Search

Mitochondrial membrane potential directly powers many critical functions of mitochondria, including ATP production, mitochondrial protein import, and metabolite transport. Its loss is a cardinal feature of aging and mitochondrial diseases, and cells closely monitor membrane potential as an indicator of mitochondrial health. Given its central importance, it is logical that cells would modulate mitochondrial membrane potential in response to demand and environmental cues, but there has been little exploration of this question. We report that loss of the Sit4 protein phosphatase in yeast increases mitochondrial membrane potential, both by inducing the electron transport chain and the phosphate starvation response. Indeed, a similarly elevated mitochondrial membrane potential is also elicited simply by phosphate starvation or by abrogation of the Pho85-dependent phosphate sensing pathway. This enhanced membrane potential is primarily driven by an unexpected activity of the ADP/ATP carrier. We also demonstrate that this connection between phosphate limitation and enhancement of mitochondrial membrane potential is observed in primary and immortalized mammalian cells as well as in Drosophila. These data suggest that mitochondrial membrane potential is subject to environmental stimuli and intracellular signaling regulation and raise the possibility for therapeutic enhancement of mitochondrial function even in defective mitochondria.

Abstract Background and objective Aurora kinase A (AURKA) is reported to be overexpressed in breast cancer. In addition to its role in regulating cell cycle and mitosis, studies have reported AURKA involvements in oncogenic signaling in suppressing BRCA1 and BRCA2. We aimed to characterize AURKA protein and mRNA expression in a breast cancer cohort of the young, investigating its relation to clinico-pathologic features and survival, and exploring age-related AURKA-associated biological processes. Methods Aurora kinase A immunohistochemical staining was performed on tissue microarrays of primary tumors from an in-house breast cancer cohort (n = 355) with information on clinico-pathologic data, molecular markers, and long and complete follow-up. A subset of the in-house cohort (n = 127) was studied by the NanoString Breast Cancer 360 expression panel for exploration of mRNA expression. METABRIC cohorts

Abstract Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like Sertoli cells, and occasionally focal spermatogenesis. Here, we show that the immature-like Sertoli cells highly expressed XIST and had two X-chromosomes, while the mature Sertoli cells lacked XIST expression and had only one X-chromosome. Sertoli cells supporting focal spermatogenesis also lacked XIST expression and the additional X-chromosome, while the spermatogonia expressed XIST despite having only one X-chromosome. XIST was expressed in Sertoli cells until puberty, where a gradual loss was observed. Our results suggest that a micro-mosaic loss of the additional X-chromosome is needed for Sertoli cells to mature and to allow focal spermatogenesis.

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease after Alzheimer’s disease. Cognitive impairments are frequent non-motor symptoms in PD and have a significant impact on everyday life and well-being. Still, rehabilitation services for people with PD predominantly target motor symptoms. Drawing on data from a national Danish survey, this study aimed to determine significant differences among people living with PD with or without perceived cognitive impairments regarding (1) contact with different healthcare professionals, and (2) unmet needs for rehabilitation services. Data were analyzed based on whether the person with PD perceived cognitive impairments or not. Statistically significant differences between results for PD patients with and without cognitive impairments were calculated. Data on 6711 individuals with PD were included in the study. Respondents’ mean age was 73.5 years, and 31% of them were experiencing cognitive impairments. Significantly more people with PD and cognitive impairments were in contact with almost all professionals compared to those without cognitive impairments. However, individuals experiencing cognitive impairments were less often in contact with the professions most experienced in cognitive rehabilitation.

Summary: Background: Presence of nerves in tumours, by axonogenesis and neurogenesis, is gaining increased attention for its impact on cancer initiation and development, and the new field of cancer neuroscience is emerging. A recent study in prostate cancer suggested that the tumour microenvironment may influence cancer progression by recruitment of Doublecortin (DCX)-expressing neural progenitor cells (NPCs). However, the presence of such cells in human breast tumours has not been comprehensively explored. Methods: Here, we investigate the presence of DCX-expressing cells in breast cancer stromal tissue from patients using Imaging Mass Cytometry. Single-cell analysis of 372,468 cells across histopathological images of 107 breast cancers enabled spatial resolution of neural elements in the stromal compartment in correlation with clinicopathological features of these tumours. In parallel, we established a 3D in vitro model mimicking breast cancer neural progenitor-innervation and examined the two cell types as they co-evolved in co-culture by using mass spectrometry-based global proteomics. Findings: Stromal presence of DCX + cells is associated with tumours of higher histological grade, a basal-like phenotype, and shorter patient survival in tumour tissue from patients with breast cancer. Global proteomics analysis revealed significant changes in the proteomic landscape of both breast cancer cells and neural progenitors in co-culture. Interpretation: These results support that neural involvement plays an active role in breast cancer and warrants further studies on the relevance of nerve elements for tumour progression. Funding: This work was supported by the Research Council of Norway through its Centre of Excellence funding scheme, project number 223250 (to L.A.A), the Norwegian Cancer Society (to L.A.A. and H.V.), the Regional Health Trust Western Norway (Helse Vest) (to L.A.A.), the Meltzer Research Fund (to H.V.) and the National Institutes of Health (NIH)/NIGMS grant R01 GM132129 (to J.A.P.).

Introduction Patients with lumbar spinal stenosis may have poor balance, decreased physical function and problems maintaining physical activity levels due to radiculopathy. Decompressive surgery is often indicated if conservative management fails to achieve a satisfactory clinical outcome. While surgical management has proven effective at treating radiculopathy, and patients report increased physical function postoperatively, objective measures of postural control and physical activity remain sparse. This study aims to investigate the effects of decompressive surgery on postural control and activity levels of elderly patients with lumbar spinal stenosis using objective measurements.Methods and analysis This is a 24-month, multicentre, prospective cohort study. Patients ≥65 years of age with MRI-verified symptomatic lumbar central canal stenosis will be recruited from two separate inclusion centres, and all participants will undergo decompressive surgery. Preoperative data are collected up to 3 months before surgery, with follow-up data collected at 3, 6, 12 and 24 months postoperatively. Postural control measurements are performed using the Wii Balance Board, mini Balance Evaluation Systems Test and Tandem test, and data concerning physical activity levels are collected using ActiGraph wGT3X-BT accelerometers. Patient-reported outcomes regarding quality-of-life and physical function are collected from the EuroQol-5D, 36-Item Short Form Health Survey and Zurich Claudication Questionnaire. Primary outcomes are the change in the sway area of centre of pressure and total activity counts per day from baseline to follow-up at 24 months. A sample size of 80 participants has been calculated.Ethics and dissemination The study has been approved by the Regional Ethics Committee of Region Zealand (ID EMN-2022-08110) and the Danish Data Protection Agency (ID REG-100-2022). Written informed consent will be required from all participants before enrolment. All results from the study, whether positive, negative or inconclusive, will be published in international peer-reviewed journals and presented at national and international scientific meetings. Study findings will be further disseminated through national patient associations.Trial registration numbers NCT06075862 and NCT06057428.

Background In occupational therapy and -science positive aspects of occupation are highlighted. Recently, this discourse has been questioned, as it might leave out occupations – referred to as unilluminated occupations (UO) – that hold value to people, without fitting the positive ideal.Aim To translate UO into Danish and to examine how occupational therapists (OTs) view and address UO.Methods A survey developed in USA was translated into Danish and distributed to OTs across Denmark. We added questions on the Danish wording of the concepts, including a content validity index (CVI). Data was subjected to a descriptive analysis.Results The respondents agreed that OTs must include examining the purpose and meaning of UO, however without having a responsibility to support performing these UO. The applied translation: high risk (risikable), unhealthy (usunde), unethical (uetiske), immoral (umoralske), and unacceptable (uacceptable) were deemed relevant in Danish, established by CVIs on 0.72–0.90.Conclusions and significance Although most respondents were positive towards examining and acknowledging clients’ purpose and meaning of UO, no clear consensus when addressing UO in interventions was seen. Further research might shed light on ways to approach UO both in assessment and intervention. The Danish terms appeared relevant to encompass UO.

Imaging Mass Cytometry (IMC) is a novel, and formidable high multiplexing imaging method emerging as a promising tool for in-depth studying of tissue architecture and intercellular communications. Several studies have reported various IMC antibody panels mainly focused on studying the immunological landscape of the tumor microenvironment (TME). With this paper, we wanted to address cancer associated fibroblasts (CAFs), a component of the TME very often underrepresented and not emphasized enough in present IMC studies. Therefore, we focused on the development of a comprehensive IMC panel that can be used for a thorough description of the CAF composition of breast cancer TME and for an in-depth study of different CAF niches in relation to both immune and breast cancer cell communication. We established and validated a 42 marker panel using a variety of control tissues and rigorous quantification methods. The final panel contained 6 CAF-associated markers (aSMA, FAP, PDGFRa, PDGFRb, YAP1, pSMAD2). Breast cancer tissues (4 cases of luminal, 5 cases of triple negative breast cancer) and a modified CELESTA pipeline were used to demonstrate the utility of our IMC panel for detailed profiling of different CAF, immune and cancer cell phenotypes.

Abstract Background DNA methylation biomarkers in circulating cell-free DNA (cfDNA) have great clinical potential for cancer management. Most methods for DNA methylation analysis require bisulfite conversion, causing DNA degradation and loss. This is particularly challenging for cfDNA, which is naturally fragmented and normally present in low amounts. The aim of the present study was to identify an optimal combination of cfDNA isolation and bisulfite conversion kits for downstream analysis of DNA methylation biomarkers in plasma. Results Of the five tested bisulfite conversion kits (EpiJET Bisulfite Conversion Kit, EpiTect Plus DNA Bisulfite Kit (EpiTect), EZ DNA Methylation-Direct Kit, Imprint DNA Modification Kit (Imprint) and Premium Bisulfite Kit), the highest and lowest DNA yield and recovery were achieved using the EpiTect kit and the Imprint kit, respectively, with more than double the amount of DNA for the EpiTect kit. Of the three tested cfDNA isolation kits (Maxwell RSC ccfDNA Plasma Kit, QIAamp Circulating Nucleic Acid Kit (CNA) and QIAamp MinElute ccfDNA Mini Kit), the CNA kit yielded around twice as much cfDNA compared to the two others kits, although with more high molecular weight DNA present. When comparing various combinations of cfDNA isolation kits and bisulfite conversion kits, the CNA kit and the EpiTect kit were identified as the best-performing combination, resulting in the highest yield of bisulfite converted cfDNA from normal plasma, as measured by droplet digital PCR (ddPCR). As a proof of principle, this kit combination was used to process plasma samples from 13 colorectal cancer patients for subsequent ddPCR methylation analysis of BCAT1 and IKZF1. Methylation of BCAT1 and/or IKZF1 was identified in 6/10 (60%) stage IV patients and 1/3 (33%) stage III patients. Conclusions Based on a thorough evaluation of five bisulfite conversion kits and three cfDNA isolation kits, both individually and in combination, the CNA kit and the EpiTect kit were identified as the best-performing kit combination, with highest DNA yield and recovery across a range of DNA input amounts. The combination was successfully used for detection of clinically relevant DNA methylation biomarkers in plasma from cancer patients.

Adolescents with intellectual disability experience psychological and social challenges in their transition to adulthood. Knowledge about the diagnosis and insight into own strengths and difficulties can help them manage the limitations and barriers they face, but suitable interventions with this purpose are scarce. The present paper presents a psychoeducational group intervention, The Super Control Project, for adolescents (15-17 years old) with mild intellectual disability (n = 23) and their parents. In a pre-post design, adolescent outcome data was obtained through teacher and parent questionnaires, and interviews with the adolescents. Parents and adolescents also evaluated the interventions' usefulness. Results indicated positive impact on participants' understanding of the diagnosis, managing of everyday challenges, and social networking. The intervention seemed to fit the participants' needs and abilities. The study encourages further implementation and rigorous evaluation.

Abstract Cancers are often associated with hypoxia and metabolic reprogramming, resulting in enhanced tumor progression. Here, we aim to study breast cancer hypoxia responses, focusing on secreted proteins from low-grade (luminal-like) and high-grade (basal-like) cell lines before and after hypoxia. We examine the overlap between proteomics data from secretome analysis and laser microdissected human breast cancer stroma, and we identify a 33-protein stromal-based hypoxia profile (33P) capturing differences between luminal-like and basal-like tumors. The 33P signature is associated with metabolic differences and other adaptations following hypoxia. We observe that mRNA values for 33P predict patient survival independently of molecular subtypes and basic prognostic factors, also among low-grade luminal-like tumors. We find a significant prognostic interaction between 33P and radiation therapy.

Mitochondrial membrane potential directly powers many critical functions of mitochondria, including ATP production, mitochondrial protein import, and metabolite transport. Its loss is a cardinal feature of aging and mitochondrial diseases, and cells closely monitor membrane potential as an indicator of mitochondrial health. Given its central importance, it is logical that cells would modulate mitochondrial membrane potential in response to demand and environmental cues, but there has been little exploration of this question. We report that loss of the Sit4 protein phosphatase in yeast increases mitochondrial membrane potential, both by inducing the electron transport chain and the phosphate starvation response. Indeed, a similarly elevated mitochondrial membrane potential is also elicited simply by phosphate starvation or by abrogation of the Pho85-dependent phosphate sensing pathway. This enhanced membrane potential is primarily driven by an unexpected activity of the ADP/ATP carrier. We also demonstrate that this connection between phosphate limitation and enhancement of mitochondrial membrane potential is observed in primary and immortalized mammalian cells as well as in Drosophila. These data suggest that mitochondrial membrane potential is subject to environmental stimuli and intracellular signaling regulation and raise the possibility for therapeutic enhancement of mitochondrial function even in defective mitochondria.

Abstract Background Phloem-feeding aphids deprive plants of assimilates, but mostly manage to avoid causing the mechanical tissue damage inflicted by chewing insects. Nevertheless, jasmonate signalling that is induced by infestation is important in mediating resistance to phloem feeders. Aphid attack induces the jasmonic acid signalling pathway, but very little is known about the specific impact jasmonates have on the expression of genes that respond to aphid attack. Results We have evaluated the function that jasmonates have in regulating Arabidopsis thaliana responses to cabbage aphid (Brevicoryne brassicae) by conducting a large-scale transcriptional analysis of two mutants: aos, which is defective in jasmonate production, and fou2, which constitutively induces jasmonic acid biosynthesis. This analysis enabled us to determine which genes' expression patterns depend on the jasmonic acid signalling pathway. We identified more than 200 genes whose expression in non-challenged plants depended on jasmonate levels and more than 800 genes that responded differently to infestation in aos and fou2 plants than in wt. Several aphid-induced changes were compromised in the aos mutant, particularly genes connected to regulation of transcription, defence responses and redox changes. Due to jasmonate-triggered pre-activation of fou2, its transcriptional profile in non-challenged plants mimicked the induction of defence responses in wt. Additional activation of fou2 upon aphid attack was therefore limited. Insect fitness experiments revealed that the physiological consequences of fou2 mutation contributed to more effective protection against B. brassicae. However, the observed resistance of the fou2 mutant was based on antibiotic rather than feeding deterrent properties of the mutant as indicated by an analysis of aphid feeding behaviour. Conclusions Analysis of transcriptional profiles of wt, aos and fou2 plants revealed that the expression of more than 200 genes is dependent on jasmonate status, regardless of external stimuli. Moreover, the aphid-induced response of more than 800 transcripts is regulated by jasmonate signalling. Thus, in plants lacking jasmonates many of the defence-related responses induced by infestation in wt plants are impaired. Constant up-regulation of jasmonate signalling as evident in the fou2 mutant causes reduction in aphid population growth, likely as a result of antibiotic properties of fou2 plants. However, aos mutation does not seem to affect aphid performance when the density of B. brassicae populations on plants is low and aphids are free to move around.

Abstract Background Glutamate plays a central position in the synthesis of a variety of organic molecules in plants and is synthesised from nitrate through a series of enzymatic reactions. Glutamate synthases catalyse the last step in this pathway and two types are present in plants: NADH- or ferredoxin-dependent. Here we report a genome wide microarray analysis of the transcriptional reprogramming that occurs in leaves and roots of the A. thaliana mutant glu1-2 knocked-down in the expression of Fd-GOGAT1 (GLU1; At5g04140), one of the two genes of A. thaliana encoding ferredoxin-dependent glutamate synthase. Results Transcriptional profiling of glu1-2 revealed extensive changes with the expression of more than 5500 genes significantly affected in leaves and nearly 700 in roots. Both genes involved in glutamate biosynthesis and transformation are affected, leading to changes in amino acid compositions as revealed by NMR metabolome analysis. An elevated glutamine level in the glu1-2 mutant was the most prominent of these changes. An unbiased analysis of the gene expression datasets allowed us to identify the pathways that constitute the secondary response of an FdGOGAT1/GLU1 knock-down. Among the most significantly affected pathways, photosynthesis, photorespiratory cycle and chlorophyll biosynthesis show an overall downregulation in glu1-2 leaves. This is in accordance with their slight chlorotic phenotype. Another characteristic of the glu1-2 transcriptional profile is the activation of multiple stress responses, mimicking cold, heat, drought and oxidative stress. The change in expression of genes involved in flavonoid biosynthesis is also revealed. The expression of a substantial number of genes encoding stress-related transcription factors, cytochrome P450 monooxygenases, glutathione S-transferases and UDP-glycosyltransferases is affected in the glu1-2 mutant. This may indicate an induction of the detoxification of secondary metabolites in the mutant. Conclusions Analysis of the glu1-2 transcriptome reveals extensive changes in gene expression profiles revealing the importance of Fd-GOGAT1, and indirectly the central role of glutamate, in plant development. Besides the effect on genes involved in glutamate synthesis and transformation, the glu1-2 mutant transcriptome was characterised by an extensive secondary response including the downregulation of photosynthesis-related pathways and the induction of genes and pathways involved in the plant response to a multitude of stresses.

Carotenoids are pigments that have a range of functions in human health. The carotenoid diatoxanthin is suggested to have antioxidant, anti-inflammatory and chemo-preventive properties. Diatoxanthin is only produced by a few groups of microalgae, where it functions in photoprotection. Its large-scale production in microalgae is currently not feasible. In fact, rapid conversion into the inactive pigment diadinoxanthin is triggered when cells are removed from a high-intensity light source, which is the case during large-scale harvesting of microalgae biomass. Zeaxanthin epoxidase (ZEP) 2 and/or ZEP3 have been suggested to be responsible for the back-conversion of high-light accumulated diatoxanthin to diadinoxanthin in low-light in diatoms. Using CRISPR/Cas9 gene editing technology, we knocked out the ZEP2 and ZEP3 genes in the marine diatom Phaeodactylum tricornutum to investigate their role in the diadinoxanthin–diatoxanthin cycle and determine if one of the mutant strains could function as a diatoxanthin production line. Light-shift experiments proved that ZEP3 encodes the enzyme converting diatoxanthin to diadinoxanthin in low light. Loss of ZEP3 caused the high-light-accumulated diatoxanthin to be stable for several hours after the cultures had been returned to low light, suggesting that zep3 mutant strains could be suitable as commercial production lines of diatoxanthin.

The family of chloroplast ALBINO3 (ALB3) proteins function in the insertion and assembly of thylakoid membrane protein complexes. Loss of ALB3b in the marine diatom Phaeodactylum tricornutum leads to a striking change of cell color from the normal brown to green. A 75% decrease of the main fucoxanthin-chlorophyll a/c-binding proteins was identified in the alb3b strains as the cause of changes in the spectral properties of the mutant cells. The alb3b lines exhibit a truncated light-harvesting antenna phenotype with reduced amounts of light-harvesting pigments and require a higher light intensity for saturation of photosynthesis. Accumulation of photoprotective pigments and light-harvesting complex stress-related proteins was not negatively affected in the mutant strains, but still the capacity for nonphotochemical quenching was lower compared with the wild type. In plants and green algae, ALB3 proteins interact with members of the chloroplast signal recognition particle pathway through a Lys-rich C-terminal domain. A novel conserved C-terminal domain was identified in diatoms and other stramenopiles, questioning if ALB3b proteins have the same interaction partners as their plant/green algae homologs.

A third vaccine dose is often required to achieve potent, long-lasting immune responses. We investigated the effect of three 8-μg doses of CVnCoV, CureVac’s severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate containing sequence-optimized unmodified mRNA encoding the spike (S) glycoprotein, administered at 0, 4, and 28 weeks, on immune responses in rhesus macaques. After the third dose, S-specific binding and neutralizing antibodies increased 50-fold compared with post-dose 2 levels, with increased responses also evident in the lower airways and against the SARS-CoV-2 B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) variants. Enhanced binding affinity of serum antibodies after the third dose correlated with higher somatic hypermutation in S-specific B cells, corresponding with improved binding properties of monoclonal antibodies expressed from isolated B cells. Administration of low-dose mRNA led to fewer cells expressing antigen in vivo at the injection site and in the draining lymph nodes compared with a 10-fold higher dose, possibly reducing engagement of precursor cells with the antigen and resulting in the suboptimal response observed after two-dose vaccination schedules in phase IIb/III clinical trials of CVnCoV. However, when immune memory is established, a third dose efficiently boosts the immunological responses and improves antibody affinity and breadth.

[2Fe-2S] protein cofactors are essential for life and are synthesized on ISCU2 scaffolds. Here, the authors show that hydrophobic interaction of two conserved N-terminal tyrosines induces ISCU2 dimerization and concomitant [2Fe-2S] cluster synthesis.

People with Parkinson’s disease (PwP) experience a variety of symptoms and fluctuations in these, which they have to cope with every day. In tailoring a person-centered treatment to PwP there is a lack of knowledge about the association between pre-dominant coping behaviors and clinical markers among PwP. To describe and compare specific clinical markers between 6 suggested coping behaviors. Thirty-four PwP, who previously had been classified into 6 different pre-dominant coping behaviors, were included in this mixed methods study. Six primary variables were included in the descriptive analysis; motor function (UPDRS-III), non-motor symptoms score (NMS-Quest), change in bradykinesia score, apathy score (LARS), personality traits (NEO-FFI), and cognitive status (evaluated by a neuropsychologist). The merged results of this mixed methods study indicate that clinical markers as apathy, burden of non-motor symptoms, cognitive impairments and personality traits, have the potential to impact the coping behavior in PwP. In a clinical setting the markers; NMS-burden, degree of apathy, cognition, and personality traits may indicate specific coping behavior. Three of the six suggested typologies of coping behaviors differed from the other groups when comparing descriptive data. In order to improve patient care and guide the development of person-centered therapies, each PwP should be approached based on those typologies.

Background and purpose: The evaluation of metaphyseal angular deformities in children includes indication and timing for corrective osteotomy, and possible need for several operations during growth. Gap-fillers are usually autologous bone grafts, which might cause donor site problems. Calcium phosphate (CaP) bone cement may be a possible alternative. Patients and methods: We performed 15 corrective osteotomies from 2007 to 2013 in 10 children, ages 5 to 18, with Norian SRS bone cement as a gap-filler, in the distal radius (12), proximal radius (1), and proximal humerus (2). Due to growth arrest and gradually increasing malalignments 3/10 children needed 1–3 additional corrections. Locking plates and screws were used except in 1 case at first surgery, aged 5 (K-wires). 2 children needed additional limb lengthening with external fixator. Results: All osteotomies healed. Postoperative radiographs and CT scans showed good alignment and gradual transformation of cement into bone. Remodeling was visible intraoperatively in patients needing multiple surgeries. Return to earlier osteotomy sites was unproblematic. No adverse events from using CaP cement were experienced. Interpretation: CaP cement is an alternative to bone grafts in upper extremity metaphyseal corrective osteotomies in children, and also when greater corrections are necessary or several surgeries indicated during the growth period.

Metallochaperones are a diverse family of trafficking molecules that provide metal ions to protein targets for use as cofactors. The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of the Sod1 intramolecular disulfide bond. Here, we present structural, spectroscopic, and cell-based data supporting a novel copper-induced mechanism for Sod1 activation. Ccs1 binding exposes an electropositive cavity and proposed "entry site" for copper ion delivery on immature Sod1. Copper-mediated sulfenylation leads to a sulfenic acid intermediate that eventually resolves to form the Sod1 disulfide bond with concomitant release of copper into the Sod1 active site. Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment.

IntroductionCurrently 1.9 billion adults worldwide are estimated to be overweight or obese. Weight loss sustainability is difficult, and weight loss rehabilitation programs have been criticised for having an individualistic approach. It has been suggested that occupational therapists could be used as part of a transdisciplinary approach because of their holistic perspective. During the development of an occupational therapy- based weight loss program five components arose as essential from earlier interviews with health professionals and citizens with obesity: diet, physical activities, social relations, habits and balancing everyday life. Before developing the program, we needed a clearer picture of which strategies should support the five components. The aim of this study was to obtain a description of strategies related to the five components that could support weight loss to become part of everyday life of people with obesity.MethodsThis study took a participatory design by using research circle (RC) methodology. Two RC groups were created, one with occupational therapists and one with citizens with obesity. Researchers participated in both RC groups. Data was obtained through democratic principles. The two RC groups met four times over a period of 4 months. Qualitative content analysis was conducted.ResultsFive themes arose: (1) Diet—Find the line between either-or, (2) Physical activity—Break the comfort zone, (3) Social relations—Stand strong together, (4) Habits—Focus on possibilities instead of bad habits, and (5) Balancing everyday life—Handling life's bumps.ConclusionThe strategies for a weight loss program including the five components should include awareness of senses and activity patterns surrounding meals, taking one step at a time when focusing of physical activities and be conscious of values, include family and friends in the program to find common ground and self-confidence and use re-placement activities. We suggest that the component of balancing everyday life should be seen as an overall component as all strategies are related to finding meaning and variation in activities which is part of an ongoing weight loss process.