Cellular strategies to promote repair in the damaged CNS using a combined therapeutic approach

Following disease or injury to the CNS, the formation of a glial scar represents a physical and molecular barrier to repair. Although some therapies have promoted axonal sprouting into the lesion site, these fibres are often tangled and disorientated. To date, there has been little evidence of regenerating fibres successfully exiting the glial scar to reform functional connections. Furthermore, remyelination after disease or injury is limited, often consisting of shorter internodes of myelin and thinner sheaths. Thus, potential therapies aimed at enhancing CNS repair should support the outgrowth of neurites, guide their exit from the glial scar and perhaps aid remyelination. Since multiple factors impede the regeneration of the CNS, a combinatorial approach to therapies including cell-transplantation may be a more promising strategy

The development of a ε-polycaprolactone (PCL) scaffold for CNS repair

Potential treatment strategies for the repair of spinal cord injury (SCI) currently favour a combinatorial approach incorporating several factors, including exogenous cell transplantation and biocompatible scaffolds. The use of scaffolds for bridging the gap at the injury site is very appealing although there has been little investigation into CNS neural cell interaction and survival on such scaffolds before implantation. Previously we demonstrated that aligned micro-grooves 12.5-25 µm wide on ε-polycaprolactone (PCL) promoted aligned neurite orientation and supported myelination. In this study we identify the appropriate substrate and its topographical features required for the design of a 3D scaffold intended for transplantation in SCI. Using an established myelinating culture system of dissociated spinal cord cells, recapitulating many of the features of the intact spinal cord, we demonstrate that astrocytes plated on the topography secrete soluble factors(s) that delay oligodendrocyte differentiation but do not prevent myelination. However, as myelination does occur after a further 10-12 days in culture this does not prevent the use of PCL as a scaffold material as part of a combined strategy for the repair of SCI

Housing affordability in the South West of England

The South West faces acute problems of housing affordability. The region is conspicuously less affordable than England as a whole, and the North and Midlands in particular. These inter-regional disparities are becoming progressively more pronounced.• The South West is the fourth least affordable region in England for all property types (after London, South East and the East of England). In 2021, median house prices were approximately ten times greater than the median earnings.• The South West is becoming less affordable over time. In 1997, median house prices were approximately four times greater than the median earnings. Affordability ratios in the South West (plus London, South East and the East of England) continue to be above the English median, and the gap is widening.• Three quarters (22 out of 29) of local authority areas in the South West have affordability ratios higher than that for England as a whole, and all have affordability ratios higher than those for the North East, North West, and Yorkshire and the Humber.• There is substantial diversity in affordability ratios between local authority areas in the South West, varying from 7.3 in Plymouth (a ratio that is still higher than those for North East, North West, and Yorkshire and the Humber) to 15.8 in Cotswolds District.• There is also substantial diversity in affordability ratios within local authority areas in the South West. The ten least affordable neighbourhoods in the South West have median house prices more than 28.3 times median earnings, these are in the Bath and NorthEast Somerset, Cotswolds, Cornwall, Bournemouth, Christchurch and Poole. Even in the most affordable neighbourhoods of Plymouth and Gloucester median house prices are still more than three times median earnings.• This is the first time that a granular assessment of affordability has been provided for the region, and it demonstrates the variation within local authorities. This is likely to be particularly important in larger, rural authorities where it might be more challenging to commute to home and other services

Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection

Background Neutrophils are important in the pathophysiology of coronavirus disease 2019 (COVID-19), but the molecular changes contributing to altered neutrophil phenotypes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We used quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes immediately following acute SARS-CoV-2 infection and during recovery. Methods Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May to December 2020). Patients were enrolled within 96 h of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID-19 acute lower respiratory tract infection (LRTI) and age-matched noninfected controls. Neutrophils were isolated from peripheral blood and analysed using mass spectrometry. COVID-19 severity and recovery were defined using the World Health Organization ordinal scale. Results Neutrophil proteomes from 84 COVID-19 patients were compared to those from 91 LRTI and 42 control participants. 5800 neutrophil proteins were identified, with &gt;1700 proteins significantly changed in neutrophils from COVID-19 patients compared to noninfected controls. Neutrophils from COVID-19 patients initially all demonstrated a strong interferon signature, but this signature rapidly declined in patients with severe disease. Severe disease was associated with increased abundance of proteins involved in metabolism, immunosuppression and pattern recognition, while delayed recovery from COVID-19 was associated with decreased granule components and reduced abundance of metabolic proteins, chemokine and leukotriene receptors, integrins and inhibitory receptors. Conclusions SARS-CoV-2 infection results in the sustained presence of circulating neutrophils with distinct proteomes suggesting altered metabolic and immunosuppressive profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines.</p

The importance of the verbal shift handover report: a multi-site case study.

Shift handover is seen as a key tool in ensuring continuity of care yet a number of studies have highlighted the role of shift handovers in adverse events. This, combined with the increased frequency of shift handovers, has led to interest in providing technological support for handover to enhance safety. The aim of this paper is to describe current practices for the conduct of shift handovers and to use this as a basis for considering the role that technology could play in supporting handover

The (in)visibility of equality, diversity, and inclusion research in event management journals

Rebecca Finkel - ORCID: 0000-0003-2120-6211 https://orcid.org/0000-0003-2120-6211The field of events management has been critiqued for being overly focused on operational and managerial concerns to the detriment of critical analysis of power and representation, of which equality, diversity, and inclusion (EDI) is an important aspect. This paper reports on an audit of the four leading events management journals over the period 2011-2021 to assess the current state of play in relation to engagement with EDI issues and consider whether this critique remains justified. After screening, 49 articles were included. Findings reveal that EDI remains a marginal issue in events management journals, often confined to special issues, with no evidence of increasing engagement over the review period. EDI needs to become more integrated in the core body of knowledge of events management to ensure that events research is socially useful to students, other researchers and practitioners, contributing to the development and reputation of the field

The (in)visibility of equality, diversity, and inclusion research in event management journals

The field of events management has been critiqued for being overly focused on operational and managerial concerns to the detriment of critical analysis of power and representation, of which equality, diversity, and inclusion (EDI) is an important aspect. This paper reports on an audit of the four leading events management journals over the period 2011-2021 to assess the current state of play in relation to engagement with EDI issues and consider whether this critique remains justified. After screening, 49 articles were included. Findings reveal that EDI remains a marginal issue in events management journals, often confined to special issues, with no evidence of increasing engagement over the review period. EDI needs to become more integrated in the core body of knowledge of events management to ensure that events research is socially useful to students, other researchers and practitioners, contributing to the development and reputation of the field

The Development of a ɛ-Polycaprolactone Scaffold for Central Nervous System Repair

Potential treatment strategies for the repair of spinal cord injury (SCI) currently favor a combinatorial approach incorporating several factors, including exogenous cell transplantation and biocompatible scaffolds. The use of scaffolds for bridging the gap at the injury site is very appealing although there has been little investigation into the central nervous system neural cell interaction and survival on such scaffolds before implantation. Previously, we demonstrated that aligned microgrooves 12.5-25 μm wide on ε-polycaprolactone (PCL) promoted aligned neurite orientation and supported myelination. In this study, we identify the appropriate substrate and its topographical features required for the design of a three-dimensional scaffold intended for transplantation in SCI. Using an established myelinating culture system of dissociated spinal cord cells, recapitulating many of the features of the intact spinal cord, we demonstrate that astrocytes plated on the topography secrete soluble factors(s) that delay oligodendrocyte differentiation, but do not prevent myelination. However, as myelination does occur after a further 10-12 days in culture, this does not prevent the use of PCL as a scaffold material as part of a combined strategy for the repair of SCI

Chromatin binding of SRp20 and ASF/SF2 and dissociation from mitotic chromosomes is modulated by histone H3 serine 10 phosphorylation

Histone H3 serine 10 phosphorylation is a hallmark of mitotic chromosomes, but its full function remains to be elucidated. We report here that two SR protein splicing factors, SRp20 and ASF/SF2, associate with interphase chromatin, are released from hyperphosphorylated mitotic chromosomes, but reassociate with chromatin late in M-phase. Inhibition of Aurora B kinase diminished histone H3 serine 10 phosphorylation and increased SRp20 and ASF/SF2 retention on mitotic chromosomes. Unexpectedly, we also found that HP1 proteins interact with ASF/SF2 in mitotic cells. Strikingly, siRNA-mediated knockdown of ASF/SF2 caused retention of HP1 proteins on mitotic chromatin. Finally, ASF/SF2-depleted cells released from a mitotic block displayed delayed G0/G1 entry, suggesting a functional consequence of these interactions. These findings underscore the evolving role of histone H3 phosphorylation and demonstrate a direct, functional, and histone-modification-regulated association of SRp20 and ASF/SF2 with chromati