Introduction A healthy diet improves glycaemic control and reduces cardiovascular risk in type 2 diabetes (T2D). However, access to dietitians is limited. Several countries have implemented mandatory interpretive front-of-pack labelling to guide consumers towards healthier food choices, but Sweden has not. Smartphone applications may offer an alternative platform to provide such information. This study evaluates the dietary and clinical impact of a novel application providing interpretive labelling to Swedish adults with T2D.

Methods and analysis This is a fully decentralised randomised controlled trial. 900 individuals with T2D for ≥2 years who regularly shop for groceries will be recruited via general practices and community advertisements. Participants will be randomised to receive either: (1) access to the FoodSwitch mobile application plus standard written dietary advice, or (2) standard written dietary advice only. The FoodSwitch application allows users to scan barcodes on packaged foods to receive recommendations of healthier alternatives within the same category. The primary outcome is the difference in change in mean self-measured glycated haemoglobin between groups after 6 months. Secondary outcomes include differences in changes in waist circumference, body weight, quality of life, medication use, hospitalisations and all-cause mortality at 26 weeks. Exploratory outcomes include omics analyses. Recruitment is ongoing. Expected study completion on 31 December 2026.

Ethics and dissemination The trial has received ethical approval from the Swedish Ethical Review Authority (2023-06622-01, 2024-06668-02, 2024-07357-02 and 2025-01095-02) and is performed in line with World Medical Association Declaration of Helsinki and the General Data Protection Regulation. Results will be published in a peer-reviewed international journal.

BackgroundJuvenile idiopathic arthritis (JIA) often affects the temporomandibular joint (TMJ) caused by an abnormal immune system that includes overactive inflammatory processes. Salivary biomarkers may be a powerful tool that can help establishing diagnosis, prognosis and monitor disease progress.ObjectiveThe objective was to investigate biomarkers in parotid saliva and blood plasma in relation to temporomandibular joint (TMJ) magnetic resonance imaging (MRI) findings in patients with JIA and healthy individuals.MethodsForty-five children aged 6 to 16 years with JIA and 16 healthy age- and sex-matched controls were included. Unstimulated parotid saliva samples and venous blood were collected. Biochemical analyses were performed for the cytokine biomarkers. The participants underwent MR imaging of the TMJs, where changes in the inflammatory and the damage domains were assessed.ResultsIn the JIA patients, lower concentrations of IL-6R and gp130 were found in parotid saliva than in plasma. Higher concentrations of IL-6 were found in parotid saliva than in plasma. IL-6, IL-6R and gp130 in parotid saliva explained the presence of bone marrow oedema and effusion in the JIA patients.ConclusionsThis study suggests that the IL-6 family in parotid saliva is associated with TMJ bone marrow oedema and effusion in patients with JIA, suggesting that IL-6 has promising properties as a parotid saliva biomarker for TMJ inflammatory activity. image

Medical devices, such as non-invasive ventilation masks, save lives in health care settings but can be a cause of tissue injuries due to the pressure and shear loads on skin and soft tissue. These pressure injuries could be painful for the individual and cause a significant economic impact on healthcare providers. In the etiology of device related pressure ulcers, inflammation plays an important role. However, the exact nature and timing of inflammatory biomarker upregulation is still unknown in the early stages of skin damage. This study aimed to explore the inflammatory profile of vulnerable skin sites following non-invasive mask application on a convenience sample of eleven hospital patients. Seventy-one inflammatory proteins were explored from sebum sampled at the skin surface after oronasal mask application. A multivariate analysis to investigate differences between loaded and control site was conducted, with a protein network analysis used to explore interactions in the early inflammation. The study revealed that 21 cytokines and chemokines were important for the separation between loaded and control site. These proteins were associated with remodeling of tissue, vascular wound healing and/or cell death.

Childhood maltreatment (CM) is a risk factor for substance use disorders (SUD) in adulthood. Understanding the mechanisms by which people are susceptible or resilient to developing SUD after exposure to CM is important for improving intervention. This case-control study investigated the impact of prospectively assessed CM on biomarkers of endocannabinoid function and emotion regulation in relation to the susceptibility or resilience to developing SUD. Four groups were defined across the dimensions of CM and lifetime SUD (N = 101 in total). After screening, participants completed two experimental sessions on separate days, aimed at assessing the behavioral, physiological, and neural mechanisms involved in emotion regulation. In the first session, participants engaged in tasks assessing biochemical (i.e., cortisol, endocannabinoids), behavioral, and psychophysiological indices of stress and affective reactivity. During the second session, the behavioral and brain mechanisms associated with emotion regulation and negative affect were investigated using magnetic resonance imaging. CM-exposed adults who did not develop SUD, operationally defined as resilient to developing SUD, had higher peripheral levels of the endocannabinoid anandamide at baseline and during stress exposure, compared to controls. Similarly, this group had increased activity in salience and emotion regulation regions in task-based measures of emotion regulation compared to controls, and CM-exposed adults with lifetime SUD. At rest, the resilient group also showed significantly greater negative connectivity between ventromedial prefrontal cortex and anterior insula compared to controls and CM-exposed adults with lifetime SUD. Collectively, these peripheral and central findings point to mechanisms of potential resilience to developing SUD after documented CM exposure.

Neuropathic pain (NP) is a chronic pain condition resulting from a lesion or disease in the somatosensory nervous system. The aim of this study was to investigate the metabolome in plasma from patients with chronic peripheral, posttraumatic/postsurgical NP compared to healthy controls. Further, we aimed to investigate the correlation between pain intensity and the metabolome in plasma. The metabolic profile in plasma samples from 16 patients with chronic NP and 12 healthy controls was analyzed using a nuclear magnetic resonance spectroscopy method. Information about pain intensity, pain duration, body mass index (BMI), age, sex, and blood pressure were obtained through a questionnaire and clinical examination. Multivariate data analysis was used to identify metabolites significant for group separation and their correlation with pain intensity and duration, BMI, and age. We found 50 out of 326 features in plasma significantly contributing to group discrimination between NP and controls. Several of the metabolites that significantly differed were involved in inflammatory processes, while others were important for central nervous system functioning and neural signaling. There was no correlation between pain intensity and levels of metabolite in NP. These findings indicate that there seems to be peripheral/systemic differences in the metabolic profile between patients with chronic NP and healthy individuals.

Purpose: Fibromyalgia (FM) is a complex pain condition, and exercise is considered the first option of treatment. Few studies have examined the effect of exercise on molecular mechanisms in FM. The aim of this study was to analyze the plasma proteome in women with FM and healthy controls (CON) before and after 15 wk of resistance exercise. This study further investigated whether clinical and exercises-related outcomes correlated with identified plasma proteins in FM.

Methods: Plasma samples from 40 FM/25 CON (baseline) and 21 FM/24 CON (postexercise) were analyzed using shotgun proteomics. Clinical/background data were retrieved through questionnaires. Exercise-related variables and pressure pain thresholds were assessed using standardized instruments. Multivariate statistics were applied to analyze the proteomic profile at baseline and postexercise, and correlation with clinical/exercise-related data.

Results: Fifteen weeks of resistance exercises improved clinical symptoms and muscle strength, and affected circulating proteins related to immunity, stress, mRNA stability, metabolic processes, and muscle structure development in FM. Pressure pain threshold was related to a specific protein profile, with proteins involved in metabolic and immune response. Subgroups of FM based on plasma proteins, FM duration, and improved muscle strength were identified.

Conclusions: Exercise seems to affect circulating proteins, clinical characteristics, and muscle strength in FM. This study contributes to better understanding of systemic protein changes in FM compared with CON and how resistance exercise affects such changes.

Insulin has metabolic and vascular effects in the human body. What mechanisms that orchestrate the effects in the microcirculation, and how the responds differ in different tissues, is however not fully understood. It is therefore of interest to search for markers in microdialysate that may be related to the microcirculation. This study aims to identify proteins related to microvascular changes in different tissue compartments after glucose provocation using in vivo microdialysis. Microdialysis was conducted in three different tissue compartments (intracutaneous, subcutaneous and intravenous) from healthy subjects. Microdialysate was collected during three time periods; recovery after catheter insertion, baseline and glucose provocation, and analyzed using proteomics. Altogether, 126 proteins were detected. Multivariate data analysis showed that the differences in protein expression levels during the three time periods, including comparison before and after glucose provocation, were most pronounced in the intracutaneous and subcutaneous compartments. Four proteins with vascular effects were identified (angiotensinogen, kininogen-1, alpha-2-HS-glycoprotein and hemoglobin subunit beta), all upregulated after glucose provocation compared to baseline in all three compartments. Glucose provocation is known to cause insulin-induced vasodilation through the nitric oxide pathway, and this study indicates that this is facilitated through the interactions of the RAS (angiotensinogen) and kallikrein-kinin (kininogen-1) systems.

Background The clinical care of chronic pain requires personalised understanding of the mechanisms involved. Temporomandibular disorders (TMD) are the most common chronic orofacial pain conditions, and oxidative stress has been proposed to be implicated in their pathophysiology, especially in arthrogenous TMD. However, few studies have explored oxidative stress in myogenous TMD (TMDM). Objective The aims of this study were to compare the salivary oxidative stress profiles between individuals with TMDM and healthy controls, and to explore associations of these markers with clinical characteristics. Methodology Saliva samples were collected from 39 individuals with TMDM and 37 age and sex-matched healthy volunteers. Psychological stress levels and clinical characteristics were assessed in all participants. The samples were analysed for total oxidant status (TOS), total antioxidative capacity (TAC) and superoxide dismutase activity (SODa). Comparisons between groups were performed using parametric and non-parametric tests depending on data distribution. Results Psychological stress was higher in TMDM compared to controls (P < .001). TAC levels were significantly higher (P < .05) whereas TOS levels were significantly lower (P < .05) in TMDM compared to controls. There were no differences in SODa levels between groups and no correlations were found between clinical characteristics and oxidative stress markers. Conclusion Individuals with TMDM showed higher levels of antioxidative markers, but lower levels of oxidative markers. These results can be explained in part by chronicity and adaptation to the disease and other factors, such as psychological stress. Longitudinal studies must be conducted to clarify the role of oxidative stress in TMDM.

The nociceptive withdrawal reflex (NWR) is used to probe spinal cord excitability in chronic pain states. Here, we used an automated and unbiased procedure for determining the NWR threshold and compared the reflex thresholds and corresponding pain ratings in a well-characterized cohort of fibromyalgia (n = 29) and matched healthy controls (n = 21). Surface electrical stimuli were delivered to the foot in a stepwise incremental and decremental manner. The surface electromyographic activity was recorded from the ipsilateral tibialis anterior muscle. Fibromyalgia patients reported significantly higher scores for psychological distress and pain-related disability and a significantly lower score for perceived state of health compared to the matched controls. The subjective pain ratings were significantly higher in patients. The NWR thresholds were similar to the controls. In the patients, but not in controls, the NWR thresholds and subjective pain ratings were significantly correlated. Our results showed an increased subjective pain sensitivity in fibromyalgia, but we found no evidence for spinal sensitization based on the reflex measures.

It has been suggested that alterations in inflammation molecules maintain chronic pain although little is known about how these factors influence homeostatic and inflammatory events in common chronic pain conditions. Nonpharmacological interventions might be associated with alterations in inflammation markers in blood. This study of patients with chronic pain investigates whether an interdisciplinary multimodal rehabilitation program (IMMRP) was associated with significant alterations in the plasma pattern of 68 cytokines/chemokines 1 year after rehabilitation and whether such changes were associated with clinical changes. Blood samples and self-reports of pain, psychological distress, and physical activity of 25 complex chronic pain patients were collected pre-IMMRP and at 12-month follow-up. Analyses of inflammatory proteins (cytokines/chemokines/growth factors) were performed directly in plasma using the multiplex immunoassay technology Meso Scale Discovery. This explorative pilot study found that 12 substances, mainly pro-inflammatory, decreased after IMMRP. In two other relatively small IMMRP studies, four of these proinflammatory markers were also associated with decreases. The pattern of cytokines/chemokines pre-IMMRP was associated with changes in psychological distress but not with pain or physical activity. The present study cannot impute cause and effect. These results together with the results of the two previous IMMRP studies suggest that there is a need for larger and more strictly controlled studies of IMMRP with respect to inflammatory markers in blood. Such studies need to consider responders/non-responders, additional therapies, involved pain mechanisms and diagnoses. This and the two other studies open up for developing biologically measurable outcomes from plasma. Such biomarkers will be an important tool for further development of IMMRP and possibly other treatments for patients w ith chronic pain.