Pubmed
Verdens største database innen bl.a. medisin, sykepleie, helsestell og prekliniske fag
Oversikt over våre siste publikasjonene registrert i PubMed og Cristin.
Verdens største database innen bl.a. medisin, sykepleie, helsestell og prekliniske fag
Background: Dietary recommendations in inflammatory bowel disease (IBD) are inconclusive, and patients may follow restrictive diets with increased risk of malnutrition. The aim of this study was to compare dietary intakes and nutritional status in men and women with newly diagnosed IBD with a general population sample, and to investigate whether intakes were in line with the Nordic Nutrition Recommendations. Methods: This was a cross-sectional study including adults≥ 40 years with IBD from the Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III cohort study. A validated food frequency questionnaire (FFQ) was used in dietary data collection, and a sample from the seventh survey of the Tromsø Study was included as a comparison group. Results: A total of 227 men and women with IBD were included. IBD patients had higher intake of grain products, sweetened beverages, energy, fat and polyunsaturated fat (PUFA), but lower intake of dairy products, alcohol and iodine compared to adults from the comparison sample (p < 0.01). Intakes of saturated fat and carbohydrates in both genders, and vitamin D in women were not within recommended levels. Anemia and hypoalbuminemia were more prevalent in IBD patients than in the comparison sample. Conclusions: Dietary intakes in newly diagnosed IBD patients were mostly in line with Nordic Nutrition Recommendations. Higher proportion of IBD patients exceeded recommended allowances of fat and added sugar than the comparison sample. Insufficient micronutrient intake, anemia and hypoalbuminemia are present challenges in IBD patients that require monitoring.
A common challenge when studying rare diseases or medical conditions is the limited number of patients, usually resulting in long inclusion periods as well as unequal sampling and storage conditions. The main purpose of this study was to demonstrate the challenges when comparing samples subject to different preanalytical conditions. We performed a global (commonly referred to as “untargeted”) liquid chromatography-high resolution mass spectrometry metabolomics analysis of blood samples from cases of sudden infant death syndrome and controls stored as dried blood spots on a chemical-free filter card for 15 years at room temperature compared with the same blood samples stored as whole blood at −80°C before preparing new dried blood spots using a chemically treated filter card. Principal component analysis plots distinctly separated the samples based on the type of filter card and storage, but not sudden infant death syndrome versus controls. Note that, 1263 out of 5161 and 642 out of 1587 metabolite features detected in positive and negative ionization mode, respectively, were found to have significant 2-fold changes in amounts corresponding to different preanalytical conditions. The study demonstrates that the dried blood spot metabolome is largely affected by preanalytical factors. This emphasizes the importance of thoroughly addressing preanalytical factors during study design and interpretation, enabling identification of real, biological differences between sample groups whilst preventing other factors or random variation to be falsely interpreted as positive results.
Importance: White matter (WM) abnormalities are commonly reported in psychiatric disorders. Whether peripartum insufficiencies in brain oxygenation, known as birth asphyxia, are associated with WM of patients with severe mental disorders is unclear. Objective: To examine the association between birth asphyxia and WM in adult patients with schizophrenia and bipolar disorders (BDs) compared with healthy adults. Design, setting, and participants: In this case-control study, all individuals participating in the ongoing Thematically Organized Psychosis project were linked to the Medical Birth Registry of Norway (MBRN), where a subset of 271 patients (case group) and 529 healthy individuals (control group) had undergone diffusion-weighted imaging (DWI). Statistical analyses were performed from June 16, 2020, to March 9, 2021. Exposures: Birth asphyxia was defined based on measures from standardized reporting at birth in the MBRN. Main outcomes and measures: Associations between birth asphyxia and WM regions of interest diffusion metrics, ie, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), were compared between groups using analysis of covariance, adjusted for age, age squared, and sex. Results: Of the 850 adults included in the study, 271 were in the case group (140 [52%] female individuals; mean [SD] age, 28.64 [7.43] years) and 579 were in the control group (245 [42%] female individuals; mean [SD] age, 33.54 [8.31] years). Birth asphyxia measures were identified in 15% to 16% of participants, independent of group. The posterior limb of the internal capsule (PLIC) showed a significant diagnostic group × birth asphyxia interaction (F(1, 843) = 11.46; P = .001), reflecting a stronger association between birth asphyxia and FA in the case group than the control group. RD, but not AD, also displayed a significant diagnostic group × birth asphyxia interaction (F(1, 843) = 9.28; P = .002) in the PLIC, with higher values in patients with birth asphyxia and similar effect sizes as observed for FA. Conclusions and relevance: In this case-control study, abnormalities in the PLIC of adult patients with birth asphyxia may suggest a greater susceptibility to hypoxia in patients with severe mental illness, which could lead to myelin damage or impeded brain development. Echoing recent early-stage schizophrenia studies, abnormalities of the PLIC are relevant to psychiatric disorders, as the PLIC contains important WM brain pathways associated with language, cognitive function, and sensory function, which are impaired in schizophrenia and BDs.
Drug induced liver injury (DILI) is a major cause of acute liver failure (ALF) and one of the leading indications for liver transplantation in Western societies. Given the wide use of both prescribed and over the counter drugs, DILI has become a major health issue with a pressing need to find novel and effective therapies. Although significant progress has been made in understanding the molecular mechanisms underlying DILI, our incomplete knowledge of its pathogenesis and inability to predict DILI is largely due to both discordance between human and animal DILI in preclinical drug development and a lack of models that faithfully recapitulate complex pathophysiological features of human DILI. This is exemplified by the hepatotoxicity of acetaminophen (APAP) overdose, a major cause ALF due to its extensive worldwide use as an analgesic. Despite intensive efforts utilizing current animal and in vitro models, the mechanisms involved in the hepatotoxicity of APAP are still not fully understood. In this expert Consensus Statement, which is endorsed by the European Drug-Induced Liver Injury Network, we aim to facilitate and outline clinically impactful knowledge discovery by detailing the requirements for more realistic human-based systems to assess hepatotoxicity to guide future drug safety testing. We present novel insights and majorplayers in APAP pathophysiology and describe emerging in vitro and in vivo pre-clinicalmodels, as well as advanced imaging and in silico technologies, which may improveprediction of clinical outcomes of DILI including APAP hepatotoxicity.
Background Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection. Methods We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP. Results Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen’s d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10). Conclusions These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders.
Background: Trauma patients have high concentrations of circulating extracellular vesicles (EVs) following injury, but the functional role of EVs in this setting is only partly deciphered. We aimed to describe in detail EV-associated procoagulant activity in individual trauma patients during the first 12 hours after injury to explore their putative function and relate findings to relevant trauma characteristics and outcome. Methods: In a prospective observational study of 33 convenience recruited trauma patients, citrated plasma samples were obtained at trauma center admission and 2, 4, 6, and 8 hours thereafter. We measured thrombin generation from isolated EVs and the procoagulant activity of phosphatidylserine (PS)-exposing EVs. Correlation and multivariable linear regression analyses were used to explore associations between EV-associated procoagulant activity and trauma characteristics as well as outcome measures. Results: EV-associated procoagulant activity was highest in the first 3 hours after injury. EV-associated thrombin generation normalized within 7 to 12 hours of injury, whereas the procoagulant activity of PS-exposing EVs declined to a level right above that of healthy volunteers. Increased EV-associated procoagulant activity at admission was associated with higher New Injury Severity Score, lower admission base excess, higher admission international normalized ratio, prolonged admission activated partial thromboplastin time, higher Sequential Organ Failure Assessment score at day 0, and fewer ventilator-free days. Conclusion: Our data suggest that EVs have a transient hypercoagulable function and may play a role in the early phase of hemostasis after injury. The role of EVs in trauma-induced coagulopathy and posttraumatic thrombosis should be studied bearing in mind this novel temporal pattern. Level of evidence: Prognostic/epidemiologic, level V.
Hippocampal region CA2 has received increased attention due to its importance in social recognition memory. While its specific function remains to be identified, there are indications that CA2 plays a major role in a variety of situations, widely extending beyond social memory. In this targeted review, we highlight lines of research which have begun to converge on a more fundamental role for CA2 in hippocampus-dependent memory processing. We discuss recent proposals that speak to the computations CA2 may perform within the hippocampal circuit.
Det er fortsatt mye vi ikke vet om sammenhengen mellom seksuelle overgrep i barndommen og senere arbeidsuførhet. Denne studien ser på om forhold ved overgrepet og overgriperen kan øke sannsynligheten for arbeidsuførhet.
Forekomststudier viser at en betydelig andel av befolkningen rapporterer å ha opplevd seksuelle overgrep i barndommen. Denne studien viser en statistisk sammenheng mellom slike rapporterte overgrep og senere arbeidsuførhet.
We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18–92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. “PSQI # 1 Subjective sleep quality” and “PSQI #5 Sleep disturbances” were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with “PSQI #5 Sleep disturbances” emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.
Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia. Its cleaved fragments, soluble TREM2 (sTREM2), can be measured in the cerebrospinal fluid (CSF). Previous studies indicate higher CSF sTREM2 in symptomatic AD; however most of these studies have included biomarker positive AD cases and biomarker negative controls. The aim of the study was to explore potential differences in the CSF level of sTREM2 and factors associated with an increased sTREM2 level in patients diagnosed with mild cognitive impairment (MCI) or dementia due to AD compared with cognitively unimpaired controls as judged by clinical symptoms and biomarker category (AT). We included 299 memory clinic patients, 62 (20.7%) with AD-MCI and 237 (79.3%) with AD dementia, and 113 cognitively unimpaired controls. CSF measures of the core biomarkers were applied to determine AT status. CSF sTREM2 was analyzed by ELISA. Patients presented with comparable CSF sTREM2 levels as the cognitively unimpaired (9.6 ng/ml [SD 4.7] versus 8.8 ng/ml [SD 3.6], p = 0.27). We found that CSF sTREM2 associated with age-related neuroinflammation and tauopathy irrespectively of amyloid β, APOE ε4 status or gender. The findings were similar in both symptomatic and non-symptomatic individuals.
Objective: To perform a radiological review of mammograms from prior screening and diagnosis of screen-detected breast cancer in BreastScreen Norway, a population-based screening program. Methods: We performed a consensus-based informed review of mammograms from prior screening and diagnosis for screen-detected breast cancers. Mammographic density and findings on screening and diagnostic mammograms were classified according to the Breast Imaging-Reporting and Data System®. Cases were classified based on visible findings on prior screening mammograms as true (no findings), missed (obvious findings), minimal signs (minor/non-specific findings), or occult (no findings at diagnosis). Histopathologic tumor characteristics were extracted from the Cancer Registry of Norway. The Bonferroni correction was used to adjust for multiple testing; p
As experimental neuroscience is moving toward more integrative approaches, with a variety of acquisition techniques covering multiple spatiotemporal scales, data management is becoming increasingly challenging for neuroscience laboratories. Often, datasets are too large to practically be stored on a laptop or a workstation. The ability to query metadata collections without retrieving complete datasets is therefore critical to efficiently perform new analyses and explore the data. At the same time, new experimental paradigms lead to constantly changing specifications for the metadata to be stored. Despite this, there is currently a serious lack of agile software tools for data management in neuroscience laboratories. To meet this need, we have developed Expipe, a lightweight data management framework that simplifies the steps from experiment to data analysis. Expipe provides the functionality to store and organize experimental data and metadata for easy retrieval in exploration and analysis throughout the experimental pipeline. It is flexible in terms of defining the metadata to store and aims to solve the storage and retrieval challenges of data/metadata due to ever changing experimental pipelines. Due to its simplicity and lightweight design, we envision Expipe as an easy-to-use data management solution for experimental laboratories, that can improve provenance, reproducibility, and sharing of scientific projects.
Cross-sectional studies have consistently reported an inverse association between perceived social support and the severity of mental health symptoms among adult survivors of childhood sexual abuse (CSA). However, there is a lack of longitudinal studies investigating the bidirectional association between social support and the severity of symptoms among adult CSA-survivors, as well as the role of relational problems in predicting perceived social support and symptom levels over time. The present study addressed these questions in a sample of primarily female CSA-survivors. Methods In a three-wave, four-year longitudinal study of 506 CSA-survivors (94.9% women, 5.1% men) recruited from support centers for sexual abuse survivors in Norway, we used cross-lagged panel structural equation modeling to examine the directionality of the longitudinal associations between perceived social support and symptoms of posttraumatic stress, anxiety, depression and insomnia. Results Cross-lagged panel analyses revealed significant weak reciprocal associations between perceived social support and depression, posttraumatic stress symptoms and anxiety symptoms, but not with insomnia symptoms. The observed effects were partly overlapping and partly inconsistent across the different symptom domains. Relational problems predicted social support cross-sectionally and longitudinally, whereas only cross-sectional associations were found between the relational problems variable and mental health symptoms. Theoretical and clinical implications of the findings are discussed, alongside methodological limitations of the study.
Objective The objective of this study was to explore how bedside micro-decisions were made between conscious patients on mechanical ventilation in intensive care and their healthcare providers. Methods Using video recordings to collect data, we explored micro-decisions between 10 mechanically ventilated patients and 60 providers in interactions at the bedside. We first identified the types of micro-decisions before using an interpretative approach to analyze the decision-making processes and create prominent themes. Results We identified six types of bedside micro-decisions; non-invited, substituted, guided, invited, shared and self-determined decisions. Three themes were identified in the decision-making processes: 1) being an observer versus a participant in treatment and care, 2) negotiating decisions about individualized care (such as tracheal suctioning or medication),and 3) balancing empowering activities with the need for energy restoration. Conclusion This study revealed that bedside decision-making processes in intensive care were characterized by a high degree of variability between and within patients. Communication barriers influenced patients’ ability to express their preferences. An increased understanding of how micro-decisions occur with non-vocal patients is needed to strengthen patient participation. Practice Implications We advise providers to make an effort to solicit patients’ preferences when caring for critically ill patients.
Purpose The stage-specific survival of young breast cancer patients has improved, likely due to diagnostic and treatment advances. We addressed whether survival improvements have reached all socioeconomic groups in a country with universal health care and national treatment guidelines. Methods Using Norwegian registry data, we assessed stage-specific breast cancer survival by education and income level of 7501 patients (2317 localized, 4457 regional, 233 distant and 494 unknown stage) aged 30–48 years at diagnosis during 2000–2015. Using flexible parametric models and national life tables, we compared excess mortality up to 12 years from diagnosis and 5-year relative survival trends, by education and income as measures of socioeconomic status (SES). Results Throughout 2000–2015, regional and distant stage 5-year relative survival improved steadily for patients with high education and high income (high SES), but not for patients with low education and low income (low SES). Regional stage 5-year relative survival improved from 85 to 94% for high SES patients (9% change; 95% confidence interval: 6, 13%), but remained at 84% for low SES patients (0% change; − 12, 12%). Distant stage 5-year relative survival improved from 22 to 58% for high SES patients (36% change; 24, 49%), but remained at 11% for low SES patients (0% change; − 19, 19%). Conclusions Regional and distant stage breast cancer survival has improved markedly for high SES patients, but there has been little survival gain for low SES patients. Socioeconomic status matters for the stage-specific survival of young breast cancer patients, even with universal health care.
Brain changes occurring in aging can be indexed by biomarkers. We used cluster analysis to identify subgroups of cognitively unimpaired individuals (n = 99, 64-93 years) with different profiles of the cerebrospinal fluid biomarkers beta amyloid 1-42 (Aβ42), phosphorylated tau (P-tau), total tau, chitinase-3-like protein 1 (YKL-40), fatty acid binding protein 3 (FABP3), and neurofilament light (NFL). Hippocampal volume and memory were assessed across multiple follow-up examinations covering up to 6.8 years. Clustering revealed one group (39%) with more pathological concentrations of all biomarkers, which could further be divided into one group (20%) characterized by tauopathy and high FABP3 and one (19%) by brain β-amyloidosis, high NFL, and slightly higher YKL-40. The clustering approach clearly outperformed classification based on Aβ42 and P-tau alone in prediction of memory decline, with the individuals with most tauopathy and FABP3 showing more memory decline, but not more hippocampal volume change. The results demonstrate that older adults can be classified based on biomarkers beyond amyloid and tau, with improved prediction of memory decline
OBJECTIVE: To report on long-term effects of a cluster randomized controlled kindergarten-based intervention trial, which aimed to increase vegetable intake among Norwegian preschool children (3-5 years at baseline). The effects of the intervention at follow-up 1 (immediately post-intervention) have previously been published. This paper presents the effects of the intervention from baseline to follow-up 2 (12 months post-intervention). RESULTS: Parental consents were obtained for 633 out of 1631 eligible children (response rate 38.8%). The effects of the intervention from baseline to follow-up 2 were assessed by mixed-model analyses taking the clustering effect of kindergartens into account. Children's vegetable intake was reported by the parents at baseline (spring 2015), at follow-up 1 (spring 2016) and at follow-up 2 (spring 2017). No significant long-term effects in child vegetable intake were found. A mean difference of - 0.1 times per day (95% CI - 0.5, 0.2) (P = 0.44) was found for the daily frequency of vegetable intake. A mean difference of - 0.2 different kinds of vegetables eaten over a month (95% CI - 1.0, 0.7) (P = 0.70) was found and for daily amount of vegetables a mean difference of - 15.0 g vegetables (95% CI - 38.0, 8.0) (P = 0.19) was found. Trial registration International Standard Randomised Controlled Trials ISRCTN51962956 (http://www.isrctn.com/ISRCTN51962956). Registered 21 June 2016 (retrospectively registered).
The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEAR-box element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma cells. The crystal structure of MITF bound to the CLEAR-box reveals how the palindromic nature of this motif induces symmetric MITF homodimer binding. In metastatic melanoma tumors and cell lines, MITF positively correlates with the expression of lysosomal and autophagosomal genes, which, interestingly, are different from the lysosomal and autophagosomal genes correlated with TFEB and TFE3. Depletion of MITF in melanoma cells and melanocytes attenuates the response to starvation-induced autophagy, whereas the overexpression of MITF in melanoma cells increases the number of autophagosomes but is not sufficient to induce autophagic flux. Our results suggest that MITF and the related factors TFEB and TFE3 have separate roles in regulating a starvation-induced autophagy response in melanoma. Understanding the normal and pathophysiological roles of MITF and related transcription factors may provide important clinical insights into melanoma therapy.
Objective To assess if recording the sensory latencies of the median and ulnar nerves one-by-one (consecutive) or at the same time (simultaneous) in the ring-finger test for carpal tunnel syndrome (CTS) will show equivalent results or if it will lead to a different clinical classification of patients. Methods We assessed the limits of agreement between the simultaneous and the consecutive method based on the median- ulnar sensory latency difference derived by both methods in 80 subjects and compared the number of minimal CTS cases identified by the two methods. Results Limits of agreement ranged from −0.23 to 0.29 ms. A significantly higher proportion of subjects with minimal CTS (only detectable by using the comparison test) was found using the simultaneous method (n = 8 and 2, respectively; p = 0.03). Conclusion The two methods have a poor to moderate agreement as indicated by the range of the limits of agreement (0.5 ms).
Background: Early childhood represents a critical period for the establishment of long-lasting healthy dietary habits. Limited knowledge exists on how to successfully increase vegetable consumption among preschool children. The overall aim of the present study was to improve vegetable intake among preschool children in a kindergarten-based randomized controlled trial. Methods: The target group was preschool children born in 2010 and 2011, attending public or private kindergartens in two counties in Norway. Data about child intake of vegetables were collected by three methods. First, parents filled in a web-based questionnaire of the child’s vegetable intake. Second, among a subsample, trained researchers observed children’s vegetable intake in the kindergarten. Thirdly, a parental web-based 24-h recall assessing the child’s vegetable intake was filled in. For allocation of kindergartens to intervention and control groups, a stratified block randomization was used. Multiple intervention components were implemented from September 2015 to February 2016 and components focused at influencing the four determinants availability, accessibility, encouragement and role modelling. The effect of the intervention from baseline (spring 2015) to follow-up 1 (spring 2016) was assessed by mixed-model analysis taking the clustering effect of kindergartens into account. Results: Parental consent was obtained for 38.8% of the children (633 out of 1631 eligible children). Based on the observational data in the kindergarten setting (n 218 in the control group and n 217 in the intervention group), a tendency to a small positive effect was seen as a mean difference of 13.3 g vegetables/day (95% CI: − 0.2, 26.9) (P = 0.054) was observed. No significant overall effects were found for the total daily vegetable intake or for the parental reported frequency or variety in vegetable intake. Conclusions: Based on the observational data in the kindergarten setting, a tendency to a small positive effect was seen with a mean difference of about 13 g vegetables/day, while no other effects on child vegetable intake were found. Additionally, further research to understand the best strategies to involve parents in dietary interventions studies is warranted.
The peroxisome proliferator activated receptors (PPARs) are important drug targets in treatment of metabolic and inflammatory disorders. Fibrates, acting as PPARα agonists, have been widely used lipid-lowering agents for decades. However, the currently available PPARα targeting agents show low subtype-specificity and consequently a search for more potent agonists have emerged. In this study, previously isolated oxohexadecenoic acids from the marine algae Chaetoceros karianus were used to design a PPARα-specific analogue. Herein we report the design, synthesis, molecular modelling studies and biological evaluations of the novel 3,5-disubstituted isoxazole analogue 6-(5-heptyl-1,2-oxazol-3-yl)hexanoic acid (1), named ADAM. ADAM shows a clear receptor preference and significant dose-dependent activation of PPARα (EC50 = 47 µM) through its ligand-binding domain (LBD). Moreover, ADAM induces expression of important PPARα target genes, such as CPT1A, in the Huh7 cell line and primary mouse hepatocytes. In addition, ADAM exhibits a moderate ability to regulate PPARγ target genes and drive adipogenesis. Molecular modelling studies indicated that ADAM docks its carboxyl group into opposite ends of the PPARα and -γ LBD. ADAM interacts with the receptor-activating polar network of amino acids (Tyr501, His447 and Ser317) in PPARα, but not in PPARγ LBD. This may explain the lack of PPARγ agonism, and argues for a PPARα-dependent adipogenic function. Such compounds are of interest towards developing new lipid-lowering remedies.
The importance of a mesoscopic description level of the brain has now been well established. Rate based models are widely used, but have limitations. Recently, several extremely efficient population-level methods have been proposed that go beyond the characterization of a population in terms of a single variable. Here, we present a method for simulating neural populations based on two dimensional (2D) point spiking neuron models that defines the state of the population in terms of a density function over the neural state space. Our method differs in that we do not make the diffusion approximation, nor do we reduce the state space to a single dimension (1D). We do not hard code the neural model, but read in a grid describing its state space in the relevant simulation region. Novel models can be studied without even recompiling the code. The method is highly modular: variations of the deterministic neural dynamics and the stochastic process can be investigated independently. Currently, there is a trend to reduce complex high dimensional neuron models to 2D ones as they offer a rich dynamical repertoire that is not available in 1D, such as limit cycles. We will demonstrate that our method is ideally suited to investigate noise in such systems, replicating results obtained in the diffusion limit and generalizing them to a regime of large jumps. The joint probability density function is much more informative than 1D marginals, and we will argue that the study of 2D systems subject to noise is important complementary to 1D systems.
Background One of the objectives of the Norwegian National Action Plan for Healthy Diets (2017-2021) is to increase the intake of fish. The aim of this study was to encourage hotel guests to choose more fish and less meat by altering the choice architecture of hotel lunch buffets with the use of placement and labeling nudges. Methods An experimental study was conducted with three conditions: meat before fish (A), fish before meat (B), and fish before meat including a sign with the text “Eat Smart” placed on the fish dish (C). Conference guests at three hotels were observed during lunch. The number of entrées taken, and the average portion size, was measured. Results The percentage of guests selecting meat decreased in both condition B (48.5%) and condition C (56.1%) compared to condition A (60.3%). The percentage of guests selecting fish increased in both condition B (27.9%) and condition C (34.9%) compared to condition A (23.8%). However, the average amount of fish consumed per guest decreased in condition B (154 grams) and C (159 grams) compared to condition A (238 grams). The effect of the two nudges varied between the hotels. Conclusions Rearranging food order and using signs can nudge conference attendees toward healthier choices. Differences between the hotels might be due to the different designs of the buffets. It is therefore crucial to include the microenvironment when doing interventions.
Aim: Spinal cord injury-induced loss of skeletal muscle mass does not progress linearly. In humans, peak muscle loss occurs during the first 6 weeks postinjury, and gradually continues thereafter. The aim of this study was to delineate the reg- ulatory events underlying skeletal muscle atrophy during the first year following spinal cord injury. Methods: Key translational, autophagic and proteolytic proteins wer e analysed by immunoblotting of human vastus lateralis muscle obtained 1, 3 and 12 months following spinal cord injury. Age-matched able-bodied control subjects were also studied. Results: Several downstream targe ts of Akt signalling decreased after spinal cord injury in skeletal muscle, without changes in resting Akt Ser 473 and Akt Thr 308 phosphorylation or total Akt protein. Abundance of mTOR protein and mTOR Ser 2448 phosphorylation, as well as FOXO1 Se r 256 phosphorylation and FOXO3 protein, decreased in response to spinal cord injury, coincident with attenuated protein abundance of E3 ubiquitin ligases, MuRF1 and MAFbx. S6 protein and Ser 235/236 phosphorylation, as well as 4E-BP1 Thr 37/46 phosphorylation, increased transiently after spinal cord injury, indicating higher levels of protein translation early after injury. Protein abundance of LC3-I and LC3-II decreased 3 months postinjury as compared with 1 month postinjury, but not compared to able-bodied control subjects, indicating lower levels of autophagy. Proteins regulating protea- somal degradation were stabl y increased in response to spinal cord injury. Conclusion: Together, these data provide indirect evidence suggesting that pro- tein translation and autophagy transiently increase, while whole proteolysis remains stably higher in skeletal muscle within the first year after spinal cord injury.
Background: Fish consumption may have beneficial effects on metabolic syndrome (MetS); however, limited information of such associations exists. This study investigated possible associations between fish consumption and changes in MetS components during a 13-year follow-up period. Methods: The sample included participants (26–69 years) from the Tromsø Study 4 (1994–1995, n = 23,907) and Tromsø Study 6 (2007–2008, n = 12,981). Data were collected using questionnaires including food frequency questions, non-fasting blood samples, and physical examinations. MetS was defined using the Joint Interim Societies (JIS) definition, in which one point was given for each MetS criteria fulfilled (metabolic score). Longitudinal analyses were performed using Linear mixed models. Results: For both genders, lean fish consumption once a week or more was significantly associated with decreased future metabolic score, decreased triglycerides, and increased high-density lipoprotein (HDL)-cholesterol, whereas decreased waist circumference and blood pressure was identified only for men (age adjusted models). Fatty fish consumption was significantly associated with increased waist circumference for both genders and increased HDL-cholesterol levels in men. Conclusion: The results suggest that fatty and lean fish consumption may influence MetS differently and that lean fish consumption in particular seems to be associated with beneficial changes in the MetS components.
This study tested a physical activity intervention and the self-determination theory (SDT) process model of health-behavior change and health among 108 adult patients with both diabetes mellitus type 2 (DM2) and coronary artery disease (CAD). Patients were randomly assigned to an organized physical activity intervention group (led by instructors) or a non-physical activity control group. At baseline and after 12 months, we measured the following: needs satisfaction, autonomous and controlled motivation for physical activity, perceived competence for physical activity and blood sugar testing, physical activity and blood sugar testing, body weight, glucose control (HbA1c), and self-perceptions of general health and vitality. The intervention produced, as hypothesized, significant changes in all study variables in favor of the experimental group (Cohen's d effect sizes: 0.23–0.72), except the non-significant result for controlled motivation and body weight. The data supported the SDT process model, in which the effect of the intervention significantly predicted indirect changes in behavior and health through motivation variables. Considering the moderate to large effects on increases in motivation, behavior, and health, promoting organized physical activity programs that are perceived as need-supportive may have important health implications for patients with DM2 and CAD.
In vitro harnessing of immune cells is the most important advance in the field of cancer immunotherapy. Results shown in the current paper may be used to harness natural killer (NK) cells in vitro. It is observed that drugs used to treat multiple sclerosis such as glatiramer acetate, dimethyl fumarate, and monomethyl fumarate upregulate the expression of chemokines receptor 10 (CCR10) on the surface of human IL-2-activated NK cells. This is corroborated with increased chemotaxis of these cells toward the concentration gradients of the ligands for CCR10, namely CCL27 and CCL28. It is also demonstrated that these three drugs enhance NK cell cytotoxicity against tumor target cells, an activity that is abrogated by prior incubation of the cells with anti-CCR10 antibody. Because CCL27 and CCL28 are secreted by selective tumor types such as malignant melanoma, squamous cell carcinomas, and colorectal cancer, respectively, it is hypothesized that activated NK cells may be harnessed in vitro with any of these drugs before utilizing them as a therapeutic modality for cancer.
Purpose To assess melanoma risk in relation to sunscreen use and to compare high– with low–sun protection factor (SPF) sunscreens in relation to sunbathing habits in a large cohort study. Materials and Methods We used data from the Norwegian Women and Cancer Study, a prospective population-based study of 143,844 women age 40 to 75 years at inclusion with 1,532,247 person-years of follow-up and 722 cases of melanoma. Multivariable Cox proportional hazards regression was used to estimate the association between sunscreen use (never, SPF < 15, SPF ≥ 15) and melanoma risk by calculating hazard ratios and 95% CIs. The population attributable fraction associated with sunscreen use was estimated. Results Sunscreen users reported significantly more sunburns and sunbathing vacations and were more likely to use indoor tanning devices. SPF ≥ 15 sunscreen use was associated with significantly decreased melanoma risk compared with SPF < 15 use (hazard ratio, 0.67; 95% CI, 0.53 to 0.83). The estimated decrease in melanoma (population attributable fraction) with general use of SPF ≥ 15 sunscreens by women age 40 to 75 years was 18% (95% CI, 4% to 30%). Conclusion Use of SPF ≥ 15 rather than SPF < 15 sunscreens reduces melanoma risk. Moreover, use of SPF ≥ 15 sunscreen by all women age 40 to 75 years could potentially reduce their melanoma incidence by 18%.
Various rodent models of arthritis are essential to dissect the full complexity of human rheumatoid arthritis (RA), a common autoimmune disease affecting joints. The SKG model of arthritis originates from a spontaneous mutation in ZAP-70 found in a BALB/c colony. This mutation affects T cell selection due to reduced TCR signalling, which allows leakage of self-reactive T cells from the thymus. To further expand the practical applicability of this unique model in arthritis research, we investigated the arthritogenicity of the SKG mutation in two common black mouse strains C57BL/6.Q and C57BL/10.Q and compared to BALB/c.Q. Mice retained the reduced TCR signalling characteristic of SKG.BALB/c mice, which leads to similar alteration in thymic selection. Importantly, mice also retained susceptibility to chronic arthritis after a single injection of mannan from Saccharomyces cerevisiae, with comparable prevalence and severity regardless of the genetic background. Further characterization of CD4+ T cells revealed a similar bias towards IL-17 production and activated T cell phenotype in all SKG strains compared to respective wild type controls. Finally, transfer of SKG thymocytes conferred susceptibility to recipients, which confirm the intrinsic defect and pathogenicity of T cells. Overall, these results underline the strong impact that the W163C ZAP-70 mutation has on T cell-driven arthritis, and they support the use of the SKG model in black mice, which is useful for further investigations of this distinctive arthritis model to better understand autoimmunity.
Little is known about olfactory glands' regulation despite their presumed importance for normal functioning of the cilia of olfactory neurons. The aim of this study was to establish an assay for olfactory gland activation by using large-scale quantitative electron microscopy (EM). In addition we wanted to test the hypothesis that cholinergic drugs activate the olfactory glands, by using our newly established EM assay. In total, over 70 000 secretory gland vesicles were quantified in over 3000 cells. Olfactory gland cell size (40.8 µm2 ± 2.0 SD), vesicle diameter (812 nm ± 57 SD) and vesicles per cell (21.6 ± 4.2 SD) were also quantified. The vesicle percentage of the cell area varied between 24% and 30%. In a blinded study we found no significant effects of cholinergic agents on parameters of vesicle number or vesicle diameter. Unexpectedly, pilocarpine treatment increased olfactory gland size, probably by inducing cell swelling. In conclusion, we have established a quantitative EM assay for olfactory gland activation and provided new data on basic olfactory gland cell characteristics. By using the EM assay, olfactory glands are shown not to be activated by cholinergic agents, which indicates an alternative regulation pathway or constitutive secretion from olfactory glands.
Regular consumption of long-chain n-3 fatty acids (LC n-3 FA) reduces postprandial triacylglycerolaemia. Functional foods and supplements are alternative sources of LC n-3 FA; however, emulsification technologies, food matrices and altered lipid oxidation levels affect their bioavailability. Moreover, which functional foods are optimal LC n-3 FA carriers is unknown. The aim of the study was to determine the bioavailability of LC n-3 FA and the postprandial TAG response after the intake of oxidised or non-oxidised cod liver oil and after the intake of emulsified or non-emulsified LC n-3 FA using novel functional food items as LC n-3 FA carriers in a randomised cross-over acute study. A total of twenty-four healthy subjects completed the study in which subjects consumed one of four different test meals containing 1·5 g LC n-3 FA, or a control meal with no LC n-3 FA. Postprandial TAG-rich lipoproteins were isolated and their fatty acid composition was measured. The LC n-3 FA from emulsified foods were more rapidly incorporated into TAG-rich lipoproteins compared with non-emulsified foods. The incorporation of LC n-3 FA was similar for oils emulsified in yogurt or juice and was unaffected by the oxidative status of the oil. Postprandial TAG levels did not differ among the various test meals. In conclusion, emulsification increases the bioavailability of LC n-3 FA through a more rapid incorporation into TAG-rich lipoproteins, and juice and yogurt are equally suited as LC n-3 FA carriers. The acute intake of oxidised cod liver oil does not influence the incorporation of LC n-3 FA into TAG-rich lipoproteins.
Background Fish consumption may prevent or improve metabolic health. The aim of this study was to identify associations between fish consumption, both fatty and lean, and metabolic syndrome and its components. Methods Associations between fish consumption and metabolic syndrome and its components were studied in a large sample from a Norwegian population (N = 23,907), using cross-sectional data from the Tromsø 4 survey (1994–1995). Metabolic syndrome was defined using the JIS definition, and dietary data was collected using food frequency questionnaires (FFQ). Blood samples were taken for biochemical assessments, and anthropometric and blood pressure measurements were carried out according to standard protocols. Results In this sample from an adult population (aged 26–70 years, mean age 44 years, SD 11.69, 48 % men), a higher fish consumption (≥1/week) was associated with a healthier lipid profile with increased HDL-C and decreased TG. Participants aged 60–70 years consuming fish once a week or more had significantly lower risk of having MetS, compared to those consuming fish less than once a week (OR 0.64, CI 0.45–0.91). When investigating fatty and lean fish separately, only lean fish consumption was associated with a reduced the risk of having MetS. Participants aged 60–70 years consuming lean fish once a week or more, had lower risk of having MetS compared to those consuming lean fish less than once a week (OR 0.65, CI 0.48–0.87). No association was found for consumption of fatty fish, or for lean fish in the age groups <45 or 45–59 years. Conclusions These results indicates that fatty and lean fish consumption influences MetS risk differently, possibly also related to age. However, further investigation is needed to establish how various fish consumption may influence MetS and its components, particularly when stratified by fatty and lean fish.
Single-motor-unit discharge characteristics in human lumbar multifidus muscle. J Neurophysiol 114: 1286–1297, 2015. First published June 18, 2015; doi:10.1152/jn.00010.2014.—The underlying neurophysiology of postural control of the lower back in humans is poorly understood. We have characterized motor unit (MU) discharge activity in the deep lumbar multifidus (LM) muscle in nine healthy subjects (20–40 yr, 3 females). Bilateral fine wire electrodes were implanted at L4 spinal level using ultrasound guidance. EMG was recorded during sponta- neous sitting and standing and during voluntary force production. Individual MUs were analyzed with regard to instantaneous discharge rate, interspike interval variability, alternation of activity between MUs, and cross correlation between concurrently active MUs quan- tified by the common drive coefficient (CDC). Significant effects of sitting vs. standing were seen on median discharge rate and interspike interval variability. Median discharge rate in 71 units was 5.4 and 6.9 pulses/s during spontaneous sitting and standing and 7.4 pulses/s during voluntary force production. Several MUs fired doublets. CDC analysis of 87 MU pairs showed a significantly higher common drive in spontaneous than in voluntary activity and significant differences between unilateral and bilateral pairs, although not when spontane- ously active in standing. In spite of common drive, MUs were re- cruited from inactivity to tonic discharge lasting for several minutes without changes in discharge rate in already active MUs, and several instances were documented where activity was rotated between MUs. We argue that this behavior is indicative of self-sustained discharge in LM motoneurons, establishing intrinsic motoneuron properties as a central mechanism for postural control of deep back muscles.
Cortical spreading depression is a slowly propagating wave of near-complete depolarization of brain cells followed by temporary suppression of neuronal activity. Accumulating evidence indicates that cortical spreading depression underlies the migraine aura and that similar waves promote tissue damage in stroke, trauma, and hemorrhage. Cortical spreading depression is characterized by neuronal swelling, profound elevation of extracellular potassium and glutamate, multiphasic blood flow changes, and drop in tissue oxygen tension. The slow speed of the cortical spreading depression wave implies that it is mediated by diffusion of a chemical substance, yet the identity of this substance and the pathway it follows are unknown. Intercellular spread between gap junction-coupled neurons or glial cells and interstitial diffusion of K(+) or glutamate have been proposed. Here we use extracellular direct current potential recordings, K(+)-sensitive microelectrodes, and 2-photon imaging with ultrasensitive Ca(2+) and glutamate fluorescent probes to elucidate the spatiotemporal dynamics of ionic shifts associated with the propagation of cortical spreading depression in the visual cortex of adult living mice. Our data argue against intercellular spread of Ca(2+) carrying the cortical spreading depression wavefront and are in favor of interstitial K(+) diffusion, rather than glutamate diffusion, as the leading event in cortical spreading depression.
Astrocytic endfeet are specialized cell compartments whose important homeostatic roles depend on their enrichment of water and ion channels anchored by the dystrophin associated protein complex (DAPC). This protein complex is known to disassemble in patients with mesial temporal lobe epilepsy and in the latent phase of experimental epilepsies. The mechanistic underpinning of this disassembly is an obvious target of future therapies, but remains unresolved. Here we show in a kainate model of temporal lobe epilepsy that astrocytic endfeet display an enhanced stimulation-evoked Ca(2+) signal that outlast the Ca(2+) signal in the cell bodies. While the amplitude of this Ca(2+) signal is reduced following group I/II metabotropic receptor (mGluR) blockade, the duration is sustained. Based on previous studies it has been hypothesized that the molecular disassembly in astrocytic endfeet is caused by dystrophin cleavage mediated by Ca(2+) dependent proteases. Using a newly developed genetically encoded Ca(2+) sensor, the present study bolsters this hypothesis by demonstrating long-lasting, enhanced stimulation-evoked Ca(2+) signals in astrocytic endfeet.
Objectives. To examine the protocol adherence to the theoretical background of Acceptance and Commitment Therapy (ACT) in a RCT of a web-based intervention including e-diaries and written personalized feedback delivered via smartphone for persons with chronic widespread pain. Methods. The data consisted of 790 written feedback. A qualitative descriptive design on how ACT and other therapeutic processes were used in the feedback which was applied. The analysis was done with a feedback coding scheme developed employing a combination of an inductive and deductive approach. Results. The coded feedback messages reflected five of the six main ACT processes in addition to communication and motivation strategies. The degree of inter-rater reliability between the researchers coding the feedback, measured by Cohen’s kappa, was 0.790. Conclusions. Based on the level of adherence to ACT-principles the treatment integrity can be judged as high. The developed coding scheme can serve as a basis for coding written therapeutic feedback and thereby serve as a tool for a reliable assessment of the treatment fidelity in ACT based interventions delivered by internet. Practice Implications. Internet-delivered psychological interventions to support people with chronic conditions are increasingly common. Such interventions can be seen as person-centered therapeutic approaches. This study indicates that ACT can reliably be delivered in a written web-based format.
Metabolic syndrome (MetS) has a huge impact on public health, and today lifestyle interventions remain the primary mode for MetS therapy. It is therefore important to elucidate the possible preventive effects of diet and foods, and their MetS-related health implications. To examine how fish consumption affects the development and prevalence of MetS, we systematically reviewed cross-sectional, prospective cohort, and intervention studies conducted among adults (humans) and, reporting consumption of fish or seafood as being related to MetS (prevalence or incidence), where MetS was defined via an established definition. The literature search in PubMed identified 502 citations, and after screening, 49 full-text articles were retrieved and assessed for eligibility. After excluding duplicates and those not meeting the inclusion criteria, seven studies from Croatia, Finland, France, Iceland, Iran, Korea, and US were included. Four studies (one follow-up and three cross-sectional) found associations between fish consumption and MetS (three among men, and one among women), suggesting that fish consumption may prevent or improve metabolic health and have a protective role in MetS prevention. This protective role might be related to gender, and men may benefit more from the consumption of fish. However, lack of controlling for potential confounders may also inflict the results. Additional research is required to further explore fish consumption and its potential role in improving or reversing MetS and its components.
Genetic predisposition to the complex hereditary disease like osteoarthritis (OA) of the large joints (hip and knee) includes the interleukin-1 gene (IL-1) cluster on chromosome 2. Using a case–control study with 500 OA patients (240 knee and 260 hip OA patients, all with joint replacement), we analysed frequencies of IL-1 gene cluster polymorphisms in Croatian Caucasian population. The control samples came from 531 healthy individuals including blood donors. We genotyped two single nucleotide polymorphisms in the IL-1 gene locus at IL-1A (−889, C>T, rs1800587) and IL-1B (+3594, C>T, rs1143634) and compared their frequencies between patients and controls. We predicted haplotypes by combining current data with our previous results on gene polymorphisms (IL-1B, rs16944 and the IL-1 receptor antagonist gene [IL-1RN] variable number tandem repeat [VNTR]) for the same population. Haplotype analyses revealed gender disparities and showed that women carriers of the 1-2-1-1 haplotype [IL-1A(rs1800587) – IL-1B(rs1143634) – IL-1B(rs16944) – IL-1RN(VNTR)] had sixfold lower risk to develop knee OA. However, carriers of the 1-1-1-2 haplotype of both sexes had over twofold higher predisposition to hip OA. Our results differ from some earlier studies in Caucasian subpopulations, which may be due to the fact that this is the first study to separate genders in assessing the IL-1-locus genetic risk of OA. The results suggest that inflammatory mediators like IL-1 might be implicated in the pathogenesis of primary OA in large joints and that as yet unidentified gender-specific factors exist in a Croatian Caucasian population
Background: An increased risk of breast cancer has been observed in night shift workers. Exposure to artificial light at night and disruption of the endogenous circadian rhythm with suppression of the melatonin synthesis have been suggested mechanisms. We investigated the hypothesis that rotating night shift work is associated with mammographic density. Methods: We conducted a cross-sectional study on the association between rotating night shift work characteristics, 6-sulfatoxymelatonin (MT6s) creatinine adjusted in a spot morning urine sample, and a computer-assisted measure of mammographic density in 640 nurses and midwives ages 40 to 60 years. The associations were evaluated using regression models adjusted for age, body mass index, menopausal status, age at menopause, age at menarche, smoking, and the calendar season of the year when mammography was conducted. Results: The adjusted means of percentage of mammographic density and absolute density were slightly higher among women working rotating night shifts but not statistically significant [percentage of mammographic density = 23.6%, 95% confidence interval (CI), 21.9%–25.4% vs. 22.5%, 95% CI, 20.8%–24.3%; absolute density = 23.9 cm2, 95% CI, 21.4–26.4 cm2 vs. 21.8 cm2, 95% CI, 19.4–24.3 cm2 in rotating night shift and day shift nurses, respectively). There were no significant associations between the current or cumulative rotating night shift work exposure metrics and mammographic density. No association was observed between morning MT6s and mammographic density. Conclusions: The hypothesis on the link between rotating night shift work, melatonin synthesis disruption, and mammographic density is not supported by the results of the present study. Impact: It is unlikely that the development of breast cancer in nurses working rotating night shifts is mediated by an increase in mammographic density. Cancer Epidemiol Biomarkers Prev; 21(7); 1028–37. ©2012 AACR.
Blue mussels (Mytilus edulis) accumulate and biotransform arsenic (As) to a larger variety of arsenicals than most seafood. Eight volunteers ingested a test meal consisting of 150 g blue mussel (680 lg As), followed by 72 h with an identical, low As controlled diet and full urine sampling. We provide a complete speciation, with individual patterns, of urinary As excretion. Total As (tAs) urinary excretion was 328 ± 47 lg, whereof arsenobetaine (AB) and dimethylarsinate (DMA) accounted for 66% and 21%, respectively. Fifteen minor urinary arsenicals were quantified with inductively coupled plasma mass spectrometry (ICPMS) coupled to reverse-phase, anion and cation-exchange high performance liquid chromatography (HPLC). Thio-arsenicals and non-thio minor arsenicals (including inorganic As (iAs) and methylarsonate (MA)) contributed 10% and 7% of the total sum of species excretion, respectively, but there were large individual differences in the excretion patterns. Apparently, formation of thioarsenicals was negatively correlated to AB formation and excretion, possibly indicating a metabolic interrelationship. The results may be of toxicological relevance since DMA and MA have been classified as possibly carcinogenic, and six of the excreted As species were thio-arsenicals which recently have been recognized as toxic, while iAs toxicity is well known
In a cancer cell the number of copies of a locus may vary due to amplification and deletion and these variations are denoted as copy number alterations (CNAs). We focus on the disparity of CNAs in tumour samples, which were compared to those in blood in order to identify the directional loss of heterozygosity.
In mammals, sex specialization is reflected by differences in brain anatomy and function. Measurable differences are documented in reproductive behavior, cognition, and emotion. We hypothesized that gonadotropin-releasing hormone (GnRH) plays a crucial role in controlling the extent of the brain's sex specificity and that changes in GnRH action during critical periods of brain development, such as puberty, will result in altered sex-specific behavioral and physiological patterns. We blocked puberty in half of the 48 same-sex Scottish mule Texel cross sheep twins with GnRH analog (GnRHa) goserelin acetate every 3weeks, beginning just before puberty. To determine the effects of GnRHa treatment on sex-specific behavior and emotion regulation in different social contexts, we employed the food acquisition task (FAT) and measurement of heart rate variability (HRV). ANOVA revealed significant sex and sex×treatment interaction effects, suggesting that treated males were more likely to leave their companions to acquire food than untreated, while the opposite effect was observed in females. Concordant results were seen in HRV; treated males displayed higher HRV than untreated, while the reverse pattern was found in females, as shown by significant sex and sex×treatment interaction effects. We conclude that long-term prepubertal GnRHa treatment significantly affected sex-specific brain development, which impacted emotion and behavior regulation in sheep. These results suggest that GnRH is a modulator of cognitive function in the developing brain and that the sexes are differentially affected by GnRH modulation.
Objective A challenging but main task for clinicians is to identify patients’ concerns related to their medical conditions. The study aim was to validate a new coding scheme for identifying patients’ cues and concerns. Methods 12 videotaped consultations between nurses and pain patients were coded according to the Verona Coding Scheme for Emotional Sequences (VR-CoDES). During a metainterview each patient watched his/her own video interview with the researcher to confirm or disconfirm the identified cues and concerns. A directive or an open format was applied. Quantitative and qualitative data analyses were performed. Results Patients’ confirmation in relation to the coding gave a sensitivity of 0.95 and specificity of 0.99 in the directive format and a sensitivity of 0.99 and specificity of 0.70 applying the open format. Through a qualitative analysis 83% of researcher-identified cues and concerns were validated. 17% were not confirmed or uncertain. Conclusion The VR-CoDES seems to capture what are experienced as real concerns to patients, and proves to be a coding scheme with a high degree of ecological validity. Practice implications The VR-CoDES provides a valid framework for detecting patients’ cues and concerns, and should be explored as a training tool to develop clinicians’ empathic accuracy. Keywords: Cues; Concerns; Empathy; Empathic accuracy; Patient–provider communication; Nurse–patient relations; Stimulated recall
Background: In Norway, women with a Somali background are more overweight and obese than their Norwegian counterparts, with an increased susceptibility to diabetes and other lifestyle-related diseases. However, there is limited information on their dietary intake. This study aimed to describe food and nutrient intake among overweight and obese women with a Somali background in Oslo. Methods: Design: Baseline data for the lifestyle intervention study. Setting: Oslo municipality. Participants: Overweight and obese women (n = 168) aged 22-82 years, were included in the intervention study between September 2020 and September 2022. A trained interviewer performed 24-hour dietary recalls on two consecutive days to assess food and beverage intake. The dietary assessment system KBS (version 7.3, University of Oslo, Oslo, Norway, database AE-18) was used for energy, food, and nutrient estimation. Results: The mean (SD) age was 46.8 (10.4) years, and the mean BMI (SD) was 33.9 kg/m2 (5.1). The main dietary intake was traditional Somali foods, such as rice, pasta, and meat. The mean energy intake was 4.3 MJ/day. The median energy percentages from carbohydrates, fat, protein, and added sugar were in accordance with the Norwegian nutrition recommendations. The total median intake of almost all micronutrients was below the recommended daily intake, except for vitamin A, niacin, vitamin B12, zinc, and selenium. Conclusions: We found that overweight and obese women with a Somali background most commonly eat cereal products such as rice, pasta, and meat. The average energy intake was low, suggesting assessment bias. Most of the macronutrient intake was in compliance with the daily recommendations. However, the intake of micronutrients was below the recommended daily intake, which may be a result of the generally low energy intake. Weekend days were not systematically included in the repeated 24-hour recall and may have resulted in underreporting of dietary intake; thus, the results need to be interpreted with caution. Further research is required to investigate the dietary intake in this population using different dietary assessment methods for developing preventive public health programs for immigrant groups. Main message: Diet is an important factor for the burden of disease in Norway and therefore it is important to improve the diet of immigrant population particularly the intake of vitamins and minerals.
Hyaluronic acid (HA) is a high-molecular-mass polysaccharide, that is endogenously produced and present in connective tissue, synovial fluid, intraoccular fluid, and skin. The basic unit of the HA polymer consists of D-glucuronic acid and N-acetyl-D-glucosamine. The Norwegian Food Safety Authority has requested VKM to evaluate the risk of adverse effects related to daily intake of food supplements with 150 mg, 120 mg, 64 mg, and 48 mg HA. Exposure from other sources of HA (food, cosmetics, and different medical applications) is not estimated.
Aim: Describe the trends in melanoma tumour thickness in Norway by T category, overall and in important subgroups such as sex, age, anatomic site, and histopathological subtype, over 35-year.
Et enkelt eksperiment med te og melk kan ha inspirert den britiske statistikeren Ronald Aylmer Fisher (1890–1962) til å lage en av verdens mest kjente statistiske tester.
The International Neuroinformatics Coordinating Facility (INCF) is an international network of national nodes with neuroinformatics expertise and infrastructure to support collaboration throughout the global brain research community. The mission of the INCF is to accelerate advances in understanding and treating the brain through the development of neuroinformatics - applying the best practices of data science to challenges in basic and clinical brain research. The major scientific output of the organisation has over the recent years been through 4 scientific programs, focusing on Digital Brain Atlasing (Waxholm Space atlases and Scalable Brain Atlas), Ontologies of Neural Structures (NeuroLex and KnowledgeSpace), Standards for Data Sharing (federated infrastructure for storage - DataSpace, Neuroimaging Analysis Pipeline – Nipype, and standard for storing basic electrophysiology data), and Multiscale Modeling (Network Interchange Format for Neuroscience - NineML, and Multi-Simulation Coordinator - MUSIC). All programs have strong engagement from the neuroinformatics community worldwide. The organization is introducing a new agile model for future work which will allow activities of the programs to continue while responding rapidly to new developments and community needs also in other areas of neuroinformatics, including training and education. Overall, INCF strategic objectives include 1) partnering with international stakeholders to promote and prioritise neuroinformatics at global, national and local levels, 2) advancing data reuse and reproducibility in brain research through the development of global standards, best practices, tools and infrastructure, 3) catalyzing community-driven collaborative brain research projects by engaging scientific, clinical, technical, industry and funding partners, and 4) serving as a globally recognized leader for the development and provision of training and educational resources in neuroinformatics.
With a new generation of three-dimensional digital brain atlases, new solutions for analyzing and integrating brain data are being developed. Digital brain atlases will serve as frameworks for services similar to current online geographical atlases, such as Google Maps and Google Earth, which provide interactive access to huge amounts of high resolution image data, together with additional information and detailed visualizations. The key aim of the INCF program on digital atlasing is to coordinate and improve the impact of atlasing projects, with a focus on the rodent brain. Several of the INCF national nodes contribute to development of infrastructures for brain atlasing in a combined effort with the European Union ICT Future Emerging Technologies Flagship project, the Human Brain Project. The templates used for digital brain atlases can be high resolution 3-D histology data or other volumetric data sets acquired with, e.g., magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). The templates can re-sliced and viewed in arbitrary angles without loss of image quality. Additional data modalities required to delineate brain regions can be added by registering high resolution microscopic images from slices through the brain to the templates. With these new atlas frameworks, and a set of tools to interact with the frameworks, research groups can connect their data to atlas space, share the data through online data systems, and search and find other relevant data through the same systems. The main role of the INCF in these efforts is to continue to support the establishment of standards for nomenclatures and spatial coordinate systems (Waxholm Space), and coordinate the development of data systems delivering services to the community. Examples of efforts at the national level include the Scalable Brain Atlas (Dutch node of the INCF) and the Rodent Brain WorkBench (Norwegian node of the INCF). New INCF special interest groups are being established, aiming at reaching out to the broader science community.
Volumetric brain atlases are typically built on top of template data sets acquired with Magnetic Resonance Imaging. A relatively high level of structural details is provided combined with the advantage of allowing the entire brain to be viewed interactively in any plane. With appropriate tools for interactive viewing, volumetric atlases are useful for planning of experiments and data analysis by registration of other data sets to the atlas. We provide a volumetric atlas of the rat brain based on ex vivo MRI anatomical (T2*) images with 39 μm isotropic voxels and diffusion tensor imaging (DTI) volumes with 78 μm isotropic voxels acquired from an 80 day old male Sprague-Dawley rat. The atlas covers 83 anatomical structures (areas, nuclei, regions, and fiber tracts) across the brain. The structures were delineated using ITK-SNAP software based on multiple types of image contrasts and anatomical reference information. White matter structures were readily distinguished from grey matter, and some structural differences could also be observed within gray matter. Delineations were aided by information from classical 2D atlases and collections of histological images from brains of comparable animals, and delineation criteria were defined for all structures. Cyto- and chemoarchitectonic features from an online 2D histological atlas (Kjonigsen et al., Front Neuroinform. 2011) were used for delineation of 16 structures in the hippocampal region. The atlas and the underlying MRI and DTI image volumes are to be made open access through the INCF Software Center. Spatial reference is provided by Waxholm Space, a standard atlas space recently defined by the International Neuroinformatics Coordinating Facility (INCF). Waxholm Space connects the atlas to a growing infrastructure of interoperable resources and services for multi-level data integration and analysis across reference spaces.
I Forskningskampanjen inviterer vi skoleelever fra hele landet til å undersøke noe i sitt nærmiljø. I september 2018 fikk over 10 000 i oppdrag å forske på den norske skolematen.
M.Sc. Marion Haugen og medarbeidere har studert nye metoder for å forklare variasjon i individuell risiko for nasofarynkskreft (kreft i overgangen mellom nese og svelg) og komplekse avhengighetsstrukturer i familiedata. Metoden for familiedata er anvendt på føflekkreft. Tid til oppsigelse av bilforsikringer med samme eier er analysert med en eksisterende metode fra forløpsanalyse som tar hensyn til eventuell avhengighet. I forløpsanalyse inkluderes variabler slik som f.eks. kjønn og alder for å undersøke deres effekt og for å modellere ulik risiko for individer (observert heterogenitet). I medisinske studier kan økonomiske årsaker gjøre det umulig å måle alle relevante variabler. Dersom variabler utelates eller er ukjente kan dette resultere i at noen individer har høyere risiko enn andre (uobservert heterogenitet). Risikoen kan også variere mellom grupper, f.eks. viser flere sykdommer en overopphopning av tilfeller innen familier. Ved analyse av slike data brukes gjerne metoder som gir avhengighet i tid til hendelse. For visse populasjoner har de observerte aldersspesifikke insidensrater for nasofarynkskreft én liten topp i de sene tenårene og én topp rundt pensjonsalder. En bimodal modell gir signifikant bedre tilpasning til dataene enn en modell med kun én topp. For føflekkreft kan man for hvert individ tenke seg tre nivåer av avhengighet: individuelt miljø, genetikk og felles miljø. Den nye metoden gir nivåenes bidrag til variasjonen i familiær risiko. Forsikringskunder reagerer ulikt på prisendringer, noen er mindre lojale enn andre. Observerbare variabler kan ikke forklare hele denne variasjonen. Den anvendte metoden gir ulik risiko for kunder, men lik risiko for biler til en kunde. Modellering av ulik risiko innen populasjoner er ofte nødvendig for å få riktig fortolkning av resultater fra forløpsanalyse. De anvendte metodene har vist seg nyttige til dette.