| 1. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 2. |
- Andersson, Patrik, 1974, et al.
(författare)
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Framtidsbilder för samhällsbyggnad
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Framtidsbilder för samhällsbyggnad 2020De kommande 15 åren står institutionen för Bygg- och miljöteknik inför stora förändringar. Därför har institutionen initierat projektet Framtidsbilder 2020 där man engagerat en framtidspanel bestående av elva yngre disputerade forskare. Arbetet inleddes med ett breddgruppsmöte där 110 personer representerande institutionens personal och studenter deltog. Vid mötet identifierades ett antal trender och osäkra utvecklingar som påverkar framtiden inom samhällsbyggnadsområdet. Deltagarna bidrog också med idéer till en önskvärd utveckling, vilket har sammanställts och utgör grunden till en gemensam önskvärd framtid/vision för institutionen. Materialet från breddgruppsmötet har bearbetats av Framtidspanelen och resulterat i fyra scenarier som beskriver hur samhällsbyggnadsområdet kan se ut år 2020. Syftet med framtidsbilderna är att de ska vara vägledande för institutionens beslut och förhållningssätt under de kommande åren.Fyra scenarierTurning TorsoSamhället präglas av en ekonomi som är på uppgång, och av ett nytänkande och öppet samhälle. Materiell status och individualism är viktigt. Detta leder till en hög arbetsbelastning samt krav på exklusiva varor av hög kvali-tet. Det finns en stor medvetenhet om miljöpåverkan och klimatförändringar och lösningarna för att klara energiförsörjningen är innovativa.Eco-metropolenDet sveper en grön våg genom dagens samhälle. Under de senaste 15 åren har vi insett att jorden skall vara en bebolig plats även åt dem som kommer efter oss. Vi söker ständigt efter nya, mer förfinade metoder att tillvarata de resurser vi har. Samhället och individen är i balans. Ekonomin är god och vi är miljömedvetna, trygga och integrerade. Nytänkande premieras och icke- materialistiska värderingar står högt i kurs. Vi tänker individuellt, men agerar mer än gärna för kollektivets bästa. Utbildning är gratis TrädgårdsstadenEtt samhälle där vi lärt oss hantera stress, men känner oss otrygga och helst umgås i slutna sociala sammanhang. Vi bor enkelt inne i stan, eller gärna på landsbygden nära storstäderna. Minskade behov av högutbildade i samhället gör att vi har svårt att rekrytera studenter till teknikutbildningar. Det traditionella tankesättet leder till kulturkrockar med företag och personer från andra länder.Gated communitiesFörsämrad ekonomi och ökad egoism har lett fram till ett stressat, otryggt och segregerat samhälle. Accelererande klimatförändringar och ökad miljö-påverkan skrämmer oss, men trots det åtgärdar vi inte problemen, utan koncentrerar oss på konsekvenserna. Arbetslöshet i samhällsbyggnadssek-torn leder till sänkt status för samhällsbyggaren. Vi har därför svårt att rekrytera studenter, och även forskningen har låg status.
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| 3. |
- Dave, Nishi, et al.
(författare)
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Nosocomial SARS-CoV-2 infections and mortality during unique COVID-19 epidemic waves
- 2023
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Quantifying the burden of nosocomial SARS-CoV-2 infections and associated mortality is necessary to assess the need for infection prevention and control measures.Objective: To investigate the occurrence of nosocomial SARS-CoV-2 infections and associated 30-day mortality among patients admitted to hospitals in Region Stockholm, Sweden.Design, Setting, and Participants: A retrospective, matched cohort study divided the period from March 1, 2020, until September 15, 2022, into a prevaccination period, early vaccination and pre-Omicron (period 1), and late vaccination and Omicron (period 2). From among 303 898 patients 18 years or older living in Region Stockholm, 538 951 hospital admissions across all hospitals were included. Hospitalized admissions with nosocomial SARS-CoV-2 infections were matched to as many as 5 hospitalized admissions without nosocomial SARS-CoV-2 by age, sex, length of stay, admission time, and hospital unit.Exposure: Nosocomial SARS-CoV-2 infection defined as the first positive polymerase chain reaction test result at least 8 days after hospital admission or within 2 days after discharge.Main Outcomes and Measures: Primary outcome of 30-day mortality was analyzed using time-to-event analyses with a Cox proportional hazards regression model adjusted for age, sex, educational level, and comorbidities.Results: Among 2193 patients with SARS-CoV-2 infections or reinfections (1107 women [50.5%]; median age, 80 [IQR, 71-87] years), 2203 nosocomial SARS-CoV-2 infections were identified. The incidence rate of nosocomial SARS-CoV-2 infections was 1.57 (95% CI, 1.51-1.64) per 1000 patient-days. In the matched cohort, 1487 hospital admissions with nosocomial SARS-CoV-2 infections were matched to 5044 hospital admissions without nosocomial SARS-CoV-2 infections. Thirty-day mortality was higher in the prevaccination period (adjusted hazard ratio [AHR], 2.97 [95% CI, 2.50-3.53]) compared with period 1 (AHR, 2.08 [95% CI, 1.50-2.88]) or period 2 (AHR, 1.22 [95% CI, 0.92-1.60]). Among patients with nosocomial SARS-CoV-2 infections, 30-day AHR comparing those with 2 or more doses of SARS-CoV-2 vaccination and those with less than 2 doses was 0.64 (95% CI, 0.46-0.88).Conclusions and Relevance: In this matched cohort study, nosocomial SARS-CoV-2 infections were associated with higher 30-day mortality during the early phases of the pandemic and lower mortality during the Omicron variant wave and after the introduction of vaccinations. Mitigation of excess mortality risk from nosocomial transmission should be a strong focus when population immunity is low through implementation of adequate infection prevention and control measures.
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| 4. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 5. |
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| 6. |
- Johansson, Anders, 1966-, et al.
(författare)
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Francisella tularensis : Tularemia
- 2012
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Ingår i: BSL3 and BSL4 agents. - Weinheim, Germany : Wiley-VCH Verlagsgesellschaft. - 9783527317158 - 9783527645114 ; , s. 71-84
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Bokkapitel (refereegranskat)abstract
- Francisella tularensis is the causative agent of tularemia. This emerging zoonosis shows several clinical manifestations complicating its diagnosis. The chapter focus on the characteristics of this bacterium, the several forms of the disease, its diagnosis and molecular epidemiology.
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| 7. |
- Johansson, Anders, 1966-, et al.
(författare)
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Francisella tularensis : Tularemia
- 2012
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Ingår i: BSL3 and BSL4 agents. - Weinheim, Germany : Wiley-VCH Verlagsgesellschaft. - 9783527317158 - 9783527645114 ; , s. 309-311
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Bokkapitel (refereegranskat)abstract
- This practical guide gives some starting points to manage biological safety issues with Francisella tularensis.
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| 8. |
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| 9. |
- Johansson, Eva-Liz, et al.
(författare)
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Comparison of different routes of vaccination for eliciting antibody responses in the human stomach
- 2004
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 22:8, s. 984-90
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Tidskriftsartikel (refereegranskat)abstract
- Determination of optimal routes to induce mucosal immune responses locally in the stomach and duodenum are important steps in the development of vaccines against Helicobacter pylori infection. In this study, we immunized H. pylori-infected individuals either nasally or rectally with a model antigen, i.e. cholera toxin B subunit, and compared the immune responses after these routes with the responses after oral or intrajejunal vaccination. Specific antibody levels in serum as well as specific antibody levels and antibody-secreting cells in biopsies from antrum and duodenum were determined by ELISA and ELISPOT methods. In contrast to oral vaccination, nasal and rectal vaccination did not induce significant increases in specific antibody-secreting cells either in the antrum or duodenum. Furthermore, when analyzing the antibody levels in saponin extracted biopsies, intrajejunal vaccination was superior to both nasal and rectal vaccination in inducing antigen-specific IgA levels in the stomach. We conclude that oral vaccination is the optimal route for induction of antigen-specific IgA antibody responses in the stomach and duodenum of humans, while nasal or rectal vaccination is less suitable for this purpose.
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| 10. |
- Johansson, Jarkko, et al.
(författare)
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Longitudinal evidence that reduced hemispheric encoding/retrieval asymmetry predicts episodic-memory impairment in aging
- 2020
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Ingår i: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- The HERA (Hemispheric Encoding/Retrieval Asymmetry) model captures hemispheric lateralization of prefrontal cortex (PFC) brain activity during memory encoding and retrieval. Reduced HERA has been observed in cross-sectional aging studies, but there is no longitudinal evidence, to our knowledge, on age-related changes in HERA and whether maintained or reduced HERA relates to well-preserved memory functioning. In the present study we set out to explore HERA in a longitudinal neuroimaging sample from the Betula study [3 Waves over 10 years; Wave-1: n = 363, W2: n = 227, W3: n = 101]. We used fMRI data from a face-name paired-associates task to derive a HERA index. In support of the HERA model, the mean HERA index was positive across the three imaging waves. The longitudinal age-HERA relationship was highly significant (p < 10(-11)), with a HERA decline occurring after age 60. The age-related HERA decline was associated with episodic memory decline (p < 0.05). Taken together, the findings provide large-scale support for the HERA model, and suggest that reduced HERA in the PFC reflects pathological memory aging possibly related to impaired ability to bias mnemonic processing according to the appropriate encoding or retrieval state.
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| 11. |
- Johansson, Jarkko, et al.
(författare)
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Model of brain maintenance reveals specific change-change association between medial-temporal lobe integrity and episodic memory
- 2022
-
Ingår i: Aging Brain. - : Elsevier. - 2589-9589. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Brain maintenance has been identified as a major determinant of successful memory aging. However, the extent to which brain maintenance in support of successful memory aging is specific to memory-related brain regions or forms part of a brain-wide phenomenon is unresolved. Here, we used longitudinal brain-wide gray matter MRI volumes in 262 healthy participants aged 55 to 80 years at baseline to investigate separable dimensions of brain atrophy, and explored the links of these dimensions to different dimensions of cognitive change. We statistically adjusted for common causes of change in both brain and cognition to reveal a potentially unique signature of brain maintenance related to successful memory aging. Critically, medial temporal lobe (MTL)/hippocampal change and episodic memory change were characterized by unique, residual variance beyond general factors of change in brain and cognition, and a reliable association between these two residualized variables was established (r = 0.36, p < 0.01). The present study is the first to provide solid evidence for a specific association between changes in (MTL)/hippocampus and episodic memory in normal human aging. We conclude that hippocampus-specific brain maintenance relates to the specific preservation of episodic memory in old age, in line with the notion that brain maintenance operates at both general and domain-specific levels.
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| 12. |
- Johansson, Jonas, et al.
(författare)
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Parlament i världen : Riksdagen och Interparlamentariska unionen
- 2017
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Under mer än hundra år har världens parlament och folkvalda haft en återkommande mötesplats för tankeutbyte och gemensamma aktioner i Interparlamentariska unionen, IPU.Från början var IPU en del av förra sekelskiftets framväxande rörelse för demokrati och fred i Europa. Samarbete mellan världens parlamentariker skulle demokratisera utrikespolitiken och skapa förutsättningar för en hållbar fred. Inom loppet av ett drygt kvartssekel hedrades hela åtta företrädare för IPU med Nobels fredspris.Trots två förödande världskrig på 1900-talet och hotet om kärnvapenkrig sedan dess har IPU behållit sin roll som mötesplats och samtalsforum. Arbetet med utvecklings- och biståndsarbete har vuxit kring frågor om hållbar utveckling och mänskliga rättigheter. Att främja kvinnors deltagande i politiken har blivit en profilfråga. Sedan millennieskiftet betonar IPU särskilt sin roll som parlamentarisk partner till FN.
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| 13. |
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| 14. |
- Johansson, Per, 1966, et al.
(författare)
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Cerebrospinal fluid substance P concentrations are elevated in patients with Alzheimer's disease.
- 2015
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Ingår i: Neuroscience letters. - : Elsevier BV. - 1872-7972 .- 0304-3940. ; 609, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptides substance P, orexin A (hypocretin-1) and neurotensin are signaling molecules that influence brain activity. We examined their cerebrospinal fluid (CSF) levels in a study population consisting of Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), other dementias (n=15), and healthy controls (n=20). CSF substance P level was increased in AD patients compared to patients with other dementias and healthy controls (P<0.05 and P<0.01, respectively). Patients with other dementia or SMCI had lower CSF orexin A level than AD patients (both P<0.05) and marginally lower level than healthy controls (both P=0.05). CSF neurotensin level was similar in all groups. In the total study population (n=80), CSF substance P level correlated positively with CSF levels of T-tau and P-tau, and in AD patients (n=32), CSF substance P level correlated positively with CSF Aβ1-42 level. In conclusion, CSF substance P level was elevated in AD patients and correlated with CSF Aβ1-42 level, a well established marker of senile plaque pathology. The role of low CSF orexin A level in other dementias or SMCI needs to be explored in further studies.
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| 15. |
- Johansson, Per, 1966, et al.
(författare)
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Mild dementia is associated with increased adrenal secretion of cortisol and precursor sex steroids in women.
- 2011
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 75:3, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Context Sex steroid levels decrease with increasing age, but little is known whether this is of importance for the age-related decline in cognitive function. Design and patients A cross-sectional study of 50 (26 men) consecutive patients under primary evaluation of cognitive impairment (D group) and 18 (9 men) matched healthy controls (C group). Measurements Sex steroid and precursor levels were determined in serum and, when measurable, in cerebrospinal fluid (CSF) using gas chromatography/mass spectroscopy (GC-MS) or liquid chromatography/mass spectroscopy (LC-MS). Sex hormone binding globulin (SHBG) and cortisol concentrations were measured using conventional assays. Results Patients in the D group had higher 24-h urine cortisol levels and increased serum levels of dehydroepiandrosterone (DHEA) and its sulphate ester dihydroepiandrosterone sulphate (DHEAS), androsterone (ADT), and oestrone (E1) and its sulphate ester E1S, compared with the controls. When men and women were analysed separately, increased serum concentrations of E1 and E1S were observed in both D men and D women, whereas increased levels of other sex steroids and cortisol were seen only in D women. Conclusions In both D men and women, serum E1 and E1S levels were increased, whereas other changes were gender specific and only seen in D women. Further studies are needed to determine whether these changes are a cause of, or merely a consequence of, cognitive impairment in elderly subjects.
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| 16. |
- Johansson, Per, 1966, et al.
(författare)
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Reduced Cerebrospinal Fluid Concentration of Apolipoprotein A-I in Patients with Alzheimer's Disease.
- 2017
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908 .- 1387-2877. ; 59:3, s. 1017-1026
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E (ApoE) has been extensively studied in Alzheimer's disease (AD), but little is known of apolipoprotein A-I (ApoA-I) in cerebrospinal fluid (CSF).Plasma lipids as well as ApoA-I and ApoE in plasma and CSF were determined and related to Mini-Mental State Examination (MMSE) score, APOE genotype, and CSF AD biomarkers.Consecutive patients with AD (n=29), stable mild cognitive impairment (n=13), other dementias (n=14), and healthy controls (n=18) were included at a single center.AD patients had higher plasma triglycerides and lower CSF ApoA-I concentration than controls (both p<0.05). CSF ApoE concentration was reduced in other dementias (p<0.01). In AD as well as other dementias, the ratios between CSF and plasma concentrations of both ApoA-I and ApoE were lower than those in the controls. ApoA-I and ApoE in plasma and CSF were not influenced by APOEɛ4 allele distribution. In the total study population (n=74), CSF ApoA-I correlated positively with MMSE score (r=0.26, p<0.05) and negatively with CSF P-tau (r=-0.25, p<0.05). CSF ApoE correlated positively with CSF concentrations of T-tau and P-tau in the total study population and in AD patients.CSF ApoA-I was reduced in AD patients and associated with measures of cognitive function and AD disease status. The mechanisms underlying the decreased CSF:plasma ratios of ApoA-I and ApoE in AD and other dementias need to be explored in further studies.
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| 17. |
- Johansson, Per, 1966, et al.
(författare)
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Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment.
- 2017
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- The role of inflammation in Alzheimer's disease (AD) and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF) samples.Consecutive patients with AD (n = 30), stable mild cognitive impairment (SMCI, n = 11), other dementias (n = 11), and healthy controls (n = 18) were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6), IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A), and three chemokines were measured using a multiplex panel.After correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52) and controls (n = 18; p = 0.002). Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI) compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). In the total study population (n = 70), CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1-42) and phosphorylated tau protein (P-tau) whereas in AD patients (n = 30), CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01).Most cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.
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| 18. |
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| 19. |
- Karalija, Nina, 1984-, et al.
(författare)
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C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition
- 2019
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Ingår i: Journal of cognitive neuroscience. - : MIT Press. - 0898-929X .- 1530-8898. ; 31:2, s. 314-325
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with C-11-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64-68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T, was associated with increased apparent affinity of C-11-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that C-11-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between C-11-raclopride BP and cognitive performance. In accordance with previous findings, we show that C-11-raclopride BP was increased in T-homozygotes. Importantly, C-11-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T, n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest C-11-raclopride BP-cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and C-11-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.
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| 20. |
- Karalija, Nina, 1984-, et al.
(författare)
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Cardiovascular factors are related to dopamine integrity and cognition in aging
- 2019
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley-Blackwell. - 2328-9503. ; 6:11, s. 2291-2303
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aging brain undergoes several changes, including reduced vascular, structural, and dopamine (DA) system integrity. Such brain changes have been associated with age‐related cognitive deficits. However, their relative importance, interrelations, and links to risk factors remain elusive.Methods: The present work used magnetic resonance imaging and positron emission tomography with 11C‐raclopride to jointly examine vascular parameters (white‐matter lesions and perfusion), DA D2‐receptor availability, brain structure, and cognitive performance in healthy older adults (n = 181, age: 64–68 years) from the Cognition, Brain, and Aging (COBRA) study.Results: Covariance was found among several brain indicators, where top predictors of cognitive performance included caudate and hippocampal integrity (D2DR availability and volumes), and cortical blood flow and regional volumes. White‐matter lesion burden was negatively correlated with caudate DA D2‐receptor availability and white‐matter microstructure. Compared to individuals with smaller lesions, individuals with confluent lesions (exceeding 20 mm in diameter) had reductions in cortical and hippocampal perfusion, striatal and hippocampal D2‐receptor availability, white‐matter microstructure, and reduced performance on tests of episodic memory, sequence learning, and processing speed. Higher cardiovascular risk as assessed by treatment for hypertension, systolic blood pressure, overweight, and smoking was associated with lower frontal cortical perfusion, lower putaminal D2DR availability, smaller grey‐matter volumes, a larger number of white‐matter lesions, and lower episodic memory performance.Interpretation: Taken together, these findings suggest that reduced cardiovascular health is associated with poorer status for brain variables that are central to age‐sensitive cognitive functions, with emphasis on DA integrity.
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| 21. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
- 2022
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
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| 22. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline
- 2024
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Ingår i: NEUROBIOLOGY OF AGING. - 0197-4580 .- 1558-1497. ; 136, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine decline is suggested to underlie aging -related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5 -year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64-68 years; 5 -year follow-up: n = 129) who underwent positron emission tomography with 11C- raclopride to assess dopamine D2 -like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A datadriven approach (k -means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age -sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide -ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5 -year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.
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| 23. |
- Karalija, Nina, 1984-, et al.
(författare)
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Sex differences in dopamine integrity and brain structure among healthy older adults : Relationships to episodic memory
- 2021
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 105, s. 272-279
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Tidskriftsartikel (refereegranskat)abstract
- Normal brain aging is a multidimensional process that includes deterioration in various brain structures and functions, with large heterogeneity in patterns and rates of decline. Sex differences have been reported for various cognitive and brain parameters, but little is known in relation to neuromodulatory aspects of brain aging. We examined sex differences in dopamine D2-receptor (D2DR) availability in relation to episodic memory, but also, grey-matter volumes, white-matter lesions, and cerebral perfusion in healthy older adults (n = 181, age: 64-68 years) from the Cognition, Brain, and Aging study. Women had higher D2DR availability in midbrain and left caudate and putamen, as well as superior episodic memory performance. Controlling for left caudate D2DR availability attenuated sex differences in memory performance. In men, lower left caudate D2DR levels were associated with lower cortical perfusion and higher burden of white-matter lesions, as well as with episodic memory performance. However, sex was not a significant moderator of the reported links to D2DR levels. Our findings suggest that sex differences in multiple associations among DA receptor availability, vascular factors, and structural connectivity contribute to sex differences in episodic memory. Future longitudinal studies need to corroborate these patterns by lead-lag associations. This manuscript is part of the Special Issue entitled 'Cognitive Neuroscience of Healthy and Pathological Aging' edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza.
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| 24. |
- Karlsson Valik, John, et al.
(författare)
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Validation of automated sepsis surveillance based on the Sepsis-3 clinical criteria against physician record review in a general hospital population : observational study using electronic health records data
- 2020
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Ingår i: BMJ Quality and Safety. - : BMJ Publishing Group Ltd. - 2044-5415 .- 2044-5423. ; 29:9, s. 735-745
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Forskningsöversikt (refereegranskat)abstract
- Background: Surveillance of sepsis incidence is important for directing resources and evaluating quality-of-care interventions. The aim was to develop and validate a fully-automated Sepsis-3 based surveillance system in non-intensive care wards using electronic health record (EHR) data, and demonstrate utility by determining the burden of hospital-onset sepsis and variations between wards.Methods: A rule-based algorithm was developed using EHR data from a cohort of all adult patients admitted at an academic centre between July 2012 and December 2013. Time in intensive care units was censored. To validate algorithm performance, a stratified random sample of 1000 hospital admissions (674 with and 326 without suspected infection) was classified according to the Sepsis-3 clinical criteria (suspected infection defined as having any culture taken and at least two doses of antimicrobials administered, and an increase in Sequential Organ Failure Assessment (SOFA) score by >2 points) and the likelihood of infection by physician medical record review.Results: In total 82 653 hospital admissions were included. The Sepsis-3 clinical criteria determined by physician review were met in 343 of 1000 episodes. Among them, 313 (91%) had possible, probable or definite infection. Based on this reference, the algorithm achieved sensitivity 0.887 (95% CI: 0.799 to 0.964), specificity 0.985 (95% CI: 0.978 to 0.991), positive predictive value 0.881 (95% CI: 0.833 to 0.926) and negative predictive value 0.986 (95% CI: 0.973 to 0.996). When applied to the total cohort taking into account the sampling proportions of those with and without suspected infection, the algorithm identified 8599 (10.4%) sepsis episodes. The burden of hospital-onset sepsis (>48 hour after admission) and related in-hospital mortality varied between wards.Conclusions: A fully-automated Sepsis-3 based surveillance algorithm using EHR data performed well compared with physician medical record review in non-intensive care wards, and exposed variations in hospital-onset sepsis incidence between wards.
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| 25. |
- Lindgren, Petter, et al.
(författare)
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A likelihood ratio-based approach for improved source attribution in microbiological forensic investigations
- 2019
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Ingår i: Forensic Science International. - : Elsevier. - 0379-0738 .- 1872-6283. ; 302
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Tidskriftsartikel (refereegranskat)abstract
- A common objective in microbial forensic investigations is to identify the origin of a recovered pathogenic bacterium by DNA sequencing. However, there is currently no consensus about how degrees of belief in such origin hypotheses should be quantified, interpreted, and communicated to wider audiences. To fill this gap, we have developed a concept based on calculating probabilistic evidential values for microbial forensic hypotheses. The likelihood-ratio method underpinning this concept is widely used in other forensic fields, such as human DNA matching, where results are readily interpretable and have been successfully communicated in juridical hearings. The concept was applied to two case scenarios of interest in microbial forensics: (1) identifying source cultures among series of very similar cultures generated by parallel serial passage of the Tier 1 pathogen Francisella tularensis, and (2) finding the production facilities of strains isolated in a real disease outbreak caused by the human pathogen Listeria monocytogenes. Evidence values for the studied hypotheses were computed based on signatures derived from whole genome sequencing data, including deep-sequenced low-frequency variants and structural variants such as duplications and deletions acquired during serial passages. In the F. tularensis case study, we were able to correctly assign fictive evidence samples to the correct culture batches of origin on the basis of structural variant data. By setting up relevant hypotheses and using data on cultivated batch sources to define the reference populations under each hypothesis, evidential values could be calculated. The results show that extremely similar strains can be separated on the basis of amplified mutational patterns identified by high-throughput sequencing. In the L. monocytogenes scenario, analyses of whole genome sequence data conclusively assigned the clinical samples to specific sources of origin, and conclusions were formulated to facilitate communication of the findings. Taken together, these findings demonstrate the potential of using bacterial whole genome sequencing data, including data on both low frequency SNP signatures and structural variants, to calculate evidence values that facilitate interpretation and communication of the results. The concept could be applied in diverse scenarios, including both epidemiological and forensic source tracking of bacterial infectious disease outbreaks.
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| 26. |
- Lundgren, Anders, 1978, et al.
(författare)
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Affinity Purification and Single-Molecule Analysis of Integral Membrane Proteins from Crude Cell-Membrane Preparations
- 2018
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 18:1, s. 381-385
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Tidskriftsartikel (refereegranskat)abstract
- The function of integral membrane proteins is critically dependent on their naturally surrounding lipid membrane. Detergent-solubilized and purified membrane proteins are therefore often reconstituted into cell-membrane mimics and analyzed for their function with single-molecule microscopy. Expansion of this approach toward a broad range of pharmaceutically interesting drug targets and biomarkers however remains hampered by the fact that these proteins have low expression levels, and that detergent solubilization and reconstitution often cause protein conformational changes and loss of membrane-specific cofactors, which may impair protein function. To overcome this limitation, we here demonstrate how antibody-modified nanoparticles can be used to achieve affinity purification and enrichment of selected integral membrane proteins directly from cell membrane preparations. Nanoparticles were first bound to the ectodomain of β-secretase 1 (BACE1) contained in cell-derived membrane vesicles. In a subsequent step, these were merged into a continuous supported membrane in a microfluidic channel. Through the extended nanoparticle tag, a weak (∼fN) hydrodynamic force could be applied, inducing directed in-membrane movement of targeted BACE1 exclusively. This enabled selective thousand-fold enrichment of the targeted membrane protein while preserving a natural lipid environment. In addition, nanoparticle-targeting also enabled simultaneous tracking analysis of each individual manipulated protein, revealing how their mobility changed when moved from one lipid environment to another. We therefore believe this approach will be particularly useful for separation in-line with single-molecule analysis, eventually opening up for membrane-protein sorting devices analogous to fluorescence-activated cell sorting.
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| 27. |
- Müller, Daniel C., et al.
(författare)
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Phospholipid Levels in Blood during Community-Acquired Pneumonia
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12–24 h), Day 2 (at 36–48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6–1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery.
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| 28. |
- Naucler, Pontus, et al.
(författare)
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HAI-Proactive : Development of an Automated Surveillance System for Healthcare-Associated Infections in Sweden
- 2020
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Ingår i: Infection control and hospital epidemiology. - : Cambridge University Press. - 0899-823X .- 1559-6834. ; 41, s. S39-S39
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Healthcare-associated infection (HAI) surveillance is essential for most infection prevention programs and continuous epidemiological data can be used to inform healthcare personal, allocate resources, and evaluate interventions to prevent HAIs. Many HAI surveillance systems today are based on time-consuming and resource-intensive manual reviews of patient records. The objective of HAI-proactive, a Swedish triple-helix innovation project, is to develop and implement a fully automated HAI surveillance system based on electronic health record data. Furthermore, the project aims to develop machine-learning–based screening algorithms for early prediction of HAI at the individual patient level. Methods: The project is performed with support from Sweden’s Innovation Agency in collaboration among academic, health, and industry partners. Development of rule-based and machine-learning algorithms is performed within a research database, which consists of all electronic health record data from patients admitted to the Karolinska University Hospital. Natural language processing is used for processing free-text medical notes. To validate algorithm performance, manual annotation was performed based on international HAI definitions from the European Center for Disease Prevention and Control, Centers for Disease Control and Prevention, and Sepsis-3 criteria. Currently, the project is building a platform for real-time data access to implement the algorithms within Region Stockholm. Results: The project has developed a rule-based surveillance algorithm for sepsis that continuously monitors patients admitted to the hospital, with a sensitivity of 0.89 (95% CI, 0.85–0.93), a specificity of 0.99 (0.98–0.99), a positive predictive value of 0.88 (0.83–0.93), and a negative predictive value of 0.99 (0.98–0.99). The healthcare-associated urinary tract infection surveillance algorithm, which is based on free-text analysis and negations to define symptoms, had a sensitivity of 0.73 (0.66–0.80) and a positive predictive value of 0.68 (0.61–0.75). The sensitivity and positive predictive value of an algorithm based on significant bacterial growth in urine culture only was 0.99 (0.97–1.00) and 0.39 (0.34–0.44), respectively. The surveillance system detected differences in incidences between hospital wards and over time. Development of surveillance algorithms for pneumonia, catheter-related infections and Clostridioides difficile infections, as well as machine-learning–based models for early prediction, is ongoing. We intend to present results from all algorithms. Conclusions: With access to electronic health record data, we have shown that it is feasible to develop a fully automated HAI surveillance system based on algorithms using both structured data and free text for the main healthcare-associated infections.Funding: Sweden’s Innovation Agency and Stockholm County CouncilDisclosures: None
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| 29. |
- Odell, Anders, et al.
(författare)
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Geometric integration in Born-Oppenheimer molecular dynamics
- 2011
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 135:22, s. 224105-
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Tidskriftsartikel (refereegranskat)abstract
- Geometric integration schemes for extended Lagrangian self-consistent Born-Oppenheimer moleculardynamics, including a weak dissipation to remove numerical noise, are developed and analyzed.The extended Lagrangian framework enables the geometric integration of both the nuclear and electronicdegrees of freedom. This provides highly efficient simulations that are stable and energy conservingeven under incomplete and approximate self-consistent field (SCF) convergence. We investigatethree different geometric integration schemes: (1) regular time reversible Verlet, (2) secondorder optimal symplectic, and (3) third order optimal symplectic. We look at energy conservation,accuracy, and stability as a function of dissipation, integration time step, and SCF convergence. Wefind that the inclusion of dissipation in the symplectic integration methods gives an efficient dampingof numerical noise or perturbations that otherwise may accumulate from finite arithmetics in aperfect reversible dynamics.
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| 30. |
- Papenberg, Goran, et al.
(författare)
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Mapping the landscape of human dopamine D2/3 receptors with [11C]raclopride
- 2019
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Ingår i: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 224:8, s. 2871-2882
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine D2/3 system is fundamental for sensory, motor, emotional, and cognitive aspects of behavior. Small-scale human histopathological and animal studies show high density of D2/3 dopamine receptors (D2/3DR) in striatum, but also demonstrate the existence of such receptors across cortical and limbic regions. Assessment of D2/3DR BPND in the extrastriatal regions with [C-11]raclopride has long been considered unreliable due to the relatively low density of D2/3DR outside the striatum. We describe the distribution and interregional links of D2/3DR availability measured with PET and [C-11]raclopride across the human brain in a large sample (N = 176; age range 64-68 years). Structural equation modeling revealed that D2/3DR availability can be organized according to anatomical (nigrostriatal, mesolimbic, mesocortical) and functional (limbic, associative, sensorimotor) dopamine pathways. D2/3DR availability in corticolimbic functional subdivisions showed differential associations to corresponding striatal subdivisions, extending animal and pharmacological work. Our findings provide evidence on the dimensionality and organization of [C-11]raclopride D2/3DR availability in the living human brain that conforms to known dopaminergic pathways.
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| 31. |
- Pesonen, Ida, et al.
(författare)
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High prevalence of interstitial lung abnormalities in middle-aged never-smokers
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms.METHODS: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing.FINDINGS: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA.INTERPRETATION: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.
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| 32. |
- Rydén, Patrik, 1969-, et al.
(författare)
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Effects of climate change on tularemia disease activity in Sweden
- 2009
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Ingår i: Global Health Action. - 1654-9880. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Tularaemia is a vector-borne infectious disease. A large majority of cases transmitted to humans by bloodfeeding arthropods occur during the summer season and is linked to increased temperatures. Therefore, the effect of climate change is likely to have an effect on tularaemia transmission patterns in highly endemic areas of Sweden. In this report, we use simulated climate change scenario data and empirical data of temperatures critical to tularaemia transmission to forecast tularaemia outbreak activity. The five high-endemic counties: Dalarna, Gävleborg, Norrbotten, Värmland and Örebro represent only 14.6% of the total population of Sweden, but have recorded 40.1-81.1% of the number of annual human tularaemia in Sweden from 1997 until 2008. We project here earlier starts and a later termination of future tularaemia outbreaks for the time period 2010-2100. For five localised outbreak areas; Gagnef (Dalarna), Ljusdal (Gävleborg), Harads (Norrbotten), Karlstad (Värmland) and Örebro municipality (Örebro), the climate scenario suggests an approximately 2°C increase in monthly average summer temperatures leading to increases in outbreak durations ranging from 3.5 weeks (Harads) to 6.6 weeks (Karlstad) between 2010 and 2100. In contrast, an analysis of precipitation scenarios indicates fairly stable projected levels of precipitation during the summer months. Thus, there should not be an increased abundance of late summer mosquitoes that are believed to be main vectors for transmission to humans in these areas. In conclusion, the results indicate that the future climate changes will lead to an increased burden of tularaemia in high-endemic areas of Sweden during the coming decades.
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| 33. |
- Salami, Alireza, et al.
(författare)
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Dopamine D-2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion
- 2019
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 39:3, s. 537-547
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) modulates corticostriatal connections. Studies in which imaging of the DA system is integrated with functional imaging during cognitive performance have yielded mixed findings. Some work has shown a link between striatal DA(measured by PET) and fMRI activations, whereas others have failed to observe such a relationship. One possible reason for these discrepant findings is differences in task demands, such that a more demanding task with greater prefrontal activations may yield a stronger association with DA. Moreover, a potential DA-BOLD association may be modulated by task performance. We studied 155 (104 normal-performing and 51 low-performing) healthy older adults (43% females) who underwent fMRI scanning while performing a working memory (WM) n-back task along with DA D-2/3 PET assessment using [C-11] raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D-2/3 receptors to BOLD response in the thalamo-striatalcortical circuit, which supports WM functioning. Critically, the DA-BOLD association in normal-performing, but not low-performing, individuals was expressed in a load-dependent fashion, with stronger associations during 3-back than 1-/2-back conditions. Moreover, normal-performing adults expressing upregulated BOLD in response to increasing task demands showed a stronger DA-BOLD association during 3-back, whereas low-performing individuals expressed a stronger association during 2-back conditions. This pattern suggests a nonlinear DA-BOLD performance association, with the strongest link at the maximum capacity level. Together, our results suggest that DA may have a stronger impact on functional brain responses during more demanding cognitive tasks.
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| 34. |
- Siebmanns, Sandra, 1974-, et al.
(författare)
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The effect of nurse-led Internet-based cognitive behavioural therapy for insomnia on patients with cardiovascular disease : A randomized controlled trial with 6-month follow-up
- 2021
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Ingår i: Nursing Open. - : John Wiley & Sons. - 2054-1058. ; 8:4, s. 1755-1768
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To test the effect of nurse-led Internet-based cognitive behavioural therapy for insomnia (I-CBTI), tailored for patients with cardiovascular disease (CVD), with a 6-month follow-up.Design: A two-arm parallel-group randomized controlled trial (RCT) registered at clinicaltrials.gov (NTC03938805) and reported according to the CONSORT checklist.Methods: Forty-eight patients (mean age 72 years, 65% men) diagnosed with CVD and insomnia were randomized to either 9-week nurse-led I-CBTI with support, or an Internet-based self-study programme without support (control group). Insomnia Severity Index (ISI) and Short Form Health Survey (SF-12) were used as primary and secondary outcomes.Results: ISI showed a significant treatment effect of I-CBTI compared to the control group at 9-week follow-up. The mean ISI score in the I-CBTI group at 9 weeks post-treatment was maintained at the 6-month follow-up. Patients' adherence to I-CBTI was associated with a better effect on both the ISI and SF-12.
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| 35. |
- Sjödin, Åke, et al.
(författare)
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Wear particles from road traffic : A field, laboratory and modelling study - final report
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is an outcome of a major research effort within the Swedish National Road Vehicle Emission Research Programme EMFO, carried out 2005-2008 in collaboration between IVL, Lund University, the City of Stockholm and VTI. Within the project extensive data have been collected by a variety of methods for measuring, sampling and analysing the chemical composition of primarily three different fractions of particulate matter - PM10, PM2.5, PM1. Emphasis has been on the PM10 fraction, in the case of which preferably the major Swedish cities experience significant problems with complying with the legally binding air quality standards. The collected data originate from indoor measurements in controlled runs with the VTI circular road simulator as well as ambient air measurements at both street and roof level in a variety of Swedish cities. Based on elemental (metals etc.) source profiles of various sources to the different particle fractions, derived from the literature or from measurements carried out within the project, several different receptor models (e.g. COPREM, PMF) were applied to the collected data to derive the contributions from exhaust, brake wear, tyre wear, road surface wear, long-range transport etc., to the measured concentrations of PM10 and other particle fractions in urban environments. Furthermore, from the measurements, emission factors (expressed in grams per vehkm) for the various particle fractions, as well as for a large number of contained metals (about 30 metals) were derived for a major city street in Stockholm. Total emission factors as well as emission factors for each of the different source types (exhaust, brake wear, tyre wear and road surface wear) have also been derived from the measurements.
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| 36. |
- Tuiskunen-Bäck, Anne, et al.
(författare)
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Acute myocarditis caused by Francisella tularensis : a case report
- 2023
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Ingår i: SN Comprehensive Clinical Medicine. - : Springer Science and Business Media LLC. - 2523-8973. ; 5:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Myocarditis is an inflammatory disease of the myocardium with either focal or diffuse involvement and usually gives rise to chest pain, dyspnea, palpitations, and fatigue. In severe cases, arrythmias, syncope, and cardiogenic shock may occur. Acute myocarditis is most commonly caused by a variety of viruses with cardiotropic properties. Rare causes of myocarditis include bacterial infections. We, herein, describe a case of acute myocarditis caused by the intracellular bacterium Francisella tularensis. A young and previously healthy male in Northern Sweden was referred to the emergency department due to intense upper-chest pain and dyspnea. ECG exhibited minimal ST-segment elevations and laboratory parameters revealed pathological levels of high-sensitivity cardiac troponin and C-reactive protein. Radiological imaging showed increased metabolism in enlarged lymph nodes in the chest and signs that could be compatible with increased metabolism in the left ventricular of the heart. The combination of acute myocarditis and enlarged lymph nodes was believed to be caused by the intracellular bacterium Francisella tularensis, endemic in the Northern Sweden, and was verified with positive serology. The patient showed full recovery after antimicrobial treatment. As this is the fifth published case of myocarditis associated with Francisella tularensis, we suggest considering tularemia in acute myocarditis in tularemia-endemic area.
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| 37. |
- Wallin, Anders, 1950, et al.
(författare)
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Cognitive medicine - a new approach in health care science.
- 2018
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Ingår i: BMC psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- The challenges of today's society call for more knowledge about how to maintain all aspects of cognitive health, such as speed/attention, memory/learning, visuospatial ability, language, executive capacity and social cognition during the life course.Medical advances have improved treatments of numerous diseases, but the cognitive implications have not been sufficiently addressed. Disability induced by cognitive dysfunction is also a major issue in groups of patients not suffering from Alzheimer's disease or related disorders. Recent studies indicate that several negative lifestyle factors can contribute to the development of cognitive impairment, but intervention and prevention strategies have not been implemented. Disability due to cognitive failure among the workforce has become a major challenge. Globally, the changing aging pyramid results in increased prevalence of cognitive disorders, and the diversity of cultures influences the expression, manifestation and consequences of cognitive dysfunction.Major tasks in the field of cognitive medicine are basic neuroscience research to uncover diverse disease mechanisms, determinations of the prevalence of cognitive dysfunction, health-economical evaluations, and intervention studies. Raising awareness for cognitive medicine as a clinical topic would also highlight the importance of specialized health care units for an integrative approach to the treatment of cognitive dysfunctions.
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| 38. |
- Widerström, Micael, 1958-, et al.
(författare)
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Heterogeneity of Staphylococcus epidermidis in prosthetic joint infections : time to reevaluate microbiological criteria?
- 2022
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 41, s. 87-97
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Tidskriftsartikel (refereegranskat)abstract
- Prosthetic joint infection (PJI) is a feared and challenging to diagnose complication after arthroplasty, with Staphylococcus epidermidis as the major pathogen. One important criteria to define PJI is the detection of phenotypically indistinguishable microorganisms with identical antibiotic susceptibility pattern in at least two different samples. However, owing to phenotypical variation within genetic clones and clonal variation within a phenotype, the criteria may be ambiguous. We investigated the extent of diversity among coagulase-negative staphylococci (CoNS) in PJI and characterised S. epidermidis isolates from PJI samples, specifically multiple S. epidermidis isolates identified in individual PJI patients. We performed a retrospective cohort study on 62 consecutive patients with PJI caused by CoNS from two hospitals in Northern Sweden. In 16/62 (26%) PJIs, multiple S. epidermidis isolates were available for whole-genome analyses. Hospital-adapted multidrug-resistant genetic clones of S. epidermidis were identified in samples from 40/62 (65%) of the patients using a combination of pulsed-field gel electrophoresis and multilocus sequence typing. Whole-genome sequencing showed the presence of multiple sequence types (STs) in 7/16 (44%) PJIs where multiple S. epidermidis isolates were available. Within-patient phenotypical variation in the antibiotic susceptibility and/or whole-genome antibiotic resistance gene content was frequent (11/16, 69%) among isolates with the same ST. The results highlight the ambiguity of S. epidermidis phenotypic characterisation as a diagnostic method in PJI and call for larger systematic studies for determining the frequency of CoNS diversity in PJIs, the implications of such diversity for microbiological diagnostics, and the therapeutic outcomes in patients.
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| 39. |
- Åberg, Daniel, 1973, et al.
(författare)
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Increased Cerebrospinal Fluid Level of Insulin-like Growth Factor-II in Male Patients with Alzheimer's Disease
- 2015
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 48:3, s. 637-646
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin-like growth factor-II (IGF-II) is important for brain development. Although IGF-II is abundant also in adult life, little is known of the role of IGF-II in Alzheimer's disease (AD). Objective and methods: This was a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 32), stable MCI (SMCI, n = 13), or other dementias (n = 15). IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 were analyzed in serum and cerebrospinal fluid (CSF). Results: Levels of IGF-II, IGFBP-1, and IGFBP-2 were similar in all groups in the total study population. Gender-specific analyses showed that in men (n = 40), CSF IGF-II level was higher in AD compared to SMCI and controls (p < 0.01 and p < 0.05, respectively). Furthermore, CSF IGFBP-2 levelwas increased inADmen versus SMCI men (p < 0.01) and tended to be increased versus control men (p = 0.09). There were no between-group differences in women (n = 40). In the total study population (n = 80) as well as in men (n = 40), CSF levels of IGF-II and IGFBP-2 correlated positively with CSF levels of the AD biomarkers total-tau and phosphorylated tau protein. Conclusion: In men, but not women, in the early stages of AD, CSF IGF-II level was elevated, and CSF IGFBP-2 level tended to be increased, compared to healthy controls.
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| 40. |
- Ahlström, Katarina, 1966, et al.
(författare)
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Exogenous carbon monoxide does not affect cell membrane energy availability assessed by sarcolemmal calcium fluxes during myocardial ischaemia-reperfusion in the pig
- 2011
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Ingår i: European Journal of Anaesthesiology. - 0265-0215 .- 1365-2346. ; 28:5, s. 356-362
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Tidskriftsartikel (refereegranskat)abstract
- Carbon monoxide is thought to be cytoprotective and may hold therapeutic promise for mitigating ischaemic injury. The purpose of this study was to test low-dose carbon monoxide for protective effects in a porcine model of acute myocardial ischaemia and reperfusion. In acute open-thorax experiments in anaesthetised pigs, pretreatment with low-dose carbon monoxide (5% increase in carboxyhaemoglobin) was conducted for 120 min before localised ischaemia (45 min) and reperfusion (60 min) was performed using a coronary snare. Metabolic and injury markers were collected by microdialysis sampling in the ventricular wall. Recovery of radio-marked calcium delivered locally by microperfusate was measured to assess carbon monoxide treatment effects during ischaemia/reperfusion on the intracellular calcium pool. Coronary occlusion and ischaemia/reperfusion were analysed for 16 animals (eight in each group). Changes in glucose, lactate and pyruvate from the ischaemic area were observed during ischaemia and reperfusion interventions, though there was no difference between carbon monoxide-treated and control groups during ischaemia or reperfusion. Similar results were observed for glycerol and microdialysate Ca-45(2+) recovery. These findings show that a relatively low and clinically relevant dose of carbon monoxide did not seem to provide acute protection as indicated by metabolic, energy-related and injury markers in a porcine myocardial ischaemia/reperfusion experimental model. We conclude that protective effects of carbon monoxide related to ischaemia/reperfusion either require higher doses of carbon monoxide or occur later after reperfusion than the immediate time frame studied here. More study is needed to characterise the mechanism and time frame of carbon monoxide-related cytoprotection.
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| 41. |
- Ahlström, Katarina, 1966, et al.
(författare)
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Metabolic responses in ischemic myocardium after inhalation of carbon monoxide.
- 2009
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Ingår i: Acta Anaesthesiol Scand. - : Wiley. - 1399-6576 .- 0001-5172. ; 53:8, s. 1036-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. METHODS: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. RESULTS: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. CONCLUSIONS: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection.
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| 42. |
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| 43. |
- Biel, Anders, 1948, et al.
(författare)
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Emotions, Morality and Public Goods: The WTA-WTP Disparity Revisited
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Empirical evidence suggests that people´s maximum willingness to pay for having a good is often substantially lower than their minimum willingness to accept not having it, and that this discrepancy tends to be especially large when valuing public goods. This paper hypothesizes that differences in emotions (e.g. regret) and moral perceptions can account for much of this discrepancy for public goods. A simple, real-money dichotomous-choice experiment is set up to test these hypotheses, which are largely supported.
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| 44. |
- Biel, Anders, 1948, et al.
(författare)
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The willingness to pay–willingness to accept gap revisited: The role of emotions and moral satisfaction
- 2011
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Ingår i: Journal of Economic Psychology. ; 32:6, s. 908-917
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Tidskriftsartikel (refereegranskat)abstract
- While many earlier studies have found that people’s maximum willingness to pay for having a good is often substantially lower than their minimum willingness to accept not having it, more recent experimental evidence suggests that this discrepancy vanishes for standard consumption goods when an incentive-compatible design without misconceptions is used. This paper hypothesises that there is nevertheless a discrepancy for goods with a perceived moral character, such as contributions to a good cause, and moreover that the reason for this discrepancy can largely be explained by differences in emotions and moral perceptions. The results from a real-money dichotomous-choice experiment, combined with measurements of emotions and morality, are consistent with these hypotheses
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| 45. |
- Birdsell, D. N., et al.
(författare)
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Coinfections identified from metagenomic analysis of cervical lymph nodes from tularemia patients
- 2018
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Ingår i: BMC Infectious Diseases. - : BMC. - 1471-2334. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Underlying coinfections may complicate infectious disease states but commonly go unnoticed because an a priori clinical suspicion is usually required so they can be detected via targeted diagnostic tools. Shotgun metagenomics is a broad diagnostic tool that can be useful for identifying multiple microbes simultaneously especially if coupled with lymph node aspirates, a clinical matrix known to house disparate pathogens. The objective of this study was to analyze the utility of this unconventional diagnostic approach (shotgun metagenomics) using clinical samples from human tularemia cases as a test model. Tularemia, caused by the bacterium Francisella tularensis, is an emerging infectious disease in Turkey. This disease commonly manifests as swelling of the lymph nodes nearest to the entry of infection. Because swollen cervical nodes are observed from many different types of human infections we used these clinical sample types to analyze the utility of shotgun metagenomics.Methods: We conducted an unbiased molecular survey using shotgun metagenomics sequencing of DNA extracts from fine-needle aspirates of neck lymph nodes from eight tularemia patients who displayed protracted symptoms. The resulting metagenomics data were searched for microbial sequences (bacterial and viral).Results: F. tularensis sequences were detected in all samples. In addition, we detected DNA of other known pathogens in three patients. Both Hepatitis B virus (HBV) and Human Parvovirus B-19 were detected in one individual and Human Parvovirus B-19 alone was detected in two other individuals. Subsequent PCR coupled with Sanger sequencing verified the metagenomics results. The HBV status was independently confirmed via serological diagnostics, despite evading notice during the initial assessment.Conclusion: Our data highlight that shotgun metagenomics of fine-needle lymph node aspirates is a promising clinical diagnostic strategy to identify coinfections. Given the feasibility of the diagnostic approach demonstrated here, further steps to promote integration of this type of diagnostic capability into mainstream clinical practice are warranted.
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| 46. |
- Block, Stephan, 1978, et al.
(författare)
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Two-dimensional flow nanometry of biological nanoparticles for accurate determination of their size and emission intensity
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 7, s. art no 12956 -
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Tidskriftsartikel (refereegranskat)abstract
- Biological nanoparticles (BNPs) are of high interest due to their key role in various biological processes and use as biomarkers. BNP size and composition are decisive for their functions, but simultaneous determination of both properties with high accuracy remains challenging. Optical microscopy allows precise determination of fluorescence/scattering intensity, but not the size of individual BNPs. The latter is better determined by tracking their random motion in bulk, but the limited illumination volume for tracking this motion impedes reliable intensity determination. Here, we show that by attaching BNPs to a supported lipid bilayer, subjecting them to hydrodynamic flows and tracking their motion via surface-sensitive optical imaging enable determination of their diffusion coefficients and flow-induced drifts, from which accurate quantification of both BNP size and emission intensity can be made. For vesicles, the accuracy of this approach is demonstrated by resolving the expected radius-squared dependence of their fluorescence intensity for radii down to 15 nm.
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| 47. |
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| 48. |
- Bonnedahl, Jonas, et al.
(författare)
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Characterization, and comparison, of human clinical and black-headed gull (Larus ridibundus) extended-spectrum beta-lactamase-producing bacterial isolates from Kalmar, on the southeast coast of Sweden
- 2010
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 65:9, s. 1939-1944
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance is one of the great challenges for modern healthcare. In Gram-negative bacteria, CTX-M-type extended-spectrum beta-lactamases (ESBLs) have been rapidly spreading through Europe since the early 2000s. In Sweden, ESBL-producing Escherichia coli are still rare, but a 3-fold increase has been seen from 2004 to 2007. Enterobacteria and normal flora of wild animals, with or without antibiotic resistance traits, constitute a potential source of human infection and colonization. We studied wild birds with the aim to understand the environmental dissemination of antibiotic resistance and, focusing on clinically relevant resistance types, we made comparisons with human clinical samples. In this study, ESBL-producing human clinical isolates and isolates from juvenile black-headed gulls from Kalmar County hospital and the city of Kalmar, respectively, on the southeast coast of Sweden, were characterized and compared. Despite a low frequency of antibiotic resistance among the isolates from gulls, ESBL-producing E. coli isolates were found, two with bla(CTX-M-14) and one with bla(CTX-M-15). The same CTX-M types were dominant among human ESBL isolates. In addition, gull isolates were dispersed among the human samples in the PhenePlate (TM) clustering system, indicating that they neither differ from the human isolates nor form any separate clonal clustering. The finding of CTX-M-type ESBLs in E. coli isolated from black-headed gulls in Sweden, where 'background resistance' is low, is consistent with an ongoing environmental spread of these plasmid-borne resistance genes. The results indicate that a potential for transfer between the human population and environment exists even in countries with a low level of antibiotic resistance.
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| 49. |
- Bonnedahl, Jonas, 1970-, et al.
(författare)
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Dissemination of Escherichia coli with CTX-M Type ESBL between Humans and Yellow-Legged Gulls in the South of France
- 2009
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Ingår i: PLOS ONE. - San Francisco, CA, United States : Public Library of Science (PLoS). - 1932-6203. ; 4:Article number: e5958
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Tidskriftsartikel (refereegranskat)abstract
- Extended Spectrum beta-Lactamase (ESBL) producing Enterobacteriaceae started to appear in the 1980s, and have since emerged as some of the most significant hospital-acquired infections with Escherichia coli and Klebsiella being main players. More than 100 different ESBL types have been described, the most widespread being the CTX-M beta-lactamase enzymes (bla(CTX-M) genes). This study focuses on the zoonotic dissemination of ESBL bacteria, mainly CTX-M type, in the southern coastal region of France. We found that the level of general antibiotic resistance in single randomly selected E. coli isolates from wild Yellow-legged Gulls in France was high. Nearly half the isolates (47,1%) carried resistance to one or more antibiotics (in a panel of six antibiotics), and resistance to tetracycline, ampicillin and streptomycin was most widespread. In an ESBL selective screen, 9,4% of the gulls carried ESBL producing bacteria and notably, 6% of the gulls carried bacteria harboring CTX-M-1 group of ESBL enzymes, a recently introduced and yet the most common clinical CTX-M group in France. Multi locus sequence type and phylogenetic group designations were established for the ESBL isolates, revealing that birds and humans share E. coli populations. Several ESBL producing E. coli isolated from birds were identical to or clustered with isolates with human origin. Hence, wild birds pick up E. coli of human origin, and with human resistance traits, and may accordingly also act as an environmental reservoir and melting pot of bacterial resistance with a potential to re-infect human populations.
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| 50. |
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