Ocular Lichen Planus: A clinicopathologic review.

Lichen planus is a chronic inflammatory dermatosis that can affect the skin, mucous membranes and nails. Cutaneous lichen planus lesions are best described by the "six Ps" - purple pruritic polygonal planar papules and plaques. Mucous membrane lesions are commonly associated with cutaneous lichen planus. Ocular involvement with lichen planus is rare and conjunctival involvement usually predominates, it can however be visually devastating. Ocular lichen planus often progresses to extensive conjunctival scarring which can be impossible to distinguish clinically from other cicatrising conjunctivitis, requiring histopathological confirmation. Here we review the ocular pathology of this condition.

Monoamines' role in islet cell function and type 2 diabetes risk.

The two monoamines serotonin and melatonin have recently been highlighted as potent regulators of islet hormone secretion and overall glucose homeostasis in the body. In fact, dysregulated signaling of both amines are implicated in ß-cell dysfunction and development of type 2 diabetes mellitus (T2DM). Serotonin is a key player in ß-cell physiology and plays a role in expansion of ß-cell mass. Melatonin regulates circadian rhythm and nutrient metabolism and reduces insulin release in human and rodent islets in vitro. Herein, we focus on the role of serotonin and melatonin in islet physiology and the pathophysiology of T2DM. This includes effects on hormone secretion, receptor expression, genetic variants influencing ß-cell function, melatonin treatment, and compounds that alter serotonin availability and signaling.

Primary orbital sarcoma in adults: a case series with emphasis on post-irradiation sarcoma.

PURPOSE: To describe a series of eight adult patients with primary orbital sarcoma and to review the existing literature on orbital sarcoma and post-irradiation sarcoma. METHODS: Report of eight cases and literature review. RESULTS: We report eight cases of primary orbital sarcoma, three of which were radiation-induced. Only one patient had a history of retinoblastoma. The most common presentations were painful proptosis and reduced vision. Most tumours arose in the extraconal compartment. The overall median age at diagnosis was 50 years. The pathology comprised a diverse group of tumours. Treatment and outcome varied between patients and their clinical circumstances. CONCLUSIONS: Adult primary orbital sarcomas are rare. They can comprise a variety of tumour types and are difficult to treat. Irradiation is a significant risk factor, and the incidence of post-irradiation sarcoma of the orbit may be increasing due to the widespread use of radiotherapy and improved survival of patients with cancer. Post-irradiation sarcoma should be considered in the differential diagnosis of an orbital space-occupying lesion in a patient with a history of radiotherapy.

Post-enucleation outcomes of patients with uveal melanoma in Scotland.

BACKGROUND/OBJECTIVES: To investigate post-enucleation outcomes and assess the effect of extrascleral extension (ESE) on these outcomes for patients with uveal melanoma (UM) managed at a tertiary referral centre in Scotland. SUBJECTS/METHODS: Retrospective review of all cases of UM managed by the Scottish Ocular Oncology Service for which enucleation was undertaken between 13/03/2008 and 31/12/2020. Primary outcomes were length of survival, time-to-metastasis (TTM) and local recurrence rate. Secondary outcomes were the effects of the presence of ESE, ESE size, and the use of adjuvant external beam radiotherapy (EBRT) on the primary outcomes. RESULTS: Of 172 enucleated UMs, 32 (18.6%) had ESE. Over a median follow-up period of 33.7 months (range = 1.1-163.7 months), 91 (52.9%) patients died. The median length of all-cause survival of 54.1 months (range = 1.1-163.7 months). One-year, 5-year, and 10-year survival rates were 84.8%, 49.1%, and 30.9%, respectively. Eighty-four (49.7%) patients had metastatic disease. The median TTM of 42.2 months (range = 0.4-106.8 months). Proportions of patients who developed metastases within 1-year, 5-years and 10-years post-enucleation were 22.7%, 52.8%, and 71.8%, respectively. There was one instance of local orbital recurrence. ESE was associated with a significantly shorter length of survival (p = 0.03). There was a trend towards a shorter length of survival and TTM with ESE > 5 mm and those who received adjuvant EBRT. CONCLUSIONS: ESE was present in one-sixth of our cohort and was associated with a significantly shorter length of survival, particularly in the presence of ESE > 5 mm or high-risk characteristics warranting adjuvant EBRT. This data will aid prognostication of the patients in our service.

The impact of macronutrient composition on metabolic regulation: An Islet-Centric view.

AIM: The influence of dietary carbohydrates and fats on weight gain is inconclusively understood. We studied the acute impact of these nutrients on the overall metabolic state utilizing the insulin:glucagon ratio (IGR). METHODS: Following in vitro glucose and palmitate treatment, insulin and glucagon secretion from islets isolated from C57Bl/6J mice was measured. Our human in vivo study included 21 normoglycaemia (mean age 51.9 ± 16.5 years, BMI 23.9 ± 3.5 kg/m2 , and HbA1c 36.9 ± 3.3 mmol/mol) and 20 type 2 diabetes (T2D) diagnosed individuals (duration 12 ± 7 years, mean age 63.6 ± 4.5 years, BMI 29.1 ± 2.4 kg/m2 , and HbA1c 52.3 ± 9.5 mmol/mol). Individuals consumed a carbohydrate-rich or fat-rich meal (600 kcal) in a cross-over design. Plasma insulin and glucagon levels were measured at -30, -5, and 0 min, and every 30 min until 240 min after meal ingestion. RESULTS: The IGR measured from mouse islets was determined solely by glucose levels. The palmitate-stimulated hormone secretion was largely glucose independent in the analysed mouse islets. The acute meal tolerance test demonstrated that insulin and glucagon secretion is dependent on glycaemic status and meal composition, whereas the IGR was dependent upon meal composition. The relative reduction in IGR elicited by the fat-rich meal was more pronounced in obese individuals. This effect was blunted in T2D individuals with elevated HbA1c levels. CONCLUSION: The metabolic state in normoglycaemic individuals and T2D-diagnosed individuals is regulated by glucose. We demonstrate that consumption of a low carbohydrate diet, eliciting a catabolic state, may be beneficial for weight loss, particularly in obese individuals.

Development of a tool to assess core cardiorespiratory physiotherapy skills: a Delphi study.

PURPOSE: This study reports on the development of an outcome measure designed to evaluate pre-registration physiotherapy students' ability in performing core cardiorespiratory skills. METHOD: A four round, e- Delphi study using an international panel of expert cardiorespiratory physiotherapists involved in pre-registration student education was undertaken. In round one participants identified what they look for in students competently performing core cardio-respiratory physiotherapy assessment and treatment skills. These items were refined in rounds two and three. Item content validity score (iCVI) of ≥ 0.8 at round four identified consensus. Scale content validity index (SCVI) was calculated. RESULTS: Response rate for round one was 46% (6/13). Additional experts were invited to participate and response rates increased to 71% (round 2), 88% (round 3) and 100% (round 4). Of the 207 items across the seven skills identified in round one, 140 were presented in round four. Of these, consensus was achieved for 128 items, with 12 being excluded. The SCVI was 0.907. CONCLUSION: This e-Delphi study enabled the development of a draft outcome measure, which aims to assess performance of seven cardiorespiratory physiotherapy skills. This tool will enable rigorous evaluation of different education methods to establish their effectiveness. However, it is first necessary to establish construct validity and assess inter and intra-rater reliability.

New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy.

Exercise itself is fundamental for good health, and when practiced regularly confers a myriad of metabolic benefits in a range of tissues. These benefits are mediated by a range of adaptive responses in a coordinated, multi-organ manner. The continued understanding of the molecular mechanisms of action which confer beneficial effects of exercise on the body will identify more specific pathways which can be manipulated by therapeutic intervention in order to prevent or treat various metabolism-associated diseases. This is particularly important as exercise is not an available option to all and so novel methods must be identified to confer the beneficial effects of exercise in a therapeutic manner. This review will focus on key emerging molecular mechanisms of mitochondrial biogenesis, autophagy and mitophagy in selected, highly metabolic tissues, describing their regulation and contribution to beneficial adaptations to exercise.

A mathematical investigation into the uptake kinetics of nanoparticles in vitro.

Nanoparticles have the potential to increase the efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding the cellular uptake kinetics of nanoparticles which could have implications for nanoparticle design and delivery. Polymersomes are nanoparticle candidates for cancer therapy which encapsulate chemotherapy drugs. Here we develop a mathematical model to simulate the uptake of polymersomes via endocytosis, a process by which polymersomes bind to the cell surface before becoming internalised by the cell where they then break down, releasing their contents which could include chemotherapy drugs. We focus on two in vitro configurations relevant to the testing and development of cancer therapies: a well-mixed culture model and a tumour spheroid setup. Our mathematical model of the well-mixed culture model comprises a set of coupled ordinary differential equations for the unbound and bound polymersomes and associated binding dynamics. Using a singular perturbation analysis we identify an optimal number of ligands on the polymersome surface which maximises internalised polymersomes and thus intracellular chemotherapy drug concentration. In our mathematical model of the spheroid, a multiphase system of partial differential equations is developed to describe the spatial and temporal distribution of bound and unbound polymersomes via advection and diffusion, alongside oxygen, tumour growth, cell proliferation and viability. Consistent with experimental observations, the model predicts the evolution of oxygen gradients leading to a necrotic core. We investigate the impact of two different internalisation functions on spheroid growth, a constant and a bond dependent function. It was found that the constant function yields faster uptake and therefore chemotherapy delivery. We also show how various parameters, such as spheroid permeability, lead to travelling wave or steady-state solutions.

Osteoblast-specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase-1 engenders insulin resistance in high-fat diet fed mice.

Supraphysiological levels of the osteoblast-enriched mineralization regulator ectonucleotide pyrophosphatase or phosphodiesterase-1 (NPP1) is associated with type 2 diabetes mellitus. We determined the impact of osteoblast-specific Enpp1 ablation on skeletal structure and metabolic phenotype in mice. Female, but not male, 6-week-old mice lacking osteoblast NPP1 expression (osteoblast-specific knockout [KO]) exhibited increased femoral bone volume or total volume (17.50% vs. 11.67%; p < .01), and reduced trabecular spacing (0.187 vs. 0.157 mm; p < .01) compared with floxed (control) mice. Furthermore, an enhanced ability of isolated osteoblasts from the osteoblast-specific KO to calcify their matrix in vitro compared to fl/fl osteoblasts was observed (p < .05). Male osteoblast-specific KO and fl/fl mice showed comparable glucose and insulin tolerance despite increased levels of insulin-sensitizing under-carboxylated osteocalcin (195% increase; p < .05). However, following high-fat-diet challenge, osteoblast-specific KO mice showed impaired glucose and insulin tolerance compared with fl/fl mice. These data highlight a crucial local role for osteoblast NPP1 in skeletal development and a secondary metabolic impact that predominantly maintains insulin sensitivity.

Rehabilitation Before and After Autologous Haematopoietic Stem Cell Transplantation (AHSCT) for Patients With Multiple Sclerosis (MS): Consensus Guidelines and Recommendations for Best Clinical Practice on Behalf of the Autoimmune Diseases Working Party, Nurses Group, and Patient Advocacy Committee of the European Society for Blood and Marrow Transplantation (EBMT).

Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly used to treat people with multiple sclerosis (MS). Supported by an evolving evidence base, AHSCT can suppress active inflammation in the central nervous system and induce long-term changes in immune cell populations, thereby stabilizing, and, in some cases, reversing disability in carefully selected MS patients. However, AHSCT is an intensive chemotherapy-based procedure associated with intrinsic risks, including profound cytopenia, infection, and organ toxicity, accompanied by an on-going degree of immuno-compromise and general deconditioning, which can be associated with a transient increase in functional impairment in the early stages after transplantation. Although international guidelines and recommendations have been published for clinical and technical aspects of AHSCT in MS, there has been no detailed appraisal of the rehabilitation needed following treatment nor any specific guidelines as to how this is best delivered by hospital and community-based therapists and wider multidisciplinary teams in order to maximize functional recovery and quality of life. These expert consensus guidelines aim to address this unmet need by summarizing the evidence-base for AHSCT in MS and providing recommendations for current rehabilitation practice along with identifying areas for future research and development.

Foreign body episcleral suture granulomas mimicking nodular anterior scleritis.

Scleritis is an idiopathic condition that may sometimes be associated with systemic immunological like disorders rheumatoid arthritis, Wegener's granulomatosis and systemic lupus erythematosus. A variety of foreign material has been reported to result in granuloma formation in various parts of the body. We report a case of inflamed episcleral granulomas mimicking severe nodular anterior scleritis in a healthy Caucasian woman who underwent strabismus surgery in her childhood. Foreign body reaction on the episcleral/scleral surface is rare. It is extremely unusual for a non-absorbable suture that was used for childhood strabismus surgery to incite an acute inflammatory episode mimicking nodular anterior scleritis as in our case. As the strabismus surgery was performed 37 years prior to her presentation with anterior scleritis, we were unable to obtain any details of this surgical procedure. We presume that a non-absorbable suture like braided polyester or prolene may have been used.

Impact of the COVID-19 pandemic on anaesthesia trainees and their training.

Coronavirus disease 2019 (COVID-19; severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] has dislocated clinical services and postgraduate training. To better understand and to document these impacts, we contacted anaesthesia trainees and trainers across six continents and collated their experiences during the pandemic. All aspects of training programmes have been affected. Trainees report that reduced caseload, sub-specialty experience, and supervised procedures are impairing learning. Cancelled educational activities, postponed examinations, and altered rotations threaten progression through training. Job prospects and international opportunities are downgraded. Work-related anxieties about provision of personal protective equipment, and risks to self and to colleagues are superimposed on concerns for family and friends and domestic disruption. These seismic changes have had consequences for well-being and mental health. In response, anaesthetists have developed innovations in teaching and trainee support. New technologies support trainer-trainee interactions, with a focus on e-learning. National training bodies and medical regulators that specify training and oversee assessment of trainees and their progression have provided flexibility in their requirements. Within anaesthesia departments, support transcends grades and job titles with lessons for the future. Attention to wellness, awareness of mental health issues and multimodal support can attenuate but not eliminate trainee distress.

Beyond mineralisation: metabolic functions for matrix mineralisation regulators.

The physiological mineralisation of skeletal tissues, as well as the pathological mineralisation of soft tissues involves a fine balance between regulators that either promote or inhibit the process. In recent years, several studies have advocated a non-skeletal role for some of these mineralisation regulators in a range of human diseases, including diabetes, cardiovascular disease, obesity and neurodegenerative disease. This is an emerging area of interest and the functional roles and mechanisms of action of these various endocrine factors, phosphatases and phosphodiesterase's in important pathologies are the focus of this review. Mechanistic insight of the pathways through which these acknowledged regulators of skeletal mineralisation act beyond the skeleton has the potential to identify druggable targets for commonly experienced morbidities, notably those related to metabolism and metabolic syndrome.

Effectiveness of expiratory muscle strength training on expiratory strength, pulmonary function and cough in the adult population: a systematic review.

BACKGROUND: Respiratory muscle strength declines in certain disease states, leading to impaired cough, reduced airway clearance and an increased risk of aspiration pneumonia. Respiratory muscle training may therefore reduce this risk. OBJECTIVES: To assess current evidence of expiratory muscle strength training (EMST) on maximum expiratory pressure, cough flow and spirometry. DATA SOURCES: Databases including CINAHL, Medline, Science Direct and PEDRo were searched. ELIGIBILITY CRITERIA: Randomised controlled trials investigating expiratory muscle strength training on maximum expiratory pressure, pulmonary function or cough in any adult population, published before December 2017. STUDY APPRAISAL: Data were extracted to a trial description form and study quality evaluated by two reviewers. Meta-analysis was performed with calculation of mean differences and 95% confidence intervals. RESULTS: Nine studies met inclusion criteria and ranged in size from 12 to 42 participants. Trials investigated EMST in healthy adults (2), multiple sclerosis (3), COPD (2), acute stroke (1) and spinal cord injury (1). Overall, EMST improved maximum expiratory pressure (15.95cmH2O; 95% CI: 7.77 to 24.12; P<0.01) with no significant impact on cough flow (4.63L/minute; 95%CI -27.48 to 36.74; P=0.78), forced vital capacity (-0.16L; 95%CI -0.35 to 0.02; P=0.09) or forced expiratory volume in 1second (-0.09L; 95%CI -0.10 to -0.08; P<0.001) vs control or sham training. CONCLUSIONS: Meta-analysis indicated a small significant increase in maximum expiratory pressure following EMST. Improvements in maximum expiratory pressure did not lead to improvements in cough or pulmonary function. LIMITATIONS: Variations in protocol design and population limited the overall effect size. Systematic Review Registration PROSPERO CRD42018104190.

Impact of Simulated Patients on Physiotherapy Students' Skill Performance in Cardiorespiratory Practice Classes: A Pilot Study.

Purpose: To date, no evidence exists that high-fidelity simulation improves skill development among physiotherapy students in the university setting. With pressures to reduce costs and maintain or improve the quality of the learning experience, and with pressures on clinical placement, it is essential to investigate methods that might improve students' skill performance before they undertake clinical practice. Our study set out to investigate (1) the impact of using simulated patients (SPs) in a practical class on physiotherapy students' skill acquisition and (2) the students' reflections on the intervention. Method: We devised a pilot study using a single-centre randomized controlled trial. A total of 28 undergraduate physiotherapy students, matched using previous practical examination grades, undertook a 2-hour practical class in which they practised their core cardiorespiratory skills. Pre-session resources were identical. The control group practised on peers; the intervention group practised on SPs. The students' skill performance was assessed 2 weeks later using the Mini-Clinical Evaluation Exercise (MiniCEX), including gathering qualitative data from the students' reflections. Twenty-eight students undertook the practical class and subsequent MiniCEX assessment. Results: A statistically significant difference was found for all aspects of the MiniCEX except medical interview (p = 0.07) and physical interview (p = 0.69), and a large effect size was found for all areas except physical interview (0.154) and medical interview (0.378). The students' reflections focused on three key themes: behaviours and attitudes, teaching the active cycle of breathing technique, and feedback. Conclusions: Our findings suggest that interacting with SPs improves student skill performance, but further research using a larger sample size and an outcome measure validated for this population is required to confirm this.

Objectif : jusqu'à présent, aucune donnée probante n'indique que la simulation haute-fidélité améliore les compétences des étudiants universitaires en physiothérapie. Compte tenu des pressions pour réduire les coûts, maintenir ou améliorer la qualité de l'expérience d'apprentissage et participer à des stages, il est essentiel d'explorer des méthodes pour améliorer le rendement des compétences avant d'entreprendre la pratique clinique. Dans la présente étude, les chercheurs ont exploré 1) les répercussions du recours à des patients simulés (PS) dans un cours pratique d'acquisition des compétences des étudiants en physiothérapie et 2) les réflexions des étudiants à l'égard de l'intervention. Méthodologie : les chercheurs ont conçu un projet pilote dans le cadre d'un essai aléatoire et contrôlé monocentrique. Au total, 28 étudiants au premier cycle en physiothérapie, jumelés d'après leurs notes antérieures aux examens pratiques, ont suivi un cours pratique de deux heures pendant lequel ils ont exercé leurs compétences de base en santé cardiorespiratoire. Ils ont tous reçu les mêmes ressources avant le cours. Les membres du groupe témoin se sont exercés sur leurs homologues, et ceux du groupe d'intervention, sur des PS. Les chercheurs ont évalué le rendement des compétences des étudiants deux semaines plus tard à l'aide du mini-exercice d'évaluation clinique (MiniCEX), qui incluait une collecte de données qualitatives sur les réflexions des étudiants. Les 28 étudiants ont suivi le cours pratique et rempli l'évaluation MiniCEX subséquente. Résultats : les chercheurs ont constaté une différence statistiquement significative dans tous les aspects du MiniCEX, sauf l'entrevue médicale (p = 0,07) et l'entrevue physique (p = 0,69), et une taille d'effet importante dans tous les secteurs sauf l'entrevue physique (0,154) et l'entrevue médicale (0,378). Les réflexions des étudiants ont porté sur trois grands thèmes : comportements et attitudes, enseignement du cycle actif de la technique respiratoire et rétroaction. Conclusion : d'après les résultats, l'interaction avec des PS améliore le rendement des compétences des étudiants, mais il faudra réaliser d'autres recherches auprès d'un plus gros échantillon et valider les résultats dans cette population pour confirmer ces observations.

Osteocalcin Regulates Arterial Calcification Via Altered Wnt Signaling and Glucose Metabolism.

Arterial calcification is an important hallmark of cardiovascular disease and shares many similarities with skeletal mineralization. The bone-specific protein osteocalcin (OCN) is an established marker of vascular smooth muscle cell (VSMC) osteochondrogenic transdifferentiation and a known regulator of glucose metabolism. However, the role of OCN in controlling arterial calcification is unclear. We hypothesized that OCN regulates calcification in VSMCs and sought to identify the underpinning signaling pathways. Immunohistochemistry revealed OCN co-localization with VSMC calcification in human calcified carotid artery plaques. Additionally, 3 mM phosphate treatment stimulated OCN mRNA expression in cultured VSMCs (1.72-fold, p < 0.001). Phosphate-induced calcification was blunted in VSMCs derived from OCN null mice (Ocn -/- ) compared with cells derived from wild-type (WT) mice (0.37-fold, p < 0.001). Ocn -/- VSMCs showed reduced mRNA expression of the osteogenic marker Runx2 (0.51-fold, p < 0.01) and the sodium-dependent phosphate transporter, PiT1 (0.70-fold, p < 0.001), with an increase in the calcification inhibitor Mgp (1.42-fold, p < 0.05) compared with WT. Ocn -/- VSMCs also showed reduced mRNA expression of Axin2 (0.13-fold, p < 0.001) and Cyclin D (0.71 fold, p < 0.01), markers of Wnt signaling. CHIR99021 (GSK3ß inhibitor) treatment increased calcium deposition in WT and Ocn -/- VSMCs (1 µM, p < 0.001). Ocn -/- VSMCs, however, calcified less than WT cells (1 µM; 0.27-fold, p < 0.001). Ocn -/- VSMCs showed reduced mRNA expression of Glut1 (0.78-fold, p < 0.001), Hex1 (0.77-fold, p < 0.01), and Pdk4 (0.47-fold, p < 0.001). This was accompanied by reduced glucose uptake (0.38-fold, p < 0.05). Subsequent mitochondrial function assessment revealed increased ATP-linked respiration (1.29-fold, p < 0.05), spare respiratory capacity (1.59-fold, p < 0.01), and maximal respiration (1.52-fold, p < 0.001) in Ocn -/- versus WT VSMCs. Together these data suggest that OCN plays a crucial role in arterial calcification mediated by Wnt/ß-catenin signaling through reduced maximal respiration. Mitochondrial dynamics may therefore represent a novel therapeutic target for clinical intervention. © 2019 American Society for Bone and Mineral Research.

Digitizing a Face-to-Face Group Fatigue Management Program: Exploring the Views of People With Multiple Sclerosis and Health Care Professionals Via Consultation Groups and Interviews.

BACKGROUND: Fatigue is one of the most common and debilitating symptoms of multiple sclerosis (MS) and is the main reason why people with MS stop working early. The MS Society in the United Kingdom funded a randomized controlled trial of FACETS-a face-to-face group-based fatigue management program for people with multiple sclerosis (pwMS)-developed by members of the research team. Given the favorable trial results and to help with implementation, the MS Society supported the design and printing of the FACETS manual and materials and the national delivery of FACETS training courses (designed by the research team) for health care professionals (HCPs). By 2015 more than 1500 pwMS had received the FACETS program, but it is not available in all areas and a face-to-face format may not be suitable for, or appeal to, everyone. For these reasons, the MS Society funded a consultation to explore an alternative Web-based model of service delivery. OBJECTIVE: The aim of this study was to gather views about a Web-based model of service delivery from HCPs who had delivered FACETS and from pwMS who had attended FACETS. METHODS: Telephone consultations were undertaken with FACETS-trained HCPs who had experience of delivering FACETS (n=8). Three face-to-face consultation groups were held with pwMS who had attended the FACETS program: London (n=4), Liverpool (n=4), and Bristol (n=7). The interviews and consultation groups were digitally recorded and transcribed. A thematic analysis was undertaken to identify key themes. Toward the end of the study, a roundtable meeting was held to discuss outcomes from the consultation with representatives from the MS Society, HCPs, and pwMS. RESULTS: Key challenges and opportunities of designing and delivering an integrated Web-based version of FACETS and maintaining user engagement were identified across 7 themes (delivery, online delivery, design, group, engagement, interactivity, and HCP relationships). Particularly of interest were themes related to replicating the group dynamics and the lack of high-quality solutions that would support the FACETS' weekly homework tasks and symptom monitoring and management. CONCLUSIONS: A minimum viable Web-based version of FACETS was suggested as the best starting point for a phased implementation, enabling a solution that could then be added to over time. It was also proposed that a separate study should look to create a free stand-alone digital toolkit focusing on the homework elements of FACETS. This study has commenced with a first version of the toolkit in development involving pwMS throughout the design and build stages to ensure a user-centered solution.

Effectiveness of high fidelity simulation versus low fidelity simulation on practical/clinical skill development in pre-registration physiotherapy students: a systematic review.

OBJECTIVE: The objective of this review is to evaluate the effectiveness of high fidelity simulation (HFS) versus low fidelity simulation (LFS) on practical/clinical skill development in pre-registration physiotherapy students. INTRODUCTION: Evidence suggests that improved skill development in university can reduce anxiety in practice, improving performance of skills and overall learning at clinical placement for health professions students. However, evidence indicates that the clinical environment is most effective for learning. As a result, there has been increased interest in the use of HFS where students can test knowledge and skills in an increasingly self-directed way. No previous reviews on the effectiveness of HFS on skill development in physiotherapy students were identified. INCLUSION CRITERIA: Experimental and quasi-experimental studies comparing HFS (simulated person, manikin, virtual simulation, video case-studies) to LFS (peer role-play, paper-based case-studies) in pre-registration physiotherapy education were included. Primary outcomes were objective measures of skills performance; secondary outcomes were students' perceptions of the impact of simulation on learning measured using quantitative outcomes. METHODS: A three-step search strategy was employed. Following an initial search of MEDLINE and CINAHL and analysis of text words, MEDLINE, CINAHL, ERIC, AMED, EThOS and Google Scholar were searched in November 2017. Reference lists of studies included at critical appraisal stage were hand-searched. Studies published in English from 1978 onwards were included. Title/abstract screening, critical appraisal and data extraction were conducted by two independent reviewers; conflicts were resolved by discussion. RESULTS: Meta-analysis was not possible due to heterogeneity; therefore, results were presented in narrative form. Three randomized controlled trials (RCT) and three quasi-experimental studies (310 participants) were included. They were conducted in the USA and Australia, and evaluated standardized patients (people who take on the role of a real patient), near-peers, computerized manikins and virtual simulation in pre-registration Bachelor of Science (Honors), Master of Science and Doctor of Physiotherapy students. One RCT was considered high quality, with the remainder moderate quality. The findings related to five main areas: i) In terms of motor skills performance, an increased number of safety fails were found with HFS (HFS = 13.5% safety fails, HFS plus video feedback = 15.4% safety fails, control [LFS] = 8.1% safety fails); ii) In terms of clinical performance, the Assessment of Physiotherapy Practice (APP) tool indicated no significant improvement in mean APP scores at week 6 of clinical placement (HFS mean APP score = 60.7 [9.1], control mean APP score = 58.7 [8.4]; P = 0.35); iii) In terms of self-efficacy, only one of two studies showed a statistically significant difference with HFS, as measured by the Acute Care Confidence Survey (P = 0.001); however, became non-significant once students were on clinical placement (P = 0.328); iv) Students did not perceive a significant difference in their communication skills with HFS, as measured on a visual analogue scale (simulation = 9.05 [1.27]; control 8.75 [1.2]; P = 0.482); and v) In terms of general perceptions, students were significantly more positive about HFS for increasing awareness of safety issues (P = 0.002), patients' emotional status (P = 0.002), handling skills (P < 0.0001) and ability to provide instructions to patients (P < 0.0001). CONCLUSIONS: Currently, there is no high quality evidence that HFS improves motor skill performance in pre-registration physiotherapy students. There is a small amount of moderate-quality evidence it may improve students' perception of their self-efficacy but no evidence that it improves communication skills. However, a lack of studies and variation in outcome measures meant that meta-analysis was not possible. At present, no recommendations can be made regarding the use of HFS to improve skill performance in this population.

ENPP1 in the Regulation of Mineralization and Beyond.

ENPP1 is well known for its role in regulating skeletal and soft tissue mineralization. It primarily exerts its function through the generation of pyrophosphate, a key inhibitor of hydroxyapatite formation. Several previous studies have suggested that ENPP1 also contributes to a range of human diseases including diabetes, cancer, cardiovascular disease, and osteoarthritis. In this review, we summarize the pathological roles of ENPP1 in mineralization and these soft tissue disorders. We also discuss the underlying mechanisms through which ENPP1 exerts its pathological effects. A fuller understanding of the pathways through which ENPP1 acts may help to develop novel therapeutic strategies for these commonly diagnosed morbidities.

Limbal Stem Cell Deficiency Secondary to Diffuse Non-necrotizing Anterior Scleritis: A Clinicopathological Report.

PURPOSE: To report a case of limbal stem cell deficiency (LSCD) secondary to diffuse non-necrotizing anterior scleritis (DNNAS). METHOD: Interventional case report with clinicopathologic correlation. A 69-year-old white woman with known Crohn disease presented with DNNAS. The acute inflammatory phase was treated with topical and systemic steroids. After DNNAS, she developed secondary LSCD with loss of limbal palisades of Vogt and conjunctivalization of the corneal surface and corneal haze. She underwent superficial keratectomy combined with autologous limbal stem cell grafting from the fellow eye. The keratectomy specimen was sent for pathological examination. RESULTS: There were no intraoperative or post-operative complications. Histopathology and immunohistochemistry showed a cytokeratin 19-positive and cytokeratin 3- and cytokeratin 12 negative epithelium in keeping with a conjunctival phenotype on the corneal surface. CONCLUSIONS: LSCD can be a rare complication of DNNAS. After control of ocular surface inflammation, autologous limbal stem cell grafting and amniotic membrane transplantation can be effective in normalizing the ocular surface.