Evaluating the communication within fire and rescue services and the NHS on the fire risk of emollients in accordance of the MHRA safety update

The Medicines and Healthcare products Regulatory Agency update in 2018 reported 50 fatal fires linked with emollient use. It detailed the fire risk and new advice aimed at fire service and health care professionals in reporting of such fire incidents and educating the public on safer use of emollients. This study investigates how this has been communicated internally and publicly, with 52 Fire and Rescue Services (FRSs) websites and, 191 Clinical Commissioning Groups (CCGs), and 21 Local Health Boards (LHBs) formularies accessed. A Freedom of Information Request (FOIR) was also made, giving further details of implementations. Our study revealed that 63% of FRSs, 32% of CCGs and, 72% of LHBs gave no safety advice within their website or formularies. Of the 37% of FRSs and 68% of CCGs that did, only 5% and 4% were sufficiently up to date. 27% of FRSs and 28% of CCGs/LHBs revealed that they had no warning/advice internally in their FOIR responses and 25% of FRSs and, 35% of CCG/LHBs had not disseminated advice on using emollient safely to the public. We suggest improvements in safety campaigns using a multiagency and national approach and recommend organizations to educate professionals to improve reporting and effective dissemination

Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency

Purpose Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved. Methods Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated. Results Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated. Conclusions This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features

Identification and Clonal Characterisation of a Progenitor Cell Sub-Population in Normal Human Articular Cartilage

Background: Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC), are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage. Methods and Findings: Human articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect. Conclusions: In conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell-based cartilage repair therapies due to its ability to maintain chondrogenicity upon extensive expansion unlike full-depth chondrocytes that lose this ability at only seven population doublings

Abstracts from the NIHR INVOLVE Conference 2017

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Early Ultraviolet Observations of Type IIn Supernovae Constrain the Asphericity of Their Circumstellar Material

We present a survey of the early evolution of 12 Type IIn supernovae (SNe IIn) at ultraviolet and visible light wavelengths. We use this survey to constrain the geometry of the circumstellar material (CSM) surrounding SN IIn explosions, which may shed light on their progenitor diversity. In order to distinguish between aspherical and spherical CSM, we estimate the blackbody radius temporal evolution of the SNe IIn of our sample, following the method introduced by Soumagnac et al. We find that higher-luminosity objects tend to show evidence for aspherical CSM. Depending on whether this correlation is due to physical reasons or to some selection bias, we derive a lower limit between 35% and 66% for the fraction of SNe IIn showing evidence for aspherical CSM. This result suggests that asphericity of the CSM surrounding SNe IIn is common—consistent with data from resolved images of stars undergoing considerable mass loss. It should be taken into account for more realistic modeling of these events

The potential effects of microplastics on human health: What is known and what is unknown

Microplastic contamination is ubiquitous in aquatic and terrestrial environments, found in water, sediments, within organisms and in the atmosphere and the biological effects on animal and plant life have been extensively investigated in recent years. There is growing evidence that humans are exposed to microplastics via ingestion of food and drink and through inhalation. Despite the prevalence of contamination, there has been limited research on the effects of microplastics on human health and most studies, to date, analyse the effects on model organisms with the likely impacts on human health being inferred by extrapolation. This review summarises the latest findings in the field with respect to the prevalence of microplastics in the human–environment, to what extent they might enter and persist in the body, and what effect, if any, they are likely to have on human health. Whilst definitive evidence linking microplastic consumption to human health is currently lacking, results from correlative studies in people exposed to high concentrations of microplastics, model animal and cell culture experiments, suggest that effects of microplastics could include provoking immune and stress responses and inducing reproductive and developmental toxicity. Further research is required to explore the potential implications of this recent contaminant in our environment in more rigorous clinical studies

Assessing the potential fire risk of laundered fabrics after contamination with emollients using ATR-FTIR spectroscopy and chemometrics

Since 2010, more than 50 UK fire deaths, have been reported as linked with emollients. This prompted the Medicines and Healthcare products Regulatory Agency (MHRA) to issue advice on their safer use in 2018. The advice was in response to concerns raised by the National Fire Chiefs Council, coroners’ reports, and flammability tests. The test results show a significant reduction in ignition time of fabrics contaminated with paraffin-based and paraffin-free skin care product residues. The MHRA report also included advice on washing clothing and bedding at high temperatures but warned this may not remove all emollient residues. This paper reports on new research on the removal of skin care products from clothing investigated by laundering contaminated 100% cotton fabric at 30, 40 and 60 °C using both biological and non-biological based detergents. As part of the experiment, non-contaminated (blank) napkin samples were included in the wash experiments to assess the possible transfer from fabrics contaminated with emollients to uncontaminated clean fabrics during washing. Washed and dried fabrics were analysed using Attenuated Total Reflectance, Fourier Transform Infrared (ATR-FTIR) spectroscopy and further interpreted via principal component analysis (PCA) and network analysis. Results suggest that the majority of the 6% white soft paraffin-based lotion and paraffin-free cream were removed at all temperatures. Residues of 21% paraffin-based cream (6% light paraffin/15% white soft paraffin) remain, and more residues persist of the 100% paraffin-based ointment (5% light paraffin/95% white soft paraffin) after washing at 30, 40 and 60 °C. The wash experiments show unequivocal transfer of the 100% ointment from the contaminated napkins to clean control napkins placed within washes at 30 °C. Furthermore, residues of the ointment were observed within the machine drum, and washing machine door seal, though this did not cause secondary transfer to subsequent wash experiments. There were no differences observed when using biological versus non-biological detergents, nor when employing a pre-wash treatment in the removal of residues of the 21% cream and 100% ointment. These results suggest that a single application of an emollient when soaked and dried into a fabric is not removed by a single wash at 30, 40 or 60 °C. Instead, the residue remains a persistent potential fire risk and, its high paraffin content presents an additional fire risk via contamination of other fabrics

Conversational assessment in memory clinic encounters: interactional profiling for differentiating dementia from functional memory disorders

Objectives: In the UK dementia is under-diagnosed, there is limited access to specialist memory clinics, and many of the patients referred to such clinics are ultimately found to have functional (non-progressive) memory disorders (FMD), rather than a neurodegenerative disorder. Government initiatives on ‘timely diagnosis’ aim to improve the rate and quality of diagnosis for those with dementia. This study seeks to improve the screening and diagnostic process by analysing communication between clinicians and patients during initial specialist clinic visits. Establishing differential conversational profiles could help the timely differential diagnosis of memory complaints. Method: This study is based on video- and audio recordings of 25 initial consultations between neurologists and patients referred to a UK memory clinic. Conversation analysis was used to explore recurrent communicative practices associated with each diagnostic group. Results: Two discrete conversational profiles began to emerge, to help differentiate between patients with dementia and functional memory complaints, based on (1) whether the patient is able to answer questions about personal information; (2) whether they can display working memory in interaction; (3) whether they are able to respond to compound questions; (4) the time taken to respond to questions; and (5) the level of detail they offer when providing an account of their memory failure experiences. Conclusion: The distinctive conversational profiles observed in patients with functional memory complaints on the one hand and neurodegenerative memory conditions on the other suggest that conversational profiling can support the differential diagnosis of functional and neurodegenerative memory disorders

Missense variants in the histone acetyltransferase complex component gene TRRAP cause autism and syndromic intellectual disability

Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants