Factors Associated with Short-Term Mortality After Surgical Oncologic Emergencies

The clinical outcome of patients with oncologic emergencies is often poor and mortality is high. It is important to determine which patients may benefit from invasive treatment, and for whom conservative treatment and/or palliative care would be appropriate. In this study, prognostic factors for clinical outcome are identified in order to facilitate the decision-making process for patients with surgical oncologic emergencies. This was a prospective registration study for patients over 18 years of age, who were consulted for surgical oncologic emergencies between November 2013 and April 2014. Multiple variables were registered upon emergency consultation, and the follow-up period was 90 days. Multivariate logistic regression analysis was performed to identify factors associated with 30- and 90-day mortality. During the study period, 207 patients experienced surgical oncologic emergencies-101 (48.8 %) men and 106 (51.2 %) women, with a median age of 64 years (range 19-92). The 30-day mortality was 12.6 % and 90-day mortality was 21.7 %. Factors significantly associated with 30-day mortality were palliative intent of cancer treatment prior to emergency consultation (p = 0.006), Eastern Cooperative Oncology Group performance score (ECOG-PS) > 0 (p for trend: p = 0.03), and raised lactate dehydrogenase (LDH) (p <0.001). Additional factors associated with 90-day mortality were low handgrip strength (HGS) (p = 0.01) and low albumin (p = 0.002). Defining the intent of prior cancer treatment and the ECOG-PS are of prognostic value when deciding on treatment for patients with surgical oncologic emergencies. Additional measurements of HGS, LDH, and albumin levels can serve as objective parameters to support the clinical assessment of individual prognosis

Convergence and divergence of elite sport policies: is there a one-size-fits-all model to develop international sporting success?

This study is based on a detailed international comparison of the elite sport policies of 15 nations as part of the SPLISS (Sports Policy Factors Leading to International Sporting Success) study. It aims to provide deeper insights into the phenomena of convergence and divergence of elite sport policies. The research uses a mixed methods approach based on document reviews, interviews with high performance directors and surveys of 3142 athletes, 1376 coaches and 246 performance directors. There appears to be no generic blueprint for achieving international sporting success. Nations that perform well in international competition show varying patterns of relative strengths and weaknesses across nine pillars, 96 critical success factors, and 750 sub-factors. While the basic raw ingredients of the recipe might be common in broad terms, the combinations in which they are mixed are diverse. Much of this diversity appears to be driven by social, cultural and political factors

Compound A influences gene regulation of the dexamethasone-activated glucocorticoid receptor by alternative cofactor recruitment

The glucocorticoid receptor (GR) is a transcription factor of which the underlying gene regulatory mechanisms are complex and incompletely understood. The non-steroidal anti-inflammatory Compound A (CpdA), a selective GR modulating compound in various cell models, has been shown to favour GR-mediated gene repression but not GR-mediated gene activation. Shifting balances towards only a particular subset of GR gene regulatory events may be of benefit in the treatment of inflammatory diseases. We present evidence to support that the combination of CpdA with Dexamethasone (DEX), a classic steroidal GR ligand, can shape GR function towards a unique gene regulatory profile in a cell type-dependent manner. The molecular basis hereof is a changed GR phosphorylation status concomitant with a change in the GR cofactor recruitment profile. We subsequently identified and confirmed the orphan nuclear receptor SHP as a coregulator that is specifically enriched at GR when CpdA and DEX are combined. Combining CpdA with DEX not only leads to stronger suppression of pro-inflammatory gene expression, but also enhanced anti-inflammatory GR target gene expression in epithelial cells, making ligand combination strategies in future a potentially attractive alternative manner of skewing and fine-tuning GR effects towards an improved therapeutic benefit

Silicon in foods: content and bioavailability

The silicon content of various foodstuffs marketed in Belgium was measured by a validated graphite furnace absorption spectrometric method. Dietary intake has been identified as the major source of silicon. However, data on its bioavailability remain scarce and insufficient. In vitro methods can provide an indication of bioavailability in case of lacking in vivo data. Bioavailability of silicon from different foodstuffs was estimated using an in vitro continuous flow gastroduodenal simulation method. The major food sources of silicon were unrefined grains, cereal products and root vegetables. The availabilities of silicon from, meat, milk and beers were high, whereas low availability was observed for seafood and cereal products. Plotting the availability data versus the total elemental silicon content of the foods revealed an exponential inverse relationship. The inverse relationship between silicon content and silicon availability was found in all foods, with the exception of various silicon containing drinks. Nevertheless, food categories classified as major silicon sources in the diet still appear to provide the highest absolute amounts of available silicon per 100 g of food including breakfast cereals, bread and baking products, and beers

Silicon in foods: content and bioavailability

The silicon content of various foodstuffs marketed in Belgium was measured by a validated graphite furnace absorption spectrometric method. Dietary intake has been identified as the major source of silicon. However, data on its bioavailability remain scarce and insufficient. In vitro methods can provide an indication of bioavailability in case of lacking in vivo data. Bioavailability of silicon from different foodstuffs was estimated using an in vitro continuous flow gastroduodenal simulation method. The major food sources of silicon were unrefined grains, cereal products and root vegetables. The availabilities of silicon from, meat, milk and beers were high, whereas low availability was observed for seafood and cereal products. Plotting the availability data versus the total elemental silicon content of the foods revealed an exponential inverse relationship. The inverse relationship between silicon content and silicon availability was found in all foods, with the exception of various silicon containing drinks. Nevertheless, food categories classified as major silicon sources in the diet still appear to provide the highest absolute amounts of available silicon per 100 g of food including breakfast cereals, bread and baking products, and beers

Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells

Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n=15) were given a test meal of 200g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p=0.003). Sub-group B (n=9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p=0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p=0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p=0.009) and 35% (p=0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification

The Anticancer Plant Triterpenoid, Avicin D, Regulates Glucocorticoid Receptor Signaling: Implications for Cellular Metabolism

Avicins, a family of apoptotic triterpene electrophiles, are known to regulate cellular metabolism and energy homeostasis, by targeting the mitochondria. Having evolved from “ancient hopanoids,” avicins bear a structural resemblance with glucocorticoids (GCs), which are the endogenous regulators of metabolism and energy balance. These structural and functional similarities prompted us to compare the mode of action of avicin D with dexamethasone (Dex), a prototypical GC. Using cold competition assay, we show that Avicin D competes with Dex for binding to the GC receptor (GR), leading to its nuclear translocation. In contrast to Dex, avicin-induced nuclear translocation of GR does not result in transcriptional activation of GC-dependent genes. Instead we observe a decrease in the expression of GC-dependent metabolic proteins such as PEPCK and FASN. However, like Dex, avicin D treatment does induce a transrepressive effect on the pro-inflammatory transcription factor NF-κB. While avicin's ability to inhibit NF-κB and its downstream targets appear to be GR-dependent, its pro-apoptotic effects were independent of GR expression. Using various deletion mutants of GR, we demonstrate the requirement of both the DNA and ligand binding domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin-GR interaction revealed that avicin molecule binds only to the antagonist confirmation of GR. These findings suggest that avicin D has properties of being a selective GR modulator that separates transactivation from transrepression. Since the gene-activating properties of GR are mainly linked to its metabolic effects, and the negative interference with the activity of transcription factors to its anti-inflammatory and immune suppressive effects, the identification of such a dissociated GR ligand could have great potential for therapeutic use

Behavioral determinants as predictors of return to work after long-term sickness absence: an application of the theory of planned behavior

Background The aim of this prospective, longitudinal cohort study was to analyze the association between the three behavioral determinants of the theory of planned behavior (TPB) model-attitude, subjective norm and self-efficacy-and the time to return-to-work (RTW) in employees on long-term sick leave. Methods The study was based on a sample of 926 employees on sickness absence (maximum duration of 12 weeks). The employees filled out a baseline questionnaire and were subsequently followed until the tenth month after listing sick. The TPB-determinants were measured at baseline. Work attitude was measured with a Dutch language version of the Work Involvement Scale. Subjective norm was measured with a self-structured scale reflecting a person's perception of social support and social pressure. Self-efficacy was measured with the three subscales of a standardised Dutch version of the general self-efficacy scale (ALCOS): willingness to expend effort in completing the behavior, persistence in the face of adversity, and willingness to initiate behavior. Cox proportional hazards regression analyses were used to identify behavioral determinants of the time to RTW. Results Median time to RTW was 160 days. In the univariate analysis, all potential prognostic factors were significantly associated (P < 0.15) with time to RTW: work attitude, social support, and the three subscales of self-efficacy. The final multivariate model with time to RTW as the predicted outcome included work attitude, social support and willingness to expend effort in completing the behavior as significant predictive factors. Conclusions This prospective, longitudinal cohort-study showed that work attitude, social support and willingness to expend effort in completing the behavior are significantly associated with a shorter time to RTW in employees on long-term sickness absence. This provides suggestive evidence for the relevance of behavioral characteristics in the prediction of duration of sickness absence. It may be a promising approach to address the behavioral determinants in the development of interventions focusing on RTW in employees on long-term sick leave

Minimization of free radical damage by metal catalysis of multivitamin/multimineral supplements

Multivitamin/multimineral complexes are the most common dietary supplements. Unlike minerals in foods that are incorporated in bioorganic structures, minerals in dietary supplements are typically in an inorganic form. These minerals can catalyze the generation of free radicals, thereby oxidizing antioxidants during digestion. Here we examine the ability of a matrix consisting of an amino acid and non-digestible oligosaccharide (AAOS) to blunt metal-catalyzed oxidations. Monitoring of ascorbate radical generated by copper shows that ascorbate is oxidized more slowly with the AAOS matrix than with copper sulfate. Measurement of the rate of oxidation of ascorbic acid and Trolox® by catalytic metals confirmed the ability of AAOS to slow these oxidations. Similar results were observed with iron-catalyzed formation of hydroxyl radicals. When compared to traditional forms of minerals used in supplements, we conclude that the oxidative loss of antioxidants in solution at physiological pH is much slower when AAOS is present