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  • 2013-2022
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  • Open Access English
    Authors: 
    Johan S. Bundgaard; Kasper Iversen; Henning Bundgaard;
    Country: Denmark
  • Open Access
    Authors: 
    Anne Toftgaard Pedersen; Jesper Kjaergaard; Christian Hassager; Martin Frydland; Jakob Hartvig Thomsen; Anika Klein; Henrik Schmidt; Jacob Eifer Møller; Sebastian Wiberg;
    Publisher: Informa UK Limited
    Country: Denmark

    Objectives: Prognostication after out-of-hospital cardiac arrest (OHCA) remains challenging. The inflammatory response after OHCA has been associated with increased mortality. This study investigates the associations and predictive value between inflammatory markers and outcome in resuscitated OHCA patients.Design: The study is based on post hoc analyses of a double-blind controlled trial, where resuscitated OHCA patients were randomized to receive either exenatide or placebo. Blood was analyzed for levels of inflammatory markers the day following admission. Primary endpoint was time to death for up to 180-days. Secondary endpoints included 180-day mortality and poor neurological outcome after 180-days, defined as a cerebral performance category (CPC) of 3 to 5.Results: Among 110 included patients we found significant associations between higher leucocyte quartile and increasing mortality in univariable analysis (OR 2.6 (95%CI 1.6-4.2), pConclusions: Total leucocyte count and neutrophil levels measured the first day following OHCA were significantly associated with 180-day all-cause mortality and may potentially act as early predictors of outcome.

  • Open Access English
    Authors: 
    Laura N.H. Verbrugge; Gunnar Bjarnason; Nora Fagerholm; Eyðfinn Magnussen; Lis Mortensen; Erla Olsen; Tobias Plieninger; Christopher M. Raymond; Anton Stahl Olafsson;
    Countries: Denmark, Finland

    Long-term livestock grazing has shaped landscapes, biodiversity, societies, cultures, and economies in the North Atlantic over time. However, overgrazing has become a major environmental sustainability challenge for this region, covering the Faroe Islands, Greenland, Iceland, Norway, and Scotland. The objective of this study was to elicit narratives and spatial patterns of local people's management preferences for sheep grazing in the Faroe Islands through a socio-cultural lens. We collected data via a Public Participation Geographic Information Systems (PPGIS) survey with an open question about hopes and concerns for sheep management in the Faroe Islands and a mapping exercise for expressing spatial preferences for sheep management. Four distinct narratives emerged from a qualitative analysis of responses to the open question (n = 184): (1) Sustainable sheep management, (2) Nature without sheep, (3) Sheep as part of Faroese culture, and (4) Sheep as nuisance. Visual inspection of narrative-specific maps with locations where either no or fewer sheep were preferred indicated that sheep management is not simply a 'sheep vs. no sheep' issue but embedded in a more nuanced consideration of the place of sheep in the landscape and society. For example, for some residents sheep-farming is not a commercial enterprise but a social activity and local source of food. Our combined methodological approach using qualitative and spatial data can help researchers in other fields identify the interplay between place-specific areas of grazing management concern and socio-cultural values, enabling more targeted land-use management policies or plans. Peer reviewed

  • Open Access
    Authors: 
    Faranak Tootoonchi; Jan O. Haerter; Andrijana Todorović; Olle Räty; Thomas Grabs; Claudia Teutschbein;
    Publisher: Elsevier BV
    Countries: Sweden, Denmark

    For climate-change impact studies at the catchment scale, meteorological variables are typically extracted from ensem-ble simulations provided by global and regional climate models, which are then downscaled and bias-adjusted for eachstudy site. For bias adjustment, different statistical methods that re-scaleclimate model outputs have been suggested inthe scientific literature. They range from simple univariate methods that adjust each meteorological variable individ-ually, to more complex and more demanding multivariate methods that take existing relationships between meteoro-logical variables into consideration. Over the past decade, several attempts have been made to evaluate such methodsin various regions. There is, however, still no guidance for choosing appropriate bias adjustment methods for a study athand. In particular, the question whether the benefits of potentially improved adjustments outweigh the cost of in-creased complexity, remains unanswered.This paper presents a comprehensive evaluation of the performance of two commonly used univariate and two multi-variate bias adjustment methods in reproducing numerous univariate, multivariate and temporal features of precipita-tion and temperature series in different catchments in Sweden. The paper culminates in a discussion on trade-offs between the potential benefits (i.e., skills and added value) and disadvantages (complexity and computational de-mand) of each method to offer plausible, defensible and actionable insights from the standpoint of climate-change im-pact studies in high latitudes.We concluded that all selected bias adjustment methods generally improved the raw climate model simulations, but that not a single method consistently outperformed the other methods. There were, however, differences in the methods' performance for particular statistical features, indicating that other practical aspects such as computationaltime and heavy theoretical requirements should also be taken into consideration when choosing an appropriate biasadjustment method

  • Open Access English
    Authors: 
    Fredriksson, Maria; Rüggeberg, Markus; Nord-Larsen, Thomas; Beck, Greeley; Thybring, Emil Engelund;
    Country: Denmark

    The material properties of wood are intimately tied to the amount of moisture contained in the wood cell walls. The moisture content depends on the environmental conditions, i.e. temperature and relative humidity, but also on material characteristics of the wood itself. The exact mechanisms governing moisture equilibrium between wood cell walls and environmental conditions remain obscure, likely because multiple material characteristics have been proposed to be involved. In this study, we used a data exploration approach to illuminate the important wood characteristics determining the cell wall moisture content in the full moisture range. Specimens of nine different wood species (two softwoods and seven hardwoods) were examined in terms of their material characteristics at multiple scales and their cell wall moisture content was measured in equilibrium with both hygroscopic conditions and at water-saturation. By statistical analysis, the chemical composition was found to be the most important predictor of the cell wall moisture content in the full moisture range. For the other wood characteristics the importance differed between the low moisture range and the humid and saturated conditions. In the low moisture range, the cellulose crystallinity and hydroxyl accessibility were found to be important predictors, while at high moisture contents the microfibril orientation in the S1 and S3 layers of the cell walls was important. Overall, the results highlighted that no single wood characteristic were decisive for the cell wall moisture content, and each of the predictors identified by the analysis had only a small effect in themselves on the cell wall moisture content. Wood characteristics with a major effect on the cell wall moisture content were, therefore, not identified. The material properties of wood are intimately tied to the amount of moisture contained in the wood cell walls. The moisture content depends on the environmental conditions, i.e. temperature and relative humidity, but also on material characteristics of the wood itself. The exact mechanisms governing moisture equilibrium between wood cell walls and environmental conditions remain obscure, likely because multiple material characteristics have been proposed to be involved. In this study, we used a data exploration approach to illuminate the important wood characteristics determining the cell wall moisture content in the full moisture range. Specimens of nine different wood species (two softwoods and seven hardwoods) were examined in terms of their material characteristics at multiple scales and their cell wall moisture content was measured in equilibrium with both hygroscopic conditions and at water-saturation. By statistical analysis, the chemical composition was found to be the most important predictor of the cell wall moisture content in the full moisture range. For the other wood characteristics the importance differed between the low moisture range and the humid and saturated conditions. In the low moisture range, the cellulose crystallinity and hydroxyl accessibility were found to be important predictors, while at high moisture contents the microfibril orientation in the S1 and S3 layers of the cell walls was important. Overall, the results highlighted that no single wood characteristic were decisive for the cell wall moisture content, and each of the predictors identified by the analysis had only a small effect in themselves on the cell wall moisture content. Wood characteristics with a major effect on the cell wall moisture content were, therefore, not identified.

  • Open Access
    Authors: 
    Katrine D. Galsgaard; Emilie Elmelund; Christian D. Johansen; Anna B. Bomholt; Hüsün S. Kizilkaya; Frederik Ceutz; Jenna E. Hunt; Hannelouise Kissow; Marie Winther-Sørensen; Charlotte M. Sørensen; +7 more
    Publisher: Elsevier BV
    Country: Denmark

    Objective: Treatment with glucagon receptor antagonists (GRAs) reduces blood glucose but causes dyslipidemia and accumulation of fat in the liver. We investigated the acute and chronic effects of glucagon on lipid metabolism in mice. Methods: Chronic effects of glucagon receptor signaling on lipid metabolism were studied using oral lipid tolerance tests (OLTTs) in overnight fasted glucagon receptor knockout (Gcgr−/−) mice, and in C57Bl/6JRj mice treated with a glucagon receptor antibody (GCGR Ab) or a long-acting glucagon analogue (GCGA) for eight weeks. Following treatment, liver tissue was harvested for RNA-sequencing and triglyceride measurements. Acute effects were studied in C57Bl/6JRj mice treated with a GRA or GCGA 1 h or immediately before OLTTs, respectively. Direct effects of glucagon on hepatic lipolysis were studied using isolated perfused mouse liver preparations. To investigate potential effects of GCGA and GRA on gastric emptying, paracetamol was, in separate experiments, administered immediately before OLTTs. Results: Plasma triglyceride concentrations increased 2-fold in Gcgr−/− mice compared to their wild-type littermates during the OLTT (P = 0.001). Chronic treatment with GCGR Ab increased, whereas GCGA treatment decreased, plasma triglyceride concentrations during OLTTs (P < 0.05). Genes involved in lipid metabolism were upregulated upon GCGR Ab treatment while GCGA treatment had opposite effects. Acute GRA and GCGA treatment, respectively, increased (P = 0.02) and decreased (P = 0.003) plasma triglyceride concentrations during OLTTs. Glucagon stimulated hepatic lipolysis, evident by an increase in free fatty acid concentrations in the effluent from perfused mouse livers. In line with this, GCGR Ab treatment increased, while GCGA treatment decreased, liver triglyceride concentrations. The effects of glucagon appeared independent of changes in gastric emptying of paracetamol. Conclusions: Glucagon receptor signaling regulates triglyceride metabolism, both chronically and acutely, in mice. These data expand glucagon´s biological role and implicate that intact glucagon signaling is important for lipid metabolism. Glucagon agonism may have beneficial effects on hepatic and peripheral triglyceride metabolism.

  • Publication . Book . Other literature type . 2022
    Open Access
    Authors: 
    Peter Sandøe; Mads Paludan Goddiksen; Helene Ane Jensen; Mikkel Willum Johansen; Søren Nielsen;
    Country: Denmark
  • Open Access English
    Authors: 
    van der Wel, Maaike; van der Smissen, Doris; Dierickx, Sigrid; Cohen, Joachim; Hudson, Peter; De Vleminck, Aline; Tutt, Lydia; Scott, David; Di Leo, Silvia; Arnfeldt, Caroline Moeller; +5 more
    Publisher: Springer Verlag
    Countries: Netherlands, Belgium, Belgium, Denmark, United Kingdom

    Abstract Purpose Having advanced cancer presents many challenges for patients and family caregivers. The FOCUS program is a psychoeducational nurse-led intervention, developed in the USA, to support dyads of patients with cancer and their family caregivers to live with the illness. The program includes a conversation manual and information resources for dyads. We aimed to develop a version of the program for dyads facing advanced cancer in six European countries. Method The Participatory and Iterative Process Framework for Language Adaptation (PIPFLA) was used to guide the translation of the program to the local contexts of Belgium, Denmark, Ireland, Italy, the Netherlands, and the UK. In several rounds, potential program users (e.g., nurses, clinicians, patients, family caregivers) and researchers from all six countries reviewed program materials and advised on adaptations. Results The PIPFLA process resulted in one European version of the program in different languages (FOCUS +). The FOCUS + conversation manual is uniform across all countries. The main adaptations included additional attention to both family caregiver and patient needs; more emphasis on self-management, advance care planning, and shared responsibilities; discussing the dyad’s outlook rather than optimism; addressing the role of nurses as educational rather than therapeutic; and more suggestions to refer dyads to health care professionals for specific care needs. The information resources for dyads were adapted to fit with local contexts. Conclusion The PIPFLA methodology is an efficient and effective framework to thoroughly translate and culturally adapt a complex USA-based program for use in six European countries in collaboration with end users.

  • Open Access English
    Authors: 
    Miguel Peña-Espinoza; Yeambell Romero-Uzqueda; Angela H. Valente; Matthew de Roode; Henrik T. Simonsen; Stig M. Thamsborg; Andrew R. Williams; Rodrigo López-Muñoz;
    Country: Denmark

    Chagas disease, caused by the protozoa Trypanosoma cruzi, is a potentially life-threatening parasitic zoonosis infecting 6-7 million people worldwide, mainly in Latin America. Due to the limited numbers of drugs available against this neglected disease and their frequent adverse effects, novel anti-chagasic agents are urgently needed. Cichorium intybus L. (chicory) is a bioactive plant with potent activity against parasitic nematodes, but its effects on protozoans are poorly known and no studies have explored its trypanocidal potential. Here, we investigated the activity of C. intybus against extracellular and intracellular stages of T. cruzi, including the prediction of trypanocidal compounds by metabolomic analyses and bioactivity-based molecular networking. Purified C. intybus extracts were prepared from leaves and roots of five C. intybus cultivars (cv. 'Benulite', 'Goldine', 'Larigot', 'Maestoso' and 'Spadona'). All C. intybus extracts induced concentration-dependent effects against T. cruzi trypomastigotes. C. intybus leaf extracts had higher trypanocidal selectivity and lower cytotoxicity on mammalian cells than root extracts. The leaf extract of C. intybus cv. Goldine also significantly reduced the number of mammalian cells infected with T. cruzi amastigotes. Metabolomic and bioactivity-based molecular networking analyses revealed 11 compounds in C. intybus leaves strongly linked with activity against trypomastigotes, including the sesquiterpene lactone lactucin, and flavonoid- and fatty acid-derivatives. Furthermore, seven distinct C. intybus molecules (including two sesquiterpene lactone-derivatives) were predicted to be involved in reducing the number of mammalian cells infected with amastigotes. This is the first report of the anti-protozoal activity of C. intybus against trypanosomatid parasites and expands our understanding of the anti-parasitic effects of this plant and its bioactive metabolites. Further studies to elucidate the anti-protozoal compound(s) in C. intybus and their mode(s) of action will improve our knowledge of using this bioactive plant as a promising source of novel broad-spectrum anti-parasitic compounds with associated health benefits and biomedical potential.

  • Open Access English
    Authors: 
    Mikael Thomsen; Anca Stoica; Kenneth Vielsted Christensen; Tue Fryland; Jens D. Mikkelsen; John Bondo Hansen;
    Country: Denmark

    Background: The gold standard for symptomatic relief of Parkinson's disease (PD) is L-DOPA. However, long-term treatment often leads to motor complications such as L-DOPA-induced dyskinesia (LID). While amantadine (GocovriTM) is the only approved therapy for dyskinesia in PD patients on the American market, it is associated with neurological side effects and limited efficacy. Thus, there remains a high unmet need for addressing LID in PD patients worldwide. Objective: The objective of this study was to evaluate the efficacy, safety and performance compared to approved treatments of the serotonin receptor 1A (5-HT1A) and 5-HT1B/D agonists buspirone and zolmitriptan in the 6-hydroxydopamine unilaterally lesioned rat model for PD. .Methods: The hemiparkinsonian 6-OHDA-lesioned rats underwent chronic treatment with L-DOPA to induce dyskinesia and were subsequently used for efficacy testing of buspirone, zolmitriptan and comparison with amantadine, measured as abnormal involuntary movement (AIM) scores after L-DOPA challenge. Safety testing was performed in model and naive animals using forelimb adjusting, rotarod and open field tests.Results: 5-HT1A and 5-HT1B/D agonism effectively reduced AIM scores in a synergistic manner. The drug combination of buspirone and zolmitriptan was safe and did not lead to tolerance development following sub -chronic administration. Head-to-head comparison with amantadine showed superior performance of buspirone and zolmitriptan in the model.Conclusions: The strong anti-dyskinetic effect found with combined 5-HT1A and 5-HT1B/D agonism renders buspirone and zolmitriptan together a meaningful treatment for LID in PD.

Advanced search in
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Include:
39,916 Research products, page 1 of 3,992
  • Open Access English
    Authors: 
    Johan S. Bundgaard; Kasper Iversen; Henning Bundgaard;
    Country: Denmark
  • Open Access
    Authors: 
    Anne Toftgaard Pedersen; Jesper Kjaergaard; Christian Hassager; Martin Frydland; Jakob Hartvig Thomsen; Anika Klein; Henrik Schmidt; Jacob Eifer Møller; Sebastian Wiberg;
    Publisher: Informa UK Limited
    Country: Denmark

    Objectives: Prognostication after out-of-hospital cardiac arrest (OHCA) remains challenging. The inflammatory response after OHCA has been associated with increased mortality. This study investigates the associations and predictive value between inflammatory markers and outcome in resuscitated OHCA patients.Design: The study is based on post hoc analyses of a double-blind controlled trial, where resuscitated OHCA patients were randomized to receive either exenatide or placebo. Blood was analyzed for levels of inflammatory markers the day following admission. Primary endpoint was time to death for up to 180-days. Secondary endpoints included 180-day mortality and poor neurological outcome after 180-days, defined as a cerebral performance category (CPC) of 3 to 5.Results: Among 110 included patients we found significant associations between higher leucocyte quartile and increasing mortality in univariable analysis (OR 2.6 (95%CI 1.6-4.2), pConclusions: Total leucocyte count and neutrophil levels measured the first day following OHCA were significantly associated with 180-day all-cause mortality and may potentially act as early predictors of outcome.

  • Open Access English
    Authors: 
    Laura N.H. Verbrugge; Gunnar Bjarnason; Nora Fagerholm; Eyðfinn Magnussen; Lis Mortensen; Erla Olsen; Tobias Plieninger; Christopher M. Raymond; Anton Stahl Olafsson;
    Countries: Denmark, Finland

    Long-term livestock grazing has shaped landscapes, biodiversity, societies, cultures, and economies in the North Atlantic over time. However, overgrazing has become a major environmental sustainability challenge for this region, covering the Faroe Islands, Greenland, Iceland, Norway, and Scotland. The objective of this study was to elicit narratives and spatial patterns of local people's management preferences for sheep grazing in the Faroe Islands through a socio-cultural lens. We collected data via a Public Participation Geographic Information Systems (PPGIS) survey with an open question about hopes and concerns for sheep management in the Faroe Islands and a mapping exercise for expressing spatial preferences for sheep management. Four distinct narratives emerged from a qualitative analysis of responses to the open question (n = 184): (1) Sustainable sheep management, (2) Nature without sheep, (3) Sheep as part of Faroese culture, and (4) Sheep as nuisance. Visual inspection of narrative-specific maps with locations where either no or fewer sheep were preferred indicated that sheep management is not simply a 'sheep vs. no sheep' issue but embedded in a more nuanced consideration of the place of sheep in the landscape and society. For example, for some residents sheep-farming is not a commercial enterprise but a social activity and local source of food. Our combined methodological approach using qualitative and spatial data can help researchers in other fields identify the interplay between place-specific areas of grazing management concern and socio-cultural values, enabling more targeted land-use management policies or plans. Peer reviewed

  • Open Access
    Authors: 
    Faranak Tootoonchi; Jan O. Haerter; Andrijana Todorović; Olle Räty; Thomas Grabs; Claudia Teutschbein;
    Publisher: Elsevier BV
    Countries: Sweden, Denmark

    For climate-change impact studies at the catchment scale, meteorological variables are typically extracted from ensem-ble simulations provided by global and regional climate models, which are then downscaled and bias-adjusted for eachstudy site. For bias adjustment, different statistical methods that re-scaleclimate model outputs have been suggested inthe scientific literature. They range from simple univariate methods that adjust each meteorological variable individ-ually, to more complex and more demanding multivariate methods that take existing relationships between meteoro-logical variables into consideration. Over the past decade, several attempts have been made to evaluate such methodsin various regions. There is, however, still no guidance for choosing appropriate bias adjustment methods for a study athand. In particular, the question whether the benefits of potentially improved adjustments outweigh the cost of in-creased complexity, remains unanswered.This paper presents a comprehensive evaluation of the performance of two commonly used univariate and two multi-variate bias adjustment methods in reproducing numerous univariate, multivariate and temporal features of precipita-tion and temperature series in different catchments in Sweden. The paper culminates in a discussion on trade-offs between the potential benefits (i.e., skills and added value) and disadvantages (complexity and computational de-mand) of each method to offer plausible, defensible and actionable insights from the standpoint of climate-change im-pact studies in high latitudes.We concluded that all selected bias adjustment methods generally improved the raw climate model simulations, but that not a single method consistently outperformed the other methods. There were, however, differences in the methods' performance for particular statistical features, indicating that other practical aspects such as computationaltime and heavy theoretical requirements should also be taken into consideration when choosing an appropriate biasadjustment method

  • Open Access English
    Authors: 
    Fredriksson, Maria; Rüggeberg, Markus; Nord-Larsen, Thomas; Beck, Greeley; Thybring, Emil Engelund;
    Country: Denmark

    The material properties of wood are intimately tied to the amount of moisture contained in the wood cell walls. The moisture content depends on the environmental conditions, i.e. temperature and relative humidity, but also on material characteristics of the wood itself. The exact mechanisms governing moisture equilibrium between wood cell walls and environmental conditions remain obscure, likely because multiple material characteristics have been proposed to be involved. In this study, we used a data exploration approach to illuminate the important wood characteristics determining the cell wall moisture content in the full moisture range. Specimens of nine different wood species (two softwoods and seven hardwoods) were examined in terms of their material characteristics at multiple scales and their cell wall moisture content was measured in equilibrium with both hygroscopic conditions and at water-saturation. By statistical analysis, the chemical composition was found to be the most important predictor of the cell wall moisture content in the full moisture range. For the other wood characteristics the importance differed between the low moisture range and the humid and saturated conditions. In the low moisture range, the cellulose crystallinity and hydroxyl accessibility were found to be important predictors, while at high moisture contents the microfibril orientation in the S1 and S3 layers of the cell walls was important. Overall, the results highlighted that no single wood characteristic were decisive for the cell wall moisture content, and each of the predictors identified by the analysis had only a small effect in themselves on the cell wall moisture content. Wood characteristics with a major effect on the cell wall moisture content were, therefore, not identified. The material properties of wood are intimately tied to the amount of moisture contained in the wood cell walls. The moisture content depends on the environmental conditions, i.e. temperature and relative humidity, but also on material characteristics of the wood itself. The exact mechanisms governing moisture equilibrium between wood cell walls and environmental conditions remain obscure, likely because multiple material characteristics have been proposed to be involved. In this study, we used a data exploration approach to illuminate the important wood characteristics determining the cell wall moisture content in the full moisture range. Specimens of nine different wood species (two softwoods and seven hardwoods) were examined in terms of their material characteristics at multiple scales and their cell wall moisture content was measured in equilibrium with both hygroscopic conditions and at water-saturation. By statistical analysis, the chemical composition was found to be the most important predictor of the cell wall moisture content in the full moisture range. For the other wood characteristics the importance differed between the low moisture range and the humid and saturated conditions. In the low moisture range, the cellulose crystallinity and hydroxyl accessibility were found to be important predictors, while at high moisture contents the microfibril orientation in the S1 and S3 layers of the cell walls was important. Overall, the results highlighted that no single wood characteristic were decisive for the cell wall moisture content, and each of the predictors identified by the analysis had only a small effect in themselves on the cell wall moisture content. Wood characteristics with a major effect on the cell wall moisture content were, therefore, not identified.

  • Open Access
    Authors: 
    Katrine D. Galsgaard; Emilie Elmelund; Christian D. Johansen; Anna B. Bomholt; Hüsün S. Kizilkaya; Frederik Ceutz; Jenna E. Hunt; Hannelouise Kissow; Marie Winther-Sørensen; Charlotte M. Sørensen; +7 more
    Publisher: Elsevier BV
    Country: Denmark

    Objective: Treatment with glucagon receptor antagonists (GRAs) reduces blood glucose but causes dyslipidemia and accumulation of fat in the liver. We investigated the acute and chronic effects of glucagon on lipid metabolism in mice. Methods: Chronic effects of glucagon receptor signaling on lipid metabolism were studied using oral lipid tolerance tests (OLTTs) in overnight fasted glucagon receptor knockout (Gcgr−/−) mice, and in C57Bl/6JRj mice treated with a glucagon receptor antibody (GCGR Ab) or a long-acting glucagon analogue (GCGA) for eight weeks. Following treatment, liver tissue was harvested for RNA-sequencing and triglyceride measurements. Acute effects were studied in C57Bl/6JRj mice treated with a GRA or GCGA 1 h or immediately before OLTTs, respectively. Direct effects of glucagon on hepatic lipolysis were studied using isolated perfused mouse liver preparations. To investigate potential effects of GCGA and GRA on gastric emptying, paracetamol was, in separate experiments, administered immediately before OLTTs. Results: Plasma triglyceride concentrations increased 2-fold in Gcgr−/− mice compared to their wild-type littermates during the OLTT (P = 0.001). Chronic treatment with GCGR Ab increased, whereas GCGA treatment decreased, plasma triglyceride concentrations during OLTTs (P < 0.05). Genes involved in lipid metabolism were upregulated upon GCGR Ab treatment while GCGA treatment had opposite effects. Acute GRA and GCGA treatment, respectively, increased (P = 0.02) and decreased (P = 0.003) plasma triglyceride concentrations during OLTTs. Glucagon stimulated hepatic lipolysis, evident by an increase in free fatty acid concentrations in the effluent from perfused mouse livers. In line with this, GCGR Ab treatment increased, while GCGA treatment decreased, liver triglyceride concentrations. The effects of glucagon appeared independent of changes in gastric emptying of paracetamol. Conclusions: Glucagon receptor signaling regulates triglyceride metabolism, both chronically and acutely, in mice. These data expand glucagon´s biological role and implicate that intact glucagon signaling is important for lipid metabolism. Glucagon agonism may have beneficial effects on hepatic and peripheral triglyceride metabolism.

  • Publication . Book . Other literature type . 2022
    Open Access
    Authors: 
    Peter Sandøe; Mads Paludan Goddiksen; Helene Ane Jensen; Mikkel Willum Johansen; Søren Nielsen;
    Country: Denmark
  • Open Access English
    Authors: 
    van der Wel, Maaike; van der Smissen, Doris; Dierickx, Sigrid; Cohen, Joachim; Hudson, Peter; De Vleminck, Aline; Tutt, Lydia; Scott, David; Di Leo, Silvia; Arnfeldt, Caroline Moeller; +5 more
    Publisher: Springer Verlag
    Countries: Netherlands, Belgium, Belgium, Denmark, United Kingdom

    Abstract Purpose Having advanced cancer presents many challenges for patients and family caregivers. The FOCUS program is a psychoeducational nurse-led intervention, developed in the USA, to support dyads of patients with cancer and their family caregivers to live with the illness. The program includes a conversation manual and information resources for dyads. We aimed to develop a version of the program for dyads facing advanced cancer in six European countries. Method The Participatory and Iterative Process Framework for Language Adaptation (PIPFLA) was used to guide the translation of the program to the local contexts of Belgium, Denmark, Ireland, Italy, the Netherlands, and the UK. In several rounds, potential program users (e.g., nurses, clinicians, patients, family caregivers) and researchers from all six countries reviewed program materials and advised on adaptations. Results The PIPFLA process resulted in one European version of the program in different languages (FOCUS +). The FOCUS + conversation manual is uniform across all countries. The main adaptations included additional attention to both family caregiver and patient needs; more emphasis on self-management, advance care planning, and shared responsibilities; discussing the dyad’s outlook rather than optimism; addressing the role of nurses as educational rather than therapeutic; and more suggestions to refer dyads to health care professionals for specific care needs. The information resources for dyads were adapted to fit with local contexts. Conclusion The PIPFLA methodology is an efficient and effective framework to thoroughly translate and culturally adapt a complex USA-based program for use in six European countries in collaboration with end users.

  • Open Access English
    Authors: 
    Miguel Peña-Espinoza; Yeambell Romero-Uzqueda; Angela H. Valente; Matthew de Roode; Henrik T. Simonsen; Stig M. Thamsborg; Andrew R. Williams; Rodrigo López-Muñoz;
    Country: Denmark

    Chagas disease, caused by the protozoa Trypanosoma cruzi, is a potentially life-threatening parasitic zoonosis infecting 6-7 million people worldwide, mainly in Latin America. Due to the limited numbers of drugs available against this neglected disease and their frequent adverse effects, novel anti-chagasic agents are urgently needed. Cichorium intybus L. (chicory) is a bioactive plant with potent activity against parasitic nematodes, but its effects on protozoans are poorly known and no studies have explored its trypanocidal potential. Here, we investigated the activity of C. intybus against extracellular and intracellular stages of T. cruzi, including the prediction of trypanocidal compounds by metabolomic analyses and bioactivity-based molecular networking. Purified C. intybus extracts were prepared from leaves and roots of five C. intybus cultivars (cv. 'Benulite', 'Goldine', 'Larigot', 'Maestoso' and 'Spadona'). All C. intybus extracts induced concentration-dependent effects against T. cruzi trypomastigotes. C. intybus leaf extracts had higher trypanocidal selectivity and lower cytotoxicity on mammalian cells than root extracts. The leaf extract of C. intybus cv. Goldine also significantly reduced the number of mammalian cells infected with T. cruzi amastigotes. Metabolomic and bioactivity-based molecular networking analyses revealed 11 compounds in C. intybus leaves strongly linked with activity against trypomastigotes, including the sesquiterpene lactone lactucin, and flavonoid- and fatty acid-derivatives. Furthermore, seven distinct C. intybus molecules (including two sesquiterpene lactone-derivatives) were predicted to be involved in reducing the number of mammalian cells infected with amastigotes. This is the first report of the anti-protozoal activity of C. intybus against trypanosomatid parasites and expands our understanding of the anti-parasitic effects of this plant and its bioactive metabolites. Further studies to elucidate the anti-protozoal compound(s) in C. intybus and their mode(s) of action will improve our knowledge of using this bioactive plant as a promising source of novel broad-spectrum anti-parasitic compounds with associated health benefits and biomedical potential.

  • Open Access English
    Authors: 
    Mikael Thomsen; Anca Stoica; Kenneth Vielsted Christensen; Tue Fryland; Jens D. Mikkelsen; John Bondo Hansen;
    Country: Denmark

    Background: The gold standard for symptomatic relief of Parkinson's disease (PD) is L-DOPA. However, long-term treatment often leads to motor complications such as L-DOPA-induced dyskinesia (LID). While amantadine (GocovriTM) is the only approved therapy for dyskinesia in PD patients on the American market, it is associated with neurological side effects and limited efficacy. Thus, there remains a high unmet need for addressing LID in PD patients worldwide. Objective: The objective of this study was to evaluate the efficacy, safety and performance compared to approved treatments of the serotonin receptor 1A (5-HT1A) and 5-HT1B/D agonists buspirone and zolmitriptan in the 6-hydroxydopamine unilaterally lesioned rat model for PD. .Methods: The hemiparkinsonian 6-OHDA-lesioned rats underwent chronic treatment with L-DOPA to induce dyskinesia and were subsequently used for efficacy testing of buspirone, zolmitriptan and comparison with amantadine, measured as abnormal involuntary movement (AIM) scores after L-DOPA challenge. Safety testing was performed in model and naive animals using forelimb adjusting, rotarod and open field tests.Results: 5-HT1A and 5-HT1B/D agonism effectively reduced AIM scores in a synergistic manner. The drug combination of buspirone and zolmitriptan was safe and did not lead to tolerance development following sub -chronic administration. Head-to-head comparison with amantadine showed superior performance of buspirone and zolmitriptan in the model.Conclusions: The strong anti-dyskinetic effect found with combined 5-HT1A and 5-HT1B/D agonism renders buspirone and zolmitriptan together a meaningful treatment for LID in PD.

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