The expression and function of IL-33 within the CNS and during the pathogenesis of Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) effecting millions of people worldwide. The pathology of MS is characterised by the demyelination of neurons. Though the root cause of MS remains elusive a combination of genetic, environmental and infectious factors are thought to contribute. IL-33 has previously been shown to be protective (e.g. atherosclerosis), or detrimental (e.g. asthma), in certain disease states. IL-33 and ST2 (IL-33R) are highly expressed within the CNS and have been shown to exacerbate Experimental Autoimmune Encephalomyelitis (mouse model of Multiple Sclerosis). In-situ staining was used to indicate expression of IL-33 and ST2 in the CNS at different stages of EAE disease. IL-33 remained unchanged throughout the time course of disease. However, ST2 expression was upregulated during cellular infiltration. Within naïve and EAE mice IL-33 and ST2 were both expressed on astrocytes and neurons. In acute and chronic MS tissues IL-33 was highly expressed by neurons and axons. Within the lesions IL-33 was present on damaged axons as well as microglia and ODCs. ST2 displayed a diffuse staining in control and MS tissues, however within the lesion site of acute and chronic MS samples ST2 surrounded damaged axons and was present on several ODCs. The potential for IL-33 to affect myelination was investigated using an in-vitro culture system. IL-33 significantly reduced myelination within rat cultures, however no significant effect was observed within the mouse culture system. The main findings from EAE tissues were corroborated in human MS tissue and the implications this may have on understanding the disease course of MS are discussed.Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) effecting millions of people worldwide. The pathology of MS is characterised by the demyelination of neurons. Though the root cause of MS remains elusive a combination of genetic, environmental and infectious factors are thought to contribute. IL-33 has previously been shown to be protective (e.g. atherosclerosis), or detrimental (e.g. asthma), in certain disease states. IL-33 and ST2 (IL-33R) are highly expressed within the CNS and have been shown to exacerbate Experimental Autoimmune Encephalomyelitis (mouse model of Multiple Sclerosis). In-situ staining was used to indicate expression of IL-33 and ST2 in the CNS at different stages of EAE disease. IL-33 remained unchanged throughout the time course of disease. However, ST2 expression was upregulated during cellular infiltration. Within naïve and EAE mice IL-33 and ST2 were both expressed on astrocytes and neurons. In acute and chronic MS tissues IL-33 was highly expressed by neurons and axons. Within the lesions IL-33 was present on damaged axons as well as microglia and ODCs. ST2 displayed a diffuse staining in control and MS tissues, however within the lesion site of acute and chronic MS samples ST2 surrounded damaged axons and was present on several ODCs. The potential for IL-33 to affect myelination was investigated using an in-vitro culture system. IL-33 significantly reduced myelination within rat cultures, however no significant effect was observed within the mouse culture system. The main findings from EAE tissues were corroborated in human MS tissue and the implications this may have on understanding the disease course of MS are discussed

Role of IL-33 and ST2 signalling pathway in multiple sclerosis: expression by oligodendrocytes and inhibition of myelination in central nervous system

Recent research findings have provided convincing evidence indicating a role for Interleukin-33 (IL-33) signalling pathway in a number of central nervous system (CNS) diseases including multiple sclerosis (MS) and Alzheimer’s disease. However, the exact function of IL-33 molecule within the CNS under normal and pathological conditions is currently unknown. In this study, we have mapped cellular expression of IL-33 and its receptor ST2 by immunohistochemistry in the brain tissues of MS patients and appropriate controls; and investigated the functional significance of these findings in vitro using a myelinating culture system. Our results demonstrate that IL-33 is expressed by neurons, astrocytes and microglia as well as oligodendrocytes, while ST2 is expressed in the lesions by oligodendrocytes and within and around axons. Furthermore, the expression levels and patterns of IL-33 and ST2 in the lesions of acute and chronic MS patient brain samples are enhanced compared with the healthy brain tissues. Finally, our data using rat myelinating co-cultures suggest that IL-33 may play an important role in MS development by inhibiting CNS myelination

Working Together to Promote Diabetes Control: A Practical Guide for Diabetes Health Care Providers in Establishing a Working Alliance to Achieve Self-Management Support

The quality of the "patient-carer" relationship is the foundation of self-management support and has been shown to influence treatment outcome in relation to psychological and somatic illness, including diabetes. It has long been accepted within applied psychology that the quality of the client-therapist relationship-termed the working alliance-is of central importance to treatment outcome and may account for a significant degree of the overall treatment effect. Diabetes healthcare providers have recently expressed a need for further training in communication techniques and in the psychological aspects of diabetes. Could we take a page from the psychological treatment manual on working alliance in therapy to guide the diabetes healthcare provider in their role of supporting the person with diabetes achieve and maintain better metabolic control? This paper examines the role of the working alliance in diabetes care and offers a practical guide to the diabetes healthcare provider in establishing a working alliance with the person with diabetes in managing diabetes

Working Together to Promote Diabetes Control: A Practical Guide for Diabetes Health Care Providers in Establishing a Working Alliance to Achieve Self-Management Support

The quality of the “patient-carer” relationship is the foundation of self-management support and has been shown to influence treatment outcome in relation to psychological and somatic illness, including diabetes. It has long been accepted within applied psychology that the quality of the client-therapist relationship—termed the working alliance—is of central importance to treatment outcome and may account for a significant degree of the overall treatment effect. Diabetes healthcare providers have recently expressed a need for further training in communication techniques and in the psychological aspects of diabetes. Could we take a page from the psychological treatment manual on working alliance in therapy to guide the diabetes healthcare provider in their role of supporting the person with diabetes achieve and maintain better metabolic control? This paper examines the role of the working alliance in diabetes care and offers a practical guide to the diabetes healthcare provider in establishing a working alliance with the person with diabetes in managing diabetes

Interstitial photothermal therapy generates durable treatment responses in neuroblastoma

Please click Download on the upper right corner to see the full descriptio

The reliability and validity of multiple mini interviews (MMIs) in values based recruitment to nursing, midwifery and paramedic practice: Findings from an evaluation study

Background: Universities in the United Kingdom (UK) are required to incorporate values based recruitment (VBR) into their healthcare student selection processes. This reflects an international drive to strengthen the quality of healthcare service provision. This paper presents novel findings in relation to the reliability and predictive validity of multiple mini interviews (MMIs); one approach to VBR widely being employed by universities. Objectives: To examine the reliability (internal consistency) and predictive validity of MMIs using end of Year One practice outcomes of under-graduate pre-registration adult, child, mental health nursing, midwifery and paramedic practice students. Design: Cross-discipline evaluation study. Setting: One university in the United Kingdom. Participants: Data were collected in two streams: applicants to A) The September 2014 and 2015 Midwifery Studies programmes; B) September 2015 adult; Child and Mental Health Nursing and Paramedic Practice programmes. Fifty-seven midwifery students commenced their programme in 2014 and 69 in 2015; 47 and 54 agreed to participate and completed Year One respectively. 333 healthcare students commenced their programmes in September 2015. Of these, 281 agreed to participate and completed their first year (180 adult, 33 child and 34 mental health nursing and 34 paramedic practice students). Methods: Stream A featured a seven station four-minute model with one interviewer at each station and in Stream B a six station model was employed. Cronbach’s alpha was used to assess MMI station internal consistency and Pearson’s moment correlation co-efficient to explore associations between participants’ admission MMI score and end of Year one clinical practice outcomes (OSCE and mentor grading). Results: Stream A: Significant correlations are reported between midwifery applicant’s MMI scores and end of Year One practice outcomes. A multivariate linear regression model demonstrated that MMI score significantly predicted end of Year One practice outcomes controlling for age and academic entry level: coefficients 0.195 (p = 0.002) and 0.116 (p = 0.002) for OSCE and mentor grading respectively. In Stream B no significant correlations were found between MMI score and practice outcomes measured by mentor grading. Internal consistency for each MMI station was ‘excellent’ with values ranging from 0.966–0.974 across Streams A and B. Conclusion: This novel, cross-discipline study shows that MMIs are reliable VBR tools which have predictive validity when a seven station model is used. These data are important given the current international use of different MMI models in healthcare student selection processes

Expression and Function of IL-33/ST2 Axis in the Central Nervous System Under Normal and Diseased Conditions

Interleukin-33 (IL-33) is a well-recognized immunomodulatory cytokine which plays critical roles in tissue function and immune-mediated diseases. The abundant expression of IL-33 in brain and spinal cord prompted many scientists to explore its unique role in the central nervous system (CNS) under physiological and pathological conditions. Indeed emerging evidence from over a decade's research suggests that IL-33 acts as one of the key molecular signaling cues coordinating the network between the immune and CNS systems, particularly during the development of neurological diseases. Here, we highlight the recent advances in our knowledge regarding the distribution and cellular localization of IL-33 and its receptor ST2 in specific CNS regions, and more importantly the key roles IL-33/ST2 signaling pathway play in CNS function under normal and diseased conditions

Challenges in quantifying changes in the global water cycle

Human influences have likely already impacted the large-scale water cycle but natural variability and observational uncertainty are substantial. It is essential to maintain and improve observational capabilities to better characterize changes. Understanding observed changes to the global water cycle is key to predicting future climate changes and their impacts. While many datasets document crucial variables such as precipitation, ocean salinity, runoff, and humidity, most are uncertain for determining long-term changes. In situ networks provide long time-series over land but are sparse in many regions, particularly the tropics. Satellite and reanalysis datasets provide global coverage, but their long-term stability is lacking. However, comparisons of changes among related variables can give insights into the robustness of observed changes. For example, ocean salinity, interpreted with an understanding of ocean processes, can help cross-validate precipitation. Observational evidence for human influences on the water cycle is emerging, but uncertainties resulting from internal variability and observational errors are too large to determine whether the observed and simulated changes are consistent. Improvements to the in situ and satellite observing networks that monitor the changing water cycle are required, yet continued data coverage is threatened by funding reductions. Uncertainty both in the role of anthropogenic aerosols, and due to large climate variability presently limits confidence in attribution of observed changes

Developing a robust tool: advancing the multiple mini interview in pre-registration student midwife selection in a UK setting

Background: Published research has shown the multiple mini interview (MMI) to be a reliable assessment instrument in medical and nursing student selection internationally. Objectives: To develop, pilot and examine the reliability of MMIs in pre-registration student midwife selection in one Higher Education Institution a UK setting. Design and setting: BSc (Hons) Midwifery Studies students at a Higher Education Institution in the UK volunteered to participate in ‘mock’ MMI circuits during the first week of their programme. DeVellis’s framework for questionnaire development underpinned the generation of interview scenarios. Participants’ responses to scenario questions were rated on a 7 point scale. Internal consistency was calculated for each station. Results: An eight station model was piloted. Communication skills were assessed at each station as a generic attribute. Station specific attributes assessed included compassion and empathy, respect for difference and diversity, honesty and integrity, intellectual curiosity and reflective nature, advocacy, respect for privacy and dignity, team working and initiative, the role of the midwife and motivation to become a midwife. Cronbach’s alpha scores for each station ranged from 0.91 – 0.97. Conclusion: The systematic development of the MMI model and scenarios resulted in ‘excellent’ reliability across all stations. These findings endorse the MMI technique as a reliable alternative to the personal interview in informing final decisions in pre-registration student midwife selection