It is important to understand the molecular mechanisms of barrier disruption in the central nervous system (CNS) of patients with multiple sclerosis (MS). The purpose of the present study was to clarify whether claudin-11 is involved in the disruption of two endothelial barriers (blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB)) and two epithelial barriers (blood-arachnoid barrier (BAB) and blood-CSF barrier (BCSFB)) in the CNS in MS. Immunohistochemical analysis revealed that, in both normal human and mouse, claudin-11 is co-localized with claudin-5 in the brain and spinal cord capillaries. The absolute protein expression level of claudin-11 was nearly equal to that of claudin-5 in rat brain capillaries, but was 2.81-fold greater in human brain capillaries. The protein expressions of claudin-11 were significantly downregulated in the brain and spinal cord capillaries of an MS patient and experimental autoimmune encephalomyelitis (EAE) mice. Specific downregulation of claudin-11 with siRNA significantly increased the transfer of membrane-impermeable FITC-dextran across human brain capillary endothelial cell (hCMEC/D3) monolayer. As for the epithelial barrier, claudin-11 protein expression was not decreased in choroid plexus epithelial cells forming the BCSFB in EAE mice, whereas it was decreased in brain and spinal cord meninges that form the BAB. Specific downregulation of claudin-11 with siRNA in a rat choroid plexus epithelial cell (TR-CSFB) monolayer significantly increased the permeability of FITC-dextran. In conclusion, our present findings indicate that claudin-11 expression at the BBB, BSCB, and BAB, but not the BCSFB, is downregulated in multiple sclerosis, impairing the functional integrity of these barriers.
Background Several countries have reported increased demand for eating disorder services during the COVID-19 pandemic, particularly for adolescents. Within New Zealand, anecdotal and media reports suggest similar changes but are limited in scope and detail. We assessed eating disorder service demand in the Waikato district in relation to the COVID-19 pandemic. Methods We retrospectively analysed records of eating disorder admissions and referrals for both children (< 18 years) and adults (≥ 18 years) during 2019 and 2020 in the Waikato, a mixed urban–rural province in northern New Zealand (population 435,000). We analysed medical admission and outpatient referral rates, and referral acuity, in relation to the COVID-19 pandemic using Welch’s t- and chi-square tests. Results 106 medical admissions met inclusion criteria (n = 37 in 2019; 69 in 2020). Admissions for eating disorders increased markedly following nationwide lockdown in March 2020 (RR = 1.7, p = 0.01), largely driven by increases in adult admissions (RR 2.0, p = 0.005). The proportion of ‘new patient’ admissions showed comparable increases for both children (RR = 2.0, p = 0.02) and adults (RR = 2.3, p = 0.03). Following lockdown, outpatient referrals increased in acuity (RR = 1.8, p = 0.047) and volume (RR = 1.6, p = 0.076) for children but not for adults. Conclusions Our study confirms a pandemic-related increase in demand for eating disorder services in the Waikato region of New Zealand, consistent with findings reported overseas. We observed contrasting increases in admissions for adults and outpatient referrals for children, exacerbating resource constraints for already stretched services and compromising provision of timely care. Plain English summary The COVID-19 pandemic has been linked to increased numbers and worsening severity of eating disorders in several settings. In New Zealand, similar trends have been noted anecdotally. We assessed clinical records to calculate rates of eating disorder-related hospital admissions and outpatient referrals during 2019 and 2020. We found significant increases in hospital admissions related to COVID-19, particularly for adults, and greater proportions of both children and adults having a first-ever eating disorder-related admission. In outpatient services, young people were referred more frequently during the pandemic and were more physically unwell when referred. These results indicate increased demand for eating disorder services as a result of the pandemic and complement findings reported overseas.
A model was proposed to enhance awareness of the various factors involved in the feedback process.
Suggestions to improve clinical teaching and supervision included defining supervisor teaching competencies, instituting evidence-based faculty development, a feedback structure and strengthening leadership support for workplace-based education.
Objective Entrustable professional activities (EPAs) are used as clinical activities in postgraduate psychiatry training in Australasia. This study aimed to explore psychiatry trainees’ perceptions of the impact of EPAs on their motivation and learning. Methods A constructivist grounded theory approach was used to conceptualize the impact of EPAs on trainees’ motivation and learning. A purposive sample of trainees was recruited from across New Zealand. Semi-structured individual interviews were used for data collection and continued until theoretical saturation was reached. Results The impact of EPAs on learning was mediated by the trainee’s appraisals of subjective control, value, and the costs of engaging with EPAs. When appraisals were positive, EPAs encouraged a focus on particular learning needs and structured learning with the supervisor. However, when appraisals were negative, EPAs encouraged a superficial approach to learning. Trainee appraisals and their subsequent impact on motivation and learning were most affected by EPA granularity, alignment of EPAs with clinical practice, and the supervisor’s conscientiousness in their approach to EPAs. Conclusions To stimulate learning, EPAs must be valued by both trainees and supervisors as constituting a coherent work-based curriculum that encompasses the key fellowship competencies. If EPAs are to be effective as clinical tasks for learning, ongoing faculty development must be the leading priority.
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