| 1. |
- Gunst, Jesper D., et al.
(författare)
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Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
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| 2. |
- Chotiwan, Nunya, et al.
(författare)
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Type I interferon shapes brain distribution and tropism of tick-borne flavivirus
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Viral tropism within the brain and the role(s) of vertebrate immune response to neurotropic flaviviruses infection is largely understudied. We combine multimodal imaging (cm-nm scale) with single nuclei RNA-sequencing to study Langat virus in wildtype and interferon alpha/beta receptor knockout (Ifnar-/-) mice to visualize viral pathogenesis and define molecular mechanisms. Whole brain viral infection is imaged by Optical Projection Tomography coregistered to ex vivo MRI. Infection is limited to grey matter of sensory systems in wildtype mice, but extends into white matter, meninges and choroid plexus in Ifnar-/- mice. Cells in wildtype display strong type I and II IFN responses, likely due to Ifnb expressing astrocytes, infiltration of macrophages and Ifng-expressing CD8+ NK cells, whereas in Ifnar-/-, the absence of this response contributes to a shift in cellular tropism towards non-activated resident microglia. Multimodal imaging-transcriptomics exemplifies a powerful way to characterize mechanisms of viral pathogenesis and tropism.
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| 3. |
- Gerdle, Björn, et al.
(författare)
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Biochemical alterations in the trapezius muscle of patients with chronic whiplash associated disorders (WAD) - A microdialysis study
- 2008
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 12:1, s. 82-93
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms behind the development of chronic trapezius myalgia in patients with whiplash associated disorders (WAD) appear to involve both peripheral and central components, but the specific contribution of alterations in muscle is not clear. Female patients with WAD and involvement of trapezius (N = 22) and female controls (N = 20; CON) were studied during an experiment compromised of rest (baseline), 20 min repetitive low.-force exercise and 120 min recovery. Their interstitial concentrations of serotonin (5-HT), glutamate, lactate, pyruvate, potassium, interleukin-6 (IL-6), and blood flow were determined in the trapezius muscle using a microdialysis technique. Pressure pain thresholds (PPT) over trapezius and tibialis anterior muscles were also assessed. In WAD, we found signs of generalized hypersensitivity according to PPT. The WAD group had significantly higher interstitial [IL-6] and [5-HT] in the trapezius than the CON. [Pyruvate] was overall significantly lower in WAD, and with lactate it showed another time-pattern throughout the test. In the multivariate regression analysis of pain intensity [5-HT] was the strongest regressor and positively correlated with pain intensity in WAD. In addition, blood flow, [pyruvate], and [potassium] influenced the pain intensity in a complex time dependent way. These findings may indicate that peripheral nociceptive processes are activated in WAD with generalized hypersensitivity for pressure and they are not identical with those reported in chronic work-related trapezius myalgia, which could indicate different pain mechanisms.
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| 4. |
- Gerdle, Björn, et al.
(författare)
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Bradykinin and kallidin levels in the trapezius muscle in patients with work-related trapezius myalgia, in patients with whiplash associated pain, and in healthy controls - A microdialysis study of women
- 2008
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Ingår i: PAIN. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959. ; 139:3, s. 578-587
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Tidskriftsartikel (refereegranskat)abstract
- The origins of chronic Muscle pain development and maintenance are debated regarding the relative contributions of peripheral nociception and central pain processing. Bradykinin (BKN) and kallidin (KAL) have been suggested to be algesic kinins involved in muscle pain. This in vivo study investigates whether there were significant differences in interstitial muscle concentrations of BKN and KAL between chronic work-related trapezius myalgia (TM), chronic whiplash associated disorders (WAD), and healthy controls (CON). These subjects were studied Lit rest, during a 20-min repetitive low-force exercise and recovery. The interstitial concentrations of BKN and KAL of trapezius were determined using the microdialysis technique. The interstitial concentration of KAL was overall significantly higher in TM than in CON. [KAL] and [BKN] increased significantly during the brief exercise in all groups. The increase in [BKN] during exercise was significantly higher in TM than in the other two groups,whereas the increase in [KAL] during exercise was highest in WAD. In chronic pain, positive correlations existed between the two kinins and the difference in pain intensity between recovery and baseline. In this in vivo study of two groups of patients with chronic pain clinically involving the trapezius muscle, we found alterations - most prominent in TM in the interstitial concentrations of BKN and KAL. The results indicated that the two kinins were involved in aspects of hyperalgesia.
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| 5. |
- Gerdle, Björn, et al.
(författare)
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INCREASED INTERSTITIAL CONCENTRATIONS OF PYRUVATE AND LACTATE IN THE TRAPEZIUS MUSCLE OF PATIENTS WITH FIBROMYALGIA: A MICRODIALYSIS STUDY
- 2010
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Ingår i: Journal of Rehabilitation Medicine. - : Foundation for Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 42:7, s. 679-687
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to compare the interstitial concentrations of pyruvate, lactate and glutamate in the trapezius muscle between patients with fibromyalgia syndrome and healthy controls. Design: Comparative cross-sectional study. Subjects: Patients with fibromyalgia (n=19) and healthy controls (n=19); all women. Methods: Subjects answered a questionnaire about different aspects of pain. Pressure pain thresholds over the trapezius and tibialis anterior muscles were determined. The interstitial concentrations of pyruvate, lactate and glutamate were determined in the resting trapezius muscle by the microdialysis technique, with samples collected every hour for 5 consecutive hours. Pain intensity was also rated. Results: Significantly higher interstitial concentrations of pyruvate and lactate were found in patients with fibromyalgia syndrome. The multivariate regression analyses of group membership and pressure pain thresholds of the trapezius confirmed the importance of pyruvate and lactate. Conclusion: Different mechanisms that may increase pyruvate and lactate in patients with fibromyalgia syndrome are discussed. Improved understanding of peripheral muscle alterations in patients with fibromyalgia syndrome could lead to mechanism-based rehabilitation.
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| 6. |
- Heir, Trond, et al.
(författare)
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Tsunami-affected Scandinavian tourists : Disaster exposure and post-traumatic stress symptoms
- 2011
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 65:1, s. 9-15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of short- and long-term mental effects of natural disasters have reported a high prevalence of post-traumatic stress. Less is known about disaster-exposed tourists repatriated to stable societies. Aims: To examine the association between exposure to the 2004 Southeast Asian tsunami and symptoms of post-traumatic stress in three Scandinavian tourist populations. Methods: Postal survey of Norwegian, Danish and Swedish Southeast Asia tourists registered by the police when arriving at national airports. Follow-up time was 6 (Norway), 10 (Denmark) and 14 months (Sweden) post-disaster; 6772 individuals were included and categorized according to disaster exposure: danger exposed (caught or chased by the waves), non-danger exposed (other disaster-related stressors) and non-exposed. Outcome measures were the Impact of Event Scale-Revised (IES-R) and Post Traumatic Stress Disorder Check List (PCL). Results: Danger exposed reported more post-traumatic stress than non-danger exposed, and the latter reported more symptoms than non-exposed (each P<0.001). Comparison of the Norwegian and Swedish data suggested that symptoms were attenuated at 14 months follow-up (P<0.001). Female gender and low education, but not age, predicted higher levels of symptoms. Conclusions: Disaster-exposed tourists repatriated to unaffected home environments show long-term post-traumatic stress disorder symptoms related to the severity of exposure.
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| 7. |
- Mallalieu, Adam, 1995, et al.
(författare)
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Sustainability criteria for introducing new technologies in low-income contexts
- 2024
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Ingår i: Proceedings of the Design Society. - : Cambridge University Press. ; 4, s. 1359-1368
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Konferensbidrag (refereegranskat)abstract
- Introducing new technologies in low-income contexts have potential for positive social impact, and such efforts are made by humanitarian engineering non-govermental organisations (NGOs). The impact can increase if a systemic sustainability perspective is considered in the design process. Sustainability criteria are identified using a literature study combined with an empirical study together with a Swedish NGO. These criteria are synthesized into a simplified Sustainability Fingerprint tool which is evaluated and deemed to be useful when introducing new technologies in low-income contexts. © 2024 Proceedings of the Design Society. All rights reserved.
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| 8. |
- Rosendal, Ebba, et al.
(författare)
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Serine Protease Inhibitors Restrict Host Susceptibility to SARS-CoV-2 Infections
- 2022
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus disease 2019, COVID-19, is a complex disease with a wide range of symptoms from asymptomatic infections to severe acute respiratory syndrome with lethal outcome. Individual factors such as age, sex, and comorbidities increase the risk for severe infections, but other aspects, such as genetic variations, are also likely to affect the susceptibility to SARS-CoV-2 infection and disease severity. Here, we used a human 3D lung cell model based on primary cells derived from multiple donors to identity host factors that regulate SARS-CoV-2 infection. With a transcriptomics-based approach, we found that less susceptible donors show a higher expression level of serine protease inhibitors SERPINA1, SERPINE1, and SERPINE2, identifying variation in cellular serpin levels as restricting host factors for SARS-CoV-2 infection. We pinpoint their antiviral mechanism of action to inhibition of the cellular serine protease, TMPRSS2, thereby preventing cleavage of the viral spike protein and TMPRSS2-mediated entry into the target cells. By means of single-cell RNA sequencing, we further locate the expression of the individual serpins to basal, ciliated, club, and goblet cells. Our results add to the importance of genetic variations as determinants for SARS-CoV-2 susceptibility and suggest that genetic deficiencies of cellular serpins might represent risk factors for severe COVID-19. Our study further highlights TMPRSS2 as a promising target for antiviral intervention and opens the door for the usage of locally administered serpins as a treatment against COVID-19.
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| 9. |
- Rosendal, Lars, et al.
(författare)
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Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise
- 2005
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 98:2, s. 477-481
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin (IL)-6, which is released from muscle tissue during intense exercise, possesses important metabolic and probably anti-inflammatory properties. To evaluate the IL-6 response to low-intensity exercise, we conducted two studies: 1) a control study with insertion of microdialysis catheters in muscle and determination of interstitial muscle IL-6 response over 2 h of rest and 2) an exercise study to investigate the IL-6 response to 20 min of repetitive low-force exercise. In both studies, a microdialysis catheter (cutoff: 3,000 kDa) was inserted into the upper trapezius muscle of six male subjects, and the catheters were perfused with Ringer-acetate at 5 mul/min. Venous plasma samples were taken in the exercise study. The insertion of microdialysis catheters into muscle resulted in an increase in IL-6 from 8 +/- 0 to 359 +/- 171 and 484 +/- 202 pg/ml after 65 and 110 min, respectively (P less than 0.001). Similarly, in the exercise study, IL-6 increased to 289 +/- 128 pg/ml after a 55-min rest (P less than 0.001). During the subsequent repetitive low-force exercise, muscle IL-6 further increased to 1,246 +/- 461 pg/ml and reached 2,132 +/- 477 pg/ml after a 30-min recovery ( all P less than 0.001). In contrast to this, plasma IL-6 did not significantly change in response to exercise. We conclude that upper extremity, low-intensity exercise results in a substantial increase in IL-6 in the interstitium of the stabilizing trapezius muscle, whereas no change is seen for plasma IL-6.
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| 10. |
- Sjogaard, Gisela, et al.
(författare)
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Muscle oxygenation and glycolysis in females with trapezius myalgia during stress and repetitive work using microdialysis and NIRS
- 2010
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Ingår i: EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 108:4, s. 657-669
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this investigation was to study female workers active in the labour market for differences between those with trapezius myalgia (MYA) and without (CON) during repetitive pegboard (PEG) and stress (STR) tasks regarding (1) relative muscle load, (2) trapezius muscle blood flow, (3) metabolite accumulation, (4) oxygenation, and (5) pain development. Among 812 female employees (age 30-60 years) at 7 companies with high prevalence of neck/shoulder complaints, clinical examination identified 43 MYA and 19 CON. At rest, during PEG, and STR the trapezius muscle was measured using (1) EMG and MMG, (2) microdialysis, and (3) NIRS. Further, subjective pain ratings were scored (VAS). EMGrms in %MVE (Maximal Voluntary EMG-activity), was significantly higher among MYA than CON during PEG (11.74 +/- A 9.09 vs. 7.42 +/- A 5.56%MVE) and STR (5.47 +/- A 5.00 vs. 3.28 +/- A 1.94%MVE). MANOVA showed a group and time effect regarding data from the microdialysis: for MYA versus CON group differences demonstrated lower muscle blood flow and higher lactate and pyruvate concentrations. Potassium and glucose only showed time effects. NIRS showed similar initial decreases in oxygenation with PEG in both groups, but only in CON a significant increase back to baseline during PEG. VAS score at rest was highest among MYA and increased during PEG, but not for CON. The results showed significant differences between CON and MYA regarding muscle metabolism at rest and with PEG and STR. Higher relative muscle load during PEG and STR, insufficient muscle blood flow and oxygenation may account for the higher lactate, pyruvate and pain responses among MYA versus CON.
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