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  • 1. Arefalk, Gabriel
    et al.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Michaëlsson, Karl
    Lind, Lars
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Smokeless tobacco (snus) and risk of heart failure: results from two Swedish cohorts2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, no suppl.A, p. E48-E49Article in journal (Refereed)
  • 2. Arefalk, Gabriel
    et al.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Michaëlsson, Karl
    Lind, Lars
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Smokeless tobacco (snus) and risk of heart failure: results from two Swedish cohorts2012In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 19, no 5, p. 1120-1127Article in journal (Refereed)
    Abstract [en]

    Background: Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.

    Design: Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers. Methods: Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

    Results: In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.

    Conclusion: Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.

  • 3.
    Axelsson, Johanna
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Tellström, Linda
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Mobil hälsa (m-hälsa) genom användning av mobiltelefon som intervention för barn med övervikt eller fetma.: En systematisk litteraturstudie.2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background:

    The presence of overweight and obesity among children is increasing in

    large parts of the world. Lack of physical activity is one of the causes of overweight and

    obesity. For children with obesity, small amounts of physical activity may have major

    positive health effects. There is a need to develop new effective strategies to increase the

    amount of physical activity among children with overweight or obesity. Mobile health

    (mHealth) is used as an umbrella term for health services transmitted by mobile devices

    and is defined as "medical or public health practice supported by mobile devices such as

    mobile phones, patient monitoring devices, personal digital assistants and other wireless

    devices." A potential strategy for influencing the amount of physical activity in children

    with overweight or obesity is mHealth through the use of mobile phones.

    Objective:

    To examine and describe what interventions with mHealth component

    through the use of mobile phones that evaluated physical activity or Body Mass Index

    (BMI) in children with overweight or obesity.

    Methods:

    A systematic literature study in which studies describing interventions with

    mHealth components for the target group of children 0-18 years of overweight or obesity

    were included. Search was conducted in three scientific databases.

    Results:

    The searches resulted in 649 studies, of which 16 met set inclusion criteria. In

    most studies, the mHealth component included the use of text messaging and in some

    studies the use of app. The function of the mHealth component was studied and divided

    into self-registration, communication, encouragement, education and reminder. The

    included studies reported different forms of BMI where two studies showed significant

    differences between the intervention and control group with the greatest reduction for

    the intervention group. Few studies reported objectively measured time in physical

    activity of moderate to high intensity.

    Conclusion:

    The most common intervention with mHealth component through the use

    of mobile phones among children with overweight or obesity was text messaging. In

    order to understand and compare how mHealth can be used, a framework for the

    description of these interventions would facilitate.

  • 4. Bassil, A K
    et al.
    Häglund, Y
    Brown, J
    Rudholm Feldreich, Tobias
    Hellström, P M
    Näslund, E
    Lee, K
    Sanger, G J
    Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract.2007In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 150, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Obestatin, encoded by the ghrelin gene may inhibit gastrointestinal (GI) motility. This activity was re-investigated.

    EXPERIMENTAL APPROACH: Rat GI motility was studied in vitro (jejunum contractility and cholinergically-mediated contractions of forestomach evoked by electrical field stimulation; EFS) and in vivo (gastric emptying and intestinal myoelectrical activity). Ghrelin receptor function was studied using a GTPgammaS assay and transfected cells.

    KEY RESULTS: Contractions of the jejunum or forestomach were unaffected by obestatin 100 nM or 0.01-1000 nM, respectively (P>0.05 each; n=4-18). Obestatin (0.1-1 nM) reduced the ability of ghrelin 1 microM to facilitate EFS-evoked contractions of the stomach (increases were 42.7+/-7.8% and 21.2+/-5.0 % in the absence and presence of obestatin 1 nM; P<0.05; n=12); higher concentrations (10-1000 nM) tended to reduce the response to ghrelin but changes were not statistically significant. Similar concentrations of obestatin did not significantly reduce a facilitation of contractions caused by the 5-HT(4) receptor agonist prucalopride, although an inhibitory trend occurred at the higher concentrations (increases were 69.3+/-14.0% and 42.6+/-8.7% in the absence and presence of 1000 nM obestatin; n=10). Obestatin (up to 10 microM) did not modulate recombinant ghrelin receptor function. Ghrelin increased gastric emptying and reduced MMC cycle time; obestatin (1000 and 30,000 pmol kg(-1) min(-1)) had no effects. Obestatin (2500 pmol kg(-1) min(-1), starting 10 min before ghrelin) did not prevent the ability of ghrelin (500 pmol kg(-1) min(-1)) to shorten MMC cycle time.

    CONCLUSIONS AND IMPLICATIONS: Obestatin has little ability to modulate rat GI motility.

  • 5.
    Berterud Andersson, Catarina
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Dennis, Katarina
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Lumbal spinal stenos och fotbäddar: Kan av formgjutna fotbäddar minska kvarstående ländrygg- och bensmärta hos patienter som opererats för lumbal spinal stenos? En kvasi-experimentell jämförande studie.2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Lumbar spinal stenosis (LSS) is a common pathological condition in the lower back. The aim of most interventions when treating LSS is to reduce pain in the lower back and leg. The current knowledge regarding orthotics and low back pain is insufficient. Objectives: The aim with this study was to investigate weather custom-made orthotics would reduce self-reported pain in the lower back and leg, in patients who had had surgery for LSS. A second aim was to compare the self-reported pain in the lower back and leg, as well as low back function of the intervention group, with the one/year follow-up of a control group, who had undergone the same surgery two years earlier. Method: Eleven persons who had undergone surgery for LSS at the Spine surgery clinic of Strängnäs got to use custom-made orthotics for six weeks. Primary outcome measure was pain intensity in the lower back and leg, evaluated with the Numeric Rating Scale (NRS). To describe the baseline characteristics of the participants, low back function was measured with the Oswestry Low Back Pain Disability Index (ODI). To detect a change of the median value for pain intensity of the participants, before compared to after the intervention, Wilcoxon signed rank sum test was conducted (CI 95%). The post-intervention measurement was compared to a control condition; i.e. data was collected from the quality register from Swespine. Results: There was no difference in self-reported pain intensity in the lower back, compared to before the intervention (p=0,76). There was no difference in self-reported pain intensity in the leg, compared to before the intervention (p=0,40). There was no difference between the self-reported pain intensity for lower back (p=0,078) or leg (p=0,85) between the follow-up of the intervention group and the result from the one-year follow-up of the control group. Conclusion: This study could not detect any differences in pain in either the lower back or the leg after six weeks of using custom-made orthotics, compared with before the intervention. No difference could be found in self-reported pain intensity between the intervention group and the control for lower back or leg.

  • 6. Blom, Elin S
    et al.
    Wang, Yijing
    Skoglund, Lena
    Uppsala universitet.
    Hansson, Anita C
    Ubaldi, Massimo
    Lourdusamy, Anbarasu
    Sommer, Wolfgang H
    Mielke, Matthew
    Hyman, Bradley T
    Heilig, Markus
    Lannfelt, Lars
    Nilsson, Lars N G
    Ingelsson, Martin
    Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain.2010In: International Journal of Alzheimer's Disease, ISSN 2090-8024, E-ISSN 2090-0252, Vol. 2011Article in journal (Refereed)
    Abstract [en]

    Several components in the Wnt pathway, including β-catenin and glycogen synthase kinase 3 beta, have been implied in AD pathogenesis. Here, mRNA brain levels from five-month-old tg-ArcSwe and nontransgenic mice were compared using Affymetrix microarray analysis. With surprisingly small overall changes, Wnt signaling was the most affected pathway with altered expression of nine genes in tg-ArcSwe mice. When analyzing mRNA levels of these genes in human brain, transcription factor 7-like 2 (TCF7L2) and v-myc myelocytomatosis viral oncogene homolog (MYC), were increased in Alzheimer's disease (AD) (P < .05). Furthermore, no clear differences in TCF7L2 and MYC mRNA were found in brains with frontotemporal lobar degeneration, suggesting that altered regulation of these Wnt-related genes could be specific to AD. Finally, mRNA levels of three neurogenesis markers were analyzed. Increased mRNA levels of dihydropyrimidinase-like 3 were observed in AD brain, suggesting that altered Wnt pathway regulation may signify synaptic rearrangement or neurogenesis.

  • 7.
    Ekdahl, Victor
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Lindblom, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Behandling av iliotibialbandssyndrom hos löpare: En strukturerad litteraturstudie2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Running is a popular form of exercise around the world. Iliotibial band syndrome (ITBS) is one of the most common overuse injuries in runners. Several different conservative treatment methods have been studied, but evidence is limited and not sufficient enough to support a specific treatment method. Objective: To describe through a structured literature review the conservative treatment methods studied on runners with ITBS and the effect these treatment methods have on pain. Method: A search to identify relevant articles was carried out in the PubMed, Cinahl, Scoupus and Web of Science databases. The search terms used were iliotibial band syndrome, iliotibial band friction syndrome and iliotibial band strain. A screening of titles and abstracts was made. Potentially relevant articles were obtained in full text, and then a relevance assessment was performed. The methodological quality of the included articles was examined. An ethical review was conducted on all included articles. Results: Four randomized controlled trials and two cohort studies were included. The interventions studied in the articles were correction of the supposed aetiological factors for running related injuries, anti-inflammatory / analgesic drugs, deep transverse friction massage, hip strengthening rehabilitation program, corticosteroid injection and shockwave treatment compared to manual therapy. Many of the interventions reduced pain, however, to varying degrees. In two of the studies there was no significant difference in decrease of pain between intervention and control group. The articles had varied methodological quality. Conclusion: Although ITBS is common in runners, relatively few studies have investigated it’s conservative treatment methods. Several of the studies indicated positive results in the form of pain reduction but there are difficulties in drawing conclusions about effect from the treatment methods due to methodological weaknesses.

  • 8.
    Flynner, Kristina
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Hagström Backe, Kerstin
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Innehållsvalidering av den svenska preliminära San Salvadourskalan: En modifierad Delphistudie2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Pain is more common among adults with severe cognitive and physical impairments than in the overall population. These persons are often nonverbal and therefore dependent upon people in the vicinity to detect and continuously chart the presence of their pain. Validated and reliable pain observation scales for the group is scanty.

    Aim: The aim of this study was to assess the content validity of the Swedish preliminary version of the San Salvadourscale for adults with severe cognitive and physical impairments.

    Method: A modified Delphi in two rounds examined content validity of the Swedish preliminary version of the San Salvadourscale. A survey was distributed over email in 2 rounds. 13 clinically experienced experts estimated the relevance in the baseline-chart, the pain questionnaire and the different degrees in it. Item content validity Index (I-CVI) was calculated for the questions, Scale content validity index universal agreement (S-CVI UA) and Scale content validity index average (S-CVI Ave) was calculated for the scale.

    Result: The I-CVI for the questions in the baseline-chart, the pain questionnaire and the text for the different degrees was above 0.78 in most cases. S-CVI UA was below 0.80 in every domain. S-CVI Ave was greater than and or equal to 0.90 in five out of six domains. And below 0.90 for the different degrees in the pain questionnaire in the second round.

    Conclusion: Based on the experts ratings of the questions I-CVI showed mostly excellent result. Further studies on the content validity of the Swedish preliminary version of the San Salvadourscale is needed to investigate whether the content validity is sufficient to measure behaviors that can indicate pain in adults with severe cognitive and physical impairments.

  • 9. Giedraitis, V
    et al.
    Hedlund, M
    Skoglund, Lena
    Uppsala universitet.
    Blom, E
    Ingvast, S
    Brundin, R
    Lannfelt, L
    Glaser, A
    New Alzheimer's disease locus on chromosome 8.2006In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 43, no 12Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Family history is one of the most consistent risk factors for dementia. Therefore, analysis of families with a distinct inheritance pattern of disease can be a powerful approach for the identification of previously unknown disease genes.

    OBJECTIVE: To map susceptibility regions for Alzheimer's disease.

    METHODS: A complete genome scan with 369 microsatellite markers was carried out in 12 extended families collected in Sweden. Age at disease onset ranged from 53 to 78 years, but in 10 of the families there was at least one member with age at onset of < or =65 years. Mutations in known early-onset Alzheimer's disease susceptibility genes have been excluded. All people were genotyped for APOE, but no clear linkage with the epsilon4 allele was observed.

    RESULTS: Although no common disease locus could be found in all families, in two families an extended haplotype was identified on chromosome 8q shared by all affected members. In one of the families, a non-parametric multimarker logarithm of the odds (LOD) score of 4.2 (p = 0.004) was obtained and analysis based on a dominant model showed a parametric LOD score of 2.4 for this region. All six affected members of this family shared a haplotype of 10 markers spanning about 40 cM. Three affected members in another family also shared a haplotype in the same region.

    CONCLUSION: On the basis of our data, we propose the existence of a dominantly acting Alzheimer's disease susceptibility locus on chromosome 8.

  • 10.
    Gunnesson, Linnea
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Zetterlund, Anna
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Fysisk aktivitetsnivå, smärtintensitet och funktionsnedsättning hos personer med ländryggssmärta: - En enkätstudie2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background

    Lower back pain is very common in the western world. It results in a great

    suffering for the person and large economic costs for the society. Today lower

    back pain is treated with information to stay active and medication for pain relief.

    There is a lack of knowledge with regards to what effect physical training has as

    prevention and treatment for acute and subacute lower back pain.

    Aim

    The aim of this study was to, among patients with acute and subacute non-specific

    lower back pain, describe their level of physical activity and evaluate differences

    between groups with different levels of activity. The aim was also to explore the

    association between pain intensity, disability and level of physical activity.

    Method

    The study was conducted as a survey. The participants was 15 patients, 6 men and

    9 women with the mean age of 49,2 years old, who had sought care for acute and

    subacute lower back pain in 6 different primary care clinics. The level of physical

    activity were estimated using the indicator questions for physical activity by

    Socialstyrelsen, the pain intensity was measured with the Numeric Rating Scale

    and the Roland Morris Disability Questionnaire was answered. Data was analyzed

    with descriptive statistics, differences were tested with Mann-Whitney U-test and

    correlations analyzed with Spearman correlations coefficient.

    Results

    Eight out of 15 participants reached the WHO recommendations of physical

    activity (> 150 min/week). Those who participated in physical training minimum

    90 mins/week had a median value of NRS 5,5 and RMDQ 8. For those who trained

    less the median values were for NRS 7,5 (p=0,153) and RMDQ 11,5 (p=0,175). A

    week correlation between NRS (r=-0,136) and level of physical activity was noted

    while such correlation between RMDQ was negligible (r=-0,158).

    Conclusion

    There were no statically significant difference between the groups who trained at

    least 90 minutes per week and those who trained less neither in regards to pain

    intensity or disability. A weak but not statistically significant correlation was

    observed between physical activity and pain intensity.

  • 11.
    Hildingsson, Victoria
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Clarström, Anders
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Kartläggning av fysioterapeutiska interventioner i multimodal smärtrehabilitering inom primärvården.: En enkätstudie.2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background:

    Chronic pain is a major public health problem which involves high costs for

    society and, of course, also great suffering for the individual. Multimodal rehabilitation

    (MMR) means that different occupational categories work together around these patients.

    Research shows moderately to strong scientific evidence for MMR in complex pain

    problems. There are a lack of evidence about which type of physiotherapeutic interventions

    that are used in multimodal pain rehabilitation.

    Aim:

    The aim was to study which physiotherapy interventions that are used in multimodal

    primary healthcare rehabilitation in Sweden.

    Method:

    Cross-sectional survey with quantitative approach based on a self-designed web

    questionnaire. The population consisted of physiotherapists working in clinics reporting to

    the Swedish Quality Registry for Pain Rehabilitation (SQRP) in primary care and the result is

    based on the 23 physiotherapists who responded to the web questionnaire.

    Results:

    The results are based on 71% of the NRS-affiliated clinics. Counseling/teaching and

    various forms of physical training formed the basis of the physiotherapist's work in MMR

    teams in primary care. Almost all patients meet physiotherapists during the treatment period.

    Group treatment or a combination of group and individual treatment were most common. The

    treatment periods were mostly between four to eleven weeks where the patient met a

    physiotherapist most often weekly or several times a week. In the primary care MMR-team,

    the physiotherapist, occupational therapist, KBT therapist, physician and rehab coordinator

    were the most common occupational categories.

    Conclusion:

    Physiotherapists have a central role in the MMR-teams in primary care, they

    primarily use evidence-based, active interventions.

  • 12.
    Hultén, Petra
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Upplevelser av behandlingskonceptet Lee Silverman Voice Treatment BIG bland personer med Parkinsons sjukdom: -­ En kvalitativ intervjustudie2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Research today mainly focus on the measurable effects of physiotherapy interventions in Parkinson’s disease and, to a lesser extent, on the treatment experiences. Research describing people’s experiences of Lee Silverman Voice Treatment BIG (LSVT BIG) is lacking.

    Purpose: To examine and describe how people with Parkinson’s disease experience individual supervised treatment based on the LSVT BIG treatment concept.

    Method: Qualitative approach including three focus groups of a total of 19 persons with Parkinson's disease who started the treatment concept LSVT BIG. Interview questions were focused on the experiences of the treatment intervention. The interviews were transcribed before a qualitative content analysis was made.

    Result: Two main themes emerged from the analysis;; Prerequisites for treatment effects included the categories of A big effort, The importance of the role of the instructor, Self-­responsibility and Support from the environment. The second theme was Treatment Effects of LSVT BIG which included the categories Physical, Psychological and Social Effects as well as Behavioral Change.

    Conclusion: For good results of LSVT BIG, a big effort is required of the individual, their relatives and the healthcare provider. The big effort requires adjustments to the treatment intervention based on the conditions of above-­mentioned parties. The role of the instructor, family support, self-­discipline and a sense of situation-­influence were defined in the results as motivational factors that provide the conditions for good treatment effects. The treatment effects were multifaceted and reflected all aspects of the biopsychosocial model. In particular, improvements of the physical functions were found, which could be transferable to activities in daily living.

  • 13. Iggman, D
    et al.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Vessby, B
    Cederholm, T
    Sjögren, P
    Risérus, U
    Adipose tissue fatty acids and insulin sensitivity in elderly men2010In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, no 5, p. 850-857Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Dietary fatty acids may affect insulin sensitivity. Adipose tissue fatty acid composition partly reflects long-term dietary intake, but data from large studies regarding relationships with insulin sensitivity are lacking. We aimed to determine the association between adipose tissue fatty acids and insulin sensitivity in elderly Swedish men. Methods In a cross-sectional analysis of the community-based Uppsala Longitudinal Study of Adult Men (n?=?795, mean age 71 years), adipose tissue biopsies were obtained and fatty acid composition was determined by gas–liquid chromatography. Insulin sensitivity was measured directly by a euglycaemic clamp. Results Palmitic acid (16:0), the major saturated fatty acid (SFA) in the diet and in adipose tissue, was negatively correlated with insulin sensitivity (r?=?-0.14), as were 16:1 n-7 (r?=?-0.15), 20:3 n-6 (r?=?-0.31), 20:4 n-6 (r?=?-0.38), 22:4 n-6 (r?=?-0.37) and 22:5 n-3 (r?=?-0.24; p?<?0.001 for all). Some minor SFAs were positively correlated; 12:0 (r?=?0.46), 14:0 (r?=?0.32), 17:0 (r?=?0.21) and 18:0 (r?=?0.41; p?<?0.001 for all), as were essential polyunsaturated fatty acids (PUFAs) 18:2 n-6 (r?=?0.10, p?<?0.01) and 18:3 n-3 (r?=? 0.16, p?<?0.001). Docosahexaenoic acid (22:6 n-3) was negatively correlated (r?=?-0.11, p?<?0.01), whereas eicosapentaenoic acid (20:5 n-3) was not (r?=?-0.02, NS). Most associations diminished or disappeared in lean individuals, indicating an effect of obesity. Conclusions/interpretation Adipose tissue enriched with palmitic acid and depleted of essential PUFAs is associated with insulin resistance. The positive association between minor SFAs and insulin sensitivity merits further investigation.

  • 14. Ingelsson, Martin
    et al.
    Ramasamy, Karunya
    Cantuti-Castelvetri, Ippolita
    Skoglund, Lena
    Uppsala universitet.
    Matsui, Toshifumi
    Orne, Jennifer
    Kowa, Hasimoto
    Raju, Susan
    Vanderburg, Charles R
    Augustinack, Jean C
    de Silva, Rohan
    Lees, Andrew J
    Lannfelt, Lars
    Growdon, John H
    Frosch, Matthew P
    Standaert, David G
    Irizarry, Michael C
    Hyman, Bradley T
    No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of the Alzheimer's disease brain.2006In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 112, no 4Article in journal (Refereed)
    Abstract [en]

    Defective splicing of tau mRNA, promoting a shift between tau isoforms with (4R tau) and without (3R tau) exon 10, is believed to be a pathological consequence of certain tau mutations causing frontotemporal dementia. By assessing protein and mRNA levels of 4R tau and 3R tau in 27 AD and 20 control temporal cortex, we investigated whether altered tau splicing is a feature also in Alzheimer's disease (AD). However, apart from an expected increase of sarcosyl-insoluble tau in AD, there were no significant differences between the groups. Next, by laser-capture microscopy and quantitative PCR, we separately analyzed CA1 hippocampal neurons with and without neurofibrillary pathology from six of the AD and seven of the control brains. No statistically significant differences in 4R tau/3R tau mRNA were found between the different subgroups. Moreover, we confirmed the absence of significant ratio differences in a second data set with laser-captured entorhinal cortex neurons from four AD and four control brains. Finally, the 4R tau/3R tau ratio in CA1 neurons was roughly half of the ratio in temporal cortex, indicating region-specific differences in tau mRNA splicing. In conclusion, this study indicated region-specific and possibly cell-type-specific tau splicing but did not lend any support to overt changes in alternative splicing of tau exon 10 being an underlying factor in AD pathogenesis.

  • 15. Kyriacou, Andreas
    et al.
    Johansson, Sverker
    Högskolan för lärande och kommunikation, Högskolan i Jönköping, HLK, Ämnesforskning.
    Why language evolution research might help in identifying biologically plausible linguistic processing primitives2006In: The Science of Aphasia VII, 7-12 Sept 2006, Sardinia, 2006Conference paper (Other (popular science, discussion, etc.))
  • 16.
    Larsson, Catarina
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Lovén, Jessica
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Multimodal smärtrehabilitering i specialistvård: En kartläggning av fysioterapeutiska interventioner2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Chronic pain is a common cause for patients seeking care. The consequences of chronic pain can be seen at both individual and social level. Research has shown moderate to strong scientific support for multimodal rehabilitation (MMR) in complex pain problems. What the physiotherapist uses for interventions within MMR and how the collaboration with other occupational categories works is poorly described.

    Aim: To study what interventions physiotherapist’s use in multimodal pain rehabilitation in specialist care settings (MMR2) in Sweden.

    Methods: Web survey study where data was collected from 71 physiotherapists working at units connected to the Swedish Quality Registry for Pain Rehabilitation (SQRP).

    Results: The most common interventions were teaching/counseling and various forms of exercise. Strategies for behavioral change, mindfulness/body awareness and homework exercises are other commonly used interventions. Acceptance and Commitment Therapy (ACT) and Cognitive Behavioral Therapy (CBT) were used in several stages of rehabilitation on many units. Rehabilitation in group were the most common form of work and the interventions are primarily patient active as physical activity. The rehabilitation period were usually 8-11 weeks, where the patient saw a physiotherapist several times a week. The teams worked closely with regular team meetings, follow-ups and sometimes joint actions such as patient education and group training.

    Conclusion: The physiotherapist's work in MMR2 is based on a biopsychosocial perspective where the focus lies in restoring and/or improving body function. Physiotherapists have broad competence and long experience, enabling their knowledge about the body and the movement system to be integrated with behavioral change technics. Together with other occupational categories, the physiotherapist's work covers all domains in the Functional Classification, Disability and Health Classification (ICF). For increased understanding of the choice of physiotherapeutic interventions within MMR2, and how these interverventions works in the clinical setting, further research is needed.

  • 17.
    Löfbom, Linda
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Vidare i livet – inte tillbaka: Upplevelser av hur funktionsnedsättning och behandling påverkar livstillfredsställelsen hos vuxna personer med mjukdelssarkom.: En kvalitativ studie2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Soft tissue sarcoma is a rare form of cancer treated with surgery, radiotherapy and cytostatic. These treatments can cause impairment that affects the life satisfaction for those affected. Life satisfaction is the subjective experience of quality of life. Purpose: Describe how life satisfaction has been affected by the diagnosis, treatment and disability of soft tissue sarcoma. Method: Qualitative approach included eight semi structured interviews. The interviews were transcribed before analysis with qualitative content analysis Result: Through the analysis, an overall theme emerged Further in life. The theme covers the categories Reaction in diagnosis, Experience of treatment, Life after illness and Feel good Conclusion: Discomfort occurs in everyday life, but individuals are not restricted by them, they experience no disability. Life satisfaction was affected during treatment. After termination of treatment, ie at the time of the interviews, the researchers felt that their life satisfaction was not affected.

  • 18. McLaughlin, David
    et al.
    Karlsson, Fredrik
    a Division of Biomedical Sciences, The University of Edinburgh, Hugh Robson Building, George Square, Edinburgh.
    Tian, Natasha
    Pratt, Thomas
    Bullock, Simon L.
    Wilson, Valerie A.
    Price, David J.
    Mason, John O.
    Specific modification of heparan sulphate is required for normal cerebral cortical development2003In: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 120, no 12, p. 1481-1488Article in journal (Refereed)
    Abstract [en]

    Proteoglycans are cell surface and extracellular matrix molecules to which long, unbranched glycosaminoglycan side chains are attached. Heparan sulphate, a type of glycosaminoglycan chain, has been proposed as a co-factor necessary for signalling by a range of growth factors. Here we provide evidence that loss of 2-O-sulphation in heparan sulphate leads to a significant reduction in cell proliferation in the developing cerebral cortex. The gene encoding heparan sulphate 2-sulphotransferase (Hs2st) is expressed in embryonic cortex and histological analysis of mice homozygous for a null mutation in Hs2st indicated a reduction in the thickness of the embryonic cerebral cortex. Using 5′-bromodeoxyuridine (BrdU) incorporation assays we found a reduction of approximately 40% in labelling indices of cortical precursor cells at E12. Comparison of the fates of cortical cells born on E13 and E15 in Hs2st−/− mutant and wildtype littermate embryos revealed no differences in the pattern of cell migration. Our findings suggest a critical role for 2-O-sulphation of heparan sulphate proteoglycan (HSPG) in regulating cell proliferation during development of the cerebral cortex, perhaps through the modulation of cellular responses to growth factor signalling.

  • 19.
    Nerpin, Elisabet
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Jarvis, Debbie
    Olivieri, M
    Gislason, T
    Olin, AC
    Jansson, Christer
    Malinovschi, Andrei
    Different relation between exhaled nitric oxide and lung function with regard to current smoking2018Conference paper (Other academic)
    Abstract [en]

    Background: Exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation. Smokingreduces FeNO by 30-60%. Weak positive relation between lung function and FeNO has been inconsistently described. This has not been separately for smokers. Therefore we investigated the relation between lung function and FeNO with regard to smoking.

    Methods: FeNO and lung function post-bronchodilation (BD) were measured in 4813 subjects from the European Community Respiratory Health Survey III. GLI reference values were used. Smoking habits were self-reported.

    Results: Current smokers with FEV1 <lower limit of normal (LLN) had lower FeNO levels (ppb, geometric mean (95%CI)) than subjects with FEV1 ≥LLN: 10.1 (9.1, 11.1) vs 11.7 (11.3, 12.2), p=0.005, while the opposite was found in non-smokers: 20.0 (18.4, 21.6) vs 18.5 (18.2, 18.8), p=0.03. This interaction with current smoking was significant both before and after adjustments for study centres, age, BMI and gender (p=0.001 and p=0.004). Current smokers with FEV1/FVC <LLN had lower FeNO than current smokers with FEV1/FVC ≥LLN: 10.5 (9.4, 11.6) vs 11.6 (11.2, 12.1), p=0.04, and the opposite was found in non-smokers: 20.8 (19.1, 22.7) vs 18.4 (18.1, 18.8), p<0.001. There was a significant interaction with current smoking both in unadjusted and adjusted models (both p<0.001).

    Conclusion: Higher FeNO relates with lower FEV1 and FEV1/FVC-ratio among non-smoking individuals, suggesting that the obstruction is related with airways inflammation. In current smokers, higher FeNO relates with better preserved lung function and this finding warrants further studies to understand the underlying mechanisms. Presented on behalf of ECRHS III (www.ecrhs.org)

  • 20.
    Nerpin, Elisabet
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Joao, F. A
    Alving, Kjell
    Jansson, Christer
    Malinovschi, Andrei
    Blood cell counts and C-reactive protein inrelation to lung function in NHANES 2007-20102018Conference paper (Other academic)
    Abstract [en]

    Background:

    Low-grade systemic inflammation is associated with impaired lung function. Few studies have examined if C-reactive protein (CRP), blood eosinophil (B-Eos), and blood neutrophil (B-Neu) counts offer additive information in relation to lung function. The aim of this study was to analyse associations between CRP, BEos, and B-Neu and effects on lung function, with special regards to additive information.

    Methods:

    Cross-sectional study on 7,753 participants, 20-80 years of age, in the National Health and Nutrition Examination Survey. Gender-based tertiles for CRP, B-Eos, and B-Neu were analyzed in relation to forced expiratory volume in 1 second (FEV1 % predicted), forced vital capacity (FVC % predicted), and FEV1/FVC ratio.

    Results:

    CRP, B-Eos, and B-Neu were inversely related to FEV1 and FVC. Only B-Eos and B-Neu were inversely related to FEV1/FVC ratio. Further, lower lung function was found with increased number of elevated

    inflammatory markers in the highest tertile (one, two or three vs. non elevated) for FEV1 (% predicted): β-coefficients (95% CI) -2.20(-2.98, -1.41), -4.43 (-5.39, -3.45), and -6.43(-8.07, -4.79), all P=0.001; FVC (% predicted): -1.70 (-2.42, -0.98), -3.17 (-4.06, -2.29), and -5.34 (-6.85, -3.84), all P=0.001.

    Conclusion:

    CRP, B-Eos, and B-Neu offer independent and additive information in relation to lower FEV1 and FVC in the general population. This indicates that a combination of biomarkers yields more information than the biomarkers assessed individually. The mechanisms appear to be different, as B-Neu and B-Eos seem to relate more closely to obstructive impairment, e.g., lower FEV1/FVC ratio, which was not found for CRP.

  • 21.
    Ohlsson, Anna B.
    et al.
    AlbaNova Univ Ctr, Dept Biochem, Royal Inst Technol, KTH,Sch Biotechnol, SE-10691 Stockholm, Sweden.
    Segerfeldt, Patrik
    Royal Inst Technol, KTH, Sch Chem Sci & Engn, Dept Chem, Ecol Chem Grp, SE-10044 Stockholm, Sweden.
    Lindström, Anders
    Dalarna University, School of Technology and Business Studies, Forest and Wood Technology.
    Borg-Karlson, Anna-Karin
    Royal Inst Technol, KTH, Sch Chem Sci & Engn, Dept Chem,Ecol Chem Grp, SE-10044 Stockholm, Sweden ; Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Berglund, Torkel
    AlbaNova Univ Ctr, Dept Biochem, Royal Inst Technol, KTH,Sch Biotechnol, SE-10691 Stockholm, Sweden.
    UV-B exposure of indoor-grown Picea abies seedlings causes an epigenetic effect and selective emission of terpenes2013In: Zeitschrift für Naturforschung C - A Journal of Biosciences, ISSN 0939-5075, E-ISSN 1865-7125, Vol. 68, no 3-4, p. 139-147Article in journal (Refereed)
    Abstract [en]

    Abstract: Terpenoids are involved in various defensive functions in plants, especially conifers. Epigenetic mechanisms, for example DNA methylation, can influence plant defence systems. The purpose of the present study was to investigate the influence of UV-B exposure on the release of terpenoids from spruce seedlings and on needle DNA methylation. Ten-week-old seedlings grown indoors were exposed to UV-B radiation during 4 h, and the volatile compounds emitted from the seedlings were analysed. Analysis of the volatiles 1, 3, and 22 d after this UV-B exposure showed that bornyl acetate, borneol, myrcene, and limonene contents increased during the first 3 days, while at day 22 the level of emission had returned to the control level. UV-B exposure decreased the level of DNA methylation in needles of young seedlings, reflected in methylation changes in CCGG sequences. Exposure of young seedlings to UV-B radiation might be a way to potentiate the general defensive capacity, improving their ability to survive in outdoor conditions. UV-B-induced defence is discussed in the light of epigenetic mechanisms.

  • 22. Ohrmalm, Christina
    et al.
    Eriksson, Ronnie
    Jobs, Magnus
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Simonson, Magnus
    Stromme, Maria
    Bondeson, Kare
    Herrmann, Bjorn
    Melhus, Asa
    Blomberg, Jonas
    Variation-tolerant capture and multiplex detection of nucleic acids: application to detection of microbes2012In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 50, no 10, p. 3208-3215Article in journal (Refereed)
    Abstract [en]

    In contrast to ordinary PCRs, which have a limited multiplex capacity and often return false-negative results due to target variation or inhibition, our new detection strategy, VOCMA (variation-tolerant capture multiplex assay), allows variation-tolerant, target-specific capture and detection of many nucleic acids in one test. Here we demonstrate the use of a single-tube, dual-step amplification strategy that overcomes the usual limitations of PCR multiplexing, allowing at least a 22-plex format with retained sensitivity. Variation tolerance was achieved using long primers and probes designed to withstand variation at known sites and a judicious mix of degeneration and universal bases. We tested VOCMA in situations where enrichment from a large sample volume with high sensitivity and multiplexity is important (sepsis; streptococci, enterococci, and staphylococci, several enterobacteria, candida, and the most important antibiotic resistance genes) and where variation tolerance and high multiplexity is important (gastroenteritis; astrovirus, adenovirus, rotavirus, norovirus genogroups I and II, and sapovirus, as well as enteroviruses, which are not associated with gastroenteritis). Detection sensitivities of 10 to 1,000 copies per reaction were achieved for many targets. VOCMA is a highly multiplex, variation-tolerant, general purpose nucleic acid detection concept. It is a specific and sensitive method for simultaneous detection of nucleic acids from viruses, bacteria, fungi, and protozoa, as well as host nucleic acid, in the same test. It can be run on an ordinary PCR and a Luminex machine and is suitable for both clinical diagnoses and microbial surveillance.

  • 23. Rudholm Feldreich, Tobias
    et al.
    Hellstrom, Per-Mikael
    Theodorsson, Elvar
    Campbell, Colin-Allan
    McLean, Peter-Geoffrey
    Naslund, Erik
    Bravo capsule system optimizes intragastric pH monitoring over prolonged time: effects of ghrelin on gastric acid and hormone secretion in the rat.2008In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 14, no 40Article in journal (Refereed)
    Abstract [en]

    AIM: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time.

    METHODS: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days. For comparison, a gastric fistula model was used. Effects of ghrelin and esomeprazole, with or without pentagastrin, on gastric pH were studied. In addition, effects of esomeprazole on plasma ghrelin, gastrin and somatostatin were analyzed.

    RESULTS: All rats recovered after surgery. The average 24-h pH during free feeding was 2.3 +/- 0.1 (n = 20) with a variation of 18% +/- 6% over 5 d. Ghrelin, 2400 pmol/kg, t.i.d. increased pH from 1.7 +/- 0.1 to 3.1 +/- 0.3 (P < 0.01) as recorded with the Bravo system. After esomeprazole (1 mg/kg, 3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 +/- 0.1, with day-to-day variation over the entire period of 8% +/- 3%. The fistula and pH studies generated similar results. Acid inhibition with esomeprazole increased plasma ghrelin from 10 +/- 2 pmol/L to 65 +/- 26 pmol/L (P < 0.001), and somatostatin from 10 +/- 2 pmol/L to 67 +/- 18 pmol/L (P < 0.001).

    CONCLUSION: pH measurements with the Bravo capsule are reliable, and comparable to those of the gastric fistula model. The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short- and long-term evaluation of effects of drugs and hormones.

  • 24. Rudholm Feldreich, Tobias
    et al.
    Wallin, B
    Theodorsson, E
    Näslund, E
    Hellström, P M
    Release of regulatory gut peptides somatostatin, neurotensin and vasoactive intestinal peptide by acid and hyperosmolal solutions in the intestine in conscious rats.2009In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 152, no 1-3Article in journal (Refereed)
    Abstract [en]

    The impact of exposure of the intestinal mucosa to acid and hyperosmolal solutions on the release of the inhibitory gut peptides somatostatin (SOM), neurotensin (NT) and vasoactive intestinal peptide (VIP) was studied in conscious rats during pentagastrin-stimulated gastric acid secretion. The animals were equipped with a chronic gastric fistula to measure acid secretion and a jejunal Thiry-Vella loop for intestinal challenge with saline, hydrochloric acid (HCl, 200 mmol L(-1)) or hyperosmolal polyethylene glycol (PEG, 1200 mOsm kg(-1)). Gut peptide concentrations were measured in intestinal perfusates, and in plasma samples collected during stimulated acid secretion, and at the end of experiments with luminal challenge of the loops. After pentagastrin-stimulation acid secretion was dose-dependently inhibited by intravenous administration of the gastrin receptor antagonist gastrazole, as well as ranitidine and esomeprazole by maximally 73+/-10%; 95+/-3%; 90+/-10%, respectively. Acid perfusion of the Thiry-Vella loop caused a prominent release of SOM both to the lumen (from 7.2+/-5.0 to 1279+/-580 pmol L(-1)) and to the circulation (from 18+/-5.2 to 51+/-9.0 pmol L(-1)) simultaneously with an inhibition of gastric acid secretion. The release of NT and VIP was not affected to the same extent. PEG perfusion of the loop caused a release of SOM as well as NT and VIP, but less. Simultaneously acid secretion was slightly decreased. In conclusion, intestinal perfusion with acid or hyperosmolal solutions mainly releases SOM, which seems to exert a major inhibitory action in the gut, as shown by inhibition of acid secretion. The other peptides NT and VIP also participate in this action but to a much lesser degree. The operative pathways of these gut peptides hence involve both endocrine (SOM) and paracrine actions (SOM, NT, VIP) in order to exert inhibitory functions on the stomach. The inhibitory action of gastrazole, was in a similar range as that of SOM implying that physiological acid-induced inhibition of gastric acid may primarily be exerted through inhibition of gastrin endocrine secretion.

  • 25. Sahlin, Kent
    et al.
    Nielsen, J.S.
    Mogensen, M
    Tonkonogi, Michail
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Repeated static contractions increase mitochondrial vulnerability toward oxidative stress in human skeletal muscle.2006In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 101, no 3, p. 833-839Article in journal (Other academic)
    Abstract [en]

    Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmic reticulum (SR) Ca2+ kinetics in human muscle. Ten male subjects performed five bouts of static knee extension with 10-min rest in between. Each bout of RSC (target torque 66% of maximal voluntary contraction torque) was maintained to fatigue. Muscle biopsies were taken preexercise and 0.3 and 24 h postexercise from vastus lateralis. Mitochondria were isolated and respiratory function measured after incubation with H2O2 (HPX) or control medium (Con). Mitochondrial function was not affected by RSC during Con. However, RSC exacerbated mitochondrial dysfunction during HPX, resulting in decreased respiratory control index, decreased mitochondrial efficiency (phosphorylated ADP-to-oxygen consumed ratio), and increased noncoupled respiration (HPX/Con post- vs. preexercise). SR Ca2+ uptake rate was lower 0.3 vs. 24 h postexercise, whereas SR Ca2+ release rate was unchanged. RSC resulted in long-lasting changes in muscle contractility, including reduced maximal torque, low-frequency fatigue, and faster torque relaxation. It is concluded that RSC increases mitochondrial vulnerability toward ROS, reduces SR Ca2+ uptake rate, and causes low-frequency fatigue. Although conclusive evidence is lacking, we suggest that these changes are related to increased formation of ROS during RSC.

  • 26. Samrani, George
    et al.
    Marklund, Petter
    Engström, Lisa
    Broman, Daniel
    Dalarna University, School of Education, Health and Social Studies. Högskolan i Skövde.
    Persson, Jonas
    Behavioral facilitation and increased brain responses from a high interference working memory context.2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 15308Article in journal (Refereed)
    Abstract [en]

    Many real-life situations require flexible behavior in changing environments. Evidence suggests that anticipation of conflict or task difficulty results in behavioral and neural allocation of task-relevant resources. Here we used a high- and low-interference version of an item-recognition task to examine the neurobehavioral underpinnings of context-sensitive adjustment in working memory (WM). We hypothesized that task environments that included high-interference trials would require participants to allocate neurocognitive resources to adjust to the more demanding task context. The results of two independent behavioral experiments showed enhanced WM performance in the high-interference context, which indicated that a high-interference context improves performance on non-interference trials. A third behavioral experiment showed that when WM load was increased, this effect was no longer significant. Neuroimaging results further showed greater engagement of inferior frontal gyrus, striatum, parietal cortex, hippocampus, and midbrain in participants performing the task in the high- than in the low-interference context. This effect could arise from an active or dormant mode of anticipation that seems to engage fronto-striatal and midbrain regions to flexibly adjust resources to task demands. Our results extend the model of conflict adaptation beyond trial-to-trial adjustments by showing that a high interference context affects both behavioral and biological aspects of cognition.

  • 27.
    Santillo, Alexander Frizell
    et al.
    Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala 75185, Sweden.
    Skoglund, Lena
    Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala 75185, Sweden.
    Lindau, Maria
    Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala 75185, Sweden.
    Eeg-Olofsson, Karin Edebol
    Uppsala Univ, Dept Neurosci Clin Neurophysiol, Uppsala 75185, Sweden.
    Tovi, Metin
    Karolinska Univ Hosp, Dept Diagnost Radiol, Stockholm, Sweden.
    Engler, Henry
    Uppsala Univ, Dept Med Sci Clin Physiol, Uppsala 75185, Sweden.
    Brundin, Rose-Marie
    Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala 75185, Sweden.
    Ingvast, Sofie
    Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala 75185, Sweden.
    Lannfelt, Lars
    Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala 75185, Sweden.
    Glaser, Anna
    Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala 75185, Sweden.
    Kilander, Lena
    Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala 75185, Sweden.
    Frontotemporal Dementia-amyotrophic Lateral Sclerosis Complex is Simulated by Neurodegeneration With Brain Iron Accumulation2009In: Alzheimer Disease and Associated Disorders, ISSN 0893-0341, E-ISSN 1546-4156, Vol. 23, no 3, p. 298-300Article in journal (Refereed)
    Abstract [en]

    We describe a case of late onset neurodegeneration with brain iron accumulation (NBIA) presenting as frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS). A male patient presented at age 66 with change of personality: disinhibition, emotional blunting, and socially inappropriate behavior, coupled with dysarthria, dystonia, and corticospinal tract involvement. Magnetic resonance imaging showed general cortical atrophy, iron deposits in the globus pallidus, and the “eye of the tiger” sign. Neuropsychologic performance was globally reduced, especially executive functions. Fluorodeoxyglucose positron emission tomography showed hypometabolism predominantly in frontal and temporal areas. Repeated neurophysiologic examinations showed signs of chronic denervation. The patient was diagnosed with NBIA but fulfilled consensus criteria for FTD and had a clinical picture of ALS, without neurophysiologic confirmation. Our finding introduces NBIA as a possible cause of FTD and as a differential diagnosis of the FTD-ALS complex.

  • 28.
    Skoglund, Lena
    Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap.
    Molecular Mechanisms of Frontotemporal Lobar Degeneration2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to identify genetic factors involved in frontotemporal lobar degeneration (FTLD), a neurodegenerative disorder clinically characterised by a progressive change in personality, behaviour and language. FTLD is a genetically complex disorder and a positive family history is found in up to 40% of the cases.

    In 10-20% of the familial cases the disease can be explained by mutations in the gene encoding the microtubule associated protein tau (MAPT). In the first study we describe the clinical and neuropathological features of a Finnish family with FTLD caused by a mutation in MAPT. We also provide evidence that the pathogenic mechanism of this mutation is through altered splicing of MAPT transcripts.

    Recently, mutations in the gene encoding progranulin (PGRN) were identified as a major cause of FTLD. In the second study we describe a Swedish family with FTLD caused by a frameshift mutation in PGRN. We provide a clinical and neuropathological description of the family, as well as evidence that the pathogenicity of this mutation is through nonsense-mediated decay of the mutant mRNA transcripts and PGRN haploinsufficiency.

    In the third study we describe a novel PGRN splice site mutation and a previously described PGRN frameshift mutation, found in a mutation screen of 51 FTLD patients. We describe the clinical and neuropathological characteristics of the mutation carriers and demonstrate that haploinsufficiency is the pathogenic mechanism of the two mutations.

    In the fourth study we investigate the prevalence of PGRN and MAPT gene dosage alterations in 39 patients with FTLD. No gene dosage alterations were identified, indicating that variations in copy number of the PGRN and MAPT genes are not a common cause of disease, at least not in this FTLD patient collection.

  • 29.
    Skoglund, Lena
    et al.
    Department of Public Health and Caring Sciences, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
    Brundin, RoseMarie
    Department of Public Health and Caring Sciences, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
    Olofsson, Tommie
    Uppsala Univ, Dept Surg Sci, S-75185 Uppsala, Sweden.
    Kalimo, Hannu
    Univ Helsinki, Dept Pathol, Helsinki, Finland ; Uppsala Univ, Dept Genet & Pathol, S-75185 Uppsala, Sweden.
    Ingvast, Sofie
    Uppsala Univ, Dept Publ Hlth & Caring Sci, S-75185 Uppsala, Sweden.
    Blom, Elin
    Uppsala Univ, Dept Publ Hlth & Caring Sci, S-75185 Uppsala, Sweden.
    Giedraitis, Vilmantas
    Uppsala Univ, Dept Publ Hlth & Caring Sci, S-75185 Uppsala, Sweden.
    Ingelsson, Martin
    Uppsala Univ, Dept Publ Hlth & Caring Sci, S-75185 Uppsala, Sweden.
    Lannfelt, Lars
    Uppsala Univ, Dept Publ Hlth & Caring Sci, S-75185 Uppsala, Sweden.
    Basun, Hans
    Uppsala Univ, Dept Publ Hlth & Caring Sci, S-75185 Uppsala, Sweden.
    Glaser, Anna
    Uppsala Univ, Dept Publ Hlth & Caring Sci, S-75185 Uppsala, Sweden.
    Frontotemporal dementia in a large Swedish family is caused by a progranulin null mutation2009In: Neurogenetics, ISSN 1364-6745, E-ISSN 1364-6753, Vol. 10, no 1, p. 27-34Article in journal (Refereed)
  • 30.
    Skoglund, Lena
    et al.
    Uppsala Univ, Dept Publ Hlth & Caring Sci, SE-75185 Uppsala, Sweden.
    Ingvast, Sofie
    Uppsala Univ, Dept Publ Hlth & Caring Sci, SE-75185 Uppsala, Sweden.
    Matsui, Toshifumi
    Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
    Freeman, Stefanie H.
    Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
    Frosch, Matthew P.
    Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
    Brundin, Rosemarie
    Uppsala Univ, Dept Publ Hlth & Caring Sci, SE-75185 Uppsala, Sweden.
    Giedraitis, Vilmantas
    Uppsala Univ, Dept Publ Hlth & Caring Sci, SE-75185 Uppsala, Sweden.
    Growdon, John H.
    Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
    Hyman, Bradley T.
    Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
    Lannfelt, Lars
    Uppsala Univ, Dept Publ Hlth & Caring Sci, SE-75185 Uppsala, Sweden.
    Ingelsson, Martin
    Uppsala Univ, Dept Publ Hlth & Caring Sci, SE-75185 Uppsala, Sweden.
    Glaser, Anna
    Uppsala Univ, Dept Publ Hlth & Caring Sci, SE-75185 Uppsala, Sweden.
    No Evidence of PGRN or MAPT Gene Dosage Alterations in a Collection of Patients with Frontotemporal Lobar Degeneration2009In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 28, no 5, p. 471-475Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Alterations in gene dosage have recently been associated with neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, and deletions of the progranulin (PGRN) locus were recently described in patients with frontotemporal lobar degeneration (FTLD). FTLD is a genetically complex neurodegenerative disorder with mutations in the PGRN and the microtubule-associated protein tau (MAPT) genes being the most common known causes of familial FTLD. In this study, we investigated 39 patients with FTLD, previously found negative for mutations in PGRN and MAPT, for copy number alterations of these 2 genes. Methods: Gene dosage analysis of PGRN and MAPT was performed using multiplex ligation-dependent probe amplification. Results: We did not identify any PGRN or MAPT gene dosage variations in the 39 FTLD patients investigated. Conclusion: We therefore conclude that alterations in gene copy number of PGRN and MAPT are not a cause of disease in this collection of FTLD patients. Copyright (C) 2009 S. Karger AG, Basel

  • 31.
    Skoglund, Lena
    et al.
    Molecular Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Matsui, Toshifumi
    Freeman, Stefanie
    Wallin, Anders
    Blom, Elin
    Frosch, Matthew P.
    Growdon, John H.
    Hyman, Bradley T.
    Lannfelt, Lars
    Ingelsson, Martin MD, PhD
    Glaser, Anna PhD
    Novel progranulin mutation detected in 2 patiens with FTLD2011In: Alzheimer Disease and Associated Disorders, ISSN 0893-0341, Vol. 25, no 2, p. 173-178Article in journal (Refereed)
  • 32.
    Skoglund, Lena
    et al.
    Uppsala universitet.
    Viitanen, M
    Kalimo, H
    Lannfelt, L
    Jönhagen, M E
    Ingelsson, M
    Glaser, A
    Herva, R
    The tau S305S mutation causes frontotemporal dementia with parkinsonism.2008In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 15, no 2Article in journal (Refereed)
    Abstract [en]

    Members of families with mutations in the tau gene are known to be heterogeneous in their clinical presentation, ranging from frontotemporal dementia to a clinical picture more resembling corticobasal degeneration or progressive supranuclear palsy. In this report, we describe a new phenotype for the tau S305S mutation, previously described as progressive supranuclear palsy. Clinically, the three affected family members showed alterations in personality and behaviour as well as cognitive decline and late levodopa-resistant parkinsonian symptoms, consistent with the diagnosis of frontotemporal dementia with parkinsonism linked to chromosome 17. One autopsied case displayed degeneration of the frontal and temporal lobes together with extensive tau pathology in both neurones and glial cells. Sarkosyl-soluble and -insoluble tau extracted from frontal cortex revealed a ratio shift with decreased levels of tau with three microtubule-binding repeats and increased levels of tau with four microtubule-binding repeats (4R tau). These findings provide further evidence for the clinical and pathological variation both within and between families with mutations in the tau gene. In addition, they support previous studies which demonstrate that the S305S mutation influences the splicing of tau exon 10 and results in an overproduction of 4R tau.

  • 33.
    Tonkonogi, Michail
    et al.
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Tonkonogi, Aleksandra
    Grundläggande muskel- och neurofysiologi2019In: Motorisk kontroll och inlärning: Med inriktning på muskoloskeletal rehabilitering / [ed] Ulrik Röijezon, Studentlitteratur AB, 2019, 1, p. 25-36Chapter in book (Other academic)
  • 34. Wan Saudi, Wan Salman
    et al.
    Halim, Md Abdul
    Rudholm Feldreich, Tobias
    Gillberg, Linda
    Rosenqvist, Evelina
    Tengholm, Anders
    Sundbom, Magnus
    Karlbom, Urban
    Näslund, Erik
    Webb, Dominic-Luc
    Sjöblom, Markus
    Hellström, Per M
    Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide.2015In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 309, no 8Article in journal (Refereed)
    Abstract [en]

    Neuropeptide S (NPS) receptor (NPSR1) polymorphisms are associated with enteral dysmotility and inflammatory bowel disease (IBD). This study investigated the role of NPS in conjunction with nitrergic mechanisms in the regulation of intestinal motility and mucosal permeability. In rats, small intestinal myoelectric activity and luminal pressure changes in small intestine and colon, along with duodenal permeability, were studied. In human intestine, NPS and NPSR1 were localized by immunostaining. Pre- and postprandial plasma NPS was measured by ELISA in healthy and active IBD humans. Effects and mechanisms of NPS were studied in human intestinal muscle strips. In rats, NPS 100-4,000 pmol·kg(-1)·min(-1) had effects on the small intestine and colon. Low doses of NPS increased myoelectric spiking (P < 0.05). Higher doses reduced spiking and prolonged the cycle length of the migrating myoelectric complex, reduced intraluminal pressures (P < 0.05-0.01), and increased permeability (P < 0.01) through NO-dependent mechanisms. In human intestine, NPS localized at myenteric nerve cell bodies and fibers. NPSR1 was confined to nerve cell bodies. Circulating NPS in humans was tenfold below the ∼0.3 nmol/l dissociation constant (Kd) of NPSR1, with no difference between healthy and IBD subjects. In human intestinal muscle strips precontracted by bethanechol, NPS 1-1,000 nmol/l induced NO-dependent muscle relaxation (P < 0.05) that was sensitive also to tetrodotoxin (P < 0.01). In conclusion, NPS inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans. Aberrant signaling and upregulation of NPSR1 could potentially exacerbate dysmotility and hyperpermeability by local mechanisms in gastrointestinal functional and inflammatory reactions.

  • 35. Webb, Dominic-Luc
    et al.
    Rudholm Feldreich, Tobias
    Gillberg, Linda
    Halim, Md Abdul
    Theodorsson, Elvar
    Sanger, Gareth J
    Campbell, Colin A
    Boyce, Malcolm
    Näslund, Erik
    Hellström, Per M
    The type 2 CCK/gastrin receptor antagonist YF476 acutely prevents NSAID-induced gastric ulceration while increasing iNOS expression.2013In: Naunyn-Schmiedeberg's Archives of Pharmacology, ISSN 0028-1298, E-ISSN 1432-1912, Vol. 386, no 1Article in journal (Refereed)
    Abstract [en]

    YF476 differs from the proton pump inhibitor (PPI) esomeprazole in mode of action by antagonizing the type 2 receptor of cholecystokinin/gastrin (CCK-2R). YF476 protection against diclofenac-induced gastric ulcers was compared to esomeprazole and correlated with plasma levels of hormones related to gastric pH (gastrin, ghrelin, and somatostatin), gastric gene expression of these hormones, their receptors, and inducible nitric oxide synthase (iNOS). YF476 or esomeprazole pretreatments were followed by diclofenac. Four hours later, gastric tissue was excised and analyzed for ulcer index. An intragastrically implanted Bravo capsule measured pH for 5 days during YF476 plus pentagastrin treatment. Changes in gene expression were assayed for gastrin, ghrelin, and somatostatin; their receptors; and iNOS. YF476 acutely (within 4 h) protected against diclofenac-induced gastric ulcers equivalent to esomeprazole. Gastric pH recorded during 5 days in the presence of pentagastrin was 1.83 (±0.06). YF476 raised pH to 3.67 (±0.09) and plasma ghrelin, gastrin, and somatostatin increased. YF476 increased gene expression of somatostatin receptor and gastrin, while ghrelin receptor decreased; transcripts coding ghrelin, somatostatin, and CCK-2R remained unchanged. In the presence of diclofenac, esomeprazole increased expression of all these transcripts and that of iNOS, while YF476 yielded only decreased CCK-2R and increased iNOS transcripts. YF476 is a potential new preventative treatment for patients at risk of nonsteroidal antiinflammatory drug (NSAID)-induced ulceration. Gastric gene expressions of ghrelin, gastrin, and somatostatin and their receptors differ between esomeprazole and YF476. Despite these differences and different modes of action to raise gastric pH, both drugs acutely increase iNOS, suggesting iNOS expression parallels pH.

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