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  • 24351. Zou, Ding
    et al.
    Wennman, Heini
    Ekblom, Örjan
    Grote, Ludger
    Arvidsson, Daniel
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Torén, Kjell
    Bergström, Göran
    Börjesson, Mats
    Hedner, Jan
    Insomnia and cardiorespiratory fitness in a middle-aged population: the SCAPIS pilot study2019Inngår i: Sleep and Breathing, ISSN 1520-9512, E-ISSN 1522-1709, Vol. 23, nr 1, s. 319-326Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundThe relationship between insomnia and cardiorespiratory fitness (CRF), a well-established risk factor for cardiovascular disease, has not been extensively studied. We aimed to assess the independent association between insomnia and CRF in a population-based cohort of subjects aged 50 to 64years.MethodsSubjects participating in the Swedish CArdioPulmonary bioImaging Study (SCAPIS) pilot cohort (n=603, men 47.9%) underwent a submaximal cycle ergometer test for estimation of maximal oxygen consumption (VO(2)max). Data on physical activity and sedentary time were collected via waist-worn accelerometers. An insomnia severity index score 10 was used to define insomnia.ResultsInsomnia was identified in 31.8% of the population. The VO(2)max was significantly lower in insomnia subjects compared with the non-insomnia group (31.26.3 vs. 32.4 +/- 6.5ml*kg(-1)*min(-1), p=0.028). There was no difference in objectively assessed physical activity or time spent sedentary between the groups. In a multivariate generalized linear model adjusting for confounders, an independent association between insomnia status and lower VO(2)max was found in men, but not in women (=-1.15 [95% CI -2.23--0.06] and -0.09 [-1.09-0.92], p=0.038 and 0.866, respectively).Conclusionsp id=ParWe found a modest, but significant, association between insomnia and lower CRF in middle-aged men, but not in women. Our results suggest that insomnia may link to cardiovascular disease via reduced CRF. Insomnia may require a specific focus in the context of health campaigns addressing CRF.

  • 24352. Zovko, Ana
    et al.
    Yektaei-Karin, Elham
    Salamon, Daniel
    Nilsson, Anders
    Wallvik, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Stenke, Leif
    Montelukast, a cysteinyl leukotriene receptor antagonist, inhibits the growth of chronic myeloid leukemia cells through apoptosis2018Inngår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 40, nr 2, s. 902-908Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The clinical outcome for patients with chronic myeloid leukemia (CML) has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs). However, their curative potential appears limited, probably as a consequence of TKI-resistant leukemic stem cells (LSCs) that persist as a result of aberrant pathways independent of the well-established oncoprotein Bcr-Abl. One such pathway involves signaling through leukotrienes (LTs), bioactive compounds that have been suggested to play a role in several other malignancies. Cysteinyl LT1 receptor (CysLT1R) has been reported to be overexpressed in a number of solid cancers, and blocking of this receptor with the antagonist montelukast (treatment approved for bronchial asthma) has resulted in the killing of cancer cells. We recently demonstrated that montelukast, alone or in combination with imatinib, can effectively reduce the growth of CML cells, while normal bone marrow cells were left unaffected. Herein, we further investigated the importance of CysLT1R for the survival of CML cells and the mechanisms by which montelukast induces cell death. Knockdown of the CysLT1R of K562 cells with siRNA reduced their growth by 25%. Montelukast had no effect on these cells, while it killed more than 50% of CysLT1R-expressing cells. Growth inhibition exerted by imatinib was unaffected by CysLT1R status. Montelukast-induced killing of K562/JURL-MK1 CML cells was paralleled by Bax overexpression, cytochrome c release, PARP-1 cleavage, and caspase-3 activation, an event further increased in a setting where montelukast was added to imatinib. Wnt/-catenin signaling was activated by CysLT1R and we observed that montelukast could induce proteins in this pathway, a finding of relevance for LSC survival. Thus, montelukast, employed at in vivo-like concentrations, induces the killing of CML cells through apoptotic pathways and may provide an additional, novel therapeutic possibility in CML.

  • 24353. Zrinzo, Ludvic
    et al.
    Akram, Harith
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, Unit Funct Neurosurg, London WC1N 3BG, England.
    Comment on "Appropriate MRI sequences are required to accurately determine lead location after deep brain stimulation surgery"2014Inngår i: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, Vol. 21, nr 12, s. 2257-2258Artikkel i tidsskrift (Fagfellevurdert)
  • 24354. Zrinzo, Ludvic
    et al.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Deep brain stimulation for dystonia2014Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 120, nr 6, s. 1496-1496Artikkel i tidsskrift (Fagfellevurdert)
  • 24355.
    Zrinzo, Ludvic
    et al.
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, United Kingdom.
    Foltynie, Thomas
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, United Kingdom.
    Limousin, Patricia
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, United Kingdom.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Image-guided and image-verified deep brain stimulation2013Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 28, nr 2, s. 254-254Artikkel i tidsskrift (Fagfellevurdert)
  • 24356.
    Zrinzo, Ludvic
    et al.
    UCL, UCL Inst Neurol, Unit Funct Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
    Foltynie, Thomas
    UCL, UCL Inst Neurol, Unit Funct Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
    Limousin, Patricia
    UCL, UCL Inst Neurol, Unit Funct Neurosurg, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Image-verified deep brain stimulation reduces risk and cost with no apparent impact on efficacy2012Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 27, nr 12, s. 1585-1586Artikkel i tidsskrift (Fagfellevurdert)
  • 24357. Zrinzo, Ludvic
    et al.
    Foltynie, Thomas
    Limousin, Patricia
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Deep brain stimulation and hemorrhage RESPONSE2012Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 116, nr 4, s. 930-932Artikkel i tidsskrift (Fagfellevurdert)
  • 24358. Zrinzo, Ludvic
    et al.
    Foltynie, Thomas
    Limousin, Patricia
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review Clinical article2012Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 116, nr 1, s. 84-94Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Object. Hemorrhagic complications carry by far the highest risk of devastating neurological outcome in functional neurosurgery. Literature published over the past 10 years suggests that hemorrhage, although relatively rare, remains a significant problem. Estimating the true incidence of and risk factors for hemorrhage in functional neurosurgery is a challenging issue. Methods. The authors analyzed the hemorrhage rate in a consecutive series of 214 patients undergoing image-guided deep brain stimulation (DBS) lead placement without microelectrode recording (MER) and with routine postoperative MR imaging lead verification. They also conducted a systematic review of the literature on stereotactic ablative surgery and DBS over a 10-year period to determine the incidence and risk factors for hemorrhage as a complication of functional neurosurgery. Results. The total incidence of hemorrhage in our series of image-guided DBS was 0.9%: asymptomatic in 0.5%, symptomatic in 0.5%, and causing permanent deficit in 0.0% of patients. Weighted means calculated from the literature review suggest that the overall incidence of hemorrhage in functional neurosurgery is 5.0%, with asymptomatic hemorrhage occurring in 1.9% of patients, symptomatic hemorrhage in 2.1% and hemorrhage resulting in permanent deficit or death in 1.1%. Hypertension and age were the most important patient-related factors associated with an increased risk of hemorrhage. Risk factors related to surgical technique included use of MER, number of MER penetrations, as well as sulcal or ventricular involvement by the trajectory. The incidence of hemorrhage in studies adopting an image-guided and image-verified approach without MER was significantly lower than that reported with other operative techniques (p < 0.001 for total number of hemorrhages, p < 0.001 for asymptomatic hemorrhage, p < 0.004 for symptomatic hemorrhage, and p = 0.001 for hemorrhage leading to permanent deficit; Fisher exact test). Conclusions. Age and a history of hypertension are associated with an increased risk of hemorrhage in functional neurosurgery. Surgical factors that increase the risk of hemorrhage include the use of MER and sulcal or ventricular incursion. The meticulous use of neuroimaging-both in planning the trajectory and for target verification-can avoid all of these surgery-related risk factors and appears to carry a significantly lower risk of hemorrhage and associated permanent deficit. (DOI: 10.3171/2011.8.JNS101407)

  • 24359. Zrinzo, Ludvic
    et al.
    Foltynie, Thomas
    Limousin, Patricia
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Response to: Editorial - Functional neurosurgery and hemorrhage2012Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 116, nr 1, s. 83-83Artikkel i tidsskrift (Fagfellevurdert)
  • 24360. Zrinzo, Ludvic
    et al.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Conclusions should be supported by the data presented2013Inngår i: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 27, nr 4, s. 545-546Artikkel i tidsskrift (Fagfellevurdert)
  • 24361. Zrinzo, Ludvic
    et al.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Errors of Image Coregistration may Necessitate Intraoperative Refinement in Functional Neurosurgery2013Inngår i: J NEUROL SURG PART A, ISSN 2193-6315, Vol. 74, nr 5, s. 335-336Artikkel i tidsskrift (Fagfellevurdert)
  • 24362. Zrinzo, Ludvic
    et al.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL Institute of Neurology, University College London, London, United Kingdom.
    Hyam, Jonathan A.
    Foltynie, Thomas
    Limousin, Patricia
    A paradigm shift toward MRI-guided and MRI-verified DBS surgery2016Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 124, nr 4, s. 1135-1137Artikkel i tidsskrift (Fagfellevurdert)
  • 24363. Zrinzo, Ludvic
    et al.
    Wilson, James
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Joyce, Eileen
    Morris, Jane
    Schmidt, Ulrike
    Exploring every ethical avenue. Commentary: The Moral Obligation to Prioritize Research Into Deep Brain Stimulation Over Brain Lesioning Procedures for Severe Enduring Anorexia Nervosa2019Inngår i: Frontiers in Psychiatry, ISSN 1664-0640, E-ISSN 1664-0640, Vol. 10, artikkel-id 326Artikkel i tidsskrift (Annet vitenskapelig)
  • 24364.
    Zrinzo, Ludvic
    et al.
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Yoshida, Fumiaki
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Thornton, John
    UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Foltynie, Thomas
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Yousry, Tarek A.
    UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK .
    Limousin, Patricia
    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, UK.
    Clinical safety of brain magnetic resonance imaging with implanted deep brain stimulation hardware: large case series and review of the literature2011Inngår i: World Neurosurgery, ISSN 1878-8750, Vol. 76, nr 1-2, s. 164-172Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Over 75,000 patients have undergone deep brain stimulation (DBS) procedures worldwide. Magnetic resonance imaging (MRI) is an important clinical and research tool in analyzing electrode location, documenting postoperative complications, and investigating novel symptoms in DBS patients. Functional MRI may shed light on the mechanism of action of DBS. MRI safety in DBS patients is therefore an important consideration.

    Methods: We report our experience with MRI in patients with implanted DBS hardware and examine the literature for clinical reports on MRI safety with implanted DBS hardware.

    Results: A total of 262 MRI examinations were performed in 223 patients with intracranial DBS hardware, including 45 in patients with an implanted pulse generator. Only 1 temporary adverse event occurred related to patient agitation and movement during immediate postoperative MR imaging. Agitation resolved after a few hours, and an MRI obtained before implanted pulse generator implantation revealed edema around both electrodes. Over 4000 MRI examinations in patients with implanted DBS hardware have been reported in the literature. Only 4 led to adverse events, including 2 hardware failures, 1 temporary and 1 permanent neurological deficit. Adverse neurological events occurred in a unique set of circumstances where appropriate safety protocols were not followed. MRI guidelines provided by DBS hardware manufacturers are inconsistent and vary among devices.

    Conclusions: The importance of MRI in modern medicine places pressure on industry to develop fully MRI-compatible DBS devices. Until then, the literature suggests that, when observing certain precautions, cranial MR images can be obtained with an extremely low risk in patients with implanted DBS hardware.

  • 24365. Zrinzo, Ludvic
    et al.
    Zrinzo, Laurence V.
    Massey, Luke A.
    Thornton, John
    Parkes, Harold G.
    White, Mark
    Yousry, Tarek A.
    Strand, Catherine
    Revesz, Tamas
    Limousin, Patricia
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Holton, Janice L.
    Targeting of the pedunculopontine nucleus by an MRI-guided approach: a cadaver study2011Inngår i: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 118, nr 10, s. 1487-1495Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Laboratory evidence suggests that the pedunculopontine nucleus (PPN) plays a central role in the initiation and maintenance of gait. Translational research has led to reports on deep brain stimulation (DBS) of the rostral brainstem in parkinsonian patients. However, initial clinical results appear to be rather variable. Possible factors include patient selection and the wide variability in anatomical location of implanted electrodes. Clinical studies on PPN DBS efficacy would, therefore, benefit from an accurate and reproducible method of stereotactic localization of the nucleus. The present study evaluates the anatomical accuracy of a specific protocol for MRI-guided stereotactic targeting of the PPN in a human cadaver. Imaging at 1.5 and 9.4 T confirmed electrode location in the intended region as defined anatomically by the surrounding fiber tracts. The spatial relations of each electrode track to the nucleus were explored by subsequent histological examination. This confirmed that the neuropil surrounding each electrode track contained scattered large neurons morphologically consistent with those of the subnucleus dissipatus and compactus of the PPN. The results support the accuracy of the described specific MR imaging protocol.

  • 24366. Zucchelli, Marco
    et al.
    Camilleri, Michael
    Nixon Andreasson, Anna
    Bresso, Francesca
    Dlugosz, Aldona
    Halfvarson, Jonas
    Törkvist, Leif
    Schmidt, Peter T
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ohlsson, Bodil
    Duerr, Richard H
    Simren, Magnus
    Lindberg, Greger
    Agreus, Lars
    Carlson, Paula
    Zinsmeister, Alan R
    D'Amato, Mauro
    Association of TNFSF15 polymorphism with irritable bowel syndrome2011Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, nr 12, s. 1671-1677Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder, affecting more than 10% of the general population worldwide. Although a genetic component is suspected, unambiguous susceptibility genes have so far not been identified. This study tested the hypothesis that genes contributing to epithelial barrier integrity, control of mucosal immune responses and interactions with bacteria in the gut are associated with IBS.

    Methods: Single nucleotide polymorphisms (SNPs) corresponding to top signals of association with Crohn's disease at 30 known susceptibility loci were tested for their effect on IBS risk in 1992 individuals from two independent case–control cohorts from Sweden and the USA. Association tests included a conservative Bonferroni correction for multiple comparisons, and were also performed on specific subgroups of patients characterised by constipation (IBS-C), diarrhoea (IBS-D) or alternating constipation and diarrhoea (IBS-A).

    Results: The Crohn's disease risk allele rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of both IBS (p=2.2×10−5; OR 1.37) and more pronouncedly, IBS-C (p=8.7×10−7; OR 1.79) in the entire sample. Similar associations and risk effects of the same magnitude were observed in the two cohorts analysed separately. A correlation between rs4263839 genotype and TNFSF15 mRNA expression was detected both in peripheral blood and in rectal mucosal biopsies from healthy individuals (combined p=0.0033).

    Conclusions: TNFSF15 is a susceptibility gene for IBS and IBS constipation. As TL1A, the protein encoded by TNFSF15, contributes to the modulation of inflammatory responses, the results support a role of immune activation in IBS.

  • 24367. Zulu, Joseph M.
    et al.
    Goicolea, Isabel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Kinsman, John
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Sandøy, Ingvild Fossgard
    Blystad, Astrid
    Mulubwa, Chama
    Makasa, Mpundu C.
    Michelo, Charles
    Musonda, Patrick
    Hurtig, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Community based interventions for strengthening adolescent sexual reproductive health and rights: how can they be integrated and sustained? A realist evaluation protocol from Zambia2018Inngår i: Reproductive Health, ISSN 1742-4755, E-ISSN 1742-4755, Vol. 15, artikkel-id 145Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Research that explores how community-based interventions for strengthening adolescent sexual reproductive health and rights (SRHR) can be integrated and sustained in community health systems, is, to the best of our knowledge, very scarce, if not absent. It is important to document mechanisms that shape integration process in order to improve health systems' responsiveness towards adolescents' SRHR. This realist evaluation protocol will contribute to this knowledge in Zambia where there is increased attention towards promoting maternal, neonatal and child health as a means of addressing the current high early pregnancy and marriage rates. The protocol will ascertain: why, how, and under what conditions the integration of SRHR interventions into Zambian community health systems will optimise (or not) acceptability and adoption of SRHR services. This study is embedded within a randomized controlled trial - "Research Initiative to Support the Empowerment of Girls (RISE) "-which aims to reduce adolescent girl pregnancies and marriages through a package of interventions including economic support to families, payment of school fees to keep girls in school, pocket money for girls, as well as youth club and community meetings on reproductive health.

    Methods: This is a multiple-case study design. Data will be collected from schools, health facilities and communities through individual and group interviews, photovoice, documentary review, and observations. The study process will involve 1) developing an initial causal theory that proposes an explanation of how the integration of a community-based intervention that aimed to integrate adolescent SRHR into the community health system may lead to adolescent-friendly services; 2) refining the causal theory through case studies; 3) identifying contextual conditions and mechanisms that shape the integration process; and 4) finally proposing a refined causal theory and set of recommendations to guide policy makers, steer further research, and inform teaching programmes.

    Discussion: The study will document relevant values as well as less formal and horizontal mechanisms which shape the integration process of SRHR interventions at community level. Knowledge on mechanisms is essential for guiding development of strategies for effectively facilitating the integration process, scaling up processes and sustainability of interventions aimed at reducing SRH problems and health inequalities among adolescents.

  • 24368.
    Zulu, Joseph M.
    et al.
    University of Zambia.
    Kinsman, John
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Hurtig, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Michelo, Charles
    University of Zambia.
    George, Asha
    University of the Western Cape.
    Schneider, Helen
    University of the Western Cape.
    Integrating community health assistant-driven sexual and reproductive health services in the community health system in Nyimba district in Zambia: mapping key actors, points of integration, and conditions shaping the process2019Inngår i: Reproductive Health, ISSN 1742-4755, E-ISSN 1742-4755, Vol. 16, nr 1, artikkel-id 122Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Although large scale public sector community health worker programs have been key in providing sexual and reproductive health (SRH) services in low- and middle-income countries, their integration process into community health systems is not well understood. This study aimed to identify the conditions and strategies through which Community Health Assistants (CHAs) gained entry and acceptability into community health systems to provide SRH services to youth in Zambia. The country's CHA program was launched in 2010.

    Methodology: A phenomenological design was conducted in Nyimba district. All nine CHAs deployed in Nyimba district were interviewed in-depth on their experiences of navigating the introduction of SRH services for youth in community settings, and the data obtained analyzed thematically.

    Results: In delivering SRH services targeting youth, CHAs worked with a range of community actors, including other health workers, safe motherhood action groups, community health workers, neighborhood health committees, teachers, as well as political, traditional and religious leaders. CHAs delivered SRH education and services in health facilities, schools, police stations, home settings, and community spaces. They used their health facility service delivery role to gain trust and entry into the community, and they also worked to build relationships with other community level actors by holding regular joint meetings, and acting as brokers between the volunteer health workers and the Ministry of Health. CHAs used their existing social networks to deliver SRH services to adolescents. By embedding the provision of information about SRH into general life skills at community level, the topic's sensitivity was reduced and its acceptability was enhanced. Further, support from community leaders towards CHA-driven services promoted the legitimacy of providing SRH for youth. Factors limiting the acceptability of CHA services included the taboo of discussing sexuality issues, a gender discriminatory environment, competition with other providers, and challenges in conducting household visits.

    Conclusion: Strengthening CHAs' ability to negotiate and navigate and gain acceptability in the community health system as they deliver SRH, requires support from both the formal health system and community networks. Limitations to the acceptability of CHA-driven SRH services are a product of challenges both in the community and in the formal health system.

  • 24369. Zulu, Joseph M
    et al.
    Michelo, Charles
    Msoni, Carol
    Hurtig, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Byskov, Jens
    Blystad, Astrid
    Increased fairness in priority setting processes within the health sector: the case of Kapiri-Mposhi District, Zambia2014Inngår i: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 14, s. 75-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The challenge of priority setting (PS) in health care within contexts of severe resource limitations has continued to receive attention. Accountability for Reasonableness (AFR) has emerged as a useful framework to guide the implementation of PS processes. In 2006, the AFR approach to enhance legitimate and fair PS was introduced by researchers and decision makers within the health sector in the EU funded research project entitled 'Response to Accountable priority setting for Trust in health systems' (REACT). The project aimed to strengthen fairness and accountability in the PS processes of health systems at district level in Zambia, Tanzania and Kenya. This paper focuses on local perceptions and practices of fair PS (baseline study) as well as at the evolution of such perceptions and practices in PS following an AFR based intervention (evaluation study), carried out at district level in Kapiri-Mposhi District in Zambia. Methods: Data was collected using in depth interviews (IDIs), focus group discussions (FGDs) and review of documents from national to district level. The study population for this paper consisted of health related stakeholders employed in the district administration, in non-governmental organizations (NGO) and in health facilities. Results: During the baseline study, concepts of legitimacy and fairness in PS processes were found to be grounded in local values of equity and impartiality. Government and other organizational strategies strongly supported devolution of PS and decision making procedures. However, important gaps were identified in terms of experiences of stakeholder involvement and fairness in PS processes in practice. The evaluation study revealed that a transformation of the views and methods regarding fairness in PS processes was ongoing in the study district, which was partly attributed to the AFR based intervention. Conclusions: The study findings suggest that increased attention was given to fairness in PS processes at district level. The changes were linked to a number of simultaneous factors among them the concepts introduced by the present project with its emphasis on fairness and enhanced participation. A responsive leadership that was increasingly accountable to its operational staff and communities emerged as one of the key elements in driving the processes forward.

  • 24370.
    Zulu, Joseph Mumba
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Department of Public Health, School of Medicine, University of Zambia, Lusaka, Zambia.
    Hurtig, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Kinsman, John
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Michelo, Charles
    Department of Public Health, School of Medicine, University of Zambia, Lusaka, Zambia.
    Innovation in health service delivery: integrating community health assistants into the health system at district level in Zambia2015Inngår i: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 15, s. 38-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: To address the huge human resources for health gap in Zambia, the Ministry of Health launched the National Community Health Assistant Strategy in 2010. The strategy aims to integrate community-based health workers into the health system by creating a new group of workers, called community health assistants (CHAs). However, literature suggests that the integration process of national community-based health worker programmes into health systems has not been optimal. Conceptually informed by the diffusion of innovations theory, this paper qualitatively aimed to explore the factors that shaped the acceptability and adoption of CHAs into the health system at district level in Zambia during the pilot phase. Methods: Data gathered through review of documents, 6 focus group discussions with community leaders, and 12 key informant interviews with CHA trainers, supervisors and members of the District Health Management Team were analysed using thematic analysis. Results: The perceived relative advantage of CHAs over existing community-based health workers in terms of their quality of training and scope of responsibilities, and the perceived compatibility of CHAs with existing groups of health workers and community healthcare expectations positively facilitated the integration process. However, limited integration of CHAs in the district health governance system hindered effective programme trialability, simplicity and observability at district level. Specific challenges at this level included a limited information flow and sense of programme ownership, and insufficient documentation of outcomes. The district also had difficulties in responding to emergent challenges such as delayed or non-payment of CHA incentives, as well as inadequate supervision and involvement of CHAs in the health posts where they are supposed to be working. Furthermore, failure of the health system to secure regular drug supplies affected health service delivery and acceptability of CHA services at community level. Conclusion: The study has demonstrated that implementation of policy guidelines for integrating community-based health workers in the health system may not automatically guarantee successful integration at the local or district level, at least at the start of the process. The study reiterates the need for fully integrating such innovations into the district health governance system if they are to be effective.

  • 24371.
    Zulu, Joseph Mumba
    et al.
    Department of Public Health, School of Medicine, University of Zambia, Lusaka, Zambia .
    Kinsman, John
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Michelo, Charles
    Department of Public Health, School of Medicine, University of Zambia, Lusaka, Zambia .
    Hurtig, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Developing the national community health assistant strategy in Zambia: a policy analysis2013Inngår i: Health Research Policy and Systems, ISSN 1478-4505, E-ISSN 1478-4505, Vol. 11, s. 24-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In 2010, the Ministry of Health in Zambia developed the National Community Health Assistant strategy, aiming to integrate community health workers (CHWs) into national health plans by creating a new group of workers, called community health assistants (CHAs). The aim of the paper is to analyse the CHA policy development process and the factors that influenced its evolution and content. A policy analysis approach was used to analyse the policy reform process.

    METHODOLOGY: Data were gathered through review of documents, participant observation and key informant interviews with CHA strategic team members in Lusaka district, and senior officials at the district level in Kapiri Mposhi district where some CHAs have been deployed.

    RESULTS: The strategy was developed in order to address the human resources for health shortage and the challenges facing the community-based health workforce in Zambia. However, some actors within the strategic team were more influential than others in informing the policy agenda, determining the process, and shaping the content. These actors negotiated with professional/statutory bodies and health unions on the need to develop the new cadre which resulted in compromises that enabled the policy process to move forward. International agencies also indirectly influenced the course as well as the content of the strategy. Some actors classified the process as both insufficiently consultative and rushed. Due to limited consultation, it was suggested that the policy content did not adequately address key policy content issues such as management of staff attrition, general professional development, and progression matters. Analysis of the process also showed that the strategy might create a new group of workers whose mandate is unclear to the existing group of health workers.

    CONCLUSIONS: This paper highlights the complex nature of policy-making processes for integrating CHWs into the health system. It reiterates the need for recognising the fact that actors' power or position in the political hierarchy may, more than their knowledge and understanding of the issue, play a disproportionate role in shaping the process as well as content of health policy reform.

  • 24372.
    Zulu, Joseph Mumba
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Department of Public Health, School of Medicine, University of Zambia, Lusaka, Zambia.
    Kinsman, John
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Michelo, Charles
    Department of Public Health, School of Medicine, University of Zambia, Lusaka, Zambia.
    Hurtig, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Hope and despair: community health assistants' experiences of working in a rural district in Zambia2014Inngår i: Human Resources for Health, ISSN 1478-4491, E-ISSN 1478-4491, Vol. 12, nr 1, artikkel-id 30Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In order to address the challenges facing the community-based health workforce in Zambia, the Ministry of Health implemented the national community health assistant strategy in 2010. The strategy aims to address the challenges by creating a new group of workers called community health assistants (CHAs) and integrating them into the health system. The first group started working in August 2012. The objective of this paper is to document their motivation to become a CHA, their experiences of working in a rural district, and how these experiences affected their motivation to work.

    METHODS: A phenomenological approach was used to examine CHAs' experiences. Data collected through in-depth interviews with 12 CHAs in Kapiri Mposhi district and observations were analysed using a thematic analysis approach.

    RESULTS: Personal characteristics such as previous experience and knowledge, passion to serve the community and a desire to improve skills motivated people to become CHAs. Health systems characteristics such as an inclusive work culture in some health posts motivated CHAs to work. Conversely, a non-inclusive work culture created a social structure which constrained CHAs' ability to learn, to be innovative and to effectively conduct their duties. Further, limited supervision, misconceptions about CHA roles, poor prioritisation of CHA tasks by some supervisors, as well as non- and irregular payment of incentives also adversely affected CHAs' ability to work effectively. In addition, negative feedback from some colleagues at the health posts affected CHA's self-confidence and professional outlook. In the community, respect and support provided to CHAs by community members instilled a sense of recognition, appreciation and belonging in CHAs which inspired them to work. On the other hand, limited drug supplies and support from other community-based health workers due to their exclusion from the government payroll inhibited CHAs' ability to deliver services.

    CONCLUSIONS: Programmes aimed at integrating community-based health workers into health systems should adequately consider multiple incentives, effective management, supervision and support from the district. These should be tailored towards enhancing the individual, health system and community characteristics that positively impact work motivation at the local level if such programmes are to effectively contribute towards improved primary healthcare.

  • 24373.
    Zulu, Joseph Mumba
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Department of Public Health, School of Medicine, University of Zambia, P.O. Box 50110, Lusaka, Zambia.
    Kinsman, John
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Michelo, Charles
    Univ Zambia, Sch Med, Dept Publ Hlth, Lusaka, Zambia.
    Hurtig, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Integrating national community-based health worker programmes into health systems: a systematic review identifying lessons learned from low-and middle-income countries2014Inngår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 14, nr 1, artikkel-id 987Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Despite the development of national community-based health worker (CBHW) programmes in several low- and middle-income countries, their integration into health systems has not been optimal. Studies have been conducted to investigate the factors influencing the integration processes, but systematic reviews to provide a more comprehensive understanding are lacking.

    METHODS: We conducted a systematic review of published research to understand factors that may influence the integration of national CBHW programmes into health systems in low- and middle-income countries. To be included in the study, CBHW programmes should have been developed by the government and have standardised training, supervision and incentive structures. A conceptual framework on the integration of health innovations into health systems guided the review. We identified 3410 records, of which 36 were finally selected, and on which an analysis was conducted concerning the themes and pathways associated with different factors that may influence the integration process.

    RESULTS: Four programmes from Brazil, Ethiopia, India and Pakistan met the inclusion criteria. Different aspects of each of these programmes were integrated in different ways into their respective health systems. Factors that facilitated the integration process included the magnitude of countries' human resources for health problems and the associated discourses about how to address these problems; the perceived relative advantage of national CBHWs with regard to delivering health services over training and retaining highly skilled health workers; and the participation of some politicians and community members in programme processes, with the result that they viewed the programmes as legitimate, credible and relevant. Finally, integration of programmes within the existing health systems enhanced programme compatibility with the health systems' governance, financing and training functions. Factors that inhibited the integration process included a rapid scale-up process; resistance from other health workers; discrimination of CBHWs based on social, gender and economic status; ineffective incentive structures; inadequate infrastructure and supplies; and hierarchical and parallel communication structures.

    CONCLUSIONS: CBHW programmes should design their scale-up strategy differently based on current contextual factors. Further, adoption of a stepwise approach to the scale-up and integration process may positively shape the integration process of CBHW programmes into health systems.

  • 24374. Zuo, H.
    et al.
    Ueland, P. M.
    Midttun, O.
    Tell, G. S.
    Fanidi, A.
    Zheng, W.
    Shu, X.
    Xiang, Y.
    Wu, J.
    Prentice, R.
    Pettinger, M.
    Thomson, C. A.
    Giles, G. G.
    Hodge, A.
    Cai, Q.
    Blot, W. J.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Stevens, V. L.
    McCullough, M. L.
    Weinstein, S. J.
    Albanes, D.
    Ziegler, R. G.
    Freedman, N. D.
    Caporaso, N. E.
    Langhammer, A.
    Hveem, K.
    Naess, M.
    Buring, J. E.
    Lee, I.
    Gaziano, J. M.
    Severi, G.
    Zhang, X.
    Stampfer, M. J.
    Han, J.
    Zeleniuch-Jacquotte, A.
    Marchand, L. L.
    Yuan, J.
    Wang, R.
    Koh, W.
    Gao, Y.
    Ericson, U.
    Visvanathan, K.
    Jones, M. R.
    Relton, C.
    Brennan, P.
    Ulvik, A.
    Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3)2019Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 30, nr 3, s. 478-485Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known.

    Materials and methods: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models.

    Results: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3years of blood draw (OR: 1.73, 95% CI: 1.34-2.23).

    Conclusion: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

  • 24375. Zuo, Hui
    et al.
    Ueland, Per Magne
    Midttun, Øivind
    Vollset, Stein E
    Tell, Grethe S
    Theofylaktopoulou, Despoina
    Travis, Ruth C
    Boutron-Ruault, Marie-Christine
    Fournier, Agnes
    Severi, Gianluca
    Kvaskoff, Marina
    Boeing, Heiner
    Bergmann, Manuela
    Fortner, Renée Turzanski
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Kotanidou, Anastasia
    Lagiou, Pagona
    Palli, Domenico
    Sieri, Sabina
    Panico, Salvatore
    Bueno-de-Mesquita, H B As
    Peeters, Petra H
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Agudo, Antonio
    Quirós Garcia, Jose Ramón
    Larrañaga, Nerea
    Sanchez, Maria-Jose
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Chuang, Shu-Chun
    Gallo, Valentina
    Brennan, Paul
    Johansson, Mattias
    Ulvik, Arve
    Results from the European Prospective Investigation into Cancer and Nutrition Link Vitamin B6 Catabolism and Lung Cancer Risk2018Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, nr 1, s. 302-308Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Circulating pyridoxal-5′-phosphate (PLP) has been linked to lung cancer risk. The PAr index, defined as the ratio 4-pyridoxic acid/(pyridoxal + PLP), reflects increased vitamin B6 catabolism during inflammation. PAr has been defined as a marker of lung cancer risk in a prospective cohort study, but analysis of a larger numbers of cases are needed to deepen the significance of this study. Here, we conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC, n = 521,330), which included 892 incident lung cancer cases and 1,748 controls matched by center, gender, date of blood collection, and date of birth. The association of PAr with risk of lung cancer was evaluated by using conditional logistic regression. Study participants with elevated PAr experienced higher risk of lung cancer in a dose–response fashion, with a doubling in PAr levels associated with 52% higher odds of lung cancer after adjustment for tobacco smoking, serum cotinine levels, educational attainment, and BMI [OR, 1.52; 95% confidence interval (CI) 1.27–1.81; P < 0.001]. Additional adjustment for intake of vegetables and fruits and physical activity did not materially affect risk association. The association of PAr with lung cancer risk was similar in both genders but slightly stronger in former smokers and in participants diagnosed with squamous cell carcinoma. This study provides robust evidence that increased vitamin B6 catabolism is independently associated with a higher risk of future lung cancer.

  • 24376. Zuo, Nianming
    et al.
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Liu, Hao
    Yang, Zhengyi
    Jiang, Tianzi
    Functional maintenance in the multiple demand network characterizes superior fluid intelligence in aging2020Inngår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 85, s. 145-153Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The multiple demand network (MDN) is conceptualized as the core processing system for multi-tasking. Increasing evidence also provides strong support for the involvement of the MDN in fluid intelligence (gF), that is, the ability to solve new problems. However, the underlying neural mechanisms of declining intelligence in old age are poorly explored, particularly whether maintenance of the functional architecture of the MDN can characterize superior intelligence in successful aging. Here, we used eigenvector centrality (EC) to explore the resting-state functional architecture of the MDN in terms of its communication across the entire brain. We found gF to be negatively associated with age and that the MDN EC competitively mediated age-related decline in gF over the aging lifespan, suggesting that excessive cross-talk from the MDN is deleterious for intelligence. Critically, older individuals with comparable MDN EC as younger individuals exhibited superior gF compared with their age-matched counterparts. Taken together, these data provide support for the maintenance of youth-like functional architecture of the MDN and its implication for superior intelligence in successful aging. 

  • 24377. Zuo, Nianming
    et al.
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Aging Research Center, Karolinska Institute and Stockholm University, Stockholm, Sweden.
    Yang, Yihong
    Yang, Zhengyi
    Sui, Jing
    Jian, Tianzi
    Activation-based association profiles differentiate network roles across cognitive loads2019Inngår i: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 40, nr 9, s. 2800-2812Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Working memory (WM) is a complex and pivotal cognitive system underlying the performance of many cognitive behaviors. Although individual differences in WM performance have previously been linked to the blood oxygenation level-dependent (BOLD) response across several large-scale brain networks, the unique and shared contributions of each large-scale brain network to efficient WM processes across different cognitive loads remain elusive. Using a WM paradigm and functional magnetic resonance imaging (fMRI) from the Human Connectome Project, we proposed a framework to assess the association and shared-association strength between imaging biomarkers and behavioral scales. Association strength is the capability of individual brain regions to modulate WM performance and shared-association strength measures how different regions share the capability of modulating performance. Under higher cognitive load (2-back), the frontoparietal executive control network (FPN), dorsal attention network (DAN), and salience network showed significant positive activation and positive associations, whereas the default mode network (DMN) showed the opposite pattern, namely, significant deactivation and negative associations. Comparing the different cognitive loads, the DMN and FPN showed predominant associations and globally shared-associations. When investigating the differences in association from lower to higher cognitive loads, the DAN demonstrated enhanced association strength and globally shared-associations, which were significantly greater than those of the other networks. This study characterized how brain regions individually and collaboratively support different cognitive loads.

  • 24378.
    Zusmanis, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Inifrån Sjukstugan: En kvalitativ studie av Storumans sjukstuga från ett medarbetarperspektiv2015Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 24379.
    Zygmuntowicz, Marcelina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Optimering vid detektion av anti-superoxiddismutas 1 (SOD1) med immunohistokemi: I transgena möss med användning av olika vävnadsförbehandlingsmetoder2016Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 24380.
    Árnadóttir, Guðrún
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Measuring the impact of body functions on occupational performance: validation of the ADL-focused occupation-based neurobehavioral evaluation (A-ONE)2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Among the instruments commonly used by occupational therapists working in the area of rehabilitation of persons with neurological disorders are evaluations of both occupation, such as activities of daily living (ADL), and body functions. While persons with neurological diagnoses typically have symptoms that represent diminished neurobehavioral functions, the resulting pattern of neurobehavioral impairments affecting ADL performance often differs among diagnostic groups. Usually, neurobehavioral impairments are evaluated in a context that is separate from and not natural for ADL task performance. The A-ONE is a unique instrument that can be used to evaluate both ADL performance (ADL scale) and, in the natural context of the ADL task performance, the underlying neurobehaviors that cause diminished ADL task performance among persons with neurological disorders (Neurobehavioral scale). The scales of the instrument are of ordinal type, and in their existing form, do not have measurement properties. Measurement properties are a requirement of evidence-based and quality assured rehabilitation services.

    The overall aim of this doctoral study was to further develop and validate the A-ONE. This included (a) internal validation to explore the potential for converting the ordinal scales of the instrument to interval scales, (b) examination of which of the neurobehavioral items would be most beneficial and clinically useful for constructing a new Neurobehavioral Impact (NBI) scale for evaluating persons with different neurological diagnoses, and (c) exploration of whether persons with right and left cerebrovascular accidents (RCVA, LCVA) differ in mean NBI measures.

     Methods: This thesis is comprised of four studies which all contribute in different ways to the validation of the scales of the A-ONE. In the first three studies, Rasch analyses, a widely accepted modern test theory methodology, was used to examine internal validity of the scales and the reliability of the A-ONE measures. In the fourth study, ANCOVA was used to explore between group differences, and Pearson correlation coefficients were used to explore relations between person measures from the different A-ONE scales.

    Results: The first study of 209 persons diagnosed with CVA and dementia provided support for converting the ordinal ADL scale to an interval scale that has potential to be used to measure change in ADL performance over time. The second and third studies, including 206 and 422 persons respectively, indicated that it is possible to construct several unidimensional versions of a new NBI scale from the neurobehavioral items of the instrument, each with different item content and hierarchical item structure. Further, some of these NBI scales could be used across different diagnostic groups. When exploring differences between 215 persons with RCVA and LCVA on the NBI scale developed for CVA, results of the ANCOVA (with ADL ability as a covariate) indicated that there is no significant difference between groups in their mean NBI measures, despite known differences in patterns of neurobehavioral impairments.

    Conclusions: The results of this thesis indicate that the A-ONE, although developed by traditional psychometric methods for the purpose of providing useful information for intervention planning, now also has the potential to be used to measure change and compare diagnostic groups. This additional feature will likely enhance both clinical and research potential of the instrument. In order to make the results of the study accessible for clinicians, conversion tables need to be developed.

  • 24381.
    Árnadóttir, Guðrún
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. 1Occupational Therapy Unit, Grensás, Landspítali University Hospital, Reykjavík; 2Division of Occupational Therapy, Faculty of Health, University of Akureyri, Akureyri, Iceland.
    Löfgren, Britta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Fisher, Anne G
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Difference in impact of neurobehavioural dysfunction on Activities of Daily Living performance between right and left hemispheric stroke2010Inngår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 42, nr 10, s. 903-907Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To explore whether persons with right- and left-sided cerebrovascular accidents differ significantly in mean impact of neurobehavioural impairments on ability to perform activities of daily living. Design and subjects: Retrospective study of data from 215 persons (103 right-sided, 112 left-sided cerebrovascular accident). The Activities of daily living-focused Occupation-based Neurobehavioral Evaluation was used to evaluate ability on an activities of daily living scale and the impact of neurobehavioural impairment on ability on another scale. Methods: To control for possible differences in activities of daily living ability between groups, analysis of covariance, with activities of daily living ability as a covariate, was used to test for a significant difference in impact of neurobehavioural impairments on activities of daily living ability between groups. Results: Expected moderate correlation (r=-0.57) was obtained between activities of daily living ability and neurobehavioural impact measures, and there was no difference in mean neurobehavioural impact measures between groups (F [1, 212] = 2.910,p = 0.090). Conclusion: This study is the first: to explore directly the impact of neurobehavioural impairment on activities of daily living ability. While persons with right-sided and left-sided cerebrovascular accidents may differ in type of neurobehavioural impairments, direct evaluation of the impact of such impairments on activities of daily living ability reveals no difference between groups.

  • 24382.
    Älander, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Arvidsson, Anton
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Det sexuella orosmolnet: Finns det ett samband mellan oro/ångest/nedstämdhet och sexuell aktivitet samt hur det påverkar den upplevda sexualfunktionen bland män med prostatacancer?2015Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Background: Prostate cancer is the most common form of cancer among men in Sweden. Many people that are diagnosed or going through treatment for the disease experiences negative side effects. It´s not uncommon with side effects that give problems with sexual health.

    Aim: The objective of the study is to investigate the connection between problems with worry/anxiety/depression and sexual activity and perceived sexual function for men with prostate cancer.

    Method: This study was conducted as a quantitative cross-sectional study, as part of a larger ongoing study, with data collected from members in the SPCF (Svenska Prostatacancer Förbundet) with help of questionnaires. Data collected from 3165 men who regardless of treatment and age were analyzed and studied by division into two groups.

    Results: The results showed that men who has problems with any form of worry/anxiety/depression are less sexually active than men who not had problems. It also shows that men with less sexual activity think themselves as less satisfied than men with no problems.

    Conclusion: The study shows that there is a connection between worry/anxiety/depression and sexual activity and perceived sexual function on men with prostate cancer. Various finds have been discovered in the study and knowledge gaps have been illustrated. Nurses can use the schedule as a help whit their work about the sexual health.

  • 24383.
    Äng, Christofer
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Undernutrition among children in Bandja: Undernutrition among under-five children in the Bandja village of Cameroon2016Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 24384.
    Ängquist, Karl-Axel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Human skeletal muscle fibre structure: effects of physical training and arterial insufficiency1978Doktoravhandling, med artikler (Annet vitenskapelig)
  • 24385.
    Ärleskog, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    THE OUTCOME OF SURGICAL AND POSTOPERATIVE PRESSURE ULCER TREATMENT IN PATIENTS WITH PARALYSIS - A retrospective study of the care plan at Norrlands University Hospital2017Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 24386.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Genetic studies in rheumatoid arthritis: familial studies and analysis of relationships to atherothrombotic comorbidity2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background. Rheumatoid arthritis (RA) is an autoimmune disease mainly affecting the joints but has also extra articular manifestations and an increased cardiovascular (CV) co-morbidity. Rheumatoid factor (RF) and antibodies against citrullinated proteins/peptides (ACPA) are diagnostically important and are related to a more severe disease. The aetiology is unknown but RA is considered a complex disease caused by both genetic and environmental factors. The heritability is estimated to be 60% with the main contribution from the HLA region. The relative homogeneity of the population in northern Sweden due to low immigration and founder effects has shown to be suitable for genetic studies.

    Objectives. The aim of this thesis has been to identify genes contributing to the susceptibility of RA and the CV co-morbidity in particular. To achieve this, multi-case families from the four northern most counties of Sweden were collected for linkage studies to identify susceptibility genes. Association studies with genetic polymorphisms in genes, involved in inflammation or being of importance for atherothrombotic manifestations (ATM) in the general population, were performed in RA-patients concerning ATM e.g. myocardial infarction, angina pectoris with intervention, stroke/TIA, deep vein thrombosis/pulmonary embolism (DVT/PE) at follow-up.

    Methods & Results. 47 families with 134 affected and 216 unaffected relatives were included in a genome-wide linkage study (GWL) performed with microsatellite markers at an average of 10cM resolution analysed using ABI PRISM 3730 DNA sequencer and non-parametric multipoint linkage in the Merlin program. Eight linked loci were identified with HLA as the most significant and a novel region on chromosome 14. In a follow-up analysis on a custom Illumina chip, with 13 additional families, yielding a total of 198 affected and 197 unaffected relatives. The majority of the 1536 single nucleotide polymorphisms (SNPs) used in the Illumina follow-up analyses was focused on chromosome 14. Statistical analyses with linkage and transmission disequilibrium test narrowed the region to 4 cM, a region containing multiple plausible RA candidate genes (Paper I). In Paper II  serum samples from 163 affected and 157 first degree relatives were analysed with EliA ACPA assay on ImmunoCAP250 for ACPA (IgA, IgG, IgM) and RF (IgA, IgM) isotypes. Both concentrations and frequencies were increased among the relatives compared with controls but lower compared with RA-patients and with a different relative distribution of the isotypes.

    The genetic contribution to ATM was studied in Paper III and IV using selected SNPs analysed using ABI PRISM 7900HT sequence detector system. In Paper III, RA-patients (n=467) were compared with age and sex matched controls (n=696) with respect to SNPs in tumor necrosis factor receptor II (TNFRII)(M196R), ß-fibrinogen -455 (G-455A), plasminogen activator inhibitor type-1 (PAI-1) (4G/5G) and Factor XIIIA (Val34Leu). Hypertension was predicted by TNFRII R allele and to a higher extent in combination with the A-allele in ß-fibrinogen. The 4G allele in PAI-1 was more frequent in patients with ischemic heart disease (IHD) and the FXIIIA Leu34 variant in patients with DVT/PE. In Paper IV, the minor allele of the polymorphism in growth differentiation factor 15 (GDF15) was found to be associated with RA (n=696) per se but also to ATM, a SNP in the 9p21.3 locus was also associated with ATM. A significant association to stroke was found in female patients homozygote for the minor allele of GDF15. Stoke among male patients was significantly associated with carrying the major allele of two SNPs in the CD40 gene. DVT/PE was associated with the minor allele of GDF15.

    Conclusion. A novel locus on chromosome 14 of importance for RA susceptibility in northern Sweden was found. The minor allele of TNFRII separately and together with the minor allele of ß-fibrinogen -455 was associated with hypertension and the 4G allele in PAI-1 was associated with IHD and  the Leu34 variant was associated with DVT/PE in RA patients. The GDF15 minor allele was associated with RA per se, ATM and DVT/PE in RA patients and a genotype in the SNP on 9p21.3 was associated with ATM. Stroke among females was associated with GDF15 and stroke among males with two SNPs in CD40.

  • 24387.
    Ärlestig, Lisbeth
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Brink, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hansson, Monika
    Jakobsson, Per Johan
    Holmdahl, Rikard
    Mathsson, Linda
    Ronnelid, Johan
    Klareskog, Lars
    Rantapää-Dahlqvist, Solbritt M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Single Nucleotide Polymorphisms within the HLA-DRB1 Gene in Relation to Antibodies Against Citrullinated Peptides in Individuals Prior to the Development of Rheumatoid Arthritis2012Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr 10, s. S180-S180Artikkel i tidsskrift (Annet vitenskapelig)
  • 24388.
    Ärlestig, Lisbeth
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Einarsdottir, Elisabet
    Research Program Unit, Molecular Medicine, University of Helsinki, Finland.
    Holmberg, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Novel risk locus on chromosome 14 in multi-case families with rheumatoid arthritis from northern SwedenManuskript (preprint) (Annet vitenskapelig)
  • 24389.
    Ärlestig, Lisbeth
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Mullazehi, Mohammed
    Department of Immunology, Genetics and Pathology, Uppsala University.
    Kokkonen, Heidi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rocklöv, Joacim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Rönnelid, Johan
    Department of Immunology, Genetics and Pathology, Uppsala University.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Antibodies against cyclic citrullinated peptides of IgG, IgA and IgM isotype and rheumatoid factor of IgM and IgA isotype are increased in unaffected members of multicase rheumatoid arthritis families from northern Sweden2012Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, nr 6, s. 825-829Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Rheumatoid factors (RFs) and antibodies against cyclic citrullinated peptides (CCPs) of IgG, IgA and IgM isotype have been shown to precede disease onset by years.

    Objective To evaluate serological risk markers in first-degree relatives from multicase families in relation to genetic and environmental risk factors.

    Methods 51 multicase families consisting of 163 individuals with rheumatoid arthritis (RA) (mean±SD age, 60±14 years; disease duration 21 years; 71.8% female) and with 157 first-degree relatives unaffected by RA (54±17 years; 59.9% female) were recruited. Isotypes of antibodies against CCPs (IgG, IgA and IgM) and RFs (IgM and IgA) were determined using automated enzyme immunoassays. Cut-off levels were established using receiver operating characteristic curves based on values for 100 unrelated healthy controls.

    Results The concentrations and frequencies of all anti-CCP and RF isotypes were significantly increased in first-degree relatives and patients with RA compared with unrelated healthy controls. The relative distribution of IgA and IgM isotypes was higher than IgG in the relatives, whereas the IgG isotype dominated in patients with RA. The patients carried human leucocyte antigen-shared epitope (HLA-SE) significantly more often than the relatives (71.4% vs 53.9%, p=0.01), while the frequency of the PTPN22 T variant was similar. HLA-SE, combined with smoking, was significantly related to all combinations of anti-CCP and RF isotypes in patients with RA. No such relationships were found for the first-degree relatives.

    Conclusions All anti-CCP and RF isotypes analysed occurred more commonly in unaffected first-degree relatives from multicase families than in controls, but with different isotype distribution from patients with RA.

  • 24390.
    Ärlestig, Lisbeth
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Polymorphisms of the genes encoding CD40 and growth differentiation factor 15 and in the 9p21.3 region in patients with rheumatoid arthritis and cardiovascular diseaseManuskript (preprint) (Annet vitenskapelig)
  • 24391.
    Ärlestig, Lisbeth
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Polymorphisms of the Genes Encoding CD40 and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease2012Inngår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 39, nr 5, s. 939-945Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM). Methods. A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 +/- 13.2 years, and mean disease duration of 15.5 +/- 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587), CD40 (rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex). Results. The distribution of genotypes of GDF15/MIC-1 differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of the GDF15/MIC-1 G allele (OR 2.21, 95% CI 1.17-4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15-3.19). Stroke/TIA in women was associated with GDF15/MIC-1 GG genotype (OR 3.75, 95% CI 1.06-13.33), while stroke/TIA in men was associated with CD40 homozygous major alleles (OR 6.48, 95% CI 1.31-32.0 and OR 2.78,95% CI 0.78-9.91, respectively). DVT/PE was associated with polymorphism in the GDF15/MIC-1 gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30-9.58). Conclusion. The gene polymorphisms analyzed were associated with different ATM in RA. The GDF15/MIC-1 gene polymorphism was also associated with RA per se, suggesting a common etiology for RA and ATM. (First Release April 15 2012; J Rheumatol 2012;39:939-45; doi:10.3899/jrheuin.111336)

  • 24392.
    Ärlestig, Lisbeth
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Polymorphism of genes related to cardiovascular disease in patients with rheumatoid arthritis2007Inngår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 25, nr 6, s. 866-871Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To analyze candidate genes, related to cardiovascular disease (CVD) in general, and potentially involved in the inflammatory process, in RA patients from northern Sweden.

    METHODS: Four hundred and sixty-seven individuals (345 females; 122 males) with RA (ACR criteria), having a mean age of 61.8 +/- 13.0 years and mean disease duration of 16.2 +/- 12.1 years, were consecutively recruited and followed-up for 3 years. The prevalence of CVD, [(ischemic heart disease (IHD), deep vein thromboses/pulmonary embolism (DVT/PE) and/or stroke/TIA] and hypertension was registered. Candidate genes encoding for Beta-fibrinogen (G-455A), Factor XIIIA (Val34Leu), plasminogen activator inhibitor type-1 (PAI-1 4G/5G), and tumor necrosis factor receptor (TNFR)II (M196R) were analysed. Controls (n = 672) were randomly selected according to age and gender from the Medical Biobank of Northern Sweden. Polymorphisms were genotyped using a TaqMan 9700HT and the 5'nuclease allelic discrimination assay.

    RESULTS: The genotypes, carriers and alleles did not differ in distribution between patients and controls. Carriage of the TNFRII R variant was more frequent among patients with hypertension (p = 0.018). The genotype distribution of PAI-1 in patients with IHD differed significantly (p = 0.002) because carriage of 4G was more frequent (p = 0.024). Combined carriage of TNFRII 196R variant and Beta-fibrinogen-455A was a stronger predictor for hypertension than each genotype separately. The distribution of FXIIIA genotypes deviated significantly in RA patients with DVT/PE (p = 0.028) with an increased frequency of the Leu34 variant.

    CONCLUSION: The unusual alleles of TNFRII, PAI-1 and FXIIIA were associated with CVD in RA patients. The combination of several of the rare types further increased the predictive values for CVD.

  • 24393.
    Åberg, Anna
    Umeå universitet, Medicinsk fakultet, Molekylärbiologi (Medicinska fakulteten).
    New insights into the role of ppGpp and DksA through their effect on transcriptional regulation of housekeeping and colonization related genes of Escherichia coli2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Bacteria have the ability to sense different environmental signals. When an environmental stress is detected, bacteria rapidly adjust their gene expression profile to be able to survive and thrive. The transduction of such environmental signals often requires the coordinated involvement of several factors that constitute complex regulatory networks. Hence, depending on the combination of signals, a unique gene expression profile required to adapt to the specific stress conditions is generated. Proteins are the best-known regulatory factors. However, non-proteinaceous molecules are also important in signal-responsive control of bacterial gene expression. Alarmones are low molecular weight non-proteinaceous regulatory factors which can characteristically be rapidly turned-over to mediate instant changes in gene expression. One such alarmone is the modified nucleotide ppGpp, which directly binds to RNA polymerase to alter its activity. The levels of this alarmone are expected to rapidly increase in response to any environmental stress that result in slow proliferation. DksA, a putative ppGpp co-regulator that likewise directly targets RNA polymerase, has been suggested to be required for both the positive and negative regulation mediated by ppGpp in Escherichia coli.

    This thesis describes dissection of the role of ppGpp and DksA on transcriptional regulation, primarily using the fim genetic determinant that encodes for the type 1 fimbriae. Type 1 fimbriae are involved in adhesion to abiotic surface and initial adhesion/invasion of bladder cells, as well as in biofilm formation. We found that ppGpp regulates phase variation by increasing the sub-population of cells that express the fimbriae. The effect of ppGpp was ultimately traced to its role in transcription of the fimB gene that encodes a recombinase involved in the phase variation process (paper 1). In contrast, we unexpectedly found that lack of DksA causes an increase, rather than a decrease, in transcription from the fimB P2 promoter in vivo. However, in vitro transcription studies demonstrated that ppGpp and DksA, both independently and co-dependently, stimulate transcription from the fimB P2 promoter. These seemingly contradictory results from the in vivo and in vitro transcriptional studies were shown to be, at least in part, a consequence of the increased association of Gre-factors with RNA polymerase that can occur in the absence of DksA in vivo (paper 2).

    The results outlined above have implications for the role of ppGpp and/or DksA in global gene expression. Using gene expression profile (microarray analysis) during the transition from logarithmic to stationary phase of E. coli, we found that while most of the genes regulated by ppGpp and DksA are regulated in the same direction by the two factors, many were not. In addition to the fim genes, genes involved in flagella functioning, taxis responses, and a few genes encoding different transport systems are also differentially regulated in ppGpp- and DksA-deficient strains in vivo. Our results clearly indicate that the effect of deficiencies in ppGpp and DksA is far more complex than phenotypic similarity of the corresponding mutants anticipated by the proposed concerted action of ppGpp and DksA on gene expression (paper 2 & 3).

  • 24394. Åberg, Anna Cristina
    et al.
    Lundin-Olsson, Lillemor
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Rosendahl, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Fall och fallskador. Åtgärder för att förebygga.2011Rapport (Annet vitenskapelig)
  • 24395. Åberg, Anna Cristina
    et al.
    Lundin-Olsson, Lillemor
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Rosendahl, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Implementation of evidence-based prevention of falls in rehabilitation units: a staff's interactive approach.2009Inngår i: Journal of rehabilitation medicine : official journal of the UEMS European Board of Physical and Rehabilitation Medicine, ISSN 1651-2081, Vol. 41, nr 13, s. 1034-1040Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To provide strategies to assist healthcare professionals in the area of rehabilitation to improve prevention of falls. DESIGN: A conceptual framework is described as a foundation for the proposal of 2 intertwined strategies, of intervention and implementation, which target the questions: Which strategies for intervention represent the current best evidence? and: How can these strategies be implemented and continuously developed? RESULTS: Strategies for multifactorial and multiprofessional fall preventive interventions are presented in terms of a "fall prevention pyramid model", including general, individualized, and acute interventions. A systematic global fall risk rating by the staff is recommended as an initial procedure. Fall event recording and follow-up are stressed as important components of local learning and safety improvement. Development of implementation strategies in 3 phases, focusing on interaction, facilitation and organizational culture, is described. CONCLUSION: A well-developed patient safety culture focusing on prevention of falls will, when successfully achieved, be seen by staff, patients and their significant others as being characteristic of the organization, and will be evident in attitudes, routines and actions. Moreover, it provides potential for positive side-effects concerning organizational and clinical improvements in additional areas.

  • 24396.
    Åberg, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Fernández-Vázquez, Jorge
    Departament de Microbiologia, Universitat de Barcelona, Avgda. Diagonal 645, 08028 Barcelona, Spain.
    Cabrer-Panes, Juan David
    Departament de Microbiologia, Universitat de Barcelona, Avgda. Diagonal 645, 08028 Barcelona, Spain.
    Sánchez, Alex
    Departament d'Estadística, Universitat de Barcelona, Avgda. Diagonal 645, 08028 Barcelona, Spain.
    Balsalobre, Carlos
    Departament de Microbiologia, Universitat de Barcelona, Avgda. Diagonal 645, 08028 Barcelona, Spain.
    Similar and divergent effects of ppGpp and DksA deficiencies on transcription in Escherichia coli2009Inngår i: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 191, nr 10, s. 3226-3236Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The concerted action of ppGpp and DksA in transcription has been widely documented. In disparity with this model, phenotypic studies showed that ppGpp and DksA might also have independent and opposing roles in gene expression in Escherichia coli. In this study we used a transcriptomic approach to compare the global transcriptional patterns of gene expression in strains deficient in ppGpp (ppGpp(0)) and/or DksA (DeltadksA). Approximately 6 and 7% of all genes were significantly affected by more than twofold in ppGpp- and DksA-deficient strains, respectively, increasing to 13% of all genes in the ppGpp(0) DeltadksA strain. Although the data indicate that most of the affected genes were copositively or conegatively regulated by ppGpp and DksA, some genes that were independently and/or differentially regulated by the two factors were found. The large functional group of chemotaxis and flagellum synthesis genes were notably differentially affected, with all genes being upregulated in the DksA-deficient strain but 60% of them being downregulated in the ppGpp-deficient strain. Revealingly, mutations in the antipausing Gre factors suppress the upregulation observed in the DksA-deficient strain, emphasizing the importance of the secondary channel of the RNA polymerase for regulation and fine-tuning of gene expression in E. coli.

  • 24397.
    Åberg, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Gideonsson, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Brännström, Kristoffer
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Arnqvist, Anna
    The Helicobacter pylori sialic acid binding adhesin SabA is regulated via a network of two-component systemsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The acid-responsive signaling system ArsRS plays a key role in regulating factors important for survival in acidic conditions during infection of the human stomach by Helicobacter pylori. In addition, ArsRS was suggested to control the disease-associated attachment protein SabA, however, mechanistic data is still lacking. We show that the repressing effect of the ArsRS system on SabA expression occurs both at acidic and neutral conditions and is mediated at the transcriptional level. Purified His6-ArsR binds PsabA DNA at several sites, with varying affinity and independent of phosphorylation status and H. pylori strains showed unique cognate PsabA sequences to tweak the ArsR binding ability, resulting in strain-dependent repression of SabA expression. By site-directed mutagenesis we reveal key amino acids for the binding activity of ArsR. Finally, we show that that ArsR binds to A/T-rich DNA as dimers or larger multimers, suggesting that ArsR has affinity for DNA structures rather than to a specific promoter DNA sequence. SabA expression is further influenced by the FlgRS and CrdRS two-component systems, illustrating a complicated crosstalk among regulatory networks in H. pylori.

  • 24398.
    Åberg, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Gideonsson, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Vallström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Olofsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Öhman, Carina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Rakhimova, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Borén, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Engstrand, Lars
    Brännström, Kristoffer
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Arnqvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism2014Inngår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 10, nr 7, artikkel-id e1004234Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    During persistent infection, optimal expression of bacterial factors is required to match the ever-changing host environment. The gastric pathogen Helicobacter pylori has a large set of simple sequence repeats (SSR), which constitute contingency loci. Through a slipped strand mispairing mechanism, the SSRs generate heterogeneous populations that facilitate adaptation. Here, we present a model that explains, in molecular terms, how an intergenically located T-tract, via slipped strand mispairing, operates with a rheostat-like function, to fine-tune activity of the promoter that drives expression of the sialic acid binding adhesin, SabA. Using T-tract variants, in an isogenic strain background, we show that the length of the T-tract generates multiphasic output from the sabA promoter. Consequently, this alters the H. pylori binding to sialyl-Lewis x receptors on gastric mucosa. Fragment length analysis of post-infection isolated clones shows that the T-tract length is a highly variable feature in H. pylori. This mirrors the host-pathogen interplay, where the bacterium generates a set of clones from which the best-fit phenotypes are selected in the host. In silico and functional in vitro analyzes revealed that the length of the T-tract affects the local DNA structure and thereby binding of the RNA polymerase, through shifting of the axial alignment between the core promoter and UP-like elements. We identified additional genes in H. pylori, with T- or A-tracts positioned similar to that of sabA, and show that variations in the tract length likewise acted as rheostats to modulate cognate promoter output. Thus, we propose that this generally applicable mechanism, mediated by promoter-proximal SSRs, provides an alternative mechanism for transcriptional regulation in bacteria, such as H. pylori, which possesses a limited repertoire of classical trans-acting regulatory factors.

  • 24399.
    Åberg, Anna-Maja
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap.
    Carbon monoxide in biological systems: An experimental and clinical study2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Carbon monoxide (CO) is a toxic gas, but it is also produced endogenously when haem is degraded. When produced in vivo, CO is believed to have positive biological effects. For example it activates the production of cyclic guanosine mono-phosphate and causes vasodilatation. CO is also believed to have anti-inflammatory properties by binding to Mitogen activated protein (MAP) kinase. Several studies in cells, mice and rats support this opinion regarding both the circulatory as well as the anti-inflammatory properties. However, studies in larger animals regarding circulatory effects have demonstrated contradictory results. The only study in humans regarding anti-inflammatory properties of CO could not demonstrate such effects.

    Methods: This thesis consists of four different models. In paper I a method for analysis of CO in blood was developed using gas chromatography. In paper II a porcine model was used to investigate the elimination time for CO. The pigs in paper II had a high concentration of CO administered via blood, and CO concentrations were followed over time and kinetically parameters calculated. Circulatory parameters were also measured to evaluate if there were any circulatory changes after CO administration. In paper III CO´s anti-inflammatory properties were investigated in an endotoxin-induced systemic inflammatory model in pigs. Paper III was a randomized study where one group inhaled CO and the other group served as controls. Plasma cytokine concentrations were measured and followed over time as an indication of the inflammatory state. In paper IV, CO concentrations in blood from blood donors at the Blood Centre in Umeå were investigated. The blood donors also completed a questionnaire about age, smoking history and other possible sources for exogenous contamination of CO in the blood.

    Results and conclusions: In paper I we developed a method suitable for analysis of low concentrations of CO in blood. The half-life of CO at levels of 250 µM in pigs was found to be 60 minutes. CO did not show anti-inflammatory effects after an endotoxin-induced systemic inflammation in pigs. In banked blood CO was present at concentrations up to six times higher than normal concentrations. This could be a risk when transfusing such blood to susceptible patients.

  • 24400. Åberg, Emma
    et al.
    Ottosson, Ann
    Granlund, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Saeedi, Baharak
    Stamm, Christina
    Brune, Thomas
    Tammelin, Ann
    Johansson, Stefan
    Harbouring group B streptococci in a neonatal intensive care unit led to an outbreak among preterm infants2019Inngår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, nr 1, s. 58-61Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report a nosocomial outbreak with group B streptococci (GBS) in a level two neonatal intensive care unit (NICU) at Sachs' Children and Youth Hospital, Stockholm, Sweden, in 2014. There were five very preterm infants with severe late-onset septicaemia, and 10 further infants were colonised. Pulsed-field gel electrophoresis and multilocus sequence typing genetic characterisation showed that one GBS strain was the cause: serotype Ia, sequence type 23, clonal complex 23. The NICU environment cultures revealed GBS reservoirs on surfaces near sick and colonised patients. We identified workflows and guidelines that could increase the risks of nosocomial infections. Conclusion: This nosocomial GBS outbreak among preterm infants demonstrates that GBS can be harboured in the NICU environment.

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