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Objective: To characterise and investigate the functional consequences of a novel TNFRSF1A splice site mutation causing tumour necrosis factor receptor associated periodic syndrome (TRAPS) in a 16-year-old male patient and his mother.Methods: Mutational DNA screening was performed in the patient and his mother. Western blotting was used to analyse protein expression levels of TNFR1. A multiplex bead immunoassay was used to quantify serum levels of range of cytokines, and an ELISA-based transcription factor assay to measure nuclear factor (NF)-kappaB transactivation. Serum levels of soluble TNFR1 (sTNFR1) were measured by ELISA and fluorescence-activated cell sorting (FACS) analysis used to measure monocyte TNFR1 cell surface expression.Results: A novel mutation, c.472+1G>A (C158delinsYERSSPEAKPSPHPRG), involving a splice site in intron 4 of TNFRSF1A, was found in the proband and affected mother leading to a 45 nucleotide insertion of intronic DNA into the mRNA, resulting in an in-frame insertion of 15 amino acids in the mature TNFR1 protein and a deletion of a cysteine residue C129 (158) in cysteine rich domain (CRD)3. The patients had reduced serum sTNFR1 and surface expression levels of TNFR1, with marked increases in pro- and anti-inflammatory cytokine. Their peripheral blood mononuclear cells (PBMC) had increased basal NF-kappaB activation compared with healthy controls and also had increased p50 nuclear expression following tumour necrosis factor (TNF) stimulation compared with PBMC from healthy controls, as well as T50M (T79M) and C88R (C117R) patients with TRAPS and patients with rheumatoid arthritis (RA).Conclusion: A novel, TRAPS causing, TNFRSF1A splice site mutation is associated with decreased sTNFR1 levels, cell surface and whole cell extract expression and increased NF-kappaB transcription factor activation. [ABSTRACT FROM AUTHOR]

Brain arteriovenous malformations (AVM) rarely occur with spatial and/or temporal co-localisation to intracranial neoplasms. Most prior reports describe this association with high-grade gliomas; however, reports of a co-occurrence with low grade gliomas are very rare. It is unclear whether such cases represent a true co-occurrence of separate pathologies or simply an unusually vascular phenotype of the neoplasm. Most such reports pre-date the era of molecularly defined gliomas. We present the first report of the spatial and temporal co-occurrence of an intracranial arteriovenous malformation traversing and within a papillary glioneuronal tumour, molecularly defined by the presence of SLC44A1::PRKCA fusion. This case was successfully managed by resection of both lesions adhering to the principles of AVM surgery. It is possible these exceptionally rare co-occurrences may have common underlying molecular drivers relating to the mitogen activated protein kinase (MAPK) pathway., (© 2024. The Author(s).)

Changes in sleep during mid-to-late life are associated with risk for Alzheimer's disease (AD). Mechanistic understanding of this association necessitates measurement tools able to quantify these sleep changes longitudinally and accurately. We conducted a systematic review with meta-analysis of validity studies of non-invasive sleep-measuring devices published since 2015 that record sleep metrics associated with AD in adults over 40 (mean 52.9, SD 6.1 years). We reviewed 52 studies, including 32 wearable and ten non-wearable single or multi-sensor devices validated against polysomnography (minimum one night). The apnoea hypopnoea index and oxygen desaturation index were accurately measured across devices. Total sleep time and sleep efficiency were significantly overestimated (p < 0.001) by mean 33.2 minutes and 7.6%, respectively. Slow wave sleep duration was inaccurately measured except by a headband device with electroencephalography. There was no significant difference in accuracy between participants with and without sleep disorders. Studies were undermined by high risk of bias from closed-access algorithms and classification thresholds, and incomplete reporting of accuracy data. Only one study investigated slow wave activity, and none investigated sleep spindles. Nonetheless, we have identified devices that could be used in future studies of sleep and AD risk and discuss some of the limitations of available research., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Young people with neurodisability experience lower levels of mental wellbeing and are at increased risk of mental illness compared with their non-disabled peers. Social participation is recognized as a protective factor against mental illness and a potential pathway to support better mental wellbeing in neurodisability., Method: This co-design study involved young people, parents and clinicians. First, possible interventions were identified through a rapid systematic evidence review. Any study designs were considered, which included people with a neurodisability aged 0-18 years, which evaluated a therapy intervention with social participation and mental health outcomes. Titles and abstracts were screened by two reviewers, from the included studies data were extracted and then presented using written summaries. Second, the summaries were discussed and prioritized in stakeholder groups with young people, parents and clinicians. Groups were audio recorded and framework analysis was used to identify and specify intervention elements and their delivery., Results: The evidence review identified 13,870 records, from which 43 were included. These records were published 1994-2017 and reported studies with 4-249 participants aged 16 months-18 years with a range of neurodisabilities. Five intervention approaches (social skills training, arts, sports, technology and play) were identified from the review. Two themes emerged from the stakeholder groups: intervention in the real world, feeling judged and feeling safe. The groups prioritized an intervention in real-world social leisure contexts (i.e. existing clubs and groups) using nine key intervention elements (e.g. feedback and positive verbal reinforcement) delivered by club leaders trained by healthcare professionals using five intervention procedures (e.g. a manual and video training)., Conclusion: This study has identified core elements of social participation interventions that may improve mental health outcomes in young people with neurodisability, which should now be tested., (© 2021 The Authors. Child: Care, Health and Development published by John Wiley & Sons Ltd.)

Aims: This study aimed to identify the frequency of sub-optimal pelvic binder placement at a tertiary-level trauma centre, produce a reproducible, quantitative measure of pelvic binder fit, and identify risk factors for sub-optimal placement., Patients and Methods: We identified all consecutive patients who had a pelvic binder in place on arrival to the Royal Brisbane and Women's Hospital in Queensland, Australia from 2012-2016. The X-Rays were reviewed by two senior clinicians for position and measured for degree of displacement if not optimally placed between the greater and lesser trochanters. Risk factors for sub-optimal position of the binder were assessed using multiple logistic regression with inclusion of all variables that had a statistical association (to p<0.05) at the univariate analysis stage. Secondary assessment was conducted of patients who had undergone CT imaging for subcutaneous body fat distribution., Results: In total, 496 X-Rays were assessed for pelvic binder fit, finding 43.5% sub-optimally placed. 39.7% binders were superior to the greater trochanter line and 3.8% inferiorly placed below the lesser trochanter line. The majority of the sub-optimally placed binders were within 60 mm of the ideal position. Female patients had a greater risk of sub-optimal binder placement compared to males (62.5% vs 37%). Increasing intertrochanteric height was found to be protective for ideal binder placement with an aOR 0.62 for each cm in increased height. There was no association with sub-optimal placement and age, sex, mechanism of trauma, injury severity score, number of body regions injured or Glasgow Coma Scale. There was strong kappa agreement between the X-Ray assessors for binder position assessment on the plain radiological imaging., Conclusion: Sub-optimal positioning of pelvic binders is common in our trauma population. This study has described the risk factors associated with higher rates of sub-optimal fit and provides a description of rapid radiological assessment for optimal fit for the bedside clinician caring for injured patients in the resuscitation room., Competing Interests: Declaration of Competing Interest We wish to confirm that the authors of ‘Identifying Risk Factors for Suboptimal Pelvic Binder Placement in Major Trauma’ have no conflict of interest to declare in the submission to Injury., (Copyright © 2020. Published by Elsevier Ltd.)

Members of the protein kinase C (PKC) family of serine-threonine kinases are important regulators of immune cell survival. Ingenol 3-angelate (PEP005) activates a broad range of PKC isoforms and induces apoptosis in acute myeloid leukemia cells by activating the PKC isoform PKCdelta. We show here that, in contrast to its effect on leukemic cells, PEP005 provides a strong survival signal to resting and activated human T cells. The antiapoptotic effect depends upon the activation of PKC. This PKC isoform is expressed in T cells but is absent in myeloid cells. Further studies of the mechanism involved in this process showed that PEP005 inhibited activated CD8(+) T cell apoptosis through the activation of NFkappaB downstream of PKC, leading to increased expression of the antiapoptotic proteins Mcl-1 and Bcl-x(L). Transfection of CD8(+) T cells with dominant-negative PKC diminished the prosurvival effect of PEP005 significantly. Ectopic expression of PKC in the acute myeloid leukemia cell line NB4 turned their response to PEP005 from an increased to decreased rate of apoptosis. Therefore, in contrast to myeloid leukemia cells, PEP005 provides a strong survival signal to T cells, and the expression of functional PKC influences whether PKC activation leads to an anti- or proapoptotic outcome in the cell types tested.

Recent theoretical analyses of domestic violence have posited the complicity of medical communities in erasing and obfuscating the cause of injuries. Although medical cultures have engaged in progressive initiatives to address and treat domestic violence, these medical and clinical models can render domestic violence invisible by framing the battered woman as evidentiary object. By analyzing this invisibility of domestic violence through the concept of public secrecy, in this article I consider Kiki Smith's 1982 installation piece Life Wants to Live. Using medical technologies, Smith's installation offers the viewer a vision of domestic violence that recognizes its inherently problematic invisibility and emphasizes the importance of lived, bodily experience.