Pregnancy has been identified as a contributor to obesity. We have shown that a diet intervention postpartum produced a 2-y weight loss of 8%. Here, we present the impact of the diet intervention on ...cost-effectiveness and explore changes in quality of life (QOL).
A total of 110 postpartum women with overweight/obesity were randomly assigned to diet (D-group) or control (C-group). D-group received a 12-wk diet intervention within primary health care followed by monthly emails up to the 1-y follow-up. C-group received a brochure. Changes in QOL were measured using the 36-item Short Form Health Survey and EQ-5D. The analysis of cost-effectiveness was a cost-utility analysis with a health care perspective and included costs of intervention for stakeholder, quality-adjusted life-years (QALYs) gained and savings in health care. The likelihood of cost-effectiveness was examined using the net monetary benefit method.
The D-group increased their QOL more than the C-group at 12 wk. and 1 y, with pronounced differences for the dimensions general health and mental health, and the mental component summary score (all p < 0.05). Cost per gained QALY was 1704-7889 USD. The likelihood for cost-effectiveness, based on a willingness to pay 50,000 USD per QALY, was 0.77-1.00.
A diet intervention that produced clinically relevant postpartum weight loss also resulted in increased QOL and was cost-effective.
Clinical trials, NCT01949558 , 2013-09-24.
The objective of this study was to examine climate impact from diet across background and sociodemographic characteristics in a population-based cohort in northern Sweden.
A cross-sectional study ...within the Västerbotten Intervention Programme. Dietary data from a 64-item food frequency questionnaire collected during 1996-2016 were used. Energy-adjusted greenhouse gas emissions (GHGE) for all participants, expressed as kg carbon dioxide equivalents/day and 4184 kJ (1000 kcal), were estimated using data from life cycle analyses. Differences in background and sociodemographic characteristics were examined between participants with low and high GHGE from diet, respectively. The variables evaluated were age, BMI, physical activity, marital status, level of education, smoking, and residence.
Västerbotten county in northern Sweden.
In total, 46 893 women and 45 766 men aged 29-65 years.
Differences in GHGE from diet were found across the majority of examined variables. The strongest associations were found between GHGE from diet and age, BMI, education, and residence (all P < 0·001), with the highest GHGE from diet found among women and men who were younger, had a higher BMI, higher educational level, and lived in urban areas.
This study is one of the first to examine climate impact from diet across background and sociodemographic characteristics. The results show that climate impact from diet is associated with age, BMI, residence and educational level amongst men and women in Västerbotten, Sweden. These results define potential target populations where public health interventions addressing a move towards more climate-friendly food choices and reduced climate impact from diet could be most effective.
In yeast, toxicity of acetaminophen (APAP), a frequently used analgesic and antipyretic drug, depends on ubiquitin-controlled processes. Previously, we showed a remarkable overlap in toxicity ...profiles between APAP and tyrosine, and a similarity with drugs like rapamycin and quinine, which induce degradation of the amino acid permease Tat2. Therefore, we investigated in yeast whether APAP reduced the expression levels of amino acid permeases. The protein levels of Tat2, Tat1, Mup1 and Hip1 were reduced, while the expression of the general permease Gap1 was increased, consistent with a nutrient starvation response. Overexpression of Tat1 and Tat2, but not Mup1, Hip1 and Gap1 conferred resistance to APAP. A tryptophan auxotrophic strain
trp1Δ
was more sensitive to APAP than wild-type and addition of tryptophan completely restored the growth restriction of
trp1∆
upon APAP exposure, while tyrosine had an additive effect on APAP toxicity. Furthermore, intracellular aromatic amino acid concentrations were reduced upon APAP exposure. This effect was less prominent in ubiquitin-deficient yeast strains that were APAP resistant and showed a reduced degradation of high affinity amino acid permeases. APAP-induced changes in intracellular amino acid concentrations were also detected in hepatoma HepG2 cells indicating significance for humans.
Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a ...simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations.
This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out.
In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
Post-translational protein modification by addition or removal of the small polypeptide ubiquitin is involved in a range of critical cellular processes, like proteasomal protein degradation, DNA ...repair, gene expression, internalization of membrane proteins, and drug sensitivity. We recently identified genes important for acetaminophen (APAP) toxicity in a comprehensive screen and our findings suggested that a small set of yeast strains carrying deletions of ubiquitin-related genes can be informative for drug toxicity profiling. In yeast, approximately 20 different deubiquitinating enzymes (DUBs) have been identified, of which only one is essential for viability. We investigated whether the toxicity profile of DUB deletion yeast strains would be informative about the toxicological mode of action of APAP. A set of DUB deletion strains was tested for sensitivity and resistance to a diverse series of compounds, including APAP, quinine, ibuprofen, rapamycin, cycloheximide, cadmium, peroxide and amino acids and a cluster analysis was performed. Most DUB deletion strains showed an altered growth pattern when exposed to these compounds by being either more sensitive or more resistant than WT. Toxicity profiling of the DUB strains revealed a remarkable overlap between the amino acid tyrosine and acetaminophen (APAP), but not its stereoisomer AMAP. Furthermore, co-exposure of cells to both APAP and tyrosine showed an enhancement of the cellular growth inhibition, suggesting that APAP and tyrosine have a similar mode of action.
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•First use of yeast DUB gene deletion strains for toxicity profiling•Distinct toxicity profiles for APAP, AMAP and phenacetin•Strong overlap between APAP and tyrosine in toxicity profile•Tyrosine enhances toxicity of APAP.
Coffee and tea are among the most commonly consumed nonalcoholic beverages worldwide, but methodological differences in assessing intake often hamper comparisons across populations. We aimed to (i) ...describe coffee and tea intakes and (ii) assess their contribution to intakes of selected nutrients in adults across 10 European countries.
Between 1995 and 2000, a standardized 24-h dietary recall was conducted among 36,018 men and women from 27 European Prospective Investigation into Cancer and Nutrition (EPIC) study centres. Adjusted arithmetic means of intakes were estimated in grams (=volume) per day by sex and centre. Means of intake across centres were compared by sociodemographic characteristics and lifestyle factors.
In women, the mean daily intake of coffee ranged from 94 g/day (~0.6 cups) in Greece to 781 g/day (~4.4 cups) in Aarhus (Denmark), and tea from 14 g/day (~0.1 cups) in Navarra (Spain) to 788 g/day (~4.3 cups) in the UK general population. Similar geographical patterns for mean daily intakes of both coffee and tea were observed in men. Current smokers as compared with those who reported never smoking tended to drink on average up to 500 g/day more coffee and tea combined, but with substantial variation across centres. Other individuals' characteristics such as educational attainment or age were less predictive. In all centres, coffee and tea contributed to less than 10% of the energy intake. The greatest contribution to total sugar intakes was observed in Southern European centres (up to ~20%).
Coffee and tea intake and their contribution to energy and sugar intake differed greatly among European adults. Variation in consumption was mostly driven by geographical region.
Acetaminophen (APAP), although considered a safe drug, is one of the major causes of acute liver failure by overdose, and therapeutic chronic use can cause serious health problems. Although the ...reactive APAP metabolite N-acetyl-p-benzoquinoneimine (NAPQI) is clearly linked to liver toxicity, toxicity of APAP is also found without drug metabolism of APAP to NAPQI. To get more insight into mechanisms of APAP toxicity, a genome-wide screen in Saccharomyces cerevisiae for APAP-resistant deletion strains was performed. In this screen we identified genes related to the DNA damage response. Next, we investigated the link between genotype and APAP-induced toxicity or resistance by performing a more detailed screen with a library containing mutants of 1522 genes related to nuclear processes, like DNA repair and chromatin remodelling. We identified 233 strains that had an altered growth rate relative to wild type, of which 107 showed increased resistance to APAP and 126 showed increased sensitivity. Gene Ontology analysis identified ubiquitin homeostasis, regulation of transcription of RNA polymerase II genes, and the mitochondria-to-nucleus signalling pathway to be associated with APAP resistance, while histone exchange and modification, and vesicular transport were connected to APAP sensitivity. Indeed, we observed a link between ubiquitin levels and APAP resistance, whereby ubiquitin deficiency conferred resistance to APAP toxicity while ubiquitin overexpression resulted in sensitivity. The toxicity profile of various chemicals, APAP, and its positional isomer AMAP on a series of deletion strains with ubiquitin deficiency showed a unique resistance pattern for APAP. Furthermore, exposure to APAP increased the level of free ubiquitin and influenced the ubiquitination of proteins. Together, these results uncover a role for ubiquitin homeostasis in APAP-induced toxicity.
To examine timing of eating across ten European countries.
Cross-sectional analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study using standardized 24 ...h diet recalls collected during 1995-2000. Eleven predefined food consumption occasions were assessed during the recall interview. We present time of consumption of meals and snacks as well as the later:earlier energy intake ratio, with earlier and later intakes defined as 06.00-14.00 and 15.00-24.00 hours, respectively. Type III tests were used to examine associations of sociodemographic, lifestyle and health variables with timing of energy intake.
Ten Western European countries.
In total, 22 985 women and 13 035 men aged 35-74 years (n 36 020).
A south-north gradient was observed for timing of eating, with later consumption of meals and snacks in Mediterranean countries compared with Central and Northern European countries. However, the energy load was reversed, with the later:earlier energy intake ratio ranging from 0·68 (France) to 1·39 (Norway) among women, and from 0·71 (Greece) to 1·35 (the Netherlands) among men. Among women, country, age, education, marital status, smoking, day of recall and season were all independently associated with timing of energy intake (all P<0·05). Among men, the corresponding variables were country, age, education, smoking, physical activity, BMI and day of recall (all P<0·05).
We found pronounced differences in timing of eating across Europe, with later meal timetables but greater energy load earlier during the day in Mediterranean countries compared with Central and Northern European countries.
Inhibitor of apoptosis proteins (IAPs) act as endogenous inhibitors of active caspases. Drosophila IAP1 (DIAP1) activity is required to keep cells from undergoing apoptosis. The central cell death ...regulators Reaper and Hid
induce apoptosis very rapidly by inhibiting DIAP1 function. We have developed a system for replacing endogenous DIAP1 with
mutant forms of the protein, allowing us to examine the roles of various domains of the protein in living and dying cells.
We found that DIAP1 is cleaved by a caspase early after the initiation of apoptosis. This cleavage is required for DIAP1 degradation,
but Rpr and Hid can still initiate apoptosis in the absence of cleavage. The cleavage of DIAP1 promotes DIAP1 degradation
in a manner dependent on the function of the ubiquitin ligase function of the DIAP1 ring domain. This ring domain function
is required for Hid-induced apoptosis. We propose a model that synthesizes our data with those of other laboratories and provide
a consistent model for DIAP1 function in living and dying cells.
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