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- Grubelnik, V, et al.
(author)
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Modelling of dysregulated glucagon secretion in type 2 diabetes by considering mitochondrial alterations in pancreatic α-cells
- 2020
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In: Royal Society open science. - : The Royal Society. - 2054-5703. ; 7:1, s. 191171-
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Journal article (peer-reviewed)abstract
- Type 2 diabetes mellitus (T2DM) has been associated with insulin resistance and the failure of β-cells to produce and secrete enough insulin as the disease progresses. However, clinical treatments based solely on insulin secretion and action have had limited success. The focus is therefore shifting towards α-cells, in particular to the dysregulated secretion of glucagon. Our qualitative electron-microscopy-based observations gave an indication that mitochondria in α-cells are altered in Western-diet-induced T2DM. In particular, α-cells extracted from mouse pancreatic tissue showed a lower density of mitochondria, a less expressed matrix and a lower number of cristae. These deformities in mitochondrial ultrastructure imply a decreased efficiency in mitochondrial ATP production, which prompted us to theoretically explore and clarify one of the most challenging problems associated with T2DM, namely the lack of glucagon secretion in hypoglycaemia and its oversecretion at high blood glucose concentrations. To this purpose, we constructed a novel computational model that links α-cell metabolism with their electrical activity and glucagon secretion. Our results show that defective mitochondrial metabolism in α-cells can account for dysregulated glucagon secretion in T2DM, thus improving our understanding of T2DM pathophysiology and indicating possibilities for new clinical treatments.
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- Munch, Marie W., et al.
(author)
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Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
- 2021
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In: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
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Journal article (peer-reviewed)abstract
- Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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- Riggi, Laura, et al.
(author)
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Early-season mass-flowering crop cover dilutes wild bee abundance and species richness in temperate regions : A quantitative synthesis
- 2024
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In: Journal of Applied Ecology. - 0021-8901 .- 1365-2664.
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Journal article (peer-reviewed)abstract
- Pollinators benefit from increasing floral resources in agricultural landscapes, which could be an underexplored co-benefit of mass-flowering crop cultivation. However, the impacts of mass-flowering crops on pollinator communities are complex and appear to be context-dependent, mediated by factors such as crop flowering time and the availability of other flower resources in the landscape. A synthesis of research is needed to develop management recommendations for effective pollinator conservation in agroecosystems. By combining 22 datasets from 13 publications conducted in nine temperate countries (20 European, 2 North American), we investigated if mass-flowering crop flowering time (early or late season), bloom state (during or after crop flowering) and extent of non-crop habitat cover in the landscape moderated the effect of mass-flowering crop cover on wild pollinator abundance and species richness in mass-flowering crop and non-crop habitats. During bloom, wild bee abundance and richness are negatively related to mass-flowering crop cover. Dilution effects were predominant in crop habitats and early in the season, except for bumblebees, which declined with mass-flowering crop cover irrespective of habitat or season. Late in the season and in non-crop habitats, several of these negative relationships were either absent or reversed. Late-season mass-flowering crop cover is positively related to honeybee abundance in crop habitats and to other bee abundance in non-crop habitats. These results indicate that crop-adapted species, like honeybees, move to forage and concentrate on late-season mass-flowering crops at a time when flower availability in the landscape is limited, potentially alleviating competition for flower resources in non-crop habitats. We found no evidence of pollinators moving from mass-flowering crop to non-crop habitats after crop bloom. Synthesis and applications: Our results confirm that increasing early-season mass-flowering crop cover dilutes wild pollinators in crop habitats during bloom. We find that dilution effects were absent late in the season. While mass-flowering crop cultivation alone is unlikely to be sufficient for maintaining pollinators, as part of carefully designed diverse crop rotations or mixtures combined with the preservation of permanent non-crop habitats, it might provide valuable supplementary food resources for pollinators in temperate agroecosystems, particularly later in the season when alternative flower resources are scarce.
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- Rodriguez, A, et al.
(author)
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Fitness, Food, and Biomarkers: Characterizing Body Composition in 19,634 Early Adolescents
- 2022
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 14:7
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Journal article (peer-reviewed)abstract
- Adolescent obesity persists as a major concern, especially in Central and Eastern Europe, yet evidence gaps exist regarding the pivotal early adolescent years. Our objective was to provide a comprehensive picture using a holistic approach of measured anthropometry in early adolescence, including body composition, cardiorespiratory fitness (CRF), and reported lifestyle characteristics. We aimed to elucidate potential sex/gender differences throughout and associations to biomarkers of disease risk for obese adolescents. Methods: Trained nurses measured 19,634 early adolescents (12–14-year-olds), we collected parental reports, and, for obese adolescents, fasting blood samples in four major Polish cities using a cross-sectional developmental design. Results: 24.7% boys and 18.6% girls were overweight/obese, and 2886 had BMI ≥ 90th percentile. With increasing age, there was greater risk of obesity among boys (p for trend = 0.001) and a decreasing risk of thinness for girls (p for trend = 0.01). Contrary to debate, we found BMI (continuous) was a useful indicator of measured fat mass (FM). There were 38.6% with CRF in the range of poor/very poor and was accounted for primarily by FM in boys, rather than BMI, and systolic blood pressure in girls. Boys, in comparison to girls, engaged more in sports (t = 127.26, p < 0.0001) and consumed more fast food (t = 188.57, p < 0.0001) and sugar-sweetened beverages (167.46, p < 0.0001). Uric acid, a potential marker for prediabetes, was strongly related to BMI in the obese subsample for both boys and girls. Obese girls showed signs of undernutrition. Conclusion: these findings show that overweight/obesity is by far a larger public health problem than thinness in early adolescence and is characterized differentially by sex/gender. Moreover, poor CRF in this age, which may contribute to life course obesity and disease, highlights the need for integrated and personalized intervention strategies taking sex/gender into account.
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