S-Methyl Cysteine Sulfoxide Does Not Ameliorate Weight Gain or Hyperlipidemia in Mice Fed a High-Fat Diet.

SCOPE: Higher intake of cruciferous and allium vegetables is associated with lower cardiometabolic risk. Little research has investigated the cardiometabolic effects of S-methyl cysteine sulfoxide (SMCSO), found abundant in these vegetables. This study hypothesizes that SMCSO will blunt development of metabolic syndrome features in mice fed high-fat feed. METHODS AND RESULTS: Fifty C57BL/6 male mice are randomly assigned to standard-chow, high-fat, or high-fat supplemented with low-SMCSO (43 mg kg-1 body weight [BW] day-1), medium-SMCSO (153 mg kg-1 BW day-1), or high-SMCSO (256 mg kg-1 BW day-1) for 12-weeks. High-fat with SMCSO did not prevent diet-induced obesity, glucose intolerance, or hypercholesterolemia. Mice fed high-fat with SMCSO has higher hepatic lipids than mice fed standard-chow or high-fat alone. Urinary SMCSO increases at 6- and 12-weeks in the low-SMCSO group, before reducing 46% and 28% in the medium- and high-SMCSO groups, respectively, at 12-weeks, suggesting possible tissue saturation. Interestingly, two SMCSO-fed groups consume significantly more feed, without significant weight gain. Due to limitations in measuring consumed feed, caution should be taken interpreting these results. CONCLUSION: SMCSO (43-256 mg kg-1 BW day-1) does not ameliorate metabolic syndrome features in high-fat fed mice. Substantial knowledge gaps remain. Further studies should administer SMCSO separately (i.e., gavage), with metabolic studies exploring tissue levels to better understand its physiological action.

Simultaneous extraction and quantitative analysis of S-Methyl-l-Cysteine Sulfoxide, sulforaphane and glucosinolates in cruciferous vegetables by liquid chromatography mass spectrometry.

Sulfur containing compounds including glucosinolates (GLS), sulforaphane (SFN) and S-methyl-l-cysteine sulfoxide (SMCSO) have been proposed to be partly responsible for the beneficial health effects of cruciferous vegetables. As such, greater understanding of their measurements within foods is important to estimate intake in humans and to inform dietary intervention studies. Herein is described a simple and sensitive method for simultaneous analysis of 20 GLS, SFN and SMCSO by liquid chromatography mass spectrometry. Analytes were effectively retained and resolved on an Xbridge C18 column. Detection can be achieved using high resolution or unit resolution mass spectrometry; the latter making the method more applicable to large studies. Quantitative analysis using calibration standards was demonstrated for 10 GLS, SFN and SMCSO. A further 10 GLS were tentatively identified using high resolution mass spectrometry. The use of surrogate GLS standards was shown to be unreliable, with closely related GLS displaying significantly different ionisation efficiencies.

Older adults' lived experiences of physical rehabilitation for acquired brain injury and their perceptions of well-being: A qualitative phenomenological study.

AIM: To explore the experiences of older adults (65+) living with acquired brain injury regarding their sense of well-being during physical rehabilitation within the Greek Healthcare System. BACKGROUND: With the increasing ageing population and the life-changing effects of acquired brain injury, there is a need to focus on care for older people and their potential to live well. Rehabilitation systems deserve greater attention, especially in improving the well-being of those who are using them. DESIGN: A qualitative study design with a hermeneutic phenomenological approach was used. METHODS: Fourteen older adults living with acquired brain injury and undergoing physical rehabilitation in Greece were purposively sampled. Semi-structured interviews were conducted to collect data and were thematically analysed using van Manen's and Clarke and Braun's methods. The COREQ checklist was followed. RESULTS: Four themes emerged from the analysis: (1) Challenges of new life situation, (2) Seeking emotional and practical support through social interaction, (3) Identifying contextual processes of rehabilitation, (4) Realising the new self. CONCLUSIONS: The subjective experiences, intersubjective relations and contextual conditions influence the sense of well-being among older adults living with acquired brain injury, thus impacting the realisation of their new self. The study makes the notion of well-being a more tangible concept by relating it to the degree of adaptation to the new situation and the potential for older adults to create a future whilst living with acquired brain injury. RELEVANCE FOR CLINICAL PRACTICE: Identifying the factors that impact older adults' sense of well-being during rehabilitation can guide healthcare professionals in enhancing the quality of care offered and providing more dignified and humanising care. PATIENT OR PUBLIC CONTRIBUTION: Older adults living with acquired brain injury were involved in the study as participants providing the research data.

Russian Orthodox framing of abortion in online journalism on religion.

When making public statements about abortion, those serving in the Russian Orthodox Church are beholden to the legacy of the Soviet health care system and the need to connect with audiences whose religious sentiments are largely nominal. This article explores framing of abortion by clerics and others serving in the Church in 150 Russian online newspaper articles. Said framing was analyzed according to typologies from prior research of morality policy and church-state relations in Russia. The frequency with which these frames were employed was measured and cross-referenced with article genres. The results show that rational-instrumental frames rooted in secular reasoning surpassed religious argumentation and appeals for state intervention, and that frames expressing disillusionment with the Russian government outpaced positive assessments of the state.

Lorsqu'ils font des déclarations publiques sur l'avortement, les membres de l'Église orthodoxe russe ont à assumer l'héritage du système de santé soviétique et la nécessité de se rapprocher d'un public dont les sentiments religieux sont en grande partie nominaux. Cet article explore le cadrage de l'avortement par des religieux et d'autres personnes servant dans l'Église dans 150 articles de journaux en ligne russes. Ce cadrage a été analysé selon des typologies issues de recherches antérieures sur la politique de la morale et les relations entre l'Église et l'État en Russie. La fréquence d'utilisation de ces cadres a été mesurée et croisée avec les genres d'articles. Les résultats montrent que les cadres rationnels-instrumentaux ancrés dans le raisonnement séculier ont dépassé l'argumentation religieuse et les appels à l'intervention de l'État, et que les cadres exprimant une désillusion à l'égard du gouvernement russe ont dépassé les évaluations positives de l'État.

S-methyl cysteine sulfoxide and its potential role in human health: a scoping review.

Higher intakes of cruciferous and allium vegetables are associated with a lower risk of cardiometabolic-related outcomes in observational studies. Whilst acknowledging the many healthy compounds within these vegetables, animal studies indicate that some of these beneficial effects may be partially mediated by S-methyl cysteine sulfoxide (SMCSO), a sulfur-rich, non-protein, amino acid found almost exclusively within cruciferous and alliums. This scoping review explores evidence for SMCSO, its potential roles in human health and possible mechanistic action. After systematically searching several databases (EMBASE, MEDLINE, SCOPUS, CINAHL Plus Full Text, Agricultural Science), we identified 21 original research articles meeting our inclusion criteria. These were limited primarily to animal and in vitro models, with 14/21 (67%) indicating favorable anti-hyperglycemic, anti-hypercholesterolemic, and antioxidant properties. Potential mechanisms included increased bile acid and sterol excretion, altered glucose- and cholesterol-related enzymes, and improved hepatic and pancreatic ß-cell function. Raising antioxidant defenses may help mitigate the oxidative damage observed in these pathologies. Anticancer and antibacterial effects were also explored, along with one steroidogenic study. SMCSO is frequently overlooked as a potential mediator to the benefits of sulfur-rich vegetables. More research into the health benefits of SMCSO, especially for cardiometabolic and inflammatory-based pathology, is warranted. Human studies are especially needed.

An improved Erk biosensor detects oscillatory Erk dynamics driven by mitotic erasure during early development.

Extracellular signal-regulated kinase (Erk) signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role of Erk signaling dynamics in vivo, as a gradient of activated diphosphorylated Erk (P-Erk) is induced by fibroblast growth factor (Fgf) signaling at the blastula margin. Here, we describe an improved Erk-specific biosensor, which we term modified Erk kinase translocation reporter (modErk-KTR). We demonstrate the utility of this biosensor in vitro and in developing zebrafish and Drosophila embryos. Moreover, we show that Fgf/Erk signaling is dynamic and coupled to tissue growth during both early zebrafish and Drosophila development. Erk activity is rapidly extinguished just prior to mitosis, which we refer to as mitotic erasure, inducing periods of inactivity, thus providing a source of heterogeneity in an asynchronously dividing tissue. Our modified reporter and transgenic lines represent an important resource for interrogating the role of Erk signaling dynamics in vivo.

Context-dependent TGFß family signalling in cell fate regulation.

The transforming growth factor-ß (TGFß) family are a large group of evolutionarily conserved cytokines whose signalling modulates cell fate decision-making across varying cellular contexts at different stages of life. Here we discuss new findings in early embryos that reveal how, in contrast to our original understanding of morphogen interpretation, robust cell fate specification can originate from a noisy combination of signalling inputs and a broad range of signalling levels. We compare this evidence with novel findings on the roles of TGFß family signalling in tissue maintenance and homeostasis during juvenile and adult life, spanning the skeletal, haemopoietic and immune systems. From these comparisons, it emerges that in contrast to robust developing systems, relatively small perturbations in TGFß family signalling have detrimental effects at later stages in life, leading to aberrant cell fate specification and disease, for example in cancer or congenital disorders. Finally, we highlight novel strategies to target and amend dysfunction in signalling and discuss how gleaning knowledge from different fields of biology can help in the development of therapeutics for aberrant TGFß family signalling in disease.

The meaning and impact on well-being of bespoke dancing sessions for those living with Parkinson's.

PURPOSE: This paper presents qualitative research findings from the evaluation of a Parkinson's Dance well-being venture in the UK. METHODS: Qualitative data was gathered to see how bespoke dancing sessions helped people with Parkinson's (PwP) to manage their conditions and improve their lives and prospects. Principles of a participatory approach were incorporated and methods included semi-structured interviewing, researchers participant observation and an elicitation-based activity. Nineteen PwP, six carers, four dance artists and seven helpers participated in the study. RESULTS: Participating in Parkinson's Dance sessions meant that PwP could experience the possibilities to dance, develop a "can do" attitude, experience fun, enjoyment, social connection, exercise, movement to music, improvement and/or maintenance of their balance, suppleness, coordination and confidence with movement, symptoms being pushed back and ability to learn new things. CONCLUSIONS: Our findings add to the evidence-base about the benefits of dance for people experiencing Parkinson's and through novel application of the Life-world based well-being framework of K. T. Galvin and Todres (2011) we propose a theoretical basis for Parkinson's Dance as a resource for well-being. There is scope to consider application of the well-being framework to other arts activities and as the basis of an arts and well-being evaluation tool.

A Sense of Control and Wellbeing in Older People Living with Frailty: A Scoping Review.

A sense of control is important for supporting older people living with frailty to develop adaptive functioning to optimize wellbeing. This scoping review examined the literature on the sense of control and wellbeing in older people living with frailty within their everyday life and care service use. Nine databases were searched using the timeframe 2000 to 2021 to identify key ideas regarding control and wellbeing in older people with frailty. The review highlighted three major themes: a) Control as conveyed in bodily expressions and daily activities, b) Sense of control and influence of place of residence, and c) Control within health and social care relationships. Maintaining a sense of control is not only an internal feeling but is impacted by physical and social environments. Greater focus is needed on the nature of relationships between older people living with frailty and those who work alongside them, which support control and wellbeing.

Sulfur compounds: From plants to humans and their role in chronic disease prevention.

Sulfur is essential for the health of plants and is an indispensable dietary component for human health and disease prevention. Its incorporation into our food supply is heavily reliant upon the uptake of sulfur into plant tissue and our subsequent intake. Dietary requirements for sulfur are largely calculated based upon requirements for the sulfur-containing amino acids (SAA), cysteine and methionine, to meet the demands for synthesis of proteins, enzymes, co-enzymes, vitamins, and hormones. SAA are found in abundance in animal sources and are relatively low in plants. However, some plants, particularly cruciferous and allium vegetables, produce many protective sulfur-containing secondary metabolites, such as glucosinolates and cysteine sulfoxides. The variety and quantity of these sulfur-containing metabolites are extensive and their effects on human health are wide-reaching. Many benefits appear to be related to sulfur's role in redox biochemistry, protecting against uncontrolled oxidative stress and inflammation; features consistent within cardiometabolic dysfunction and many chronic metabolic diseases of aging. This narrative explores the origins and importance of sulfur, its incorporation into our food supply and dietary sources. It also explores the overarching potential of sulfur for human health, particularly around the amelioration of oxidative stress and chronic inflammation, and subsequent chronic disease prevention.

Nodal signaling establishes a competency window for stochastic cell fate switching.

Specification of the germ layers by Nodal signaling has long been regarded as an archetype of how graded morphogens induce different cell fates. However, this deterministic model cannot explain why only a subset of cells at the early zebrafish embryo margin adopt the endodermal fate, whereas their immediate neighbours, experiencing a similar signaling environment, become mesoderm. Combining pharmacology, quantitative imaging and single cell transcriptomics, we demonstrate that sustained Nodal signaling establishes a bipotential progenitor state from which cells can switch to an endodermal fate or differentiate into mesoderm. Switching is a random event, the likelihood of which is modulated by Fgf signaling. This inherently imprecise mechanism nevertheless leads to robust endoderm formation because of buffering at later stages. Thus, in contrast to previous deterministic models of morphogen action, Nodal signaling establishes a temporal window when cells are competent to undergo a stochastic cell fate switch, rather than determining fate itself.

A review of trial and real-world data applying elements of a realist approach to identify behavioural mechanisms supporting practitioners to taper opioids.

This evidence synthesis applying realist concepts and behavioural science aimed to identify behavioural mechanisms and contexts that facilitate prescribers tapering opioids. We identified relevant opioid-tapering interventions and services from a 2018 international systematic review and a 2019 England-wide survey, respectively. Interventions and services were eligible if they provided information about contexts and/or behavioural mechanisms influencing opioid-tapering success. A stakeholder group (n = 23) generated draft programme theories based around the 14 domains of the Theoretical Domains Framework. We refined these using the trial and service data. From 71 articles and 21 survey responses, 56 and 16 respectively were included, representing primary care, hospital, specialist pain facilities and prison services. We identified 6 programme theories comprising 5 behavioural mechanisms: prescribers' knowledge about how to taper; build prescribers' beliefs about capabilities to initiate tapering discussions and manage psychological consequences of tapering; perceived professional role in tapering; the environmental context enabling referral to specialists; and facilitating positive social influence by aligning patient: prescriber expectations of tapering. No interventions are addressing all 6 mechanisms supportive of tapering. Work is required to operationalise programme theories according to organisational structures and resources. An example operationalisation is combining tapering guidelines with information about local excess opioid problems and endorsing these with organisational branding. Prescribers being given the skills and confidence to initiate tapering discussions by training them in cognitive-based interventions and incorporating access to psychological and physical support in the patient pathway. Patients being provided with leaflets about the tapering process and informed about the patient pathway.

Establishment and interpretation of NODAL and BMP signaling gradients in early vertebrate development.

Transforming growth factor ß (TGF-ß) family ligands play crucial roles in orchestrating early embryonic development. Most significantly, two family members, NODAL and BMP form signaling gradients and indeed in fish, frogs and sea urchins these two opposing gradients are sufficient to organize a complete embryonic axis. This review focuses on how these gradients are established and interpreted during early vertebrate development. The review highlights key principles that are emerging, in particular the importance of signaling duration as well as ligand concentration in both gradient generation and their interpretation. Feedforward and feedback loops involving other signaling pathways are also essential for providing spatial and temporal information downstream of the NODAL and BMP signaling pathways. Finally, new data suggest the existence of buffering mechanisms, whereby early signaling defects can be readily corrected downstream later in development, suggesting that signaling gradients do not have to be as precise as previously thought.

A network of transcription factors governs the dynamics of NODAL/Activin transcriptional responses.

SMAD2, an effector of the NODAL/Activin signalling pathway, regulates developmental processes by sensing distinct chromatin states and interacting with different transcriptional partners. However, the network of factors that controls SMAD2 chromatin binding and shapes its transcriptional programme over time is poorly characterised. Here, we combine ATAC-seq with computational footprinting to identify temporal changes in chromatin accessibility and transcription factor activity upon NODAL/Activin signalling. We show that SMAD2 binding induces chromatin opening genome wide. We discover footprints for FOXI3, FOXO3 and ZIC3 at the SMAD2-bound enhancers of the early response genes, Pmepa1 and Wnt3, respectively, and demonstrate their functionality. Finally, we determine a mechanism by which NODAL/Activin signalling induces delayed gene expression, by uncovering a self-enabling transcriptional cascade whereby activated SMADs, together with ZIC3, induce the expression of Wnt3. The resultant activated WNT pathway then acts together with the NODAL/Activin pathway to regulate expression of delayed target genes in prolonged NODAL/Activin signalling conditions. This article has an associated First Person interview with the first author of the paper.

A systematic review of the qualitative literature on older individuals' experiences of care and well-being during physical rehabilitation for acquired brain injury.

AIMS: To acquire an in-depth understanding of how older individuals diagnosed with acquired brain injury (ABI) experience their well-being and care when undergoing physical rehabilitation. DESIGN: Systematic literature review. DATA SOURCES: The electronic databases of PubMed, CINAHL, APA PsycInfo, ASSIA and SCOPUS were searched from 2005 to 2020. Extensive reference checking was also conducted. REVIEW METHODS: A systematic review was conducted following PRISMA guidelines, including predominantly qualitative studies. Studies' quality was appraised using the critical apraisal skills programme (CASP) tool. RESULTS: Seventeen studies met the inclusion criteria. Following methods of thematic synthesis, four overarching interpretive themes were identified: (a) Rehabilitation processes and their impact on older individuals' well-being; (b) Identity and embodiment concerns of older individuals during rehabilitation; (c) Institutional factors affecting older individuals' care and well-being experiences; and (d) Older individuals' participation in creative activities as part of rehabilitation. CONCLUSION: Organizational and structural care deficiencies as well as health disparities can adversely impact older individuals' autonomous decision-making and goal-setting potentials. The discrepancy between older individuals' expectations and the reality of returning home along with the illusionary wish to return to a perceived normality, can further negatively affect older individuals' sense of well-being. Constructive communication, emotional support, family involvement in rehabilitation and creating a stimulating, enriching social environment can humanize and facilitate older individuals' adjustment to their new reality following ABI. IMPACT: There is a lack of qualitative research on older individuals' ABI rehabilitation experiences, especially traumatic brain injury incidents. Further study should consider patients' concerns over their involvement in decision-making and goal setting about their care. Overall, this review reveals the need to examine further the significance of humanizing care and the factors that affect older individuals' sense of well-being.

Making the invisible more visible: Reflections on practice-based humanising lifeworld-led research - existential opportunities for supporting dignity, compassion and wellbeing.

BACKGROUND: The need for dignity and compassion in healthcare is enshrined in policy, but is often difficult to enact in practice and what is precisely meant by these concepts is unclear. In this paper, we have explored theoretical underpinnings which form the basis of a lifeworld-led approach which was used in a research study to support the humanity of service providers and users alike. AIM: In this article, we share our analysis of what we have learnt after undertaking an innovative appreciative action research project with patients and staff in a stroke ward with the aim of exploring if a novel phenomenologically driven and philosophically derived humanising framework could be applied in health care. Following the research, we wanted to develop a theoretical understanding of the processes occurring during the research in order to provide a framework and language which could be used to support practical lifeworld developments in the future. We analysed the approach through Participatory and Appreciative Action Reflection. FINDINGS: As researchers, we found that the approach was underpinned by four key existential principles. The first principle was recognising a mutually arising reality rather than a reality 'out there'. The second was recognising a reality which was constantly changing rather than 'fixed'. The third was recognising that we needed to work from within, as part of a human living system rather than trying to control reality from the 'outside'. Finally, we recognised that this reality could only be accessed through human knowing, including embodied knowing rather than intellectual knowing alone. These principles challenged many of the usual ways of thinking and working within research and healthcare contexts. CONCLUSION: Understanding the processes and reality in this way gave new perspectives; enhancing our understandings and views of ourselves, what is important and most importantly what is possible in caring systems.

Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways.

The transcriptional effector SMAD4 is a core component of the TGF-ß family signaling pathways. However, its role in vertebrate embryo development remains unresolved. To address this, we deleted Smad4 in zebrafish and investigated the consequences of this on signaling by the TGF-ß family morphogens, BMPs and Nodal. We demonstrate that in the absence of Smad4, dorsal/ventral embryo patterning is disrupted due to the loss of BMP signaling. However, unexpectedly, Nodal signaling is maintained, but lacks robustness. This Smad4-independent Nodal signaling is sufficient for mesoderm specification, but not for optimal endoderm specification. Furthermore, using Optical Projection Tomography in combination with 3D embryo morphometry, we have generated a BMP morphospace and demonstrate that Smad4 mutants are morphologically indistinguishable from embryos in which BMP signaling has been genetically/pharmacologically perturbed. Smad4 is thus differentially required for signaling by different TGF-ß family ligands, which has implications for diseases where Smad4 is mutated or deleted.

A criteria-based rehabilitation program for chronic mid-portion Achilles tendinopathy: study protocol for a randomised controlled trial.

BACKGROUND: Achilles tendinopathy (AT) is a common overuse injury in running-related sports where patients experience pain and impaired function which can persist. A graded rehabilitation program has been successful in reducing pain and improving function to enable a return to sport. The aim of this study is to compare the effectiveness of a criteria-based rehabilitation program including strength and reactive strength targets, with a previously successful rehabilitation program on changes in pain and function using the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire. Secondary aims will be to assess changes in calf strength, reactive strength, and lower limb running and forward hop biomechanics over the course of a 12-week rehabilitation program, and long-term follow-up investigations. METHODS: Sixty eligible participants with chronic mid-portion AT who train in running-based sports will be included in this study. They will be randomly assigned to a group that will follow an evidence-based rehabilitation program of daily exercises with progression guided by symptoms or a group performing 3 high-intensity rehabilitation sessions per week with individualised load targets progressing to reactive strength exercises. Testing will take place at baseline, week 6 and 12. Plantar flexor peak torque will be measured using isokinetic dynamometry, reactive strength will be measured using a drop jump and lower limb biomechanical variables will be measured during a single leg forward hurdle hop test and treadmill running using 3D motion analysis. Follow-up interviews will take place at 6, 12 and 24 months after beginning the program which will assess patient participation in sport and possible re-injury. DISCUSSION: This is the first study to propose an individualised criteria-based graded rehabilitation program in patients in with chronic mid-portion Achilles tendinopathy where progression is guided by strength and reactive strength outcome measures. This study will provide a comprehensive assessment of plantar flexor strength, reactive strength and lower limb biomechanical variables in running and forward hopping with the VISA-A questionnaire as the primary outcome measure and long term post-intervention follow-up assessments performed. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT04384874 ). Registered retrospectively on April 23rd 2020.

The experience of families following traumatic brain injury in adult populations: A meta-synthesis of narrative structures.

BACKGROUND: Traumatic brain injury has a significant effect on uninjured family members. Typically, this has been examined with a focus on psychopathological outcomes including stress, depression and anxiety. However, in recent years there has been increasing interest in the subjective experiences of families post-injury leading to a plethora of qualitative studies. Therefore, an in-depth examination and synthesis of this literature is now relevant and timely. OBJECTIVE: To examine the subjective experiences of families following traumatic brain injury in adult populations in the sub/post-acute period through the synthesis of original qualitative research. DESIGN: This paper presents a meta-synthesis using Thomas and Harden's framework of 'thematic synthesis' rooted in a critical realist philosophy. DATA SOURCES: In July 2019 five electronic databases, were searched for the terms 'traumatic brain injury', 'family' and 'qualitative'. Studies were included if the primary research reported qualitative data about the subjective experiences of family members of adults with traumatic brain injury and had been published in a peer reviewed journal. Studies with mixed brain injury samples, child or adolescent traumatic brain injury or disorders of consciousness were excluded. Hand searching and citation searches were also completed. REVIEW METHODS: Two reviewers screened titles, abstracts and full text and reached consensus through critical discussion. Thirty papers were finally agreed for inclusion in this review. Each study was then assessed for relevance, resonance and rigour using the Critical Appraisal Skills Programme (CASP) tool. Line by line coding of the findings in each paper was conducted as the basis for a thematic analysis and synthesis. RESULTS: Descriptive themes were identified followed later by analytical themes. This final stage was informed by a narrative lens and from these, eight narrative functions belonging to four dimensions were identified from the subjective experiences of families post-traumatic brain injury. Specifically, these were: (1) Displacing and Anchoring; (2) Rupturing and Stabilising; (3) Isolating and Connecting; (4) Harming and Healing. CONCLUSIONS: The interpretation of the narrative functions revealed the substantial existential work involved in negotiating lives, maintaining family system equilibrium and moving forward. As such, family members have their own unique narrative needs. Despite contemporary service models built around the injured person, service providers are well placed to support families in this everyday narrative work through actively attending to narrative structures and understanding the implications of these for family experience. The study protocol was registered with PROSPERO (International prospective register of systematic reviews) in July 2018 (Registration number: CRD42018085824). Tweetable abstract: This synthesis showed the immense and invisible work required for family members to maintain family system equilibrium and negotiate their lives post-TBI.