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- Reinders, I., et al.
(författare)
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Effectiveness and cost-effectiveness of personalised dietary advice aiming at increasing protein intake on physical functioning in community-dwelling older adults with lower habitual protein intake: rationale and design of the PROMISS randomised controlled trial
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Short-term metabolic and observational studies suggest that protein intake above the recommended dietary allowance of 0.83 g/kg body weight (BW)/day may support preservation of lean body mass and physical function in old age, but evidence from randomised controlled trials is inconclusive. Methods and analysis The PRevention Of Malnutrition In Senior Subjects in the EU (PROMISS) trial examines the effect of personalised dietary advice aiming at increasing protein intake with or without advice regarding timing of protein intake to close proximity of usual physical activity, on change in physical functioning after 6 months among community-dwelling older adults (>= 65 years) with a habitual protein intake of <1.0 g/kg adjusted (a)BW/day. Participants (n=264) will be recruited in Finland and the Netherlands, and will be randomised into three groups; two intervention groups and one control group. Intervention group 1 (n=88) receives personalised dietary advice and protein-enriched food products in order to increase their protein intake to at least 1.2 g/kg aBW/day. Intervention group 2 (n=88) receives the same advice as described for intervention group 1, and in addition advice to consume 7.5-10 g protein through protein-(en)rich(ed) foods within half an hour after performing usual physical activity. The control group (n=88) receives no intervention. All participants will be invited to attend lectures not related to health. The primary outcome is a 6-month change in physical functioning measured by change in walk time using a 400 m walk test. Secondary outcomes are: 6-month change in the Short Physical Performance Battery score, muscle strength, body composition, self-reported mobility limitations, quality of life, incidence of frailty, incidence of sarcopenia risk and incidence of malnutrition. We also investigate cost-effectiveness by change in healthcare costs. Discussion The PROMISS trial will provide evidence whether increasing protein intake, and additionally optimising the timing of protein intake, has a positive effect on the course of physical functioning after 6 months among community-dwelling older adults with a habitual protein intake of Ethics and dissemination The study has been approved by the Ethics Committee of the Helsinki University Central Hospital, Finland (ID of the approval: HUS/1530/2018) and The Medical Ethical Committee of the Amsterdam UMC, location VUmc, Amsterdam, the Netherlands (ID of the approval: 2018.399). All participants provided written informed consent prior to being enrolled onto the study. Results will be submitted for publication in peer-reviewed journals and will be made available to stakeholders (ie, older adults, healthcare professionals and industry).
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- Dunlop, Malcolm G, et al.
(författare)
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Cumulative impact of 10 common genetic variants on colorectal cancer risk in 42,333 individuals from eight populations
- 2012
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Ingår i: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1468-3288 .- 0017-5749.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. DESIGN: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. RESULTS: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10(-16)), confirmed in external validation sets (Sweden p=1.2×10(-6), Finland p=2×10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. CONCLUSION: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.
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- Melis, Diana R., et al.
(författare)
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Quinoline-triazole half-sandwich iridium(iii) complexes : Synthesis, antiplasmodial activity and preliminary transfer hydrogenation studies
- 2020
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 49:33, s. 11543-11555
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Tidskriftsartikel (refereegranskat)abstract
- Iridium(iii) half-sandwich complexes containing 7-chloroquinoline-1,2,3-triazole hybrid ligands were synthesised and their inhibitory activities evaluated against the Plasmodium falciparum malaria parasite. Supporting computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming a kinetic product that, upon heating over time, forms a more stable cyclometallated thermodynamic product. Single crystal X-ray diffraction confirmed the proposed molecular structures of both isolated kinetic and thermodynamic products. Complexation with iridium significantly enhances the in vitro activity of selected ligands against the chloroquine-sensitive (NF54) Plasmodium falciparum strain, with selected complexes being over one hundred times more active than their respective ligands. No cross-resistance was observed in the chloroquine-resistant (K1) strain. No cytotoxicity was observed for selected complexes tested against the mammalian Chinese Hamster Ovarian (CHO) cell line. In addition, speed-of-action assays and β-haematin inhibition studies were performed. Through preliminary qualitative and quantitative cell-free experiments, it was found that the two most active neutral, cyclometallated complexes can act as transfer hydrogenation catalysts, by reducing β-nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of a hydrogen source, sodium formate.
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