Diagnosis, assessment and treatment of childhood eczema in primary care:cross-sectional study

Background: The majority of children with eczema in the UK are looked after in primary care yet we know little about their care in this setting. Aim: To compare the diagnosis, assessment, and treatment of eczema in primary care with published diagnostic criteria and management guidelines. Design & setting: Cross-sectional study using data from a randomised controlled feasibility study. General practices, UK. Method: Baseline data from children aged 1 month to 5 years recruited ‘in-consultation’ for the Choice of Moisturiser in Eczema Treatment (COMET) feasibility study was used. These included clinician diagnosis and global severity assessment; the parent-completed Patient Orientated Eczema Measure (POEM); a questionnaire about eczema treatments, including use of topical corticosteroid (TCS); and, the Eczema Area Severity Index (EASI) carried out by trained researchers. Descriptive analyses were undertaken to compare diagnoses with UK diagnostic criteria, severity assessments, and treatment with the National Institute for Health and Care Excellent (NICE) guidance. Results: Data were available for 90 participants. Only 46% of participants labelled as having eczema met the UK diagnostic criteria. Agreement between the global severity assessment by a healthcare practitioner with the EASI and POEM measures of eczema severity were 44% and 48% respectively. Emollients and TCSs were underused with 44% of participants not using any emollient and 46% using one or more TCSs. The ‘match’ between eczema severity and TCSs potency was poor. Conclusion: Discrepancies were found between the diagnosis, assessment, and treatment of children with eczema in primary care, and UK diagnostic criteria and guidelines. Further investigation to explore the reasons for this discordance, and whether it matters, is needed

Transdifferentiated Human Vascular Smooth Muscle Cells are a New Potential Cell Source for Endothelial Regeneration

Endothelial dysfunction is widely implicated in cardiovascular pathological changes and development of vascular disease. In view of the fact that the spontaneous endothelial cell (EC) regeneration is a slow and insufficient process, it is of great interest to explore alternative cell sources capable of generating functional ECs. Vascular smooth muscle cell (SMC) composes the majority of the vascular wall and retains phenotypic plasticity in response to various stimuli. The aim of this study is to test the feasibility of the conversion of SMC into functional EC through the use of reprogramming factors. Human SMCs are first dedifferentiated for 4 days to achieve a vascular progenitor state expressing CD34, by introducing transcription factors OCT4, SOX2, KLF4 and c-MYC. These SMC-derived progenitors are then differentiated along the endothelial lineage. The SMC-converted ECs exhibit typical endothelial markers expression and endothelial functions in vitro, in vivo and in disease model. Further comprehensive analysis indicates that mesenchymal-to-epithelial transition is requisite to initiate SMCs reprogramming into vascular progenitors and that members of the Notch signalling pathway regulate further differentiation of the progenitors into endothelial lineage. Together, we provide the first evidence of the feasibility of the conversion of human SMCs towards endothelial lineage through an intermediate vascular progenitor state induced by reprogramming.British Heart Foundation [RG/14/6/31144, RM/13/2/30158]; Oak Foundation; International Cooperation and Exchanges NSFC [81220108004]; China Scholarship CouncilSCI(E)ARTICLE

Generation of KCL036 research grade human embryonic stem cell line carrying a mutation in the HTT gene

The KCL036 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation affecting one allele of the HTT gene encoding huntingtin (38 trinucleotide repeats; 14 for the normal allele). The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro and in vivo assays

Generation of KCL026 research grade human embryonic stem cell line carrying a mutation in SMN1 gene

AbstractThe KCL026 human embryonic stem cell line was derived from an embryo donated for research that carried a mutation in the SMN1 gene encoding survival of motor neuron 1, telomeric (exons 7 and 8 deletion). Mutations in this gene are associated with spinal muscular atrophy. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro assays

Origin and differentiation of vascular smooth muscle cells

Vascular smooth muscle cells (SMCs), a major structural component of the vessel wall, not only play a key role in maintaining vascular structure but also perform various functions. During embryogenesis, SMC recruitment from their progenitors is an important step in the formation of the embryonic vascular system. SMCs in the arterial wall are mostly quiescent but can display a contractile phenotype in adults. Under pathophysiological conditions, i.e. vascular remodelling after endothelial dysfunction or damage, contractile SMCs found in the media switch to a secretory type, which will facilitate their ability to migrate to the intima and proliferate to contribute to neointimal lesions. However, recent evidence suggests that the mobilization and recruitment of abundant stem/progenitor cells present in the vessel wall are largely responsible for SMC accumulation in the intima during vascular remodelling such as neointimal hyperplasia and arteriosclerosis. Therefore, understanding the regulatory mechanisms that control SMC differentiation from vascular progenitors is essential for exploring therapeutic targets for potential clinical applications. In this article, we review the origin and differentiation of SMCs from stem/progenitor cells during cardiovascular development and in the adult, highlighting the environmental cues and signalling pathways that control phenotypic modulation within the vasculature

Generation of KCL031 clinical grade human embryonic stem cell line

AbstractThe KCL031 human embryonic stem cell line was derived from a normal healthy blastocyst donated for research. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment and under current Good Manufacturing Practice (cGMP) standards. Pluripotent state and differentiation potential were confirmed by in vitro and in vivo assays

Generation of KCL016 research grade human embryonic stem cell line carrying a mutation in VHL gene

AbstractThe KCL016 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation affecting splicing site of the VHL gene encoding von Hippel–Lindau tumor suppressor E3 ubiquitin protein ligase (676+3A>T). The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro assays

Generation of KCL034 clinical grade human embryonic stem cell line

AbstractThe KCL034 human embryonic stem cell line was derived from a normal healthy blastocyst donated for research. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment and under current Good Manufacturing Practice (cGMP) standards. Pluripotent state and differentiation potential were confirmed by in vitro assays. The line was also validated for sterility, specific and non-specific human pathogens

Generation of KCL036 research grade human embryonic stem cell line carrying a mutation in the HTT gene

The KCL036 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation affecting one allele of the HTT gene encoding huntingtin (38 trinucleotide repeats; 14 for the normal allele). The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro and in vivo assays