessment save time, improve quality of care, and save costs? Results of a pre-/post- clinical study.

Purpose: Demand for stroke services is increasing. To save time and costs, stroke care could be reorganised using a transdisciplinary assessment model embracing overlapping allied health professional skills. The study compares transdisciplinary assessment to discipline-specific allied health assessment on an acute stroke unit, by evaluating assessment time, quality of care, and cost implications.

Establishing Methods to Assess Baby-Friendly Hospital Initiative Compliance Using the Global Standards and Women's Self-Reported Experiences.

The World Health Organization recommends assessing compliance with key clinical practices of the Baby-Friendly Hospital Initiative (BFHI; Steps 3-9) using birthing women's self-reports. Globally, compliance is mainly assessed using health staff reports, and the use of women's self-reports in selected countries has deviated from the Global Standards for the BFHI. Therefore, we aimed to provide insight into the appropriate method of incorporating women's self-reports in assessing compliance with Steps 3-9 of the BFHI.

LINE-1 retrotransposons contribute to mouse PV interneuron development.

Retrotransposons are mobile DNA sequences duplicated via transcription and reverse transcription of an RNA intermediate. Cis-regulatory elements encoded by retrotransposons can also promote the transcription of adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mammalian neurons.

Maternal physical activity and sitting time and its association with placental morphology and blood flow during gestation: Findings from the Queensland Family Cohort study.

Objectives: Antenatal exercise is associated with placental morphological alterations, however research in this area is limited. Given the emphasis on the beneficial effects of antenatal exercise, it is important to understand its effect on placental function and the relationship to foetal development. The aim of this study was to investigate the association between physical activity, sitting time, and placental outcomes measured during gestation.

The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease.

The differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls.

Every repeat is unique: Exploring the genomic impact of human L1 retrotransposons at locus-specific resolution.

Fully understanding the impact of the human retrotransposon L1 requires that each of ∼500,000 L1 copies be evaluated as a potentially unique genomic entity. In this issue of Cell Genomics, Lanciano et al. strive toward this goal, illuminating the reciprocal regulatory influence between individual L1s and their genomic integration sites.

Microtissue Culture Provides Clarity on the Relative Chondrogenic and Hypertrophic Response of Bone-Marrow-Derived Stromal Cells to TGF-β1, BMP-2, and GDF-5.

Chondrogenic induction of bone-marrow-derived stromal cells (BMSCs) is typically accomplished with medium supplemented with growth factors (GF) from the transforming growth factor-beta (TGF-β)/bone morphogenetic factor (BMP) superfamily. In a previous study, we demonstrated that brief (1-3 days) stimulation with TGF-β1 was sufficient to drive chondrogenesis and hypertrophy using small-diameter microtissues generated from 5000 BMSC each. This biology is obfuscated in typical large-diameter pellet cultures, which suffer radial heterogeneity.

A systematic review of the cost-effectiveness of maternity models of care.

Objectives: In this systematic review, we aimed to identify the full extent of cost-effectiveness evidence available for evaluating alternative Maternity Models of Care (MMC) and to summarize findings narratively.

Methods: Articles that included a decision tree or state-based (Markov) model to explore the cost-effectiveness of an MMC, and at least one comparator MMC, were identified from a systematic literature review. The MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases were searched for papers published in English, Arabic, and French.