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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.

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.

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.

This article analyses the use of research evidence (RE) in three policy processes, at the local level, dealing with physical activity. We analysed an extensive number of policy documents and a total of 14 interviews with policymakers. Results show an unsystematic way of using RE, where demographic and statistical data as well as expert consultation were mostly used. Lack of transparency of RE use complicated the tracking of sources from introduction to actual policy impact. It can be concluded that the policymakers engaged in health issues have a wider use of RE than the policymakers working with more sports-oriented issues.

Abstract Background Currently 1.9 billion adults worldwide are estimated to be overweight or obese. In Denmark the municipalities hold the responsibility to deliver weight loss programmes to overweight and obese citizens. There is a tendency to assume that weight loss programmes that show positive effects in specialized hospital settings are directly transferrable to municipal settings. However, municipality-based weight loss programmes have not produced clinically significant reductions in body weight. One reason for this may be that much research evidence regarding obesity programming neglects the perspectives of people with obesity. The first step in developing a weight loss programme designed for municipal settings is to understand what people with obesity want and need from a programme. The aim of this study was to examine what people with obesity find important in a weight loss programme for weight loss and weight maintenance. Methods We used a qualitative, explorative, descriptive design with individual interviews. We included men and women age 17 and older with a BMI ≥ 25 kg/m2. Participants were recruited from the wait lists of 13 municipality programmes and through Facebook posts. Data were analyzed using content analysis. Results Thirty-four participants with overweight or obesity were individually interviewed (ages between 19 and 74). Findings suggest that weight loss programmes should; a) support participants in structuring days; b) consider the use of replacement activities to reduce cognitive and emotional burden; c) aide individuals to increase self-efficacy and; d) include family and friends as well as health professionals and peers in the weight loss process. Diet and exercise, while important, should be balanced with other meaningful activities in everyday life. Conclusion Participants in this study wished to balance weight loss related activities with overall everyday life as well as finding the believe in their ability to lose weight in social relations.

Abstract Background With declining wild fish populations, farmed salmon has gained popularity as a source for healthy long-chain highly unsaturated fatty acids (LC-HUFA). However, the introduction of plant oil in farmed salmon feeds has reduced the content of these beneficial LC-HUFA. The synthetic capability for LC-HUFAs depends upon the dietary precursor fatty acids and the genetic potential, thus there is a need for in-depth understanding of LC-HUFA synthetic genes and their interactions with other genes involved in lipid metabolism. Several key genes of LC-HUFA synthesis in salmon belong to the fatty acid desaturases 2 (fads2) family. The present study applied whole transcriptome analysis on two CRISPR-mutated salmon strains (crispants), 1) Δ6abc/5 Mt with mutations in Δ5fads2, Δ6fads2-a, Δ6fads2-b and Δ6fads2-c genes, and 2) Δ6bc Mt with mutations in Δ6fads2-b and Δ6fads2-c genes. Our purpose is to evaluate the genetic effect fads2 mutations have on other lipid metabolism pathways in fish, as well as to investigate mosaicism in a commercial species with a very long embryonal period. Results Both Δ6abc/5 Mt and Δ6bc Mt crispants demonstrated high percentage of indels within all intended target genes, though different indel types and percentage were observed between individuals. The Δ6abc/5 Mt fish displayed several disruptive indels which resulted in over 100 differentially expressed genes (DEGs) enriched in lipid metabolism pathways in liver. This includes up-regulation of srebp1 genes which are known key transcription regulators of lipid metabolism as well as a number of down-stream genes involved in fatty acid de-novo synthesis, fatty acid β-oxidation and lipogenesis. Both elovl5 and elovl2 genes were not changed, suggesting that the genes were not targeted by Srebp1. The mutation of Δ6bc Mt surprisingly resulted in over 3000 DEGs which were enriched in factors encoding genes involved in mRNA regulation and stability. Conclusions CRISPR-Cas9 can efficiently mutate multiple fads2 genes simultaneously in salmon. The results of the present study have provided new information on the transcriptional regulations of lipid metabolism genes after reduction of LC-HUFA synthesis pathways in salmon.

Abstract The aquaculture industry has been dealing with salmon lice problems forming serious threats to salmonid farming. Several treatment approaches have been used to control the parasite. Treatment effectiveness must be optimized, and the systematic genetic differences between subpopulations must be studied to monitor louse species and enhance targeted control measures. We have used IIb‐RAD sequencing in tandem with a random forest classification algorithm to detect the regional genetic structure of the Norwegian salmon lice and identify important markers for sex differentiation of this species. We identified 19,428 single nucleotide polymorphisms (SNPs) from 95 individuals of salmon lice. These SNPs, however, were not able to distinguish the differential structure of lice populations. Using the random forest algorithm, we selected 91 SNPs important for geographical classification and 14 SNPs important for sex classification. The geographically important SNP data substantially improved the genetic understanding of the population structure and classified regional demographic clusters along the Norwegian coast. We also uncovered SNP markers that could help determine the sex of the salmon louse. A large portion of the SNPs identified to be under directional selection was also ranked highly important by random forest. According to our findings, there is a regional population structure of salmon lice associated with the geographical location along the Norwegian coastline.

Available genomics studies have mostly focused on planktonic centric diatom. Here, the authors report the genome assembly of the marine biofilm-forming diatom Seminavis robusta and the resequencing data of a panel of accessions to reveal their evolutionary adaptations.

Fetal exposure to certain phthalate esters can disrupt testis development in rodents and lead to male reproductive disorders, but with a causal link less certain in humans. Di(2-ethylhexyl) phthalate (DEHP) is one of the most common phthalates found in the environment and in rodents it is known to induce serious testis toxicity, as well as male reproductive disorders including cryptorchidism, hypospadias, impaired spermatogenesis and reduced fertility. In this study, we show that perinatal DEHP exposure disrupts gap junction localization in fetal and postnatal rat testis and correlate these findings to morphological changes. The protein Connexin 43 (CX43), normally expressed strongly in testicular gap junctions, was markedly downregulated in Leydig cells of DEHP-exposed fetal testes. In the postnatal testes, CX43 expression was recovered in the DEHP-exposed animals, even though Leydig cell clusters and malformed cords with intratubular Leydig cells were still present.

Neurons with internal memory have been proposed for biological and bio-inspired neural networks, adding important functionality. We introduce an internal time-limited charge-based memory into a III–V nanowire (NW) based optoelectronic neural node circuit designed for handling optical signals in a neural network. The new circuit can receive inhibiting and exciting light signals, store them, perform a non-linear evaluation, and emit a light signal. Using experimental values from the performance of individual III–V NWs we create a realistic computational model of the complete artificial neural node circuit. We then create a flexible neural network simulation that uses these circuits as neuronal nodes and light for communication between the nodes. This model can simulate combinations of nodes with different hardware derived memory properties and variable interconnects. Using the full model, we simulate the hardware implementation for two types of neural networks. First, we show that intentional variations in the memory decay time of the nodes can significantly improve the performance of a reservoir network. Second, we simulate the implementation in an anatomically constrained functioning model of the central complex network of the insect brain and find that it resolves an important functionality of the network even with significant variations in the node performance. Our work demonstrates the advantages of an internal memory in a concrete, nanophotonic neural node. The use of variable memory time constants in neural nodes is a general hardware derived feature and could be used in a broad range of implementations.

Abstract Background Although important syntheses and theoretical works exist in relation to understanding the organisational factors that facilitate research use, these contributions differ in their scope and object of study as well as their theoretical underpinnings. Therefore, from an exploratory angle, it may be useful to map out the current literature on organisational factors of research use in public health policy-making when revisiting existing theories and frameworks to gain further theoretical insights. Methods Herein, a scoping review technique and thematic content analysis were used to bring together findings from both synthesised and empirical studies of different types to map out the organisational factors that facilitate research use in public health policy-making. Results A total of 14 reviews and 40 empirical studies were included in the analysis. These were thematically coded and the intra-organisational factors reported as enabling research use were examined. Five main categories of organisational factors that advance research use in policy organisations – (1) individual factors, (2) the management of research integration, (3) organisational systems and infrastructures of research use, (4) institutional structures and rules for policy-making, and (5) organisational characteristics – were derived as well as 18 subcategories and a total of 64 specific factors, where 27 factors were well supported by research. Conclusions Using a scoping review methodology, the intra-organisational factors influencing research use in policy-making (including individual factors) were systematically mapped and the theories applied in this area of research were assessed. The review findings confirm the importance of an intra-organisational perspective when exploring research use, showing that many organisational factors are critical facilitators of research use but also that many factors and mechanisms are understudied. The synthesis shows a lack of studies on politicians and the need for more theoretically founded research. Despite increased efforts to update the existing evidential and theoretical basis of research use, we still need frameworks that combine different approaches and theories to help us grasp the complex organisational mechanisms that facilitate research use in policy settings.

The arthropod salmon louse (Lepeophtheirus salmonis) is a major threat to Atlantic salmon aquaculture and wild salmonids. Essentially like in monoculture, very high concentrations of susceptible hosts may result in high reproduction and severe production of waves of pests. Pest management is crucial both for fish health and protection of wild fish populations from aquaculture influence. Various methods have been utilized to control salmon lice infestations, such as pesticide use, physical treatments, construction modifications, fallowing, breeding, vaccination, and biological control. Most of the methods are partially successful, but none completely fulfills the necessary pest control strategy. Like in agriculture, lice/pest management is an arms race, but the marine environment makes it even more difficult to precisely hit the target pest and avoid unintended negative effects on general wildlife. In this study, we provide an overview of the methods and principles of salmon lice management and address current possibilities and limitations. We also highlight the potential of emerging strategies and enabling technologies, like genome editing, RNA interference, and machine learning, in arthropod management in aquaculture.

Abstract Background The prevalence of obesity has increased significantly worldwide within the last decade. As obesity is recognised as a contributing factor when developing various health threatening chronic diseases, prevention initiatives focusing on weight loss are becoming more important. Because of the time spent at the workplace, workplaces can be optimal arenas for weight loss programs and these programs have been effective to decrease body weight. Thus, reasons for engaging in weight loss interventions needs exploring, in order to engage more workplaces in weight loss interventions. Such information provides important knowledge that may help to inform decisions of municipalities, employers and other public health decision makers, when and if implementing weight loss interventions. The aim of this study was therefore to explore reasons for employee engagement in weight loss projects at the workplace and the incentives a municipality, a manager at a home-care centre, and a project manager have to launch such project. Methods A stratified case study was conducted. A representative from the municipality, the manager at a home-care centre, the project manager of the weight loss intervention and six health-care workers were interviewed at the end of a one-year weight loss intervention at the workplace. Data were analysed using Systematic Text Condensation. Results Analysis identified different views and considerations for engaging in a weight loss intervention at the workplace. For the representative of the municipality the possible economical gain of the project was in focus. The project manager and the manager of the home-care centre both reflected mainly on improvement of the healthcare workers health. For the project manager, achieving good scientific results was highlighted as well. However, the employees were influenced by several factors, such as their own health and weight loss, the pressure from the environment and their struggle for recognition. Conclusions This study concluded that if targeting the increasing worldwide obesity problem through workplace initiated weight loss programs, the sales pitch to managements and employers have to be tailored in order to increase the participation and the motivation for the initiative. Trial registration ClinicalTrial.gov: NCT01015716, registration data 14.12.2010 (Prospectively registered).

Abstract Background To decrease the morbidity burden of cardiovascular disease and to avoid the development of potentially preventable complications, early assessment and treatment of acute coronary syndrome (ACS) are important. The aim of this study has therefore been to explore the possible association between patients’ estimated intensity of chest pain when first seen by the ambulance crew in suspected ACS, and the subsequent outcome before and after arrival in hospital. Methods Data was collected both prospectively and retrospectively. The inclusion criteria were chest pain raising suspicion of ACS and a reported intensity of pain ≥4 on the visual analogue scale. Results All in all, 1603 patients were included in the study. Increased intensity of chest pain was related to: 1) more heart-related complications before hospital admission; 2) a higher proportion of heart failure, anxiety and chest pain after hospital admission; 3) a higher proportion of acute myocardial infarction and 4) a prolonged hospitalisation. However, there was no significant association with mortality neither in 30 days nor in three years. Adjustment for possible confounders including age, a history of smoking and heart failure showed similar results. Conclusion The estimated intensity of chest pain reported by the patients on admission by the ambulance team was associated with the risk of complications prior to hospital admission, heart failure, anxiety and chest pain after hospital admission, the final diagnosis and the number of days in hospital. Trial registration ClinicalTrials.gov 151:2008/4564 Identifier: NCT00792181. Registred 17 November 2008 ‘retrospectively registered’.

Abstract Introduction Neuroinflammation has been established to be part of the neuropathological changes in Parkinson’s disease (PD) and atypical parkinsonism (APD). Activated microglia play a key role in neuroinflammation by release of cytokines. Evidence of the disparity, if any, in the neuroinflammatory response between PD and APD is sparse. In this study, we investigated CSF cytokine profiles in patients with PD, multiple system atrophy (MSA), or progressive supranuclear palsy (PSP). Methods On a sensitive electrochemiluminescence-based platform (Quickplex, Meso Scale Discovery®), we examined a panel of C-reactive protein (CRP) and eight selected cytokines, IFN-γ, IL-10, IL-18, IL-1β, IL-4, IL-6, TGF-β1, and TNF-α, among patients with PD (n = 46), MSA (n = 35), and PSP (n = 39) or controls (n = 31). Additionally, CSF total tau protein levels were measured as a marker of nonspecific neurodegeneration for correlation estimates. Results CRP and the pro-inflammatory cytokines TNF-α, IL-1β, and Il-6 were statistically significantly elevated in MSA and PSP patients compared to PD patients but not compared to control patients. No analytes differed statistically significantly between MSA and PSP patients. The best diagnostic discrimination, evaluated by ROC curve (AUC 0.77, p = 007, 95% CI 0.660–0.867), between PD and MSA patients was seen for a subset of analytes: CRP, TNF-α, IL-1β, and IFN-γ. Conclusion Among the investigated cytokines and CRP, we found a statistically significant increase of microglia-derived cytokines in MSA and PSP patients compared to PD patients.

Background: Current assessments of motor symptoms in Parkinson's disease are often limited to clinical rating scales.Objectives: To develop a computer application using the Microsoft Kinect sensor to assess performance-related bradykinesia.Methods: The developed application (Motorgame) was tested in patients with Parkinson's disease and healthy controls. Participants were assessed with the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) and standardized clinical side effect rating scales, i.e., UKU Side Effect Rating Scale and Simpson-Angus Scale. Additionally, tests of information processing (Symbol Coding Task) and motor speed (Token Motor Task), together with a questionnaire, were applied.Results: Thirty patients with Parkinson's disease and 33 healthy controls were assessed. In the patient group, there was a statistically significant (p < 0.05) association between prolonged time of motor performance in the Motorgame and upper body rigidity and bradykinesia (MDS-UPDRS) with the strongest effects in the right hand (p < 0.001). In the entire group, prolonged time of motor performance was significantly associated with higher Simson-Angus scale rigidity score and higher UKU hypokinesia scores (p < 0.05). A shortened time of motor performance was significantly associated with higher scores on information processing (p < 0.05). Time of motor performance was not significantly associated with Token Motor Task, duration of illness, or hours of daily physical activity. The Motorgame was well-accepted.Conclusions: In the present feasibility study the Motorgame was able to detect common motor symptoms in Parkinson's disease in a statistically significant and clinically meaningful way, making it applicable for further testing in larger samples.

Collaboration between research and policy is an essential element for knowledge-based public health. However, only half of the Danish municipalities have experience with collaborating with researchers or other stakeholders. Through content analysis of interviews and policy documents the study explores the involvement of external stakeholders in local health policymaking and public officials' perceptions on involving them. Main involvement was through a personal contact or through a regular hearing. The purpose of involvement was mostly tactical or to solve problems. Politicians had substantial influence on the involvement of external stakeholders, allowing only a few to contribute in a closed policymaking process.

Phenylalanine hydroxylase (PAH) is a crucial enzyme involved in tyrosine biosynthesis, having roles in neurological and physiological processes. The purpose of PAH has received little attention in crustaceans despite extensive investigations in other arthropods. Here, we characterize the PAH gene for the first time in the parasite Lepeophtheirus salmonis, a copepod that is responsible for huge economic losses in salmonid fish farming. Phylogenetic and sequence analyses confirmed that LsPAH is closely related to the metazoan PAH with conserved ACT regulatory and catalytic domains. Temporal expression patterns revealed that LsPAH is expressed throughout all developmental stages peaking during the copepodite stages, suggesting an essential role in developmental physiology. We used RNAi to knockdown LsPAH expression in the nauplius I stage to study developmental function during the larval stages. PAH knockdown impaired larval development, molting and swimming ability with severe morphological defects. This study provides insight into the role of PAH in copepods and demonstrates the importance of this metabolic gene in salmon louse growth and development.

Objective Obesity is an increasing public health challenge and most weight loss programmes are still inadequate to support sustainable weight loss. One reason for the continued lack of success might be the dominant biomedical, individualised approach to weight loss. Holistic approaches that focus on overall health and well-being in addition to weight loss are increasingly recommended. In Denmark, health professionals in the municipalities are responsible for developing and conducting weight loss programmes. The objective of this study was to explore what health professional’s perceived as an ideal, holistic weight loss programme that could be feasibly implemented in the municipalities.Design A phenomenological-hermeneutical qualitative study was performed using semistructured interviews.Setting Thirty-two Danish municipalities were weight loss programmes are developed and conducted.Participants Thirty-five health professionals with experience conducting weight loss programmes.Results Three themes emerged from the analysis: Support from the social network are important both during and after a weight loss, Changing the self-belief by positive discussions and doing activities, Maintaining changes through daily life.Conclusion Future municipal weight loss programmes should emphasise overall health and well-being instead of weight loss and adopt a holistic approach including a focus on social relationships, meaningful activities and successes as part of a balanced daily life.