CCL4 induces inflammatory signalling and barrier disruption in the neurovascular endothelium

Background: During neuroinflammation many chemokines alter the function of the blood-brain barrier (BBB) that regulates the entry of macromolecules and immune cells into the brain. As the milieu of the brain is altered, biochemical and structural changes contribute to the pathogenesis of neuroinflammation and may impact on neurogenesis. The chemokine CCL4, previously known as MIP-1β, is upregulated in a wide variety of central nervous system disorders, including multiple sclerosis, where it is thought to play a key role in the neuroinflammatory process. However, the effect of CCL4 on BBB endothelial cells (ECs) is unknown. Materials and methods: Expression and distribution of CCR5, phosphorylated p38, F-actin, zonula occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) were analysed in the human BBB EC line hCMEC/D3 by Western blot and/or immunofluorescence in the presence and absence of CCL4. Barrier modulation in response to CCL4 using hCMEC/D3 monolayers was assessed by measuring molecular flux of 70 ​kDa RITC-dextran and transendothelial lymphocyte migration. Permeability changes in response to CCL4 in vivo were measured by an occlusion technique in pial microvessels of Wistar rats and by fluorescein angiography in mouse retinae. Results: CCR5, the receptor for CCL4, was expressed in hCMEC/D3 cells. CCL4 stimulation led to phosphorylation of p38 and the formation of actin stress fibres, both indicative of intracellular chemokine signalling. The distribution of junctional proteins was also altered in response to CCL4: junctional ZO-1 was reduced by circa 60% within 60 ​min. In addition, surface VE-cadherin was redistributed through internalisation. Consistent with these changes, CCL4 induced hyperpermeability in vitro and in vivo and increased transmigration of lymphocytes across monolayers of hCMEC/D3 cells. Conclusion: These results show that CCL4 can modify BBB function and may contribute to disease pathogenesis

Experiences of acquired brain injury survivors participating in online and hybrid performance arts programmes: an ethnographic study

Background: Performance arts can benefit people with acquired brain injury (ABI). This study explored the online delivery during COVID-19 restrictions, of a performance art intervention through the experiences of participants, artists and facilitators. Methods: Two community-based programmes were delivered. Online ethnographic observations and semi-structured interviews with participants, artists and facilitators were completed. Results: The programmes benefited participants by addressing loneliness and isolation; building confidence through peer support; improving physical limitations through movement; improving communication through music and vocal work; and using poetry, visual arts, metaphor and performance to make sense of participants’ experiences. Participants had mixed experiences of participation, but it was an acceptable alternative to in-person arts interventions for those who overcame digital challenges. Conclusions: ABI survivors can engage in online performance art programmes and find participation valuable for their health, well-being, and recovery. More work is needed to explore the generalisability of these findings, especially given digital poverty

Inclusão digital e políticas públicas no meio rural: um estudo sobre os territórios digitais.

Este estudo tem como objetivo discutir as políticas públicas de inclusão digital no meio rural e, para isso, utilizou-se como exemplo empírico o projeto Territórios Digitais, contrastando sua caracterização com referências bibliográficas deste campo de estudos. Os Territórios Digitais é uma proposta de fortalecimento interministerial por meio das TICs como forma de, então, enfrentar os desafios econômicos e sociais no espaço rural via o estabelecimento de telecentros rurais aqui chamados ?Casas Digitais?. Entre os resultados, evidenciou que devido ao contingente de ?excluídos digitais? encontrados no meio rural o que se percebe é que a proposta das Casas Digitais teoricamente é boa, quando comparado a outras iniciativas de inclusão digital via telecentros, mas sua avaliação ainda é incipiente, por partir do princípio de que esta política é recente. Um dos desafios para a sobrevivência desta ação está na permanência dos usuários. Para tanto, há a necessidade de atender às demandas destas pessoas no que se refere ao acesso de sites de interesse e serviços agregados, tendo como prioridade a melhoria da educação na comunidade em que estão inseridos

Experiences of acquired brain injury survivors participating in online and hybrid performance arts programmes: an ethnographic study.

BACKGROUND: Performance arts can benefit people with acquired brain injury (ABI). This study explored the online delivery during COVID-19 restrictions, of a performance art intervention through the experiences of participants, artists and facilitators. METHODS: Two community-based programmes were delivered. Online ethnographic observations and semi-structured interviews with participants, artists and facilitators were completed. RESULTS: The programmes benefited participants by addressing loneliness and isolation; building confidence through peer support; improving physical limitations through movement; improving communication through music and vocal work; and using poetry, visual arts, metaphor and performance to make sense of participants' experiences. Participants had mixed experiences of participation, but it was an acceptable alternative to in-person arts interventions for those who overcame digital challenges. CONCLUSIONS: ABI survivors can engage in online performance art programmes and find participation valuable for their health, well-being, and recovery. More work is needed to explore the generalisability of these findings, especially given digital poverty

Transvesical endoscopic port in abdominal surgery: an updated perspective

Transvesical endoscopic port in abdominal surgery: an updated perspective.Natural orifice transluminal endoscopic surgery (NOTES) generated a huge hope among surgeons because it promised scarless surgery and eventually less pain and surgical stress. However, serious limitations regarding reliable visceral closing methods remain unsolved. This article provides an update in development and future applications of transvesical access in the field of surgery.(undefined

CCL4 induces inflammatory signalling and barrier disruption in the neurovascular endothelium

Background: During neuroinflammation many chemokines alter the function of the blood-brain barrier (BBB) that regulates the entry of macromolecules and immune cells into the brain. As the milieu of the brain is altered, biochemical and structural changes contribute to the pathogenesis of neuroinflammation and may impact on neurogenesis. The chemokine CCL4, previously known as MIP-1β, is upregulated in a wide variety of central nervous system disorders, including multiple sclerosis, where it is thought to play a key role in the neuroinflammatory process. However, the effect of CCL4 on BBB endothelial cells (ECs) is unknown. Materials and methods: Expression and distribution of CCR5, phosphorylated p38, F-actin, zonula occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) were analysed in the human BBB EC line hCMEC/D3 by Western blot and/or immunofluorescence in the presence and absence of CCL4. Barrier modulation in response to CCL4 using hCMEC/D3 monolayers was assessed by measuring molecular flux of 70 ​kDa RITC-dextran and transendothelial lymphocyte migration. Permeability changes in response to CCL4 in vivo were measured by an occlusion technique in pial microvessels of Wistar rats and by fluorescein angiography in mouse retinae. Results: CCR5, the receptor for CCL4, was expressed in hCMEC/D3 cells. CCL4 stimulation led to phosphorylation of p38 and the formation of actin stress fibres, both indicative of intracellular chemokine signalling. The distribution of junctional proteins was also altered in response to CCL4: junctional ZO-1 was reduced by circa 60% within 60 ​min. In addition, surface VE-cadherin was redistributed through internalisation. Consistent with these changes, CCL4 induced hyperpermeability in vitro and in vivo and increased transmigration of lymphocytes across monolayers of hCMEC/D3 cells. Conclusion: These results show that CCL4 can modify BBB function and may contribute to disease pathogenesis

A Protocol to Understand the Implementation and Experiences of an Online Community-Based Performance Arts Programme Through and Beyond the COVID-19 Pandemic, Brain Waves.

INTRODUCTION: Individuals living with acquired brain injury experience numerous psychological, physical, and social challenges. Since the COVID-19 pandemic, many have experienced additional isolation, mental health issues and have had limited access to social and physical activities otherwise available in the community. MATERIALS AND METHODS: Brain Waves is a 12-week online performance arts programme developed during the COVID-19 pandemic, for people with acquired brain injury (ABI). The research component of Brain Waves is a qualitative study, using Interpretative Phenomenological Analysis (IPA) and ethnographic methods (Observations and Interviews). The study will recruit two distinct populations: individuals living with acquired brain injury (including people who have experienced traumatic brain injury and stroke who are participating in the programme) and stakeholders (facilitators, involved in the delivery of Brain Waves). This paper presents the protocol for a project which aims to gain an understanding of the implementation and experiences of creating and participating in an online community-based performance arts programme

Evaluation of a community-based performance arts programme for people who have experienced stroke in the UK: protocol for the SHAPER-Stroke Odysseys study.

INTRODUCTION: Stroke survivors, once in the community, face challenges with their long-term rehabilitation care and present higher levels of loneliness, depression and anxiety than the rest of the population. A community-based performance arts programme, Stroke Odysseys (SO), has been devised to tackle the challenges of living with stroke in the UK. In this study, we aim to evaluate the implementation, impact and experiences of SO for stroke survivors. METHODS AND ANALYSIS: Scaling-up Health Arts Programmes: Implementation and Effectiveness Research (SHAPER)-SO aims to scale-up SO to 75 participants and 47 stakeholders, while simultaneously evaluating the effectiveness and implementation of the programme. The main research aim is to evaluate the implementation, effectiveness, impact and experiences of a community-based performance arts programme (SO for stroke survivors). This mixed-methods study will evaluate the experience and impact of SO on those participating using mixed methods (interviews, observations and surveys) before and after each stage and carry out non-participant observations during a percentage of the workshops, training and tour. Data will be analysed using quantitative and qualitative approaches. This is a study within the SHAPER programme. ETHICS AND DISSEMINATION: Ethical approval has been granted by the King's College London PNM Research Ethics Panel, REC reference: LRS/DP-20/21-21549. Written informed consent will be sought for participants and stakeholders. The results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04864470