Reflections and Experiences of a Co-Researcher involved in a Renal Research Study

Background Patient and Public Involvement (PPI) is seen as a prerequisite for health research. However, current Patient and public involvement literature has noted a paucity of recording of patient and public involvement within research studies. There have been calls for more recordings and reflections, specifically on impact. Renal medicine has also had similar criticisms and any reflections on patient and public involvement has usually been from the viewpoint of the researcher. Roles of patient and public involvement can vary greatly from sitting on an Advisory Group to analysing data. Different PPI roles have been described within studies; one being a co-researcher. However, the role of the co-researcher is largely undefined and appears to vary from study to study. Methods The aims of this paper are to share one first time co-researcher's reflections on the impact of PPI within a mixed methods (non-clinical trial) renal research study. A retrospective, reflective approach was taken using data available to the co-researcher as part of the day-to-day research activity. Electronic correspondence and documents such as meeting notes, minutes, interview thematic analysis and comments on documents were re-examined. The co-researcher led on writing this paper. Results This paper offers a broad definition of the role of the co-researcher. The co-researcher reflects on undertaking and leading on the thematic analysis of interview transcripts, something she had not previously done before. The co-researcher identified a number of key themes; the differences in time and responsibility between being a coresearcher and an Advisory Group member; how the role evolved and involvement activities could match the co-researchers strengths (and the need for flexibility); the need for training and support and lastly, the time commitment. It was also noted that it is preferable that a co-researcher needs to be involved from the very beginning of the grant application. Conclusions The reflections, voices and views of those undertaking PPI has been largely underrepresented in the literature. The role of co-researcher was seen to be rewarding but demanding, requiring a large time commitment. It is hoped that the learning from sharing this experience will encourage others to undertake this role, and encourage researchers to reflect on the needs of those involved.Peer reviewedFinal Published versio

Impaired development of the cerebral cortex in infants with congenital heart disease is correlated to reduced cerebral oxygen delivery

Neurodevelopmental impairment is the most common comorbidity associated with complex congenital heart disease (CHD), while the underlying biological mechanism remains unclear. We hypothesised that impaired cerebral oxygen delivery in infants with CHD is a cause of impaired cortical development, and predicted that cardiac lesions most associated with reduced cerebral oxygen delivery would demonstrate the greatest impairment of cortical development. We compared 30 newborns with complex CHD prior to surgery and 30 age-matched healthy controls using brain MRI. The cortex was assessed using high resolution, motion-corrected T2-weighted images in natural sleep, analysed using an automated pipeline. Cerebral oxygen delivery was calculated using phase contrast angiography and pre-ductal pulse oximetry, while regional cerebral oxygen saturation was estimated using near-infrared spectroscopy. We found that impaired cortical grey matter volume and gyrification index in newborns with complex CHD was linearly related to reduced cerebral oxygen delivery, and that cardiac lesions associated with the lowest cerebral oxygen delivery were associated with the greatest impairment of cortical development. These findings suggest that strategies to improve cerebral oxygen delivery may help reduce brain dysmaturation in newborns with CHD, and may be most relevant for children with CHD whose cardiac defects remain unrepaired for prolonged periods after birth

A genome-wide meta-analysis of palmoplantar pustulosis implicates TH2 responses and cigarette smoking in disease pathogenesis

\ua9 2024 The AuthorsBackground: Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. Although the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets. Objectives: We sought to identify genetic determinants of PPP and investigate whether cigarette smoking contributes to disease pathogenesis. Methods: We performed a genome-wide association meta-analysis of 3 North-European cohorts (n = 1,456 PPP cases and 402,050 controls). We then used the scGWAS program to investigate the cell-type specificity of the association signals. We also undertook genetic correlation analyses to examine the similarities between PPP and other immune-mediated diseases. Finally, we applied Mendelian randomization to analyze the causal relationship between cigarette smoking and PPP. Results: We found that PPP is not associated with the main genetic determinants of plaque psoriasis. Conversely, we identified genome-wide significant associations with the FCGR3A/FCGR3B and CCHCR1 loci. We also observed 13 suggestive (P < 5 7 10−6) susceptibility regions, including the IL4/IL13 interval. Accordingly, we demonstrated a significant genetic correlation between PPP and TH2-mediated diseases such as atopic dermatitis and ulcerative colitis. We also found that genes mapping to PPP-associated intervals were preferentially expressed in dendritic cells and often implicated in T-cell activation pathways. Finally, we undertook a Mendelian randomization analysis, which supported a causal role of cigarette smoking in PPP. Conclusions: The first genome-wide association study of PPP points to a pathogenic role for deregulated TH2 responses and cigarette smoking

Heterologous expression of cytotoxic sesquiterpenoids from the medicinal mushroom Lignosus rhinocerotis in yeast

Background: Genome mining facilitated by heterologous systems is an emerging approach to access the chemical diversity encoded in basidiomycete genomes. In this study, three sesquiterpene synthase genes, GME3634, GME3638, and GME9210, which were highly expressed in the sclerotium of the medicinal mushroom Lignosus rhinocerotis, were cloned and heterologously expressed in a yeast system. Results: Metabolite profile analysis of the yeast culture extracts by GC-MS showed the production of several sesquiterpene alcohols (C 15 H 26 O), including cadinols and germacrene D-4-ol as major products. Other detected sesquiterpenes include selina-6-en-4-ol, ß-elemene, ß-cubebene, and cedrene. Two purified major compounds namely (+)-torreyol and a-cadinol synthesised by GME3638 and GME3634 respectively, are stereoisomers and their chemical structures were confirmed by 1 H and 13 C NMR. Phylogenetic analysis revealed that GME3638 and GME3634 are a pair of orthologues, and are grouped together with terpene synthases that synthesise cadinenes and related sesquiterpenes. (+)-Torreyol and a-cadinol were tested against a panel of human cancer cell lines and the latter was found to exhibit selective potent cytotoxicity in breast adenocarcinoma cells (MCF7) with IC 50 value of 3.5 ± 0.58 µg/ml while a-cadinol is less active (IC 50 = 18.0 ± 3.27 µg/ml). Conclusions: This demonstrates that yeast-based genome mining, guided by transcriptomics, is a promising approach for uncovering bioactive compounds from medicinal mushrooms

Healthcare costs of pregnancy in systemic lupus erythematosus: retrospective observational analysis from a US health claims database

<div><p></p><p>Objective:</p><p>Systemic lupus erythematosus is a complex autoimmune disease, most frequently affecting women of childbearing age. Women with lupus are at increased risk of pregnancy complications that are exacerbated by active disease. Despite this, their use of medications and hospital resources has not been extensively studied.</p><p>Methods:</p><p>Retrospective analyses of the Truven Health MarketScan database (2006−2012) aimed to quantify drug and resource utilization in pregnant women with lupus, as well as the incidence of pregnancy complications in these patients. Records of women aged 12−54 were reviewed and both lupus patients and pregnancies identified. Pregnant women with lupus were matched 1:5 with either pregnant women without lupus, or non-pregnant women with lupus.</p><p>Results:</p><p>Pregnancies with lupus were associated with increased complications when compared to pregnancies without lupus. During pregnancy, the use of immunosuppressants decreased in pregnant women with lupus, as did rheumatologist visits, while the number of women not treated with any immunosuppressant increased. Pregnant women with lupus showed higher overall treatment costs than controls. However, compared to non-pregnant women with lupus, medication costs actually dropped, possibly due to the withdrawal of medications from these patients or women becoming pregnant while disease activity was low.</p><p>Conclusions:</p><p>The large database analyses reported here revealed that pregnancies in women with lupus were associated with a higher risk of complications, higher healthcare costs, and fewer prescribed medications, including immunosuppressants, than the control groups. The increased risk of complications and decreased immunosuppressant use suggest that patients require additional guidance from physicians to give them the best chance of experiencing a safe pregnancy. Indeed, despite the recognized role active lupus plays in increasing pregnancy complications, women with lupus had fewer rheumatology visits during pregnancy, although their visits to their general practitioner/primary healthcare provider increased, highlighting the need for team-based co-ordination care between OBGYN physicians and rheumatologists.</p></div

Model-based indices of early-stage cardiovascular failure and its therapeutic management in Fontan patients

International audienceInvestigating the causes of failure of Fontan circulation in individual patients remains challenging despite detailed combined inva-sive cardiac catheterisation and magnetic resonance (XMR) exams at rest and during stress. In this work, we use a biomechanical model of the heart and Fontan circulation with the components of systemic and pulmonary beds to augment the diagnostic assessment of the patients undergoing the XMR stress exam. We apply our model in 3 Fontan patients and one biventricular "control" case. In all subjects, we obtained important biophysical factors of cardiovascular physiology-contractil-ity, contractile reserve and changes in systemic and pulmonary vascular resistance-which contribute to explaining the mechanism of failure in individual patients. Finally, we used the patient-specific model of one Fontan patient to investigate the impact of changes in pulmonary vas-cular resistance, aiming at in silico testing of pulmonary vasodilation treatments