Implementation of an Electronic Clinical Decision Support System for the Early Recognition and Management of Dysglycemia in an Inpatient Mental Health Setting Using CogStack: Protocol for a Pilot Hybrid Type 3 Effectiveness-Implementation Randomized Controlled Cluster Trial.

BACKGROUND: Severe mental illnesses (SMIs), including schizophrenia, bipolar affective disorder, and major depressive disorder, are associated with an increased risk of physical health comorbidities and premature mortality from conditions including cardiovascular disease and diabetes. Digital technologies such as electronic clinical decision support systems (eCDSSs) could play a crucial role in improving the clinician-led management of conditions such as dysglycemia (deranged blood sugar levels) and associated conditions such as diabetes in people with a diagnosis of SMI in mental health settings. OBJECTIVE: We have developed a real-time eCDSS using CogStack, an information retrieval and extraction platform, to automatically alert clinicians with National Health Service Trust-approved, guideline-based recommendations for dysglycemia monitoring and management in secondary mental health care. This novel system aims to improve the management of dysglycemia and associated conditions, such as diabetes, in SMI. This protocol describes a pilot study to explore the acceptability, feasibility, and evaluation of its implementation in a mental health inpatient setting. METHODS: This will be a pilot hybrid type 3 effectiveness-implementation randomized controlled cluster trial in inpatient mental health wards. A ward will be the unit of recruitment, where it will be randomly allocated to receive either access to the eCDSS plus usual care or usual care alone over a 4-month period. We will measure implementation outcomes, including the feasibility and acceptability of the eCDSS to clinicians, as primary outcomes, alongside secondary outcomes relating to the process of care measures such as dysglycemia screening rates. An evaluation of other implementation outcomes relating to the eCDSS will be conducted, identifying facilitators and barriers based on established implementation science frameworks. RESULTS: Enrollment of wards began in April 2022, after which clinical staff were recruited to take part in surveys and interviews. The intervention period of the trial began in February 2023, and subsequent data collection was completed in August 2023. Data are currently being analyzed, and results are expected to be available in June 2024. CONCLUSIONS: An eCDSS can have the potential to improve clinician-led management of dysglycemia in inpatient mental health settings. If found to be feasible and acceptable, then, in combination with the results of the implementation evaluation, the system can be refined and improved to support future successful implementation. A larger and more definitive effectiveness trial should then be conducted to assess its impact on clinical outcomes and to inform scalability and application to other conditions in wider mental health care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04792268; https://clinicaltrials.gov/study/NCT04792268. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49548.

The NFκB Dif is required for behavioral and molecular correlates of sleep homeostasis in Drosophila.

The nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, genetic studies of the role of specific NFκB transcription factors in sleep have been limited. Drosophila fruit flies carry three genes encoding NFκB transcription factors, Dorsal, Dorsal Immunity Factor (Dif), and Relish. We previously found that loss of the Relish gene from fat body suppressed daily nighttime sleep, and abolished infection-induced sleep. Here we show that Dif regulates daily sleep and recovery sleep following prolonged wakefulness. Mutants of Dif showed reduced daily sleep and suppressed recovery in response to sleep deprivation. Pan-neuronal knockdown of Dif strongly suppressed daily sleep, indicating that in contrast to Relish, Dif functions from the central nervous system to regulate sleep. Based on the unique expression pattern of a Dif- GAL4 driver, we hypothesized that its effects on sleep were mediated by the pars intercerebralis (PI). While RNAi knock-down of Dif in the PI reduced daily sleep, it had no effect on the recovery response to sleep deprivation. However, recovery sleep was suppressed when RNAi knock-down of Dif was distributed across a wider range of neurons. Induction of the nemuri (nur) antimicrobial peptide by sleep deprivation was reduced in Dif mutants and pan-neuronal over-expression of nur also suppressed the Dif mutant phenotype by significantly increasing sleep and reducing nighttime arousability. Together, these findings indicate that Dif functions from brain to target nemuri and to promote deep sleep.

Identification of a core transcriptional program driving the human renal mesenchymal-to-epithelial transition.

During kidney development, nephron epithelia arise de novo from fate-committed mesenchymal progenitors through a mesenchymal-to-epithelial transition (MET). Downstream of fate specification, transcriptional mechanisms that drive establishment of epithelial morphology are poorly understood. We used human iPSC-derived renal organoids, which recapitulate nephrogenesis, to investigate mechanisms controlling renal MET. Multi-ome profiling via snRNA-seq and ATAC-seq of organoids identified dynamic changes in gene expression and chromatin accessibility driven by activators and repressors throughout MET. CRISPR interference identified that paired box 8 (PAX8) is essential for initiation of MET in human renal organoids, contrary to in vivo mouse studies, likely by activating a cell-adhesion program. While Wnt/ß-catenin signaling specifies nephron fate, we find that it must be attenuated to allow hepatocyte nuclear factor 1-beta (HNF1B) and TEA-domain (TEAD) transcription factors to drive completion of MET. These results identify the interplay between fate commitment and morphogenesis in the developing human kidney, with implications for understanding both developmental kidney diseases and aberrant epithelial plasticity following adult renal tubular injury.

A systematic review of discrete choice experiments in stroke rehabilitation.

OBJECTIVES: Existing research qualitatively explores consumer preferences for stroke rehabilitation interventions. However, it remains unclear which intervention characteristics are most important to consumers, and how these preferences may influence uptake and participation. Discrete choice experiments (DCE) provide a unique way to quantitatively measure preferences for health and health care. This study aims to explore how DCEs have been used in stroke rehabilitation and to identify reported consumer preferences for rehabilitation interventions. MATERIAL AND METHODS: A systematic review of published stroke rehabilitation DCEs was completed (PROSPERO registration: CRD42021282578). Six databases (including CINAHL, MEDLINE, EconLIT) were searched from January 2000-March 2023. Data extracted included topic area, sample size, aim, attributes, design process, and preference outcomes. Descriptive and thematic analyses were conducted, and two methodological checklists applied to review quality. RESULTS: Of 2,446 studies screened, five were eligible. Studies focused on exercise preference (n = 3), the structure and delivery of community services (n = 1), and self-management programs (n = 1). All had small sample sizes (range 50-146) and were of moderate quality (average score of 77%). Results indicated people have strong preferences for one-to-one therapy (over group-based), light-moderate intensity of exercise, and delivery by qualified therapists (over volunteers). CONCLUSIONS: Few DCEs have been conducted in stroke rehabilitation, suggesting consumer preferences could be more rigorously explored. Included studies were narrow in the scope of attributes included, limiting their application to practice and policy. Further research is needed to assess the impact of differing service delivery models on uptake and participation.

Exploring the Use of Digital Interventions by People with Severe Mental Illness to Support Their Physical Health: A Mixed Methods Study.

People with severe mental illness (SMI) are more likely to experience physical health conditions than the general population. Little is known about the experience of people with SMI using digital health interventions (DHIs) to support their physical health. We explored how people with SMI use DHIs to support their physical health, the acceptability, factors affecting use, and impact on physical health. This was a three-stage mixed methods study (1) online survey of people with SMI; (2) interviews with a subsample of participants from Stage 1; (3) stakeholder workshops. Participants were generally satisfied with the DHIs they used. The most popular DHIs were targeted at diet, exercise, and weight management. Factors that encouraged use included simplicity and data-linkage. Concerns included costs, data security, and reliability of information. Positive impacts included accountability and tangible physical health benefits. Mental health impacted engagement with DHIs. DHIs were seen as a useful tool to monitor physical health but could not replace contact with clinical services. DHIs were considered useful and acceptable by people with SMI and may be used as an extension of clinical care. The specific needs and priorities of people with SMI should be considered both in developing and recommending interventions.

Prospective study design and data analysis in UK Biobank.

Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.

Alzheimer's disease-associated P460L variant of EphA1 dysregulates receptor activity and blood-brain barrier function.

INTRODUCTION: Genome-wide association studies link susceptibility to late-onset Alzheimer's disease (LOAD) with EphA1. Sequencing identified a non-synonymous substitution P460L as a LOAD risk variant. Other Ephs regulate vascular permeability and immune cell recruitment. We hypothesized that P460L dysregulates EphA1 receptor activity and impacts neuroinflammation. METHODS: EphA1/P460L receptor activity was assayed in isogenic Human Embryonic Kidney (HEK) cells. Soluble EphA1/P460L (sEphA1/sP460L) reverse signaling in brain endothelial cells was assessed by T-cell recruitment and barrier function assays. RESULTS: EphA1 and P460L were expressed in HEK cells, but membrane and soluble P460L were significantly reduced. Ligand engagement induced Y781 phosphorylation of EphA1 but not P460L. sEphA1 primed brain endothelial cells for increased T-cell recruitment; however, sP460L was less effective. sEphA1 decreased the integrity of the brain endothelial barrier, while sP460L had no effect. DISCUSSION: These findings suggest that P460L alters EphA1-dependent forward and reverse signaling, which may impact blood-brain barrier function in LOAD. HIGHLIGHTS: EphA1-dependent reverse signaling controls recruitment of T cells by brain endothelial cells. EphA1-dependent reverse signaling remodels brain endothelial cell contacts. LOAD-associated P460L variant of EphA1 shows reduced membrane expression and reduced ligand responses. LOAD-associated P460L variant of EphA1 fails to reverse signal to brain endothelial cells.

Unbiased kidney-centric molecular categorization of chronic kidney disease as a step towards precision medicine.

Current classification of chronic kidney disease (CKD) into stages using indirect systemic measures (estimated glomerular filtration rate (eGFR) and albuminuria) is agnostic to the heterogeneity of underlying molecular processes in the kidney thereby limiting precision medicine approaches. To generate a novel CKD categorization that directly reflects within kidney disease drivers we analyzed publicly available transcriptomic data from kidney biopsy tissue. A Self-Organizing Maps unsupervised artificial neural network machine-learning algorithm was used to stratify a total of 369 patients with CKD and 46 living kidney donors as healthy controls. Unbiased stratification of the discovery cohort resulted in identification of four novel molecular categories of disease termed CKD-Blue, CKD-Gold, CKD-Olive, CKD-Plum that were replicated in independent CKD and diabetic kidney disease datasets and can be further tested on any external data at kidneyclass.org. Each molecular category spanned across CKD stages and histopathological diagnoses and represented transcriptional activation of distinct biological pathways. Disease progression rates were highly significantly different between the molecular categories. CKD-Gold displayed rapid progression, with significant eGFR-adjusted Cox regression hazard ratio of 5.6 [1.01-31.3] for kidney failure and hazard ratio of 4.7 [1.3-16.5] for composite of kidney failure or a 40% or more eGFR decline. Urine proteomics revealed distinct patterns between the molecular categories, and a 25-protein signature was identified to distinguish CKD-Gold from other molecular categories. Thus, patient stratification based on kidney tissue omics offers a gateway to non-invasive biomarker-driven categorization and the potential for future clinical implementation, as a key step towards precision medicine in CKD.

Cone-beam CT-based Navigation With Augmented Fluoroscopy of the Airways for Image-guided Bronchoscopic Biopsy of Peripheral Pulmonary Nodules: A Prospective Clinical Study.

BACKGROUND: Cone-beam computed tomography (CBCT) and augmented fluoroscopy (AF), in which intraprocedural CBCT data is fused with fluoroscopy, have been utilized as a novel image-guidance technique for biopsy of peripheral pulmonary lesions. The aim of this clinical study is to determine the safety and diagnostic performance of CBCT-guided bronchoscopy with advanced software tools for procedural planning and navigational guidance with AF of the airways for biopsy of peripheral pulmonary nodules. METHODS: Fifty-two consecutive subjects were prospectively enrolled in the AIRWAZE study (December 2018 to October 2019). Image-guided bronchoscopic biopsy procedures were performed under general anesthesia with specific ventilation protocols in a hybrid operating room equipped with a ceiling-mounted C-arm system. Procedural planning and image-guided bronchoscopy with CBCT and AF were performed using the Airwaze investigational device. RESULTS: A total of 58 pulmonary lesions with a median size of 19.0 mm (range 7 to 48 mm) were biopsied. The overall diagnostic yield at index procedure was 87.9% (95% CI: 77.1%-94.0%). No severe adverse events related to CBCT-guided bronchoscopy, such as pneumothorax, bleeding, or respiratory failure, were observed. CONCLUSION: CBCT-guided bronchoscopic biopsy with augmented fluoroscopic views of the airways and target lesion for navigational guidance is technically feasible and safe. Three-dimensional image-guided navigation biopsy is associated with high navigational success and a high diagnostic yield for peripheral pulmonary nodules.

Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer's polygenic risk reveals autobiographical deficits and cingulate cortex correlates.

BACKGROUND: Genome-wide association studies demonstrate that Alzheimer's disease (AD) has a highly polygenic architecture, where thousands of independent genetic variants explain risk with high classification accuracy. This AD polygenic risk score (AD-PRS) has been previously linked to preclinical cognitive and neuroimaging features observed in asymptomatic individuals. However, shared variance between AD-PRS and neurocognitive features are small, suggesting limited preclinical utility. METHODS: Here, we recruited sixteen clinically asymptomatic individuals (mean age 67; range 58-76) with either extremely low / high AD-PRS (defined as at least 2 standard deviations from the wider sample mean (N = 4504; N EFFECTIVE = 90)) with comparable age sex and education level. We assessed group differences in autobiographical memory and T1-weighted structural neuroimaging features. RESULTS: We observed marked reductions in autobiographical recollection (Cohen's d = - 1.66; P FDR = 0.014) and midline structure (cingulate) thickness (Cohen's d = - 1.55, P FDR = 0.05), with no difference in hippocampal volume (P > 0.3). We further confirm the negative association between AD-PRS and cingulate thickness in a larger study with a comparable age (N = 31,966, ß = - 0.002, P = 0.011), supporting the validity of our approach. CONCLUSIONS: These observations conform with multiple streams of prior evidence suggesting alterations in cingulate structures may occur in individuals with higher AD genetic risk. We were able to use a genetically informed research design strategy that significantly improved the efficiency and power of the study. Thus, we further demonstrate that the recall-by-genotype of AD-PRS from wider samples is a promising approach for the detection, assessment, and intervention in specific individuals with increased AD genetic risk.

Physiological Replication of the Human Glomerulus Using a Triple Culture Microphysiological System.

The function of the glomerulus depends on the complex cell-cell/matrix interactions and replication of this in vitro would aid biological understanding in both health and disease. Previous models do not fully reflect all cell types and interactions present as they overlook mesangial cells within their 3D matrix. Herein, the development of a microphysiological system that contains all resident renal cell types in an anatomically relevant manner is presented. A detailed transcriptomic analysis of the contributing biology of each cell type, as well as functionally appropriate albumin retention in the system, is demonstrated. The important role of mesangial cells is shown in promoting the health and maturity of the other cell types. Additionally, a comparison of the incremental advances that each individual cell type brings to the phenotype of the others demonstrates that glomerular cells in simple 2D culture exhibit a state more reflective of the dysfunction observed in human disease than previously recognized. This in vitro model will expand the capability to investigate glomerular biology in a more translatable manner by the inclusion of the important mesangial cell compartment.

The NFκB Dif is required for behavioral and molecular correlates of sleep homeostasis in Drosophila.

The nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, efforts have been limited toward understanding how specific NFκB transcription factors function in sleep. Drosophila fruit flies carry three genes encoding NFκB transcription factors, Dorsal, Dorsal Immunity Factor (Dif), and Relish. We previously found that loss of the Relish gene from fat body suppressed daily nighttime sleep, and abolished infection-induced sleep. Here we show that Dif regulates daily sleep and recovery sleep following prolonged wakefulness. Mutants of Dif showed reduced daily sleep and suppressed recovery in response to sleep deprivation. Pan-neuronal knockdown of Dif strongly suppressed daily sleep, indicating that in contrast to Relish, Dif functions from the central nervous system to regulate sleep. Based on the distribution of a Dif-associated GAL4 driver, we hypothesized that its effects on sleep were mediated by the pars intercerebralis (PI). While RNAi knock-down of Dif in the PI reduced daily sleep, it had no effect on the recovery response to sleep deprivation. However, recovery sleep was suppressed when RNAi knock-down of Dif was distributed across a wider range of neurons. Induction of the nemuri (nur) antimicrobial peptide by sleep deprivation was suppressed in Dif mutants and pan-neuronal over-expression of nur also suppressed the Dif mutant phenotype. Together, these findings indicate that Dif functions from brain to target nemuri and to promote sleep.

Intranasal mRNA-LNP vaccination protects hamsters from SARS-CoV-2 infection.

Intranasal vaccination represents a promising approach for preventing disease caused by respiratory pathogens by eliciting a mucosal immune response in the respiratory tract that may act as an early barrier to infection and transmission. This study investigated immunogenicity and protective efficacy of intranasally administered messenger RNA (mRNA)-lipid nanoparticle (LNP) encapsulated vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Syrian golden hamsters. Intranasal mRNA-LNP vaccination systemically induced spike-specific binding [immunoglobulin G (IgG) and IgA] and neutralizing antibodies. Intranasally vaccinated hamsters also had decreased viral loads in the respiratory tract, reduced lung pathology, and prevented weight loss after SARS-CoV-2 challenge. Together, this study demonstrates successful immunogenicity and protection against respiratory viral infection by an intranasally administered mRNA-LNP vaccine.

Alzheimer's disease-associated complement gene variants influence plasma complement protein levels.

BACKGROUND: Alzheimer's disease (AD) has been associated with immune dysregulation in biomarker and genome-wide association studies (GWAS). GWAS hits include the genes encoding complement regulators clusterin (CLU) and complement receptor 1 (CR1), recognised as key players in AD pathology, and complement proteins have been proposed as biomarkers. MAIN BODY: To address whether changes in plasma complement protein levels in AD relate to AD-associated complement gene variants we first measured relevant plasma complement proteins (clusterin, C1q, C1s, CR1, factor H) in a large cohort comprising early onset AD (EOAD; n = 912), late onset AD (LOAD; n = 492) and control (n = 504) donors. Clusterin and C1q were significantly increased (p < 0.001) and sCR1 and factor H reduced (p < 0.01) in AD plasma versus controls. ROC analyses were performed to assess utility of the measured complement biomarkers, alone or in combination with amyloid beta, in predicting AD. C1q was the most predictive single complement biomarker (AUC 0.655 LOAD, 0.601 EOAD); combining C1q with other complement or neurodegeneration makers through stepAIC-informed models improved predictive values slightly. Effects of GWS SNPs (rs6656401, rs6691117 in CR1; rs11136000, rs9331888 in CLU; rs3919533 in C1S) on protein concentrations were assessed by comparing protein levels in carriers of the minor vs major allele. To identify new associations between SNPs and changes in plasma protein levels, we performed a GWAS combining genotyping data in the cohort with complement protein levels as endophenotype. SNPs in CR1 (rs6656401), C1S (rs3919533) and CFH (rs6664877) reached significance and influenced plasma levels of the corresponding protein, whereas SNPs in CLU did not influence clusterin levels. CONCLUSION: Complement dysregulation is evident in AD and may contribute to pathology. AD-associated SNPs in CR1, C1S and CFH impact plasma levels of the encoded proteins, suggesting a mechanism for impact on disease risk.

How is physical healthcare experienced by staff, service users, and carers in adult community mental health services in a south London mental health trust? A service evaluation.

Background: Adults with a serious mental illness (SMI) are at greater risk of physical health morbidity and premature death than the general population, largely as a result of preventable physical health issues. Staff working in mental health services have a role to play in addressing these inequalities, but little is known about how they perceive their role and how this impacts on their practice. Understanding this better would enable services to improve their approach and support better health outcomes for SMI patients. A service evaluation was undertaken to investigate how physical healthcare is approached within adult community mental health teams (CMHTs) at a South London (UK) Mental Health Trust. Methods: This was a prospective, cross-sectional evaluation design. Interviews and focus groups were conducted with clinical staff, service users and carers (non-professional caregivers e.g., family or friends, of adults living with an SMI), to understand their experiences and to identify key barriers and facilitators to supporting physical healthcare support for adults with SMI. Thematic analysis was conducted to identify key themes which were classified into five main categories. Results: 50 participants took part in the study, 38 were clinical staff, eight were service users and four were carers. We found staff widely recognised the importance of supporting physical healthcare. However, there was variability in how staff approached physical healthcare in routine practice, and differences in how physical healthcare is experienced by service users and carers. Staff were keen to engage in changes to the way physical healthcare is delivered in CMHTs. However, they sought clearer guidance on their roles and responsibilities, and wanted to better understand the rationale for changes in community mental health practice, such as increased screening for physical healthcare. Service users and carers felt equally that the role of CMHTs in physical healthcare was unclear, which limited their ability to access it and understand the benefit for their overall care. Staff articulated gaps in leadership and training that impacted on their ability to implement the overall vision for physical healthcare within the Trust. Conclusion: Mental health staff recognise the role they play in supporting the physical health of adults living with SMI. This evaluation provides insight into common barriers and facilitators faced by staff, service users and carers when providing or accessing physical healthcare within adult CMHTs. These findings indicate a more comprehensive and better articulated approach to physical healthcare in mental health Trusts is needed to ensure service users and their carers understand what support is available and how to access it and to equip staff to provide and sustain that care in routine practice.

The Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project: Study design and methodology.

INTRODUCTION: Sequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late-onset AD although early-onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations, resulting in a lack of understanding of its molecular etiology. METHODS: Whole-genome sequencing and harmonization of clinical, neuropathological, and biomarker data of over 5000 EOAD cases of diverse ancestries. RESULTS: A publicly available genomics resource for EOAD with extensive harmonized phenotypes. Primary analysis will (1) identify novel EOAD risk loci and druggable targets; (2) assess local-ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits. DISCUSSION: This novel resource complements over 50,000 control and late-onset AD samples generated through the Alzheimer's Disease Sequencing Project (ADSP). The harmonized EOAD/ADSP joint call will be available through upcoming ADSP data releases and will allow for additional analyses across the full onset range. HIGHLIGHTS: Sequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late-onset AD although early-onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations. This results in a significant lack of understanding of the molecular etiology of this devastating form of the disease. The Early-Onset Alzheimer's Disease Whole-genome Sequencing Project is a collaborative initiative to generate a large-scale genomics resource for early-onset Alzheimer's disease with extensive harmonized phenotype data. Primary analyses are designed to (1) identify novel EOAD risk and protective loci and druggable targets; (2) assess local-ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits. The harmonized genomic and phenotypic data from this initiative will be available through NIAGADS.

3D vascularised proximal tubules-on-a-multiplexed chip model for enhanced cell phenotypes.

Modelling proximal tubule physiology and pharmacology is essential to understand tubular biology and guide drug discovery. To date, multiple models have been developed; however, their relevance to human disease has yet to be evaluated. Here, we report a 3D vascularized proximal tubule-on-a-multiplexed chip (3DvasPT-MC) device composed of co-localized cylindrical conduits lined with confluent epithelium and endothelium, embedded within a permeable matrix, and independently addressed by a closed-loop perfusion system. Each multiplexed chip contains six 3DvasPT models. We performed RNA-seq and compared the transcriptomic profile of proximal tubule epithelial cells (PTECs) and human glomerular endothelial cells (HGECs) seeded in our 3D vasPT-MCs and on 2D transwell controls with and without a gelatin-fibrin coating. Our results reveal that the transcriptional profile of PTECs is highly dependent on both the matrix and flow, while HGECs exhibit greater phenotypic plasticity and are affected by the matrix, PTECs, and flow. PTECs grown on non-coated Transwells display an enrichment of inflammatory markers, including TNF-a, IL-6, and CXCL6, resembling damaged tubules. However, this inflammatory response is not observed for 3D proximal tubules, which exhibit expression of kidney signature genes, including drug and solute transporters, akin to native tubular tissue. Likewise, the transcriptome of HGEC vessels resembled that of sc-RNAseq from glomerular endothelium when seeded on this matrix and subjected to flow. Our 3D vascularized tubule on chip model has utility for both renal physiology and pharmacology.

Are Perceptions of Government Intervention Related to Support for Prevention? An Australian Survey Study.

BACKGROUND: In Australia, despite the success of tobacco control policy interventions, policymakers remain resistant to policy-based approaches to diet, alcohol, physical inactivity and obesity, concerned about community perceptions of such interventions as "nanny-statist". We examined how people's general positions on government intervention related to their positions on different preventive policy options. METHODS: Data were from a 2018 nationally representative cross-sectional telephone survey of 2601 Australian adults. Survey questions related to endorsement of different conceptualisations of government intervention (nanny state, paternalistic, shared responsibility and communitarian) and support for specific health interventions, using forced-choice questions about preferences for individual/treatment measures versus population/preventive health measures. We analysed associations between scores on different conceptualisations of government intervention and support of different policy options for tobacco and diet, and preferences for prevention over treatment. RESULTS: The Nanny State Scale showed an inverse relationship with support for tobacco- and diet-related interventions, and alternative conceptualisations (paternalistic, shared responsibility and communitarian) showed a positive relationship. Effect sizes in all cases were small. Those aged 55+ demonstrated greater support for policy action on tobacco and diet, and greater preference for systemic rather than individual-level interventions. CONCLUSION: General disposition towards government intervention, although correlated with support for specific policy actions, is not deterministic.