How do women with a history of SEED-AN experience navigating their lives away from and beyond their illness - A narrative inquiry study

The purpose of this study was to explore through narrative inquiry methodology the experiences of four participants as they navigated their lives away from severe and enduring anorexia nervosa (SEED-AN, Robinson, 2009). Whilst positions of what recovery can mean emerged its aim was to open up the ‘how’; how may a person journey away from a life dominated by anorexia nervosa? These first-person narratives stretched across early developmental disturbances to being caught between dread of the past, repetition in the future and their experiences in the present time. This study emerged from my own long experience of anorexia, my professional relationship within my private practice and as co-founder of Anorexic Aid, now B-eat, a UK national charity for eating disorders. This insider-researcher perspective provided what I believe to be a unique subjective and reflective dimension to this study. To analyse and frame the narratives in a way that enabled the reader to travel alongside the participants’ journey Bettelheim’s (1976) framework used to analyse fairy-tales was adapted and became a scaffold to begin the analysis. A cross-case analysis followed with Connelly & Clandinin’s (1990) three-stage narrative inquiry analytic tool adapted for this purpose. From scrutinising the transcripts in this way what began to emerge was a sense whereby relationships for all the participants were viewed as unsafe and unreliable and their sense of self shifted between invisible and invincible. There followed two distinct stages the first I refer to as ‘transition’ whereby from consistent, containing relationships new relational configurations displayed a shift from concrete ‘knowing’ to experiencing the idea of possibilities in the future. They also began to develop a capacity, to be reflective and reflexive. The second stage I have named ‘Integration’, where the narratives demonstrated a more grounded sense of ‘self and other’, of relinquishing the need to be special, of taking in the idea of being ‘ordinary’ and good enough. This study has provided a depth of understanding of SEED that appears to be little attended to in current research, the confusion of what are ‘normal and socially acceptable’ thoughts, feelings and actions and what may be eating disorder residues particularly around food, body shape and exercise. This study has further highlighted organisational challenges for the provision of therapy within the public sector which remains time-limited and focused on symptom alleviation; it conveys the importance of therapeutic consistency. A further outcome from this study that is relevant to all our clients who have experienced a long history of struggling with mental health has been to shine a torch on the importance of hope and encouragement in the therapeutic endeavour. It expands the importance of mentalisation and provides an additional concept of understanding ‘relapse’ as a positive experience, one not to be viewed negatively but rather a flag towards unprocessed material. To summarise this study has identified the primacy of emotional nourishment achieved with and through human relatedness

Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway

Circulating levels of chylomicron remnants (CMRs) increase postprandially and their composition directly reflects dietary lipid intake. These TG-rich lipoproteins likely contribute to the development of endothelial dysfunction, albeit via unknown mechanisms. Here, we investigated how the FA composition of CMRs influences their actions on human aortic endothelial cells (HAECs) by comparing the effects of model CMRs—artificial TG-rich CMR-like particles (A-CRLPs)—containing TGs extracted from fish, DHA-rich algal, corn, or palm oils. HAECs responded with distinct transcriptional programs according to A-CRLP TG content and oxidation status, with genes involved in antioxidant defense and cytoprotection most prominently affected by n-3 PUFA-containing A-CRLPs. These particles were significantly more efficacious inducers of heme oxygenase-1 (HO-1) than n-6 PUFA corn or saturated FA-rich palm CRLPs. Mechanistically, HO-1 induction by all CRLPs requires NADPH oxidase 4, with PUFA-containing particles additionally dependent upon mitochondrial reactive oxygen species. Activation of both p38 MAPK and PPARβ/δ culminates in increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression/nuclear translocation and HO-1 induction. These studies define new molecular pathways coupling endothelial cell activation by model CMRs with adaptive regulation of Nrf2-dependent HO-1 expression and may represent key mechanisms through which dietary FAs differentially impact progression of endothelial dysfunction

High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F-2 alpha concentrations relative to a control high-oleic acid meal: a randomized controlled trial

Background: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear. Objectives: The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high–oleic acid meals; the secondary objective was to characterize the effects of linoleic acid–enriched high-fat meals relative to the control meal. Design: We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high–oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high–linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35–70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L). Results: Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (Δ 0–3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse–reflection index was not significantly different. Plasma 8-isoprostane F(2α) analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed. Conclusions: These data show differential postprandial 8-isoprostane F(2α) responses to high-fat meals containing EPA + DHA–rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid–derived lipid mediators are required to determine possible divergent functional effects of single meals rich in either DHA or EPA. This trial was registered at clinicaltrials.gov as NCT01618071

Floral enhancement of arable field margins increases moth abundance and diversity

Moth populations have declined across large parts of north-western Europe since the mid-20th century due, in part, to agricultural intensification. Agri-environment schemes (AES) are widely implemented across Europe to protect biodiversity in agricultural landscapes. Grass field margins enriched with wildflowers typically out-perform grass-only margins in terms of increasing insect abundance and diversity. However, the effect of wildflower enrichment on moths remains largely unstudied. Here, the relative importance of larval hostplants and nectar resources for adult moths within AES field margins are investigated. Two treatments and a control were compared: (i) a plain grass mix, the control, (ii) a grass mix enriched with only moth-pollinated flowers, and (iii) a grass mix enriched with 13 wildflower species. Abundance, species richness and Shannon diversity were up to 1.4, 1.8 and 3.5 times higher, respectively, in the wildflower treatment compared to plain grass. The difference in diversity between treatments became greater in the second year. There was no difference in total abundance, richness or diversity between the plain grass treatment and grass enriched with moth-pollinated flowers. The increase in abundance and diversity in the wildflower treatment was due primarily to the provision of larval hostplants, with nectar provision playing a smaller role. The relative abundance of species whose larval hostplants included sown wildflowers increased in the second year, suggesting colonisation of the new habitat. Implications for insect conservation. We show that, at the farm scale, moth diversity can be greatly enhanced and abundance moderately enhanced by sowing diverse wildflower margins, providing these insects with both larval hostplants and floral resources, compared to grass-only margins

Abundance changes and habitat availability drive species’ responses to climate change

There is little consensus as to why there is so much variation in the rates at which different species’ geographic ranges expand in response to climate warming[1,2]. Here, we show for British butterfly species that the relative importance of species’ abundance trends and habitat availability vary over time. Species with high habitat availability expanded more rapidly from the 1970s to mid-1990s, when abundances were generally stable, whereas habitat availability effects were confined to the subset of species with stable abundances from the mid-1990s to 2009, when abundance trends were generally declining. This suggests that stable (or positive) abundance trends are a prerequisite for range expansion. Given that species’ abundance trends vary over time[3] for non-climatic as well as climatic reasons, assessment of abundance trends will help improve predictions of species’ responses to climate change, and help understand the likely success of different conservation strategies for facilitating their expansions

Community interventions for people with complex emotional needs that meet the criteria for personality disorder diagnoses: systematic review of economic evaluations and expert commentary

Background: Diagnoses of personality disorder are prevalent among people using community secondary mental health services. Identifying cost-effective community-based interventions is important when working with finite resources. / Aims: To assess the cost-effectiveness of primary or secondary care community-based interventions for people with complex emotional needs who meet criteria for a diagnosis of personality disorder to inform healthcare policy-making. / Method: Systematic review (PROSPERO: CRD42020134068) of databases. We included economic evaluations of interventions for adults with complex emotional needs associated with a diagnosis of personality disorder in community mental health settings published before 18 September 2019. Study quality was assessed using the CHEERS statement. / Results: Eighteen studies were included. The studies mainly evaluated psychotherapeutic interventions. Studies were also identified that evaluated altering the setting in which care was delivered and joint crisis plans. No strong economic evidence to support a single intervention or model of community-based care was identified. / Conclusions: Robust economic evidence to support a single intervention or model of community-based care for people with complex emotional needs is lacking. The strongest evidence was for dialectical behaviour therapy, with all three identified studies indicating that it is likely to be cost-effective in community settings compared with treatment as usual. More robust evidence is required on the cost-effectiveness of community-based interventions on which decision makers can confidently base guidelines or allocate resources. The evidence should be based on consistent measures of costs and outcomes with sufficient sample sizes to demonstrate impacts on these

Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: A workshop summary

AbstractAs experience is gained with toxicology testing and as new assays and technologies are developed, it is critical for stakeholders to discuss opportunities to advance our overall testing strategies. To facilitate these discussions, a workshop on practices for assessing immunotoxicity for environmental chemicals was held with the goal of sharing perspectives on immunotoxicity testing strategies and experiences, developmental immunotoxicity (DIT), and integrated and alternative approaches to immunotoxicity testing. Experiences across the chemical and pharmaceutical industries suggested that standard toxicity studies, combined with triggered-based testing approaches, represent an effective and efficient approach to evaluate immunotoxic potential. Additionally, discussions on study design, critical windows, and new guideline approaches and experiences identified important factors to consider before initiating DIT evaluations including assay choice and timing and the impact of existing adult data. Participants agreed that integrating endpoints into standard repeat-dose studies should be considered for fulfilling any immunotoxicity testing requirements, while also maximizing information and reducing animal use. Participants also acknowledged that in vitro evaluation of immunosuppression is complex and may require the use of multiple assays that are still being developed. These workshop discussions should contribute to developing an effective but more resource and animal efficient approach for evaluating chemical immunotoxicity

Pharmacokinetic, neurochemical, stereological and neuropathological studies on the potential effects of paraquat in the substantia nigra pars compacta and striatum of male C57BL/6J mice

AbstractThe pharmacokinetics and neurotoxicity of paraquat dichloride (PQ) were assessed following once weekly administration to C57BL/6J male mice by intraperitoneal injection for 1, 2 or 3 weeks at doses of 10, 15 or 25mg/kg/week. Approximately 0.3% of the administered dose was taken up by the brain and was slowly eliminated, with a half-life of approximately 3 weeks. PQ did not alter the concentration of dopamine (DA), homovanillic acid (HVA) or 3,4-dihydroxyphenylacetic acid (DOPAC), or increase dopamine turnover in the striatum. There was inconsistent stereological evidence of a loss of DA neurons, as identified by chromogenic or fluorescent-tagged antibodies to tyrosine hydroxylase in the substantia nigra pars compacta (SNpc). There was no evidence that PQ induced neuronal degeneration in the SNpc or degenerating neuronal processes in the striatum, as indicated by the absence of uptake of silver stain or reduced immunolabeling of tyrosine-hydroxylase-positive (TH+) neurons. There was no evidence of apoptotic cell death, which was evaluated using TUNEL or caspase 3 assays. Microglia (IBA-1 immunoreactivity) and astrocytes (GFAP immunoreactivity) were not activated in PQ-treated mice 4, 8, 16, 24, 48, 96 or 168h after 1, 2 or 3 doses of PQ.In contrast, mice dosed with the positive control substance, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 10mg/kg/dose×4 doses, 2h apart), displayed significantly reduced DA and DOPAC concentrations and increased DA turnover in the striatum 7 days after dosing. The number of TH+ neurons in the SNpc was reduced, and there were increased numbers of degenerating neurons and neuronal processes in the SNpc and striatum. MPTP-mediated cell death was not attributed to apoptosis. MPTP activated microglia and astrocytes within 4h of the last dose, reaching a peak within 48h. The microglial response ended by 96h in the SNpc, but the astrocytic response continued through 168h in the striatum.These results bring into question previous published stereological studies that report loss of TH+ neurons in the SNpc of PQ-treated mice. This study also suggests that even if the reduction in TH+ neurons reported by others occurs in PQ-treated mice, this apparent phenotypic change is unaccompanied by neuronal cell death or by modification of dopamine levels in the striatum