Search

BackgroundSecretion of saliva is controlled by autonomic nerve signals via regulation of Ca2+-dependent ion transport across acinar cell membranes. Oxidative stress may affect this process, leading to a decrease in saliva production. This study investigates elements of the Ca2+ regulatory pathway and their vulnerability to hydrogen peroxide-induced oxidative stress.MethodsRat parotid and submandibular salivary gland acinar cell lines were exposed to different hydrogen peroxide concentrations to simulate oxidative stress. Cell viability and intracellular reactive oxygen species were measured, mRNA levels were assessed via RT-qPCR, and protein expression was studied using western blot and immunofluorescence microscopy.ResultsElevated concentrations of hydrogen peroxide reduced cell viability and increased intracellular levels of reactive oxygen species and led to a decrease in cholinergic receptor muscarinic 3 and adrenoreceptor alpha 1A mRNA and protein levels in both cell lines. In parotid gland cells, both mRNA and protein levels of stromal interaction molecule 1 and Orai1 decreased with increasing concentrations of hydrogen peroxide. In contrast, in submandibular gland cells stromal interaction molecule 1 and Orai1 displayed differential mRNA and protein expression levels.ConclusionOur study revealed that hydrogen peroxide exposure alters rat parotid and submandibular acinar cells, increasing reactive oxygen species and reducing autonomic receptor expression. Differential mRNA and protein expression of stromal interaction molecule 1 and Orai1 highlight complex oxidative stress effects on Ca2⁺ signaling. Most likely these effects will be deleterious to salivary secretion, but some effects may be protective.

IntroductionNormal oral fibroblasts (NOFs) are located in the connective tissue of the oral mucosa. The NOFs play an important role in wound healing, tumor progression, and metastasis. They are subjected to influence by external and internal stimuli, among them extracellular vesicles (EVs), that are considered as important players in cell to cell communication, especially in carcinogenesis and metastatic processes. During tumorigenesis, stromal NOFs may undergo activation into cancer-associated fibroblasts (CAFs) that modify their phenotype to provide pro-oncogenic signals that in turn facilitate tumor initiation, progression, and metastasis. The aim of the study was to reveal the effect of EVs derived from local (oral squamous cell carcinoma – OSCC) and distant (pancreatic adenocarcinoma – PDAC; malignant melanoma brain metastasis – MBM) cancer origin on NOFs and their possible change into a CAF-like direction.MethodsThe effect of each of the cancer EV types on NOFs proliferation, viability, and migration was tested. Also, changes in gene expression of the well-established CAF biomarkers ACTA2, FAP, PDGFR, and two putative CAF biomarkers, the Ca2+- activated ion channels ANO1 and KCNMA, were studied.ResultsObtained results indicate that NOFs receive and process signals transmitted by EVs originating from both OSCC, PDAC, and MBM. The fibroblast response was dependent on EV origin and concentration, and duration of EV exposure.ConclusionThe present results indicate that the molecular cargo of the EVs direct NOFs towards a pro-tumorigenic phenotype.

Abstract Understanding how the nutritional properties of food resources drive foraging choices is important for the management and conservation of wildlife populations. For moose (Alces alces), recent experimental and observational studies during the winter have shown macronutrient balancing between available protein (AP) and highly metabolizable macronutrients (total non‐structural carbohydrates [TNC] and lipids). Here, we combined the use of continuous‐recording camera collars with plant nutrient analyses and forage availability measurements to obtain a detailed insight into the food and nutritional choices of three wild moose in Norway over a 5‐day period in summer. We found that moose derived their macronutrient energy primarily from carbohydrates (74.2%), followed by protein (13.1%), and lipids (12.7%). Diets were dominated by deciduous tree browse (71%). Willows (Salix spp.) were selected for and constituted 51% of the average diet. Moose consumed 25 different food items during the study period of which 9 comprised 95% of the diet. Moose tightly regulated their intake of protein to highly metabolizable macronutrients (AP:TNC + lipids) to a ratio of 1:2.7 (0.37 ± 0.002SD). They did this by feeding on foods that most closely matched the target macronutrient ratio such as Salix spp., or by combining nutritionally imbalanced foods (complementary feeding) in a non‐random manner that minimized deviations from the intake target. The observed patterns of macronutrient balancing aligned well with the findings of winter studies. Differential feeding on nutritionally balanced downy birch (Betula pubescens) leaves versus imbalanced twigs+leaves across moose individuals indicated that macronutrient balancing may occur on as fine a scale as foraging bites on a single plant species. Utilized forages generally met the suggested requirement thresholds for the minerals calcium, phosphorus, copper, molybdenum, and magnesium but tended to be low in sodium. Our findings offer new insights into the foraging behavior of a model species in ungulate nutritional ecology and contribute to informed decision‐making in wildlife and forest management.

T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically presents at an advanced stage, with marked leukocytosis, B symptoms, hepatosplenomegaly, and bone marrow failure. It usually follows an aggressive course from presentation, and the prognosis is often considered dismal; the median overall survival is less than one year with conventional chemotherapy. This case report describes a patient with T-PLL who, after an unusually protracted inactive phase, ultimately progressed to a highly invasive, organ-involving disease. After initial treatments failed, a novel treatment approach resulted in a significant response.

Abstract Background Women with pre-pregnancy obesity have an increased risk of retaining or gaining weight postpartum and may benefit from weight loss treatment. However, evidence is lacking for weight loss strategies in women with BMIs in the higher obesity classes. A dietary treatment for postpartum weight loss resulted in a 10% weight reduction in lactating women with a mean BMI of 30 kg/m2. We aimed to examine the effects of this dietary treatment on changes in weight, markers of lipid and glucose metabolism, waist and hip circumference and postpartum weight retention (PPWR) in postpartum women with higher BMIs than tested previously. Methods At baseline, approximately 8 weeks postpartum, 29 women with a mean (SD) BMI = 40.0 (5.2) kg/m2 were randomised to a 12-week dietary treatment (n 14) or to a control treatment (n 15). Measurements were made at baseline and after 3 and 12 months. Data was analysed using mixed model. Results The mean weight change in the diet group was -2.3 (3.1) kg compared to 1.7 (3.1) kg in the control group after 3 months (P = 0.003) and -4.2 (5.6) kg compared to 4.8 (11.8) kg in the control group after 12 months (P = 0.02). The dietary treatment led to reduced waist circumference (P

Background and aimsDiabetes-related foot ulcers (DFU) are a persistent healthcare challenge, impacting both patients and healthcare systems, with adverse effects on quality of life and productivity. Our primary aim was to examine the trends in lifetime prevalence of DFU, as well as other micro- and macrovascular complications in the Trøndelag Health Study (HUNT) in Norway.MethodsThis study consists of individuals ≥20 years with diabetes participating in the population-based cross-sectional HUNT surveys (1995-2019). Prevalence ratios, comparing the lifetime prevalence of DFU and other relevant micro- and macrovascular complications between the HUNT surveys, were calculated using Poisson regression.ResultsThe lifetime prevalence (95% confidence interval (CI)) of a DFU requiring three or more weeks to heal was 11.0% (9.5-12.7) in HUNT2, 7.5% (6.3-8.8) in HUNT3 and 5.3% (4.4-6.3) in HUNT4. The decrease in DFU prevalence from 1995 to 2019 was observed in both men and women, for all age groups, and for both type 1 and type 2 diabetes. The highest lifetime prevalence of DFU was found among those with type 1 diabetes. The decrease in HbA1c from HUNT2 to HUNT4 did not differ between those with and without a DFU. The prevalence of chronic kidney disease (eGFR

ABSTRACTCold weather injuries (CWIs) are a challenge during military training, exercises and operations in Arctic conditions. Soldier performance in these challenging conditions depends on protective equipment, knowledge, personal experience, routines, and leadership. Despite the Norwegian Armed Forces’ goal of zero freezing cold injuries (FCIs), there has been a persistently high incidence of FCIs among the younger soldiers with an average of 120–150 new FCIs recorded each year. Therefore, an expert working group with representatives from medical, defence and research background was established in 2020. Their task was to develop a communication package to help prevent CWIs among military personnel. Training videos and an updated and improved official website were created with a focus on practical recommendations and advice to prevent CWIs and especially FCIs. Risks, prevention and symptoms of FCIs were emphasised. The main goal of the training videos was to supplement current teaching on guidance for CWI prevention in CWOs to prevent FCIs, but following the advice may prevent non-freezing cold injuries (NFCIs) and hypothermia. This informative paper describes the background, working methods and possible implications of the training videos, which may be a potential way forward to improve cold weather training and operations.

Abstract Background Numerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent. Methods This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age). Results Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ P interaction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ P interaction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ P interaction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ P interaction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ P interaction ≤ 0.99). Conclusions Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

Abstract Periodontitis is an inflammatory condition caused by bacteria and represents a serious health problem worldwide as the inflammation damages the supporting tissues of the teeth and may predispose to systemic diseases. Porphyromonas gingivalis is considered a keystone periodontal pathogen that releases bacterial extracellular vesicles (bEVs) containing virulence factors, such as gingipains, that may contribute to the pathogenesis of periodontitis. This study aimed to isolate and characterize bEVs from three strains of P. gingivalis, investigate putative bEV uptake into human oral fibroblasts, and determine the gingipain activity of the bEVs. bEVs from three bacterial strains, ATCC 33277, A7A1‐28, and W83, were isolated through ultrafiltration and size‐exclusion chromatography. Vesicle size distribution was measured by nano‐tracking analysis (NTA). Transmission electron microscopy was used for bEV visualization. Flow cytometry was used to detect bEVs and gingipain activity was measured with an enzyme assay using a substrate specific for arg‐gingipain. The uptake of bEVs into oral fibroblasts was visualized using confocal microscopy. NTA showed bEV concentrations from 108 to 1011 particles/mL and bEV diameters from 42 to 356 nm. TEM pictures demonstrated vesicle‐like structures. bEV‐gingipains were detected both by flow cytometry and enzyme assay. Fibroblasts incubated with bEVs labeled with fluorescent dye displayed intracellular localization consistent with bEV internalization. In conclusion, bEVs from P. gingivalis were successfully isolated and characterized, and their uptake into human oral fibroblasts was documented. The bEVs displayed active gingipains demonstrating their origin from P. gingivalis and the potential role of bEVs in periodontitis.

In this study the authors investigate household transmission of SARS-CoV-2 in Norway. They find that the secondary attack rate was higher for Omicron than Delta, but that among three-dose vaccinated contacts the secondary attack rate was lower for both variants compared to contacts with two doses.

Purpose: To assess image quality of a deep learning reconstruction (DLR) algorithm across dose levels using a semi-anthropomorphic upper-abdominal phantom, and compare with filtered back projection (FBP) and hybrid iterative reconstruction (IR). Material and methods: CT scans obtained at five dose levels (CTDIvol 5, 10, 15, 20 and 25 mGy) were reconstructed with FBP, hybrid IR (IR50, IR70 and IR90) and DLR of low (DLL), medium (DLM) and high strength (DLH) in 0.625 mm and 2.5 mm slices. CT number, homogeneity, noise, contrast, contrast-to-noise ratio (CNR), noise texture deviation (NTD; a measure of IR-specific artifacts), noise power spectrum (NPS) and task-based transfer function (TTF) were compared between reconstruction algorithms. Results: CT numbers were highly consistent across reconstruction algorithms. Image noise was significantly reduced with higher levels of DLR. Noise texture (NPS and NTD) was with DLR maintained at comparable levels to FBP, contrary to increasing levels of hybrid IR. Images reconstructed with DLR of low and high strength in 0.625 mm slices showed similar noise characteristics to 2.5 mm slice FBP and IR50, respectively. Dose-reduction potential based on image noise with IR50 as reference was estimated to 35% for DLM and 74% for DLH. Conclusions: The novel DLR algorithm demonstrates robust noise reduction with maintained noise texture characteristics despite higher algorithm strength, and may have overcome important limitations of IR. There may be potential for dose reduction and additional benefit from thin-slice reconstruction.

The COVID-19 pandemic has resulted in increased attention on infection prevention measures. This study aims to assess whether changes in hand hygiene procedures, use of personal protective equipment and moisturizers during the first year of the COVID-19 pandemic were associated with changes in the occurrence of skin symptoms among healthcare workers, cleaners, and day-care workers. A total of 602 participants (40%) responded to an electronic questionnaire, including questions on previous and current occupational exposure and skin problems. Increased frequency of hand washing, use of hand disinfectants, use of disposable gloves and moisturizers were all associated with an increased symptom score on the hands, wrists, forearms. Participants who increased their use of masks or respirators had a higher risk of facial skin symptoms, compared with those with non-increased occupational exposure. In conclusion, a change of behaviour among healthcare workers, cleaners and day-care workers during the first year of the COVID-19 pandemic, with an increase in occupational exposures and use of moisturizers, was associated with higher occurrence of facial skin symptoms and symptoms on the hands, wrists and forearms.

To optimize students’ levels of skills, knowledge, and competence in higher education, teachers have been encouraged to work systematically to understand how their pedagogical approaches affect the students’ learning process and learning outcomes. The purpose of this study was to examine the efficacy of a student-centered learning design (SCL) in the subject of PE. A total of 24 PETE students were given the responsibility to create the schedule for their own education in a subject for a semester. During the semester, the students wrote reflections note on three occasions related to their learning process and learning outcome. The thematical analysis of the reflection notes revealed two main findings concerning the learning process: an invitation to participate and develop professional ownership, and mixed reflections on the need for teacher scaffolding. Furthermore, the analyses revealed two main findings concerning the learning outcome: improved learning and meaningful learning. Our findings indicate that students’ participation, motivation, enjoyment, and learning outcomes increased due to the use of SCL as a pedagogical strategy. These findings are supported by other investigations, identifying SCL as a preferred strategy according to students’ learning process and learning outcomes. The main pedagogical implication of our findings is a recommendation to implement SCL as a pedagogical strategy for student learning in teacher education.

Abstract At northern latitudes, large spatial and temporal variation in the nutritional composition of available foods poses challenges to wild herbivores trying to satisfy their nutrient requirements. Studies conducted in mostly captive settings have shown that animals from a variety of taxonomic groups deal with this challenge by adjusting the amounts and proportions of available food combinations to achieve a target nutrient balance. In this study, we used proportions‐based nutritional geometry to analyze the nutritional composition of rumen samples collected in winter from 481 moose (Alces alces) in southern Sweden and examine whether free‐ranging moose show comparable patterns of nutrient balancing. Our main hypothesis was that wild moose actively regulate their rumen nutrient composition to offset ecologically imposed variation in the nutritional composition of available foods. To test this, we assessed the macronutritional composition (protein, carbohydrates, and lipids) of rumen contents and commonly eaten foods, including supplementary feed, across populations with contrasting winter diets, spanning an area of approximately 10,000 km2. Our results suggest that moose balanced the macronutrient composition of their rumen, with the rumen contents having consistently similar proportional relationship between protein and nonstructural carbohydrates, despite differences in available (and eaten) foods. Furthermore, we found that rumen macronutrient balance was tightly related to ingested levels of dietary fiber (cellulose and hemicellulose), such that the greater the fiber content, the less protein was present in the rumen compared with nonstructural carbohydrates. Our results also suggest that moose benefit from access to a greater variety of trees, shrubs, herbs, and grasses, which provides them with a larger nutritional space to maneuver within. Our findings provide novel theoretical insights into a model species for ungulate nutritional ecology, while also generating data of direct relevance to wildlife and forest management, such as silvicultural or supplementary feeding practices.

Abstract Background Lung region segmentation is an important stage of automated image-based approaches for the diagnosis of respiratory diseases. Manual methods executed by experts are considered the gold standard, but it is time consuming and the accuracy is dependent on radiologists’ experience. Automated methods are relatively fast and reproducible with potential to facilitate physician interpretation of images. However, these benefits are possible only after overcoming several challenges. The traditional methods that are formulated as a three-stage segmentation demonstrate promising results on normal CT data but perform poorly in the presence of pathological features and variations in image quality attributes. The implementation of deep learning methods that can demonstrate superior performance over traditional methods is dependent on the quantity, quality, cost and the time it takes to generate training data. Thus, efficient and clinically relevant automated segmentation method is desired for the diagnosis of respiratory diseases. Methods We implement each of the three stages of traditional methods using deep learning methods trained on five different configurations of training data with ground truths obtained from the 3D Image Reconstruction for Comparison of Algorithm Database (3DIRCAD) and the Interstitial Lung Diseases (ILD) database. The data was augmented with the Lung Image Database Consortium (LIDC-IDRI) image collection and a realistic phantom. A convolutional neural network (CNN) at the preprocessing stage classifies the input into lung and none lung regions. The processing stage was implemented using a CNN-based U-net while the postprocessing stage utilize another U-net and CNN for contour refinement and filtering out false positives, respectively. Results The performance of the proposed method was evaluated on 1230 and 1100 CT slices from the 3DIRCAD and ILD databases. We investigate the performance of the proposed method on five configurations of training data and three configurations of the segmentation system; three-stage segmentation and three-stage segmentation without a CNN classifier and contrast enhancement, respectively. The Dice-score recorded by the proposed method range from 0.76 to 0.95. Conclusion The clinical relevance and segmentation accuracy of deep learning models can improve though deep learning-based three-stage segmentation, image quality evaluation and enhancement as well as augmenting the training data with large volume of cheap and quality training data. We propose a new and novel deep learning-based method of contour refinement.

Abstract Background More than one third of Norwegian women and men between 20 and 40 years of age have elevated cholesterol concentration. Parental metabolic health around conception or during pregnancy may affect the offspring’s cardiovascular disease risk. Lipids are important for fetal development, but the determinants of cord blood lipids have scarcely been studied. We therefore aimed to describe the associations between maternal and paternal peri-pregnancy lipid and metabolic profile and newborn cord blood lipid and metabolic profile. Methods This study is based on 710 mother–father–newborn trios from the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). The sample included in this study consisted of parents with and without self-reported hypercholesterolemia the last 6 months before pregnancy and their partners and newborns. Sixty-four cord blood metabolites detected by nuclear magnetic resonance spectroscopy were analyzed by linear mixed model analyses. The false discovery rate procedure was used to correct for multiple testing. Results Among mothers with hypercholesterolemia, maternal and newborn plasma high-density lipoprotein cholesterol, apolipoprotein A1, linoleic acid, docosahexaenoic acid, alanine, glutamine, isoleucine, leucine, valine, creatinine, and particle concentration of medium high-density lipoprotein were significantly positively associated (0.001 ≤ q ≤ 0.09). Among mothers without hypercholesterolemia, maternal and newborn linoleic acid, valine, tyrosine, citrate, creatinine, high-density lipoprotein size, and particle concentration of small high-density lipoprotein were significantly positively associated (0.02 ≤ q ≤ 0.08). Among fathers with hypercholesterolemia, paternal and newborn ratio of apolipoprotein B to apolipoprotein A1 were significantly positively associated (q = 0.04). Among fathers without hypercholesterolemia, no significant associations were found between paternal and newborn metabolites. Sex differences were found for many cord blood lipids. Conclusions Maternal and paternal metabolites and newborn sex were associated with several cord blood metabolites. This may potentially affect the offspring’s long-term cardiovascular disease risk.

Background: A novel deep learning image reconstruction (DLIR) algorithm for CT has recently been clinically approved. Purpose: To assess low-contrast detectability and dose reduction potential for CT images reconstructed with the DLIR algorithm and compare with filtered back projection (FBP) and hybrid iterative reconstruction (IR). Material and methods: A customized upper-abdomen phantom containing four cylindrical liver inserts with low-contrast lesions was scanned at CT dose indexes of 5, 10, 15, 20 and 25 mGy. Images were reconstructed with FBP, 50% hybrid IR (IR50), and DLIR of low strength (DLL), medium strength (DLM) and high strength (DLH). Detectability was assessed by 20 independent readers using a two-alternative forced choice approach. Dose reduction potential was estimated separately for each strength of DLIR using a fitted model, with the detectability performance of FBP and IR50 as reference. Results: For the investigated dose levels of 5 and 10 mGy, DLM improved detectability compared to FBP by 5.8 and 6.9 percentage points (p.p.), and DLH improved detectability by 9.6 and 12.3 p.p., respectively (all p

Background: Progressive multifocal leukoencephalopathy (PML) is a rare devastating brain infection caused by the JC polyomavirus (JCPyV) in patients with impaired cellular immune responses. In the absence of effective anti-viral therapy, it is unclear if the use of interleukin-7 (IL-7) could enhance cellular immune responses required to survive PML. Case report: A 78-year-old woman who had been treated with corticosteroids for pulmonary sarcoidosis 25 years earlier developed PML associated with severe idiopathic T-cell lymphopenia characterized by expression of programmed cell death-1 (PD-1) receptors on circulating CD4+ and CD8+ T-cells. The patient was diagnosed 12 weeks after her initial symptoms, and treatment with mirtazapine was started immediately. The disease progressed, however, and treatment with IL-7 was initiated 17 weeks after initial symptomatology begun. Results: At week 21, clinical improvement was observed and despite persistent JCPyV positive cerebrospinal fluid until week 36, the patient continued to improve remarkably, both clinically and radiologically, along with increasing peripheral lymphocytes and declining PD-1 expression. Treatment was well tolerated without late complications. More than one year after treatment (week 71) the patient cared for herself, and had no signs of PML recurrence, relapse of sarcoidosis, or cancer. A mild increase, however, in serum angiotensin-converting enzyme and plasma soluble interleukin-2 receptor was observed. Conclusion: Faced with PML and lymphopenia, in the absence of conventional therapies to reverse the underlying immunodeficiency, IL-7 therapy may be helpful in combatting the JC polyomavirus.

Abstract Background Pregnancy has been identified as a contributor to obesity. We have shown that a diet intervention postpartum produced a 2-y weight loss of 8%. Here, we present the impact of the diet intervention on cost-effectiveness and explore changes in quality of life (QOL). Methods A total of 110 postpartum women with overweight/obesity were randomly assigned to diet (D-group) or control (C-group). D-group received a 12-wk diet intervention within primary health care followed by monthly emails up to the 1-y follow-up. C-group received a brochure. Changes in QOL were measured using the 36-item Short Form Health Survey and EQ-5D. The analysis of cost-effectiveness was a cost-utility analysis with a health care perspective and included costs of intervention for stakeholder, quality-adjusted life-years (QALYs) gained and savings in health care. The likelihood of cost-effectiveness was examined using the net monetary benefit method. Results The D-group increased their QOL more than the C-group at 12 wk. and 1 y, with pronounced differences for the dimensions general health and mental health, and the mental component summary score (all p

Although often overlooked in our daily lives, saliva performs a host of necessary physiological functions, including lubricating and protecting the oral cavity, facilitating taste sensation and digestion and maintaining tooth enamel. Therefore, salivary gland dysfunction and hyposalivation, often resulting from pathogenesis of the autoimmune disease Sjögren’s syndrome or from radiotherapy of the head and neck region during cancer treatment, severely reduce the quality of life of afflicted patients and can lead to dental caries, periodontitis, digestive disorders, loss of taste and difficulty speaking. Since their initial discovery in the 1970s, P2 purinergic receptors for extracellular nucleotides, including ATP-gated ion channel P2X and G protein-coupled P2Y receptors, have been shown to mediate physiological processes in numerous tissues, including the salivary glands where P2 receptors represent a link between canonical and non-canonical saliva secretion. Additionally, extracellular nucleotides released during periods of cellular stress and inflammation act as a tissue alarmin to coordinate immunological and tissue repair responses through P2 receptor activation. Accordingly, P2 receptors have gained widespread clinical interest with agonists and antagonists either currently undergoing clinical trials or already approved for human use. Here, we review the contributions of P2 receptors to salivary gland function and describe their role in salivary gland dysfunction. We further consider their potential as therapeutic targets to promote physiological saliva flow, prevent salivary gland inflammation and enhance tissue regeneration.

Abstract Background Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). Methods To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. Results Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. Conclusion The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. Trial registration ClinicalTrials.gov identifier NCT02627872; Retrospectively registered on December 9, 2015.

Abstract Background Smoking is the main risk factor for chronic obstructive pulmonary disease (COPD). Women with COPD who smoke experienced a higher risk of hospitalization and worse decline of lung function. Yet the mechanisms of these gender-related differences in clinical presentations in COPD remain unknown. The aim of our study is to identify proteins and molecular pathways associated with COPD pathogenesis, with emphasis on elucidating molecular gender difference. Method We employed shotgun isobaric tags for relative and absolute quantitation (iTRAQ) proteome analyses of bronchoalveolar lavage (BAL) cells from smokers with normal lung function (n = 25) and early stage COPD patients (n = 18). Multivariate modeling, pathway enrichment analysis, and correlation with clinical characteristics were performed to identify specific proteins and pathways of interest. Results More pronounced alterations both at the protein- and pathway- levels were observed in female COPD patients, involving dysregulation of the FcγR-mediated phagocytosis-lysosomal axis and increase in oxidative stress. Alterations in pathways of the phagocytosis-lysosomal axis associated with a female-dominated COPD phenotype correlated well with specific clinical features: FcγR-mediated phagocytosis correlated with FEV1/FVC, the lysosomal pathway correlated with CT

The objective was to investigate which predictive equations provide the best estimates of resting energy expenditure (REE) in postpartum women with overweight and obesity. Lactating women with overweight or obesity underwent REE measurement by indirect calorimetry, and fat-free mass (FFM) was assessed by dual-energy X-ray absorptiometry at three postpartum stages. Predictive equations based on body weight and FFM were obtained from the literature. Performance of the predictive equations were analysed as the percentage of women whose REE was accurately predicted, defined as a predicted REE within ±10 % of measured REE. REE data were available for women at 10 weeks (n 71), 24 weeks (n 64) and 15 months (n 57) postpartum. Thirty-six predictive equations (twenty-five weight-based and eleven FFM-based) were validated. REE was accurately predicted in ≥80 % of women at all postpartum visits by six predictive equations (two weight-based and four FFM-based). The weight-based equation with the highest performance was that of Henry (weight, height, age 30–60 years) (HenryWH30−60), with an overall mean of 83 % accurate predictions. The HenryWH30−60 equation was highly suitable for predicting REE at all postpartum visits (irrespective of the women's actual age), and the performance was sustained across changes in weight and lactation status. No FFM-based equation was remarkably superior to HenryWH30−60 for the total postpartum period.

When a patient’s platelet count is low, the sample is assessed for platelet clumps to distinguish between thrombocytopenia and pseudothrombocytopenia. Microscopic examination of blood smear is the standard method for identifying platelet clumps at Diakonhjemmet Hospital AS, but the method is time-consuming and may be challenging due to artefacts. The purpose of this project was to evaluate if two alternative methods, direct microscopic examination of EDTA whole blood and buffy coat, were suitable for identification of platelet clumps. In addition, the samples were analyzed by Sysmex XE-5000 before and after removal of 10 uL buffycoat, to investigate if platelet and leukocyte parameters were influenced to an extent that supplementary analysis after removal would not be possible. We included 57 samples with platelet counts lower than 90 x 109/L. Microscopic examination of buffy coat had a sensitivity of 97 % when compared to blood smear. In addition, the method was time-saving and easier to perform. Direct microscopic examination of whole blood was the easiest method to perform and most time-saving. However, the sensitivity was 64 % when compared to blood smear, and detecting possible platelets clumps was challenging due to the amount of erythrocytes present. Based on this, we do not recommended whole blood as an alternative method for identifying platelet clumps. Furthermore, the results show that there was no statistically significant difference in platelet and leukocyte parameters before and after removal of buffy coat. In addition, the observed difference in percent was less than the analytical variation, which indicates that the differences are of no clinical significance. We conclude that buffy coat may be used as an alternative method to blood smear to identify platelet clumps.

Background: A farming environment confers strong protection against allergy development. We have previously shown that farming mothers consume more full-fat dairy than control mothers, who instead consume more low-fat dairy, margarine, and oils; margarine and oil intake was associated with increased risk of allergy development in their children. Objectives: The aims of this study were to investigate the differences in diet between children in farming and control families at 1 year of age, to investigate the relation between the diets of the mothers and their children, and to relate the children's diet to allergy development. Design: The diet of 1-year-old children from dairy farming families (n=28) and from control families in the same rural area (n=37) was assessed by 24-h dietary recalls, followed by 24-h food diaries. Allergy was diagnosed by pediatricians at 3 years of age using strict predefined criteria. Results: Farm children had a higher intake of farm milk, whole cream, cholesterol, saturated fat, and fat in total and tended to eat more butter, while controls consumed more carbohydrates and poultry and tended to eat more margarine. Farm children also had higher intakes of homemade porridge/gruel, oily fish, and iodine. The intake of butter and whole milk in children and mothers correlated significantly in farm families but not in controls. A weak negative association was found between seafood intake and allergy development, while allergy was positively associated with the intake of pork as well as zinc in the control group; these intakes also correlated with each other. Conclusions: Consistent with mothers in farming families, the children consumed more full-fat dairy and saturated fat than did controls, but this could not be linked to the low risk of allergy in the farming group. Seafood intake might protect against allergy development, in accordance with earlier findings.

Adipose tissue is highly involved in whole-body metabolism and is the main site for lipid synthesis, storage and mobilization in ruminants. Therefore, knowledge about adipose tissue responses to different diets is important, especially in growing heifers as the feeding regimes of replacement heifers affect their future success as dairy cows. However, at gene expression level such knowledge is limited. As part of a larger feed trial, adipose tissue biopsies from 24 Norwegian Red heifers were collected at 12 months of age (12MO) and at month seven of gestation (PREG) and analyzed by next-generation mRNA sequencing. Between these two sampling points, all heifers had gone through a successful conception and a feed change from four dietary treatments of high or low energy (HE/LE) and protein (HP/LP) content (treatments LPHE, HPHE, LPLE and HPLE) to a low-energy, low-protein pregnancy feed given to all animals. Gene expression differences between different feed treatments at 12MO are described in an earlier publication from our group. The main objectives of this study were to investigate the long-term effects of diets differing in protein and energy density level on gene expression in adipose tissue of growing replacement dairy heifers. To achieve this, we examined the post-treatment effects between the treatment groups at month seven of gestation; 6 months after the termination of experimental feeding, and the long-term gene expression changes occurring in the adipose tissue between 12MO and PREG. Post-treatment group comparisons showed evidence of long-term effects of dietary treatment on adipose gene expression. Differences between protein treatments were smaller than between energy treatments. Adipose gene expression changes from 12MO to PREG were much larger for the HE than the LE treatments and seemed to mostly be explained by the characteristics of the diet change. 97 genes displayed a unidirectional expression change for all groups from 12MO to PREG, and are considered to be treatment-independent, possibly caused by pregnancy or increased age. This study provides candidate genes and key regulators for further studies on pregnancy preservation (TGFB1, CFD) and metabolic regulation and efficiency (PI3K, RICTOR, MAP4K4,) in dairy cattle.

Abstract The research literature on food selection by large herbivores is extensive. Still, we are generally lacking in our knowledge of the influence of potentially interacting chemical contents of the food. We made a qualitative review of a systematic literature search of studies that empirically link chemical contents of food to the food selection by northern cervids (genera Alces, Capreolus, Cervus, Dama, Odocoileus, Rangifer). We found that although the majority of the 98 relevant studies measuring any given food constituent (energy, protein, fiber, minerals, plant secondary metabolites) provided support for it acting as a driver of food selection (in either a negative or positive way), there was little support for the traditional hypotheses of maximization or limitation of any single constituent. Rather, because of the animals’ need to acquire an appropriate intake of several constituents at the same time, our review highlights how new empirical studies need to focus on several food constituents in synchrony: (1) Study designs should capture sufficient variation in the content of food constituents in order to tease apart their many co‐variations; and (2) insights about nutritional drivers may be lost if one uses only composite currencies such as crude energy, crude fiber, ash, or tannins, which may mask contrasting selection patterns of the lumped constituents. Season had an apparent influence on the selection of some food constituents, particularly various fiber fractions. In contrast, our review revealed a lack of evidence that cervids more strongly select for protein in summer than they do in winter. Our overall conclusion of the review is that interacting chemical contents of food make the nutritional value of a given food type into a varying entity. To better elucidate this variation, we need new technologies that non‐invasively capture nutrient intake of free‐ranging animals, across seasons.

Adipose tissue is no longer considered a mere energy reserve, but a metabolically and hormonally active organ strongly associated with the regulation of whole-body metabolism. Knowledge of adipose metabolic regulatory function is of great importance in cattle management, as it affects the efficiency and manner with which an animal converts feedstuff to milk, meat and fat. However, the molecular mechanisms regulating metabolism in bovine adipose tissue are still not fully elucidated. The emergence of next-generation sequencing technologies has facilitated the analysis of metabolic function and regulation at the global gene expression level. The aim of this study was to investigate the effect of diets differing in protein and energy density level on gene expression in adipose tissue of growing replacement dairy heifers using next-generation RNA sequencing (RNAseq). Norwegian Red heifers were fed either a high- or low-protein concentrate (HP/LP) and a high- or low-energy roughage (HE/LE) diet from 3 months of age until confirmed pregnancy to give four treatments (viz, HPHE, HPLE, LPHE, LPLE) with different growth profiles. Subcutaneous adipose tissue sampled at 12 months of age was analyzed for gene expression differences using RNAseq. The largest difference in gene expression was found between LPHE and LPLE heifers, for which 1092 genes were significantly differentially expressed, representing an up-regulation of mitochondrial function, lipid, carbohydrate and amino acid metabolism as well as changes in the antioxidant system in adipose tissue of LPHE heifers. Differences between HPHE and HPLE heifers were much smaller, and dominated by genes representing NAD biosynthesis, as was the significantly differentially expressed genes (DEG) common to both HE-LE contrasts. Differences between HP and LP groups within each energy treatment were minimal. This study emphasizes the importance of transcriptional regulation of adipose tissue energy metabolism, and identifies candidate genes for further studies on early-stage obesity and glucose load in dairy cattle.

Background: The Swedish board for health and social welfare (SoS) has presented four questions on dietary habits as indicators of adherence to dietary recommendations. However, these questions have not been evaluated. Objective: To evaluate if four questions on dietary habits correlate with dietary intake assessed by food records. Design: A total of 279 medical and nursing students, 170 women and 109 men, completed four questions on usual consumption frequency of vegetables, fruits, fish, and sweets. Depending on scoring from 0 to 12 points, subjects were classified as having low (0–4 points), average (5–8 points), or high (9–12 points) adherence to dietary recommendations as proposed by SoS. Nutrient intake was calculated from 3-day food records. Mean dietary intake, expressed per 10 MJ of fibre, ascorbic acid, folate, vitamin D, sucrose, fish, and fruits and vegetables, was analysed for each group and differences assessed by ANOVA. Results: Energy intake was 11.8±3.0 MJ in male and 8.5±2.2 MJ in female students. Most students, 64%, were classified as average adherers to dietary recommendations, whereas only 6% were classified as low and 30% as high. Dietary intake of fibre, ascorbic acid, and folate was significantly higher in the high adherence group compared to both the other groups (p

To examine the effects of Diet (D) and Exercise (E) interventions on cardiovascular fitness, waist circumference, blood lipids, glucose metabolism, inflammation markers, insulin-like growth factor 1 (IGF-1) and blood pressure in overweight and obese lactating women.At 10-14 wk postpartum, 68 Swedish women with a self-reported pre-pregnancy BMI of 25-35 kg/m(2) were randomized to a 12-wk behavior modification treatment with D, E, both or control using a 2×2 factorial design. The goal of D treatment was to reduce body weight by 0.5 kg/wk, accomplished by decreasing energy intake by 500 kcal/d and monitoring weight loss through self-weighing. The goal of E treatment was to perform 4 45-min walks per wk at 60-70% of max heart-rate using a heart-rate monitor. Effects were measured 12 wk and 1 y after randomization. General Linear Modeling was used to study main and interaction effects adjusted for baseline values of dependent variable.There was a significant main effect of the D treatment, decreasing waist circumference (P = 0.001), total cholesterol (P = 0.007), LDL-cholesterol (P = 0.003) and fasting insulin (P = 0.042), at the end of the 12-wk treatment. The decreased waist circumference (P

BACKGROUND: Obesity and cardiovascular diseases are increasing globally and any association between reproduction and these conditions is of concern. Unfortunately, little is known about normal levels of metabolic risk factors in women of different body mass index throughout the reproductive cycle. This study is one of the first to describe the metabolic risk profile of lactating overweight or obese women at 8-12 weeks postpartum. METHODS: During 2007-2009, 66 overweight or obese Swedish lactating women without known diseases underwent detailed measurements of their metabolic profiles, dietary intake and general health before entering a lifestyle intervention trial. Baseline measurements took place between 8-12 wk postpartum. Almost all women were exclusively breastfeeding their term infants. RESULTS: The women were regarded as healthy, as reflected in the absence of diagnosed diseases, their own perceptions and in normal hemoglobin, albumin and fasting plasma glucose values. Four women were diagnosed with metabolic syndrome. In these cases, underlying conditions included large waist circumference, low HDL cholesterol values, high triglyceride values and relatively high blood pressure. The metabolic profile differed between overweight and obese women; obese women had significantly higher levels of fasting insulin (p = 0.017), borderline higher HOMA values (p = 0.057) and significantly higher triglyceride values (p = 0.029), as well as larger waist and hip circumferences (p

Introduction: Normal oral fibroblasts (NOFs) are located in the connective tissue of the oral mucosa. The NOFs play an important role in wound healing, tumor progression, and metastasis. They are subjected to influence by external and internal stimuli, among them extracellular vesicles (EVs), that are considered as important players in cell to cell communication, especially in carcinogenesis and metastatic processes. During tumorigenesis, stromal NOFs may undergo activation into cancer-associated fibroblasts (CAFs) that modify their phenotype to provide pro-oncogenic signals that in turn facilitate tumor initiation, progression, and metastasis. The aim of the study was to reveal the effect of EVs derived from local (oral squamous cell carcinoma – OSCC) and distant (pancreatic adenocarcinoma – PDAC; malignant melanoma brain metastasis – MBM) cancer origin on NOFs and their possible change into a CAF-like direction. Methods: The effect of each of the cancer EV types on NOFs proliferation, viability, and migration was tested. Also, changes in gene expression of the wellestablished CAF biomarkers ACTA2, FAP, PDGFR, and two putative CAF biomarkers, the Ca2+- activated ion channels ANO1 and KCNMA, were studied. Results: Obtained results indicate that NOFs receive and process signals transmitted by EVs originating from both OSCC, PDAC, and MBM. The fibroblast response was dependent on EV origin and concentration, and duration of EV exposure. Conclusion: The present results indicate that the molecular cargo of the EVs direct NOFs towards a pro-tumorigenic phenotype. [ABSTRACT FROM AUTHOR]

Animals representing a wide range of taxonomic groups are known to select specific food combinations to achieve a nutritionally balanced diet. The nutrient balancing hypothesis suggests that, when given the opportunity, animals select foods to achieve a particular target nutrient balance, and that balancing occurs between meals and between days. For wild ruminants who inhabit landscapes dominated by human land use, nutritionally imbalanced diets can result from ingesting agricultural crops rich in starch and sugar (nonstructural carbohydrates [NCs]), which can be provided to them by people as supplementary feeds. Here, we test the nutrient balancing hypothesis by assessing potential effects that the ingestion of such crops by Alces alces (moose) may have on forage intake. We predicted that moose compensate for an imbalanced intake of excess NC by selecting tree forage with macro‐nutritional content better suited for their rumen microbiome during wintertime. We applied DNA metabarcoding to identify plants in fecal and rumen content from the same moose during winter in Sweden. We found that the concentration of NC‐rich crops in feces predicted the presence of Picea abies (Norway spruce) in rumen samples. The finding is consistent with the prediction that moose use tree forage as a nutritionally complementary resource to balance their intake of NC‐rich foods, and that they ingested P. abies in particular (normally a forage rarely eaten by moose) because it was the most readily available tree. Our finding sheds new light on the foraging behavior of a model species in herbivore ecology, and on how habitat alterations by humans may change the behavior of wildlife. [ABSTRACT FROM AUTHOR]

Understanding how the nutritional properties of food resources drive foraging choices is important for the management and conservation of wildlife populations. For moose (Alces alces), recent experimental and observational studies during the winter have shown macronutrient balancing between available protein (AP) and highly metabolizable macronutrients (total non‐structural carbohydrates [TNC] and lipids). Here, we combined the use of continuous‐recording camera collars with plant nutrient analyses and forage availability measurements to obtain a detailed insight into the food and nutritional choices of three wild moose in Norway over a 5‐day period in summer. We found that moose derived their macronutrient energy primarily from carbohydrates (74.2%), followed by protein (13.1%), and lipids (12.7%). Diets were dominated by deciduous tree browse (71%). Willows (Salix spp.) were selected for and constituted 51% of the average diet. Moose consumed 25 different food items during the study period of which 9 comprised 95% of the diet. Moose tightly regulated their intake of protein to highly metabolizable macronutrients (AP:TNC + lipids) to a ratio of 1:2.7 (0.37 ± 0.002SD). They did this by feeding on foods that most closely matched the target macronutrient ratio such as Salix spp., or by combining nutritionally imbalanced foods (complementary feeding) in a non‐random manner that minimized deviations from the intake target. The observed patterns of macronutrient balancing aligned well with the findings of winter studies. Differential feeding on nutritionally balanced downy birch (Betula pubescens) leaves versus imbalanced twigs+leaves across moose individuals indicated that macronutrient balancing may occur on as fine a scale as foraging bites on a single plant species. Utilized forages generally met the suggested requirement thresholds for the minerals calcium, phosphorus, copper, molybdenum, and magnesium but tended to be low in sodium. Our findings offer new insights into the foraging behavior of a model species in ungulate nutritional ecology and contribute to informed decision‐making in wildlife and forest management. [ABSTRACT FROM AUTHOR]