| 1. |
- Cedervall, Ylva, et al.
(författare)
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Timed Up-and-Go Dual-Task Testing in the Assessment of Cognitive Function : A Mixed Methods Observational Study for Development of the UDDGait Protocol
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- New methods to screen for and identify early-stage dementia disorders are highly sought after. The purpose of this pilot study is to develop a study protocol for a dual-task test aimed at aiding the early detection of dementia disorders. We used the Timed Up-and-Go (TUG) test, which is a mobility task involving starting in a sitting position, standing up, walking three meters to cross a line on the floor, turning around, walking back and sitting down again. We combined TUG with the verbal task of naming different animals. Pilot study participants were 43 individuals with and without established dementia diagnoses who attended a clinic for memory assessment. Video-recorded test performances were systematically analysed. Deviant test performances concerning the interplay between test administration and participants' responses to the assessment instructions were revealed and led to refinements being made to the final study protocol. Exploration of the dual-task test outcome measures in a sub-sample of 22 persons, ten with and twelve without dementia, indicated that step-length and number of named animals after the turning point of the dual-task test might constitute appropriate measures for examining this kind of sample. We concluded that the refined study protocol is feasible for testing individuals undergoing initial memory assessments and healthy controls. Follow-up studies with larger samples are being carried out and will bring new knowledge to this area of research. It may also provide an opportunity for further studies exploring possibilities for broad clinical implementation.
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| 2. |
- Uvnäs-Moberg, Kerstin, et al.
(författare)
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Neuroendocrine mechanisms involved in the physiological effects caused by skin-to-skin contact - With a particular focus on the oxytocinergic system
- 2020
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Ingår i: Infant Behavior and Development. - : Elsevier. - 0163-6383 .- 1879-0453 .- 1934-8800. ; 61:November
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Forskningsöversikt (refereegranskat)abstract
- The positive clinical effects caused by skin-to-skin contact immediately after birth or after repeated skin-to-skin contact of premature infants (kangaroo care) or fullterm infants are well documented in the literature. However, information regarding the physiological mechanisms mediating these effects are surprisingly scarce and incomplete. In this article the oxytocinergic system and the cutaneous sensory pathways by which the oxytocinergic system is activated in response to skin-to-skin contact are presented in more detail. In addition, we discuss how the effects of skin-to-skin treatment can be attributed to different aspects of the effect spectrum of the oxytocinergic or calm and connection system.The structure of the oxytocinergic system, comprising the peripheral (circulating, hormonal) and the central (neurotransmitter) components, as well as, the pathways and mechanisms by which these functions are coordinated are described. Also the various effects induced by the oxytocinergic system (the calm and connection system) are reviewed.The sensory pathways, which include visual, auditory, olfactory and tactile stimuli, given and received by both mother and newborn and which activate the oxytocinergic system in response to skin-to-skin contact, are reviewed. A special emphasis is placed on the role of cutaneous sensory nerves and their activation by touch, light pressure and in particular warmth. The important role of the rise and the pulsatility of maternal temperature in mediating the positive effects of skin-to-skin contact in the newborn is highlighted. The concept of maternal giving of warmth and its possible link to the experience of trust and safety in the newborn is discussed from an evolutionary perspective.The effects induced by skin-to-skin contact can be attributed to the different functions of the oxytocinergic system. Ameliorated social interaction (e.g., more tactile and auditory interaction, more sensitive and synchronous interaction between mother and baby, the baby’s crawling behavior) are expressions of oxytocin’s ability to stimulate social interaction. The decreased levels of fear and stress are expressions of oxytocin’s ability to reduce the activity of the amygdala and of the stress system, e.g. the activity in the HPA-axis and the sympathetic nervous system. Increased HRV, increased activity in endocrine system of the gastrointestinal tract as well as stimulation of growth and maturation are examples of oxytocin’s ability to stimulate the activity of the parasympathetic nervous system and other peripheral and central mechanisms related to restoration and growth.The propensity of different types of treatment with skin-to-skin contact to induce long-term effects is also highlighted. We propose that the sustained effects caused by skin-to-skin contact are induced by an enduring shift in the balance between the oxytocinergic system (the calm and connection system) and the stress system (fight flight reaction) in favor of the oxytocinergic system. This shift leads to a sustained decrease in the HPA-axis and the sympathetic nervous system probably involving alpha 2-adrenoceptors.It is of clinical importance to be aware of the mechanisms by which skin-to-skin contact induces short and longterm positive effects in parents and newborns. If ward routines are adapted to ascertain a maximal stimulation of these mechanisms, the function of the oxytocinergic system will be optimized, which will be linked to a better clinical outcome for parents and newborns.
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| 3. |
- Hansson, Elisabeth, 1955, et al.
(författare)
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Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation
- 2016
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Ingår i: IBRO Reports. - : Elsevier BV. - 2451-8301. ; 1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to test pharmaceutical compounds targeting astrocytes showing inflammatory dysregulation. The primary rat brain cultures were treated with different batches of serum with or without microglia added to make the cells inflammatory-reactive. Lipopolysaccharide (LPS) and tryptase were used as inflammatory inducers. Expression levels of Toll-like receptor 4 (TLR4), Na+/K+-ATPase, and matrix metalloprotease-13 (MMP-13), as well as actin filament organization, pro-inflammatory cytokines, and intracellular Ca2+ release, were evaluated. LPS combined with tryptase upregulated TLR4 expression, whereas Na+/K+-ATPase expression was downregulated, ATP-evoked Ca2+ transients were increased, actin filaments were reorganized and ring structures instead of stress fibers were observed. Other aims of the study were to prevent astrocytes from becoming inflammatory-reactive and to restore inflammatory dysregulated cellular changes. A combination of the μ-opioid antagonist (−)-naloxone in ultra-low concentrations, the non-addictive μ-opioid agonist (−)-linalool, and the anti-epileptic agent levetiracetam was examined. The results indicated that this drug cocktail prevented the LPS- and tryptase-induced inflammatory dysregulation. The drug cocktail could also restore the LPS- and tryptase-treated cells back to a normal physiological level in terms of the analyzed parameters. © 2016 The Author(s)
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| 4. |
- Leclair, Valerie, et al.
(författare)
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Distinct HLA associations with autoantibody-defined subgroups in idiopathic inflammatory myopathies
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 96
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Tidskriftsartikel (refereegranskat)abstract
- Background In patients with idiopathic inflammatory myopathies (IIM), autoantibodies are associated with specific clinical phenotypes suggesting a pathogenic role of adaptive immunity. We explored if autoantibody profiles are associated with specific HLA genetic variants and clinical manifestations in IIM. Methods We included 1348 IIM patients and determined the occurrence of 14 myositis-specific or-associated autoantibodies. We used unsupervised cluster analysis to identify autoantibody-defined subgroups and logistic regression to estimate associations with clinical manifestations, HLA-DRB1, HLA-DQA1, HLA-DQB1 alleles, and amino acids imputed from genetic information of HLA class II and I molecules. Findings We identified eight subgroups with the following dominant autoantibodies: anti-Ro52, -U1RNP, -PM/Scl,-Mi2,-Jo1,-Jo1/Ro52,-TIF1 gamma or negative for all analysed autoantibodies. Associations with HLA-DRB1*11, HLA-DRB1*15, HLA-DQA1*03, and HLA-DQB1*03 were present in the anti-U1RNP-dominated subgroup. HLA-DRB1*03, HLA-DQA1*05, and HLA-DQB1*02 alleles were overrepresented in the anti-PM/Scl and anti-Jo1/ Ro52-dominated subgroups. HLA-DRB1*16, HLA-DRB1*07 alleles were most frequent in anti-Mi2 and HLA- DRB1*01 and HLA-DRB1*07 alleles in the anti-TIF1 gamma subgroup. The HLA-DRB1*13, HLA-DQA1*01 and HLA-DQB1*06 alleles were overrepresented in the negative subgroup. Significant signals from variations in class I molecules were detected in the subgroups dominated by anti-Mi2, anti-Jo1/Ro52, anti-TIF1 gamma, and the negative subgroup. Interpretation Distinct HLA class II and I associations were observed for almost all autoantibody-defined subgroups. The associations support autoantibody profiles use for classifying IIM which would likely reflect underlying pathogenic mechanisms better than classifications based on clinical symptoms and/or histopathological features. Funding See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript. Copyright (c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 5. |
- Hansson, Elisabeth, 1955, et al.
(författare)
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Anti-inflammatory effects induced by ultralow concentrations of bupivacaine in combination with ultralow concentrations of sildenafil (Viagra) and vitamin D3 on inflammatory reactive brain astrocytes
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Network coupled cells, such as astrocytes, regulate their cellular homeostasis via Ca2+ signals spread between the cells through gap junctions. Intracellular Ca2+ release is controlled by different signaling pathways that can be stimulated by ATP, glutamate and serotonin (5-HT). Based on our findings, all these pathways are influenced by inflammatory agents and must be restored to fully recover the Ca2+ signaling network. An ultralow concentration of the local anesthetic agent bupivacaine reduced 5-HT-evoked intracellular Ca2+ release, and an ultralow concentration of the phosphodiesterase-5 inhibitor sildenafil in combination with vitamin D3 reduced ATP-evoked intracellular Ca2+ release. Combinations of these three substances downregulated 5-HT-, glutamate- and ATP-evoked intracellular Ca2+ release to a more normal Ca2+ signaling state. Furthermore, inflammatory Toll-like receptor 4 expression decreased with a combination of these three substances. Substance P receptor neurokinin (NK)-1 expression was reduced by ultralow concentrations of bupivacaine. Here, bupivacaine and sildenafil (at extremely low concentrations) combined with vitamin D3 have potential anti-inflammatory properties. According to the present study, drug combinations at the right concentrations, especially extremely low concentrations of bupivacaine and sildenafil, affect different cellular biochemical mechanisms and represent a potential solution for downregulating inflammatory parameters, thereby restoring cells or networks to normal physiological homeostasis. © 2019 Hansson, Skiöldebrand. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 6. |
- Ka, Sojeong, et al.
(författare)
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Differentially expressed genes in hypothalamus in relation to genomic regions under selection in two chicken lines resulting from divergent selection for high or low body weight
- 2011
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Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 12:3, s. 211-221
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Tidskriftsartikel (refereegranskat)abstract
- Long-term divergent selection for low or high body weight from the same founder population has generated two extremely divergent lines of chickens, the high- (HWS) and low-weight (LWS) selected lines. At selection age (56 days), the lines differ by more than nine times in body weight. The HWS line chickens are compulsive feeders, whereas in the LWS line, some individuals are anorexic and others have very low appetite. Previous studies have implicated the central nervous system and particularly the hypothalamus in these behavioural differences. Here, we compared the mRNA expression in hypothalamus tissue from chickens on day 4 post-hatch using oligonucleotide arrays and found that the divergent selection had resulted in minor but multiple expression differences. Differentially expressed genes were enriched in processes 'DNA metabolism, repair, induction of apoptosis and metabolism'. Several differentially expressed genes participate in the regulation of neuronal plasticity and development, including apoptosis, or are neurotransmittor receptor subtypes. Less change was seen when comparing hypothalamic neuropeptide mediators of appetite such as the melanocortin receptors. The genomic locations of these differentially expressed genes were then compared to the locations of growth QTLs and to a genome-wide map of chromosomal regions that have been under divergent selection between the lines. The results indicate which differentially expressed hypothalamic genes have responded to the divergent selection and that the results predict that it is more likely to find causative genes among these most differentially expressed genes. Because of such differential gene expression in hypothalamus, the lines may adapt behaviourally different particularly to the post-hatch situation when independent feeding to obtain energy is established.
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| 7. |
- Eriksson, Olle, 1954-, et al.
(författare)
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Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms.
- 2016
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls.Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women.Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain".There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation.Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies.
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| 8. |
- Lisney, Thomas J., et al.
(författare)
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Using electroretinograms to assess flicker fusion frequency in domestic hens Gallus gallus domesticus
- 2012
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Ingår i: Vision Research. - : Elsevier BV. - 0042-6989 .- 1878-5646. ; 62, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- The assessment of flicker fusion frequency (FFF), the stimulus frequency at which a flickering light stimulus can no longer be resolved and appears continuous, and critical flicker fusion frequency (CFF; the highest frequency at any light intensity that an observer can resolve flicker) are useful methods for comparing temporal resolution capabilities between animals. Behavioural experiments have found that average CFFs in domestic chickens (Gallus gallus domesticus) are in the range of ca. 75-87 Hz, measured in response to full spectrum (i.e. white light plus UV) stimuli. In order to examine whether the chicken retina is able to detect flicker at higher frequencies, we used electroretinograms (ERGs) to assess FFF/CFF in adult hens from two commercial genotypes, Lohmann Selected Leghorns (LSLs) and Lohmann Browns (LBs). ERGs were recorded in response to flickering light at ten full spectrum light intensities ranging from 0.7 to 2740 cd m(-2). Two methods were used to determine FFF/CFF from the ERG recordings and these methods yielded very similar results, with average FFF ranging from ca. 20 Hz at 0.7 cd m(-2) to an average CFF of ca. 105 Hz at 2740 cd m(-2). In some individuals, CFFs of 118-119 Hz were recorded. The Intensity/FFF (I/FFF) curves are double-branched with a break point representing the rod-cone transition occurring between 2.5 and 5.9 cd m(-2). No significant differences in the I/FFF curves were found between the two genotypes. At stimulus light intensities >250 cd m(-2), the ERG-derived FFF and CFF values are all higher than those from behavioural studies using the same stimuli. Although hens do not appear to be able to consciously perceive flicker above approximately 90 Hz, the finding that the ERG responses are able to remain in phase with light flickering at frequencies >100 Hz means that the retinae of domestic poultry housed in artificial light conditions may be able to resolve flicker from fluorescent lamps. As range of detrimental effects have been reported in humans as a result of exposure to such "invisible flicker", the possibility exists that flicker from fluorescent lamps also acts as stressor in domesticated birds.
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| 9. |
- Põlajeva, Jelena, et al.
(författare)
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Glioma-derived macrophage migration inhibitory factor (MIF) promotes mast cell recruitment in a STAT5-dependent manner
- 2014
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 8:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Recently, glioma research has increased its focus on the diverse types of cells present in brain tumors. We observed previously that gliomas are associated with a profound accumulation of mast cells (MCs) and here we investigate the underlying mechanism. Gliomas express a plethora of chemoattractants. First, we demonstrated pronounced migration of human MCs toward conditioned medium from cultures of glioma cell lines. Subsequent cytokine array analyses of media from cells, cultured in either serum-containing or -free conditions, revealed a number of candidates which were secreted in high amounts in both cell lines. Among these, we then focused on macrophage migration inhibitory factor (MIF), which has been reported to be pro-inflammatory and -tumorigenic. Infiltration of MCs was attenuated by antibodies that neutralized MIF. Moreover, a positive correlation between the number of MCs and the level of MIF in a large cohort of human glioma tissue samples was observed. Further, both glioma-conditioned media and purified MIF promoted differential phosphorylation of a number of signaling molecules, including signal transducer and activator of transcription 5 (STAT5), in MCs. Inhibition of pSTAT5 signaling significantly attenuated the migration of MCs toward glioma cell-conditioned medium shown to contain MIF. In addition, analysis of tissue microarrays (TMAs) of high-grade gliomas revealed a direct correlation between the level of pSTAT5 in MCs and the level of MIF in the medium. In conclusion, these findings indicate the important influence of signaling cascades involving MIF and STAT5 on the recruitment of MCs to gliomas.
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| 10. |
- Essner, Ann, et al.
(författare)
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Comparison of Polar® RS800CX heart rate monitor and electrocardiogram for measuring inter-beat intervals in healthy dogs
- 2015
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Ingår i: Physiology and Behavior. - : Elsevier. - 0031-9384 .- 1873-507X. ; 138:January, s. 247-253
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to assess the criterion validity, relative reliability and level of agreement ofPolar® RS800CX heart rate monitor measuring inter-beat intervals (IBIs), compared to simultaneously recordedelectrocardiogram (ECG) in dogs.Methods: Five continuous minutes of simultaneously recorded IBIs from Polar® RS800CX and Cardiostore ECG in11 adult healthy dogs maintaining standing position were analyzed. Polar® data was statistically compared toECG data to assess for systematic differences between the methods. Three different methods for handling missingIBI data were used. Criterion validities were calculated by intraclass correlation coefficients (ICCs) and corresponding95% confidence intervals (CIs). Relative reliabilities and levels of agreement were calculated by ICCsand the Bland and Altman analysis for repeated measurements per subject.Results: Correlation coefficients between IBI data from ECG and Polar® RS800CX varied between 0.73 and 0.84depending on how missing values were handled. Polar® was over- and underestimating IBI data compared toECG. The mean difference in log transformed (base10) IBI data was 0.8%, and 93.2% of the values were withinthe limits of agreement. Internally excluding three subjects presenting IBI series containing more than 5% erroneousIBIs resulted in ICCs between 0.97 and 0.99. Bland and Altman analysis (n = 8) showed mean differencewas 1.8 ms, and 98.5% of the IBI values were plotted inside limits of agreement.Conclusion: This study showed that Polar® systematically biased recorded IBI series and that it was fundamentalto detect measurement errors. For Polar® RS800CX heart rate monitor to be used interchangeably to ECG, byshowing excellent criterion validity and reliable IBI measures in group and individual samples, only less than5% of artifacts could be accepted.
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