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

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Is prioritisation of funding in elite sport effective? An analysis of the investment strategies in 16 countries

Abstract Research question: This paper explores the extent to which nations prioritise elite sport funding; whether such nations are more successful than those whose funding is more diversified; and, if the sports that receive the most funding are also the most successful. Research methods: Data on public expenditure for elite sport programmes (2011/2012) were collected on a sport-specific basis in 16 nations (n=445 funded sports). The Herfindahl index and concentration ratios of the four/eight most funded sports (CR4/CR8) are used as proxies for prioritization. Success was measured using top 3 and top 8 places during the Olympic Games and World Championships. Descriptive analysis and linear regression are applied to identify the relationship between the distribution of funding and success. Results and findings: Generally, all sample nations are prioritisers. Nations with smaller total elite sport budgets tended to prioritise more. There is a slight negative association between the distribution of funding within a country and subsequent success, indicating that the sample countries that prioritise more tended to be less successful. Sample nations that diversify their funding more, are found to be successful in a wider range of sports. In addition, the data illustrated only low allocative efficiency for some nations. Implications: The study produced ambiguous conclusions that prioritisation as a deliberate strategic choice is an efficient way to invest funding. The findings have important implications for high performance managers and suggests that a more diverse resource allocation policy may help to avoid unintended negative consequences. Keywords: Targeted funding; elite sport policy; allocative efficiency; prioritisation; SPLIS

A Novel Stable Isotope Approach for Determining the Impact of Thickening Agents on Water Absorption

Research on the bioavailability of water from thickened fluids has recently been published and it concluded that the addition of certain thickening agents (namely, modified maize starch, guar gum, and xanthan gum) does not significantly alter the absorption of water from the healthy, mature human gut. Using xanthan gum as an example, our “proof of concept” study describes a simple, accurate, and noninvasive alternative to the methodology used in that first study, and involves the measurement and comparison of the dilution space ratios of the isotopes 2H and 18O and subsequent calculation of total body water. Our method involves the ingestion of a thickening agent labeled with 2H 1 day after ingestion of 18O. Analyses are based on the isotopic enrichment of urine samples collected prior to the administration of each isotope, and daily urine samples collected for 15 days postdosing. We urge that further research is needed to evaluate the impact of various thickening agents on the bioavailability of water from the developing gut and in cases of gut pathology and recommend our methodology

De geprotocolleerde Interapy-behandeling van depressie via het internet; resultaten van een gerandomiseerde trial

Psychologische behandelingen via internet bieden een nieuwe mogelijkheid voor de geestelijke gezondheidszorg. In samenwerking met de Stichting Mentrum ggz Amsterdam heeft Interapy een behandeling voor depressie via internet opgezet. De behandeling bestaat uit cognitief-gedragstherapeutische interventies, zoals psycho-educatie, schrijfopdrachten, registratie, activatie, het uitdagen van negatieve automatische gedachten en terugvalpreventie. Dit artikel beschrijft de procedure, de behandeling en de resultaten van een vergelijkende studie onder cliënten die matig tot ernstig depressief waren. De cliënten die direct actief werden behandeld (N = 32) verbeterden significant meer dan de cliënten in de psycho-educatieconditie (N = 14). Deze tweede groep kreeg de actieve behandeling ongeveer twaalf weken later. De effecten waren groot. In de actief behandelde groep liet 75 procent van de cliënten klinisch relevante verbetering zien, in de psycho-educatieconditie was dat percentage 36. Uit de follow-up na zes weken bleek dat de verbeteringen standhielden

Flow Cytometric Analysis and Sorting of Murine Enteric Nervous System Cells:An Optimized Protocol

Isolation of neurons and glia from the enteric nervous system (ENS) enables ex vivo studies, including the analysis of genomic and transcriptomic profiles. While we previously reported a fluorescence-activated cell sorting (FACS)-based isolation protocol for human ENS cells, no equivalent exists for mice. As directly applying the human protocol to mouse tissue resulted in low recovery of live ENS cells, we optimized tissue dissociation using mouse colons. A 30 min Liberase-based digestion showed optimal recovery of viable ENS cells, with CD56 and CD24 emerging as the most reliable markers to select and subdivide these cells. ENS’ identity was further validated by FACS, using neuronal (TUBB3) and glial (SOX10) markers and reverse transcriptase quantitative PCR on sorted fractions. Overall, the mouse ENS expression profile significantly overlapped with the human one, showing that current dissociation protocols yield a mixed population of enteric neurons and glia. Nonetheless, using the imaging flow cytometer BD S8 FACS Discover and ELAVL4 as a neuronal soma-associated marker, we observed enrichment of neurons in a CD56/CD24TIP population. In conclusion, we present here a protocol for high-purity FACS-based isolation of viable mouse ENS cells, suitable for downstream applications.</p

Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

<p>Abstract</p> <p>Background</p> <p>Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia.</p> <p>Methods/Design</p> <p>One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an <it>aerobic exercise program in a rehabilitation centre</it> or a <it>flexibility and relaxation program in a rehabilitation centre</it>. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a <it>daily physical activity program set at home making use of pedometers</it>. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures.</p> <p>Discussion</p> <p>The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life.</p> <p>Trial registration</p> <p>The present study is registered within The Netherlands National Trial Register (ref: NTR2124)</p

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

Biallelic and monoallelic ESR2 variants associated with 46,XY disorders of sex development

Purpose: Disorders or differences of sex development (DSDs) are rare congenital conditions characterized by atypical sex development. Despite advances in genomic technologies, the molecular cause remains unknown in 50% of cases. Methods: Homozygosity mapping and whole-exome sequencing revealed an ESR2 variant in an individual with syndromic 46, XY DSD. Additional cases with 46, XY DSD underwent whole-exome sequencing and targeted next-generation sequencing of ESR2. Functional characterization of the identified variants included luciferase assays and protein structure analysis. Gonadal ESR2 expression was assessed in human embryonic data sets and immunostaining of estrogen receptor-beta (ER-beta) was performed in an 8-week-old human male embryo. Results: We identified a homozygous ESR2 variant, c.541_543del p. (Asn181del), located in the highly conserved DNA-binding domain of ER-beta, in an individual with syndromic 46, XY DSD. Two additional heterozygous missense variants, c.251G>T p.(Gly84Val) and c.1277T>G p.(Leu426Arg), located in the N-terminus and the ligand-binding domain of ER-beta, were found in unrelated, nonsyndromic 46, XY DSD cases. Significantly increased transcriptional activation and an impact on protein conformation were shown for the p.(Asn181del) and p.(Leu426Arg) variants. Testicular ESR2 expression was previously documented and ER-beta immunostaining was positive in the developing intestine and eyes. Conclusion: Our study supports a role for ESR2 as a novel candidate gene for 46, XY DSD