Inhibition of Intimal Thickening By PRH (Proline-Rich Homeodomain) in Mice.

BACKGROUND: Late vein graft failure is caused by intimal thickening resulting from endothelial cell (EC) damage and inflammation which promotes vascular smooth muscle cell (VSMC) dedifferentiation, migration, and proliferation. Nonphosphorylatable PRH (proline-rich homeodomain) S163C:S177C offers enhanced stability and sustained antimitotic effect. Therefore, we investigated whether adenovirus-delivered PRH S163C:S177C protein attenuates intimal thickening via VSMC phenotype modification without detrimental effects on ECs. METHODS: PRH S163C:S177C was expressed in vitro (human saphenous vein-VSMCs and human saphenous vein-ECs) and in vivo (ligated mouse carotid arteries) by adenoviruses. Proliferation, migration, and apoptosis were quantified and phenotype was assessed using Western blotting for contractile filament proteins and collagen gel contraction. EC inflammation was quantified using VCAM (vascular cell adhesion protein)-1, ICAM (intercellular adhesion molecule)-1, interleukin-6, and monocyte chemotactic factor-1 measurement and monocyte adhesion. Next Generation Sequencing was utilized to identify novel downstream mediators of PRH action and these and intimal thickening were investigated in vivo. RESULTS: PRH S163C:S177C inhibited proliferation, migration, and apoptosis and promoted contractile phenotype (enhanced contractile filament proteins and collagen gel contraction) compared with virus control in human saphenous vein-VSMCs. PRH S163C:S177C expression in human saphenous vein-ECs significantly reduced apoptosis, without affecting cell proliferation and migration, while reducing TNF (tumor necrosis factor)-α-induced VCAM-1 and ICAM-1 and monocyte adhesion and suppressing interleukin-6 and monocyte chemotactic factor-1 protein levels. PRH S163C:S177C expression in ligated murine carotid arteries significantly impaired carotid artery ligation-induced neointimal proliferation and thickening without reducing endothelial coverage. Next Generation Sequencing revealed STAT-1 (signal transducer and activator of transcription 1) and HDAC-9 (histone deacetylase 9) as mediators of PRH action and was supported by in vitro and in vivo analyses. CONCLUSIONS: We observed PRH S163C:S177C attenuated VSMC proliferation, and migration and enhanced VSMC differentiation at least in part via STAT-1 and HDAC-9 signaling while promoting endothelial repair and anti-inflammatory properties. These findings highlight the potential for PRH S163C:S177C to preserve endothelial function whilst suppressing intimal thickening, and reducing late vein graft failure.

Pharmacological Inhibition of MMP-12 Exerts Protective Effects on Angiotensin II-Induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice.

Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation and elastin degradation, in conjunction with superimposed atherosclerosis. Previous genetic ablation studies have proposed contradictory roles for MMP-12 in AAA development. In this study, we aimed to elucidate if pharmacological inhibition of MMP-12 activity with a phosphinic peptide inhibitor protects from AAA formation and progression in angiotensin (Ang) II-infused Apoe-/- mice. Complimentary studies were conducted in a human ex vivo model of early aneurysm development. Administration of an MMP-12 inhibitor (RXP470.1) protected hypercholesterolemia Apoe-/- mice from Ang II-induced AAA formation and rupture-related death, associated with diminished medial thinning and elastin fragmentation alongside increased collagen deposition. Proteomic analyses confirmed a beneficial effect of MMP-12 inhibition on extracellular matrix remodeling proteins combined with inflammatory pathways. Furthermore, RXP470.1 treatment of mice with pre-existing AAAs exerted beneficial effects as observed through suppressed aortic dilation and rupture, medial thinning, and elastin destruction. Our findings indicate that pharmacological inhibition of MMP-12 activity retards AAA progression and improves survival in mice providing proof-of-concept evidence to motivate translational work for MMP-12 inhibitor therapy in humans.

Revisiting Snodgrass and Vanderwart in photograph form: The Keele Photo Stimulus Set (KPSS).

Over the last 40 years, object recognition studies have moved from using simple line drawings, to more detailed illustrations, to more ecologically valid photographic representations. Researchers now have access to various stimuli sets, however, existing sets lack the ability to independently manipulate item format, as the concepts depicted are unique to the set they derive from. To enable such comparisons, Rossion and Pourtois (2004) revisited Snodgrass and Vanderwart's (1980) line drawings and digitally re-drew the objects, adding texture and shading. In the current study, we took this further and created a set of stimuli that showcase the same objects in photographic form. We selected six photographs of each object (three color/three grayscale) and collected normative data and RTs. Naming accuracy and agreement was high for all photographs and appeared to steadily increase with format distinctiveness. In contrast to previous data patterns for drawings, naming agreement (H values) did not differ between grey and color photographs, nor did familiarity ratings. However, grey photographs received significantly lower mental imagery agreement and visual complexity scores than color photographs. This suggests that, in comparison to drawings, the ecological nature of photographs may facilitate deeper critical evaluation of whether they offer a good match to a mental representation. Color may therefore play a more vital role in photographs than in drawings, aiding participants in judging the match with their mental representation. This new photographic stimulus set and corresponding normative data provide valuable materials for a wide range of experimental studies of object recognition.

Optimizing lipid management-impact of the COVID 19 pandemic upon cardiovascular risk in England.

BACKGROUND: We sought to understand the impact of the COVID-19 pandemic on lipid-lowering therapy prescribing as a potential cause of the excess cardiovascular mortality seen post-pandemic in England. We examined temporal changes over 3 years in the prescribing of high-intensity and non-high-intensity statin therapy and ezetimibe. SOURCES OF DATA: We utilized data available via the National Health Service (NHS) Business Services Authority (NHSBSA) Information Services Data Warehouse, extracting 3 monthly data from October 2018 to December 2021 on high- and low-intensity statin and ezetimibe prescribing, (commencement, cessation or continuation) through each time period of study and those before, and after, the period of interest. AREAS OF AGREEMENT: Optimizing lipid management is a key component of the NHS Long Term Plan ambition to reduce deaths from cardiovascular disease, stroke and dementia. AREAS OF CONTROVERSY: The COVID-19 pandemic and associated lockdown have seen a significant reduction in prescribing of lipid-lowering therapies. If cardiovascular risk is not to worsen in the forthcoming years, urgent action is needed to ensure that the impact of the pandemic upon optimization of cholesterol and the historical undertreatment of cholesterol is reversed and improved. AREAS TIMELY FOR DEVELOPING RESEARCH: Prescription data available via NHSBSA can support our understanding of the implications of policy and behaviour and highlight the impact of guidelines in practise. GROWING POINTS: Understanding the impact of the COVID-19 pandemic upon cholesterol management and the opportunities for newer lipid-lowering therapies delivered using a population health approach have the potential to enhance lipid-lowering and improve cardiovascular mortality and morbidity and reduce health inequalities.

Recognition, remember-know, and confidence judgments: no evidence of cross-contamination here!

ABSTRACTWe report three experiments designed to reveal the mechanisms that underlie subjective experiences of recognition by examining effects of how those experiences are measured. Prior research has explored the potential influences of collecting metacognitive measures on memory performance. Building on this work, here we systematically evaluated whether cross-measure contamination occurs when remember-know (RK) and/or confidence (C) judgments are made after old/new recognition decisions. In Experiment 1, making either RK or C judgments did not significantly influence recognition relative to a standard no-judgment condition. In Experiment 2, making RK judgments in addition to C judgments did not significantly affect recognition or confidence. In Experiment 3, making C judgments in addition to RK judgments did not significantly affect recognition or patterns of RK responses. Cross-contamination was not apparent regardless of whether items were studied using a shallow or deep levels-of-processing task - a manipulation that yielded robust effects on recognition, RK judgments, and C. Our results indicate that under some conditions, participants can independently evaluate their recognition, subjective recognition experience, and confidence. Though contamination across measures of metamemory and memory is always possible, it may not be inevitable. This has implications for the mechanisms that underlie subjective experiences that accompany recognition judgments.

Feminizing care pathways: Mixed-methods study of reproductive options, decision making, pregnancy, post-natal care and parenting amongst women with kidney disease.

AIMS: To identify the needs, experiences and preferences of women with kidney disease in relation to their reproductive health to inform development of shared decision-making interventions. DESIGN: UK-wide mixed-methods convergent design (Sep 20-Aug 21). METHODS: Online questionnaire (n = 431) with validated components. Purposively sampled semi-structured interviews (n = 30). Patient and public input throughout. FINDINGS: Kidney disease was associated with defeminization, negatively affecting current (sexual) relationships and perceptions of future life goals. There was little evidence that shared decision making was taking place. Unplanned pregnancies were common, sometimes influenced by poor care and support and complicated systems. Reasons for (not) wanting children varied. Complicated pregnancies and miscarriages were common. Women often felt that it was more important to be a "good mother" than to address their health needs, which were often unmet and unrecognized. Impacts of pregnancy on disease and options for alternates to pregnancy were not well understood. CONCLUSION: The needs and reproductive priorities of women are frequently overshadowed by their kidney disease. High-quality shared decision-making interventions need to be embedded as routine in a feminized care pathway that includes reproductive health. Research is needed in parallel to examine the effectiveness of interventions and address inequalities. IMPACT: We do not fully understand the expectations, needs, experiences and preferences of women with kidney disease for planning and starting a family or deciding not to have children. Women lack the knowledge, resources and opportunities to have high-quality conversations with their healthcare professionals. Decisions are highly personal and related to a number of health, social and cultural factors; individualized approaches to care are essential. Healthcare services need to be redesigned to ensure that women are able to make informed choices about pregnancy and alternative routes to becoming a parent. PATIENT OR PUBLIC CONTRIBUTION: The original proposal for this research came from listening to the experiences of women in clinic who reported unmet needs and detailed experiences of their pregnancies (positive and negative). A patient group was involved in developing the funding application and helped to refine the objectives by sharing their experiences. Two women who are mothers living with kidney disease were co-opted as core members of the research team. We hosted an interim findings event and invited patients and wider support services (adoption, fertility, surrogacy, education and maternal chronic kidney disease clinics) from across the UK to attend. We followed the UK national standards for patient and public involvement throughout.

Utility of cephalic drains in infants receiving extracorporeal membrane oxygenation.

INTRODUCTION: The addition of cephalic drains (CDs) in extracorporeal membrane oxygenation (ECMO) to augment venous drainage may offer benefit, though their use is varied. Our objective was to describe our institution's experience with CDs including flow rates and patency. We also compared complication rates between patients with and without a CD. METHODS: This retrospective cohort study included infants <12 months of age cannulated for ECMO between January 1, 2010 and September 30, 2019 at a single institution. Flow data were obtained for those with a CD. Demographic and complication rates were obtained for all. RESULTS: Of 264 patients in the final cohort, 220 (83%) had a CD of which 93.2% remained patent to decannulation. CDs typically provided 30% or more of ECMO flow throughout the ECMO run. The median time to CD clot was 139 h (range 48-635 h). Patients with a clotted CD had longer ECMO runs than those whose CD remained patent (median 382 h [IQR 217-538] vs 139 h [IQR 91-246], p < 0.001). Survival to discharge was lower for those with clotted versus patent CD (14% vs 70%, p < 0.001). Mechanical complications were more common in patients with CD (p = 0.005). Seizures were more common in those without a CD (p = 0.021). CONCLUSIONS: In this cohort, the majority of CDs placed remained patent at decannulation and provided substantial additional venous drainage. Mechanical problems were common in patients with CDs, but without clinical sequelae. Further study is warranted to elucidate CD impact on short- and long-term outcomes.

Monocyte Differentiation and Heterogeneity: Inter-Subset and Interindividual Differences.

The three subsets of human monocytes, classical, intermediate, and nonclassical, show phenotypic heterogeneity, particularly in their expression of CD14 and CD16. This has enabled researchers to delve into the functions of each subset in the steady state as well as in disease. Studies have revealed that monocyte heterogeneity is multi-dimensional. In addition, that their phenotype and function differ between subsets is well established. However, it is becoming evident that heterogeneity also exists within each subset, between health and disease (current or past) states, and even between individuals. This realisation casts long shadows, impacting how we identify and classify the subsets, the functions we assign to them, and how they are examined for alterations in disease. Perhaps the most fascinating is evidence that, even in relative health, interindividual differences in monocyte subsets exist. It is proposed that the individual's microenvironment could cause long-lasting or irreversible changes to monocyte precursors that echo to monocytes and through to their derived macrophages. Here, we will discuss the types of heterogeneity recognised in monocytes, the implications of these for monocyte research, and most importantly, the relevance of this heterogeneity for health and disease.

Macrophages bind LDL using heparan sulfate and the perlecan protein core.

The retention of low-density lipoprotein (LDL) is a key process in the pathogenesis of atherosclerosis and largely mediated via smooth-muscle cell-derived extracellular proteoglycans including the glycosaminoglycan chains. Macrophages can also internalize lipids via complexes with proteoglycans. However, the role of polarized macrophage-derived proteoglycans in binding LDL is unknown and important to advance our understanding of the pathogenesis of atherosclerosis. We therefore examined the identity of proteoglycans, including the pendent glycosaminoglycans, produced by polarized macrophages to gain insight into the molecular basis for LDL binding. Using the quartz crystal microbalance with dissipation monitoring technique, we established that classically activated macrophage (M1)- and alternatively activated macrophage (M2)-derived proteoglycans bind LDL via both the protein core and heparan sulfate (HS) in vitro. Among the proteoglycans secreted by macrophages, we found perlecan was the major protein core that bound LDL. In addition, we identified perlecan in the necrotic core as well as the fibrous cap of advanced human atherosclerotic lesions in the same regions as HS and colocalized with M2 macrophages, suggesting a functional role in lipid retention in vivo. These findings suggest that macrophages may contribute to LDL retention in the plaque by the production of proteoglycans; however, their contribution likely depends on both their phenotype within the plaque and the presence of enzymes, such as heparanase, that alter the secreted protein structure.

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.

BACKGROUND: Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data. RESULTS: A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups. CONCLUSIONS: Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.).

Correction: Precise measurement of selenium isotopes by HG-MC-ICPMS using a 76-78 double-spike.

[This corrects the article DOI: 10.1039/C9JA00331B.].

Managing stroke risk in patients with atrial fibrillation: a cross-sectional analysis of socio-demographic inequalities in a London borough.

BACKGROUND: Stroke prevention is essential for patients with atrial fibrillation (AF), but some receive sub-optimal management. We reviewed those with a recorded AF diagnosis assessed with CHA2DS2-VASc stroke risk score (SRS) and socio-demographic determinants of anticoagulation prescribing. The objective was to compare with national guidance recommendations, which recommend anticoagulant therapy for SRS ≥ 2, to determine if there were inequalities in management. METHODS: A cross-sectional design was used to analyze records from all (n = 41) general practices in one London borough. Patients were excluded if they were <18 years, had AF resolved or diagnosed < 3 months. Logistic regression identified socio-demographic factors associated with high SRS and anticoagulant prescribing. RESULTS: Of 2913 patients, 2885 (99.0%) had an SRS, and 2411 (83.6%) a score ≥ 2 and 82.9% (1999 of 2411) were prescribed anticoagulation. Women (compared with men), Black and Mixed/Multiple ethnic groups (compared with White), and those living in most deprived areas (compared with least) were more likely to have a score ≥ 2. Patients with a high SRS from Black and Mixed/Multiple ethnic groups and aged 18-74 years were less likely to be prescribed anticoagulation. CONCLUSION: We found evidence of age and ethnic inequity in anticoagulation prescribing for stroke prevention in patients with AF.

Secondary magnetite in ancient zircon precludes analysis of a Hadean geodynamo.

Zircon crystals from the Jack Hills, Western Australia, are one of the few surviving mineralogical records of Earth's first 500 million years and have been proposed to contain a paleomagnetic record of the Hadean geodynamo. A prerequisite for the preservation of Hadean magnetization is the presence of primary magnetic inclusions within pristine igneous zircon. To date no images of the magnetic recorders within ancient zircon have been presented. Here we use high-resolution transmission electron microscopy to demonstrate that all observed inclusions are secondary features formed via two distinct mechanisms. Magnetite is produced via a pipe-diffusion mechanism whereby iron diffuses into radiation-damaged zircon along the cores of dislocations and is precipitated inside nanopores and also during low-temperature recrystallization of radiation-damaged zircon in the presence of an aqueous fluid. Although these magnetites can be recognized as secondary using transmission electron microscopy, they otherwise occur in regions that are indistinguishable from pristine igneous zircon and carry remanent magnetization that postdates the crystallization age by at least several hundred million years. Without microscopic evidence ruling out secondary magnetite, the paleomagnetic case for a Hadean-Eoarchean geodynamo cannot yet been made.

Staphylococcus aureus second immunoglobulin-binding protein drives atopic dermatitis via IL-33.

BACKGROUND: Staphylococcus aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in patients with AD is unclear. OBJECTIVE: We sought to identify the S aureus-derived virulence factor(s) that initiates the cutaneous type 2-promoting immune response responsible for AD. METHODS: In vitro human keratinocyte cell culture, ex vivo human skin organ explants, and the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse were used as model systems to assess type 2-promoting immune responses to S aureus. Identification of the bioactive factor was accomplished using fast protein liquid chromatography and mass spectrometry. Bioactivity was confirmed by cloning and expression in an Escherichia coli vector system, and S aureus second immunoglobulin-binding protein (Sbi) mutant strains confirming loss of activity. RESULTS: S aureus was unique among staphylococcal species in its ability to induce the rapid release of constitutive IL-33 from human keratinocytes independent of the Toll-like receptor pathway. Using the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse model, we showed that IL-33 was essential for inducing the immune response to S aureus in vivo. By fractionation and candidate testing, we identified Sbi as the predominant staphylococcus-derived virulence factor that directly drives IL-33 release from human keratinocytes. Immunohistology of skin demonstrated that corneodesmosin, a component of corneodesmosomes that form key intercellular adhesive structures in the stratum corneum, was disrupted, resulting in reduction of skin barrier function. CONCLUSIONS: S aureus-derived Sbi is a unique type 2-promoting virulence factor capable of initiating the type 2-promoting cytokine activity underlying AD.

Monocyte M1/M2 profile is altered in paediatric burn patients with hypertrophic scarring.

Hypertrophic scars (HTS) remain a common outcome of burn injury, particularly in children. They can arise from variations in the wound healing stages, such as an excessive inflammatory response or inefficient remodelling. Of the cells contributing to these healing stages, macrophages and fibrocytes are crucial. Specifically, the inflammatory phase is dominated by M1 macrophages, the proliferation/remodelling stages by M2 macrophages, and scar tissue contains numerous fibrocytes. As the progenitors to these cells, monocytes, can also exhibit M1- and M2-skewing, we proposed that their profile, or circulating fibrocyte counts, could be used to predict poor healing outcomes. To investigate this, we obtained blood samples from paediatric controls and burns patients, which were then divided into HTS and NoHTS groups upon scar assessment at 12 months. The samples were assessed by whole blood flow cytometry to quantify fibrocytes and monocyte subset proportions and to determine monocyte levels of M1 (CD86, CD120b, CD319) and M2 (CD93, CD163, CD200R) markers. Both burns groups had higher proportions of classical monocytes compared to controls, indicating increased cell turnover and/or entry of other subsets into the wound. In burns patients who took more than 21 days to heal, the HTS group had lower M2 (CD200R) expression with the ratio of M1/M2 (CD86/CD200R) being significantly higher. These results suggest an elevated early inflammatory monocyte response contributes to development of HTS. Correlations of marker expression with remaining healing time revealed a significant positive correlation with M1 (CD120b) and M1/M2 (CD120b/CD200R), suggesting a potential role for CD120b as an indicator of healing delay. Fibrocytes did not significantly differ between the groups. In conclusion, increased monocyte inflammation likely contributes to slower healing and development of scarring, but further studies are needed to determine the predictive power of monocyte inflammatory profile.

Intraoperative dextrose rate during exploratory laparotomies in neonates and the incidence of postoperative hyperglycemia: A retrospective observational study.

INTRODUCTION: Compared with the older pediatric population, neonates have greater perioperative morbidity and mortality. Difficulty with glucose regulation may be a contributing modifiable risk factor during perioperative anesthetic management. To mitigate the risk of hyperglycemia in neonates, some providers empirically halve the preoperative rate of dextrose-containing infusions during surgery. AIM: To assess the association between halving the preoperative maintenance dextrose rate and postoperative euglycemia in neonatal intensive care unit patients undergoing exploratory laparotomies. METHODS: Neonatal intensive care unit patients who underwent exploratory laparotomy under general anesthesia from 1/1/2014 to 11/21/2019 were included in this analysis. Hyperglycemia and hypoglycemia were defined as >150 mg/dL and <46 mg/dL. A calculated dextrose ratio was utilized to categorize patients into full and half intraoperative dextrose rate cohorts. Univariate analyses were performed with Fisher's exact test, the Wilcoxon rank sum test, or Spearman's correlation. Multivariable analyses with regression models were conducted after graphical evaluation of a predetermined set of independent variables. RESULTS: 107 patients were included in the full dextrose rate cohort and 96 patients in the half dextrose rate cohort with postoperative hyperglycemia occurring in 47 and 28 patients, respectively. On univariate analysis, halving the preoperative dextrose rate was associated with decreased postoperative hyperglycemia (odds ratio: 0.53; 95% CI: 0.28-0.98, P = 0.041). This association continued in the regression model (adjusted odds ratio: 0.49; 95% CI: 0.25-0.80, P = 0.008) after controlling for preoperative dextrose rate, preoperative serum glucose, preoperative pH, surgical duration, postmenstrual age at surgery, and the presence of necrotizing enterocolitis. Only one patient was hypoglycemic postoperatively, and they were in the full dextrose cohort. CONCLUSION: Halving of preoperative dextrose rates intraoperatively during exploratory laparotomy in neonatal intensive care unit patients was associated with a decreased risk of postoperative hyperglycemia without substantially increasing the occurrence of postoperative hypoglycemia. The practice of halving preoperative dextrose rates may be an effective empirical approach for intraoperative glucose management in the high-risk neonatal population when blood glucose monitoring is challenging.

Engaging and supporting women with chronic kidney disease with pre-conception decision-making (including their experiences during COVID 19): A mixed-methods study protocol.

AIM: To report a protocol for a qualitative study to better understand the key factors that influence decision making about pregnancy from women's perspectives and to use these data to develop a theoretical model for shared decision-making tools for the multiple stakeholders. DESIGN: Mixed-method design using online surveys (with validated components) and purposively sampled follow-up semi structured interviews. METHODS: Funded from September 2020 for 12 months. Online surveys of adult women (aged 18-50) identified via all Wales kidney database (n ≥ 500), additional recruitment through multidisciplinary healthcare professionals, relevant third sector organizations and social media. Follow-up in-depth qualitative interviews with n = 30 women. Linear regression models to identify associations between shared decision-making preferences and clinical and psychosocial variables. Qualitative interviews will use a visual timeline task to empower women in taking control over their narratives. Qualitative data will be fully transcribed and analysed thematically, based around a chronological and theoretical (theoretical domains framework) structure that maps out key challenges and opportunities for improved decision support in the care pathway. Visual timelines will be used during stakeholder consultation activities, to enable us to co-create a map of current support, gaps in provision, and opportunities for interventions. Quantitative data will be analysed descriptively to characterize our cohort. We will assemble a multidisciplinary shared decision-making intervention development group and provide ongoing stakeholder consultation activities with patient and public representatives. DISCUSSION: Outcomes will support new learning into; the ways women's knowledge of kidney disease may affect family planning and pregnancy, their needs in terms of psychological and social support, and how they weigh up the pros and cons of starting a family. IMPACT: Evidence will inform the design of new shared decision-making tools to better support women with the complex and often emotional decisions about having children while living with kidney disease.

Measuring the intensive care experience: A cross-sectional survey of patient and family experiences of critical care.

AIMS AND OBJECTIVES: To report patient and family intensive care experiences using the Measuring the Intensive Care Experience (MICE) tool across two intensive care units (ICU). BACKGROUND: The patient and family experience of care is an important indicator for quality improvement of ICUs, yet few studies evaluate both patient and family experiences in relation to overall care quality as well as specifically measuring quality of medical care, nursing care and organisational care as well as overall experience of the quality of intensive care. DESIGN: A cross-sectional survey. METHODS: A 23 item survey was administered to ICU patients and their family members across two ICUs, a regional 189-bed hospital and a metropolitan 227-bed hospital in Queensland, Australia. The response rate was 272 of 394 ICU patients (36.4%). STROBE guidelines were used in reporting this study. RESULTS: Findings indicate a highly positive overall experience of ICU care among patients and families. However, patients reported areas of unmet needs following their stay in ICU broadly related to (1) symptom management, education and information support, and (2) improving the incorporation of patient and family care ICU-related shared decision-making. CONCLUSIONS: Supportive interventions are needed that target improve symptom management and inform and education ICU patients. RELEVANCE TO CLINICAL PRACTICE: The MICE survey facilitated the identification of a range of areas requiring quality improvement. Improving the integration of patients and families into shared decision-making and support is a key aspect for quality improvement.

Nature versus Number: Monocytes in Cardiovascular Disease.

Monocytes play a key role in cardiovascular disease (CVD) as their influx into the vessel wall is necessary for the development of an atherosclerotic plaque. Monocytes are, however, heterogeneous differentiating from classical monocytes through the intermediate subset to the nonclassical subset. While it is recognized that the percentage of intermediate and nonclassical monocytes are higher in individuals with CVD, accompanying changes in inflammatory markers suggest a functional impact on disease development that goes beyond the increased proportion of these 'inflammatory' monocyte subsets. Furthermore, emerging evidence indicates that changes in monocyte proportion and function arise in dyslipidemia, with lipid lowering medication having some effect on reversing these changes. This review explores the nature and number of monocyte subsets in CVD addressing what they are, when they arise, the effect of lipid lowering treatment, and the possible implications for plaque development. Understanding these associations will deepen our understanding of the clinical significance of monocytes in CVD.

Lipid profiling in maternal and fetal circulations in preeclampsia and fetal growth restriction-a prospective case control observational study.

BACKGROUND: While many risk factors for preeclampsia, such as increased body mass index, advanced maternal age, chronic hypertension, diabetes, are now established in clinical practice, maternal lipid profile has not been included in the risk assessment for preeclampsia. We aim to characterize the serum levels of Total Cholesterol (TC), High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglycerides (TG), Apolipoprotein A1, Apolipoprotein B and their ratios TC/HDL and ApoB/ApoA1 in the maternal and fetal circulations of normal pregnancy, preeclampsia (PE), fetal growth restriction (FGR) and PE + FGR. METHODS: A prospective cross-sectional case control study was conducted measuring maternal and fetal lipid levels by enzymatic analysis and immune-turbidimetric enzymatic assays. FGR was defined by elevated umbilical artery Doppler resistance in association with estimated fetal weight < 10%. Kruskal Wallis non-parametric analysis of variance was used to test for homogeneity across the clinical groups for each of the variables, Mann-Whitney tests for pairwise comparisons and Spearman rank correlation were used to quantify gestational age-related changes. RESULTS: (1) TG levels were elevated in maternal PE and cord blood PE + FGR groups compared to normal pregnancies. (2) A statistically significant elevation of fetal ApoB levels was observed in PE, FGR and PE + FGR compared to normal pregnancies. Apolipoprotein levels A1 and B were not different between maternal groups. (3) TC, HDL, LDL and TC/HDL levels did not show any significant gestational variation or between clinical groups in the maternal or fetal circulation. CONCLUSIONS: Elevation in maternal TG levels may have a role in the pathogenesis of PE. The implications of elevated maternal and fetal TG levels and elevated fetal Apolipoprotein B levels deserves further exploration of their role in long term cardiovascular risk in the mother as well as the offspring.