Factors that impact on the quality of life of intestinal failure patients treated with home parenteral nutrition: protocol for a multicentre, longitudinal observational study

\ua9 2024 BMJ Publishing Group. All rights reserved. Background: Home parenteral nutrition (HPN) refers to the intravenous administration of macronutrients, micronutrients and fluid. The aims of treatment are to increase survival and improve quality of life (QoL). However, patients struggle with physiological symptoms, time-consuming invasive therapy and an increased occurrence of depression and social isolation. Our aim is to understand how HPN impacts the QoL of patients, and the contribution played by the complications of treatment, for example, liver disease. Methods and analysis: A multicentre, longitudinal, observational study will be conducted using routinely collected clinical data. Participants will also be asked to complete three QoL questionnaires (EuroQol-5 Dimensions, Short Form 36 and HPN-QoL) at baseline and 12 months. The primary outcome is mean change in QoL scores over 12 months. Secondary outcomes include how factors including liver function, gut microbiota, number of infusions of PN per week, nutritional composition of PN and nutritional status impact on QoL scores. Ethics and dissemination: Ethical approval was obtained from HRA and Health and Care Research Wales Research Ethics Committee (21/SC/0316). The study was eligible for portfolio adoption, Central Portfolio Management System ID 50506. Results will be disseminated through peer-reviewed scientific journals and presented at national and international meetings

Exploring research institutes: Structures, functioning and typology

Research institutes play an important role as part of the innovation landscape, which includes industrial, academic and governmental organisations. Although there is often much confusion over what constitutes an institute and there can even be a number of different terms associated with such organisational forms, including centres, networks, programmes and laboratories. Indeed institutes can enable multidisciplinary research and the translation of knowledge generated to deliver societal benefits and address industrial requirements. However, despite the benefits offered by establishing research institutes, there has been a distinct lack of studies in this area. Therefore, this paper provides the findings from an initial research study into the structure, functioning and typology of institutes. Following a literature review on institutes, a benchmarking study involving examination of 25 research institutes associated with the energy sector has been carried out. This study identified key features of the institutes, in regard to the research area, technology readiness level, funding, partners, organisational structure, leadership and governance arrangements. Subsequent analysis of these findings has resulted in three main types of institute being identified. The pros and cons for each institute type are provided along with recommendations on the development and management of research institutes

Depressed Adolescents’ Pupillary Response to Peer Acceptance and Rejection: The Role of Rumination

Heightened emotional reactivity to peer feedback is predictive of adolescents’ depression risk. Examining variation in emotional reactivity within currently depressed adolescents may identify subgroups that struggle the most with these daily interactions. We tested whether trait rumination, which amplifies emotional reactions, explained variance in depressed adolescents’ physiological reactivity to peer feedback, hypothesizing that rumination would be associated with greater pupillary response to peer rejection and diminished response to peer acceptance. Twenty currently depressed adolescents (12–17) completed a virtual peer interaction paradigm where they received fictitious rejection and acceptance feedback. Pupillary response provided a time-sensitive index of physiological arousal. Rumination was associated with greater initial pupil dilation to both peer rejection and acceptance, and diminished late pupillary response to peer acceptance trials only. Results indicate that depressed adolescents high on trait rumination are more reactive to social feedback regardless of valence, but fail to sustain cognitive-affective load on positive feedback

A Case of Treatment Resistance and Complications in a Patient with Stiff Person Syndrome and Cerebellar Ataxia

BACKGROUND: Antibodies against glutamic acid decarboxylase (GAD) are associated with Stiff Person Syndrome (SPS). CASE REPORT: A 50-year-old woman presented with symptoms progressed over 9 years, resulting in a cerebellar ataxia and right upper limb tremor. Investigations revealed elevated serum and CSF anti-GAD antibody titres (98.6 and 53.4 μ/ml, respectively). Treatment included intravenous immunoglobulin and immunomodulation (infliximab and rituximab), improving her stiffness, but with no impact on the ataxia-related symptoms. Subsequent high-dose steroids led to diabetic ketoacidosis and unmasking of an insulin-dependent diabetes mellitus. DISCUSSION: This case illustrates several key features: (1) the combined clinical picture of SPS and cerebellar ataxia is a rare phenotype associated with anti-GAD antibodies; (2) the cerebellar ataxia described was progressive and poorly responsive to immunomodulatory therapy; and (3) the potential for development of further autoimmune sequelae in response to immunosuppression, namely, the development of insulin-dependent diabetes in response to treatment with high-dose oral steroids

Dermoscopy for melanoma detection and triage in primary care: a systematic review.

OBJECTIVE: Most skin lesions first present in primary care, where distinguishing rare melanomas from benign lesions can be challenging. Dermoscopy improves diagnostic accuracy among specialists and is promoted for use by primary care physicians (PCPs). However, when used by untrained clinicians, accuracy may be no better than visual inspection. This study aimed to undertake a systematic review of literature reporting use of dermoscopy to triage suspicious skin lesions in primary care settings, and challenges for implementation. DESIGN: A systematic literature review and narrative synthesis. DATA SOURCES: We searched MEDLINE, Cochrane Central, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and SCOPUS bibliographic databases from 1 January 1990 to 31 December 2017, without language restrictions. INCLUSION CRITERIA: Studies including assessment of dermoscopy accuracy, acceptability to patients and PCPs, training requirements, and cost-effectiveness of dermoscopy modes in primary care, including trials, diagnostic accuracy and acceptability studies. RESULTS: 23 studies met the review criteria, representing 49 769 lesions and 3708 PCPs, all from high-income countries. There was a paucity of studies set truly in primary care and the outcomes measured were diverse. The heterogeneity therefore made meta-analysis unfeasible; the data were synthesised through narrative review. Dermoscopy, with appropriate training, was associated with improved diagnostic accuracy for melanoma and benign lesions, and reduced unnecessary excisions and referrals. Teledermoscopy-based referral systems improved triage accuracy. Only three studies examined cost-effectiveness; hence, there was insufficient evidence to draw conclusions. Costs, training and time requirements were considered important implementation barriers. Patient satisfaction was seldom assessed. Computer-aided dermoscopy and other technological advances have not yet been tested in primary care. CONCLUSIONS: Dermoscopy could help PCPs triage suspicious lesions for biopsy, urgent referral or reassurance. However, it will be important to establish further evidence on minimum training requirements to reach competence, as well as the cost-effectiveness and patient acceptability of implementing dermoscopy in primary care. TRIAL REGISTRATION NUMBER: CRD42018091395.CRU

The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells.

An open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells. Deletion of Nanog leads to chromatin compaction and the remodeling of heterochromatin domains. Forced expression of NANOG in epiblast stem cells is sufficient to decompact chromatin. NANOG associates with satellite repeats within heterochromatin domains, contributing to an architecture characterized by highly dispersed chromatin fibers, low levels of H3K9me3, and high major satellite transcription, and the strong transactivation domain of NANOG is required for this organization. The heterochromatin-associated protein SALL1 is a direct cofactor for NANOG, and loss of Sall1 recapitulates the Nanog-null phenotype, but the loss of Sall1 can be circumvented through direct recruitment of the NANOG transactivation domain to major satellites. These results establish a direct connection between the pluripotency network and chromatin organization and emphasize that maintaining an open heterochromatin architecture is a highly regulated process in embryonic stem cells.We thank Ludovic Vallier for constitutive Nanog-EpiSC, Gabrielle Brons for 129S2 EpiSC, Prim Singh for H3K9me3 antibody, Maria Elena Torres Padilla for TALE-mClover and luciferase plasmids, Wellcome Trust Sanger Institute for pCyL43 plasmid and Andras Nagy for PB-TET and rtTA plasmids. We are grateful to David Oxley and Judith Webster Novo et al. for mass spectrometry support, Simon Walker for imaging support and Anne Segonds- Pichon for statistical advice. We thank Wolf Reik and Jon Houseley for comments on the manuscript and members of Wolf Reik’s group for helpful discussions. P.J.R.-G. is supported by the Wellcome Trust [WT093736], BBSRC [M022285] and the European Commission Network of Excellence EpiGeneSys [HEALTH-F4-2010-257082]. The work was also supported with funds from the Canadian Institutes of Health Research to J.E. [Team Grant EPS-129129] and D.P.B.-J. D.P.B-J. holds the Canada Research Chair in Molecular and Cellular Imaging. I.C. is supported by the MRC

Evaluation of the ECOSSE model for simulating soil organic carbon under Miscanthus and short rotation coppice-willow crops in Britain

In this paper, we focus on the impact on soil organic carbon (SOC) of two dedicated energy crops: perennial grass Miscanthus x Giganteus (Miscanthus) and short rotation coppice (SRC)-willow. The amount of SOC sequestered in the soil is a function of site-specific factors including soil texture, management practices, initial SOC levels and climate; for these reasons, both losses and gains in SOC were observed in previous Miscanthus and SRC-willow studies. The ECOSSE model was developed to simulate soil C dynamics and greenhouse gas emissions in mineral and organic soils. The performance of ECOSSE has already been tested at site level to simulate the impacts of land-use change to short rotation forestry (SRF) on SOC. However, it has not been extensively evaluated under other bioenergy plantations, such as Miscanthus and SRC-willow. Twenty-nine locations in the United Kingdom, comprising 19 paired transitions to SRC-willow and 20 paired transitions to Miscanthus, were selected to evaluate the performance of ECOSSE in predicting SOC and SOC change from conventional systems (arable and grassland) to these selected bioenergy crops. The results of the present work revealed a strong correlation between modelled and measured SOC and SOC change after transition to Miscanthus and SRC-willow plantations, at two soil depths (0–30 and 0–100 cm), as well as the absence of significant bias in the model. Moreover, model error was within (i.e. not significantly larger than) the measurement error. The high degrees of association and coincidence with measured SOC under Miscanthus and SRC-willow plantations in the United Kingdom, provide confidence in using this process-based model for quantitatively predicting the impacts of future land use on SOC, at site level as well as at national level

Evaluation of the ECOSSE model for simulating soilcarbon under short rotation forestry energy crops in Britain

Understanding and predicting the effects of land-use change to short rotation forestry (SRF) on soil carbon (C) is an important requirement for fully assessing the C mitigation potential of SRF as a bioenergy crop. There is little current knowledge of SRF in the UK and in particular a lack of consistent measured data sets on the direct impacts of land use change on soil C stocks. The ECOSSE model was developed to simulate soil C dynamics and greenhouse gas (GHG) emissions in mineral and organic soils. The ECOSSE model has already been applied spatially to simulate land-use change impacts on soil C and GHG emissions. However, it has not been extensively evaluated under SRF. Eleven sites comprising 29 transitions in Britain, representing land-use change from nonwoodland land uses to SRF, were selected to evaluate the performance of ECOSSE in predicting soil C and soil C change in SRF plantations. The modelled C under SRF showed a strong correlation with the soil C measurements at both 0–30 cm (R = 0.93) and 0–100 cm soil depth (R = 0.82). As for the SRF plots, the soil C at the reference sites have been accurately simulated by the model. The extremely high correlation for the reference fields (R ≥ 0.99) shows a good performance of the model spin-up. The statistical analysis of the model performance to simulate soil C and soil C changes after land-use change to SRF highlighted the absence of significant error between modelled and measured values as well as the absence of significant bias in the model. Overall, this evaluation reinforces previous studies on the ability of ECOSSE to simulate soil C and emphasize its accuracy to simulate soil C under SRF plantations

Effects of a Single Intra-Articular Injection of a Microsphere-Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study

Background: Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs. Methods: In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit. Results: The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: −3.12 versus −2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments. Conclusions: FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point)