| 1. |
- Sweeney, M. D., et al.
(författare)
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Vascular dysfunction-The disregarded partner of Alzheimer's disease
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:1, s. 158-167
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 2. |
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| 3. |
- Antel, C., et al.
(författare)
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Feebly-interacting particles : FIPs 2022 Workshop Report
- 2023
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Ingår i: European Physical Journal C. - : Springer. - 1434-6044 .- 1434-6052. ; 83:12
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Forskningsöversikt (refereegranskat)abstract
- Particle physics today faces the challenge of explaining the mystery of dark matter, the origin of matter over anti-matter in the Universe, the origin of the neutrino masses, the apparent fine-tuning of the electro-weak scale, and many other aspects of fundamental physics. Perhaps the most striking frontier to emerge in the search for answers involves new physics at mass scales comparable to familiar matter, below the GeV-scale, or even radically below, down to sub-eV scales, and with very feeble interaction strength. New theoretical ideas to address dark matter and other fundamental questions predict such feebly interacting particles (FIPs) at these scales, and indeed, existing data provide numerous hints for such possibility. A vibrant experimental program to discover such physics is under way, guided by a systematic theoretical approach firmly grounded on the underlying principles of the Standard Model. This document represents the report of the FIPs 2022 workshop, held at CERN between the 17 and 21 October 2022 and aims to give an overview of these efforts, their motivations, and the decadal goals that animate the community involved in the search for FIPs.
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| 4. |
- Lohr, J. M., et al.
(författare)
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United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)
- 2017
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 5:2, s. 153-199
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Tidskriftsartikel (refereegranskat)abstract
- Background:There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Methods: Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers. Results: The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as strong' and plenary voting revealed strong agreement' for 99 (98%) recommendations. Conclusions:The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research.
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| 5. |
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| 6. |
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| 7. |
- Verhaaren, C. B., et al.
(författare)
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Searches for Long-Lived Particles at the Future FCC-ee
- 2022
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Ingår i: Frontiers in Physics. - : Frontiers Media S.A.. - 2296-424X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The electron-positron stage of the Future Circular Collider, FCC-ee, is a frontier factory for Higgs, top, electroweak, and flavour physics. It is designed to operate in a 100 km circular tunnel built at CERN, and will serve as the first step towards ≥100 TeV proton-proton collisions. In addition to an essential and unique Higgs program, it offers powerful opportunities to discover direct or indirect evidence of physics beyond the Standard Model. Direct searches for long-lived particles at FCC-ee could be particularly fertile in the high-luminosity Z run, where 5 × 1012 Z bosons are anticipated to be produced for the configuration with two interaction points. The high statistics of Higgs bosons, W bosons and top quarks in very clean experimental conditions could offer additional opportunities at other collision energies. Three physics cases producing long-lived signatures at FCC-ee are highlighted and studied in this paper: heavy neutral leptons (HNLs), axion-like particles (ALPs), and exotic decays of the Higgs boson. These searches motivate out-of-the-box optimization of experimental conditions and analysis techniques, which could lead to improvements in other physics searches.
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| 8. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 9. |
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| 10. |
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| 11. |
- Farmer, A. D., et al.
(författare)
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Regional gastrointestinal contractility parameters using the wireless motility capsule : inter-observer reproducibility and influence of age, gender and study country
- 2018
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 47:3, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- Background:The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. Aims: To describe normative values for motility/contractility parameters across age, gender and testing centres.Methods:Healthy participants underwent a standardised wireless motility capsule assessment following an overnight fast and consumption of a meal of known nutritional content. Traces were divided into regions of interest and analysed using 2 software packages (MotiliGI and GIMS Data Viewer). Inter-observer agreement was independently assessed by 2 investigators.Results:Normative data for motility/contractility parameters (maximum amplitude, mean peak amplitude, contraction frequency and motility index) are presented for 107 individuals (62 male, median age 40years, range 18-78). MotiliGI-Gastric, small bowel and colonic maximal contraction amplitude correlated with age (r = .24, P = .01; r = .22, P = .02; and r = .2, P = .04 respectively). Small bowel motility index was higher in females than males (150.412 vs 122 +/- 7.6, P = .04). Inter-observer agreement was excellent for transit times, pH and contractility/motility parameters. GIMS Data viewer-Gastric, small bowel and colonic log(e) motility index correlated with the respective area under the contraction curve, total contractions, sum of amplitudes and contraction frequency (all r>.35, P < .0003) but not with transit times.Conclusions: Our analysis provides normative data for motility/contractility parameters. Log motility index summarises a number of measures. In future, the measurement of contractile activity with the wireless motility capsule may potentially aid in the diagnosis of disease states such as visceral myopathic disorders.
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| 12. |
- Krarup, Anne L., et al.
(författare)
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Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain.
- 2011
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Ingår i: Alimentary pharmacology & therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 33:10, s. 1113-22
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Tidskriftsartikel (refereegranskat)abstract
- Background Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor ‘transient receptor potential vanilloid 1’(TRPV1) are a potential drug class for GERD treatment. Aim To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain. Methods Twenty-two healthy men (20–31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. Data analysis: intention-to-treat. Results A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10–38%] and 28%, respectively (CI: 14–43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1–3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0–5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported ‘feeling cold’ and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4 ± 0.3 °C and 0.7 ± 0.3 °C, respectively, P < 0.05). Conclusions AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD (ClinicalTrials.gov identifier: NCT00711048).
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| 13. |
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| 14. |
- Pistocchi, A., et al.
(författare)
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Treatment of micropollutants in wastewater : Balancing effectiveness, costs and implications
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 850
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Tidskriftsartikel (refereegranskat)abstract
- In this contribution, we analyse scenarios of advanced wastewater treatment for the removal of micropollutants. By this we refer to current mainstream, broad spectrum processes including ozonation and sorption onto activated carbon. We argue that advanced treatment requires properly implemented tertiary (nutrient removal) treatment in order to be effective. We review the critical aspects of the main advanced treatment options, their advantages and disadvantages. We propose a quantification of the costs of implementing advanced treatment, as well as upgrading plants from secondary to tertiary treatment when needed, and we illustrate what drives the costs of advanced treatment for a set of standard configurations. We propose a cost function to represent the total costs (investment, operation and maintenance) of advanced treatment. We quantify the implications of advanced treatment in terms of greenhouse gas emissions. Based on the indicators of total toxic discharge, toxicity at the discharge points and toxicity across the stream network discussed in Pistocchi et al. (2022), we compare costs and effectiveness of different scenarios of advanced treatment. In principle the total toxic load and toxicity at the points of discharge could be reduced by about 75 % if advanced treatment processes were implemented virtually at all wastewater treatment plants, but this would entail costs of about 4 billion euro/year for the European Union as a whole. We consider a “compromise” scenario where advanced treatment is required at plants of 100 thousand population equivalents (PE) or larger, or at plants between 10 and 100 thousand PE if the dilution ratio at the discharge point is 10 or less. Under this scenario, the length of the stream network exposed to high toxicity would not increase significantly compared to the previous scenario, and the other indicators would not deteriorate significantly, while the costs would remain at about 1.5 billion Euro/year. Arguably, costs could be further reduced, without a worsening of water quality, if we replace a local risk assessment to generic criteria of plant capacity and dilution in order to determine if a WWTP requires advanced treatment.
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| 15. |
- Ud-din, Moeen, et al.
(författare)
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DIgestive COmplications in DIabetes : the DICODI population study
- 2023
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 58:1, s. 3-6
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDiabetes type 1 and type 2 may develop gastrointestinal complications e.g., gastroparesis and gastroenteropathy. Concomitant celiac disease and pancreatic exocrine insufficiency occur with high prevalence in diabetes and with symptomatic overlap. Consequently, it is a challenge to disentangle symptoms of these conditions and separate them from functional dyspepsia. We aim to develop a clinical decision-support tool to differentiate the underlying disease in a plethora of gastrointestinal symptoms.MethodsAn internet-based computerized survey will collect basic characteristics (diabetes type, age, gender, duration, HbA1c, treatment) and patient reported outcomes by validated questionnaires focusing on (1) gastroparesis using Gastroparesis Cardinal Symptom Index; (2) gastroenteropathy using Gastrointestinal Symptom Rating Scale; (3) celiac disease using Celiac Symptom Index and (4) pancreatic exocrine insufficiency with Pancreatic Exocrine Insufficiency Questionnaire. Logistic regression and multiple regression analyses will identify risk factors and gastrointestinal complications. Cluster analyses and machine learning will classify different symptoms and co-existing presentations, into a likely diagnosis. We seek biomarkers for autonomic neuropathy by characterizing development of retinopathy using the Visual Function Questionnaire-25 and peripheral neuropathy by the Michigan neuropathy questionnaire. Participants are re-examined yearly for disease progression over time.ResultsFrom focus group studies gastrointestinal symptoms are of major concern in diabetes. Potentially, estimates of symptom prevalence, risk factor identification and classifications of gastrointestinal complications can be unraveled for feedback to health care providers.ConclusionThe web-based DICODI project will open up possibilities to detect gastrointestinal complications of diabetes in a societal setting, benefitting people living with diabetes, health care professionals, and society.
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| 16. |
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| 17. |
- Abdullahi, Asli M., et al.
(författare)
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The present and future status of heavy neutral leptons
- 2023
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Ingår i: Journal of Physics G. - : Institute of Physics Publishing (IOPP). - 0954-3899 .- 1361-6471. ; 50:2
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Tidskriftsartikel (refereegranskat)abstract
- The existence of nonzero neutrino masses points to the likely existence of multiple Standard Model neutral fermions. When such states are heavy enough that they cannot be produced in oscillations, they are referred to as heavy neutral leptons (HNLs). In this white paper, we discuss the present experimental status of HNLs including colliders, beta decay, accelerators, as well as astrophysical and cosmological impacts. We discuss the importance of continuing to search for HNLs, and its potential impact on our understanding of key fundamental questions, and additionally we outline the future prospects for next-generation future experiments or upcoming accelerator run scenarios.
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| 18. |
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| 19. |
- Dominguez-Munoz, J. Enrique, et al.
(författare)
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Recommendations from the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis
- 2018
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 18:8, s. 847-854
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Forskningsöversikt (refereegranskat)abstract
- Background: In collaboration with United European Gastroenterology, the working group on ‘Harmonizing diagnosis and treatment of chronic pancreatitis across Europe’ (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach. Methods: Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system. Results: Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life. Conclusions: The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements.
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| 20. |
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| 21. |
- Frokjaer, J. B., et al.
(författare)
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Integrity of central nervous function in diabetes mellitus assessed by resting state EEG frequency analysis and source localization
- 2017
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Ingår i: Journal of Diabetes and Its Complications. - : Elsevier BV. - 1056-8727. ; 31:2, s. 400-406
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes mellitus (DM) is associated with structural and functional changes of the central nervous system. We used electroencephalography (EEG) to assess resting state cortical activity and explored associations to relevant clinical features. Multichannel resting state EEG was recorded in 27 healthy controls and 24 patients with longstanding DM and signs of autonomic dysfunction. The power distribution based on wavelet analysis was summarized into frequency bands with corresponding topographic mapping. Source localization analysis was applied to explore the electrical cortical sources underlying the EEG. Compared to controls, DM patients had an overall decreased EEG power in the delta (1-4 Hz) and gamma (30-45 Hz) bands. Topographic analysis revealed that these changes were confined to the frontal region for the delta band and to central cortical areas for the gamma band. Source localization analysis identified sources with reduced activity in the left postcentral gyrus for the gamma band and in right superior parietal lobule for the alpha 1 (8-10 Hz) band. DM patients with clinical signs of autonomic dysfunction and gastrointestinal symptoms had evidence of altered resting state cortical processing. This may reflect metabolic, vascular or neuronal changes associated with diabetes.
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| 22. |
- Graven-Nielsen, Christoffer S., et al.
(författare)
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Opioids in the Treatment of Chronic Idiopathic Diarrhea in Humans : A Systematic Review and Treatment Guideline
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:7
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Forskningsöversikt (refereegranskat)abstract
- In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid effects on gut function in chronic diarrhea. PubMed and Embase were searched regarding effects of opioid agonists on the gastrointestinal tract in humans with chronic or experimentally induced diarrhea. A total of 1472 relevant articles were identified and, after thorough evaluation, 11 clinical trials were included. Generally, studies reported a reduction in stool frequency and an increase in transit time during treatment with the opioid receptor agonists loperamide, asimadoline, casokefamide, and codeine compared with placebo. Loperamide and diphenoxylate significantly improved stool consistency compared with placebo, whereas asimadoline showed no such effects. Compared with placebo, loperamide treatment caused less abdominal pain and urgency. Asimadoline showed no significant subjective improvements, but fedotozine was superior to placebo in reducing abdominal pain and bloating in selected patients. Only two relevant studies were published within the last 20 years, and standardized endpoint measures are lacking. Most trials included few participants, and further evidence is needed from larger, prospective studies. Likewise, consensus is needed to standardize endpoints for stool frequency, transit time, and consistency to conduct future meta-analyses on opioids in management of chronic idiopathic diarrhea.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Shelemin, A., et al.
(författare)
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Nucleation and Growth of Magnetron-Sputtered Ag Nanoparticles as Witnessed by Time-Resolved Small Angle X-Ray Scattering
- 2019
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Ingår i: Particle and Particle Systems Characterization. - : John Wiley & Sons. - 0934-0866 .- 1521-4117.
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Tidskriftsartikel (refereegranskat)abstract
- Kinetic aspects of the synthesis of Ag nanoparticles (NPs) by magnetron sputtering are studied by in situ and time‐resolved small angle X‐ray scattering (SAXS). Part of the NPs are found to become confined within a capture zone at 1–10 mm from the surface of the target and circumscribed by the plasma ring. Three regimes of the NP growth are identified: 1) early growth at which the average NP diameter rapidly increases to 90 nm; 2) cycling instabilities at which the SAXS signal periodically fluctuates either due to expelling of large NPs from the capture zone or due to the axial rotation of the NP cloud; and 3) steady‐state synthesis at which stable synthesis of the NPs is achieved. The NP confinement within the capture zone is driven by the balance of forces, the electrostatic force being dominant. On reaching the critical size, large NPs acquire an excessive charge and become expelled from the capture zone via the electrostatic interactions. As a result, significant NP deposits are formed on the inner walls of the aggregation chamber as well as in the central area of the target.
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| 27. |
- Tack, J., et al.
(författare)
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An expert consensus definition of failure of a treatment to provide adequate relief (F-PAR) for chronic constipation - an international Delphi survey
- 2017
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Ingår i: Alimentary Pharmacology & Therapeutics. - : Wiley. - 0269-2813. ; 45:3, s. 434-442
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Tidskriftsartikel (refereegranskat)abstract
- Background As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better. To establish the definition of failure of a treatment to provide adequate relief (F-PAR) to support this management and referral process in patients with chronic constipation. We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms. The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom-severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed). We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief.
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| 28. |
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| 29. |
- Brock, C., et al.
(författare)
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Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:11, s. 3698-3705
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVELong-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal symptoms.RESEARCH DESIGN AND METHODSFifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (SF-36 Short Form Survey) were collected.RESULTSDiabetic patients had autonomous neuropathy, evidenced by decreased electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients were less sensitive to painful stimulation (P = 0.007), had prolonged latencies of evoked potentials (P 0.001), and showed diminished amplitude of the N2-P2 component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P < 0.02), and the shift (expressed in mm) correlated negatively with physical health (P < 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P = 0.03). Cingulate source shift was correlated negatively with physical health (P = 0.005) and positively with postprandial fullness (P 0.001).CONCLUSIONSThis study provides evidence for interaction between autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved treatment modalities targeting pharmacological neuroprotection or neuromodulation.
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| 30. |
- Brock, Christina, et al.
(författare)
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The Retinal Nerve Fiber Layer Thickness Is Associated with Systemic Neurodegeneration in Long-Term Type 1 Diabetes
- 2023
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Ingår i: Translational Vision Science & Technology. - : Association for Research in Vision and Ophthalmology (ARVO). - 2164-2591. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine whether the retinal nerve fiber layer thickness can be used as an indicator for systemic neurodegeneration in diabetes.Methods: We used existing data from 38 adults with type 1 diabetes and established polyneuropathy. Retinal nerve fiber layer thickness values of four scanned quadrants (superior, inferior, temporal, and nasal) and the central foveal thickness were extracted directly from optical coherence tomography. Nerve conduction velocities were recorded using standardized neurophysiologic testing of the tibial and peroneal motor nerves and the radial and median sensory nerves, 24-hour electrocardiographic recordings were used to retrieve time- and frequency-derived measures of heart rate variability, and a pain catastrophizing scale was used to assess cognitive distortion.Results: When adjusted for hemoglobin A1c, the regional thickness of the retinal nerve fiber layers was (1) positively associated with peripheral nerve conduction velocities of the sensory and motor nerves (all P < 0.036), (2) negatively associated with time and frequency domains of heart rate variability (all P < 0.033), and (3) negatively associated to catastrophic thinking (all P < 0.038).Conclusions: Thickness of the retinal nerve fiber layer was a robust indicator for clinically meaningful measures of peripheral and autonomic neuropathy and even for cognitive comorbidity.Translational Relevance: The findings indicate that the thickness of the retinal nerve fiber layer should be studied in adolescents and people with prediabetes to determine whether it is useful to predict the presence and severity of systemic neurodegeneration.
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| 31. |
- Drewes, A. M., et al.
(författare)
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Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction-Recommendations of the Nordic Working Group
- 2016
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Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 11, s. 111-122
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Opioid-induced bowel dysfunction (OIBD) is an increasing problem due to the common use of opioids for pain worldwide. It manifests with different symptoms, such as dry mouth, gastro-oesophageal reflux, vomiting, bloating, abdominal pain, anorexia, hard stools, constipation and incomplete evacuation. Opioid-induced constipation (OIC) is one of its many symptoms and probably the most prevalent. The current review describes the pathophysiology, clinical implications and treatment of OIBD. Methods: The Nordic Working Group was formed to provide input for Scandinavian specialists in multiple, relevant areas. Seven main topics with associated statements were defined. The working plan provided a structured format for systematic reviews and included instructions on how to evaluate the level of evidence according to the GRADE guidelines. The quality of evidence supporting the different statements was rated as high, moderate or low. At a second meeting, the group discussed and voted on each section with recommendations (weak and strong) for the statements. Results: The literature review supported the fact that opioid receptors are expressed throughout the gastrointestinal tract. When blocked by exogenous opioids, there are changes in motility, secretion and absorption of fluids, and sphincter function that are reflected in clinical symptoms. The group supported a recent consensus statement for OIC, which takes into account the change in bowel habits for at least one week rather than focusing on the frequency of bowel movements. Many patients with pain receive opioid therapy and concomitant constipation is associated with increased morbidity and utilization of healthcare resources. Opioid treatment for acute postoperative pain will prolong the postoperative ileus and should also be considered in this context. There are no available tools to assess OIBD, but many rating scales have been developed to assess constipation, and a few specifically address OIC. A clinical treatment strategy for OIBD/OIC was proposed and presented in a flowchart. First-line treatment of OIC is conventional laxatives, lifestyle changes, tapering the opioid dosage and alternative analgesics. Whilst opioid rotation may also improve symptoms, these remain unalleviated in a substantial proportion of patients. Should conventional treatment fail, mechanism-based treatment with opioid antagonists should be considered, and they show advantages over laxatives. It should not be overlooked that many reasons for constipation other than OIBD exist, which should be taken into consideration in the individual patient. Conclusion and implications: It is the belief of this Nordic Working Group that increased awareness of adverse effects and OIBD, particularly OIC, will lead to better pain treatment in patients on opioid therapy. Subsequently, optimised therapy will improve quality of life and, from a socio-economic perspective, may also reduce costs associated with hospitalisation, sick leave and early retirement in these patients.
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| 32. |
- Drewes, Christina, et al.
(författare)
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Quality of life in patients with intracranial tumors: does tumor laterality matter?
- 2016
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 125:6, s. 1400-1407
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Traditionally, the dominant (usually left) cerebral hemisphere is regarded as the more important one, and everyday clinical decisions are influenced by this view. However, reported results on the impact of lesion laterality are inconsistent in the scarce literature on quality of life (QOL) in patients with brain tumors. The authors aimed to study which cerebral hemisphere is the most important to patients with intracranial tumors with respect to health-related QOL (HRQOL). METHODS Two hundred forty-eight patients with unilateral, unifocal gliomas or meningiomas scheduled for primary surgery were included in this prospective cohort study. Generic HRQOL was measured using the EQ-5D-3L questionnaire preoperatively and after 4-6 weeks. Cross-sectional and longitudinal analyses of data were performed. RESULTS Tumor volumes were significantly larger in right-sided tumors at diagnosis, and language or speech problems were more common in left-sided lesions. Otherwise, no differences existed in baseline data. The median EQ-5D-3L index was 0.73 (range -0.24 to 1.00) in patients with right-sided tumors and 0.76 (range -0.48 to 1.00) in patients with left-sided tumors (p = 0.709). Due to the difference in tumor volumes at baseline, histopathology and tumor volumes were matched in 198 patients. EQ-5D-3L index scores in this 1:1 matched analysis were 0.74 (range -0.7 to 1.00) for patients with right-sided and 0.76 (range -0.48 to 1.00) for left-sided lesions (p = 0.342). In the analysis of longitudinal data, no association was found between tumor laterality and postoperative EQ-5D-3L index scores (p = 0.957) or clinically significant change in HRQOL following surgery (p = 0.793). CONCLUSIONS In an overall patient-reported QOL perspective, tumor laterality does not appear to be of significant importance for generic HRQOL in patients with intracranial tumors. This may imply that right-sided cerebral functions are underestimated by clinicians.
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| 33. |
- Frokjaer, J. B., et al.
(författare)
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Macrostructural Brain Changes in Patients with Longstanding Type 1 Diabetes Mellitus - a Cortical Thickness Analysis Study
- 2013
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Ingår i: Experimental and Clinical Endocrinology & Diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 121:6, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Longstanding diabetes mellitus (DM) is associated with the risk of complications Methods: 15 patients with longstanding (average 24.6 years) type 1 DM and 20 healthy controls were Results: No differences between patients and controls were found in regard to number of white matter Conclusions: Patients with longstanding type 1 diabetes showed cortical thinning involving sensory
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| 34. |
- Frøkjaer, J B, et al.
(författare)
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Esophageal distension parameters as potential biomarkers of impaired gastrointestinal function in diabetes patients.
- 2012
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Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 24:11
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal (GI) symptoms, such as nausea, vomiting, bloating, postprandial fullness, and abdominal pain, are frequent in patients with diabetes mellitus (DM). The pathogenesis is complex and multi-factorial. To determine easy accessible and valid biomarkers for disordered GI function in DM patients, we aimed to study esophageal mechanical parameters and their relation to symptoms typically arising from the digestive tract.
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| 35. |
- Jansson-Rehnberg, Ann-Sofie, et al.
(författare)
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Diarrhoea of unknown cause: medical treatment in a stepwise manner Management of Idiopathic Diarrhoea Based on Experience of Step-Up Medical Treatment
- 2024
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Ingår i: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. - : TAYLOR & FRANCIS LTD. - 0036-5521 .- 1502-7708.
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Forskningsöversikt (refereegranskat)abstract
- The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.
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| 36. |
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| 37. |
- Krarup, Anne L., et al.
(författare)
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Exploration of the effects of gender and mild esophagitis on esophageal pain thresholds in the normal and sensitized state of asymptomatic young volunteers
- 2013
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 25:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Clinical data suggest gender differences in gastrointestinal pain, but very little experimental data exist. Esophageal painful thresholds to mechanical, thermal, electric, and chemical stimuli can be measured with the esophageal multimodal pain model. The aim was to measure the effect of gender and mild esophagitis on esophageal pain perception. Methods Thirty-five healthy asymptomatic volunteers [19 men, median age 29 (22-56 years)] underwent upper GI endoscopy, 24 h pH/impedance measurement, and multimodal esophageal pain stimulation before and after sensitization with acid. Stimulus intensities at painful thresholds were recorded. Key Results Men had higher pain thresholds (PT) to mechanical stimulation (mean volume: men 20.9 +/- 10 mL vs women 15.2 +/- 6.8 mL, P = 0.02) and more men tolerated the maximum acid challenge (58% vs 20%, P = 0.03). There were no differences between genders for PT to 1 thermal stimulation [mean stimulation time (men, women): heat; 20 +/- 5 s vs 21 +/- 6 s or cold; 33.3 +/- 20.1 s vs 20.7 +/- 21.4 s, P > 0.2], 2 electrical current (mean current: men 17.6 +/- 9.2 mA vs women 12.9 +/- 3.7 mA, P = 0.11), or 3 acid volume [median volume: men 200 (20; 200) mL vs women 133 (40; 200) mL, P = 0.2]. Fifteen asymptomatic subjects had mild esophagitis (10 men, all Los Angeles A). There were no differences in esophageal PT between subjects with normal endoscopy or mild esophagitis (all P > 0.3). Conclusions & Inferences The effects of gender and mild esophagitis on esophageal multimodal pain perception have been measured in asymptomatic volunteers. The study suggests that gender, not mild esophagitis, tends to influence mechanical and chemical esophageal pain.
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| 38. |
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| 39. |
- Lelic, D., et al.
(författare)
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Brain networks encoding rectal sensation in type 1 diabetes
- 2013
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 237, s. 96-105
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Tidskriftsartikel (refereegranskat)abstract
- Introduction It has been shown that patients with type 1 diabetes mellitus and gastrointestinal (GI) symptoms have abnormal processing of sensory information following stimulation in the oesophagus. In order to find less invasive stimuli to study visceral afferent processing and to further elaborate the gut–brain network in diabetes, we studied brain networks following rectal electrical stimulations. Methods Twelve type 1 diabetes patients with GI symptoms and twelve healthy controls were included. A standard ambulatory 24-h electrocardiography was performed. 122-channel-evoked brain potentials to electrical stimulation in the rectum were recorded. Brain source-connectivity analysis was done. GI symptoms were assessed with the gastroparesis cardinal symptom index and quality of life (QOL) with SF-36. Any changes in brain source connectivity were correlated to duration of the disease, heart beat-to-beat intervals (RRs), clinical symptoms, and QOL of the patients. Results Diabetic patients with GI symptoms showed changes relative to controls in the operculum–cingulate network with the operculum source localized deeper and more anterior (P ⩽ 0.001) and the cingulate source localized more anterior (P = 0.03). The shift of operculum source was correlated with the duration of the disease, severity of GI symptoms, and decreased RR (P < 0.05). The shift of the cingulate source was correlated with the mental QOL (P = 0.04). In healthy controls, the contribution of the cingulate source to the network was higher than the contribution of the operculum source (P ⩽ 0.001), whereas in patients the contribution of the two sources was comparable. Conclusion This study gives further evidence for CNS involvement in diabetes. Since network reorganizations were correlated to GI symptoms, irregularities of rectal-evoked potentials can be viewed as a proxy for abnormal bottom-up visceral afferent processing. The network changes might serve as a biomarker for disturbed sensory visceral processing of GI symptoms in diabetes patients.
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| 40. |
- Lelic, D, et al.
(författare)
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The brain networks encoding visceral sensation in patients with gastrointestinal symptoms due to diabetic neuropathy.
- 2014
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Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 26:1, s. 46-58
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence points to association between long-term diabetes mellitus and abnormal brain processing. The aim of this study was to investigate central changes due to electrical stimulation in esophagus in patients with upper gastrointestinal (GI) symptoms due to diabetic neuropathy.
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| 41. |
- Olausson, Eva A, et al.
(författare)
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Measurement of gastric emptying by radiopaque markers in patients with diabetes: correlation with scintigraphy and upper gastrointestinal symptoms
- 2013
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Scintigraphy, the gold standard to measure gastric emptying, is expensive and not widely available. Therefore, we compared emptying of radiopaque markers (ROM) from the stomach, by use of fluoroscopy, with scintigraphy in patients with insulin-treated diabetes. Methods On the same day we measured gastric emptying of 20 ROM using fluoroscopy and scintigraphic emptying of a standard solid meal. The subjects also completed a validated gastrointestinal (GI) symptom questionnaire. Key Results We included 115 patients with insulin-treated diabetes (median age 53, range 21–69 years; 59 women). A moderately strong correlation was demonstrated between scintigraphic (% retained at 2 h) and ROM emptying (markers retained at 6 h) (r = 0.47; P < 0.0001). Eighty-three patients had delayed gastric emptying with scintigraphy, whereas only 29 patients had delayed emptying of ROM. Of the 29 patients with delayed emptying of ROM, 28 also had delayed scintigraphic emptying. The sensitivity and specificity of the ROM test was 34% and 97%, respectively. Significant correlations were only noted between scintigraphic gastric emptying and GI symptom severity, with the strongest correlations for fullness/early satiety (r = 0.34; P < 0.001) and nausea/vomiting (r = 0.30; P < 0.001). Conclusions & Inferences A gastric emptying test with ROM is a widely available screening method to detect delayed gastric emptying in patients with diabetes, where a positive result seems reliable. However, a normal ROM test does not exclude delayed gastric emptying, and if the clinical suspicion of gastroparesis remains, scintigraphy should be performed. Results from scintigraphy also correlate with GI symptom severity, which ROM test did not.
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| 42. |
- Olausson, Eva A, et al.
(författare)
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Postprandial Plasma Glucose Response and Gastrointestinal Symptom Severity in Patients With Diabetic Gastroparesis.
- 2014
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Ingår i: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 8:4, s. 881-888
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Tidskriftsartikel (refereegranskat)abstract
- Gastroparesis is a well-known diabetic complication. The pathogenesis is not fully understood. However, it is important to early diagnose these patients. This study evaluated the plasma glucose response after a test meal, and gastrointestinal (GI) symptom severity in patients with clinical suspicion of diabetic gastroparesis, and assessed its usefulness to predict gastroparesis. In all, 83 subjects with insulin-treated diabetes mellitus (DM) type 1 and 2 were included; 53 subjects had gastroparesis and 30 had normal gastric emptying determined by gastric scintigraphy. GI symptom severity during the preceding 2 weeks was evaluated with a validated questionnaire. The test meal consisted of 100 g meat, 40 g pasta, 150 g carrot, and 5 g oil. The subjects ingested the meal under fasting conditions, and plasma glucose was followed during 180 minutes. Patients with gastroparesis demonstrated a blunted plasma glucose response after a test meal versus patients with normal gastric emptying (P < .005), reflected by lower maximum increase in plasma glucose response and incremental area under the curve of the plasma glucose, but a similar time to the maximum plasma glucose level. All GI symptoms were more severe in patients with gastroparesis. GI symptom severity had the best discriminative value to identify patients with gastroparesis with an area under the receiver operating curve of 0.83 (optimal cutoff: sensitivity 87%, specificity 80%). Patients with diabetic gastroparesis have a blunted postprandial plasma glucose response. Combining this information with the presence of GI symptoms can help clinicians identify diabetic patients with gastroparesis.
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| 43. |
- Sagberg, Lisa M., et al.
(författare)
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Accuracy of operating neurosurgeons' prediction of functional levels after intracranial tumor surgery.
- 2017
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 126:4, s. 1173-1180
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE In the absence of practical and reliable prognostic tools in intracranial tumor surgery, decisions regarding patient selection, patient information, and surgical management are usually based on neurosurgeons' clinical judgment, which may be influenced by personal experience and knowledge. The objective of this study was to assess the accuracy of the operating neurosurgeons' predictions about patients' functional levels after intracranial tumor surgery. METHODS In a prospective single-center study, the authors included 299 patients who underwent intracranial tumor surgery between 2011 and 2015. The operating neurosurgeons scored their patients' expected functional level at 30 days after surgery using the Karnofsky Performance Scale (KPS). The expected KPS score was compared with the observed KPS score at 30 days. RESULTS The operating neurosurgeons underestimated their patients' future functional level in 15% of the cases, accurately estimated their functional levels in 23%, and overestimated their functional levels in 62%. When dichotomizing functional levels at 30 days into dependent or independent functional level categories (i.e., KPS score < 70 or ≥ 70), the predictive accuracy was 80%, and the surgeons underestimated and overestimated in 5% and 15% of the cases, respectively. In a dichotomization based on the patients' ability to perform normal activities (i.e., KPS score < 80 or ≥ 80), the predictive accuracy was 57%, and the surgeons underestimated and overestimated in 3% and 40% of cases, respectively. In a binary regression model, the authors found no predictors of underestimation, whereas postoperative complications were an independent predictor of overestimation (p = 0.01). CONCLUSIONS Operating neurosurgeons often overestimate their patients' postoperative functional level, especially when it comes to the ability to perform normal activities at 30 days. This tendency to overestimate surgical outcomes may have implications for clinical decision making and for the accuracy of patient information.
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| 44. |
- Schwartzkopf, Matthias, et al.
(författare)
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Real-time insight into nanostructure evolution during the rapid formation of ultra-thin gold layers on polymers
- 2021
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Ingår i: Nanoscale Horizons. - : ROYAL SOC CHEMISTRY. - 2055-6764 .- 2055-6756. ; 6:2, s. 132-138
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Tidskriftsartikel (refereegranskat)abstract
- Ultra-thin metal layers on polymer thin films attract tremendous research interest for advanced flexible optoelectronic applications, including organic photovoltaics, light emitting diodes and sensors. To realize the large-scale production of such metal-polymer hybrid materials, high rate sputter deposition is of particular interest. Here, we witness the birth of a metal-polymer hybrid material by quantifying in situ with unprecedented time-resolution of 0.5 ms the temporal evolution of interfacial morphology during the rapid formation of ultra-thin gold layers on thin polystyrene films. We monitor average non-equilibrium cluster geometries, transient interface morphologies and the effective near-surface gold diffusion. At 1 s sputter deposition, the polymer matrix has already been enriched with 1% gold and an intermixing layer has formed with a depth of over 3.5 nm. Furthermore, we experimentally observe unexpected changes in aspect ratios of ultra-small gold clusters growing in the vicinity of polymer chains. For the first time, this approach enables four-dimensional insights at atomic scales during the gold growth under non-equilibrium conditions.
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| 45. |
- Softeland, E., et al.
(författare)
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Rectal Sensitivity in Diabetes Patients with Symptoms of Gastroparesis
- 2014
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Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6745 .- 2314-6753.
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Tidskriftsartikel (refereegranskat)abstract
- In a clinical setting, diabetic autonomic complications (cardiac, gastrointestinal, urogenital, etc.) are often handled as separate entities. We investigated rectal sensitivity to heat, mechanical distension, and electrical stimulations in 20 patients with diabetes and symptoms of gastroparesis, to evaluate the extent of visceral neuronal damage. Furthermore, to evaluate the relation between the nervous structures we examined gastric emptying and cardiac autonomic function with the hypothesis being an association between these. We found that 60% of patients had delayed gastric empting. Rectal hyposensitivity was a general finding as they tolerated 67% higher thermal, 42% more mechanical, and 33% higher electrical current intensity compared to healthy controls. In patients, most heart rate variability parameters were reduced; they reported significantly more gastrointestinal symptoms and a reduced quality of life in all SF-36 domains. Shortened RR interval correlated with reduced rectal temperature sensitivity, and gastric retention rate was negatively associated with symptoms of nausea and vomiting. To conclude, in these patients with signs and symptoms of diabetic gastroparesis, rectal sensitivity was reduced, and heart rate variability was impaired. Thus, we suggest regarding diabetic autonomic neuropathy as a diffuse disorder. Symptoms of widespread autonomic dysfunction and sensory disorders should be expected and treated in these patients.
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| 46. |
- Søfteland, Eirik, et al.
(författare)
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Association between visceral, cardiac and sensorimotor polyneuropathies in diabetes mellitus.
- 2014
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 28:3, s. 370-7
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal complaints are common in diabetes mellitus. However, its association to peripheral sensorimotor and autonomic neuropathies is not well investigated. The aim was to assess skin, muscle, bone and visceral sensitivity in diabetes patients with sensorimotor neuropathy, and correlate these with gastrointestinal symptoms and degree of cardiac autonomic neuropathy.
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| 47. |
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