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3.
  • Antonelli, Alexandre, 1978, et al. (författare)
  • Madagascar's extraordinary biodiversity : Evolution, distribution, and use
  • 2022
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 378:6623, s. 962-
  • Tidskriftsartikel (refereegranskat)abstract
    • Madagascar's biota is hyperdiverse and includes exceptional levels of endemicity. We review the current state of knowledge on Madagascar's past and current terrestrial and freshwater biodiversity by compiling and presenting comprehensive data on species diversity, endemism, and rates of species description and human uses, in addition to presenting an updated and simplified map of vegetation types. We report a substantial increase of records and species new to science in recent years; however, the diversity and evolution of many groups remain practically unknown (e.g., fungi and most invertebrates). Digitization efforts are increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge and identifying gaps in our understanding, particularly as species richness corresponds closely to collection effort. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. We highlight humid forests as centers of diversity and endemism because of their role as refugia and centers of recent and rapid radiations. However, the distinct endemism of other areas, such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest, is also biologically important despite lower species richness. The documented uses of Malagasy biodiversity are manifold, with much potential for the uncovering of new useful traits for food, medicine, and climate mitigation. The data presented here showcase Madagascar as a unique " living laboratory" for our understanding of evolution and the complex interactions between people and nature. The gathering and analysis of biodiversity data must continue and accelerate if we are to fully understand and safeguard this unique subset of Earth's biodiversity.
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4.
  • de Winter, J M, et al. (författare)
  • KBTBD13 is an actin-binding protein that modulates muscle kinetics
  • 2020
  • Ingår i: Journal of Clinical Investigation. - : Stanford University Press. - 0021-9738 .- 1558-8238. ; 130:2, s. 754-767
  • Tidskriftsartikel (refereegranskat)abstract
    • The mechanisms that modulate the kinetics of muscle relaxation are critically important for muscle function. A prime example of the impact of impaired relaxation kinetics is nemaline myopathy caused by mutations in KBTBD13 (NEM6). In addition to weakness, NEM6 patients have slow muscle relaxation, compromising contractility and daily life activities. The role of KBTBD13 in muscle is unknown, and the pathomechanism underlying NEM6 is undetermined. A combination of transcranial magnetic stimulation-induced muscle relaxation, muscle fiber- and sarcomere-contractility assays, low-angle x-ray diffraction, and superresolution microscopy revealed that the impaired muscle-relaxation kinetics in NEM6 patients are caused by structural changes in the thin filament, a sarcomeric microstructure. Using homology modeling and binding and contractility assays with recombinant KBTBD13, Kbtbd13-knockout and Kbtbd13(R408c)-knockin mouse models, and a GFP-labeled Kbtbd13-transgenic zebrafish model, we discovered that KBTBD13 binds to actin - a major constituent of the thin filament - and that mutations in KBTBD13 cause structural changes impairing muscle-relaxation kinetics. We propose that this actin-based impaired relaxation is central to NEM6 pathology.
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5.
  • Abele, H., et al. (författare)
  • Particle physics at the European Spallation Source
  • 2023
  • Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
  • Forskningsöversikt (refereegranskat)abstract
    • Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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6.
  • Caravaca, A. S., et al. (författare)
  • Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonresolving inflammation underlies a range of chronic inflammatory diseases, and therapeutic acceleration of resolution of inflammation may improve outcomes. Neural reflexes regulate the intensity of inflammation (for example, through signals in the vagus nerve), but whether activation of the vagus nerve promotes the resolution of inflammation in vivo has been unknown. To investigate this, mice were subjected to electrical vagus nerve stimulation (VNS) or sham surgery at the cervical level followed by zymosan-induced peritonitis. The duration of inflammation resolution was significantly reduced and efferocytosis was significantly increased in mice treated with VNS as compared with sham. Lipid mediator (LM) metabololipidomics revealed that mice treated with VNS had higher levels of specialized proresolving mediators (SPMs), particularly from the omega-3 docosahexaenoic (DHA) and docosapentaenoic (n-3 DPA) metabolomes, in peritoneal exudates. VNS also shifted the ratio between proinflammatory and proresolving LMs toward a proresolving profile, but this effect by VNS was inverted in mice deficient in 12/15-lipoxgenase (Alox15), a key enzyme in this SPM biosynthesis. The significant VNS-mediated reduction of neutrophil numbers in peritoneal exudates was absent in mice deficient in the cholinergic α7-nicotinic acetylcholine receptor subunit (α7nAChR), an essential component of the inflammatory reflex. Thus, VNS increased local levels of SPM and accelerated resolution of inflammation in zymosan-induced peritonitis by a mechanism that involves Alox15 and requires the α7nAChR. 
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7.
  • Gau, Rémi, et al. (författare)
  • Brainhack : Developing a culture of open, inclusive, community-driven neuroscience
  • 2021
  • Ingår i: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 109:11, s. 1769-1775
  • Tidskriftsartikel (refereegranskat)abstract
    • Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.
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8.
  • Axelsson, Malin, et al. (författare)
  • Lived experiences: a focus group pilot study within the MentALLY project of mental healthcare among European users
  • 2020
  • Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundMental healthcare is an important component in societies' response to mental health problems. Although the World Health Organization highlights availability, accessibility, acceptability and quality of healthcare as important cornerstones, many Europeans lack access to mental healthcare of high quality. Qualitative studies exploring mental healthcare from the perspective of people with lived experiences would add to previous research and knowledge by enabling in-depth understanding of mental healthcare users, which may be of significance for the development of mental healthcare. Therefore, the aim of the current study was to describe experiences of mental healthcare among adult Europeans with mental health problems.MethodIn total, 50 participants with experiences of various mental health problems were recruited for separate focus group interviews in each country. They had experiences from both the private and public sectors, and with in- and outpatient mental healthcare. The focus group interviews (N=7) were audio recorded, transcribed verbatim and analysed through thematic analysis. The analysis yielded five themes and 13 subthemes.ResultsThe theme Seeking and trying to find help contained three subthemes describing personal thresholds for seeking professional help, not knowing where to get help, and the importance of receiving help promptly. The theme Awaiting assessment and treatment contained two subthemes including feelings of being prioritized or not and feelings of being abandoned during the often-lengthy referral process. The theme Treatment: a plan with individual parts contained three subthemes consisting of demands for tailored treatment plans in combination with medications and human resources and agreement on treatment. The theme Continuous and respectful care relationship contained two subthemes describing the importance of continuous care relationships characterised by empathy and respect. The theme Suggestions for improvements contained three subthemes highlighting an urge to facilitate care contacts and to increase awareness of mental health problems and a wish to be seen as an individual with potential.ConclusionFacilitating contacts with mental healthcare, a steady contact during the referral process, tailored treatment and empathy and respect are important aspects in efforts to improve mental healthcare. Recommendations included development of collaborative practices between stakeholders in order to increase general societal awareness of mental health problems.
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9.
  • Taslimi, Y., et al. (författare)
  • Profiling inflammatory response in lesions of cutaneous leishmaniasis patients using a non-invasive sampling method combined with a high-throughput protein detection assay
  • 2020
  • Ingår i: Cytokine. - : Elsevier BV. - 1043-4666. ; 130:June
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cutaneous leishmaniasis (CL) is an infection caused by Leishmania (L.) protozoa transmitted through the bite of infected sand fly. Previously, invasive sampling of blood and skin along with low throughput methods were used for determination of inflammatory response in CL patients. Aims/Methodology: We established a novel approach based on a non-invasive adhesive tape-disc sampling combined with a powerful multiplexing technique called proximity extension assay for profiling 92 inflammatory cytokines, chemokines and surface molecules in the lesions of CL patients infected with L. tropica. Sample collection was done non-invasively by using adhesive tape-discs from lesion and normal skin of 33 L. tropica positive patients. Results: Out of 92 inflammatory proteins, the level of 34 proteins was significantly increased in the lesions of CL patients compared to their normal skin. This includes the chemokines CCL2, CCL3, CCL4, CXCL1, CXCL5, CXCL9, CXCL10 and CXCL11, together with the interleukins IL-6, IL-8, IL-18, LIF and OSM. The remaining significantly changed inflammatory proteins include 7 surface molecules and receptors: CD5, CD40, CDCP1, 4E-BP1, TNFRSF9, IL-18R1 and OPG as well as 16 other cytokines and proteins: MMP-1, CSF-1, VEGFA, uPA, EN-RAGE, LAP TGF-beta 1, HGF, MMP-10, CASP-8, TNFSF14, STAMPB, ADA, TRAIL and ST1A1. Further, 13 proteins showed an increasing trend, albeit not statistically significant, in the CL lesions, including TGF-alpha, CCL23, MCP-2, IL-12B, CXCL6, IL-24, FGF-19, TNF beta, CD6, TRANCE, IL10, SIR2 and CCL20. Conclusion: We herein report a novel approach based on a non-invasive sampling method combined with the high-throughput protein assay for profiling inflammatory proteins in CL lesions. Using this approach, we could profile inflammatory proteins in the lesions from CL patients. This new non-invasive approach may have implications for studying skin inflammatory mediators in CL and other skin disorders.
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10.
  • Yammine, S.G., et al. (författare)
  • Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition
  • 2023
  • Ingår i: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons.Results: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5−Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk.Conclusion: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.
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  • Yang, D. P., et al. (författare)
  • Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection
  • 2022
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 185:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroepithelial crosstalk is critical for gut physiology. However, the mechanisms by which sensory neurons communicate with epithelial cells to mediate gut barrier protection at homeostasis and during inflammation are not well understood. Here, we find that Nav1.8+CGRP+ nociceptor neurons are juxtaposed with and signal to intestinal goblet cells to drive mucus secretion and gut protection. Nociceptor ablation led to decreased mucus thickness and dysbiosis, while chemogenetic nociceptor activation or capsaicin treatment induced mucus growth. Mouse and human goblet cells expressed Ramp1, receptor for the neuropeptide CGRP. Nociceptors signal via the CGRP-Ramp1 pathway to induce rapid goblet cell emptying and mucus secretion. Notably, commensal microbes activated nociceptors to control homeostatic CGRP release. In the absence of nociceptors or epithelial Ramp1, mice showed increased epithelial stress and susceptibility to colitis. Conversely, CGRP administration protected nociceptor-ablated mice against colitis. Our findings demon-strate a neuron-goblet cell axis that orchestrates gut mucosal barrier protection.
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  • Andersson, Claes, et al. (författare)
  • Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines. L1000 gene expression signatures for MBZ treated THP-1 monocytes also connected negatively to MEK inhibitors. MEK/ERK phosphoprotein activity testing of a number of TBAs showed that only MBZ increased the activity in both THP-1 monocytes and PMA differentiated macrophages. Distal effects on ERK phosphorylation of the substrate P90RSK and release of IL1B followed the same pattern. The effect of MBZ on MEK/ERK phosphorylation was inhibited by RAF/MEK/ERK inhibitors in THP-1 models, CD3/IL2 stimulated PBMCs and a MAPK reporter HEK-293 cell line. MBZ was also shown to increase ERK activity in CD4+ T-cells from lupus patients with known defective ERK signalling. Given these mechanistic features MBZ is suggested suitable for treatment of diseases characterized by defective ERK signalling, notably difficult to treat autoimmune diseases.
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14.
  • Bahrami, F., et al. (författare)
  • Blood transcriptional profiles distinguish different clinical stages of cutaneous leishmaniasis in humans
  • 2022
  • Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890. ; 149, s. 165-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Cutaneous leishmaniasis (CL) is a neglected tropical disease with severe morbidity and socioeconomic sequelae. A better understanding of underlying immune mechanisms that lead to different clinical outcomes of CL could inform the rational design of intervention measures. While transcriptomic analyses of CL lesions were recently reported by us and others, there is a dearth of information on the expression of immune-related genes in the blood of CL patients. Herein, we investigated immune-related gene expression in whole blood samples collected from individuals with different clinical stages of CL along with healthy volunteers in an endemic CL region where Leishmania (L.) tropica is prevalent. Study participants were categorized into asymptomatic (LST+) and healthy uninfected (LST-) groups based on their leishmanin skin test (LST). Whole blood PAXgene samples were collected from volunteers, who had healed CL lesions, and patients with active L. tropica cutaneous lesions. Quality RNA extracted from 57 blood samples were subjected to Dual-color reverse-transcription multiplex ligation-dependent probe amplification (dcRT-MLPA) assay for profiling 144 immune-related genes. Results show significant changes in the expression of genes involved in interferon signaling pathway in the blood of active CL patients, asymptomatics and healed individuals. Nonetheless, distinct profiles for several immune-related genes were identified in the healed, the asymptomatic, and the CL patients compared to the healthy controls. Among others, IFI16 and CCL11 were found as immune transcript signatures for the healed and the asymptomatic individuals, respectively. These results warrant further exploration to pinpoint novel blood biomarkers for different clinical stages of CL.
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15.
  • Bonagas, Nadilly, et al. (författare)
  • Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
  • 2022
  • Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
  • Tidskriftsartikel (refereegranskat)abstract
    • The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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16.
  • Burgman, A., et al. (författare)
  • The ESSnuSB Design Study: Overview and Future Prospects
  • 2023
  • Ingår i: Universe. - : MDPI. - 2218-1997. ; 9:8
  • Forskningsöversikt (refereegranskat)abstract
    • ESSnuSB is a design study for an experiment to measure the CP violation in the leptonic sector at the second neutrino oscillation maximum using a neutrino beam driven by the uniquely powerful ESS linear accelerator. The reduced impact of systematic errors on sensitivity at the second maximum allows for a very precise measurement of the CP violating parameter. This review describes the fundamental advantages of measurement at the second maximum, the necessary upgrades to the ESS linac in order to produce a neutrino beam, the near and far detector complexes, and the expected physics reach of the proposed ESSnuSB experiment, concluding with the near future developments aimed at the project realization.
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17.
  • Cinato, Mathieu, et al. (författare)
  • Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractility
  • 2023
  • Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The adult heart develops hypertrophy to reduce ventricular wall stress and maintain cardiac function in response to an increased workload. Although pathological hypertrophy generally prog-resses to heart failure, physiological hypertrophy may be car-dioprotective. Cardiac-specific overexpression of the lipid-droplet protein perilipin 5 (Plin5) promotes cardiac hypertrophy, but it is unclear whether this response is beneficial. We analyzed RNA -sequencing data from human left ventricle and showed that car-diac PLIN5 expression correlates with up-regulation of cardiac contraction-related processes. To investigate how elevated cardiac Plin5 levels affect cardiac contractility, we generated mice with cardiac-specific overexpression of Plin5 (MHC-Plin5 mice). These mice displayed increased left ventricular mass and cardiomyocyte size but preserved heart function. Quantitative proteomics identified sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) as a Plin5-interacting protein. In situ proximity ligation assay further confirmed the Plin5/SERCA2 interaction. Live imaging showed in-creases in intracellular Ca2+ release during contraction, Ca2+ removal during relaxation, and SERCA2 function in MHC-Plin5 versus WT cardiomyocytes. These results identify a role of Plin5 in improving cardiac contractility through enhanced Ca2+ signaling.
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18.
  • de Boniface, J., et al. (författare)
  • Omitting axillary dissection in breast cancer with sentinel-node metastases
  • 2024
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 390:13, s. 1163-1175
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups.METHODS We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44.RESULTS Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy–only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy–only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin.CONCLUSIONS The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).
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19.
  • de la Vega, Maria Pagnon, et al. (författare)
  • The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid beta fibril formation
  • 2021
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:606
  • Tidskriftsartikel (refereegranskat)abstract
    • Point mutations in the amyloid precursor protein gene (APP) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid beta (A beta). Here, we describe the Uppsala APP mutation (Delta 690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) A beta 42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the Uppsala APP mutation alters APP processing by increasing beta-secretase cleavage and affecting alpha-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated A beta, A beta Upp1-42(Delta 19-24), accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain.
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20.
  • Donahue, Mary, et al. (författare)
  • Wireless optoelectronic devices for vagus nerve stimulation in mice
  • 2022
  • Ingår i: Journal of Neural Engineering. - : IOP Publishing. - 1741-2560 .- 1741-2552. ; 19:6, s. 066031-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Vagus nerve stimulation (VNS) is a promising approach for the treatment of a wide variety of debilitating conditions, including autoimmune diseases and intractable epilepsy. Much remains to be learned about the molecular mechanisms involved in vagus nerve regulation of organ function. Despite an abundance of well-characterized rodent models of common chronic diseases, currently available technologies are rarely suitable for the required long-term experiments in freely moving animals, particularly experimental mice. Due to challenging anatomical limitations, many relevant experiments require miniaturized, less invasive, and wireless devices for precise stimulation of the vagus nerve and other peripheral nerves of interest. Our objective is to outline possible solutions to this problem by using nongenetic light-based stimulation. Approach. We describe how to design and benchmark new microstimulation devices that are based on transcutaneous photovoltaic stimulation. The approach is to use wired multielectrode cuffs to test different stimulation patterns, and then build photovoltaic stimulators to generate the most optimal patterns. We validate stimulation through heart rate analysis. Main results. A range of different stimulation geometries are explored with large differences in performance. Two types of photovoltaic devices are fabricated to deliver stimulation: photocapacitors and photovoltaic flags. The former is simple and more compact, but has limited efficiency. The photovoltaic flag approach is more elaborate, but highly efficient. Both can be used for wireless actuation of the vagus nerve using light impulses. Significance. These approaches can enable studies in small animals that were previously challenging, such as long-term in vivo studies for mapping functional vagus nerve innervation. This new knowledge may have potential to support clinical translation of VNS for treatment of select inflammatory and neurologic diseases.
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21.
  • Heggebo, L. C., et al. (författare)
  • Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden
  • 2023
  • Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
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22.
  • Holbein, Christina E., et al. (författare)
  • Health behaviours reported by adults with congenital heart disease across 15 countries
  • 2020
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 10, s. 1077-1087
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Health behaviours are essential to maintain optimal health and reduce the risk of cardiovascular complications in adults with congenital heart disease. This study aimed to describe health behaviours in adults with congenital heart disease in 15 countries and to identify patient characteristics associated with optimal health behaviours in the international sample. Design: This was a cross-sectional observational study. Methods: Adults with congenital heart disease (n = 4028, median age = 32 years, interquartile range 25–42 years) completed self-report measures as part of the Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study (APPROACH-IS). Participants reported on seven health behaviours using the Health Behaviors Scale-Congenital Heart Disease. Demographic and medical characteristics were assessed via medical chart review and self-report. Multivariate path analyses with inverse sampling weights were used to investigate study aims. Results: Health behaviour rates for the full sample were 10% binge drinking, 12% cigarette smoking, 6% recreational drug use, 72% annual dental visit, 69% twice daily tooth brushing, 27% daily dental flossing and 43% sport participation. Pairwise comparisons indicated that rates differed between countries. Rates of substance use behaviours were higher in younger, male participants. Optimal dental health behaviours were more common among older, female participants with higher educational attainment while sports participation was more frequent among participants who were younger, male, married, employed/students, with higher educational attainment, less complex anatomical defects and better functional status. Conclusions: Health behaviour rates vary by country. Predictors of health behaviours may reflect larger geographic trends. Our findings have implications for the development and implementation of programmes for the assessment and promotion of optimal health behaviours in adults with congenital heart disease. © The European Society of Cardiology 2019.
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23.
  • Hvidsten, D., et al. (författare)
  • The distribution limit of the common tick, Ixodes ricinus, and some associated pathogens in north-western Europe
  • 2020
  • Ingår i: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • In north-western Europe, the common tick, Ixodes ricinus, is widely established, its distribution appears to be increasing and the spread of tick-borne diseases is of increasing concern. The project Flatt i Nord (Ticks in northern Norway) commenced in spring 2009 with the intention of studying the ticks distribution and that of its pathogens in northern Norway. Several methods were used: cloth-dragging, collecting from trapped small mammals, and collecting from pets. Since 2010, the occurrence of ticks in the region of northern Norway was determined directly by cloth-dragging 167 times in 109 separate locations between the latitudes of 64 degrees N and 70 degrees N (included seven locations in the northern part of Trondelag County). The northernmost location of a permanent I. ricinus population was found to be Nordoyvagen (66.2204 degrees N, 12.59 degrees E) on the Island of Donna. In a sample of 518 nymphal and adult ticks, the Borrelia prevalence collected close to this distribution limit varied but was low (1-15 %) compared with the locations in Trondelag, south of the study area (15-27 %). Five specimens (1 %) were positive for Rickettsia helvetica. The length of the vegetation growing season (GSL) can be used as an approximate index for the presence of established populations of I. ricinus. The present study suggests that the threshold GSL for tick establishment is about 170 days, because the median GSL from 1991 to 2015 was 174-184 days at sites with permanent tick populations, showing a clear increase compared with the period 1961-1990. This apparent manifestation of climate change could explain the northward extension of the range of I. ricinus.
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24.
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25.
  • Lévesque, Valérie, et al. (författare)
  • Implantable Cardioverter-Defibrillators and Patient-Reported Outcomes in Adults with Congenital Heart Disease : an International Study
  • 2020
  • Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271 .- 1556-3871. ; 17:5, s. 768-776
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are increasingly used to prevent sudden deaths in the growing population of adults with congenital heart disease (CHD). Yet, little is known about their impact on patient-reported outcomes (PROs).OBJECTIVE: We assessed and compared PROs in adults with CHD with and without ICDs.METHODS: A propensity-based matching weight analysis was conducted to evaluate PROs in an international cross-sectional study of adults with CHD from 15 countries across 5 continents.RESULTS: A total of 3,188 patients were included: 107 with ICDs and 3,081 weight-matched controls without ICDs. ICD recipients averaged 40.1±12.4 years of age, with >95% having moderate or complex CHD. Defibrillators were implanted for primary and secondary prevention in 38.3% and 61.7%, respectively. Perceived health status, psychological distress, sense of coherence, and health behaviours did not differ significantly in patients with and without ICDs. However, ICD recipients had a more threatening view of their illness (relative % difference 8.56, P=0.011). Those with secondary compared to primary prevention indications had a significantly lower quality of life score (linear analogue scale 72.0±23.1 versus 79.2±13.0, P=0.047). Marked geographic variations were observed. Overall sense of well-being, assessed by a summary score that combines various PROs, was significantly lower in ICD recipients (versus controls) from Switzerland, Argentina, Taiwan, and USA.CONCLUSIONS: In an international cohort of adults with CHD, ICDs were associated with a more threatening illness perception, with a lower quality of life in those with secondary compared to primary prevention indications. However, marked geographic variability in PROs was observed.
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26.
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27.
  • Moons, Philip, 1968, et al. (författare)
  • Physical Functioning, Mental Health, and Quality of Life in Different Congenital Heart Defects : Comparative Analysis in 3538 Patients From 15 Countries
  • 2021
  • Ingår i: Canadian Journal of Cardiology. - : Elsevier BV. - 0828-282X .- 1916-7075. ; 37:2, s. 215-223
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We compared physical functioning, mental health, and quality of life (QoL) of patients with different subtypes of congenital heart disease (CHD) in a large international sample and investigated the role of functional class in explaining the variance in outcomes across heart defects.METHODS: In the cross-sectional Assessment of Patterns of Patient-Reported Outcome in Adults with Congenital Heart Disease-International Study (APPROACH-IS), we enrolled 4028 adult patients with CHD from 15 countries. Diagnostic groups with at least 50 patients were included in these analyses, yielding a sample of 3538 patients (median age: 32 years; 52% women). Physical functioning, mental health, and QoL were measured with the SF-12 health status survey, Hospital Anxiety and Depression Scale (HADS), linear analog scale (LAS) and Satisfaction with Life Scale, respectively. Functional class was assessed using the patient-reported New York Heart Association (NYHA) class. Multivariable general linear mixed models were applied to assess the relationship between the type of CHD and patient-reported outcomes, adjusted for patient characteristics, and with country as random effect.RESULTS: Patients with coarctation of the aorta and those with isolated aortic valve disease reported the best physical functioning, mental health, and QoL. Patients with cyanotic heart disease or Eisenmenger syndrome had worst outcomes. The differences were statistically significant, above and beyond other patient characteristics. However, the explained variances were small (0.6% to 4.1%) and decreased further when functional status was added to the models (0.4% to 0.9%).CONCLUSIONS: Some types of CHD predict worse patient-reported outcomes. However, it appears that it is the functional status associated with the heart defect rather than the heart defect itself that shapes the outcomes.
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28.
  • Nilsson, Johan S., et al. (författare)
  • Immune phenotypes of nasopharyngeal cancer
  • 2020
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11, s. 1-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Nasopharyngeal cancer (NPC) features intralesional immune cells, but data are lacking on presence/distribution of T-cells and dendritic cells (DCs). Based on intralesional distribution of lymphocytes, a series of NPC biopsies (n = 48) were classified into “inflamed”, “excluded”, and “deserted” phenotypes. In addition, CD8+ T-cells and CD207+ DCs were quantified. The data were analyzed in relation to Epstein–Barr virus-encoded small RNA (EBER), Epstein-Barr virus (EBV) DNA, and survival. Separately, data on gene expression from a public database were analyzed. 61.7% of NPC lesions were “inflamed”, 29.8% were “excluded”, and 8.5% were “deserted”. While CD8+ cells were present in cancer cell areas and in surrounding stroma, CD207+ cells were observed largely in cancer cell areas. High CD8+ T-cell presence was associated with EBV+ disease, but no such pattern was observed for CD207+ DCs. There was a difference in disease-free survival in favor of “inflamed” over “excluded” NPC. Gene expression analysis revealed differences between NPC and control tissue (e.g., with regard to interferon activity) as well as between subgroups of NPC based on CD8 expression (high vs. low). In conclusion, NPC lesions are heterogeneous with regard to distribution of CD8+ T-cells and CD207+ DCs. NPC can be classified into immune phenotypes that carry prognostic information. CD207+ DCs may represent a target for immunotherapy with potential to facilitate the antigen cross-presentation necessary to execute cytotoxic T-lymphocyte responses.
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29.
  • Sjöström, Jenny K., 1978-, et al. (författare)
  • Late Holocene peat paleodust deposition in south-western Sweden : exploring geochemical properties, local mineral sources and regional aeolian activity
  • 2022
  • Ingår i: Chemical Geology. - : Elsevier. - 0009-2541 .- 1872-6836. ; 602
  • Tidskriftsartikel (refereegranskat)abstract
    • Atmospheric mineral dust not only interacts with the climate system by scattering incoming solar radiation and affecting atmospheric photochemistry, but also contributes critical nutrients to marine and terrestrial ecosystems. In a high-resolution analysis of paleodust deposition, peat development and soil dust sources, we assess the interplay between dust deposition and bog development of the Davidsmosse bog in south-western Sweden. Analyses of the 5400-year record (458 cm) included radiocarbon dating, bulk density, ash content, chemical and mineralogical composition and carbon stable isotopes, subsequently explored using principal component analysis. Fourteen dust events (DEs) were recorded (cal BP) in the peat sequence: 3580–3490; 3280; 3140; 3010–2840; 2740; 2610; 2480; 2340; 2240–2130; 1690; 1240; 960, 890–760, and 620–360. The majority of the DEs were coupled to increases in peat accumulation rates and increased nutrient content (N, P and K) suggesting that the DEs contributed with nutrients to the bog ecosystem, promoting increased accumulation. We also analyzed the chemical and mineral composition of potential mineral source deposits (separated into 6 grain-size fractions) from sites within a 4 km radius as well as aeolian dunes closer to the coast (25 km). The composition deposited on the present-day bog surface indicates that the bulk of the contemporary minerals have a local origin (<1.5 km), but the DEs may be of a more distant origin. The results also indicate that quartz and plagioclase feldspar content consistently increase with increasing grain-size, both in the source samples as well as in the peat sequence, and that the Si/Al ratio can be used to infer grain size changes in the peat. Two longer phases saw numerous DEs, between 2800 and 2130 cal BP and a stepwise increase from 960 towards 360 cal BP. The episodic character of the events, together with the inferred coarse grain size, suggest that the particles were deposited by (winter) storms. Future studies should include grain size analysis as well as a more in-depth comparison with regional paleo dust and storm records to increase knowledge on both transport processes (creep, saltation, suspension) and the climate processes driving late Holocene dust and storm events in Scandinavia.
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30.
  • Thoma, Daniel S., et al. (författare)
  • Soft tissue management at implants: : Summary and consensus statements of group 2. The 6th EAO Consensus Conference 2021
  • 2021
  • Ingår i: Clinical Oral Implants Research. - : John Wiley & Sons. - 0905-7161 .- 1600-0501. ; 32:S21, s. 174-180
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The task of working Group 2 at the 6th Consensus Meeting of the European Association for Osseointegration was to comprehensively assess the effects of soft tissue augmentation procedures at dental implant sites on clinical, radiographic and patient-reported outcome measures (PROMs) including an overview on available outcome measures and methods of assessment.Materials and methods: Three systematic reviews and one critical review were performed in advance on (i) the effects of soft tissue augmentation procedures on clinical, radiographic and aesthetic outcomes, (ii) reliability and validity of outcome measures and methods of assessment and (iii) PROMs applied in clinical studies for soft tissue augmentation procedures at dental implant sites. Major findings, consensus statements, clinical recommendations and implications for future research were discussed in the group and approved during the plenary sessions.Results: The four reviews predominantly revealed: Soft tissue augmentation procedures in conjunction with immediate and delayed implant placement result in superior aesthetic outcomes compared to no soft tissue augmentation in the zone of aesthetic priority. Soft tissue augmentation procedures have a limited effect on marginal bone level changes compared to implant sites without soft tissue augmentation. Clinically relevant parameters (gingival index, mucosal recession) and plaque control improve at implant sites when the width of keratinised mucosa is increased. A variety of aesthetic indices have been described with good reliability. Pink Esthetic Score and Complex Esthetic Index are the most validated aesthetic indices for single implants, though. Superimposed digital surface scans are most accurate to assess profilometric tissue changes. PROMs following soft tissue augmentation procedures have been assessed using various forms of questionnaires. Soft tissue augmentation had a limited effect on PROMs.Conclusions: Soft tissue augmentation procedures are widely applied in conjunction with implant therapy. Depending on the indication of these interventions, clinical, radiographic and aesthetic outcomes may improve, whereas the effect on PROMs is limited.
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31.
  • Timmins, Iain R., et al. (författare)
  • International pooled analysis of leisure-time physical activity and premenopausal breast cancer in women from 19 cohorts
  • 2024
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 42:8, s. 927-939
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer.METHODS: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity.RESULTS: Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity.CONCLUSION: This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.
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32.
  • Van Bulck, Liesbet, et al. (författare)
  • Healthcare system inputs and patient-reported outcomes : a study in adults with congenital heart defect from 15 countries
  • 2020
  • Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The relationship between healthcare system inputs (e.g., human resources and infrastructure) and mortality has been extensively studied. However, the association between healthcare system inputs and patient-reported outcomes remains unclear. Hence, we explored the predictive value of human resources and infrastructures of the countries' healthcare system on patient-reported outcomes in adults with congenital heart disease.METHODS: This cross-sectional study included 3588 patients with congenital heart disease (median age = 31y; IQR = 16.0; 52% women; 26% simple, 49% moderate, and 25% complex defects) from 15 countries. The following patient-reported outcomes were measured: perceived physical and mental health, psychological distress, health behaviors, and quality of life. The assessed inputs of the healthcare system were: (i) human resources (i.e., density of physicians and nurses, both per 1000 people) and (ii) infrastructure (i.e., density of hospital beds per 10,000 people). Univariable, multivariable, and sensitivity analyses using general linear mixed models were conducted, adjusting for patient-specific variables and unmeasured country differences.RESULTS: Sensitivity analyses showed that higher density of physicians was significantly associated with better self-reported physical and mental health, less psychological distress, and better quality of life. A greater number of nurses was significantly associated with better self-reported physical health, less psychological distress, and less risky health behavior. No associations between a higher density of hospital beds and patient-reported outcomes were observed.CONCLUSIONS: This explorative study suggests that density of human resources for health, measured on country level, are associated with patient-reported outcomes in adults with congenital heart disease. More research needs to be conducted before firm conclusions about the relationships observed can be drawn.TRIAL REGISTRATION: ClinicalTrials.gov: NCT02150603. Registered 30 May 2014.
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33.
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34.
  • Al-Motlaq, M., et al. (författare)
  • Position statement of the international network for child and family centered care : Child and family centred care during the COVID19 pandemic
  • 2021
  • Ingår i: Journal of Pediatric Nursing. - : Elsevier BV. - 0882-5963 .- 1532-8449. ; 61, s. 140-143
  • Tidskriftsartikel (refereegranskat)abstract
    • It is the position of the International Network for Child and Family Centered Care (INCFCC) that COVID19 restrictions pose tremendous challenges for the health care team in their efforts to provide child and family centered care (CFCC). COVID-19 restrictions impact on the family's right to be presernt with their ill child and to contribute to the caring process. A limited number of articles have discussed challenges about the successful delivery of CFCC during the COVID-19 pandemic. Based on current literature, the INCFCC stresses the need for continuous facilitation implementation of child and family centred care as, it is essential for children's physical and psychological wellbeing. Furthermore we believe that the families' presence and participation holds more benefits than risks to the health of children, their families, and the health care team. 
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35.
  • Andresen, Amanda K H, et al. (författare)
  • Radiographic features in 2D imaging as predictors for justified CBCT examinations of canine-induced root resorption.
  • 2021
  • Ingår i: Dento-Maxillo-Facial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 51:1
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: This retrospective observational study aimed to evaluate the diagnostic accuracy of two-dimensional radiographs on canine-induced root resorption (CIRR) in lateral incisors and identify predictors of CIRR in patients with impacted maxillary canines (IMC).METHODS: Ninety-nine patients aged 9-17 years, with 156 IMCs, were included in the study. All had CBCT-volumes and two-dimensional radiographs consisting of at least one panoramic radiograph. Two radiologists jointly viewed all cases twice. First, radiographic features related to the IMC and possible CIRR were recorded from two-dimensional radiographs. Then, CIRR was determined from CBCT and according to position and extension classified as mild, moderate and severe.RESULTS: CIRRs was detected in 80% of lateral incisors (mild: 45%; moderate: 44%; severe: 11%). The sensitivity was generally low at mild and moderate cut-offs (29 and 29%), and somewhat higher for severe (50%). Corresponding specificities were 48%, 63% and 68%. Canine cusp-tip superimposing the lateral incisor's middle third and root/crown ratio >1 was positively associated with mild CIRR, with an odds ratio (OR) of 3.8 and 6.7, respectively. In addition, the root development stage was positively associated with moderate/severe CIRR when the canine root was nearly or fully developed (OR = 3.1).CONCLUSIONS: The diagnostic accuracy of two-dimensional radiographs was inadequate for detecting CIRR amongst patients referred for CBCT examinations. Based on our results, none of the suggested two-dimensional radiographic features could predict moderate/severe CIRR except for root development stage. IMC in a later stage of root development seems to be associated with a higher risk of moderate/severe CIRR.
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36.
  • Anker, Ilka, et al. (författare)
  • Preoperative Electrophysiology in Patients With Ulnar Nerve Entrapment at the Elbow-Prediction of Surgical Outcome and Influence of Age, Sex and Diabetes.
  • 2022
  • Ingår i: Frontiers in clinical diabetes and healthcare. - : Frontiers Media S.A.. - 2673-6616. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of preoperative electrophysiology on outcome of surgical treatment in ulnar nerve entrapment at the elbow (UNE) is not clarified. Our aim was to evaluate influence of preoperative electrophysiologic grading on outcome and analyse how age, sex, and in particular diabetes affect such grading. Electrophysiologic protocols for 406 UNE cases, surgically treated at two hand surgery units reporting to the Swedish National Quality Register for Hand Surgery (HAKIR; 2010-2016), were retrospectively assessed, and graded as normal, reduced conduction velocity, conduction block or axonal degeneration. Outcome of surgery after primary and revision surgery was evaluated using QuickDASH and a doctor reported outcome measure (DROM) grading. No differences in QuickDASH or DROM were found between the four groups with different electrophysiologic grading preoperatively, or at three and 12 months or at follow up, respectively. When dichotomizing the electrophysiologic grading into normal and pathologic electrophysiology, cases with normal electrophysiology had worse QuickDASH than cases with pathologic electrophysiology preoperatively (p=0.046). Presence of a conduction block or axonal degeneration indicated a worse outcome by DROM grading (p=0.011). Primary surgeries had electrophysiologic more pronounced nerve pathology compared to revision surgeries (p=0.017). Cases of older age, men, and those with diabetes had more severe electrophysiologic nerve affection (p<0.0001). In the linear regression analysis, increasing age (unstandardized B=0.03, 95% CI 0.02-0.04; p<0.0001) and presence of diabetes (unstandardized B=0.60, 95% CI 0.25-0.95; p=0.001) were associated with a higher risk of a worse electrophysiologic classification. Female sex was associated with a better electrophysiologic grading (unstandardized B=-0.51, 95% CI -0.75- -0.27; p<0.0001). We conclude that older age, male sex, and concomitant diabetes are associated with more severe preoperative electrophysiologic nerve affection. Preoperative electrophysiologic grade of ulnar nerve affection may influence surgical outcome.
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37.
  • Arif, Muhammad, et al. (författare)
  • Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction
  • 2021
  • Ingår i: Elife. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Myocardial infarction (MI) promotes a range of systemic effects, many of which are unknown. Here, we investigated the alterations associated with MI progression in heart and other metabolically active tissues (liver, skeletal muscle, and adipose) in a mouse model of MI (induced by ligating the left ascending coronary artery) and sham-operated mice. We performed a genomewide transcriptomic analysis on tissue samples obtained 6- and 24 hr post MI or sham operation. By generating tissue-specific biological networks, we observed: (1) dysregulation in multiple biological processes (including immune system, mitochondrial dysfunction, fatty-acid beta-oxidation, and RNA and protein processing) across multiple tissues post MI and (2) tissue-specific dysregulation in biological processes in liver and heart post MI. Finally, we validated our findings in two independent MI cohorts. Overall, our integrative analysis highlighted both common and specific biological responses to MI across a range of metabolically active tissues.
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38.
  • Berg, Staffan, et al. (författare)
  • Evaluation in pig of an intestinal administration device for oral peptide delivery
  • 2023
  • Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 353, s. 792-801
  • Tidskriftsartikel (refereegranskat)abstract
    • The bioavailability of peptides co-delivered with permeation enhancers following oral administration remains low and highly variable. Two factors that may contribute to this are the dilution of the permeation enhancer in the intestinal fluid, as well as spreading of the released permeation enhancer and peptide in the lumen by intestinal motility. In this work we evaluated an Intestinal Administration Device (IAD) designed to reduce the luminal dilution of drug and permeation enhancer, and to minimize movement of the dosage form in the intestinal lumen. To achieve this, the IAD utilizes an expanding design that holds immediate release mini tablets and places these in contact with the intestinal epithelium, where unidirectional drug release can occur. The expanding conformation limits movement of the IAD in the intestinal tract, thereby enabling drug release at a single focal point in the intestine. A pig model was selected to study the ability of the IAD to promote intestinal absorption of the peptide MEDI7219 formulated together with the permeation enhancer sodium caprate. We compared the IAD to intestinally administered enteric coated capsules and an intestinally administered solution. The IAD restricted movement of the immediate release tablets in the small intestine and histological evaluation of the mucosa indicated that high concentrations of sodium caprate were achieved. Despite significant effect of the permeation enhancer on the integrity of the intestinal epithelium, the bioavailability of MEDI7219 was of the same order of magnitude as that achieved with the solution and enteric coated capsule formulations (2.5–3.8%). The variability in plasma concentrations of MEDI7219 were however lower when delivered using the IAD as compared to the solution and enteric coated capsule formulations. This suggests that dosage forms that can limit intestinal dilution and control the position of drug release can be a way to reduce the absorptive variability of peptides delivered with permeation enhancers but do not offer significant benefits in terms of increasing bioavailability.
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39.
  • Bergström, Sofia, et al. (författare)
  • Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease
  • 2021
  • Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:7, s. 1456-1470
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Decreased amyloid beta (A beta) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer's disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. Methods: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. Results: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of A beta 42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. Interpretation: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.
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40.
  • Botzanowski, Boris, et al. (författare)
  • Noninvasive Stimulation of Peripheral Nerves using Temporally-Interfering Electrical Fields
  • 2022
  • Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 11:17
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation (PNS) noninvasively without surgically implanted devices are enabling for fundamental research and clinical translation. Here, it is demonstrated how relatively high-frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. This principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model is validated. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve is demonstrated. This method is simple, relying on the repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques.
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41.
  • Broekman, Maarten J. E., et al. (författare)
  • Evaluating expert-based habitat suitability information of terrestrial mammals with GPS-tracking data
  • 2022
  • Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 31:8, s. 1526-1541
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Macroecological studies that require habitat suitability data for many species often derive this information from expert opinion. However, expert-based information is inherently subjective and thus prone to errors. The increasing availability of GPS tracking data offers opportunities to evaluate and supplement expert-based information with detailed empirical evidence. Here, we compared expert-based habitat suitability information from the International Union for Conservation of Nature (IUCN) with habitat suitability information derived from GPS-tracking data of 1,498 individuals from 49 mammal species.Location: Worldwide.Time period: 1998-2021.Major taxa studied: Forty-nine terrestrial mammal species.Methods: Using GPS data, we estimated two measures of habitat suitability for each individual animal: proportional habitat use (proportion of GPS locations within a habitat type), and selection ratio (habitat use relative to its availability). For each individual we then evaluated whether the GPS-based habitat suitability measures were in agreement with the IUCN data. To that end, we calculated the probability that the ranking of empirical habitat suitability measures was in agreement with IUCN's classification into suitable, marginal and unsuitable habitat types.Results: IUCN habitat suitability data were in accordance with the GPS data (> 95% probability of agreement) for 33 out of 49 species based on proportional habitat use estimates and for 25 out of 49 species based on selection ratios. In addition, 37 and 34 species had a > 50% probability of agreement based on proportional habitat use and selection ratios, respectively.Main conclusions: We show how GPS-tracking data can be used to evaluate IUCN habitat suitability data. Our findings indicate that for the majority of species included in this study, it is appropriate to use IUCN habitat suitability data in macroecological studies. Furthermore, we show that GPS-tracking data can be used to identify and prioritize species and habitat types for re-evaluation of IUCN habitat suitability data.
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42.
  • Callus, Edward, et al. (författare)
  • Phenotypes of adults with congenital heart disease around the globe : a cluster analysis.
  • 2021
  • Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To derive cluster analysis-based groupings for adults with congenital heart disease (ACHD) when it comes to perceived health, psychological functioning, health behaviours and quality of life (QoL).METHODS: This study was part of a larger worldwide multicentre study called APPROACH-IS; a cross sectional study which recruited 4028 patients (2013-2015) from 15 participating countries. A hierarchical cluster analysis was performed using Ward's method in order to group patients with similar psychological characteristics, which were defined by taking into consideration the scores of the following tests: Sense Of Coherence, Health Behavior Scale (physical exercise score), Hospital Anxiety Depression Scale, Illness Perception Questionnaire, Satisfaction with Life Scale and the Visual Analogue Scale scores of the EQ-5D perceived health scale and a linear analogue scale (0-100) measuring QoL.RESULTS: 3768 patients with complete data were divided into 3 clusters. The first and second clusters represented 89.6% of patients in the analysis who reported a good health perception, QoL, psychological functioning and the greatest amount of exercise. Patients in the third cluster reported substantially lower scores in all PROs. This cluster was characterised by a significantly higher proportion of females, a higher average age the lowest education level, more complex forms of congenital heart disease and more medical comorbidities.CONCLUSIONS: This study suggests that certain demographic and clinical characteristics may be linked to less favourable health perception, quality of life, psychological functioning, and health behaviours in ACHD. This information may be used to improve psychosocial screening and the timely provision of psychosocial care.
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43.
  • Capezza, Antonio Jose, et al. (författare)
  • Acylation of agricultural protein biomass yields biodegradable superabsorbent plastics
  • 2021
  • Ingår i: Communications Chemistry. - : Springer Nature. - 2399-3669. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Superabsorbent polymers (SAP) are a central component of hygiene and medical products requiring high liquid swelling, but these SAP are commonly derived from petroleum resources. Here, we show that sustainable and biodegradable SAP can be produced by acylation of the agricultural potato protein side-stream (PPC) with a non-toxic dianhydride (EDTAD). Treatment of the PPC yields a material with a water swelling capacity of ca. 2400%, which is ten times greater than the untreated PPC. Acylation was also performed on waste potato fruit juice (PFJ), i.e. before the industrial treatment to precipitate the PPC. The use of PFJ for the acylation implies a saving of 320 000 tons as CO2 in greenhouse gas emissions per year by avoiding the industrial drying of the PFJ to obtain the PPC. The acylated PPC shows biodegradation and resistance to mould growth. The possibilities to produce a biodegradable SAP from the PPC allows for future fabrication of environment-friendly and disposable daily-care products, e.g. diapers and sanitary pads.
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44.
  • Capezza, Antonio Jose, et al. (författare)
  • Carboxylated Wheat Gluten Proteins : A Green Solution for Production of Sustainable Superabsorbent Materials
  • 2020
  • Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 21:5, s. 1709-1719
  • Tidskriftsartikel (refereegranskat)abstract
    • Functionalized wheat gluten (WG) protein particles with the ability to absorb fluids within the superabsorbent range are presented. Ethyleneditetraacetic dianhydride (EDTAD), a nontoxic acylation agent, was used for the functionalization of the WG protein at higher protein content than previously reported and no additional chemical cross-linking. The 150-550 μm protein particles had 50-150 nm nanopores induced by drying. The EDTAD treated WG were able to absorb 22, 5, and 3 times of, respectively, water, saline and blood, per gram of dry material (g/g), corresponding to 1000, 150 and 100% higher values than for the as-received WG powder. The liquid retention capacity after centrifugation revealed that almost 50% of the saline liquid was retained within the protein network, which is similar to that for petroleum-based superabsorbent polymers (SAPs). An advantageous feature of these biobased particulate materials is that the maximum swelling is obtained within the first 10 min of exposure, that is, in contrast to many commercial SAP alternatives. The large swelling in a denaturation agent (6 M urea) solution (about 32 g/g) suggests that the secondary entangled/folded structure of the protein restricts protein network expansion and when disrupted allows the absorption of even higher amounts of liquid. The increased liquid uptake, utilization of inexpensive protein coproducts, easy scalable protocols, and absence of any toxic chemicals make these new WG-based SAP particles an interesting alternative to petroleum-based SAP in, for example, absorbent disposable hygiene products.
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45.
  • Capezza, Antonio Jose, et al. (författare)
  • Extrusion of Porous Protein-Based Polymers and Their Liquid Absorption Characteristics
  • 2020
  • Ingår i: Polymers. - : MDPI. - 2073-4360. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The production of porous wheat gluten (WG) absorbent materials by means of extrusion processing is presented for the future development of sustainable superabsorbent polymers (SAPs). Different temperatures, formulations, and WG compositions were used to determine a useful protocol that provides the best combination of porosity and water swelling properties. The most optimal formulation was based on 50 wt.% WG in water that was processed at 80 degrees C as a mixture, which provided a porous core structure with a denser outer shell. As a green foaming agent, food-grade sodium bicarbonate was added during the processing, which allowed the formation of a more open porous material. This extruded WG material was able to swell 280% in water and, due to the open-cell structure, 28% with non-polar limonene. The results are paving the way towards production of porous bio macromolecular structures with high polar/non-polar liquid uptake, using extrusion as a solvent free and energy efficient production technique without toxic reagents.
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46.
  • Casteigt, Benjamin, et al. (författare)
  • Atrial arrhythmias and patient-reported outcomes in adults with congenital heart disease : An international study
  • 2021
  • Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271 .- 1556-3871. ; 18:5, s. 793-800
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Atrial arrhythmias (ie, intra-atrial reentrant tachycardia and atrial fibrillation) are a leading cause of morbidity and hospitalization in adults with congenital heart disease (CHD). Little is known about their effect on quality of life and other patient-reported outcomes (PROs) in adults with CHD. Objective The purpose of this study was to assess the impact of atrial arrhythmias on PROs in adults with CHD and explore geographic variations. Methods Associations between atrial arrhythmias and PROs were assessed in a cross-sectional study of adults with CHD from 15 countries spanning 5 continents. A propensity-based matching weight analysis was performed to compare quality of life, perceived health status, psychological distress, sense of coherence, and illness perception in patients with and those without atrial arrhythmias. Results A total of 4028 adults with CHD were enrolled, 707 (17.6%) of whom had atrial arrhythmias. After applying matching weights, patients with and those without atrial arrhythmias were comparable with regard to age (mean 40.1 vs 40.2 years), demographic variables (52.5% vs 52.2% women), and complexity of CHD (15.9% simple, 44.8% moderate, and 39.2% complex in both groups). Patients with atrial arrhythmias had significantly worse PRO scores with respect to quality of life, perceived health status, psychological distress (ie, depression), and illness perception. A summary score that combines all PRO measures was significantly lower in patients with atrial arrhythmias (-3.3%; P = .0006). Differences in PROs were consistent across geographic regions. Conclusion Atrial arrhythmias in adults with CHD are associated with an adverse impact on a broad range of PROs consistently across various geographic regions.
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47.
  • Castro-Espin, Carlota, et al. (författare)
  • Dietary patterns related to biological mechanisms and survival after breast cancer diagnosis : results from a cohort study
  • 2023
  • Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 128, s. 1301-1310
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Inflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival.Methods: The diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality.Results: We included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR1–SD 0.92; 95%CI 0.87–0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR1–SD 1.06; 95%CI 1.00–1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality.Conclusions: Greater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors.
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48.
  • Chew, Michelle S., et al. (författare)
  • Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index
  • 2022
  • Ingår i: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 128:1, s. 26-36
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality.METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE.RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds.CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE.CLINICAL TRIAL REGISTRATION: NCT03436238.
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49.
  • Coguiec, Estelle, et al. (författare)
  • Photoperiodism and overwintering in boreal and sub-Arctic Calanus finmarchicus populations
  • 2023
  • Ingår i: Marine Ecology Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 712, s. 49-65
  • Tidskriftsartikel (refereegranskat)abstract
    • The copepod Calanus finmarchicus, a key species in the North Atlantic, generally spends the non-productive season by descending into deep waters and entering diapause, a physiological state characterized by reduced metabolism and arrested development. In the open ocean, overwintering depths are below 600 m, where temperature and light conditions are favourable to initiate diapause. However, C. finmarchicus has also been reported diapausing in areas with shallow water depth such as fjords, coastal waters and shelf seas. In these environments, the temperature and light conditions are different, and it has been hypothesized that under such conditions C. finmarchicus may remain active throughout winter. Here, we investigated changes in the swimming activity of C. finmarchicus from shallow fjords in the eastern North Atlantic during overwintering in response to ambient photoperiod. We conducted monthly experiments with populations from 2 fjords from different latitudes (sub-Arctic Ramfjord, 69 degrees N and boreal Loch Etive, 56 degrees N), measuring the locomotor activity of individual C. finmarchicus stage CVs exposed to a natural light:dark cycle. At both locations, peaks in activity in response to the light cycle were observed to shift from nocturnal during the early overwintering phase to diurnal during mid and late overwintering phase, with a minimal intensity observed during the mid-overwintering phase. In Ramfjord, activity and rhythmicity were generally lower than in Loch Etive. We conclude that C. finmarchicus remains active throughout its overwintering period when in shallow (<200 m) locations but down-regulates its locomotor activity during the main overwintering phase, which we describe as a winter resting state as distinct from classical diapause.
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50.
  • Crona, Beatrice, et al. (författare)
  • Four ways blue foods can help achieve food system ambitions across nations
  • 2023
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 616:7955, s. 104-112
  • Tidskriftsartikel (refereegranskat)abstract
    • Blue foods, sourced in aquatic environments, are important for the economies, livelihoods, nutritional security and cultures of people in many nations. They are often nutrient rich1, generate lower emissions and impacts on land and water than many terrestrial meats2, and contribute to the health3, wellbeing and livelihoods of many rural communities4. The Blue Food Assessment recently evaluated nutritional, environmental, economic and justice dimensions of blue foods globally. Here we integrate these findings and translate them into four policy objectives to help realize the contributions that blue foods can make to national food systems around the world: ensuring supplies of critical nutrients, providing healthy alternatives to terrestrial meat, reducing dietary environmental footprints and safeguarding blue food contributions to nutrition, just economies and livelihoods under a changing climate. To account for how context-specific environmental, socio-economic and cultural aspects affect this contribution, we assess the relevance of each policy objective for individual countries, and examine associated co-benefits and trade-offs at national and international scales. We find that in many African and South American nations, facilitating consumption of culturally relevant blue food, especially among nutritionally vulnerable population segments, could address vitamin B12 and omega-3 deficiencies. Meanwhile, in many global North nations, cardiovascular disease rates and large greenhouse gas footprints from ruminant meat intake could be lowered through moderate consumption of seafood with low environmental impact. The analytical framework we provide also identifies countries with high future risk, for whom climate adaptation of blue food systems will be particularly important. Overall the framework helps decision makers to assess the blue food policy objectives most relevant to their geographies, and to compare and contrast the benefits and trade-offs associated with pursuing these objectives.
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