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- Appelgren, Daniel, et al.
(författare)
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Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections.
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (rs = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation.
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2. |
- Boen, Rune, et al.
(författare)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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3. |
- Carlströmer Berthén, Nellie, et al.
(författare)
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The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finland
- 2023
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finlandby Nellie Carlströmer Berthén 1,2,*,† , Eszter Tompa 3,† , Susanne Olausson 1,2, Clara Nyberg 1, Dag Nyman 1,2, Malin Ringbom 1,4, Linda Perander 1,4, Joel Svärd 3, Per-Eric Lindgren 3,5, Pia Forsberg 3, Peter Wilhelmsson 3,5,‡, Johanna Sjöwall 3,6,‡ and Marika Nordberg 1,4,‡ 1Borrelia Research Group of the Aland Islands, 22100 Mariehamn, The Aland Islands, Finland2Bimelix AB, 22100 Mariehamn, The Aland Islands, Finland3Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linkoping University, 581 83 Linkoping, Sweden4The Aland Islands Healthcare Services, 22100 Mariehamn, The Aland Islands, Finland5Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, 551 85 Jonkoping, Sweden6Department of Infectious Diseases, Vrinnevi Hospital, 603 79 Norrkoping, Sweden*Author to whom correspondence should be addressed.†These authors contributed equally to the study.‡These authors contributed equally to the study.Microorganisms 2023, 11(5), 1100; https://doi.org/10.3390/microorganisms11051100Received: 30 March 2023 / Revised: 17 April 2023 / Accepted: 19 April 2023 / Published: 22 April 2023(This article belongs to the Special Issue Research on Ticks and Tick-Borne Pathogens)Download Browse Figures Versions NotesArticle Views585 AbstractThe AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite.
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4. |
- De Brandt, Jana, 1991-, et al.
(författare)
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The Borg Cycle Strength Test (BCST) for prescribing supramaximal high-intensity interval training (HIIT) in COPD
- 2023
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 62:Supplement 67
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Prescription of supramaximal HIIT is ideally based on an all-out test. This is, however, not suitable for people with COPD, leading to the use of workloads obtained during a maximal incremental test (CPET), which are less specific for the prescription of supramaximal HIIT. Hence, we evaluated the feasibility of a submaximal anaerobic test, the BCST, that has been used in older adults to prescribe supramaximal HIIT, and the anaerobic cycle capacity of people with COPD vs. matched healthy controls (HC).Methods: Sixteen persons with COPD and HC performed a CPET and a BCST. The BCST is an incremental stepwise test (30s cycling, 30s rest) with two end-of-test criteria: 1) Rating of perceived exertion (RPE) ≥17 or 2) cadence <75 RPM for >5s. End-of-test RPE, symptoms, peak workload (Wpeak) and cardiorespiratory demand were obtained to assess feasibility.Results: A higher Wpeak and lower RPE, symptoms and cardiorespiratory demand were observed in the BCST vs. CPET in both groups (Table1). Absolute BCST Wpeak was significantly lower, while relative BCST Wpeak (%Wpeak CPET) was similar in people with COPD (146±24%) vs. HC (157±17%)(P=0.114).Conclusion: In people with COPD, the BCST is a feasible short-duration submaximal anaerobic test specific for prescribing supramaximal HIIT. Compared to the CPET, it allows for higher workloads with lower cardiorespiratory demand and symptom burden.
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5. |
- Jakobsson, Johan, et al.
(författare)
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Acute physiological effects of supramaximal high-intensity interval training in people with or without COPD
- 2023
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Ingår i: Medicine & Science in Sports & Exercise. - : Wolters Kluwer. - 0195-9131 .- 1530-0315. ; 55, s. 549-549
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Tidskriftsartikel (refereegranskat)abstract
- High-intensity exercise is essential for optimal development of cardiorespiratory fitness and health. This is, however, challenging for most people with chronic obstructive pulmonary disease (COPD) due to ventilatory limitations, leading to exercise at lower intensities accompanied by suboptimal stress on the cardiovascular and muscular system.PURPOSE: To compare the acute effects of a novel concept of short-duration supramaximal high-intensity interval training (HIIT) vs. moderate-intensity continuous training (MICT) in people with COPD and matched healthy controls (HC).METHODS: Sixteen people with mild to severe COPD (75 ± 6 yr; 8 males; 73 ± 13 FEV1%pred; 119 ± 37 W max aerobic power [MAP]) and 14 HC (74 ± 5 yr; 8 males; 106 ± 14 FEV1%pred; 169 ± 38 W MAP) performed HIIT and MICT on a cycle ergometer in a randomized order. HIIT consisted of 10x6s sprints interspersed with 1-min recovery and was performed at two intensities: 60% of max mean power output for 6-sec (MPO6) and 80%MPO6, estimated from the Borg cycle strength test. MICT consisted of 20-min at 60% of MAP, derived from a cardiopulmonary exercise test. Cardiorespiratory parameters, blood lactate concentration, ratings of exertion/symptoms, and exercise modality preference were obtained.RESULTS: Exercise characteristics and physiological data collected at the end of exercise are shown in Table 1. All HIIT sessions were completed, while 1 in 3 people with COPD did not complete MICT. The HIIT modality was preferred by 13/16 (COPD) and 12/14 (HC).CONCLUSION: Short-duration supramaximal HIIT was feasible and enabled a 3.5-fold increase in exercise intensity vs. MICT in people with COPD and HC. Notably, despite the higher exercise intensities, the cardiorespiratory demand during HIIT was similar to MICT and clinically relevant reductions in symptoms were seen in favor of HIIT, in people with COPD. Also, >80% of participants preferred HIIT over MICT.
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6. |
- Jakobsson, Johan, et al.
(författare)
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Innovative exercise for optimizing exercise intensity in COPD
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 60:Suppl. 66
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-intensity exercise is essential for optimal physiological exercise adaptations but challenging to perform for most people with COPD due to ventilatory limitations, leading to use of lower exercise intensities accompanied by suboptimal stress on the cardiovascular and muscular system. This study compared the acute effects of a novel concept of short-duration supramaximal high-intensity interval training (HIIT) vs. traditional moderate-intensity continuous training (MICT) in people with COPD.Methods: Thirteen people with COPD (75±6 yr; 8 males; 72±13 FEV1%pred; 124±37 Wpeak) performed short-duration supramaximal HIIT and MICT on a cycle ergometer in a randomized order. HIIT consisted of 10x6s sprints interspersed with 1-min recovery and was performed at two intensities (HIIT60% & HIIT80%). MICT consisted of 20-min at 60% of CPET Wpeak. Cardiorespiratory parameters, blood lactate concentration, ratings of exertion/symptoms, and exercise modality preference were obtained.Results: Exercise characteristics and physiological data are seen in Table 1. All patients completed HIIT, while 4 out of 13 stopped MICT prematurely. Notably, 85% preferred HIIT over MICT.Conclusion: The novel concept of short-duration supramaximal HIIT enabled a 3 to 4-fold increase in exercise intensity vs. MICT. Notably, the cardiorespiratory demand during HIIT was similar to MICT, and clinically relevant reductions in symptoms were even seen in favor of HIIT.
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7. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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