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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.

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

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.

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]

Background and aims: Diabetes-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. Methods: This 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. Results: The 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 <60 mL/min/1.73 m² (eGFR categories G3-G5)) increased in both individuals with and without a DFU. Conclusion: Results from the HUNT surveys show a substantial decline in the lifetime prevalence of DFU from 1995 to 2019. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

IntroductionPupils spend a significant portion of their time at school. As a result, the school serves as an important setting for both learning and the formation of healthy behaviors. Many children, and even fewer young people, do not fulfill the (inter)national health recommendations of 60 minutes of moderate to vigorous physical activity (MVPA) per day. The aim of this study was to examine pupils' MVPA during schooltime in a longitudinal perspective, including the transition from primary to secondary school.MethodsThe MVPA of 234 pupils' was measured objectively using accelerometer monitors for seven consecutive days, in the spring of 2017, 2018, and 2019. Statistical analyses by Friedman, Wilcoxon and Mann–Whitney U-test were used to answer the research questions.ResultsThe results showed a significant decrease in the pupils' MVPA and fulfilment of health recommendations during schooltime, from 7th to 8th grade. The analyses also showed that MVPA during schooltime was higher among boys than girls, and also contributed more to boys' fulfilment of the health recommendations at all three time periods.DiscussionThe results indicate that the transition between primary and secondary school is vulnerable concerning pupils' MVPA during schooltime. As schooltime accounted for significantly more MVPA for boys than for girls at all three time periods, we question whether physical activity is sufficiently facilitated for girls in school.

Regular physical activity (PA) is positive for the health of young people, but previous research has indicated that the proportion of the population attaining recommended levels of activity decreases with age. Several studies indicate that the PA pupils get during school hours represents an important part of their total PA. The purpose of this study was to examine the relation between the size of the school’s total outdoor area and pupils’ PA behavior during schooltime. ActiGraph GT1M accelerometers were used to measure objectively 12–13-year-old schoolchildren’s minutes of moderate-to-vigorous PA (MVPA) during schooltime. The pupils (n = 300, 155 girls and 145 boys) came from 18 primary schools in two medium-sized municipalities in mid-Norway. Linear regression analysis was used to examine the relationship between the schools’ total outdoor area and outdoor area per pupil in relation to pupils’ weekly minutes of MVPA during schooltime. The results show no association with either the schools’ total outdoor area or the outdoor area per pupil, and the pupils’ weekly minutes of MVPA during schooltime. This finding indicates that there are probably factors in the school environment affecting young people’s level of activity during schooltime, other than the size of the schools’ outdoor area.

The unique properties and applications of nanotechnology in targeting drug delivery, cosmetics, fabrics, water treatment and food packaging have received increased focus the last two decades. The application of nanoparticles in medicine is rapidly evolving, requiring careful investigation of toxicity before clinical use. Chitosan, a derivative of the natural polysaccharide chitin, has become increasingly relevant in modern medicine because of its unique properties as a nanoparticle. Chitosan is already widely used as a food additive and in food packaging, bandages and wound dressings. Thus, with an increasing application worldwide, cytotoxicity assessment of nanoparticles prepared from chitosan is of great interest. The purpose of this review is to provide an updated status of cytotoxicity studies scrutinizing the safety of chitosan nanoparticles used in biomedical research. A search in Ovid Medline from 23 March 1998 to 4 January 2022, with the combination of the search words Chitosan or chitosan, nanoparticle or nano particle or nanosphere or nanocapsule or nano capsule, toxicology or toxic or cytotoxic and mucosa or mucous membrane resulted in a total of 88 articles. After reviewing all the articles, those involving non-organic nanoparticles and cytotoxicity assays conducted exclusively on nanoparticles with anti-tumor effect (i.e., having cytotoxic effect) were excluded, resulting in 70 articles. Overall, the chitosan nanoparticles included in this review seem to express low cytotoxicity regardless of particle composition or cytotoxicity assay and cell line used for testing. Nonetheless, all new chitosan derivatives and compositions are recommended to undergo careful characterization and cytotoxicity assessment before being implemented on the market.

Antimicrobial chemicals are used as preservatives in cosmetics, pharmaceuticals, and food to prevent the growth of bacteria and fungi in the products. Unintentional exposure in humans to such chemicals is well documented, but whether they also interfere with human oral microbiome composition is largely unexplored. In this study, we explored whether the oral bacterial composition is affected by exposure to antibacterial and environmental chemicals. Gingival fluid, urine, and interview data were collected from 477 adults (18–47 years) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan, triclocarban, parabens, benzophenone-3, bisphenols, and 2,4- and 2,5-dichlorophenols (DCPs) were quantified (by mass spectrometry). Microbiome analysis was based on 16S amplicon sequencing. Diversity and differential abundance analyses were performed to identify how microbial communities may change when comparing groups of different chemical exposure. We identified that high urine levels (>75th percentile) of propyl parabens were associated with a lower abundance of bacteria genera TM7 [G-3], Helicobacter, Megasphaera, Mitsuokella, Tannerella, Propionibacteriaceae [G-2], and Dermabacter, as compared with low propylparaben levels (

The HEARO cochlear implantation surgery aims to replace the conventional wide mastoidectomy approach with a minimally invasive direct cochlear access. The main advantage of the HEARO access would be that the trajectory accommodates the optimal and individualized insertion parameters such as type of cochlear access and trajectory angles into the cochlea. To investigate the quality of electrode insertion with the HEARO procedure, the insertion process was inspected under fluoroscopy in 16 human cadaver temporal bones. Prior to the insertion, the robotic middle and inner ear access were performed through the HEARO procedures. The status of the insertion was analyzed on the post-operative image with Siemens Artis Pheno (Siemens AG, Munich, Germany). The completion of the full HEARO procedure, including the robotic inner ear access and fluoroscopy electrode insertion, was possible in all 16 cases. It was possible to insert the electrode in all 16 cases through the drilled tunnel. However, one case in which the full cochlea was not visible on the post-operative image for analysis was excluded. The post-operative analysis of the electrode insertion showed an average insertion angle of 507°, which is equivalent to 1.4 turns of the cochlea, and minimal and maximal insertion angles were recorded as 373° (1 cochlear turn) and 645° (1.8 cochlear turn), respectively. The fluoroscopy inspection indicated no sign of complications during the insertion.

The end-state comfort (ESC) effect refers to the consistent tendency of healthy adults to end their movements in a comfortable end posture. In children with and without developmental coordination disorder (DCD), the results of studies focusing on ESC planning have been inconclusive, which is likely to be due to differences in task constraints. The present pilot study focused on the question whether children with and without DCD were able to change their planning strategy and were more likely to plan for ESC when demanded by complex object manipulations at the end of a task. To this end, we examined ESC planning in 18 children with and without DCD (aged 5–11years) using the previously used sword-task and the newly developed hammer-task. In the sword-task, children had to insert a sword in a wooden block, which could be relatively easily completed with an uncomfortable end-posture. In the hammer-task, children had to strike down a nail in a wooden pounding bench, which required additional force and speed demands, making it relatively difficult to complete the movement with an uncomfortable end-posture. In line with our hypothesis, the results demonstrated that children with and without DCD were more likely to plan for ESC on the hammer-task compared with the sword-task. Thus, while children with and without DCD show inconsistent ESC planning on many previously used tasks, the present pilot study shows that many of them are able to take into account the end-state of their movements if demanded by task constraints.

Objective: Assessing the effects of caffeine withdrawal on migraine.Background: The effects of caffeine withdrawal on migraineurs are at large unknown.Methods: This was a randomized, double-blind, crossover study (NCT03022838), designed to enroll 80 adults with episodic migraine and a daily consumption of 300–800 mg caffeine. Participants substituted their estimated dietary caffeine with either placebo capsules or capsulated caffeine tablets for 5 weeks before switching the comparators for 5 more weeks.Results: The study was terminated due to low recruitment. Ten subjects with a mean age of 46.3 ± 9.9 years, BMI of 24.9 ± 3.7, and a mean blood pressure of 134/83 ± 17/12 mmHg were enrolled. The average consumption of caffeine per day was 539 ± 196.3 mg. The average monthly headache days and migraine attack frequency at baseline was 11.5 ± 4.9 and 5.2 ± 1.2, respectively. At baseline Pittsburgh Sleep Quality Index was 5.8 ± 2.5 and HIT-6 was 62.8 ± 3.9. There were no differences in these or in parameters from actigraphy during the caffeine period compared with the placebo period. One subject withdrew just after entering the study. In the remaining nine, withdrawal triggered severe migraine attacks in seven, causing one more drop-out, and a typical caffeine withdrawal syndrome in two. Caffeine continuation did not trigger migraines, but one attack occurred in the wake of caffeine reintroduction.Conclusions: The study failed to answer how caffeine withdrawal affects migraineurs over time, but showed that abrupt withdrawal of caffeine is a potent trigger for migraine attacks.

Research on physical activity (PA) behavior reveals an overall decrease worldwide from early childhood and throughout adulthood. The ability to illuminate which factors promote activity for whom and in which phase of life, therefore, becomes a key concept in extending our understanding of individuals' physical activity trajectories. Accordingly, this study investigates latent trajectories of objectively measured PA in adolescents (n = 306) over 3 years from ages 13 to 15. Further, it was tested whether eagerness for physical activity, perceived athletic competence, and parental support were associated with the different trajectories of PA. Latent class growth analysis revealed two PA trajectories (trajectory 1: “decrease from very high” and trajectory 2: “steeper decrease from high”). Trajectory 1 had a higher PA level at baseline and less PA decline than trajectory 2. Trajectory 1, “decrease from very high,” was associated with higher levels of eagerness for physical activity and perception of competence at all three time points. Furthermore, the effect size of differences between trajectory 1, “decrease from very high,” and trajectory 2, “steeper decrease from high,” increased from baseline (age 13, seventh grade) to posttest (age 15, ninth grade). This finding indicates a stronger experience of PA as enjoyable, personally relevant, and self-confirming behavior (i.e., “I regard myself as a person who exercises”) within the most active adolescents and even stronger as they get older. Consistent with previous research, the PA level declined from seventh to ninth grade. Being more eager for PA and perceiving oneself more as athletically competent is related to higher levels of PA. This highlights the importance of optimizing environmental factors that increase adolescents' experience of eagerness for physical activity and physical athletic competence.

This study investigated the association between perceived parental support and eagerness for physical activity (EPA) among adolescents, and the association between EPA and physical activity. We further examined whether perceived athletic competence (PAC) mediates a presumed association between EPA and physical activity level, when controlling for gender. This study included 320 adolescents (aged 12–13) from 18 schools in two medium-sized Norwegian municipalities. Questionnaires and accelerometers were assessed during spring 2017. Structural equation modeling was applied to examine the associations. Standard regression coefficients are presented. Data demonstrated that perceived parental support was positively associated with EPA (β = 0.52), and eagerness was positively associated with PAC (β = 0.52). Both EPA (β = 0.20) and PAC (β = 0.24) were also positively associated with moderate to vigorous physical activity (MVPA). When mediating the relationship between EPA and MVPA, through PAC, the effect on MVPA increased (from β = 0.20 to β = 0.32). Analysis revealed that 87% of the adolescents fulfilled the national health recommendations for physical activity. This study highlights the relevance of EPA and PAC in studies of physical activity among adolescents, and the impact of perceived parental support for adolescents' EPA and physical activity level.

Microalgae are regarded as a promising alternative that can replace fishmeal and fish oil in aquaculture. Under N-limitation, many microalgae species change their carbon storage patterns in favor of neutral lipids (NLs) mainly in the form of triacylglycerol (TAG), but fatty acids in polar lipids (PL) are nutritionally more available for fish than those esterified into NLs. In the present study, the effect of N-limitation on the lipid content and fatty acid profiles in different lipid classes of Phaeodactylum tricornutum, Isochrysis aff. galbana clone T-Iso, Rhodomonas baltica, and Nannochloropsis oceanica were investigated. The microalgae cells were cultivated by two different methods, batch and semi-continuous culture, to create strong and moderate N-limitation, and this in turn will significantly affect the biomass and lipid productivity. All four species accumulated lipids mainly in the form of TAG, in response to strong nitrogen limitation. N. oceanica, however, accumulated 51% of the dry weight as lipid in moderate nitrogen limitation and up to 87% of the fatty acid was in TAG. Isochrysis aff. galbana clone T-Iso was the only species where the fraction of polyunsaturated fatty acid (PUFA), especially the fraction of docosahexaenoic acid (DHA), increased with increasing nitrogen limitation. Total lipid productivity showed no increase in batch culture although stronger nitrogen limitation led to lipid accumulation. P. tricornutum had the highest eicosapentaenoic acid (EPA) content, while N. oceanica showed the highest EPA productivity due to the high content of lipid. The highest DHA productivity was found in Isochrysis aff. galbana clone T-Iso from moderate N-limitation, mainly due to the high biomass productivity. Based on the results from the current study, N. oceanica and T-Iso are two promising microalgae strains ass long-term sustainable sources of n-3 long chain -PUFAs under moderate N-limitation. As shown in the present study, increased lipid content in microalgal cells due to strong N-limitation induction may not increase the lipid productivity because biomass production is usually reduced. Therefore, a combination of approaches such as metabolic engineering, conditioning and selection may be needed to further increase the n-3 LC-PUFA productivity without substantial loss of biomass.