Living beyond placenta accreta spectrum: parent's experience of the postnatal journey and recommendations for an integrated care pathway.

Placenta Accreta Spectrum is associated with significant clinical maternal morbidity and mortality, which has been extensively described in the literature. However, there is a dearth of research on the lived experiences of pregnant people and their support partners. The aim of this study is to describe living beyond a pregnancy and birth complicated by PAS for up to four years postpartum. Participants experiences inform the development of an integrated care pathway of family centered support interventions. An Interpretative Phenomenological Analysis approach was applied to collect data through virtual interviews over a 3-month period from February to April 2021. Twenty-nine participants shared their stories; six people with a history of PAS and their support partners were interviewed together (n = 12 participants), six were interviewed separately (n = 12 participants), and five were interviewed without their partner. Pregnant people were eligible for inclusion if they had a diagnosis of PAS within the previous 5 years. This paper focuses on the postnatal period, with data from the antenatal and intrapartum periods described separately. One superordinate theme "Living beyond PAS" emerged from interviews, with 6 subordinate themes as follows; "Living with a different body", "The impact on relationships", "Coping strategies", "Post-traumatic growth", "Challenges with normal care" and recommendations for "What needs to change". These themes informed the development of an integrated care pathway for pregnant people and their support partners to support them from diagnosis up to one year following the birth. Parents described the challenges of the postnatal period in terms of the physical and emotional impact, and how some were able to make positive life changes in the aftermath of a traumatic event. An integrated care pathway of simple supportive interventions, based on participant recommendations, delivered as part of specialist multidisciplinary team care may assist pregnant people and their support partners in alleviating some of these challenges

Circulating myeloid populations have prognostic utility in alcohol-related liver disease

Introduction: Alcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased nearly five-fold over the last 30 years. Severe alcohol-related hepatitis almost always occurs in patients with a background of chronic liver disease with extensive fibrosis or cirrhosis, can precipitate ‘acute on chronic’ liver failure and has a high short-term mortality. Patients with alcohol-related liver disease have impaired immune responses, and increased susceptibility to infections, thus prompt diagnosis of infection and careful patient management is required. The identification of early and non-invasive diagnostic and prognostic biomarkers in ARLD remains an unresolved challenge. Easily calculated predictors of infection and mortality are required for use in patients who often exhibit variable symptoms and disease severity and may not always present in a specialized gastroenterology unit.Methods: We have used a simple haematological analyser to rapidly measure circulating myeloid cell parameters across the ARLD spectrum.Results and Discussion: We demonstrate for the first time that immature granulocyte (IG) counts correlate with markers of disease severity, and our data suggests that elevated counts are associated with increased short-term mortality and risk of infection. Other myeloid populations such as eosinophils and basophils also show promise. Thus IG count has the potential to serve alongside established markers such as neutrophil: lymphocyte ratio as a simply calculated predictor of mortality and risk of infectious complications in patients with alcohol-related hepatitis. This would allow identification of patients who may require more intensive management

Inhibition of vascular adhesion protein-1 modifies hepatic steatosis in vitro and in vivo

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance and dyslipidaemia and currently is estimated to affect up to a third of all individuals in developed countries. Current standard of care for patients varies according to disease stage, but includes lifestyle interventions common insulin sensitizers, antioxidants and lipid modifiers. However, to date specific therapies have shown little histological or fibrosis stage improvement in large clinical trials, and there is still no licensed therapy for NAFLD. Given the high prevalence, limited treatment options and significant screening costs for the general population, new treatments are urgently required. AIM: To assess the potential for inhibition of the amine oxidase enzyme vascular adhesion protein-1 (VAP-1) to modify hepatic lipid accumulation in NAFLD. METHODS: We have used immunochemical and qPCR analysis to document expression of VAP-1 and key functional proteins and transporters across the NAFLD spectrum. We then utilised hepatocytes in culture and human precision cut liver slices in concert with selective enzyme activity inhibitors to test the effects of activating the semicarbazide-sensitive amine oxidase activity of VAP-1 on hepatic lipid uptake and triglyceride export. A murine model of NAFLD was also used to determine the consequences of VAP-1 knockout and gene expression arrays were used to quantify the effects of VAP-1 activity on key lipid modifying and proinflammatory gene expression. RESULTS: We confirmed that increasing severity of NAFLD and progression to cirrhosis was associated with a significant increase in hepatocellular VAP-1 expression. Hepatocytes in vitro exposed to recombinant VAP-1 and its substrate methylamine showed increased lipid accumulation as determined by quantification of Oil Red O uptake. This was recapitulated using hydrogen peroxide, and lipid accumulation was accompanied by changes in expression of the lipid transporter molecules FABP3, FATP6, insulin receptor subunits and PPARα. Human liver tissue exposed to recombinant VAP-1 or substrates for endo/exogenous VAP-1 produced less triglyceride than untreated tissue and demonstrated an increase in steatosis. This response could be inhibited by using bromoethylamine to inhibit the SSAO activity of VAP-1, and mice deficient in VAP-1/AOC3 also demonstrated reduced steatosis on high fat diet. Exposure of human liver tissue to methylamine to activate VAP-1 resulted in increased expression of FABP2 and 4, FATP3-5, caveolin-1, VLDLR, PPARGC1 and genes associated with the inflammatory response. CONCLUSION: Our data confirm that the elevations in hepatic VAP-1 expression reported in nonalcoholic steatohepatitis can contribute to steatosis, metabolic disturbance and inflammation. This suggests that targeting the semicarbazide sensitive amine oxidase capacity of VAP-1 may represent a useful adjunct to other therapeutic strategies in NAFLD

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials

Total immersion : Designing for affective symbiosis in a virtual reality game with haptics, biosensors, and emotive agents

Peer reviewe

Vitamin D status in cats with feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a lentivirus that can lead to a syndrome of acquired immune dysfunction. Infected cats often remain asymptomatic for several years before immune dysfunction leads to an increased risk for the development of systemic diseases, neoplasia and opportunistic infections. FIV is structurally related to human immunodeficiency virus (HIV) and the pathogenesis of FIV‐related disease is similar to that seen in HIV‐infected patients. Observational studies have documented an association between low plasma vitamin D and HIV infection. Vitamin D status has been shown to be associated with HIV‐related disease progression, morbidity and mortality. The objective of this study was to examine the hypothesis that vitamin D status, as assessed by serum 25‐hydroxyvitamin D [25(OH)D] concentrations, are lower in cats with FIV infection compared to healthy control cats. Serum 25(OH)D concentrations were measured in 20 healthy cats, 39 hospitalized ill cats and 59 cats infected with FIV. Cats which were FIV infected had significantly lower 25(OH)D concentrations compared to healthy control cats. Serum 25(OH)D concentrations were not significantly different between FIV‐infected cats and hospitalized ill cats. Further investigations are warranted to determine whether vitamin D status influences the prognosis of cats infected with FIV