DAF-18/PTEN inhibits germline zygotic gene activation during primordial germ cell quiescence.

Quiescence, an actively-maintained reversible state of cell cycle arrest, is not well understood. PTEN is one of the most frequently lost tumor suppressors in human cancers and regulates quiescence of stem cells and cancer cells. The sole PTEN ortholog in Caenorhabditis elegans is daf-18. In a C. elegans loss-of-function mutant for daf-18, primordial germ cells (PGCs) divide inappropriately in L1 larvae hatched into starvation conditions, in a TOR-dependent manner. Here, we further investigated the role of daf-18 in maintaining PGC quiescence in L1 starvation. We found that maternal or zygotic daf-18 is sufficient to maintain cell cycle quiescence, that daf-18 acts in the germ line and soma, and that daf-18 affects timing of PGC divisions in fed animals. Importantly, our results also implicate daf-18 in repression of germline zygotic gene activation, though not in germline fate specification. However, TOR is less important to germline zygotic gene expression, suggesting that in the absence of food, daf-18/PTEN prevents inappropriate germline zygotic gene activation and cell division by distinct mechanisms.

Chromosome 18 Loss of Heterozygosity in Small Intestinal Neuroendocrine Tumours: Multi-Omic and Tumour Composition Analyses.

INTRODUCTION: Small intestinal neuroendocrine tumours (siNETs) are rare neoplasms which present with low mutational burden and can be subtyped based on copy number variation (CNV). Currently, siNETs can be molecularly classified as having chromosome 18 loss of heterozygosity (18LOH), multiple CNVs (MultiCNV), or no CNVs. 18LOH tumours have better progression-free survival when compared to MultiCNV and NoCNV tumours, however, the mechanism underlying this is unknown, and clinical practice does not currently consider CNV status. METHODS: Here, we use genome-wide tumour DNA methylation (n = 54) and gene expression (n = 20 matched to DNA methylation) to better understand how gene regulation varies by 18LOH status. We then use multiple cell deconvolution methods to analyse how cell composition varies between 18LOH status and determine potential associations with progression-free survival. RESULTS: We identified 27,464 differentially methylated CpG sites and 12 differentially expressed genes between 18LOH and non-18LOH (MultiCNV + NoCNV) siNETs. Although few differentially expressed genes were identified, these genes were highly enriched with the differentially methylated CpG sites compared to the rest of the genome. We identified differences in tumour microenvironment between 18LOH and non-18LOH tumours, including CD14+ infiltration in a subset of non-18LOH tumours which had the poorest clinical outcomes. CONCLUSIONS: We identify a small number of genes which appear to be linked to the 18LOH status of siNETs, and find evidence of potential epigenetic dysregulation of these genes. We also find a potential prognostic marker for worse progression-free outcomes in the form of higher CD14 infiltration in non-18LOH siNETs.

Telemedicine use among patients with metastatic breast cancer during the COVID-19 pandemic: Differences by race, age, and region.

PURPOSE: Our objective was to describe differences in telemedicine use among women with metastatic breast cancer (mBC) by race, age, and geographic region. METHODS: This was a retrospective cohort study of women with recurrent or de novo mBC treated in US community cancer practices that initiated a new line of therapy between March 2020 and February 2021. Multivariable modified Poisson regression models were used to calculate adjusted rate ratios (RR) and robust 95% confidence intervals (CI) associated with telemedicine visits within 90 days of therapy initiation. RESULTS: Overall, among 3412 women with mBC, 751 (22%) patients had telemedicine visits following therapy initiation, with lower risks observed among older women (<50 years: 24%; 50-64 years: 22%; 65-74 years: 21%; ≥75 years: 20%). Greater telemedicine use was observed among Asian women (35%) compared to White (21%), Black (18%), and Hispanic (21%) women. Fewer telemedicine visits occurred in Southern (12%) and Midwestern (17%) states versus Northeastern (37%) or Western (36%) states. In multivariable models, women ages ≥75 years had significantly lower risks of telemedicine visits (RR = 0.76, 95% CI 0.62-0.95) compared to ages <50 years. Compared to patients in Northeastern states, women in Midwestern (RR = 0.46, 95% CI 0.37-0.57) and Southern (RR = 0.31, 95% CI 0.26-0.37) states had significantly lower risks of telemedicine visits; but not women in Western states (RR = 0.96, 95% CI 0.83-1.12). No statistically significant differences in telemedicine use were found between racial groups in overall multivariable models. CONCLUSIONS: In this study of community cancer practices, older mBC patients and those living in Southern and Midwestern states were less likely to have telemedicine visits. Preferences for communication and delivery of care may have implications for measurement of exposures and endpoints in pharmacoepidemiologic studies of cancer patients.

Health professionals' and beauty therapists' perspectives on female genital cosmetic surgery: an interview study.

BACKGROUND: Female genital cosmetic surgery (FGCS) changes the structure and appearance of healthy external genitalia. We aimed to identify discourses that help explain and rationalise FGCS and to derive from them possibilities for informing clinical education. METHODS: We interviewed 16 health professionals and 5 non-health professionals who deal with women's bodies using a study-specific semi-structured interview guide. We analysed transcripts using a three-step iterative process: identifying themes relevant to indications for FGCS, identifying the discourses within which they were positioned, and categorising and theorising discourses. RESULTS: We identified discourses that we categorised within four themes: Diversity and the Normal Vulva (diversity was both acknowledged and rejected); Indications for FGCS (Functional, Psychological, Appearance); Ethical Perspectives; and Reasons Women Seek FGCS (Pubic Depilation, Media Representation, Pornography, Advertising Regulations, Social Pressure, Genital Unfamiliarity). CONCLUSIONS: Vulvar aesthetics constitute a social construct to which medical practice and opinion contribute and by which they are influenced; education and reform need to occur on all fronts. Resources that not only establish genital diversity but also challenge limited vulvar aesthetics could be developed in consultation with women, healthcare practitioners, mental health specialists, and others with knowledge of social constructs of women's bodies.

Proof of Concept for the Use of Immersive Virtual Reality in Upper Limb Rehabilitation of Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a debilitating disease which gradually reduces motor function and mobility. Virtual reality (VR) has been successfully utilised in support of existing therapeutic approaches for many different conditions, and new innovative and experimental features could be the future of VR rehabilitation. The Quest is a new headset by Oculus, with its built-in tracking, relatively low cost, portability and lack of reliance on expensive processing heavy PCs to power it, and could be an ideal system to facilitate at-home or clinic-based upper limb rehabilitation. A hand-tracking-based rehabilitation game aimed at people with MS was developed for Oculus Quest using Unity. Two distinct games were made to replicate different types of hand exercises, piano playing for isolated finger flexion and maze tracking for coordination and arm flexion. This pilot study assesses the value of such approach along with evaluating intrinsic and extrinsic methods of providing feedback, namely, positive scoring, negative scoring and audio response. One physiotherapist and two individuals with MS were surveyed. Participant response was positive although small sample size impacts the user testing validity of the results. Future research is recommended to build off the data gathered as a pilot study and increase sample size to collect richer feedback.

Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site.

Neuroendocrine neoplasms (NENs) arise from cells of neuronal and endocrine differentiation. While they are a rare entity, an increasing proportion of patients with NEN present with metastatic disease and no evident primary site using routine imaging or histopathology. NENs of unknown primary site have a poorer prognosis, often due to the challenge of selecting appropriate evidence-based management. We review the available literature and guidelines for the management of NENs of unknown primary site including clinical features, biochemical tests, histopathology, imaging, surgical exploration and localised and systemic treatments. We also discuss novel molecular techniques currently under investigation to aid primary site identification.

The Co-design of Hand Rehabilitation Exercises for Multiple Sclerosis Using Hand Tracking System.

Multiple sclerosis (MS) often affects motor function, leading to an adverse effect on daily living. Rehabilitation is important in terms of improving mobility and activities of daily living. Virtual environments (VE) are increasing in popularity within this research area, but research in terms of VE is still rare, for both the upper and lower limb, in people with MS. Leap Motion (LM), a hand motion tracking system, has demonstrated success in stroke research but has yet to be investigated within MS. Following a co-design approach, five participants with MS discussed in a focus group (FG) their hand mobility issues, their thoughts about this technology-based rehabilitation and motivational factors. Findings were incorporated into the design of a series of gamified upper limb rehabilitation exercises, using LM, on Unity Game Engine. Three participants returned and engaged in user testing session and a FG in order to evaluate and discuss their experience. Overall participants found the proposed technology-based exercises to be engaging, immersive and a desirable approach to rehabilitation. Participant feedback underlined the usefulness of co-creation, especially in accommodating the range of motivators and user preferences. However, the study highlighted the loss of tracking of hand movements with LM as one of the limitations. Participants stated they would be likely to use this approach at home if there was a definite rehabilitation benefit and related more to visualising which muscle groups or actions they were aiming to improve.

Conscientious objection to abortion, the law and its implementation in Victoria, Australia: perspectives of abortion service providers.

BACKGROUND: In Victoria, Australia, the law regulating abortion was reformed in 2008, and a clause ('Section 8') was introduced requiring doctors with a conscientious objection to abortion to refer women to another provider. This study reports the views of abortion experts on the operation of Section 8 of the Abortion Law Reform Act in Victoria. METHODS: Nineteen semi-structured qualitative interviews were conducted with purposively selected Victorian abortion experts in 2015. Interviews explored the impact of abortion law reform on service provision, including the understanding and implementation of Section 8. Interviews were transcribed verbatim and analysed thematically. RESULTS: The majority of participants described Section 8 as a mechanism to protect women's right to abortion, rather than a mechanism to protect doctors' rights. All agreed that most doctors would not let moral or religious beliefs impact on their patients, and yet all could detail negative experiences related to Section 8. The negative experiences arose because doctors had: directly contravened the law by not referring; attempted to make women feel guilty; attempted to delay women's access; or claimed an objection for reasons other than conscience. Use or misuse of conscientious objection by Government telephone staff, pharmacists, institutions, and political groups was also reported. CONCLUSION: Some doctors are not complying with Section 8, with adverse effects on access to care for some women. Further research is needed to inform strategies for improving compliance with the law in order to facilitate timely access to abortion services.

Food perception without ingestion leads to metabolic changes and irreversible developmental arrest in C. elegans.

BACKGROUND: Developmental physiology is very sensitive to nutrient availability. For instance, in the nematode Caenorhabditis elegans, newly hatched L1-stage larvae require food to initiate postembryonic development. In addition, larvae arrested in the dauer diapause, a non-feeding state of developmental arrest that occurs during the L3 stage, initiate recovery when exposed to food. Despite the essential role of food in C. elegans development, the contribution of food perception versus ingestion on physiology has not been delineated. RESULTS: We used a pharmacological approach to uncouple the effects of food (bacteria) perception and ingestion in C. elegans. Perception was not sufficient to promote postembryonic development in L1-stage larvae. However, L1 larvae exposed to food without ingestion failed to develop upon return to normal culture conditions, instead displaying an irreversible arrest phenotype. Inhibition of gene expression during perception rescued subsequent development, demonstrating that the response to perception without feeding is deleterious. Perception altered DAF-16/FOXO subcellular localization, reflecting activation of insulin/IGF signaling (IIS). The insulin-like peptide daf-28 was specifically required, suggesting perception in chemosensory neurons, where it is expressed, regulates peptide synthesis and possibly secretion. However, genetic manipulation of IIS did not modify the irreversible arrest phenotype caused by food perception, revealing that wild-type function of the IIS pathway is not required to produce this phenotype and that other pathways affected by perception of food in the absence of its ingestion are likely to be involved. Gene expression and Nile red staining showed that food perception could alter lipid metabolism and storage. We found that starved larvae sense environmental polypeptides, with similar molecular and developmental effects as perception of bacteria. Environmental polypeptides also promoted recovery from dauer diapause, suggesting that perception of polypeptides plays an important role in the life history of free-living nematodes. CONCLUSIONS: We conclude that actual ingestion of food is required to initiate postembryonic development in C. elegans. We also conclude that polypeptides are perceived as a food-associated cue in this and likely other animals, initiating a signaling and gene regulatory cascade that alters metabolism in anticipation of feeding and development, but that this response is detrimental if feeding does not occur.

ChAMP: updated methylation analysis pipeline for Illumina BeadChips.

SUMMARY: The Illumina Infinium HumanMethylationEPIC BeadChip is the new platform for high-throughput DNA methylation analysis, effectively doubling the coverage compared to the older 450 K array. Here we present a significantly updated and improved version of the Bioconductor package ChAMP, which can be used to analyze EPIC and 450k data. Many enhanced functionalities have been added, including correction for cell-type heterogeneity, network analysis and a series of interactive graphical user interfaces. AVAILABILITY AND IMPLEMENTATION: ChAMP is a BioC package available from https://bioconductor.org/packages/release/bioc/html/ChAMP.html. CONTACT: a.teschendorff@ucl.ac.uk or s.beck@ucl.ac.uk or a.feber@ucl.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

' a one stop shop in their own community': Medical abortion and the role of general practice.

BACKGROUND: The introduction to Australia of modern medical abortion methods, which require less specialist expertise and equipment than the more traditional surgical methods, have brought an as yet unrealised potential to improve access to abortion services. AIMS: To investigate the potential for expanding the role of general practice in the provision of medical abortion in Victoria. MATERIALS AND METHODS: In 2015, in-depth interviews were conducted with 19 experts in abortion service provision in Victoria. A semi-structured interview schedule was used to guide the interviews. Interviews were transcribed verbatim and transcripts analysed thematically. RESULTS: Participants were largely very supportive of the provision of early medical abortion in general practice as a way of increasing abortion access for women, particularly in rural and regional communities. Access to abortion was seen as an essential component of women's comprehensive health care and therefore general practitioners (GPs) were perceived as ideally placed to provide this service. However, this would require development and implementation of new service models, careful consideration of GP and nurse roles, strengthening of partnerships with other health professionals and services in the community, and enhanced training, support and mentoring for clinicians. CONCLUSION: The application of these findings by relevant health services and agencies has the potential to increase provision of medical abortion services in general practice settings, better meeting the health-care needs of women seeking this service.

How do women seeking abortion choose between surgical and medical abortion? Perspectives from abortion service providers.

BACKGROUND: Depending on availability, many Australian women seeking an abortion will be faced with the choice between surgical or medical abortion. Little is known about the factors that influence Australian women's choice of method. AIM: Through the perspectives of abortion service providers, this study aimed to explore the factors that contribute to Australian women's decision to have a surgical or medical abortion. MATERIALS AND METHODS: In 2015, in-depth interviews were conducted with fifteen Victorian-based key informants (KIs) directly providing or working within a service offering medical abortion. Ten KIs were working at a service that also provided surgical abortion. Interviews were semi-structured, conducted face-to-face or over the telephone, transcribed verbatim and analysed thematically. RESULTS: KIs described varying levels of awareness of medical abortion, with poorer awareness in regional areas. When it comes to accessing information, women were informed by: their own research (often online); their own experiences and the experiences of others; and advice from health professionals. Women's reasons for choosing surgical or medical abortion range from the pragmatic (timing and location of the method, support at home) to the subjective (perceived risk, emotional impact, privacy, control, and physical ability). CONCLUSIONS: Women benefit from an alternative to surgical abortion and are well-placed to choose between the two methods, however, challenges remain to ensure that all women are enabled to make an informed choice. KIs identify the need to: promote the availability of medical abortion; address misconceptions about this method; and increase general practitioner involvement in the provision of medical abortion.

The Molecular Biology of Midgut Neuroendocrine Neoplasms.

Midgut neuroendocrine neoplasms (NENs) are one of the most common subtypes of NEN, and their incidence is rising globally. Despite being the most frequently diagnosed malignancy of the small intestine, little is known about their underlying molecular biology. Their unusually low mutational burden compared to other solid tumors and the unexplained occurrence of multifocal tumors makes the molecular biology of midgut NENs a particularly fascinating field of research. This review provides an overview of recent advances in the understanding of the interplay of the genetic, epigenetic, and transcriptomic landscape in the development of midgut NENs, a topic that is critical to understanding their biology and improving treatment options and outcomes for patients.

Heritable epigenetic variation facilitates long-term maintenance of epigenetic and genetic variation.

How genetic and phenotypic variation are maintained has long been one of the fundamental questions in population and quantitative genetics. A variety of factors have been implicated to explain the maintenance of genetic variation in some contexts (e.g. balancing selection), but the potential role of epigenetic regulation to influence population dynamics has been understudied. It is well recognized that epigenetic regulation, including histone methylation, small RNA expression, and DNA methylation, helps to define differences between cell types and facilitate phenotypic plasticity. In recent years, empirical studies have shown the potential for epigenetic regulation to also be heritable for at least a few generations without selection, raising the possibility that differences in epigenetic regulation can act alongside genetic variation to shape evolutionary trajectories. Heritable differences in epigenetic regulation that arise spontaneously are termed "epimutations." Epimutations differ from genetic mutations in 2 key ways-they occur at a higher rate and the loci at which they occur often revert back to their original state within a few generations. Here, we present an extension of the standard population genetic model with selection to incorporate epigenetic variation arising via epimutation. Our model assumes a diploid, sexually reproducing population with random mating. In addition to spontaneous genetic mutation, we included parameters for spontaneous epimutation and back-epimutation, allowing for 4 potential epialleles at a single locus (2 genetic alleles, each with 2 epigenetic states), each of which affect fitness. We then analyzed the conditions under which stable epialleles were maintained. Our results show that highly reversible epialleles can be maintained in long-term equilibrium under neutral conditions in a manner that depends on the epimutation and back-epimutation rates, which we term epimutation-back-epimutation equilibrium. On the other hand, epialleles that compensate for deleterious mutations cause deviations from the expectations of mutation-selection balance by a simple factor that depends on the epimutation and back-epimutation rates. We also numerically analyze several sets of fitness parameters for which large deviations from mutation-selection balance occur. Together, these results demonstrate that transient epigenetic regulation may be an important factor in the maintenance of both epigenetic and genetic variation in populations.

The indignities of shielding during the COVID-19 pandemic for people with sickle cell disorders: an interpretative phenomenological analysis.

This article seeks to understand the first-hand experiences of people with sickle cell, a recessively inherited blood disorder, who were identified as clinically extremely vulnerable during the COVID-19 pandemic. Part of a larger sequential mixed-methods study, this article uses a selective sample of eight qualitative semi-structured interviews, which were analysed using interpretative phenomenological analysis (IPA). The first stage of IPA focused on practical concerns participants had correlated to understanding shielding and their feelings about being identified as clinically extremely vulnerable. In a secondary stage of analysis, we examined the emotions that it brought forth and the foundations of those based on discriminations. This article adds to our theoretical understanding of embodiment and temporality with respect to chronicity and early ageing. It explains how people with sickle cell disorders have an embodied ethics of crisis and expertise. It also elucidates how people's experiences during the pandemic cannot be seen in void but illustrates ableism, racism, and ageism in society writ large.

Views of Specialist Clinicians and People With Multiple Sclerosis on Upper Limb Impairment and the Potential Role of Virtual Reality in the Rehabilitation of the Upper Limb in Multiple Sclerosis: Focus Group Study.

BACKGROUND: Finding enjoyable and effective long-term approaches to rehabilitation for improving the upper limb (UL) function of people with multiple sclerosis (MS) is challenging. Using virtual reality (VR) could be a solution to this challenge; however, there is a lack of reporting on the views of people with MS and clinicians on VR-based approaches and recommendations for games for rehabilitation. OBJECTIVE: This study aims to identify common UL problems and their related current therapeutic approaches for people with MS, and to explore the opinions of people with MS and specialist clinicians on VR and obtain suggestions for the development and design of VR games. METHODS: Separate focus groups were conducted with people with MS, recruited through the MS Society UK's research network, and clinicians, recruited through the MS Trust Therapists in MS network. A total of 10 people with MS (2 focus groups) and 8 clinicians (5 physiotherapists, 2 occupational therapists, and 1 MS nurse in 2 focus groups) were involved. The focus groups were recorded and transcriptions were analyzed using theme-based content analysis. RESULTS: People with MS commonly reported that their UL problems interfered with activities of daily living and resulted in the loss of meaningful hobbies such as writing. Many people with MS neglected UL exercise and found strategies for adapting to the UL impairments. Similarly, clinicians stated UL rehabilitation was neglected within their service and that it was challenging to find interesting treatment strategies. VR was suggested by both participant groups as a solution, as it was convenient for people with MS to access and it could provide a more engaging and disguised approach to exercise. There were shared concerns with cybersickness and disengagement with using VR approaches. Both groups agreed games should be meaningful and adaptable for users but suggested different VR activities, with clinicians suggesting games directly reflecting activities of daily living and people with MS suggesting more abstract activities. CONCLUSIONS: VR was well received by both people with MS and clinicians for UL rehabilitation. Recommendations were made for the development of VR rehabilitation games which are personalized and customizable for the varying abilities of people with MS.

Donor whole blood DNA methylation is not a strong predictor of acute graft versus host disease in unrelated donor allogeneic haematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) is used to treat many blood-based disorders and malignancies, however it can also result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed to develop a donor-specific epigenetic classifier to reduce incidence of aGVHD by improving donor selection. Genome-wide DNA methylation was assessed in a discovery cohort of 288 HCT donors selected based on recipient aGVHD outcome; this cohort consisted of 144 cases with aGVHD grades III-IV and 144 controls with no aGVHD. We applied a machine learning algorithm to identify CpG sites predictive of aGVHD. Receiver operating characteristic (ROC) curve analysis of these sites resulted in a classifier with an encouraging area under the ROC curve (AUC) of 0.91. To test this classifier, we used an independent validation cohort (n = 288) selected using the same criteria as the discovery cohort. Attempts to validate the classifier failed with the AUC falling to 0.51. These results indicate that donor DNA methylation may not be a suitable predictor of aGVHD in an HCT setting involving unrelated donors, despite the initial promising results in the discovery cohort. Our work highlights the importance of independent validation of machine learning classifiers, particularly when developing classifiers intended for clinical use.

An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo.

BACKGROUND: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan. METHODS: Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture. RESULTS: We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo. CONCLUSIONS: Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.

Dance for Multiple Sclerosis: A Systematic Review.

BACKGROUND: Evidence of the benefits of dance for people with Parkinson disease is well established, but only recently has dance been investigated for people with multiple sclerosis (MS). The purpose of this review was to identify and evaluate the feasibility and effectiveness of dance interventions to improve functional, psychosocial, and participation outcomes in people with MS. METHODS: Eight databases and gray literature sources were searched from inception to March 2022. Quantitative, mixed-methods, and qualitative studies evaluating dance interventions for adults with MS were included. Included studies were critically appraised using the Mixed Methods Appraisal Tool, and results were analyzed through a parallel-results convergent synthesis. RESULTS: Thirteen studies were included, with a total of 174 participants. Various dance genres were investigated, and only 1 mild adverse event was reported. Four to 12 weeks of twice-weekly, 60-minute dance sessions were feasible in those with mild to moderate relapsing-remitting MS. Positive effects were identified mainly in motor outcomes, with qualitative themes indicating psychological and social benefits. CONCLUSIONS: A variety of dance interventions are likely feasible and potentially beneficial for people with mild to moderate relapsing-remitting MS, but studies were generally of low-moderate quality. High-quality studies are needed to determine the effectiveness of dance interventions for people with MS, including those with progressive forms of MS and higher levels of disability.