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Myxovirus resistance (Mx) proteins are products of interferon stimulated genes (ISGs) and Mx proteins of different species have been reported to mediate antiviral activity against a number of viruses, including influenza A viruses (IAV). Ferrets are widely considered to represent the ‘gold standard’ small animal model for studying pathogenesis and immunity to human IAV infections, however little is known regarding the antiviral activity of ferret Mx proteins. Herein, we report induction of ferret (f)Mx1/2 in a ferret lung cell line and in airway tissues from IAV-infected ferrets, noting that fMx1 was induced to higher levels that fMx2 both in vitro and in vivo. Overexpression confirmed cytoplasmic expression of fMx1 as well as its ability to inhibit infection and replication of IAV, noting that this antiviral effect of fMx1was modest when compared to cells overexpressing either human MxA or mouse Mx1. Together, these studies provide the first insights regarding the role of fMx1 in cell innate antiviral immunity to influenza viruses. Understanding similarities and differences in the antiviral activities of human and ferret ISGs provides critical context for evaluating results when studying human IAV infections in the ferret model.

Fear of physical activity (PA) is discussed as a barrier to regular exercise in patients with heart failure (HF), but HF-specific theoretical concepts are lacking. This study examined associations of fear of PA, heart-focused anxiety and trait anxiety with clinical characteristics and self-reported PA in outpatients with chronic HF. It was also investigated whether personality-related coping styles for dealing with health threats impact fear of PA via symptom perception. This cross-sectional study enrolled 185 HF outpatients from five hospitals (mean age 62 ± 11 years, mean ejection fraction 36.0 ± 12%, 24% women). Avoidance of PA, sports/exercise participation (yes/no) and the psychological characteristics were assessed by self-reports. Fear of PA was assessed by the Fear of Activity in Situations-Heart Failure (FActS-HF15) questionnaire. In multivariable regression analyses higher NYHA class (b = 0.26, p = 0.036) and a higher number of HF drugs including antidepressants (b = 0.25, p = 0.017) were independently associated with higher fear of PA, but not with heart-focused fear and trait anxiety. Of the three anxiety scores only increased fear of PA was independently associated with more avoidance behavior regarding PA (b = 0.45, SE = 0.06, p < 0.001) and with increased odds of no sports/exercise participation (OR = 1.34, 95% CI 1.03-1.74, p = 0.028). Attention towards cardiac symptoms and symptom distress were positively associated with fear of PA (p < 0.001), which explained higher fear of PA in patients with a vigilant (directing attention towards health threats) coping style (p = 0.004). Fear of PA assessed by the FActS-HF15 is a specific type of anxiety in patients with HF. Attention towards and being distressed by HF symptoms appear to play a central role in fear of PA, particularly in vigilant patients who are used to direct their attention towards health threats. These findings provide approaches for tailored interventions to reduce fear of PA and to increase PA in patients with HF. ClinicalTrials.gov ID: NCT02898246.

Background We investigate and try to find out the optimal duration and intensity for the treatment and content useful for clinical work. The aim of our study is to evaluate the effects of lifestyle intervention on the management of childhood overweight and to explore the factors that contribute to the outcome, as well as the costs for the health care system. The hypotheses of the study are that lifestyle intervention is efficient in reducing BMI-SDS and thus effective in preventing overweight from progressing to obesity, and it is also cost-effective. Methods and analyses We aim to recruit 80 children and they randomize either to an intervention group or a control group with standard care. The intervention group receives intensive, family-based diet, and physical activity counseling, delivered by a multidisciplinary team of a pediatrician, a nurse, and a clinical nutritionist. The control group does not receive any lifestyle intervention during the study. The inclusion criteria are age of 6–12 years, weight-for-height ≥  + 40% or ≥  + 30%, and increasing curve. All participants fill out the study questionnaires and plasma samples are taken at baseline and at 12 months. Outcome variables will be compared between intervention and control groups. Discussion If the effects of this lifestyle intervention are positive and it is also cost-effective, the implication of our study will be of great importance to the treatment of childhood obesity and to improve the health care system. Trial registration ClinicalTrials.gov NCT06126679. Registered on 25 October 2028 in Finland. ORCID: 0009-0009-6659-5290.

Aims/hypothesis Low-grade inflammation and endothelial dysfunction may play a role in the pathogenesis of type 2 diabetes and cardiovascular disease. We evaluated whether a diet high in fatty fish, bilberries and wholegrain products (Healthy Diet) improves biomarkers reflecting inflammation and endothelial dysfunction in individuals with impaired glucose metabolism. Methods We recruited individuals with impaired glucose metabolism and features of the metabolic syndrome into a 12 week, parallel design, dietary intervention trial conducted at the Department of Clinical Nutrition, University of Eastern Finland (Kuopio, Finland). Randomisation was performed by matching according to sex and medians of age, BMI and fasting plasma glucose of the study population at screening. The primary endpoint in the present study was the change in plasma inflammatory markers and the measurements were performed blinded to group assignment. High-sensitivity (hs) C-reactive protein (CRP) and E-selectin responses were also analysed separately in participants not using statins ( n  = 76). Results Altogether, 131 individuals were assigned to either the Healthy Diet ( n  = 44), a whole-grain-enriched diet (WGED) ( n  = 42) or a control ( n  = 45) diet, and 104 participants (mean ± SD: age 59 ± 7 years; BMI 31.1 ± 3.5 kg/m 2 ) who had completed the study, were analysed (Healthy Diet n  = 36, WGED n  = 34 and control diet n  = 34). Plasma E-selectin decreased only in the Healthy Diet group. This occurred in all group participants ( p  < 0.05) and also after excluding participants using statins ( p  < 0.05). Plasma hsCRP levels decreased in the Healthy Diet (median −17%, p  < 0.05) and WGED (median −27%, p  < 0.01) groups in participants not using statins. Controlling for confounding factors, including BMI or insulin sensitivity, did not alter the results. A greater increase in plasma concentration of very-long-chain n -3 fatty acids and in the intake of fibre during the study was associated with a greater decrease in plasma E-selectin ( p  < 0.05). The intake of test breads consumed during the Healthy Diet and WGED interventions was inversely associated with the change in hsCRP levels ( p  < 0.001). Conclusions/interpretation Our results suggest that the combined effect of fatty fish, bilberries and wholegrain products may improve endothelial dysfunction and inflammation in overweight and obese individuals at high risk of developing diabetes. Trial registration: ClinicalTrials.gov NCT00573781 Funding: The study was funded by the Academy of Finland (117844 and 118590 [to M. Uusitupa]; 131460 [to K. Poutanen]; 130469 [to H. Mykkänen] and 131593 [to V. D. F. de Mello]); the Kuopio University Hospital (5106, 5168, 5254 [to M. Uusitupa]); the Finnish Diabetes Research Foundation; the Sigrid Juselius Foundation; the Nordic Centre of Excellence on ‘Systems biology in controlled dietary interventions and cohort studies’ (SYSDIET; 070014); and the European Commission in the Communities 6th Framework Programme, Project HEALTHGRAIN (FOOD-CT-2005-514008).

BackgroundFrequent weight loss attempts are related to maladaptive eating behaviours and higher body mass index (BMI). We studied associations of several type 2 diabetes (T2D) risk factors with weight loss history, defined as the frequency of prior weight loss attempts, among Finnish adults at increased risk for T2D.MethodsThis study (n = 2684, 80% women) is a secondary analysis of the 1-year StopDia lifestyle intervention with digital intervention group, digital intervention + face-to-face counselling group, or control group. The frequency of prior weight loss attempts was categorized into five groups: no attempts/no attempts to lose weight, but trying to keep weight stable/1–2 attempts/3 or more attempts/ continuous attempts. Data on emotional eating and social/emotional nutrition self-efficacy were collected with a digital questionnaire. We assessed baseline differences between categories of weight loss history as well as the intervention effects.ResultsAltogether 84% of participants had attempted weight loss. Those with one or more weight loss attempts had higher BMI, larger waist circumference, and more emotional eating compared to ‘no attempts’ and ‘no attempts to lose weight, but trying to keep weight stable’ categories. The ‘no attempts’ category had the highest baseline fasting insulin, whereas it showed the largest decrease in this measure with the intervention. This change in fasting insulin in the ‘no attempts’ category was significantly different from all the other categories. Emotional nutrition self-efficacy slightly improved in the ‘no attempts’ category, which was significantly different from its concomitant decrease in the categories ‘1-2 attempts’ and ‘3 or more attempts’. The intervention group assignment did not affect the results.ConclusionsMultiple attempts to lose weight may unfavourably affect T2D risk factors as well as lifestyle intervention outcomes. More research is needed on how weight loss frequency could affect T2D risk factors and how to design lifestyle interventions for individuals with frequent previous weight loss attempts.

Consumption of energy- and nutrient-dense snacks are recommended for older people to maintain adequate nutrition. We evaluated the effects of dairy-based and energy-enriched berry products consumed as snacks on nutritional and functional status among vulnerable older people receiving home care services. Randomised controlled study. The study sample consisted of 85 home care clients, with mean age of 81.9 (SD 7.1) years in the intervention group (n=50) and 83.7 (SD 8.1) years in the control group (n=35), and 72% women in both groups. In the intervention group, the participants consumed both high-protein dairy-based products and energy-enriched berry purées for three months. The snack products provided nearly 300 kcal and 14 g protein per day. The Mini Nutritional Assessment (MNA), body mass index (BMI), mid-arm muscular area (MAMA) and concentrations of plasma albumin and prealbumin and blood haemoglobin were used to determine nutritional status, and handgrip strength was used to determine functional status at baseline and after the intervention. Results: After adjustment for age and gender, the intervention showed a significant effect on MNA scores (2.1, 95% [CI]: 1.0 to 3.3) (p=0.003), albumin concentration (2.0 g/L, 95% [CI]: 1.1 to 3.2) (p=0.006) and handgrip strength of the right hand in women (2.4 kg, 95% [CI]: 1.2 to 3.3) (p=0.007). The MNA scores improved in the intervention group, while albumin concentration and handgrip strength decreased in the control group. Regular use of dairy- and energy-enriched berry-based snacks may improve or maintain nutritional and functional status among older people in home care.

In inflammatory bowel disease, dysregulated T cells express pro-inflammatory cytokines. Using a chronic azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis model resembling ulcerative colitis, we evaluated whether and when treatment with the Janus kinase (JAK) inhibitor tofacitinib could be curative. Comparing the treatment with two and three cycles of tofacitinib medication in drinking water – intermittently with DSS induction – revealed that two cycles were not only sufficient but also superior over the 3-x regimen. The two cycles of the 2-x protocol paralleled the second and third cycles of the longer protocol. T cells were less able to express interferon gamma (IFN-γ) and the serum levels of IFN-γ, interleukin (IL)-2, IL-6, IL-17, and tumor necrosis factor (TNF) were significantly reduced in sera, while those of IL-10 and IL-22 increased under the 2-x protocol. Likewise, the frequency and effector phenotype of regulatory T cells (Tregs) increased. This was accompanied by normal weight gain, controlled clinical scores, and restored stool consistency. The general and histologic appearance of the colons revealed healing and tissue intactness. Importantly, two phases of tofacitinib medication completely prevented AOM-incited pseudopolyps and the hyper-proliferation of epithelia, which was in contrast to the 3-x regimen. This implies that the initial IBD-induced cytokine expression is not necessarily harmful as long as inflammatory signaling can later be suppressed and that time-restricted treatment allows for anti-inflammatory and tissue-healing cytokine activities.

RIG-I is an innate sensor of RNA virus infection and its activation induces interferon-stimulated genes (ISGs). In vitro studies using human cells have demonstrated the ability of synthetic RIG-I agonists (3pRNA) to inhibit IAV replication. However, in mouse models of IAV the effectiveness of 3pRNA reported to date differs markedly between studies. Myxoma resistance (Mx)1 is an ISG protein which mediates potent anti-IAV activity, however most inbred mouse strains do not express a functional Mx1. Herein, we utilised C57BL/6 mice that do (B6.A2G-Mx1) and do not (B6-WT) express functional Mx1 to assess the ability of prophylactic 3pRNA treatment to induce ISGs and to protect against subsequent IAV infection. In vitro, 3pRNA treatment of primary lung cells from B6-WT and B6.A2G-Mx1 mice resulted in ISG induction however inhibition of IAV infection was more potent in cells from B6.A2G-Mx1 mice. In vivo, a single intravenous injection of 3pRNA resulted in ISG induction in lungs of both B6-WT and B6.A2G-Mx1 mice, however potent and long-lasting protection against subsequent IAV challenge was only observed in B6.A2G-Mx1 mice. Thus, despite broad ISG induction, expression of a functional Mx1 is critical for potent and long-lasting RIG-I agonist-mediated protection in the mouse model of IAV infection.

Objective: Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome. Design: Randomized controlled and individualized weight reduction intervention. Subjects: Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60±7 years were randomized either to a weight reduction (WR) ( n =28) or a control ( n =18) group lasting for 33 weeks. Measurements: Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction ⩾5%, n =9) and control group ( n =10). The results were confirmed using quantitative PCR. Results: In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S I and the change in body weight was found ( r =−0.44, P =0.026). Downregulation of gene expression ( P <0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (−39±16%, P <0.0001). Moreover, its expression correlated with insulin sensitivity ( r =−0.34, P =0.005) before the intervention and with body adiposity both before ( r =0.42, P =0.007) and after ( r =0.30, P =0.056) the intervention. Conclusion: Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.

Objectives: To investigate the associations of dietary factors with overweight, body fat percentage (BF%), waist circumference (WC) and hip circumference (HC) among children. Design: Cross-sectional analysis of the Physical Activity and Nutrition in Children (PANIC) Study among 510 children (263 boys, 247 girls) aged 6–8 years from Kuopio, Finland. Methods: The children’s weight, height, WC and HC were measured. Overweight was defined by International Obesity Task Force body mass index cutoffs. The BF% was measured by dual-energy X-ray absorptiometry, nutrient intakes and meal frequency by 4-day food records and eating behaviour by Children’s Eating Behaviour Questionnaire. Results: Daily consumption of all the three main meals was inversely associated with overweight (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.18–0.75), BF% ( β −0.12, P =0.012), WC ( β −0.16, P =0.002) and HC ( β −0.15, P =0.002). Enjoyment of food, food responsiveness and emotional overeating were directly associated with overweight (OR 1.57, 95% CI 1.04–2.35; OR 4.68, 95% CI 2.90–7.54; OR 2.60, 95% CI 1.52–4.45, respectively), BF% ( β 0.13, P =0.004; β 0.30, P <0.001; β 0.09, P =0.035, respectively), WC ( β 0.14, P =0.003; β 0.40, P <0.001; β 0.19, P <0.001, respectively) and HC ( β 0.15, P =0.001; β 0.38, P <0.001; β 0.15, P =0.001, respectively). Satiety responsiveness was inversely associated with overweight (OR 0.42, 95% CI 0.26–0.67), BF% ( β −0.20, P <0.001), WC ( β −0.26, P <0.001) and HC ( β −0.26, P <0.001). Slowness in eating was inversely associated with overweight (OR 0.61, 95% CI 0.41–0.92), WC ( β −0.16, P =0.001) and HC ( β −0.17, P <0.001). Protein intake was directly associated with BF% ( β 0.11, P =0.017), WC ( β 0.11, P =0.020) and HC ( β 0.13, P =0.008). Conclusions: Promoting regular consumption of main meals and healthy eating behaviours should be emphasized in the prevention of overweight among children. More research is needed on the association of protein-rich foods with body adiposity in children.