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Abstract Background Patients are the most important stakeholders in the care of any disease and have an educational need to learn about their condition and the treatment they should receive. Considering this need for patient-focused materials, we present a directed approach for mucopolysaccharidosis (MPS) VI and MPS IVA, a pair of rare, inherited diseases that affects multiple organs and parts of the body. Independent guidelines on the treatment of these diseases were recently published, providing evidence- and expertise-driven recommendations to optimize patient management. However, while healthcare providers may have the training and knowledge to understand these guidelines, patients and their caregivers can find the technical content challenging. Hence, we aimed to develop plain language summaries (PLS) of the MPS VI and MPS IVA guidelines with patients as the primary audience. Results A review of the guidelines by an expert team identified six domains of information relevant to patients: The multidisciplinary team, regular tests and check-ups, disease-modifying and supportive treatments, general anesthetics, ear-nose-throat/respiratory care, and surgeries. This information was adapted into a series of infographics specific to either MPS VI or MPS IVA, designed to appeal to patients and clearly present information in a concise manner. Conclusions The use of patient-friendly materials, like the infographics we have developed, has the potential to better inform patients and engage them in their care. We issue a “call to arms” to the medical community for the development of similar PLS materials in rare diseases intended to inform and empower patients.

Abstract Introduction Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA. Methods Twenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers. Results A total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance). Conclusion This manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps.

Abstract Introduction Mucopolysaccharidosis (MPS) VI or Maroteaux-Lamy syndrome (253200) is an autosomal recessive lysosomal storage disorder caused by deficiency in N-acetylgalactosamine-4-sulfatase (arylsulfatase B). The heterogeneity and progressive nature of MPS VI necessitates a multidisciplinary team approach and there is a need for robust guidance to achieve optimal management. This programme was convened to develop evidence-based, expert-agreed recommendations for the general principles of management, routine monitoring requirements and the use of medical and surgical interventions in patients with MPS VI. Methods 26 international healthcare professionals from various disciplines, all with expertise in managing MPS VI, and three patient advocates formed the Steering Committee group (SC) and contributed to the development of this guidance. Members from six Patient Advocacy Groups (PAGs) acted as advisors and attended interviews to ensure representation of the patient perspective. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with expertise and experience managing patients with MPS VI and the manuscript has been evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers. Results A total of 93 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions. Consensus was reached on all statements after two rounds of voting. The greatest challenges faced by patients as relayed by consultation with PAGs were deficits in endurance, dexterity, hearing, vision and respiratory function. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance). Conclusion This manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS VI and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps.

Glycosaminoglycans (GAGs), dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS), are the primary biomarkers in patients with mucopolysaccharidoses (MPS); however, little is known about other biomarkers. To explore potential biomarkers and their correlation with GAGs, blood samples were collected from 46 MPS II patients, 34 MPS IVA patients, and 5 MPS IVB patients. We evaluated the levels of 8 pro-inflammatory factors (EGF, IL-1β, IL-6, MIP-1α, TNF-α, MMP-1, MMP-2, and MMP-9), collagen type II, and DS, HS (HS0S, HSNS), and KS (mono-sulfated, di-sulfated) in blood.Eight biomarkers measured were significantly elevated in untreated MPS II patients, compared with those in normal controls: EGF, IL-1β, IL-6, HS0S, HSNS, DS, mono-sulfated KS, and di-sulfated KS. The same eight biomarkers remained elevated in ERT-treated patients. However, only three biomarkers remained elevated in post-HSCT MPS II patients: EGF, mono-sulfated KS, and di-sulfated KS. Post-HSCT patients with MPS II showed that IL-1β and IL-6 were normalized as HS and DS levels decreased. Eight biomarkers were significantly elevated in untreated MPS IVA patients: EGF, IL-1β, IL-6, MIP-1α, MMP-9, HSNS, mono-sulfated KS, and di-sulfated KS, and four biomarkers were elevated in MPS IVA patients under ERT: IL-6, TNF-α, mono-sulfated KS, and di-sulfated KS. There was no reduction of KS in the ERT-treated MPS IVA patient, compared with untreated patients. Two biomarkers were significantly elevated in untreated MPS IVB patients: IL-6 and TNF-α.Reversely, collagen type II level was significantly decreased in untreated and ERT-treated MPS II patients and untreated MPS IVA patients.In conclusion, selected pro-inflammatory factors can be potential biomarkers in patients with MPS II and IV as well as GAGs levels. Keywords: Morquio syndrome, Hunter syndrome, Glycosaminoglycans, Cytokines, Inflammation

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the lysosomal enzymes essential for catabolism of glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction of multiple organs, resulting in distinct clinical manifestations. A range of methods have been developed to measure specific GAGs in various human samples to investigate diagnosis, prognosis, pathogenesis, GAG interaction with other molecules, and monitoring therapeutic efficacy. We established ELISA, liquid chromatography tandem mass spectrometry (LC-MS/MS), and an automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) to identify epitopes (ELISA) or disaccharides (MS/MS) derived from different GAGs (dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate). These methods have a high sensitivity and specificity in GAG analysis, applicable to the analysis of blood, urine, tissues, and cells. ELISA is feasible, sensitive, and reproducible with the standard equipment. HT-MS/MS yields higher throughput than conventional LC-MS/MS-based methods while the HT-MS/MS system does not have a chromatographic step and cannot distinguish GAGs with identical molecular weights, leading to a limitation of measurements for some specific GAGs. Here we review the advantages and disadvantages of these methods for measuring GAG levels in biological specimens. We also describe an unexpected secondary elevation of keratan sulfate in patients with MPS that is an indirect consequence of disruption of catabolism of other GAGs.

Purpose – The visitor economy of Forks now clearly relies upon a niche form of tourism – as fans of The Twilight Saga are drawn to the setting and filming location of the films. The purpose of this study is to consider the process of diversification and subsequently present recommendations that could inform a future diversification strategy for Forks, in preparation for a post-film tourism scenario. Design/methodology/approach – The research methods employed in this study have two interlinked but distinct elements. Firstly, the Twilight Effect in Forks (WA, USA) is considered as an illustrative case study to shed light on the issues facing a destination that has seen a tourism boom as a direct result of popular culture – The Twilight Saga Franchise. Secondly, a scenario thinking and planning approach is applied when considering the “long-view” future of tourism in Forks. Findings – This article presents a post-film tourism future scenario for Forks; it suggests tourism diversification and a shift towards cultural heritage and wellness. Forks is well placed to afford such tourism experiences, as it offers unique cultural and natural characteristics; furthermore, these could be utilised to create and maintain a distinctive destination image. In doing so a more socially and environmentally sustainable industry can be established, one which supports the local community, including the Quileute tribe. Originality/value – The article offers original discussions within the film-tourism literature with novel approaches to understanding the management and pre-planning opportunities for destinations that have become popular film tourism locations, with the application of a “Tourism Diversification Model”. The model is adapted from Ansoff Matrix and can be applied as a framework in future studies exploring destination diversification. The investigation of Forks as a post-film tourism case study alone is unique, and the discussions and findings presented are original.

Purpose – Is humanity heading to immortal living? If so, what areas of society are playing an active role in achieving this? In order to understand this, the study explores the relationship between immortality and the wellness and medical tourism industry to seek potential relationships between them and ultimately, asks difficult questions about the growth of these tourism sectors and the potential need for greater regulation of them. Design/methodology/approach – Taking a pragmatic philosophical approach and through the examination of refined information from secondary sources and published material and reports, the study presents original theoretical knowledge and a model exploring tourism and human immortality. Findings – This paper argues that continued growth in the wellness and medical markets today could lead to a world where transhumanists and cyborgs are present in our world, even taking over from Homo sapiens. The study presents a model highlighting the potential role of wellness and medical tourism markets, illustrating the potential for future consumer services that could further fuel the search for immortality. Thus, how such markets and consumer desires are (in)directly supporting humanities desire for (non-human) immortal existence. Originality/value – Today, individuals are driven by wellness practices and medical and cosmetic desires and are willing to travel the globe in search of companies who are either capable of carrying out the desired procedures or seeking prices more affordable to them. This research offers novel insights into these complex relationships and maps the affiliation between wellness and medical practices and the concept of immortality.

Purpose – By drawing on current reports, this paper positions that Homo sapiens could in the near future be faced with an increasingly uninhabitable planet. It emphasises the importance of adventure tourism and its associated activities as a means of supporting individuals to develop more outdoor survival skills. Design/methodology/approach – This study applies a scenario narrative approach in exploring and presenting potential future ideas. The significance of narratives lies at the essential examination of current trends and drivers that could be shaping future scenarios. This paper, through the exploration of past and current trends supports the researcher in presenting future views. The scenario narratives in this research are established via desk-based research and inspection of academic journals, industry reports, ideas and knowledge. Findings – If society is pushed to the brink of extinction due to a catastrophic event(s), people will require survival skills, similar to those shared by our hunter-gather nomad ancestor. Thus, this paper highlights the value and importance of the industry in encouraging soft and hard outdoor adventure in the coming years. It recognises how different adventure travel activities can support people in rekindling with our more basic instincts and ultimately, surviving in different natural environments. Originality/value – This paper offers original theoretical knowledge within the adventure tourism literature. Offering original consideration to the value of exploring the past as a method of understanding the future, the paper presents an original spectrum of soft and hard skills-based adventure tourism activities.

Purpose – The natural environment is facing unprecedented times owing to rising temperatures from carbon emissions, which travel-related industries contribute significantly towards. The recent global COVID-19 outbreak should be a wake-up call for the industry, as vulnerabilities have been laid bare. The current challenges should be used as a motivation to change the meaning of travel to support the global warming crisis. This paper aims emphasis that, by means of new stories, new values, beliefs and ultimately travel behaviours can be rewritten. Design/methodology/approach/ – This study embraces a pragmatic approach to research. To ensure plausibility, credibility and relevance, the research carried out multi-disciplinary analysis of secondary data, information, knowledge and draws on current developing trends. Findings – The travel community needs to take responsibility and start reducing its carbon footprint and as carbon neutrality is increasingly a global priority. Accordingly, this research considers potential future travel-related behaviours that could support more carbon-neutral travel. Significantly, it notes how the COVID-19 outbreak has offered insights into potential positive changes. To benefit from these changes, new stories for industry providers are necessary to encourage more carbon-neutral travel practices. Originality/value – This paper offers timely and original discussions on the future of travel as a result of COVID-19 impacts. It draws on the power of storytelling as a means of achieving behavioural change in the travel community to support the challenge of climate change.

Purpose – Human fascination in the unidentified flying objects (UFOs) and alien paranormal phenomenon is rich in history, explored widely in popular culture and many personal beliefs exist across society. The tourism industry offers a range of places where consumers can encounter such a phenomenon. Reports continue to highlight the growth in consumers participating at UFO and alien tourism attractions and locations. Significantly, the purpose of this paper is to shine a light on the relationship between UFOs, aliens and the tourism industry. Design/methodology/approach – This paper takes a pragmatic philosophical approach by embracing a multi-disciplinary analysis. This study examines a range of secondary data information, statistics, reports and research studies. Findings – By identifying the current impotence of the UFO and alien tourism markets and the growing consumer participation in it, this paper presents a theoretical starting point in the form of a model, which maps the current landscape of the industry from supply and demand perspectives. This study should be seen as a stepping stone towards further research into the UFO and alien tourism industry and provide researchers with a theoretical platform and novel ideas through which to explore the subject. Originality/value – The phenomenon includes an established eclectic mix of attractions and likewise tourist motivations for visiting are wide and diverse. However, the subject lacks academic consideration. Thus, this paper presents original research and timely discussions on the topic.