| 1. |
- Klonoff, D. C., et al.
(författare)
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A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings
- 2022
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Ingår i: Journal of Diabetes Science and Technology. - : SAGE Publications. - 1932-2968.
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Tidskriftsartikel (refereegranskat)abstract
- Background: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. Methods: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low–glucose and low-glucose hypoglycemia; very high–glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. Results: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. Conclusion: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.
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| 2. |
- Moser, O., et al.
(författare)
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Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA)
- 2020
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63, s. 2501-2520
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (i.e. before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.
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| 3. |
- Baumgart, Mona, et al.
(författare)
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Design of buried charged networks in artificial proteins
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Soluble proteins are universally packed with a hydrophobic core and a polar surface that drive the protein folding process. Yet charged networks within the central protein core are often indispensable for the biological function. Here, we show that natural buried ion-pairs are stabilised by amphiphilic residues that electrostatically shield the charged motif from its surroundings to gain structural stability. To explore this effect, we build artificial proteins with buried ion-pairs by combining directed computational design and biophysical experiments. Our findings illustrate how perturbation in charged networks can introduce structural rearrangements to compensate for desolvation effects. We validate the physical principles by resolving high-resolution atomic structures of the artificial proteins that are resistant towards unfolding at extreme temperatures and harsh chemical conditions. Our findings provide a molecular understanding of functional charged networks and how point mutations may alter the protein's conformational landscape.
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| 4. |
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| 5. |
- Mader, Sophie L., et al.
(författare)
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Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The heat shock protein 90 (Hsp90) is a molecular chaperone that employs the free energy of ATP hydrolysis to control the folding and activation of several client proteins in the eukaryotic cell. To elucidate how the local ATPase reaction in the active site couples to the global conformational dynamics of Hsp90, we integrate here large-scale molecular simulations with biophysical experiments. We show that the conformational switching of conserved ion pairs between the N-terminal domain, harbouring the active site, and the middle domain strongly modulates the catalytic barrier of the ATP-hydrolysis reaction by electrostatic forces. Our combined findings provide a mechanistic model for the coupling between catalysis and protein dynamics in Hsp90, and show how long-range coupling effects can modulate enzymatic activity.
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| 6. |
- Moser, Othmar, et al.
(författare)
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Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scannedCGM(isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed byJDRFand supported by the American Diabetes Association (ADA)
- 2020
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Ingår i: PEDIATRIC DIABETES. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 21:8, s. 1375-1393
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Tidskriftsartikel (refereegranskat)abstract
- Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.
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| 7. |
- Müller, Niels A., et al.
(författare)
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A single gene underlies the dynamic evolution of poplar sex determination.
- 2020
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Ingår i: Nature Plants. - : Springer Nature. - 2055-0278 .- 2055-026X. ; 6:6, s. 630-637
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Tidskriftsartikel (refereegranskat)abstract
- Although hundreds of plant lineages have independently evolved dioecy (that is, separation of the sexes), the underlying genetic basis remains largely elusive. Here we show that diverse poplar species carry partial duplicates of the ARABIDOPSIS RESPONSE REGULATOR 17 (ARR17) orthologue in the male-specific region of the Y chromosome. These duplicates give rise to small RNAs apparently causing male-specific DNA methylation and silencing of the ARR17 gene. CRISPR–Cas9-induced mutations demonstrate that ARR17 functions as a sex switch, triggering female development when on and male development when off. Despite repeated turnover events, including a transition from the XY system to a ZW system, the sex-specific regulation of ARR17 is conserved across the poplar genus and probably beyond. Our data reveal how a single-gene-based mechanism of dioecy can enable highly dynamic sex-linked regions and contribute to maintaining recombination and integrity of sex chromosomes.
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| 8. |
- Riepl, Daniel, 1994-, et al.
(författare)
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Long-range charge transfer mechanism of the III2IV2 mycobacterial supercomplex
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Aerobic life is powered by membrane-bound redox enzymes that shuttle electrons to oxygen and transfer protons across a biological membrane. Structural studies suggest that these energy-transducing enzymes operate as higher-order supercomplexes, but their functional role remains poorly understood and highly debated. Here we resolve the functional dynamics of the 0.7 MDa III2IV2 obligate supercomplex from Mycobacterium smegmatis, a close relative of M. tuberculosis, the causative agent of tuberculosis. By combining computational, biochemical, and high-resolution (2.3 Å) cryo-electron microscopy experiments, we show how the mycobacterial supercomplex catalyses long-range charge transport from its menaquinol oxidation site to the binuclear active site for oxygen reduction. Our data reveal proton and electron pathways responsible for the charge transfer reactions, mechanistic principles of the quinone catalysis, and how unique molecular adaptations, water molecules, and lipid interactions enable the proton-coupled electron transfer (PCET) reactions. Our combined findings provide a mechanistic blueprint of mycobacterial supercomplexes and a basis for developing drugs against pathogenic bacteria.
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| 9. |
- van den Akker, Chris H. P., et al.
(författare)
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Reevaluating the FDA's warning against the use of probiotics in preterm neonates : a societal statement by ESPGHAN and EFCNI
- 2024
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : John Wiley & Sons. - 0277-2116 .- 1536-4801. ; 78:6, s. 1403-1408
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Tidskriftsartikel (refereegranskat)abstract
- The recent advisory issued by the United States Food and Drug Administration, cautioning against the routine administration of probiotics in preterm neonates, has sparked a lively debate within the scientific community. This commentary presents a perspective from members of the Special Interest Group on Gut Microbiota and Modifications within the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and other authors who contributed to the ESPGHAN position paper on probiotics for preterm infants, as well as representatives from the European Foundation for the Care of Newborn Infants. We advocate for a more nuanced and supportive approach to the use of certain probiotics in this vulnerable population, balancing the demonstrated benefits and risks.
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| 10. |
- van Kalsbeek, Rebecca J., et al.
(författare)
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The PanCareFollowUp Care Intervention : A European harmonised approach to person-centred guideline-based survivorship care after childhood, adolescent and young adult cancer
- 2022
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 162, s. 34-44
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Tidskriftsartikel (refereegranskat)abstract
- Background: Long-term follow-up (LTFU) care, although endorsed, is not available for the majority of adult survivors of childhood, adolescence and young adult (CAYA) cancer. Barriers to implementation include lack of time, knowledge, personnel and funding. Sustainable solutions are urgently needed to address the needs of CAYA cancer survivors to improve the quality of life and reduce the burden of late effects on survivors, health care systems and society. The European Union–funded PanCareFollowUp project, initiated by the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer, was established to facilitate the implementation of person-centred survivorship care across Europe. Patients and methods: The PanCareFollowUp Care Intervention was co-developed with survivors as part of the PanCareFollowUp project. It is a person-centred approach to survivorship care, supported by guidelines and with flexibility to adapt to local health care settings. The Care Intervention consists of three steps: (1) previsit completion of a Survivor Questionnaire (by the survivor) and Treatment Summary (by the health care provider [HCP]), (2) a clinic visit including shared decision-making, and (3) a follow-up call to finalise the individualised Survivorship Care Plan. Results: We developed the key components of the PanCareFollowUp Care Intervention: a PanCareFollowUp Survivor Questionnaire, Treatment Summary template, Survivorship Care Plan template, and educational materials for HCPs and survivors. Wide implementation of the PanCareFollowUp Care Intervention will be supported with a freely distributed Replication Manual on completion of the PanCareFollowUp project. Conclusions: The PanCareFollowUp Care Intervention will support the implementation of person-centred, guideline-based LTFU care in different health care settings across Europe to improve survivors’ health and well-being.
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