Intact and cleaved plasma soluble urokinase receptor in patients with metastatic colorectal cancer treated with oxaliplatin with or without cetuximab

Circulating forms of the urokinase plasminogen activator receptor (uPAR) are associated with prognosis in patients with colorectal cancer. Preclinical studies have shown that uPAR can influence the state of phosphorylation and signalling activity of the epidermal growth factor receptor (EGFR) in a ligand‐independent manner. The purpose of the study was to evaluate whether plasma soluble intact and cleaved uPAR(I‐III)+(II‐III) levels could identify a subpopulation of patients with metastatic colorectal cancer (mCRC) where treatment with cetuximab would have a beneficial effect. Plasma samples were available from 453 patients treated in the NORDIC VII study. Patients were randomized between FLOX and FLOX + cetuximab. The levels of uPAR(I‐III)+(II‐III) were determined by time‐resolved fluorescence immunoassay. We demonstrated that higher baseline plasma uPAR(I‐III)+(II‐III) levels were significantly associated with shorter progression‐free survival (PFS) (HR = 1.30, 1.14–1.48, p = 0.0001) and overall survival (OS) (HR = 1.75, 1.52–2.02, p < 0.0001). Multivariate Cox analysis showed that plasma uPAR(I‐III)+(II‐III) was an independent biomarker of short OS (HR = 1.45, 1.20–1.75, p = 0.0001). There were no significant interactions between plasma uPAR(I‐III)+(II‐III) levels, KRAS mutational status and treatment either PFS (p = 0.43) or OS (p = 0.095). However, further explorative analyses indicated that patients with low levels of circulating suPAR and a KRAS wild‐type tumor have improved effect from treatment with FLOX + cetuximab as compared to patients with KRAS wild‐type and high levels of suPAR. These results thus support the preclinical findings and should be further tested in an independent clinical data set.     

Food patterns and dietary quality associated with organic food consumption during pregnancy; data from a large cohort of pregnant women in Norway

ABSTRACT: BACKGROUND: Little is known about the consumption of organic food during pregnancy. The aim of this study was to describe dietary characteristics associated with frequent consumption of organic food among pregnant women participating in the Norwegian Mother and Child Cohort Study (MoBa). METHODS: The present study includes 63 808 women who during the years 2002-2007 answered two questionnaires, a general health questionnaire at gestational weeks 15 and a food frequency questionnaire at weeks 17-22. The exploration of food patterns by Principal component analyses (PCA) was followed by ANOVA analyses investigating how these food patterns as well as intake of selected food groups were associated with consumption of organic food. RESULTS: The first principal component (PC1) identified by PCA, accounting for 12% of the variation, was interpreted as a 'health and sustainability component', with high positive loadings for vegetables, fruit and berries, cooking oil, whole grain bread and cereal products and negative loadings for meat, including processed meat, white bread, and cakes and sweets. Frequent consumption of organic food, which was reported among 9.1% of participants (n=5786), was associated with increased scores on the 'health and sustainability component' (p<0.001). The increase in score represented approximately 1/10 of the total variation and was independent of sociodemographic and lifestyle characteristics. Participants with frequent consumption of organic food had a diet with higher density of fiber and most nutrients such as folate, beta-carotene and vitamin C, and lower density of sodium compared to participants with no or low organic consumption. CONCLUSION: The present study showed that pregnant Norwegian women reporting frequent consumption of organically produced food had dietary pattern and quality more in line with public advice for healthy and sustainable diets. A methodological implication is that the overall diet needs to be included in future studies of potential health outcomes related to consumption of organic food during pregnancy.     

Validation of model-guided placement of external ventricular drains

Purpose

   Inaccurate placement of external ventricular drains (EVDs) is a common issue in cerebrospinal diversion procedures. The conventional freehand technique results in a high fraction of sub-optimally placed catheters, and the use of image guidance can improve these results. The purpose of this paper is the validation of the use of an average model for guidance of EVD procedures.

Methods

Three neurosurgeons have tested the model-based technique on three normal volunteers, and we have compared the model-based technique to the freehand technique and neuronavigation based on volunteer-specific images.

Results

Our results show that the surgeons perform significantly better when using the model-based technique than when using the freehand technique.

Conclusions

Our results suggest that the use of an average model may improve the accuracy of catheter placements. However, further refinement of the method and testing in a clinical setting is required.     

Acute low-load resistance exercise with and without blood flow restriction increased protein signalling and number of satellite cells in human skeletal muscle

Purpose

To investigate hypertrophic signalling after a single bout of low-load resistance exercise with and without blood flow restriction (BFR).

Methods

Seven subjects performed unilateral knee extensions at 30 % of their one repetition maximum. The subjects performed five sets to failure with BFR on one leg, and then repeated the same amount of work with the other leg without BFR. Biopsies were obtained from m. vastus lateralis before and 1, 24 and 48 h after exercise.

Results

At 1-h post-exercise, phosphorylation of p70S6K^Thr389 and p38MAPK^{Thr180/Tyr182} was elevated in the BFR leg, but not in the free-flow leg. Phospho-p70S6K^Thr389 was elevated three- to fourfold in both legs at 24-h post-exercise, but back to baseline at 48 h. The number of visible satellite cells (SCs) per muscle fibre was increased for all post-exercise time points and in both legs (33–53 %). The proportion of SCs with cytoplasmic extensions was elevated at 1-h post in the BFR leg and the number of SCs positive for myogenin and/or MyoD was increased at 1- and 24-h post-exercise for both legs combined.

Conclusion

Acute low-load resistance exercise with BFR resulted in early (1 h) and late (24 h) enhancement of phospho-p70S6K^Thr389, an early response of p38MAPK, and an increased number of SCs per muscle fibre. Enhanced phospho-p70S6K^Thr389 at 24-h post-exercise and increases in SC numbers were seen also in the free-flow leg. Implications of these findings for the hypertrophic effects of fatiguing low-load resistance exercise with and without BFR are discussed.     

Human cervical carcinoma xenograft models for studies of the physiological microenvironment of tumors

Objective  To establish and characterize experimental tumor models of advanced squamous cell carcinoma of the uterine cervix. Methods  Permanent cell lines (CK-160 and TS-415) were established from pelvic lymph node metastases of two cervical carcinoma patients. Xenografted tumors were initiated by inoculating 5 × 10⁵ cells into the gastrocnemius muscle of BALB/c nu/nu mice. The tumors were characterized with respect to histological appearance, fraction of necrotic tissue (NF), pimonidazole hypoxic fraction (HF_Pim), interstitial fluid pressure (IFP), extracellular pH (pH_e), metastatic propensity, and radiation sensitivity. Results  The xenografted tumors reflected the donor patients’ tumors in histological appearance, metastatic propensity, and radiation sensitivity and showed significant intertumor heterogeneity in growth rate, NF, HF_Pim, IFP, and pH_e. Conclusions  CK-160 and TS-415 xenografts possess properties making them relevant models for studies of the physiological microenvironment of cervical carcinoma and its influence on metastatic dissemination and response to treatment.     

Adult family members and their resemblance of coronary heart disease risk factors: The Cardiovascular Disease Study in Finnmark

Coronary heart disease tends to run in families, and the familial resemblance of major risk factors for the disease was examined among various types of adult family members. Family units were assembled from a total of 4,738 men and women who took part in a cross sectional health survey in four Norwegian municipalities where all inhabitants between 20 and 52 years of age were invited. After adjusting for age and other confounders, correlation coefficients were derived as a measure of the degree of resemblance. Viewed across all types of investigated familial relationships, similarity was found to be stronger for total cholesterol than for high-density lipoprotein cholesterol and triglycerides, and also stronger for systolic than for diastolic blood pressure. Between husbands and wives (3,060 subjects), correlations were small (between 0.02 and 0.06), except for 0.11 for total cholesterol. Lipid and blood pressure correlations ranged from 0.13 to 0.27 for parents and their offspring (471 subjects, p < 0.05) and from 0.11 to 0.22 among siblings (2,166 subjects, p < 0.01). Sibling correlations were consistent across age groups. Furthermore, reports from each individual on daily smoking (yes or no) revealed that husbands and wives had similar habits in 63.5% of all marriages as compared with the expected 49.4% had no smoking similarity at all been present. Smoking concordance was also demonstrated among siblings (p < 0.01). The persistent pattern of lipid and blood pressure aggregation among genetically related individuals from 20 to 52 years of age and the much weaker such similarity between husbands and wives, point towards genes or commonly shared environment at early ages as a major reason why coronary heart disease runs in families.     

Cumulative effects of negative life events and family stress on children’s mental health: the Bergen Child Study

Purpose

Numerous studies have documented that lower socioeconomic status (SES) is associated with increased mental health problems in children. One proposed pathway for this association has been differential exposure to accumulated risk factors in children of lower SES. The aim of the current study was to investigate the socioeconomic distribution of exposure to negative life events and family stress and to examine the direct and interactive association between lower SES and exposure to life events and family stress in relation with mental health problems.

Methods

Using cross-sectional data from the second wave of the Bergen Child Study (conducted in 2006), the current study investigated the association between lower SES and exposure to negative life events, family life stressors, and mental health problems in a sample of 2043 Norwegian 11–13 years and their parents. Information about mental health was self-reported by the children using the Strengths and Difficulties Questionnaire, whereas information about SES and exposure to negative life events and family stressors were provided by their parents.

Results

The findings showed that lower SES was associated with more symptoms of emotional-, conduct-, hyperactivity/inattention-, and peer problems and that exposure to life events and family stress explained some of this association (10–29% of the total effects).

Conclusions

Low SES and higher prevalence of negative life events and family stressors were associated with more symptoms of mental health problems. Overall, the effect sizes were smaller than previous investigations (f ²s?=?0.015–0.031), perhaps suggesting a buffering effect of the social safety net in place in Norway.

     

A comparison between in vitro jejunal mast cell degranulation and intragastric challenge in patients with suspected food intolerance

Fifteen patients with suspected food intolerance were investigated. Ten patients showed a positive reaction to double-blind intragastric food challenge. Mast cell degranulation induced by in vitro challenge with foods or food antigens on mucosal specimens corresponded well with the results of intragastric food challenge. There was agreement in 13 positive and 18 negative tests; there was disagreement in 5 tests. Thus only one in vitro challenge failed to produce mast cell degranulation when the intragastric challenge gave a clinical reaction, and four mucosal specimens showed mast cell degranulations despite no clinical reaction. The results of radioallergosorbent and skin tests afforded little information as to whether the patient would react to the intragastric food challenge.