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Summary The present study investigated the risk of incident hip fractures according to serum concentrations of vitamin K 1 and 25-hydroxyvitamin D in elderly Norwegians during long-term follow-up. The results showed that the combination of low concentrations of both vitamin D and K 1 provides a significant risk factor for hip fractures. Introduction This case-cohort study aims to investigate the associations between serum vitamin K 1 and hip fracture and the possible effect of 25-hydroxyvitamin D (25(OH)D) on this association. Methods The source cohort was 21,774 men and women aged 65 to 79 years who attended Norwegian community-based health studies during 1994–2001. Hip fractures were identified through hospital registers during median follow-up of 8.2 years. Vitamins were determined in serum obtained at baseline in all hip fracture cases ( n  = 1090) and in a randomly selected subcohort ( n  = 1318). Cox proportional hazards regression with quartiles of serum vitamin K 1 as explanatory variable was performed. Analyses were further performed with the following four groups as explanatory variable: I: vitamin K 1  ≥ 0.76 and 25(OH)D ≥ 50 nmol/l, II: vitamin K 1  ≥ 0.76 and 25(OH)D < 50 nmol/l, III: vitamin K 1  < 0.76 and 25(OH)D ≥ 50 nmol/l, and IV: vitamin K 1  < 0.76 and 25(OH)D < 50 nmol/l. Results Age- and sex-adjusted analyses revealed an inverse association between quartiles of vitamin K 1 and the risk of hip fracture. Further, a 50 % higher risk of hip fracture was observed in subjects with both low vitamin K 1 and 25(OH)D compared with subjects with high vitamin K 1 and 25(OH)D (HR 1.50, 95 % CI 1.18–1.90). The association remained statistically significant after adjusting for body mass index, smoking, triglycerides, and serum α-tocopherol. No increased risk was observed in the groups low in one vitamin only. Conclusion Combination of low concentrations of vitamin K 1 and 25(OH)D is associated with increased risk of hip fractures.

Purpose Chronic fatigue (CF) affects 25–30% of lymphoma survivors, but interventions designed to reduce fatigue are lacking. The main aim of this study was to test the feasibility of a multidimensional intervention study in lymphoma survivors with CF. Secondary aims were to describe individual changes in fatigue, quality of life (QoL) and physical performance from pre (T0) to post (T1) intervention. Methods This feasibility study was as a one-armed intervention study performed in 2021. Hodgkin or aggressive non-Hodgkin lymphoma survivors received mailed study information and Chalder Fatigue Questionnaire and were asked to respond if they suffered from fatigue. The 12-week intervention included patient education, physical exercise, a cognitive behavioural therapy (CBT)-based group program and nutritional counselling. Feasibility data included patient recruitment, completion of assessments, adherence to the intervention and patient-reported experience measures. Participants responded to questionnaires and underwent physical tests at T0 and T1. Results Seven lymphoma survivors with CF were included. Of all assessments, 91% and 83% were completed at T0 and T1, respectively. Adherence to the interventional components varied from 69% to 91%. At T1, all participants rated exercise as useful, of whom five rated the CBT-based program and five rated individual nutritional counselling as useful. Five participants reported improved fatigue, QoL and physical performance. Conclusion Lymphoma survivors with CF participating in a multidimensional intervention designed to reduce the level of fatigue showed high assessment completion rate and intervention adherence rate. Most of the participants evaluated the program as useful and improved their level of fatigue, QoL and physical performance after the intervention. Trial registration ClinicalTrials.gov , identifier: NCT04931407. Registered 16. April 2021-Retrospectively registered. https://www.clinicaltrials.gov/ct2/show/NCT04931407

Small intestinal lamina propria (SI-LP) CD103+ dendritic cells (DCs) are imprinted with an ability to metabolize vitamin A (retinol), a property underlying their enhanced capacity to induce the gut-homing receptors CC chemokine receptor-9 and α4β7 on responding T cells. In this study, we demonstrate that imprinting of CD103+ DCs is itself critically dependent on vitamin A and occurs locally within the small intestine (SI). The major vitamin A metabolite retinoic acid (RA) induced retinol-metabolizing activity in DCs both in vitro and in vivo, suggesting a direct role for RA in this process. Consistent with this, SI-LP CD103+ DCs constitutively received RA signals in vivo at significantly higher levels than did colonic CD103+ DCs. Remarkably, SI CD103+ DCs remained imprinted in mice depleted of dietary but not of systemic retinol. We found that bile contained high levels of retinol, induced RA receptor-dependent retinol-metabolizing activity in bone marrow-derived DCs, and imprinted these cells with the ability to generate gut-tropic T cells. Taken together, these results suggest a novel and unexpected role for bile in SI-LP CD103+ DC imprinting.

NutritionDay is a yearly point-prevalence study of malnutrition in hospitals from more than 50 countries. The aim of the present study was to quantify the frequency of malnutrition and the proportion of malnourished patients receiving nutritional treatment in two university hospitals in Norway using data from nutritionDay. All units at Oslo University Hospital (OUH) and University Hospital of Northern Norway (UNN) were invited to participate in nutritionDay 2014, and 28 out of 85 eligible units agreed to take part. Malnutrition was diagnosed based on body mass index (BMI), weight reduction and food intake in the previous week, according to national guidelines and ESPEN criteria. Data from 488 patients were available, representing 90.1% of occupied beds in participating units. Thirty percent of the patients were diagnosed malnourished when national criteria were used, and only 41% of these patients received nutritional treatment. The estimated malnutrition rate was 11% when the ESPEN consensus criteria were used. Data on weight or height were frequently missing in the patient records, and BMI could only be calculated in two-thirds of the patients. The frequency of low BMI (<18.5 kg/m 2 ) was only 5%. Involuntary weight loss was present in 37% of the patients, and 60% had eaten less than normal in the previous week. Oncology units had the highest frequency of patients with low BMI, and the highest weight loss and overall malnutrition rate. Surgery and geriatric units had the highest rate of patients with low food intake. In this study, nearly 60% of the malnourished patients did not receive any nutritional treatment, and this indicates a potential for improved nutritional care and cost savings. Low food intake and weight loss were frequent at these two Norwegian hospitals, and in line with previous reports from nutritionDay in other countries.

The objective of this study was to evaluate the impact of pre-analytical factors on the short and long term stability of ascorbic acid (AA), the main form of vitamin C in whole blood and plasma. The effects of various anticoagulants, acidification, storage temperature and time were tested. A recently developed fast and sensitive HPLC method was used to measure AA levels. AA baseline values observed in heparin plasma were significantly higher than values observed in EDTA, citrate and Stabilyte plasma, as well as in serum. pH and temperature were identified as additional critical pre-analytical factors during the short, medium and long term handling and storage. Thus, assessment of reliable and accurate AA status in biological samples demonstrates to be highly dependent on whether the initial conditions during sample handling are controlled. In conclusion, heparin tubes should be used for blood sample collection. As AA is rapidly degraded, sample collection should be followed by immediate centrifugation and plasma acidification. To avoid further degradation during sample handling, samples should be stored at -70°C without delay and analyzed within 80 days.

Summary We investigated the risk of hip fracture according to circulating alpha-tocopherol, a plant-derived substance with antioxidant properties, in community-dwelling older Norwegians. We found a linear increasing risk of hip fracture with lower serum alpha-tocopherol concentrations, with a 51 % higher risk in the lowest compared to the highest quartile. Introduction Oxidative stress is a suggested contributing cause of osteoporosis and fractures. Vitamin E (α-tocopherol) has potent antioxidant properties in humans. The relationship between circulating α-tocopherol and fracture risk is not established. The aim of this study was to investigate the association between serum α-tocopherol concentrations and risk of hip fracture during up to 11 years of follow-up. Methods We performed a case-cohort analysis among 21,774 men and women aged 65–79 years who participated in four community-based health studies in Norway 1994–2001. Serum α-tocopherol concentrations at baseline were determined in 1,168 men and women who subsequently suffered hip fractures (median follow-up 8.2 years) and in a random sample ( n  = 1,434) from the same cohort. Cox proportional hazard regression adapted for gender-stratified case-cohort data was performed. Results Median (25, 75 percentile) serum α-tocopherol was 30.0 (22.6, 38.3) μmol/L, and it showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11 (95 % confidence interval (CI) 1.04–1.20) per 10-μmol/L decrease in serum α-tocopherol, adjusted for gender and study center. The lowest compared to the highest quartile conferred an HR of 1.51 (95 % CI 1.17–1.95), adjusted for gender and study center. Adjustment for smoking, month of blood sample, BMI, education, physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D) yielded similar results. Taking serum total cholesterol concentration into account attenuated the association somewhat: HR of hip fracture was 1.37 (95 % CI 1.05–1.77) in first versus fourth quartile of serum α-tocopherol/total cholesterol ratio. Conclusions Low serum concentrations of α-tocopherol were associated with increased risk of hip fracture in older Norwegians.

Objective: To assess the effect of an increased consumption of vegetables and fruit on body weight, risk factors for cardiovascular disease (CVD) and antioxidant defense in obese patients with sleep-related breathing disorders (SRBD). Design: Randomized, controlled trial of an intervention to increase the intake of vegetables to 400 g/day and fruit to 300 g/day. Dietary intake was calculated from a food frequency questionnaire. Antioxidant status was assessed with the ferric-reducing/antioxidant power (FRAP) assay. Plasma carotenoids were biomarkers for the intake of vegetables and fruit. Setting: A hospital clinic preventing risk factors for CVD. Subjects: Subjects were 103 men and 35 women with a body mass index of 36.75.8 kg/m2 of which 57 (86%) in the control and 68 (94%) in the intervention group completed the study. Intervention: Group-based behavioral program during 3 months. Results: The mean between group differences in body weight was -2.0% (95% CI -3.6, -0.5), P<0.0001. The mean between group difference in systolic and diastolic blood pressure (BP) was -7.1 mm Hg (95% CI: -11.6, -2.6), P=0.0022 and -3.9 mm Hg (95% CI: -7.0, -0.9), P=0.0120, respectively. The mean change in daily intake of vegetables and fruit was 12 g (95% CI: -33, 57) and -4 g (95% CI: -79, 71) versus 245 g (95% CI: 194, 296) and 248 g (95% CI: 176, 320) in the control and intervention groups, respectively. This was reflected in higher concentrations of -carotene and -carotene. No change in FRAP was seen. In a multiple regression analysis the change in intake of vegetables was a significant contributor (Radj2=0.073 (95% CI: 0.019, 0.214)) to the change in weight. Conclusion: Targeted dietary advice to increase the intake of vegetables and fruit among subjects with SRBD contributed to weight reduction and reduced systolic and diastolic BP, but had no effect on antioxidant defense measured with FRAP.

Lifestyle modifications to reduce risk factors for cardiovascular diseases such as blood pressure (BP) and smoking have been emphasized. Fruits and vegetables may modify such risk factors. The major aim of this randomized, controlled trial was to investigate the effects of (1) kiwifruits and (2) an antioxidant-rich diet compared with (3) a control group on BP and platelet aggregation (that is, whole-blood platelet aggregation) after 8 weeks in male smokers (age 44–74 years, n =102). The kiwifruit group received 3 kiwifruits per day, whereas the antioxidant-rich diet group received a comprehensive combination of antioxidant-rich foods. In the kiwifruit group, reductions of 10 mm Hg in systolic BP and 9 mm Hg in diastolic BP were observed ( P =0.019 and P =0.016 (change from baseline in the kiwifruit group compared with change from baseline in the control group)). In the antioxidant-rich diet group, a reduction of 10 mm Hg in systolic BP was observed among hypertensives ( P =0.045). Additionally, a 15% reduction in platelet aggregation and an 11% reduction in angiotensin-converting enzyme activity was observed in the kiwifruit group ( P =0.009 and P =0.034). No effects on these parameters were observed in the antioxidant-rich diet group. This study suggest that intake of kiwifruit may have beneficial effects on BP and platelet aggregation in male smokers.

Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. However, more subtle gradations in GGT could be informative because its expression is enhanced by oxidative stress and it could be released by several conditions inducing cellular stress. Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes. A total of 4,088 healthy men working in a steel manufacturing company were examined in 1994 and 1998. Diabetes was defined as a serum fasting glucose concentration of more than 126 mg/dl or the use of diabetes medication. There was a strong dose-response relation between serum GGT concentrations at baseline and the incidence of diabetes. In contrast to the 31% of men with GGT concentrations under 9 U/l, adjusted relative risks for incidence of diabetes for GGT concentrations 10-19, 20-29, 30-39, 40-49, and over 50 U/l were 8.0, 13.3, 12.6, 19.6 and 25.8, respectively. The associations of age and BMI with incident diabetes became stronger the higher the value of baseline serum GGT concentration. This study suggests that an increase in GGT concentration within its physiological range is a sensitive and early biomarker for the development of diabetes.

Recent studies have highlighted a central role for intestinal dendritic cells (DCs) and vitamin A metabolite retinoic acid (RA) in the generation of α4β7+ CCR9+“gut tropic” effector T cells. Here, using RA-responsive element reporter mice, we demonstrate that both splenic and mesenteric lymph node (MLN) DCs enhanced retinoic acid receptor (RAR) signaling in CD8+ T cells; however, only a subset of MLN DCs, expressing the integrin α-chain CD103, induced an early RAR signal that is required for efficient CCR9 induction. MLN-primed CD8+ T cells also received enhanced RAR-dependent signals compared with splenic-primed CD8+ T cells in vivo. Further DC-mediated induction of gut homing receptors was inhibited at a high antigen dose without influencing RAR signaling events, and resulted in less efficient CD8+ T-cell entry into the small intestinal mucosa. These results highlight a complex interplay between antigen dose and DC subset-induced RAR signaling events in the generation of tissue tropic effector T-cell subsets.