Vitamin B12 status in infancy and the effect of a vitamin B12 injection in infants with subclinical vitamin B12 deficiency: study protocol for a register-based randomised controlled trial.

INTRODUCTION: Vitamin B12 (cobalamin) is crucial for optimal child development and growth, yet deficiency is common worldwide. The aim of this study is twofold; (1) to describe vitamin B12 status and the status of other micronutrients in Norwegian infants, and (2) in a randomised controlled trial (RCT), investigate the effect of vitamin B12 supplementation on neurodevelopment in infants with subclinical vitamin B12 deficiency. METHODS AND ANALYSIS: Infant blood samples, collected at public healthcare clinics, are analysed for plasma cobalamin levels. Infants with plasma cobalamin <148 pmol/L are immediately treated with hydroxocobalamin and excluded from the RCT. Remaining infants (cobalamin ≥148 pmol/L) are randomly assigned (in a 1:1 ratio) to either a screening or a control group. In the screening group, baseline samples are immediately analysed for total homocysteine (tHcy), while in the control group, the baseline samples will be analysed after 12 months. Screening group infants with plasma tHcy >6.5 µmol/L, are given an intramuscular injection of hydroxocobalamin (400 µg). The primary outcomes are cognitive, language and motor development assessed using the Bayley Scales of Infant and Toddler Development at 12 months of age. ETHICS AND DISSEMINATION: The study has been approved by the Regional Committee for Medical and Health Research Ethics (ref: 186505). Investigators who meet the Vancouver requirements will be eligible for authorship and be responsible for dissemination of study findings. Results will extend current knowledge on consequences of subclinical vitamin B12 deficiency during infancy and may inform future infant feeding recommendations. TRIAL REGISTRATION NUMBER: NCT05005897.

A Cross-Sectional Study of the Relationship Between Mental Health Problems and Overweight and Obesity in Adolescents.

Background: There is a suggested coexistence between obesity and mental health discomfort in adolescence. The objective of this study was to explore if mental health indices covaried with body mass index (BMI) in adolescence and if there were gender-related disparities. Methods: Data were collected in two cross-sectional surveys of 10th-grade students (15 to 16 years old) carried out in 2002 and 2017. The questionnaires included self-reported height and weight, questions covering mental health using the Strengths and Difficulties Questionnaire (SDQ), lifestyle, and sociodemographic variables. We estimated the associations between SDQ subscale scores and BMI and the prevalence of overweight and obesity in linear and logistic multivariable models. We also estimated the extent to which gender modified these associations. Results: BMI was positively associated with peer problems [beta (ß): 0.08, (95% confidence interval 0.01, 0.14)], indicating that for every point increase in peer problems subscore, BMI increased by 0.08 kg/m2. The association between internalizing (i.e., peer and emotional) problems and BMI and conduct problems and BMI was different for boys and girls (p < 0.05 for all effect modifications). Conclusion: In this repeated cross-sectional study across 15 years, we found that peer problems were associated with BMI in Norwegian adolescents. We also found that there is a possibility that adolescent boys and girls report different mental health symptoms related to increased BMI. This finding implicates a need for gender-specific attention when assessing risk factors for increased BMI in adolescents.

Consumption of energy drinks among adolescents in Norway: a cross-sectional study.

BACKGROUND: Energy drink (ED) consumption is increasing all over the world. We sought to describe the consumption of EDs among adolescents in Norway, and to explore the determinants of daily and high consumption. METHODS: Population-based cross-sectional data were collected from a sample of 31,091 secondary school students in grade 8-13 aged 12-19 years. School grade, residency, socioeconomic status (SES), physical activity and leisure screen time were included in multiple regression analyses, in order to investigate their associations with daily and high (≥four times weekly) ED consumption. RESULTS: 52.3% of the respondents were ED consumers and 3.5% were high consumers. Boys consumed twice as much ED as girls (boys: 36.3 ml/day, girls: 18.5 ml/day, geometric means), and the proportion of male high consumers was 3.7-times higher than that of females. The adjusted odd ratio (OR) of upper secondary school (grades 11-13, ages 15-19) students being high ED consumers were higher than for lower secondary school (grades 8-10, ages 12-15) students (OR 1.1(confidence interval (CI):1.0-1.3)), as well as higher for rural than urban residents (OR 1.3 (CI: 1.1-1.5)). Gradients for the increased ORs of being a high ED consumer were found for decreased SES, decreased frequency of physical activity and increased daily leisure screen time. CONCLUSIONS: More than half of the respondents reported that they were ED consumers. Daily and high consumption were independently associated with male gender, physical inactivity, high leisure screen time, low socioeconomic status and rural residency.

Tissue inhibitor of metalloproteinases-1 in the postoperative monitoring of colorectal cancer.

The aim of this study was to investigate whether the pre- and postoperative plasma levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) were associated with outcome in colorectal cancer (CRC). Pre- and postoperative plasma TIMP-1 from 280 curatively resected CRC patients and carcinoembryonic antigen (CEA) in corresponding serum samples were measured and correlated with patient outcome (death, local recurrence (LR) and distant metastases (DM)). The results showed that the course of plasma TIMP-1 from pre- to postoperative levels correlated with patient outcome (P=0.005). However, postoperative plasma TIMP-1 alone was strongly associated with patient outcome, high TIMP-1 predicting short survival (P=0.002). Combining postoperative TIMP-1 and CEA demonstrated that high TIMP-1 and CEA levels predicted poor outcome (P<0.0001); multivariate analysis identifying both parameters as strong prognostic factors for survival, LR and DM (P<0.0001). In conclusion, postoperative plasma TIMP-1 predicts patient outcome both alone and in combination with CEA. Postoperative TIMP-1 may be a marker of residual disease after primary surgery for CRC.

Tumor tissue concentrations of the proteinase inhibitors tissue inhibitor of metalloproteinases-1 (TIMP-1) and plasminogen activator inhibitor type 1 (PAI-1) are complementary in determining prognosis in primary breast cancer.

The purpose of this study was to investigate the association between tumor tissue levels of total tissue inhibitor of metalloproteinases-1 (TIMP-1) and prognosis in patients with primary breast cancer and to analyze whether measurement of TIMP-1 in tumor extracts added prognostic information to that obtained from measurements of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 (PAI-1). An established sandwich enzyme-linked immunosorbent assay was thoroughly validated for the measurement of total TIMP-1 in tumor tissue extracts and used to determine levels of total TIMP-1 in 341 detergent-extracted tumor tissue samples from patients with primary breast cancer. The median age of the patients was 56 years (range, 29-75 years), and 164 were lymph node-negative, and 177 were lymph node-positive. The median follow-up time of the patients was 8.5 years (range, 7.3-11.3 years), and during follow-up 153 patients experienced recurrence of disease, and 136 patients died. In univariate survival analysis, we found a significant association between tumor tissue TIMP-1 level and both shorter recurrence-free survival (p = 0.0004) and shorter overall survival (p = 0.03). In multivariate survival analysis, higher tumor tissue TIMP-1 levels significantly and independently predicted shorter recurrence-free survival (p < 0.05, hazard ratios >1, comparing quartiles II-IV with I). In addition, we found that measurement of TIMP-1 levels added prognostic information to that obtained from measurement of PAI-1. In conclusion, high levels of TIMP-1 in tumor tissue extracts are significantly associated with a poor prognosis in patients with primary breast cancer. Furthermore TIMP-1 adds prognostic information to that obtained from PAI-1. However, further validation in independent data sets is needed.