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  • 251. Ahmed, Syed Masud
    et al.
    Hadi, Abdullahel
    Razzaque, Abdur
    Ashraf, Ali
    Juvekar, Sanjay
    Ng, Nawi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Indonesia.
    Kanungsukkasem, Uraiwan
    Soonthornthada, Kusol
    Van Minh, Hoang
    Huu Bich, Tran
    Clustering of chronic non-communicable disease risk factors among selected Asian populations: levels and determinants2009Inngår i: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 2, nr 1, s. 68-75Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The major chronic non-communicable diseases (NCDs) operate through a cluster of common risk factors, whose presence or absence determines not only the occurrence and severity of the disease, but also informs treatment approaches. Primary prevention based on mitigation of these common risk factors through population-based programmes is the most cost-effective approach to contain the emerging epidemic of chronic NCDs.

    OBJECTIVES: This study was conducted to explore the extent of risk factors clustering for the major chronic NCDs and its determinants in nine

    INDEPTH Health and Demographic Surveillance System (HDSS) sites of five Asian countries. DESIGN: Data originated from a multi-site chronic NCD risk factor prevalence survey conducted in 2005. This cross-sectional survey used a standardised questionnaire developed by the WHO to collect core data on common risk factors such as tobacco use, intake of fruits and vegetables, physical inactivity, blood pressure levels, and body mass index. Respondents included randomly selected sample of adults (25-64 years) living in nine rural HDSS sites in Bangladesh, India, Indonesia, Thailand, and Vietnam.

    RESULTS: Findings revealed a substantial proportion (>70%) of these largely rural populations having three or more risk factors for chronic NCDs. Chronic NCD risk factors clustering was associated with increasing age, being male, and higher educational achievements. Differences were noted among the different sites, both between and within country.

    CONCLUSIONS: Since there is an extensive clustering of risk factors for the chronic NCDs in the populations studied, the interventions also need to be based on a comprehensive approach rather than on a single factor to forestall its cumulative effects which occur over time. This can work best if it is integrated within the primary health care system and the HDSS can be an invaluable epidemiological resource in this endeavor.

  • 252.
    Ahmed, Zina
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Poly-ADP ribos polymeras (PARP) inhibitorers effekt på bröstcancer: Poly-ADP ribos polymeras (PARP) inhibitorers effekt på bröstcancer2015Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 253. Ahmeti, Artan
    et al.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Molecular & Clinical Sciences Research Institute, St George University London.
    Ibrahimi, Pranvera
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Clinic of Cardiology, University Clinical Centre of Kosova.
    Elezi, Shpend
    Haliti, Edmond
    Poniku, Afrim
    Batalli, Arlind
    Bajraktari, Gani
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Clinic of Cardiology, University Clinical Centre of Kosova; Medical Faculty, University of Prishtina.
    Quality of life questionnaire predicts poor exercise capacity only in HFpEF and not in HFrEF2017Inngår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, artikkel-id 268Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most widely used measure of quality of life (QoL) in HF patients. This prospective study aimed to assess the relationship between QoL and exercise capacity in HF patients.

    Methods: The study subjects were 118 consecutive patients with chronic HF (62 +/- 10 years, 57 females, in NYHA I-III). Patients answered a MLHFQ questionnaire in the same day of complete clinical, biochemical and echocardiographic assessment. They also underwent a 5 min walk test (6-MWT), in the same day, which grouped them into; Group I: <= 300 m and Group II: > 300 m. In addition, left ventricular (LV) ejection fraction (EF), divided them into: Group A, with preserved EF (HFpEF) and Group B with reduced EF (HFrEF).

    Results: The mean MLHFQ total scale score was 48 (+/- 17). The total scale, and the physical and emotional functional MLHFQ scores did not differ between HFpEF and HFpEF. Group I patients were older (p = 0.003), had higher NYHA functional class (p = 0.002), faster baseline heart rate (p = 0.006), higher prevalence of smoking (p = 0.015), higher global, physical and emotional MLHFQ scores (p < 0.001, for all), larger left atrial (LA) diameter (p = 0.001), shorter LV filling time (p = 0.027), higher E/e' ratio (0.02), shorter isovolumic relaxation time (p = 0.028), lower septal a' (p = 0.019) and s' (p = 0.023), compared to Group II. Independent predictors of 6-MWT distance for the group as a whole were increased MLHFQ total score (p = 0.005), older age (p = 0.035), and diabetes (p = 0.045), in HFpEF were total MLHFQ (p = 0.007) and diabetes (p = 0.045) but in HFrEF were only LA enlargement (p = 0.005) and age (p = 0.013. A total MLHFQ score of 48.5 had a sensitivity of 67% and specificity of 63% (AUC on ROC analysis of 72%) for limited exercise performance in HF patients.

    Conclusions: Quality of life, assessment by MLHFQ, is the best correlate of exercise capacity measured by 6-MWT, particularly in HFpEF patients. Despite worse ejection fraction in HFrEF, signs of raised LA pressure independently determine exercise capacity in these patients.

  • 254.
    Ahnlund, Anna-Ella
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Svennberg, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Att främja anknytning när barnet föds för tidigt: -Barnsjuksköterskors erfarenheter2019Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Bakgrund: Prematura födslar leder ofta till sämre förutsättningar för barnet att utveckla en trygg anknytning. Barnsjuksköterskor på neonatala vårdavdelningar har därför en betydande roll i att främja anknytningen mellan prematurfödda barn och dess föräldrar.

    Motiv: Forskning visar att barnsjuksköterskor i neonatalvården ofta upplever svårigheter i arbetet med att stödja föräldrarna i processen att knyta an till sitt prematurfödda barn. Få studier belyser ämnet ur barnsjuksköterskans perspektiv vilket kan ha betydelse för framtida arbete. Det är därför av intresse att söka mer kunskap om barnsjuksköterskors erfarenheter av att främja anknytningen.

    Syfte: Att belysa barnsjuksköterskors erfarenheter av att främja anknytning mellan föräldrar och prematurfödda barn på neonatala vårdavdelningar.

    Metod: En semistrukturerad intervjustudie med åtta barnsjuksköterskor vid neonatala vårdavdelningar i sydöstra Sverige. Data är analyserad med hjälp av innehållsanalys.

    Resultat: Analysen resulterade i fyra kategorier: Möjliggöra närhet mellan barnet och föräldrarna, Stödja föräldrarna till delaktighet, Stärka föräldrarnas känsla av föräldraskap, samt Hinder i arbetet med att främja anknytning.

    Diskussion: Resultatet stärks och diskuteras gentemot tidigare forskning som visar att anknytningen främjas mellan föräldrar och barn när de upplever närhet till varandra, när föräldrar är delaktiga i barnets omvårdnad och när föräldrar känner trygghet i sin föräldraroll. Resultatet visar att barnsjuksköterskor ofta upplever att de saknar tillräckligt med kompetens för att stödja de föräldrar som hamnar i kris, något som också visats i tidigare forskning. Det framkom även att barnsjuksköterskor ofta saknar formell kompetens i att främja anknytning, något som däremot inte framkommer i tidigare forskning.

    Konklusion: Barnsjuksköterskors erfarenheter visar att anknytningen främjas när ansvaret för barnet på ett tryggt sätt förflyttas till föräldrarna. Ökad kunskap till barnsjuksköterskor i att stödja föräldrar i kris, kan leda till förbättringar i arbetet med att främja anknytningen mellan föräldrar och prematurfödda barn. Även organisatoriska förändringar som möjliggör samvård kan leda till att arbetet med att främja anknytning underlättas.

  • 255.
    Ahrgren, Rikard
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Post-tonsillectomy hemorrhage in the County of Norrbotten, Sweden between 2008-20132014Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 256.
    Aili, Margareta
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Role of YopE and LcrH in effector translocation, HeLa cell cytotoxicity and virulence2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In order to establish an extra-cellular infection the gram-negative bacteria Yersinia pseudotuberculosis uses a type III secretion system (T3SS) to translocate a set of anti-host effectors into eukaryotic cells. The toxins disrupt signalling pathways important for phagocytosis, cytokine production and cell survival. Secretion and translocation via this T3SS is strictly regulated on several levels. In this context, the function of YopE and LcrH during Yersinia infections has been analysed.

    YopE is an essential translocated effector that disrupts the actin cytoskeleton of infected eukaryotic cells, by inactivating small GTPases through its GTPase activating protein (GAP) activity. However, cytotoxicity can be uncoupled from in vitro GAP activity towards the RhoA, Rac1 and Cdc42 GTPases. Furthermore, in vivo studies of the YopE GAP activity revealed that only RhoA and Rac1 are targeted, but this is not a pre-requisite for Yersinia virulence. Hence, YopE must target one or more additional GTPases to cause disease in mice.

    YopE was the only Yersinia effector that blocks LDH release from infected cells. Moreover, translocated YopE could regulate the level of subsequent effector translocation by a mechanism that involved the YopE GAP function and another T3S component, YopK. Loss of translocation control elevated total T3S gene expression in the presence of eukaryotic cells. This indicated the existence of a regulatory loop for feedback control of T3S gene expression in the bacteria that originates from the interior of the eukaryotic cell after effector translocation is completed. This might represent the true virulence function of YopE.

    Exoenzyme S (ExoS) of Pseudomonas aeruginosa has a YopE-like GAP domain with similar activity towards RhoA, Rac1 and Cdc42. However, ExoS is unable to complement hyper-translocation resulting from loss of YopE. This indicates a unique function for YopE in translocation control in Yersinia that might be dependent on correct intracellular localisation. It follows that the Membrane Localisation Domain in YopE was important for translocation control, but dispensable for cytotoxicity and blockage of LDH release.

    YopD and its cognate chaperone LcrH are negative regulatory elements of the T3S regulon and together with YopB, are involved in the effector translocation process. Randomly generated point mutants in LcrH specifically effected stability and secretion of both the YopB and YopD substrates in vitro and prevented their apparent insertion as translocon pores in the membranes of infected cells. Yet, these mutants still produced stable substrates in the presence of eukaryotic cells and most could mediate at least partial effector translocation. Thus, only minimal amounts of the YopB and YopD translocator proteins are needed for translocation and the LcrH chaperone may regulate this process from inside the bacteria.

  • 257.
    Aili, Margareta
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Isaksson, Elin L
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Carlsson, Sara E
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Wolf-Watz, Hans
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Rosqvist, Roland
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Francis, Matthew S
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Regulation of Yersinia Yop-effector delivery by translocated YopE2008Inngår i: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 298, nr 3-4, s. 183-192Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The bacterial pathogen Yersinia pseudotuberculosis uses a type III secretion (T3S) system to translocate Yop effectors into eukaryotic cells. Effectors are thought to gain access to the cytosol via pores formed in the host cell plasma membrane. Translocated YopE can modulate this pore formation through its GTPase-activating protein (GAP) activity. In this study, we analysed the role of translocated YopE and all the other known Yop effectors in the regulation of effector translocation. Elevated levels of Yop effector translocation into HeLa cells occurred by YopE-defective strains, but not those defective for other Yop effectors. Only Yersinia devoid of YopK exhibits a similar hyper-translocation phenotype. Since both yopK and yopE mutants also failed to down-regulate Yop synthesis in the presence of eukaryotic cells, these data imply that translocated YopE specifically regulates subsequent effector translocation by Yersinia through at least one mechanism that involves YopK. We suggest that the GAP activity of YopE might be working as an intra-cellular probe measuring the amount of protein translocated by Yersinia during infection. This may be a general feature of T3S-associated GAP proteins, since two homologues from Pseudomonas aeruginosa, exoenzyme S (ExoS) and exoenzyme T (ExoT), can complement the hyper-translocation phenotypes of the yopE GAP mutant.

  • 258.
    Aili, Margareta
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Telepnev, Max
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Hallberg, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Wolf-Watz, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Rosqvist, Roland
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    In vitro GAP activity towards RhoA, Rac1 and Cdc42 is not a prerequisite for YopE induced HeLa cell cytotoxicity2003Inngår i: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 34, nr 6, s. 297-308Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The YopE cytotoxin of Yersinia is an essential virulence determinant that is translocated into the eukaryotic target cell via a plasmid-encoded type III secretion system. YopE possess a GTPase activating protein activity that in vitro has been shown to down regulate RhoA, Rac1, and Cdc42. Translocated YopE induces de-polymerisation of the actin microfilament structure in the eukaryotic cell which results in a rounding up of infected cells described as a cytotoxic effect. Here, we have investigated the importance of different regions of YopE for induction of cytotoxicity and in vitro GAP activity. Sequential removal of the N- and C-terminus of YopE identified the region between amino acids 90 and 215 to be necessary for induction of cytotoxicity. Internal deletions containing the essential arginine at position 144 resulted in a total loss of cytotoxic response. In-frame deletions flanking the arginine finger defined a region important for the cytotoxic effect to amino acids 166–183. Four triple-alanine substitution mutants in this region, YopE166-8A, 169-71A, 175-7A and 178-80A were still able to induce cytotoxicity on HeLa cells although they did not show any in vitro GAP activity towards RhoA, Rac1 or Cdc42. A substitution mutant in position 206-8A showed the same phenotype, ability to induce cytotoxic response but no in vitro GAP activity. We speculate that YopE may have additional unidentified targets within the eukaryotic cell.

  • 259.
    Aisenbrey, Christopher
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Byström, Roberth
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Oliveberg, Mikael
    Department of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, Sweden.
    Gröbner, Gerhard
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    SOD1 associates to membranes in its folded apo-stateManuskript (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied by misfolding and intracellular deposition of superoxide dismutase 1 (SOD1). Although the molecular details behind this misfolding process are yet poorly understood, increasing evidence suggest that SOD1 is most susceptible to misfolding in its metal-free and relatively unstable apo-state. Here, we addressed the question, if misfolding and aggregation of SOD1 involves erroneous interactions with membranes as has been implicated for the Aβ peptide in Alzheimers disease. To examine this possibility we subjected various apo SOD1 variants to the presence of different membrane systems. The results reveal that wild type apoSOD1 but to less extent destabilized ALS mutations interact with charged vesicles under physiologically relevant conditions, thereby acquiring pronounced helical structural features. As the data further show, the protein binds to the membranes by an electrostatically driven mechanism, which requires a folded apo-state conformation and a negative membrane surface potential. Unfolded SOD1 molecules show no appreciable affinity to the membrane surfaces yielding a correlation between increased stability, i. e. occupancy of folded molecules and extend of membrane association. Since this trend opposes the correlation between decreased SOD1 stability and progression of neural damage, the results suggest that membrane association is not part of the ALS mechanism. An explanation could be that the observed membrane association of apo SOD1 is reversible and does not ‘bleed out’ in irreversible aggregation as observed for other precursors of protein-misfolding diseases.

  • 260. Aitio, Antero
    et al.
    Bernard, Alfred
    Fowler, Bruce A.
    Nordberg, Gunnar F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Miljömedicin.
    Biological Monitoring and Biomarkers2007Inngår i: Handbook on the Toxicology of Metals, 3rd Edition / [ed] Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg and Lars T. Friberg, San Diego: Elsevier, 2007, 3, s. 65-78Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Biomonitoring was developed for the assessment of the health risks from exposure to metals at work, and the approaches and concepts of biomonitoring are derived from such exposures. At present, biomonitoring is increasingly used to assess exposure from the environment. Biomonitoring and assessment of external exposure are complementing activities, where the exposure assessments are much more widely applied, especially when the number of chemicals concerned is considered; environmental analysis also offers the distinct advantage of speciation analysis, which is very poorly developed for biomonitoring. Biomonitoring, on the other hand, provides information on exposure from all sources, and via all absorption routes, and also considers accumulation of the chemical in the body. Biomonitoring using exposure biomarkers thus considers interindividual differences in the absorption, whereas use of effect biomarkers also considers interindividual differences in sensitivity. Few effect biomarkers, however, have been validated. Biomarkers of susceptibility have so far not been adapted for use in metal toxicology. The major challenges of biomonitoring are the development of monitoring methods, which are inexpensive enough to be applied at a frequency that makes possible meaningful biomonitoring of metals with a short half-time; development of exposure biomarker guidance values specific to individual species of different metals; expansion of the repertoire of validated effect biomarkers; and validation and application to effect monitoring of the "omic" technologies.

  • 261. Ajeani, Judith
    et al.
    Ayiasi, Richard Mangwi
    Tetui, Moses
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Makerere University School of Public Health (MakSPH), Makerere University College of Health Sciences, Kampala, Uganda.
    Ekirapa-Kiracho, Elizabeth
    Namazzi, Gertrude
    Kananura, Rornald Muhumuza
    Kiwanuka, Suzanne Namusoke
    Beyeza-Kashesya, Jolly
    A cascade model of mentorship for frontline health workers in rural health facilities in Eastern Uganda: processes, achievements and lessons2017Inngår i: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 10, artikkel-id 1345497Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is increasing demand for trainers to shift from traditional didactic training to innovative approaches that are more results-oriented. Mentorship is one such approach that could bridge the clinical knowledge gap among health workers.

    Objectives: This paper describes the experiences of an attempt to improve health-worker performance in maternal and newborn health in three rural districts through a mentoring process using the cascade model. The paper further highlights achievements and lessons learnt during implementation of the cascade model.

    Methods: The cascade model started with initial training of health workers from three districts of Pallisa, Kibuku and Kamuli from where potential local mentors were selected for further training and mentorship by central mentors. These local mentors then went on to conduct mentorship visits supported by the external mentors. The mentorship process concentrated on partograph use, newborn resuscitation, prevention and management of Post-Partum Haemorrhage (PPH), including active management of third stage of labour, preeclampsia management and management of the sick newborn. Data for this paper was obtained from key informant interviews with district-level managers and local mentors.

    Results: Mentorship improved several aspects of health-care delivery, ranging from improved competencies and responsiveness to emergencies and health-worker professionalism. In addition, due to better district leadership for Maternal and Newborn Health (MNH), there were improved supplies/medicine availability, team work and innovative local problem-solving approaches. Health workers were ultimately empowered to perform better.

    Conclusions: The study demonstrated that it is possible to improve the competencies of frontline health workers through performance enhancement for MNH services using locally built capacity in clinical mentorship for Emergency Obstetric and Newborn Care (EmONC). The cascade mentoring process needed strong external mentorship support at the start to ensure improved capacity among local mentors to provide mentorship among local district staff.

  • 262. Ajob, Leith
    et al.
    Brännström, Ingrid
    Ott, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Werneke, Ursula
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Fellow of the Royal College of Psychiatrists (FRCPsych).
    ABC om Wernickes encefalopati2017Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, nr ELZTArtikkel i tidsskrift (Fagfellevurdert)
  • 263. Ajroud-Driss, Senda
    et al.
    Adams, David
    Coelho, Teresa
    Polydefkis, Michael
    Gonzalez-Duarte, Alejandra
    Quan, Dianna
    Kristen, Arnt
    Berk, John
    Agarwal, Sonalee
    Partisano, Angela
    Gollob, Jared
    Sweester, Marianne
    Chen, Jihong
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Impact of Patisiran on overall health status in hATTR amyloidosis: Results from the APOLLO trial2018Inngår i: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 23, nr 4, s. 272-273Artikkel i tidsskrift (Annet vitenskapelig)
  • 264. Ajroud-Driss, Senda
    et al.
    Adams, David
    Coelho, Teresa
    Polydefkis, Michael
    Gonzalez-Duarte, Alejandra
    Quan, Dianna
    Kristen, Arnt
    Berk, John L.
    Partisano, Angela M.
    Gollob, Jared
    Sweetser, Marianne T.
    Chen, Jihong
    Agarwal, Sonalee
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Impact of Patisiran on Overall Health Status in hATTR Amyloidosis: Results from the APOLLO Trial2019Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 92, nr 15Artikkel i tidsskrift (Annet vitenskapelig)
  • 265. Akesson, Agneta
    et al.
    Barregard, Lars
    Bergdahl, Ingvar A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Nordberg, Gunnar F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordberg, Monica
    Skerfving, Staffan
    Non-Renal Effects and the Risk Assessment of Environmental Cadmium Exposure2014Inngår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 122, nr 5, s. 431-438Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Exposure to cadmium (Cd) has long been recognized as a health hazard, both in industry and in general populations with high exposure. Under the currently prevailing health risk assessment, the relationship between urinary Cd (U-Cd) concentrations and tubular proteinuria is used. However, doubts have recently been raised regarding the justification of basing the risk assessment on this relationship at very low exposure. Objectives: Our objective was to review available information on health effects of Cd exposure with respect to human health risk assessment. Discussion: The associations between U-Cd and urinary proteins at very low exposure may not be due to Cd toxicity, and the clinical significance of slight proteinuria may also be limited. More importantly, other effects have been reported at very low Cd exposure. There is reason to challenge the basis of the existing health risk assessment for Cd. Our review of the literature found that exposure to low concentrations of Cd is associated with effects on bone, including increased risk of osteoporosis and fractures, and that this observation has implications for the health risk assessment of Cd. Other effects associated with Cd should also be considered, in particular cancer, although the information is still too limited for appropriate use in quantitative risk assessment. Conclusion: Non-renal effects should be considered critical effects in the health risk assessment of Cd.

  • 266.
    Akhatova, Elena
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Do clinical pharmacy servicesimprove outcomes for patientswith heart failure (HF)?: Do clinical pharmacy servicesimprove outcomes for patientswith heart failure (HF)?2015Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 267.
    Akhatova, Elena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Information och rådgivningvid e-handelpå apotek i Sverige.2018Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
  • 268.
    Akhtari, Mohammad Mehdi
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    3D Structural similarity check between CT and SCT2014Independent thesis Advanced level (degree of Master (Two Years)), 10 poäng / 15 hpOppgave
    Abstract [en]

    The aim of the current work was to develop and test a method for comparing the geometrical representation of a patient using computed tomography (CT), and CT like images derived from magnetic resonance images (MRI). It would be beneficial to use MRI alone for both target delineation and treatment planning to save time and costs. This was first investigated in Umea university Hospital by introducing substitute computed tomography (SCT) obtained from MRI images and which can be used as CT equivalent information. The data that is used in this report are from five patients with intracranial tumors; A MATLAB code has been developed to compare DDRs based on s-CT data with CT based DRR’s for these five patients.

  • 269.
    Akhter Urmi, Sharmeen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Parental attitude towards their autistic child and the underlying factors regulating parental attitude in Bangladesh: A Study Protocol2018Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [en]

    Background Autism is a global health crisis. Among other developing countries, Bangladesh has the highest rate on prevalence of autism which ranges from 0.15%-0.84%. Several factors have been found to influence parent’s attitude towards autistic child such as lack of knowledge and understanding of autism, societal stigma, cultural belief in karma, parent’s expectations, parent’s uncertainty about child’s future, worry about child’s educational development, parent’s guilt as caregivers, hampering family relationship. Bangladesh is still lacking in knowledge and awareness of autism, thus, giving rise to negative attitude among parents towards their autistic child. The aim of the study is to understand parental attitude towards their autistic child comparing both the father and mother’s attitude and to explore the underlying factors regulating their attitude.

    Methods This will be a qualitative study protocol with abductive approach following emergent design conducted with semi-structured interviews with open-ended questions among both the parents having an autistic child diagnosed for minimum 6 months, living together in Dhakaand registered on files of Center for Neurodevelopment and Autism in Children (CNAC) in Bangabandhu Sheikh Mujib Medical University (BSMMU).

    Conclusion This study is expected to bring out deeper understanding of parental attitude towards their autistic child providing a baseline for interventions and evaluations of support programs for autistic child and their parents in Bangladesh. This study will influence for having autism support groups, autistic child-family support group, social support groups and trained social workers in public sector workers for reducing stigma of autism.

  • 270.
    Akimoto, Chizuru
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Backlund, Irene
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Andersson, Jörgen
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nilsson, Ann-Charloth
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Alstermark, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    No GGGGCC-hexanucleotide repeat expansion in C9ORF72 in parkinsonism patients in Sweden2013Inngår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, Vol. 14, nr 1, s. 26-29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An intronic GGGGCC-hexanucleotide repeat expansion in C9ORF72 was recently identified as a major cause of amyotrophic lateral sclerosis and frontotemporal dementia. Some amyotrophic lateral sclerosis patients have signs of parkinsonism, and many parkinsonism patients develop dementia. In this study we examined if the hexanucleotide repeat expansion was present in parkinsonism patients, to clarify if there could be a relationship between the repeat expansion and disease. We studied the size of the hexanucleotide repeat expansion in a well defined population-based cohort of 135 Parkinson's disease patients and 39 patients with atypical parkinsonism and compared with 645 Swedish control subjects. We found no correlation between Parkinson's disease or atypical parkinsonism and the size of the GGGGCC repeat expansion in C9ORF72. In conclusion, this GGGGCC-repeat expansion in C9ORF72 is not a cause of parkinsonism in the Swedish population.

  • 271.
    Akimoto, Chizuru
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Volk, Alexander E.
    van Blitterswijk, Marka
    Van den Broeck, Marleen
    Leblond, Claire S.
    Lumbroso, Serge
    Camu, William
    Neitzel, Birgit
    Onodera, Osamu
    van Rheenen, Wouter
    Pinto, Susana
    Weber, Markus
    Smith, Bradley
    Proven, Melanie
    Talbot, Kevin
    Keagle, Pamela
    Chesi, Alessandra
    Ratti, Antonia
    van der Zee, Julie
    Alstermark, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Calini, Daniela
    Nordin, Angelica
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Tradowsky, Daniela C.
    Just, Walter
    Daoud, Hussein
    Angerbauer, Sabrina
    DeJesus-Hernandez, Mariely
    Konno, Takuya
    Lloyd-Jani, Anjali
    de Carvalho, Mamede
    Mouzat, Kevin
    Landers, John E.
    Veldink, Jan H.
    Silani, Vincenzo
    Gitler, Aaron D.
    Shaw, Christopher E.
    Rouleau, Guy A.
    van den Berg, Leonard H.
    Van Broeckhoven, Christine
    Rademakers, Rosa
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Kubisch, Christian
    A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories2014Inngår i: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 51, nr 6, s. 419-424Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.

  • 272.
    Akner, G.
    et al.
    School of Health and Medical Sciences, Örebro University, 70185 Örebro, Sweden.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Personalized geriatric medicine2014Inngår i: European Geriatric Medicine, ISSN 1878-7649, E-ISSN 1878-7657, Vol. 5, nr 3, s. 145-146Artikkel i tidsskrift (Annet vitenskapelig)
  • 273.
    Akpan, Joyce
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    The Prevalence of Potentially Inappropriate Drug Prescription among Elderly Patients Registered in Balder Clinic in Åmål, Sweden2017Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 274. Akram, Harith
    et al.
    Dayal, Viswas
    Mahlknecht, Philipp
    Georgiev, Dejan
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Jahanshahi, Marjan
    Ashburner, John
    Behrens, Tim
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK.
    Zrinzo, Ludvic
    Connectivity derived thalamic segmentation in deep brain stimulation for tremor2018Inngår i: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 18, s. 130-142Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

  • 275. Akram, Harith
    et al.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Zrinzo, Ludvic
    Connectivity derived thalamic segmentation: Separating myth from reality2019Inngår i: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 22, artikkel-id UNSP 101758Artikkel i tidsskrift (Fagfellevurdert)
  • 276. Akram, Harith
    et al.
    Limousin, Patricia
    Hyam, Jonathan
    Hariz, Marwan I.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London.
    Zrinzo, Ludvic
    Aim for the Suprasternal Notch: Technical Note to Avoid Bowstringing after Deep Brain Stimulation2015Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 93, nr 4, s. 227-230Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Bowstringing may occur when excessive fibrosis develops around extension cables in the neck after deep brain stimulation (DBS) surgery. Though the occurrence of this phenomenon is rare, we have noted that it tends to cause maximal discomfort when the cables cross superficially over the convexity of the clavicle. We hypothesise that bowstringing may be avoided by directing the extension cables towards the suprasternal notch. Methods: When connecting DBS leads to an infraclavicular pectoral implantable pulse generator (IPG), tunnelling is directed towards the suprasternal I notch, before being directed laterally towards the IPG pocket. In previously operated patients with established fibrosis, the fibrous tunnel is opened and excised as far cranially as possible, allowing medial rerouting of cables. Using this approach, we reviewed our series of patients who underwent DBS surgery over 10 years. Results: In 429 patients, 7 patients (2%) with cables tunnelled over the convexity of the clavicle complaining of bowstringing underwent cable exploration and rerouting. This eliminated bowstringing and provided better cosmetic results. When the cable trajectory was initially directed towards the suprasternal notch, no bowstringing was observed. Conclusion:The tunnelling trajectory appears to influence postoperative incidence of fibrosis associated with DBS cables. Modifying the surgical technique may reduce the incidence of this troublesome adverse event. (C) 2015 S.Karger AG, Basel

  • 277. Akram, Harith
    et al.
    Miller, Sarah
    Lagrata, Susie
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ashburner, John
    Behrens, Tim
    Matharu, Manjit
    Zrinzo, Ludvic
    Optimal deep brain stimulation site and target connectivity for chronic cluster headache2017Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, nr 20, s. 2083-2091Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate the mechanism of action of deep brain stimulation for refractory chronic cluster headache and the optimal target within the ventral tegmental area. Methods: Seven patients with refractory chronic cluster headache underwent high spatial and angular resolution diffusion MRI preoperatively. MRI-guided and MRI-verified electrode implantation was performed unilaterally in 5 patients and bilaterally in 2. Volumes of tissue activation were generated around active lead contacts with a finite-element model. Twelve months after surgery, voxel-based morphometry was used to identify voxels associated with higher reduction in headache load. Probabilistic tractography was used to identify the brain connectivity of the activation volumes in responders, defined as patients with a reduction of >= 30% in headache load. Results: There was no surgical morbidity. Average follow-up was 34 +/- 14 months. Patients showed reductions of 76 +/- 33% in headache load, 46 +/- 41% in attack severity, 58 +/- 41% in headache frequency, and 51 +/- 46% in attack duration at the last follow-up. Six patients responded to treatment. Greatest reduction in headache load was associated with activation in an area cantered at 6 mm lateral, 2 mm posterior, and 1 mm inferior to the midcommissural point of the third ventricle. Average responders' activation volume lay on the trigeminohypothalamic tract, connecting the trigeminal system and other brainstem nuclei associated with nociception and pain modulation with the hypothalamus, and the prefrontal and mesial temporal areas. Conclusions: We identify the optimal stimulation site and structural connectivity of the deep brain stimulation target for cluster headache, explicating possible mechanisms of action and disease pathophysiology.

  • 278. Akram, Harith
    et al.
    Sotiropoulos, Stamatios N.
    Jbabdi, Saad
    Georgiev, Dejan
    Mahlknecht, Philipp
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
    Ashburner, John
    Behrens, Tim
    Zrinzo, Ludvic
    Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson's disease2017Inngår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 158, s. 332-345Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.

    Methods: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.

    Results: All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H-2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -3(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.

    Interpretation: These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.

  • 279. Akram, Harith
    et al.
    Wu, Chengyuan
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Yousry, Tarek
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK.
    Behrens, Timothy
    Ashburner, John
    Zrinzo, Ludvic
    L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease2017Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, nr 6, s. 874-883Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. Methods: To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to L-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3x3x2.5mm(3) voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an L-dopa challenge. False discovery rate-corrected P was set at < 0.05 for a 2-tailed t test. Results: A greater improvement in UPDRS-III scores following L-dopa administration was characterized by higher resting-state functional connectivity between the prefrontal cortex and the striatum (P=0.001) and lower resting-state functional connectivity between the pallidum (P=0.001), subthalamic nucleus (P=0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas). Conclusions: Our findings show characteristic basal ganglia resting-state functional connectivity patterns associated with different degrees of L-dopa responsiveness in patients with advanced Parkinson's disease. L-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response.

  • 280. Akram, Neelam
    et al.
    Palovaara, Joakim
    Forsberg, Jeremy
    Lindh, Markus V.
    Milton, Debra L.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Luo, Haiwei
    Gonzalez, Jose M.
    Pinhassi, Jarone
    Regulation of proteorhodopsin gene expression by nutrient limitation in the marine bacterium Vibrio sp AND42013Inngår i: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 15, nr 5, s. 1400-1415Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Proteorhodopsin (PR), a ubiquitous membrane photoprotein in marine environments, acts as a light-driven proton pump and can provide energy for bacterial cellular metabolism. However, knowledge of factors that regulate PR gene expression in different bacteria remains strongly limited. Here, experiments with Vibrio sp. AND4 showed that PR phototrophy promoted survival only in cells from stationary phase and not in actively growing cells. PR gene expression was tightly regulated, with very low values in exponential phase, a pronounced peak at the exponential/stationary phase intersection, and a marked decline in stationary phase. Thus, PR gene expression at the entry into stationary phase preceded, and could therefore largely explain, the stationary phase light-induced survival response in AND4. Further experiments revealed nutrient limitation, not light exposure, regulated this differential PR expression. Screening of available marine vibrios showed that the PR gene, and thus the potential for PR phototrophy, is found in at least three different clusters in the genus Vibrio. In an ecological context, our findings suggest that some PR-containing bacteria adapted to the exploitation of nutrient-rich micro-environments rely on a phase of relatively slowly declining resources to mount a cellular response preparing them for adverse conditions dispersed in the water column.

  • 281.
    Akrawi, Shehrazad
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Hur upplever landstingsanställda farmaceuter i VästraGötalandsregionen sin yrkesroll?2015Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 282. Akre, Olof
    et al.
    Garmo, Hans
    Adolfsson, Jan
    Lambe, Mats
    Bratt, Ola
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Mortality among men with locally advanced prostate cancer managed with noncurative intent: a nationwide study in PCBaSe Sweden2011Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, nr 3, s. 554-563Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 283.
    Akselsen, Gunn
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Legemiddelbruk hos eldre på sykehjem: Identifisering av potensielt uhensiktsmessige legemidler utfra NORGEP-NH kriteriene hos pasienter boende på sykehjem i to norske kommuner2016Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
  • 284.
    Aksenova, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Muñoz, Iván
    Volkov, Kirill
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ariño, Joaquín
    Mironova, Ludmila
    The HAL3-PPZ1 dependent regulation of nonsense suppression efficiency in yeast and its influence on manifestation of the yeast prion-like determinant [ISP(+)].2007Inngår i: Genes to Cells, ISSN 1356-9597, E-ISSN 1365-2443, Vol. 12, nr 4, s. 435-546Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The efficiency of stop codons read-through in yeast is controlled by multiple interactions of genetic and epigenetic factors. In this study, we demonstrate the participation of the Hal3-Ppz1 protein complex in regulation of read-through efficiency and manifestation of non-Mendelian anti-suppressor determinant [ISP(+)]. Over-expression of HAL3 in [ISP(+)] strain causes nonsense suppression, whereas its inactivation displays as anti-suppression of sup35 mutation in [isp(-)] strain. [ISP(+)] strains carrying hal3Delta deletion cannot be cured from [ISP(+)] in the presence of GuHCl. Since Hal3p is a negative regulatory subunit of Ppz1 protein phosphatase, consequences of PPZ1 over-expression and deletion are opposite to those of HAL3. The observed effects are mediated by the catalytic function of Ppz1 and are probably related to the participation of Ppz1 in regulation of eEF1Balpha elongation factor activity. Importantly, [ISP(+)] status of yeast strains is determined by fluctuation in Hal3p level, since [ISP(+)] strains have less Hal3p than their [isp(-)] derivatives obtained by GuHCl treatment. A model considering epigenetic (possibly prion) regulation of Hal3p amount as a mechanism underlying [ISP(+)] status of yeast cell is suggested.

  • 285.
    Aksenova, Anna
    et al.
    Department of Biology, Tufts University, Medford, Massachusetts, United States of America.
    Volkov, Kirill
    School of Biology, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
    Maceluch, Jaroslaw
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Pursell, Zachary F
    Department of Biochemistry, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America.
    Rogozin, Igor B
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.
    Kunkel, Thomas A
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Heath, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.
    Pavlov, Youri I
    Eppley Institute for Research in Cancer, Department of Biochemistry and Molecular Biology, and Department of Microbiology and Pathology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
    Johansson, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Mismatch repair-independent increase in spontaneous mutagenesis in yeast lacking non-essential subunits of DNA polymerase ε2010Inngår i: PLoS genetics, ISSN 1553-7404, Vol. 6, nr 11, s. e1001209-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Yeast DNA polymerase ε (Pol ε) is a highly accurate and processive enzyme that participates in nuclear DNA replication of the leading strand template. In addition to a large subunit (Pol2) harboring the polymerase and proofreading exonuclease active sites, Pol ε also has one essential subunit (Dpb2) and two smaller, non-essential subunits (Dpb3 and Dpb4) whose functions are not fully understood. To probe the functions of Dpb3 and Dpb4, here we investigate the consequences of their absence on the biochemical properties of Pol ε in vitro and on genome stability in vivo. The fidelity of DNA synthesis in vitro by purified Pol2/Dpb2, i.e. lacking Dpb3 and Dpb4, is comparable to the four-subunit Pol ε holoenzyme. Nonetheless, deletion of DPB3 and DPB4 elevates spontaneous frameshift and base substitution rates in vivo, to the same extent as the loss of Pol ε proofreading activity in a pol2-4 strain. In contrast to pol2-4, however, the dpb3Δdpb4Δ does not lead to a synergistic increase of mutation rates with defects in DNA mismatch repair. The increased mutation rate in dpb3Δdpb4Δ strains is partly dependent on REV3, as well as the proofreading capacity of Pol δ. Finally, biochemical studies demonstrate that the absence of Dpb3 and Dpb4 destabilizes the interaction between Pol ε and the template DNA during processive DNA synthesis and during processive 3' to 5'exonucleolytic degradation of DNA. Collectively, these data suggest a model wherein Dpb3 and Dpb4 do not directly influence replication fidelity per se, but rather contribute to normal replication fork progression. In their absence, a defective replisome may more frequently leave gaps on the leading strand that are eventually filled by Pol ζ or Pol δ, in a post-replication process that generates errors not corrected by the DNA mismatch repair system.

  • 286.
    Akuamoah-Boateng, Henrietta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Self-reported vision health status among older people in the Kassena-Nankana District, Ghana2013Inngår i: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 6, s. 1-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: If current trends continue, Ghana's aged population will increase in the coming decades. Currently, there is little knowledge on the health of the aged in Ghana. Research on vision problems among this group is virtually non-existent. This research gap needs to be filled immediately in order to promote the general health among older people in Ghana.

    Objective: The objective of the study was to analyse vision health and its determinants among the older adult population in a district in one of the poorest regions in Ghana - the Kassena-Nankana district.

    Methods: Data were obtained from the WHO multi-country studies unit (SAGE). A total of 4,294 people over the age of 50 responded to the survey. Data analysis was conducted using Stata statistical package. The aim of the analysis was to identify the prevalence of self-reported vision problems and assistive device use. Age, level of education, marital status, living arrangement, socio-economic status and proportion of people aged 50 and over in a household were used as determinants of vision health.

    Results: In total, 54 and 63% (p-value, 0.00) of men and women reported having far-sightedness, while 35% of men and 40.6% of women reported having near-sightedness (p-value, 0.00). In total, 33.5% of men and 38.6% of women reported having both near-sightedness and far-sightedness (p-value, 0.00). Of those who reported having either vision problems, 2.9% reported the use of visual assistive devices. Men had a higher assistive device use of 4.5% compared to 2.1% among women (p = 0.002). Age and household socio-economic status was positively associated with reporting vision problems and assistive device use, respectively.

    Conclusions: The results from this analysis showed that despite the high reporting of vision problems, only 2.9% reported using assistive devices. This outcome shows that there is a need to prevent vision problems and increase access to assistive devices among older people in the Kassena-Nankana district in Ghana.

  • 287.
    Akula, Ilona
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Hjärtfunktion vid ärftlig transtyretin-amyloidos: Jämförelse av hjärtfrekvensvariabilitet och ekokardiografi mellan två amyloidfibrilltyper2015Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 288. Akyurek, L. M.
    et al.
    Funa, K.
    Wanders, A.
    Larsson, E.
    Fellstrom, B. C.
    Inhibition of transplant arteriosclerosis in rat aortic grafts by low molecular weight heparin derivatives1995Inngår i: Transplantation, Vol. 59, nr 11, s. 1517-24Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The effects of low molecular weight heparin derivatives with a low anticoagulant activity on transplant arteriosclerosis (TA) in a rat aortic transplant model were investigated. TA was induced by ischemia in the syngeneic transplants and primarily by immunological mechanisms in the allogeneic transplants. Treatment with the heparin derivatives, OAM 71262 or LA-heparin, was administered in a dosage of 250 micrograms/kg/hr by mini-osmotic pumps during 8 weeks. No immunosuppressive regimen was given to the recipient rats in either model. All rats were killed 8 weeks after aortic grafting. The grafts were examined for intimal and medial changes using an image analysis system. Heparin derivatives had a beneficial effect on both the intimal thickening and the medial injury in the syngeneic transplants, but not in the allogeneic grafts. In the syngeneic LA-heparin treated grafts, the thickness of the intima was less than that in the syngeneic control grafts (P < 0.05). In the syngeneic transplants, a significant increase was observed in the media after treatment with OAM 71262 (P < 0.01) as well as those with LA-heparin (P < 0.001). In the syngeneic grafts treated with both heparin derivatives, a significant reduction in the antigen expression of alpha-actin-containing smooth muscle cells in the intima, transforming growth factor-beta 1 both in the media and adventitia, and platelet-derived growth factor-beta receptors in the adventitia was observed immunohistochemically. In summary, low molecular weight heparin derivatives with low anticoagulant activity partially inhibited ischemia-induced syngeneic TA, whereas no such effect could be demonstrated in nonimmunosuppressed recipients with allogeneic grafts.

  • 289. Akyurek, M. L.
    et al.
    Funa, K.
    Wanders, A.
    Larsson, E.
    Fellstrom, B. C.
    Expression of CD11b and ICAM-1 in an in vivo model of transplant arteriosclerosis1995Inngår i: Transpl Immunol, Vol. 3, nr 2, s. 107-13Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adhesion molecules play a crucial role in transplant rejection in regulating the interaction of inflammatory cells with cells in the vascular wall. In an aortic transplantation model, we have previously analysed the early adhesion process (7.5 min to 24 h) and the impact of cold ischaemia time (1-24 h) upon transplant arteriosclerosis during the first 2 months after transplantation in the rat. The aim of this investigation was to study adhesion molecules in accelerated transplant arteriosclerosis in a rat model by analysing the immunohistochemical expression of CD11b and ICAM-1 up to 2 months and followed by a semiquantitative evaluation and multivariant analysis. Antigen expression of CD11b and ICAM-1 adhesion molecules was stronger in the aortic allografts than in the ischaemia-induced syngeneic aortic grafts in the whole vessel wall. Neither ICAM-1 nor CD11b antigen expression correlated significantly with time periods of ischaemia/reperfusion injury in allogeneic or syngeneic aortic transplants. CD11b and ICAM-1 are induced by allogeneic stimuli in transplanted aortas suggesting a role in the pathogenesis of transplant arteriosclerosis. Our findings have implications for understanding the role of cell adhesion activation in the vascular wall subject to chronic graft rejection.

  • 290. Akyurek, M. L.
    et al.
    Larsson, E.
    Funa, K.
    Wanders, A.
    Kaijser, M.
    Fellstrom, B. C.
    Experimental transplant arteriosclerosis: inhibition by angiopeptin and low molecular weight heparin derivatives1995Inngår i: Transplant Proc, Vol. 27, nr 6, s. 3555-6Artikkel i tidsskrift (Fagfellevurdert)
  • 291. Akyurek, M. L.
    et al.
    Wanders, A.
    Aurivillius, M.
    Larsson, E.
    Funa, K.
    Fellstrom, B. C.
    Effects of angiopeptin on transplant arteriosclerosis in the rat1995Inngår i: Transpl Int, Vol. 8, nr 2, s. 103-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The influence of the somatostatin analogue angiopeptin on transplant arteriosclerosis was investigated using two aortic transplantation rat models. One was characterized by ischemia/reperfusion-induced changes in syngeneic transplants while immunologically induced changes dominated in the other allogeneic model. Angiopeptin, 100 micrograms/kg per day, was administered continuously until the sacrifice of the rats after 8 weeks. No additional immunosuppression was used in either model. An image analysis system was used to quantify the intimal and medial thicknesses of the grafts. In the syngeneic grafts, the intimal thickness was less than 50% of that of control grafts (P < 0.05), but no difference was seen in the allogeneic model. The expression of selected cells, TGF-beta s, and PDGF and PDGF alpha-receptors was detected immunohistochemically and displayed a similar picture in control and angiopeptin-treated grafts in both models. We conclude that angiopeptin has no clear immunosuppressive properties but may counteract ischemia-induced transplant arteriosclerosis.

  • 292.
    Al Bitar, Ghiath
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Diabetes and Edentulism: Analysis of WHO Study on global AGEing and adult health (SAGE) Wave 12015Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
  • 293.
    Al Mamun, Mohammad Feroz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Pokharel, Arpan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Reasons behind the use of tanning beds:: A Scoping Review2016Independent thesis Advanced level (degree of Master (Two Years)), 10 poäng / 15 hpOppgave
    Abstract [en]

    Background:

    Tanning beds emit short, energetic and harmful rays, UV-A and UV-B which leads to various ocular and skin diseases; moreover, DNA damage and the initiation of carcinogenic changes are associated with regular use of it. Basal cell carcinoma and melanoma incidence rate have been rapidly increasing over a few decades due to unregulated consumption of solar bed. It has been classified as carcinogenic device and different organizations regularly advice for the prohibition of it. Despite the proven association of ocular and skin diseases and cancer from the large epidemiological data solar bed consumption is not degraded; furthermore, tanning bed has been developed as a culture in the modern western world. The exploration of tanning bed displayed that it is interconnected with the ancient sun worshippers, an advent of vitamin D and carbon arc lamps with quartz lens, heliotherapy clinics and to the modern sun stimulated indoor tanning. This scoping review provides a broad understanding of the reasons behind the popularity and the current consumption of indoor tanning bed.

    Aim:

    The aim of our study is to analyse and summarize the factors that contribute to the practice of indoor tanning beds in an overall population; furthermore, attitudes, perception, belief, behaviour and motivation factors of indoor tanners were undertaken to explore and find gaps in the existing literatures.

     Method:

    By using a scoping review twenty articles both qualitative and quantitative were identified and selected from the Umeå University Library website by using only one database, “Web of Science TM Core Collection Studies (v.5.21)” during the months of March and April 2016.  Boolean logic was used to identify both qualitative and quantitative studies with keywords such as “Indoor tanning”, “Tanning bed”, “Qualitative Study”, “attitude”, “belief”, “behaviour”, “motivation” and “perception”. The relevant articles that were published and written only in English language and free to download a full copy of the articles through the Umeå University Library website and without any financial transactions and contacts with organizations and authors were included. In terms of population, our target study group is broad which includes both male and female population who are active and passive users of the tanning beds. The age of the participants in our study range from 11 years to 94 years.

    Results:

    Seven themes are reported to be the main reasons behind the consumption of carcinogenic tanning bed. These are: - (1) Modern Healthism, (2) Influence from family and friends, (3) Social occasions and holidays, (4) Physical and Mental Gain, (5) Complex cognition, (6) Addiction and (7) Tactful marketing.  Modern healthism, tanning industries and salon’s tactful marketing help to set up image-based modern norms, attractive, healthy golden brown skin, in societal level influencing families and friends, which further develops indoor tanning as a culture and beautifying practice during special events like social occasions and holidays. The cognition regarding physical and mental gain perceived from an individual and societal perspective and contradictory findings from ongoing researches with respect to the hazards of solar beds create complex cognition among active and passive tanners, like ambivalence, cognitive dissonance, temporal discounting, rationalization and optimistic bias. However, in the adolescent phase, there is increasing consumption of the tanning beds which can be further explained by complex cognitive, the adolescent egocentrism. The complex cognition enhances the regular use of addictive tanning bed which further leads to dependence and skin cancers or the diseases of the eyes and the skin.

    Conclusions: Consumption of risky tanning bed has been developed as a culture or beauty norms that are still ingrained in the mind of tanners, i.e., golden brown tanned skin is attractive, which is created under the influence of modern healthism. The reasons behind the use of carcinogenic solar bed can be well explained by the concepts of cognitive science and psychology, i.e., ambivalence, adolescent egocentrism, cognitive dissonance, temporal discounting, rationalization, optimistic bias, and addiction. In order to tackle with solar bed dependence and its health related hazards, health workers should develop and implement promotive and preventive health programs which incorporate social norms and factors, tanner’s cognition and psychology. Policy makers and health actors should ban solar beds or avoid the use of it in the minors, i.e., under 18 years through embracing the evidence suggested by epidemiological studies.

  • 294. Al Nimer, Faiez
    et al.
    Elliott, Christina
    Bergman, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Khademi, Mohsen
    Dring, Ann M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Aeinehband, Shahin
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Christensen, Jeppe Romme
    Sellebjerg, Finn
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linington, Christopher
    Olsson, Tomas
    Piehl, Fredrik
    Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination2016Inngår i: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 3, nr 1, artikkel-id e191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. Methods: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study comparing patients with MS (n = 147) with controls (n = 50) and patients with relapsing-remitting MS (n = 75) with patients with progressive MS (n = 72); (2) in CSF and brain tissue microdialysates from a case series of 7 patients with progressive MS; and (3) in CSF at baseline and 60 weeks after natalizumab treatment in a cohort study of 17 patients with progressive MS. Correlation to neurofilament light, a marker of neuroaxonal injury, was tested. The effect of LCN2 on myelination and neurodegeneration was studied in a rat in vitro neuroglial cell coculture model. Results: Intrathecal production of LCN2 was increased predominantly in patients with progressive MS (p < 0.005 vs relapsing-remitting MS) and displayed a positive correlation to neurofilament light (p = 0.005). Levels of LCN2 in brain microdialysates were severalfold higher than in the CSF, suggesting local production in progressive MS. Treatment with natalizumab in progressive MS reduced LCN2 levels an average of 13% (p < 0.0001). LCN2 was found to inhibit remyelination in a dose-dependent manner in vitro. Conclusions: LCN2 production is predominantly increased in progressive MS. Although this moderate increase does not support the use of LCN2 as a biomarker, the correlation to neurofilament light and the inhibitory effect on remyelination suggest that LCN2 might contribute to neurodegeneration through myelination-dependent pathways.

  • 295. Al Nimer, Faiez
    et al.
    Thelin, Eric
    Nystrom, Harriet
    Dring, Ann M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Piehl, Fredrik
    Nelson, David W.
    Bellander, Bo-Michael
    Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 7, artikkel-id e0132177Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R-2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R-2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R-2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that SNF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further

  • 296.
    Al Rabiey, Ahmed
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Detektion av aktin i paraffinsnitt från human vävnad2015Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 297.
    Al- Rubaye, Ali Kadhim Qasim
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Health Behavioral Risk Factors Associated to Quality of Life: A Cross-Sectional Study in Northern Sweden2019Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [en]

    Introduction: Obesity, smoking, low level of physical activity, lack of fruit and vegetable intake, and harmful consumption of alcohol, are all established risk factors that have undesirable effects on health. These behavioural risk factors have a joint adverse effect on both morbidity and mortality. This thesis aims to explore the relationship between these risk factors and the quality of life among adults population with an age range between 16 to 84 year old livings in Northern Sweden.

    Methodology: This cross-sectional study is based on data from Sweden‘s national public health survey Hälsa på lika villkor – HLV (Health on Equal Terms) that was conducted between February and May 2014 in the four Northern counties in Sweden: Norrbotten, Västerbotten, Västernorrland, and Jämtland. With a response rate of 50%, the final sample consisted of 25.667 individuals. In this study, individuals with missing data from any of the study variables were dropped to assure complete analysis. The final study population was 17,138 (67% of those who responded to the HET 2014 survey) Multivariable linear regression was used to statistically analyze the relationship between the outcome variable, the EQ5D utility score which is a standardized instrument widely used for measuring the generic health status, and the following independent variables: BMI, physical activity, smoking status, fruit and vegetable intake, and alcohol consumption. The association was presented in terms of coefficient factor and CI 95%.

    Results: The findings showed that risk factors namely obesity, less than the recommended daily level of physical activity, low daily consumption of fruits and vegetables, daily use of tobacco and the heavy episodic drinking of alcohol had significantly associated with Low EQ5D.

    Conclusion: The results of the study suggest that HRQoL measured by EQ5D-3L might have a significant relation with lifestyle behaviours. This finding would emphasize the role of public health interventions for better overall health to the population. More research is needed to fully understand and explore the determinants of the relationship between the lifestyle behaviours and the HRQol.

  • 298.
    Ala, Sofia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Asplund, André
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Oral Hygiene at Nursing Homes for Older People as Disclosed in Interviews with Nursing Staff2015Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    As the elderly population increases and many elderly keep their natural teeth, a consequence of this is an increased need for oral care to maintain a good oral health. In 2012 about 86,800 people older than 65 years lived in nursing homes in Sweden according to the National Board of Health and Welfare, cared for by nursing aides and nursing assistants. The aim of this study was to explore nursing staffs’ experiences of oral hygiene in two different nursing homes in rural parts of northern Sweden. We chose to use a qualitative approach with fourteen individual semi-structured interviews with the nursing staff. Qualitative content analysis was used to analyze the interviews. Our results showed that the nursing staff are well aware of the importance and need of oral care and having the best ambitions to do a good job. Although this attitude exists we found that the reality was a struggle to handle. This was mainly attributed to an effect of lack of resources and problems related to residents’ cooperation. The nursing staff were willing to do their best in every situation when helping the older persons with their oral hygiene. It is also of great importance to the nursing staff to respect the older person's autonomy and not to harm them. Sometimes these two concepts are not possible to combine which leads to the nursing staff having a moral struggle trying to do their best while still respecting the older person’s autonomy.

     

  • 299.
    Alabi, Olusola
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Exploring awareness and knowledge of tuberculosis spread among household members of tuberculosis patients in Nigeria2013Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
  • 300.
    Alaerts, Maaike
    et al.
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Venken, Tine
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Lenaerts, An-Sofie
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    De Zutter, Sonia
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Del-Favero, Jurgen
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Lack of association of an insertion/deletion polymorphism in the G protein-coupled receptor 50 with bipolar disorder in a Northern Swedish population2006Inngår i: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 16, nr 6, s. 235-236Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    GPR50 is a G protein-coupled receptor, located on Xq28 and related to the melatonin receptor family. It is suggested as a functional and positional candidate gene for bipolar disorder (BP). Recently an insertion/deletion polymorphism in GPR50, Delta502-505, was found to be associated with BP in a Scottish association sample (P=0.007). When the analysis was restricted to female subjects, the association increased in significance (P=0.00023). We attempted to replicate this finding in a Northern Swedish association sample, but no significant association was detected (P=0.7, women only: P=0.65).

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