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Article ; Online: The molecular structure of IFT-A and IFT-B in anterograde intraflagellar transport trains.

Lacey, Samuel E / Foster, Helen E / Pigino, Gaia

2023 Volume 30, Issue 5, Page(s) 584–593

Abstract: Anterograde intraflagellar transport (IFT) trains are essential for cilia assembly and maintenance. These trains are formed of 22 IFT-A and IFT-B proteins that link structural and signaling cargos to microtubule motors for import into cilia. It remains ... ...

Abstract	Anterograde intraflagellar transport (IFT) trains are essential for cilia assembly and maintenance. These trains are formed of 22 IFT-A and IFT-B proteins that link structural and signaling cargos to microtubule motors for import into cilia. It remains unknown how the IFT-A/-B proteins are arranged into complexes and how these complexes polymerize into functional trains. Here we use in situ cryo-electron tomography of Chlamydomonas reinhardtii cilia and AlphaFold2 protein structure predictions to generate a molecular model of the entire anterograde train. We show how the conformations of both IFT-A and IFT-B are dependent on lateral interactions with neighboring repeats, suggesting that polymerization is required to cooperatively stabilize the complexes. Following three-dimensional classification, we reveal how IFT-B extends two flexible tethers to maintain a connection with IFT-A that can withstand the mechanical stresses present in actively beating cilia. Overall, our findings provide a framework for understanding the fundamental processes that govern cilia assembly.
MeSH term(s)	Flagella/metabolism ; Molecular Structure ; Biological Transport ; Cilia/metabolism ; Chlamydomonas reinhardtii ; Carrier Proteins/metabolism
Chemical Substances	Carrier Proteins
Language	English
Publishing date	2023-01-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126708-X
ISSN	1545-9985 ; 1545-9993
ISSN (online)	1545-9985
ISSN	1545-9993
DOI	10.1038/s41594-022-00905-5
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Article ; Online: Beyond pGALS: the need for a multifaceted musculoskeletal decision-making tool ('pGALSplus') in community-based clinical practice.

Mercer, Vicky / Smith, Nicola / Jandial, Sharmila / Guglieri, Michela / Jones, Simon A / Foster, Helen E

Rheumatology advances in practice

2024 Volume 8, Issue 1, Page(s) rkae004

Abstract: Musculoskeletal (MSK) problems in children are common, and health-care professionals must identify those requiring onward referral. Paediatric gait, arms, legs and spine (pGALS) is an MSK assessment to discern abnormal joints. We aimed to identify MSK ... ...

Abstract	Musculoskeletal (MSK) problems in children are common, and health-care professionals must identify those requiring onward referral. Paediatric gait, arms, legs and spine (pGALS) is an MSK assessment to discern abnormal joints. We aimed to identify MSK assessments to add to pGALS (pGALSplus) to facilitate decision-making in the context of exemplar conditions representing a spectrum of MSK presentations, namely JIA, mucopolysaccharidoses, muscular dystrophy and developmental co-ordination disorder. A literature review identified 35 relevant articles that focused on clinical assessments [including questionnaire(s), physical examination and functional tests] used by health-care professionals in the context of the exemplar conditions. We provide a description of these assessments and the rationale regarding how they, or components of such tools, might be useful within pGALSplus. This process provides a foundation for further work to develop and validate pGALSplus.
Language	English
Publishing date	2024-01-23
Publishing country	England
Document type	Journal Article ; Review
ISSN	2514-1775
ISSN (online)	2514-1775
DOI	10.1093/rap/rkae004
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Article ; Online: Update the WHO EML to improve global paediatric rheumatology.

Foster, Helen E / Scott, Christiaan

Nature reviews. Rheumatology

2020 Volume 16, Issue 3, Page(s) 123

MeSH term(s)	Antirheumatic Agents/supply & distribution ; Child ; Global Health ; Humans ; Morbidity/trends ; Quality Improvement/statistics & numerical data ; Rheumatic Diseases/drug therapy ; Rheumatic Diseases/epidemiology ; Rheumatology/trends ; World Health Organization
Chemical Substances	Antirheumatic Agents
Language	English
Publishing date	2020-01-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2491532-4
ISSN	1759-4804 ; 1759-4790
ISSN (online)	1759-4804
ISSN	1759-4790
DOI	10.1038/s41584-020-0368-6
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Article ; Online: A mixed methods evaluation of the Paediatric Musculoskeletal Matters (PMM) online portfolio.

Smith, Nicola / Foster, Helen E / Jandial, Sharmila

Pediatric rheumatology online journal

2021 Volume 19, Issue 1, Page(s) 85

Abstract: Background: The PMM Portfolio is comprised of the Paediatric Musculoskeletal Matters (PMM) website, the paediatric Gait, Arms, Legs and Spine (pGALS) app and e-learning modules (ELM). The target audiences are non-specialists in paediatric ... ...

Abstract	Background: The PMM Portfolio is comprised of the Paediatric Musculoskeletal Matters (PMM) website, the paediatric Gait, Arms, Legs and Spine (pGALS) app and e-learning modules (ELM). The target audiences are non-specialists in paediatric musculoskeletal medicine. Our study aimed to evaluate impact on learning and clinical practice. Methods: Mixed methods (analytics, online survey, interviews) were used with PMM and ELM registered users and purposive sampling of users using international contacts within paediatrics and paediatric rheumatology. Data was analysed using descriptive statistics and qualitative techniques. A Paired T-Test compared self-rated confidence before and after use of the PMM Portfolio. Results: There has been wide reach for all the e-resources; PMM website (662,827 hits, 262,476 users, 214 countries, data 31st July 2020); pGALS app (12,670 downloads, 70 countries, data 31st July 2020); ELM (150 users, 30 countries, data 30th May 2019). There were 164 responses (students, trainees and health care professionals) to the survey from 25 countries. Most responders deemed the PMM Portfolio useful / very useful for their learning with significantly increased self-rated confidence in their clinical examination and reasoning skills following access to the PMM website, p = < 0.01, pGALS app, p = < 0.01 and ELM, p = < 0.01. The most popular PMM website pages related to clinical assessment techniques (especially pGALS). There was high uptake of the pGALS app and pGALS ELM especially from trainees and allied health professionals. Many clinicians reported the PMM Portfolio to be useful when used to teach others. User feedback reported that easy navigation, open access, clinical images and cases were the most valued features. User feedback highlighted need to increase awareness of the e-resources through training programmes. Conclusions: The PMM Portfolio was developed to aid learning for clinicians who are not specialists in paediatric MSK medicine. Our evaluation demonstrates wide international reach and positive feedback on learning. The PMM Portfolio is a highly useful e-resource for paediatric rheumatologists in their teaching of others to raise awareness, facilitate early diagnosis and referral of children with suspected disease. The wide user engagement informed future PMM Portfolio development and the mixed method of evaluation is transferable to other e-resources.
MeSH term(s)	Child ; Health Education ; Humans ; Internet ; Musculoskeletal Diseases
Language	English
Publishing date	2021-06-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2279468-2
ISSN	1546-0096 ; 1546-0096
ISSN (online)	1546-0096
ISSN	1546-0096
DOI	10.1186/s12969-021-00567-5
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Article ; Online: A cryo-ET survey of microtubules and intracellular compartments in mammalian axons.

Foster, Helen E / Ventura Santos, Camilla / Carter, Andrew P

The Journal of cell biology

2021 Volume 221, Issue 2

Abstract: The neuronal axon is packed with cytoskeletal filaments, membranes, and organelles, many of which move between the cell body and axon tip. Here, we used cryo-electron tomography to survey the internal components of mammalian sensory axons. We determined ... ...

Abstract	The neuronal axon is packed with cytoskeletal filaments, membranes, and organelles, many of which move between the cell body and axon tip. Here, we used cryo-electron tomography to survey the internal components of mammalian sensory axons. We determined the polarity of the axonal microtubules (MTs) by combining subtomogram classification and visual inspection, finding MT plus and minus ends are structurally similar. Subtomogram averaging of globular densities in the MT lumen suggests they have a defined structure, which is surprising given they likely contain the disordered protein MAP6. We found the endoplasmic reticulum in axons is tethered to MTs through multiple short linkers. We surveyed membrane-bound cargos and describe unexpected internal features such as granules and broken membranes. In addition, we detected proteinaceous compartments, including numerous virus-like capsid particles. Our observations outline novel features of axonal cargos and MTs, providing a platform for identification of their constituents.
MeSH term(s)	Animals ; Axons/metabolism ; Axons/ultrastructure ; Capsid/metabolism ; Capsid/ultrastructure ; Cell Compartmentation ; Cryoelectron Microscopy ; Cytoskeleton/metabolism ; Cytoskeleton/ultrastructure ; Drosophila melanogaster/metabolism ; Drosophila melanogaster/ultrastructure ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum/ultrastructure ; Ganglia, Spinal/metabolism ; Intracellular Space/metabolism ; Mammals/metabolism ; Microtubules/metabolism ; Microtubules/ultrastructure ; Multivariate Analysis ; Nerve Tissue Proteins/metabolism ; Tomography
Chemical Substances	Nerve Tissue Proteins
Language	English
Publishing date	2021-12-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202103154
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Article ; Online: 'Snakes & Ladders': factors influencing access to appropriate care for children and young people with suspected juvenile idiopathic arthritis - a qualitative study.

Rapley, Tim / May, Carl / Smith, Nicola / Foster, Helen E

Pediatric rheumatology online journal

2021 Volume 19, Issue 1, Page(s) 43

Abstract: Background: Many children and young people with juvenile idiopathic arthritis (JIA) experience delay in diagnosis and access to right care. The reasons for delay are multi-factorial and influenced by patient and family, clinician and organisational ... ...

Abstract	Background: Many children and young people with juvenile idiopathic arthritis (JIA) experience delay in diagnosis and access to right care. The reasons for delay are multi-factorial and influenced by patient and family, clinician and organisational factors. Our aim was to explore the experiences of care, from initial symptoms to initial referral to paediatric rheumatology. Methods: We analysed one-to-one and joint qualitative interviews with families of children with JIA (n = 36) presenting to a regional paediatric rheumatology service in the UK. We interviewed 51 family members (including mothers, fathers, patients, grandmothers and an aunt) and 10 health professionals (including orthopaedic surgeons, paediatricians, paediatric immunologist, General Practitioner and nurse) and a teacher involved in the care pathway of these JIA patients. Interviews were audio-recorded and analysed according to the standard procedures of rigorous qualitative analysis - coding, constant comparison, memoing and deviant case analysis. Results: The median age of the children was 6 years old (range 1-17), with a spread of JIA subtypes. The median reported time to first PRh MDT visit from symptom onset was 22 weeks (range 4-364 weeks). Three key factors emerged in the pathways to appropriate care: (i) the persistence of symptoms (e.g. 'change' such as limp or avoidance of previously enjoyed activities); (ii) the persistence of parents help-seeking actions (e.g. repeat visits to primary and hospital care with concern that their child is not 'normal'; iii) the experience and skills of health professionals resulting in different trajectories (e.g. no-real-concern-at-this-point or further-investigation-is-required). JIA was more likely to be considered amongst health practitioner if they had prior experiences of a child with JIA (moreso with a 'protracted pathway') or exposure to paediatric rheumatology in their training. Conversely JIA was more likely to be overlooked if the child had comorbidity such as learning disability or a chronic illness. Conclusions: Care pathways are often 'turbulent' prior to a diagnosis of JIA with physical and emotional distress for families. There is need for greater awareness about JIA amongst health care professionals and observations of change (from family and non-health care professionals such as teachers) are key to trigger referral for paediatric rheumatology opinion.
MeSH term(s)	Adolescent ; Arthritis, Juvenile/therapy ; Child ; Child, Preschool ; Female ; Health Services Accessibility ; Humans ; Infant ; Male ; Qualitative Research
Language	English
Publishing date	2021-03-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2279468-2
ISSN	1546-0096 ; 1546-0096
ISSN (online)	1546-0096
ISSN	1546-0096
DOI	10.1186/s12969-021-00531-3
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Article: A Mixed Method Study: Defining the Core Learning Needs of Nurses Delivering Care to Children and Young People with Rheumatic Disease to Inform Paediatric Musculoskeletal Matters, a Free Online Educational Resource.

Smith, Nicola / English, Christine / Davies, Barbara / Wyllie, Ruth / Foster, Helen E / Rapley, Tim

Children (Basel, Switzerland)

2022 Volume 9, Issue 6

Abstract: Children and young people with rheumatic diseases and their families are often supported by nurses who may not have had specialist training in paediatric rheumatology. The purpose of our study was to establish the core learning needs of all nurses who ... ...

Abstract	Children and young people with rheumatic diseases and their families are often supported by nurses who may not have had specialist training in paediatric rheumatology. The purpose of our study was to establish the core learning needs of all nurses who may encounter these children and young people in their clinical practice and use this information to inform the content and format of Paediatric Musculoskeletal Matters Nursing (PMM-Nursing) Engagement with nurses working in different roles and with various levels of experience in musculoskeletal medicine informed these learning needs and PMM-Nursing content. Mixed methods ascertained learning needs under the following themes: (1) Need for increased awareness about rheumatic disease; (2) Impact of experience and nursing role; (3) Need for increased knowledge about rheumatic disease and management. In addition, our methods informed design components for an impactful learning and information resource. Representatives from stakeholder nursing groups, social sciences, and web development used this information to create a suitable framework for PMM-Nursing. The content of PMM-Nursing is now live and freely available.
Language	English
Publishing date	2022-06-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children9060844
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Article ; Online: An iceberg I can't handle: a qualitative inquiry on perceptions towards paediatric rheumatology among healthcare workers in Kenya.

Migowa, Angela / Bernatsky, Sasha / Ngugi, Anthony / Foster, Helen E / Muriuki, Peter / Lusambili, Adelaide / Luchters, Stanley

Pediatric rheumatology online journal

2023 Volume 21, Issue 1, Page(s) 6

Abstract: Background: Delay in diagnosis and access to specialist care is a major problem for many children and young people with rheumatic disease in sub-Saharan Africa. Most children with symptoms of rheumatic disease present to non-specialists for care. There ... ...

Abstract	Background: Delay in diagnosis and access to specialist care is a major problem for many children and young people with rheumatic disease in sub-Saharan Africa. Most children with symptoms of rheumatic disease present to non-specialists for care. There is an urgent need to understand and scale-up paediatric rheumatology knowledge and skills amongst non-specialist healthcare workers to promote early diagnosis, prompt referral, and management. Purpose: We evaluated the knowledge, attitudes and practices towards diagnosis and care of paediatric rheumatology patients among health care workers in Kenya. Methods: We conducted 12 focus group discussions with clinical officers (third-tier community health workers) nurses, general practitioners and paediatricians across 6 regions in Kenya. Interviews were conducted on zoom, audio-recorded, transcribed, and analysed using NVIVO software. Results: A total of 68 individuals participated; 11 clinical officers, 12 nurses, 10 general practitioners, 27 paediatricians and 7 others. Most (n = 53) were female, and the median age was 36 years (range 31-40 years). Fifty per cent of the participants (34 of 68) worked in public health facilities. Our study revealed gaps in knowledge of paediatric rheumatology amongst healthcare workers which contributes to delayed diagnosis and poor management. Healthcare workers reported both positive and negative attitudes towards diagnosis and care of paediatric rheumatology patients. Perceived complexity and lack of knowledge in diagnosis, management and lack of health system clinical pathways made all cadres of healthcare workers feel helpless, frustrated, inadequate and incompetent to manage paediatric rheumatology patients. Positive attitudes arose from a perceived feeling that paediatric rheumatology patients pose unique challenges and learning opportunities. Conclusion: There is an urgent need to educate healthcare workers and improve health systems to optimize clinical care for paediatric rheumatology patients.
MeSH term(s)	Child ; Humans ; Female ; Adolescent ; Adult ; Male ; Rheumatology ; Kenya ; Qualitative Research ; Rheumatic Diseases/diagnosis ; Rheumatic Diseases/therapy ; Community Health Workers
Language	English
Publishing date	2023-01-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2279468-2
ISSN	1546-0096 ; 1546-0096
ISSN (online)	1546-0096
ISSN	1546-0096
DOI	10.1186/s12969-023-00790-2
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Article ; Online: Bridging gaps: a qualitative inquiry on improving paediatric rheumatology care among healthcare workers in Kenya.

Migowa, Angela / Bernatsky, Sasha / Ngugi, Anthony K / Foster, Helen E / Muriuki, Peterrock / Riang'a, Roselyter M / Luchters, Stanley

Pediatric rheumatology online journal

2023 Volume 21, Issue 1, Page(s) 144

Abstract: Background: Due to the paucity of paediatric rheumatologists in Kenya, it is paramount that we explore strategies to bridge clinical care gaps for paediatric rheumatology patients in order to promote early diagnosis, prompt referral, and optimal ... ...

Abstract	Background: Due to the paucity of paediatric rheumatologists in Kenya, it is paramount that we explore strategies to bridge clinical care gaps for paediatric rheumatology patients in order to promote early diagnosis, prompt referral, and optimal management. Purpose: To identify proposed interventions which can improve the ability of non-specialist healthcare workers to care for paediatric rheumatology patients across Kenya. Methods: We conducted 12 focus group discussions with clinical officers (community physician assistants), nurses, general practitioners and paediatricians across six regions in Kenya. Interviews were conducted, audio-recorded, transcribed verbatim, and analysed using MAXQDA 2022.2 software. Results: A total of 68 individuals participated in the study; 11 clinical officers, 12 nurses, 10 general practitioners, 27 paediatricians and eight other healthcare workers. Proposed patient interventions included patient education and psychosocial support. Community interventions were outreach awareness campaigns, mobilising financial support for patients' care, mobilising patients to access diagnostic and therapeutic interventions. Healthcare worker interventions include diagnostic, management, and referral guidelines, as well as research and educational interventions related to symptom identification, therapeutic strategies, and effective patient communication skills. In addition, it was highlighted that healthcare systems should be bolstered to improve insurance coverage and access to integrated multi-disciplinary clinical care. Conclusions: Study participants were able to identify potential initiatives to improve paediatric rheumatology care in Kenya. Additional efforts are underway to design, implement and monitor the impact of some of these potential interventions.
MeSH term(s)	Child ; Humans ; Rheumatology ; Kenya ; Health Personnel ; Qualitative Research ; Focus Groups
Language	English
Publishing date	2023-12-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2279468-2
ISSN	1546-0096 ; 1546-0096
ISSN (online)	1546-0096
ISSN	1546-0096
DOI	10.1186/s12969-023-00935-3
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Article ; Online: Improving musculoskeletal health for children and young people - A 'call to action'.

Foster, Helen E / Scott, Christiaan / Tiderius, Carl J / Dobbs, Matthew B

Best practice & research. Clinical rheumatology

2020 Volume 34, Issue 5, Page(s) 101566

Abstract: This chapter describes the musculoskeletal (MSK) context in children and young people as an important contributor to the global non-communicable disease burden. Through selected MSK conditions, we describe the impact on patients, families and communities ...

Abstract	This chapter describes the musculoskeletal (MSK) context in children and young people as an important contributor to the global non-communicable disease burden. Through selected MSK conditions, we describe the impact on patients, families and communities and highlight the challenges that need to be addressed. We focus on opportunities for better working together and describe exemplar initiatives to raise awareness, workforce capacity building, models of care and research agendas to have a greater global context.
MeSH term(s)	Adolescent ; Child ; Humans ; Musculoskeletal Diseases/diagnosis ; Musculoskeletal Diseases/epidemiology ; Musculoskeletal Diseases/therapy ; Workforce
Keywords	covid19
Language	English
Publishing date	2020-07-26
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2052323-3
ISSN	1532-1770 ; 1521-6942
ISSN (online)	1532-1770
ISSN	1521-6942
DOI	10.1016/j.berh.2020.101566
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