| 1. |
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| 2. |
- Klasson, Caritha, et al.
(author)
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Sex Differences in the Effect of Vitamin D on Fatigue in Palliative Cancer Care : A Post Hoc Analysis of the Randomized, Controlled Trial 'Palliative-D'
- 2022
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In: Cancers. - : MDPI AG. - 2072-6694. ; 14:3
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Journal article (peer-reviewed)abstract
- In the randomized, placebo-controlled, double-blind trial 'Palliative-D', vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; -1.50 ESAS points (95%CI -2.57 to -0.43; p = 0.007) but not in women; -0.75 (95%CI -1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (-0.33 (95%CI -0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.
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| 3. |
- Klasson, Caritha, et al.
(author)
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Vitamin D and Fatigue in Palliative Cancer : A Cross-Sectional Study of Sex Difference in Baseline Data from the Palliative D Cohort
- 2021
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In: Journal of Palliative Medicine. - : Mary Ann Liebert Inc. - 1096-6218 .- 1557-7740. ; 24:3, s. 433-437
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Journal article (peer-reviewed)abstract
- Background: Fatigue is one of the most distressing symptoms in patients with advanced cancer. Previous studies have shown an association between low vitamin D levels and fatigue. Objectives: The aim of this study was to investigate the association between vitamin D levels and self-assessed fatigue in cancer patients admitted to palliative care, with focus on possible sex differences. Design: This is a cross-sectional study. Subjects: Baseline data from 530 screened patients, 265 women and 265 men, from the randomized placebo-controlled trial "Palliative-D" were analyzed. Measurements: Vitamin D status was measured as 25-hydroxyvitamin D (25-OHD) and fatigue was assessed with EORTC-QLQ-PAL15 and with Edmonton Symptom Assessment System (ESAS). Results: In men, there was a significant correlation between 25-OHD and fatigue measured with the "Tiredness question" (Q11) in EORTC-QLQ-PAL15 (p < 0.05), where higher 25-OHD levels were associated with less fatigue. No correlation between 25-OHD and fatigue was seen for women. Fatigue measured with ESAS did not show any significant association with 25-OHD levels neither in men nor in women. Conclusion: Low vitamin D levels were associated with more fatigue in men but not in women. The study underscores the importance of subgroup analysis of men and women when evaluating the effect of vitamin D in clinical trials since the effect may differ between the sexes. The ongoing "Palliative-D study" will reveal whether vitamin D supplementation may counteract fatigue in both men and women.ClinicalTrial.gov: NCT03038516.
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| 4. |
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| 5. |
- Xu, Hong, et al.
(author)
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Decreased Mortality Over Time During the First Wave in Patients With COVID-19 in Geriatric Care : Data From the Stockholm GeroCovid Study.
- 2021
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In: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 22:8, s. 1565-1573
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To describe temporal changes in treatment, care, and short-term mortality outcomes of geriatric patients during the first wave of the COVID-19 pandemic.DESIGN: Observational study.SETTING AND PARTICIPANTS: Altogether 1785 patients diagnosed with COVID-19 and 6744 hospitalized for non-COVID-19 causes at 7 geriatric clinics in Stockholm from March 6 to July 31, 2020, were included.METHODS: Across admission month, patient vital signs and pharmacological treatment in relationship to risk for in-hospital death were analyzed using the Poisson regression model. Incidence rates (IRs) and incidence rate ratios (IRRs) of death are presented.RESULTS: In patients with COVID-19, the IR of mortality were 27%, 17%, 10%, 8%, and 2% from March to July, respectively, after standardization for demographics and vital signs. Compared with patients admitted in March, the risk of in-hospital death decreased by 29% [IRR 0.71, 95% confidence interval (CI) 0.51-0.99] in April, 61% (0.39, 0.26-0.58) in May, 68% (0.32, 0.19-0.55) in June, and 86% (0.14, 0.03-0.58) in July. The proportion of patients admitted for geriatric care with oxygen saturation <90% decreased from 13% to 1%, which partly explains the improvement of COVID-19 patient survival. In non-COVID-19 patients during the pandemic, mortality rates remained relatively stable (IR 1.3%-2.3%). Compared with non-COVID-19 geriatric patients, the IRR of death declined from 11 times higher (IRR 11.7, 95% CI 6.11-22.3) to 1.6 times (2.61, 0.50-13.7) between March and July in patients with COVID-19.CONCLUSIONS AND IMPLICATIONS: Mortality risk in geriatric patients from the Stockholm region declined over time throughout the first pandemic wave of COVID-19. The improved survival rate over time was only partly related to improvement in saturation status at the admission of the patients hospitalized later throughout the pandemic. Lower incidence during the later months could have led to less severe hospitalized cases driving down mortality.
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| 6. |
- Ahlström, Christer, et al.
(author)
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Fit-for-duty test for estimation of drivers sleepiness level: Eye movements improve the sleep/wake predictor
- 2013
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In: Transportation Research Part C. - : Elsevier. - 0968-090X .- 1879-2359. ; 26, s. 20-32
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Journal article (peer-reviewed)abstract
- Driver sleepiness contributes to a considerable proportion of road accidents, and a fit-for-duty test able to measure a drivers sleepiness level might improve traffic safety. The aim of this study was to develop a fit-for-duty test based on eye movement measurements and on the sleep/wake predictor model (SWP, which predicts the sleepiness level) and evaluate the ability to predict severe sleepiness during real road driving. Twenty-four drivers participated in an experimental study which took place partly in the laboratory, where the fit-for-duty data were acquired, and partly on the road, where the drivers sleepiness was assessed. A series of four measurements were conducted over a 24-h period during different stages of sleepiness. Two separate analyses were performed; a variance analysis and a feature selection followed by classification analysis. In the first analysis it was found that the SWP and several eye movement features involving anti-saccades, pro-saccades, smooth pursuit, pupillometry and fixation stability varied significantly with different stages of sleep deprivation. In the second analysis, a feature set was determined based on floating forward selection. The correlation coefficient between a linear combination of the acquired features and subjective sleepiness (Karolinska sleepiness scale, KSS) was found to be R = 0.73 and the correct classification rate of drivers who reached high levels of sleepiness (KSS andgt;= 8) in the subsequent driving session was 82.4% (sensitivity = 80.0%, specificity = 84.2% and AUC = 0.86). Future improvements of a fit-for-duty test should focus on how to account for individual differences and situational/contextual factors in the test, and whether it is possible to maintain high sensitive/specificity with a shorter test that can be used in a real-life environment, e.g. on professional drivers.
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| 7. |
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| 8. |
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| 9. |
- Correa, Fernando, et al.
(author)
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Activated microglia decrease histone acetylation and Nrf2-inducible anti-oxidant defence in astrocytes: Restoring effects of inhibitors of HDACs, p38 MAPK and GSK3β.
- 2011
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In: Neurobiology of disease. - : Elsevier BV. - 1095-953X .- 0969-9961. ; 44:1, s. 142-51
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Journal article (peer-reviewed)abstract
- Histone deacetylase (HDAC) inhibitors have promising neuroprotective and anti-inflammatory properties although the exact mechanisms are unclear. We have earlier showed that factors from lipopolysaccharide (LPS)-activated microglia can down-regulate the astroglial nuclear factor-erythroid 2-related factor 2 (Nrf2)-inducible anti-oxidant defence. Here we have evaluated whether histone modification and activation of GSK3β are involved in these negative effects of microglia. Microglia were cultured for 24h in serum-free culture medium to achieve microglia-conditioned medium from non-activated cells (MCM(0)) or activated with 10ng/mL of LPS to produce MCM(10). Astrocyte-rich cultures treated with MCM(10) showed a time-dependent (0-72h) increase in astroglial HDAC activity that correlated with lower levels of acetylation of histones H3 and H4 and decreased levels of the transcription factor Nrf2 and γ-glutamyl cysteine ligase modulatory subunit (γGCL-M) protein levels. The HDAC inhibitors valproic acid (VPA) and trichostatin-A (TSA) elevated the histone acetylation levels, restored the Nrf2-inducible anti-oxidant defence and conferred protection from oxidative stress-induced (H(2)O(2)) death in astrocyte-rich cultures exposed to MCM(10). Inhibitors of GSK3β (lithium) and p38 MAPK (SB203580) signaling pathways restored the depressed histone acetylation and Nrf2-related transcription whereas an inhibitor of Akt (Ly294002) caused a further decrease in Nrf2-related transcription. In conclusion, the study shows that well tolerated drugs such as VPA and lithium can restore an inflammatory induced depression in the Nrf2-inducible antioxidant defence, possibly via normalised histone acetylation levels.
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| 10. |
- Correa, Fernando, et al.
(author)
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Dual TNF alpha-Induced Effects on NRF2 Mediated Antioxidant Defence in Astrocyte-Rich Cultures: Role of Protein Kinase Activation
- 2012
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In: Neurochemical Research. - : Springer Science and Business Media LLC. - 0364-3190 .- 1573-6903. ; 37:12, s. 2842-2855
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Journal article (peer-reviewed)abstract
- Tumor necrosis factor-alpha (TNF alpha) is a pleiotropic molecule that can have both protective and detrimental effects in neurodegeneration. Here we have investigated the temporal effects of TNF alpha on the inducible Nrf2 system in astrocyte-rich cultures by determination of glutathione (GSH) levels, gamma glutamylcysteine ligase (gamma GCL) activity, the protein levels of Nrf2, Keap1, the catalytic and modulatory subunit of gamma GCL (gamma GCL-C and gamma GCL-M respectively). Astrocyte-rich cultures were exposed for 24 or 72 h to different concentrations of TNF alpha. Acute exposure (24 h) of astrocyte-rich cultures to 10 ng/mL of TNF alpha increased GSH, gamma GCL activity, the protein levels of gamma GCL-M, gamma GCL-C and Nrf2 in parallel with decreased levels of Keap1. Antioxidant responsive element (ARE)-mediated transcription was blocked by inhibitors of ERK1/2, JNK and Akt whereas inactivation of p38 and GSK3 beta further enhanced transcription. In contrast treatment with TNF alpha for 72 h decreased components of the Nrf2 system in parallel with an increase of Keap1. Stimulation of the Nrf2 system by tBHQ was intact after 24 h but blocked after 72 h treatment with TNF alpha. This down-regulation after 72 h correlated with activation of p38 MAPK and GSK3 beta, since inhibition of these signalling pathways reversed this effect. The upregulation of the Nrf2 system by TNF alpha (24 h treatment) protected the cells from oxidative stress through elevated gamma GCL activity whereas the down-regulation (72 h treatment) caused pronounced oxidative toxicity. One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer's disease, the effect of TNF alpha is detrimental.
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| 11. |
- Correa, Fernando, et al.
(author)
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The Nrf2-inducible antioxidant defense in astrocytes can be both up- and down-regulated by activated microglia:Involvement of p38 MAPK.
- 2011
-
In: Glia. - : Wiley. - 1098-1136 .- 0894-1491. ; 59:5, s. 785-99
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Journal article (peer-reviewed)abstract
- The effects of microglia-conditioned medium (MCM) on the inducible Nrf2 system in astrocyte-rich cultures were investigated by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the modulatory subunit of γGCL (γGCL-M) and activated MAP kinases (ERK1/2, JNK and p38). Microglia were either cultured for 24 h in serum-free culture medium to achieve microglia-conditioned medium from non-activated cells (MCM(0) ), used as control condition, or activated with different concentrations (0.1-1,000 ng mL(-1) ) of lipopolysaccharide (LPS) to produce MCM(0.1-1,000) . Acute exposure (24 h) to MCM(100) increased GSH, γGCL activity, the protein levels of γGCL-M, Nrf2, and activated JNK and ERK1/2 in astrocyte-rich cultures. In contrast, treatment with MCM(10) for 24 h decreased components of the Nrf2 system in parallel with activation of p38 MAPK. Stimulation of the Nrf2 system by tBHQ was partly intact after 24 h but blocked after 72 h treatment with MCM(10) and MCM(100) . This down-regulation after 72 h correlated with activation of p38 MAPK and lack of ERK1/2 and JNK activation. The negative effects were partly reversed by an inhibitor of p38 which restored tBHQ mediated protection against oxidative stress. In conclusion, the study showed a negative effect of MCM(10) on the inducible anti-oxidant defense in astrocyte-rich cultures at both 24 and 72 h that correlated with activation of p38 and was partly reversed by a p38 inhibitor. A transient protective effect of MCM(100) on astrocyte-rich cultures against H(2)O(2) toxicity was observed at 24 h which coincided with activation of JNK and ERK1/2.
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| 12. |
- Correa, Fernando, et al.
(author)
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Time-Dependent Effects of Systemic Lipopolysaccharide Injection on Regulators of Antioxidant Defence Nrf2 and PGC-1α in the Neonatal Rat Brain.
- 2013
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In: Neuroimmunomodulation. - : S. Karger AG. - 1423-0216 .- 1021-7401. ; 20:4, s. 185-193
-
Journal article (peer-reviewed)abstract
- Background/Aims: Both excitotoxicity and neuroinflammation are associated with oxidative stress. One transcription factor, nuclear factor E2-related factor 2 (Nrf2), and one transcription cofactor, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), increase the endogenous antioxidant defence and can thus modulate neuronal cell death. Here, we investigated the temporal effects (after 24 and 72 h) of systemic (i.p.) administration of lipopolysaccharide (LPS) on the cerebral Nrf2 and PGC-1α systems. Methods and Results: Seven-day-old rat pups were injected with LPS (0.3 mg/kg). After 24 h, the protein levels of γ-glutamylcysteine ligase modulatory subunit, γ-glutamylcysteine ligase catalytic subunit, Nrf2, PGC-1α and manganese superoxide dismutase (MnSOD) were increased in parallel with decreased levels of Keap1. These effects were correlated with an increased level of phosphorylated Akt and elevated acetylation of histone 4. In contrast, 72 h following LPS, a decrease in the components of the Nrf2 system in parallel with an increase in Keap1 was observed. The down-regulation after 72 h correlated with phosphorylation of p38 mitogen-activated protein kinase, while there were no changes in PGC-1α and MnSOD protein levels or the acetylation/methylation pattern of histones. Conclusion: Systemic LPS in neonatal rats induced time-dependent changes in brain Nrf2 and PGC-1α that correlated well with the protective effect observed after 24 h (pre-conditioning) and the deleterious effects observed after 72 h (sensitizing) of systemic LPS reported earlier. Collectively, the results point towards Nrf2 and PGC-1α as a possible mechanism behind these effects.
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| 13. |
- D'angelo, Barbara, et al.
(author)
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Expression of the Nrf2-system at the blood-CSF barrier is modulated by neonatal inflammation and hypoxia-ischemia
- 2013
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In: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 36:3, s. 479-490
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Journal article (peer-reviewed)abstract
- ORIGINAL ARTICLE Expression of the Nrf2-system at the blood-CSF barrier is modulated by neonatal inflammation and hypoxia-ischemia Barbara D ’ Angelo & C. Joakim Ek & Mats Sandberg & Carina Mallard Received: 29 May 2012 /Revised: 14 September 2012 /Accepted: 10 October 2012 /Published online: 30 October 2012 # SSIEM and Springer Science+Business Media Dordrecht 2012 Abstract Transcription factor NF-E2-related factor-2 (Nrf2) is a key regulator of endogenous anti-oxidant sys- tems shown to play a neuroprotective role in the adult by preserving blood – brain barrier function. The choroid plex- us, site for the blood-CSF barrier, has been suggested to be particularly important in maintaining brain barrier function in development. We investigated the expression of Nrf2- and detoxification-system genes in choroid plexus following systemic LPS injections, unilateral cerebral hypoxia- ischemia (HI) as well as the combination of LPS and HI (LPS/HI). Plexuses were collected at different time points after LPS, HI and LPS/HI in 9-day old mice. mRNA levels of Nrf2 and many of its target genes were analyzed by quantitative PCR. Cell death was analyzed by caspase-3 immunostaining and TUNEL. LPS caused down-regulation of the Nrf2-system genes while HI increased expression at earlier time points. LPS exposure prior to HI prevented many of the HI-induced gene increases. None of the insults resulted in any apparent cell death to choroidal epithelium. These data imply that the function of the inducible anti- oxidant system in the choroid plexus is down-regulated by inflammation, even if choroid cells are not structurally damaged. Further, LPS prevented the endogenous antioxi- dant response following HI, suggesting the possibility that the choroid plexus may be at risk if LPS is united with an insult that increases oxidative stress such as hypoxia- ischemia.
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| 14. |
- D'angelo, Barbara, et al.
(author)
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GSK3β inhibition protects the immature brain from hypoxic-ischaemic insult via reduced STAT3 signalling
- 2016
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In: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 101, s. 13-23
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Journal article (peer-reviewed)abstract
- Hypoxic-ischaemic (HI) injury is an important cause of neurological morbidity in neonates. HI leads to pathophysiological responses, including inflammation and oxidative stress that culminate in cell death. Activation of glycogen synthase kinase 3β (GSK3β) and the signal transducer and activator of transcription (STAT3) promotes brain inflammation. The purpose of this study was to test whether inhibition of GSK3β signalling protects against neonatal HI brain injury. Mice were subjected to HI at postnatal day (PND) 9 and treated with a selective GSK3β inhibitor, SB216763. Brain injury and caspase-3 activation, anti-oxidant and inflammatory mRNA responses and activation of STAT3 were analysed. Our results show that HI reduced phosphorylation of GSK3β, thus promoting its kinase activity. The GSK3β inhibitor reduced caspase-3 activation and neuronal cell death elicited by HI and reverted the effects of HI on gene expression of the anti-oxidant enzyme sod2 and mitochondrial factor pgc1α. The HI insult activated STAT3 in glial cells and GSK3β inhibition attenuated STAT3 phosphorylation and its nuclear translocation following HI. Further, GSK3β inhibition reduced HI-induced gene expression of pro-inflammatory cytokines tnfα and Il-6, while promoted the anti-inflammatory factor Il-10. In summary, data show that GSK3β inhibition is neuroprotective in neonatal HI brain injury likely via reduced pro-inflammatory responses by blocking STAT3 signalling. Our study suggests that pharmacological interventions built upon GSK3β silencing strategies could represent a novel therapy in neonatal brain injury. © 2015 Elsevier Ltd. All rights reserved.
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| 15. |
- de-Wahl Granelli, Anne, 1970, et al.
(author)
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Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study in 39,821 newborns.
- 2009
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In: BMJ (Clinical research ed.). - 1468-5833. ; 338
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the use of pulse oximetry to screen for early detection of life threatening congenital heart disease. DESIGN: Prospective screening study with a new generation pulse oximeter before discharge from well baby nurseries in West Götaland. Cohort study comparing the detection rate of duct dependent circulation in West Götaland with that in other regions not using pulse oximetry screening. Deaths at home with undetected duct dependent circulation were included. SETTING: All 5 maternity units in West Götaland and the supraregional referral centre for neonatal cardiac surgery. PARTICIPANTS: 39,821 screened babies born between 1 July 2004 and 31 March 2007. Total duct dependent circulation cohorts: West Götaland n=60, other referring regions n=100. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and likelihood ratio for pulse oximetry screening and for neonatal physical examination alone. RESULTS: In West Götaland 29 babies in well baby nurseries had duct dependent circulation undetected before neonatal discharge examination. In 13 cases, pulse oximetry showed oxygen saturations
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| 16. |
- Kawamura, Takuya, et al.
(author)
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Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic-Ischemic Brain Injury in Neonatal Mice
- 2023
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In: Asn Neuro. - 1759-0914. ; 15
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Journal article (peer-reviewed)abstract
- A clinical challenge remains in the treatment of hypoxic-ischemic brain injury in newborns. Nicotinamide adenine dinucleotide (NAD+) has beneficial effects in animal models of adult stroke. Here, we aimed to understand the short- and long-term neuroprotective effects of NAD+-promoting substance nicotinamide mononucleotide (NMN) in a well-established brain injury model in neonatal mice. Postnatal day (PND) 9 male and female mice were subjected to cerebral hypoxia-ischemia and treated with saline or NMN (50 mg/kg) immediately after hypoxia-ischemia. At different time points after hypoxia-ischemia, hippocampal NAD+, caspase-3 activity, protein expression of SIRT1, SIRT6, release of high mobility group box-1 (HMGB1), long-term neuropathological outcome, short-term developmental behavior, and long-term motor and memory function were evaluated. Neonatal hypoxia-ischemia reduced NAD+ and SIRT6 levels, but not SIRT1, in the injured hippocampus, while HMGB1 release was significantly increased. NMN treatment normalized hippocampal NAD+ and SIRT6 levels, while caspase-3 activity and HMGB1 release were significantly reduced. NMN alleviated tissue loss in the long-term and improved early developmental behavior, as well as motor and memory function. This study shows that NMN treatment provides neuroprotection in a clinically relevant neonatal animal model of hypoxia-ischemia in mice suggesting as a possible novel treatment for neonatal brain injury.Summary StatementNeonatal hypoxia-ischemia reduces nicotinamide adenine dinucleotide (NAD+) and SIRT6 levels in the injured hippocampus.Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia-ischemia.Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD+ and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release.NMN improves early developmental behavior, as well as motor and memory function. Graphical AbstractThis is a visual representation of the abstract.
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| 17. |
- Nygren, Gudrun, 1957, et al.
(author)
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The prevalence of autism spectrum disorders in toddlers: a population study of 2-year-old Swedish children.
- 2012
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In: Journal of Autism and Developmental Disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 42:7, s. 1491-1497
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Journal article (peer-reviewed)abstract
- Autism Spectrum Disorder (ASD) is more common than previously believed. ASD is increasingly diagnosed at very young ages. We report estimated ASD prevalence rates from a population study of 2-year-old children conducted in 2010 in Gothenburg, Sweden. Screening for ASD had been introduced at all child health centers at child age 21/2 years. All children with suspected ASD were referred for evaluation to one center, serving the whole city of Gothenburg. The prevalence for all 2-year-olds referred in 2010 and diagnosed with ASD was 0.80%. Corresponding rates for 2-year-olds referred to the center in 2000 and 2005 (when no population screening occurred) were 0.18 and 0.04%. Results suggest that early screening contributes to a large increase in diagnosed ASD cases.
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| 18. |
- Olsén, Lena, et al.
(author)
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Methadone in healthy goats : Pharmacokinetics, behaviour and blood pressure
- 2013
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In: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 95:1, s. 231-237
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Journal article (peer-reviewed)abstract
- The pharmacokinetics and effects of the opioid methadone on behaviour, arterial blood pressure, heart rate and haematocrit were studied in goats. Two goats received methadone (0.2 mg/kg) intravenously and the terminal half-life was 88 and 91 min, the volume of distribution 8.4 and 6.1 L/kg, and clearance 86 and 123 mL/min/kg. In a crossover study eight goats received methadone (0.6 mg/kg) or 0.15 M NaCl subcutaneously (SC). After SC administration bioavailability was complete and the terminal half-life was 215 +/- 84 min (mean +/- SD), T-max 31 +/- 15 min and C-max 45 +/- 11 ng/mL. Blood pressure and haematocrit increased while heart rate did not change. The goats did not ruminate and they climbed, scratched, gnawed and showed tail-flicking after SC methadone in contrast to NaCl administration. The use of methadone in goats may be restricted due to the inhibition of rumination and the rather short half-life.
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| 19. |
- Patil, Jaspal, et al.
(author)
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Spirulina diet to lactating mothers protects the antioxidant system and reduces inflammation in post-natal brain after systemic inflammation.
- 2018
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In: Nutritional neuroscience. - 1476-8305. ; 21:1, s. 59-69
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Journal article (peer-reviewed)abstract
- This study concerns: (1) the long-term effects of peripheral lipopolysaccharide (LPS) in neonatal rats on inflammation and antioxidant parameters in brain and (2) the effects of a Spirulina-enriched diet given to lactating mothers on protective and inflammatory parameters in brains of suckling pups subjected to peripheral inflammation.Five-day old rat pups were treated with LPS (i.p. 2mg/kg). After 3, 7, 30, and 65 days, mRNA, miRNA, and protein levels of pro-inflammatory cytokines and the Nuclear factor E2-related factor 2 (Nrf2)-system were examined. In a sub-group, a Spirulina-enriched diet was given to the mothers 24 hours before the pups were treated with LPS, then the effects on antioxidant and inflammatory parameters were evaluated.The main findings were: (1) interleukin 1 beta (IL-1β) was upregulated in cortex 3, 7, and 30 days after LPS treatment, (2) Nrf2 and the catalytic subunit of γ-glutamylcysteinyl ligase were decreased in cortex 7 days after LPS in parallel with increased levels of phosphorylated p38 and decreased levels of histone H3 acetylation, and (3) a Spirulina-enriched diet to lactating mothers normalized both the increased IL-1β expression and the decreased antioxidant parameters after LPS. The protective effects of Spirulina were correlated with decreased levels of phosphorylated p38 and high levels of the antioxidant miRNA-146a.A Spirulina diet given to lactating mothers can protect against neuroinflammation and decreased antioxidant defence in brain of suckling pups subjected to peripheral inflammation, possibly via decreased activation of p38 and high levels of the antioxidant miRNA-146a.
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| 20. |
- Patil, Jaspal, et al.
(author)
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Sustained Effects of Neonatal Systemic Lipopolysaccharide on IL-1 beta and Nrf2 in Adult Rat Substantia Nigra Are Partly Normalized by a Spirulina-Enriched Diet
- 2016
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In: Neuroimmunomodulation. - : S. Karger AG. - 1021-7401 .- 1423-0216. ; 23:4, s. 250-259
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Journal article (peer-reviewed)abstract
- Background/Aim: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin (IL)-1 beta, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxi-some proliferator-activated receptor gamma coactivator (PGC)-1 alpha in rat SN. Method and Results: Five-day-old rat pups were treated with LPS (i. p. 2 mg/kg). After 65 days, the mRNA level of IL-1 beta was significantly increased, in parallel with a decrease in that of the rate-limiting enzyme in glutathione synthesis, the gamma-glutamylcysteine ligase catalytic subunit (gamma GCLc), Nrf2, and brain-derived neurotrophic factor (BDNF). Protein levels of gamma GCLc and Nrf2 were decreased while IL-1 beta protein was significantly increased. These LPS-induced long-term changes correlated with a decrease in phosphorylated (active) AKT (pAKT) and phosphorylated (inactive) GSK-3 beta (pGSK-3 beta). In another set of experiments, a 0.1% Spirulina-containing diet was given to lactating mothers 24 h before the LPS treatment of the pups. The Spirulina-supplemented diet decreased IL-1 beta protein expression in SN and elevated the mRNA level of gamma GCLc, Nrf2 protein, PGC-1 alpha protein, and pAKT. Conclusion: Early-life infection can negatively affect Nrf2, pAKT, and pGSK-3 beta for a long time in SN. A diet en-riched with antioxidant and anti-inflammatory phytochemicals can partly restore some, but not all, of the effects on the antioxidant defense, possibly via normalizing effects on pAKT. (C) 2016 S. Karger AG, Basel
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| 21. |
- Sandberg, David, 1980, et al.
(author)
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The Characteristics of Sleepiness During Real Driving at Night - A Study of Driving Performance, Physiology and Subjective Experience
- 2011
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In: Sleep. - 1550-9109 .- 0161-8105. ; 34:10, s. 1317-1325
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Journal article (peer-reviewed)abstract
- Study Objectives: Most studies of sleepy driving have been carried out in driving simulators. A few studies of real driving are available, but these have used only a few sleepiness indicators. The purpose of the present study was to characterize sleepiness in several indicators during real driving at night, compared with daytime driving. Design: Participants drove 55 km (at 90km/h) on a 9-m-wide rural highway in southern Sweden. Daytime driving started at 09: 00 or 11: 00 (2 groups) and night driving at 01: 00 or 03: 00 (balanced design). Setting: Instrumented car on a real road in normal traffic. Participants: Eighteen participants drawn from the local driving license register. Interventions: Daytime and nighttime drives. Measurement and Results: The vehicle was an instrumented car with video monitoring of the edge of the road and recording of the lateral position and speed. Electroencephalography and electrooculography were recorded, together with ratings of sleepiness every 5 minutes. Pronounced effects of night driving were seen for subjective sleepiness, electroencephalographic indicators of sleepiness, blink duration, and speed. Also, time on task showed significant effects for subjective sleepiness, blink duration, lane position, and speed. Sleepiness was highest toward the end of the nighttime drive. Night driving caused a leftward shift in lateral position and a reduction of speed. The latter two findings, as well as the overall pattern of sleepiness indicators, provide new insights into the effects of night driving. Conclusion: Night driving is associated with high levels of subjective, electrophysiologic, and behavioral sleepiness.
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| 22. |
- Sandberg, Matilda, 1990-, et al.
(author)
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Contradictions Within the Swedish Welfare System : Social Services’ Homelessness Strategies Under Housing Inequality
- 2023
-
In: Social Inclusion. - Lisbon, Portugal : Cogitatio Press. - 2183-2803. ; 11:3
-
Journal article (peer-reviewed)abstract
- Sweden has seen a rise in homelessness alongside its strained housing market. References are increasingly being made to structural problems with housing provision, rather than individual issues. Housing has been organized through the local social services, which are responsible for supporting homeless people. With a foundation in housing studies, this article analyzes the Swedish social services’ challenges and actions in a time in which affordable housing is in shortage, and housing inequality a reality, through the lens of social services. The focus is on the intersection between the regular housing market and housing provision (primary welfare system), the social services needs‐tested support (secondary welfare system), and the non‐profit and for‐profit organizations (tertiary welfare system), with emphasis on the first two. The article is based on interviews with people working for the City of Malmö and illustrates how the housing shortage problem is moved around within the welfare system whilst also showing that social services’ support for homeless individuals appears insufficient. Social services act as a “first line” gatekeeper for those who have been excluded from the regular housing market. Moreover, recently implemented restrictions aim to make sure that the social services do not act as a “housing agency,” resulting in further exclusion from the housing market. The article highlights how the policies of the two welfare systems interact with and counteract each other and finally illustrates how homeless individuals fall between them. It highlights the need to link housing and homelessness in both research and practice to gain a deeper understanding of the complexities of housing markets and how homelessness is sustained.
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| 23. |
- Sandberg, Mikael, 1956-
(author)
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Ingen tid för forskning - om professorers arbetsvillkor 2018
- 2018
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Reports (other academic/artistic)abstract
- SULF:s professorers förening, SPF har genomfört en enkätundersökning för att studera hur professorer ser på sina arbetsförhållanden, med fokus på bland annat forskningstid i tjänst, kollegialitet kontra linjestyrning, samt bredare systemfrågor. Undersökningens huvudsakliga slutsats är att tid för forskning i tjänst skiljer sig radikalt mellan professorer anställda i vid svenska universitet och högskolor. Det finns alltså inte en generell andel forskning i den tjänst som benämns ”professor”. Det föreligger en stor variation mellan professorer gällande vilken forskningstid de har i tjänst, med spridning mellan 0 till 100 procent. Detta var den fråga som flest kommenterade, och professorer beskrev bland annat problem med beroende av externfinansiering samt osäkerhet och oförutsägbarhet i fakultets- eller institutionstid för forskning. Detta påvisar det osäkra läget för svenska professorers forskning. Att SULF ska driva frågan om minst 50 procents forskning i tjänst för professorer och minst 30 procent för lektorer får därmed överväldigande stöd i undersökningen. I fritextsvar lyfts bland annat fram betydelsen av att räkna in tid också för andra uppdrag. Enkätsvaren visar också stöd för att emeriti skall få behålla anknytning i form av service för forskare och lärare såsom epost, adress, kopieringsservice, med mera. Begreppet ”kollegialitet”, som det diskuterats i SULF:s förbundsdialog, får överväldigande stöd i enkäten, och svaren stödjer en linjestyrning som är underordnad kollegial struktur. Dock visar fritextsvar att kollegialitet i själva verket tolkas på många olika sätt och att det inte är givet inom professorsgruppen hur det skall förstås. Fritextssvar betonar också betydelsen av att säkerställa korrekta beslutsprocesser. Undersökningen kan därmed ses som att den visar på vissa övergripande problem i svensk akademi. Trots att enkätsvaren anger närmast ett totalt motstånd mot styrning påverkad av kapital, vänskapskorruption eller politik, anser cirka en tredjedel idag inte att regelverk eller beslutprocesser vid deras lärosäte säkerställer detta. Enkätundersökningen genomfördes i slutet av februari till början av mars 2018. Alla SULF-anslutna professorer som gick att identifiera samt nå via det centrala medlemsregistret ingick i denna totalundersökning (det vill säga det totala antalet medlemmar som i medlemsregistret angett sin titel som professor samt angivit mejladress fick uppmaningen att svara på enkäten). Enkäten besvarades av drygt 730 respondenter, cirka en tredjedel kvinnor. Svarsfrekvensen var cirka 48 procent beroende på fråga i enkäten. Ett stort antal – totalt 190 personer - skrev också fritextkommentarer som till stor del återges i rapporten.
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| 24. |
- Sandberg, Mats, 1953, et al.
(author)
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NRF2-regulation in brain health and disease: Implication of cerebral inflammation
- 2014
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In: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 79, s. 298-306
-
Journal article (peer-reviewed)abstract
- The nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulator of endogenous inducible defense systems in the body. Under physiological conditions NRF2 is mainly located in the cytoplasm. However, in response to oxidative stress, NRF2 translocates to the nucleus and binds to specific DNA sites termed "anti-oxidant response elements"or "electrophile response elements"to initiate transcription of cytoprotective genes. Acute oxidative stress to the brain, such as stroke and traumatic brain injury is increased in animals that are deficient in NRF2. Insufficient NRF2 activation in humans has been linked to chronic diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. New findings have also linked activation of the NRF2 system to anti-inflammatory effects via interactions with NF-κB. Here we review literature on cellular mechanisms of NRF2 regulation, how to maintain and restore NRF2 function and the relationship between NRF2 regulation and brain damage. We bring forward the hypothesis that inflammation via prolonged activation of key kinases (p38 and GSK-3β) and activation of histone deacetylases gives rise to dysregulation of the NRF2 system in the brain, which contributes to oxidative stress and injury. © 2013 Elsevier B.V. All rights reserved.
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| 25. |
- Sandberg, Susanne, 1977-, et al.
(author)
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Peer assessment of contributions into group projects as a tool for group monitoring and individual learning in the multi-cultural classroom
- 2017
-
In: Proceedings of the 59th Annual Meeting of the Academy of International Business. - : Academy of International Business. ; , s. 158-159
-
Conference paper (peer-reviewed)abstract
- The increased internationalisation of higher education creates opportunities and challenges when planning education for a cross-cultural classroom environment. Students from different nationalities and cultures are brought together for both individual and collaborative learning processes. The pedagogical topic and issues to be discussed are related to the usage of peer assessment of contributions into group projects as a tool for group monitoring and individual learning in a cross-cultural classroom environment. Students at an international master programme in international business strategy in Sweden have reported on their perceptions on both their own and the other group members’ contributions into the group work. The potential contribution and usefulness of such a tool, as well as the usage of group reports in courses with individual grading, will be further problematized and discussed for a cross-cultural learning environment.
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| 26. |
- Singh-Mallah, Gagandeep, et al.
(author)
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N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice
- 2021
-
In: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 15
-
Journal article (peer-reviewed)abstract
- Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases. Sirtuin-6 is thought to regulate inflammatory and oxidative pathways, such as the extracellular release of the alarmin high mobility group box-1 (HMGB1). The expression and role of sirtuin-6 in neonatal brain injury are unknown. In a well-established model of neonatal brain injury, which encompasses inflammation (lipopolysaccharide, LPS) and hypoxia-ischemia (LPS+HI), we investigated the protein expression of sirtuin-6 and HMGB1, as well as thiol oxidation. Furthermore, we assessed the effect of the antioxidant N-acetyl cysteine (NAC) on sirtuin-6 expression, nuclear to cytoplasmic translocation, and release of HMGB1 in the brain and blood thiol oxidation after LPS+HI. We demonstrate reduced expression of sirtuin-6 and increased release of HMGB1 in injured hippocampus after LPS+HI. NAC treatment restored sirtuin-6 protein levels, which was associated with reduced extracellular HMGB1 release and reduced thiol oxidation in the blood. The study suggests that early reduction in sirtuin-6 is associated with HMGB1 release, which may contribute to neonatal brain injury, and that antioxidant treatment is beneficial for the alleviation of these injurious mechanisms.
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| 27. |
- Singh-Mallah, Gagandeep, et al.
(author)
-
The Role of Mitochondrial and Endoplasmic Reticulum Reactive Oxygen Species Production in Models of Perinatal Brain Injury
- 2019
-
In: Antioxidants & Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 31:9, s. 643-663
-
Journal article (peer-reviewed)abstract
- Recent Advances and Critical Issues: Mechanisms underlying ER stress-associated ROS production have been primarily elucidated using either non-neuronal cells or adult neurodegenerative experimental models. Findings from mature brain cannot be simply transferred to the immature brain. Therefore, age-specific studies investigating ER stress modulators may help investigate ER stress-associated ROS pathways in the immature brain. New therapeutics such as mitochondrial site-specific ROS inhibitors that selectively inhibit superoxide (O-2(center dot-))/hydrogen peroxide (H2O2) production are currently being developed. Future Directions: Because ER stress and oxidative stress accentuate each other, a combinatorial therapy utilizing both antioxidants and ER stress inhibitors may prove to be more protective against perinatal brain injury. Moreover, multiple relevant targets need to be identified for targeting ROS before they are formed. The role of organelle-specific ROS in brain repair needs investigation.
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| 28. |
- Sørvoll, Jardar, et al.
(author)
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Housing And Welfare In Sweden, Norway And The Wider Nordic Region
- 2024. - 1
-
In: The Routledge Handbook of Housing and Welfare. - London : Routledge. - 9781032074337 - 9781003212690 ; , s. 88-106
-
Book chapter (peer-reviewed)abstract
- In this chapter, the authors discuss the historical development and the current state of the housing and welfare regimes in the Nordic countries, using Sweden and Norway as our main cases. The two neighbouring countries on the Scandinavian peninsula are often classified as generous social democratic welfare regimes with a high level of universalism and de-commodification. In the first postwar decades, however, Sweden and Norway chose different paths in the sphere of housing policy. In Sweden, there are four main forms of tenure. Ownership rights (owner-occupied housing) are mainly enjoyed in single-family houses. The Norwegian housing regime is a liberal and selective sector of what is still a generous welfare regime with many universal benefits and services. Sweden and Norway both experienced a gradual “system shift” in housing policy in the 1980s, 1990s and after the millennium.
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| 29. |
- Wang, Xiaoyang, 1965, et al.
(author)
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N-acetylcysteine reduces lipopolysaccharide-sensitized hypoxic-ischemic brain injury.
- 2007
-
In: Annals of neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 61:3, s. 263-71
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Maternal inflammation/infection alone or in combination with birth asphyxia increases the risk for perinatal brain injury. Free radicals are implicated as major mediators of inflammation and hypoxia-ischemia (HI)-induced perinatal brain injury. This study evaluated the neuroprotective efficacy of a scavenging agent, N-acetylcysteine (NAC), in a clinically relevant model. METHODS: Lipopolysaccharide (LPS)-sensitized HI brain injury was induced in 8-day-old neonatal rats. NAC was administered in multiple doses, and brain injury was evaluated at 7 days after HI. RESULTS: NAC (200mg/kg) provided marked neuroprotection with up to 78% reduction of brain injury in the pre+post-HI treatment group and 41% in the early (0 hour) post-HI treatment group, which was much more pronounced protection than another free radical scavenger, melatonin. Protection by NAC was associated with the following factors: (1) reduced isoprostane activation and nitrotyrosine formation; (2) increased levels of the antioxidants glutathione, thioredoxin-2, and (3) inhibition of caspase-3, calpain, and caspase-1 activation. INTERPRETATION: NAC provides substantial neuroprotection against brain injury in a model that combines infection/inflammation and HI. Protection by NAC was associated with improvement of the redox state and inhibition of apoptosis, suggesting that these events play critical roles in the development of lipopolysaccharide-sensitized HI brain injury.
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| 30. |
- Welin, Anna-Karin, 1965, et al.
(author)
-
White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheep brain.
- 2005
-
In: Pediatric research. - 0031-3998. ; 58:1, s. 100-5
-
Journal article (peer-reviewed)abstract
- Free radicals seem to be involved in the development of cerebral white matter damage after asphyxia in the premature infant. The immature brain may be at increased risk of free radical mediated injury, as particularly the preterm infant has a relative deficiency in brain antioxidants systems, such as superoxide dismutase and glutathione peroxidase. In vitro studies show that immature oligodendrocytes express an intrinsic vulnerability to reactive oxygen species and free radical scavengers are able to protect immature oligodendrocytes from injury. The aim of this study was to examine the formation of ascorbyl radicals as a marker of oxidative stress in the preterm brain in association with cerebral white matter injury after intrauterine asphyxia. Fetal sheep at 0.65 gestation were chronically instrumented with vascular catheters and an occluder cuff around the umbilical cord. A microdialysis probe was placed in the periventricular white matter. Fetal asphyxia was induced by occlusion of the umbilical cord for 25 min (n = 10). Microdialysis samples were collected for 72 h and analyzed for ascorbyl radicals using electron spin resonance. Five instrumented fetuses served as controls. Three days after the insult, fetal brains were examined for morphologic injury. Umbilical cord occlusion resulted in prolonged and marked increase in ascorbyl radical production in the brain in connection with white matter injury, with activation of microglia cells in periventricular white matter and axonal injury. These data suggest that reperfusion injury following asphyxia in the immature brain is associated with marked free radical production.
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| 31. |
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