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  • 301.
    Alaish, Ram
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundgren, David
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Werner, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel disease naive to thiopurine treatment2017Inngår i: International journal of clinical pharmacology and therapeutics, ISSN 0946-1965, Vol. 55, nr 7, s. 594-600Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To determine if 6-mercaptopurine (MP) is better tolerated than azathioprine (AZA) as the initial thiopurine treatment in patients suffering from inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is advocated in patients intolerant to AZA. However, no study has determined if MP is more suited than AZA as a first-line treatment for patients who are naive to thiopurine treatment. Study: The tolerance of AZA and MP treatments in clinical practice was retrospectively evaluated from start to 12 months after initiating treatment in 113 patients with IBD who were all naive to thiopurines (82 patients treated with AZA and 31 patients with MP). Results: 65% of the patients treated with AZA and 61% of the patients treated with MP tolerated their treatment during 12 months (i.e., no group difference, p = 0.742). No difference in reported side effects between the two treatments was observed. The mean equivalent initial dose (0.92 vs. 0.61 mg/kg; p < 0.001) and the mean equivalent dose at 12 months (1.98 vs. 1.65 mg/kg; p = 0.014) was significantly higher in the MP group vs. the AZA group. The proportion of patients with.MCV = 7 at 12 months was numerically higher in the MP group than in the AZA group (53% vs. 31%; p = 0.090). Conclusions: In this retrospective observational study, no differences in tolerance or adherence between AZA and MP were observed in patients naive to thiopurines. However, MP treatment was at a higher equivalent thiopurine dose than AZA treatment, which tended to be associated with better treatment response.

  • 302.
    Alakpa, Enateri V.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Jayawarna, Vineetha
    Burgess, Karl E. V.
    West, Christopher C.
    Peault, Bruno
    Ulijn, Rein V.
    Dalby, Matthew J.
    Improving cartilage phenotype from differentiated pericytes in tunable peptide hydrogels2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 6895Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Differentiation of stem cells to chondrocytes in vitro usually results in a heterogeneous phenotype. This is evident in the often detected over expression of type X collagen which, in hyaline cartilage structure is not characteristic of the mid-zone but of the deep-zone ossifying tissue. Methods to better match cartilage developed in vitro to characteristic in vivo features are therefore highly desirable in regenerative medicine. This study compares phenotype characteristics between pericytes, obtained from human adipose tissue, differentiated using diphenylalanine/serine (F2/S) peptide hydrogels with the more widely used chemical induced method for chondrogenesis. Significantly higher levels of type II collagen were noted when pericytes undergo chondrogenesis in the hydrogel in the absence of induction media. There is also a balanced expression of collagen relative to aggrecan production, a feature which was biased toward collagen production when cells were cultured with induction media. Lastly, metabolic profiles of each system show considerable overlap between both differentiation methods but subtle differences which potentially give rise to their resultant phenotype can be ascertained. The study highlights how material and chemical alterations in the cellular microenvironment have wide ranging effects on resultant tissue type.

  • 303. Alakurtti, Kati
    et al.
    Johansson, Jarkko J.
    Joutsa, Juho
    Laine, Matti
    Backman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Rinne, Juha O.
    Long-term test-retest reliability of striatal and extrastriatal dopamine D-2/3 receptor binding: study with [C-11]raclopride and high-resolution PET2015Inngår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, nr 7, s. 1199-1205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the relatively low variability of [C-11]raclopride binding, providing suggestive evidence that extrastriatal D-2/3 binding can be studied in vivo with [C-11]raclopride PET to be verified in future studies.

  • 304.
    Al-Alawi, Kamila
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Team-based approach in the management of diabetes at primary health care level in Muscat, Oman: challenges and opportunities2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Introduction: The growth of type 2 diabetes is considered an alarming epidemic in Oman. The efficient team-based approach to diabetes management in primary health care is an essential component for providing ideal diabetic care. This thesis aimed to explore the current situation related to team-based management of type 2 diabetes in public Primary Health Care Centres (PHCCs) under the Ministry of Health (MOH) in Oman, including the various challenges associated with diabetes management and the most preferable Human Resources for Health (HRH) management mechanism, and to examine how this could be optimized from provider and patient perspectives.

    Materials and methods: The entire project was conducted in Muscat Governorate and was based on one quantitative and three qualitative studies. In the quantitative study, 26 public PHCCs were approached through cross-sectional study. The core diabetes management team recommended by the MOH for PHCCs in Oman was explored in terms of their competencies, values, skills, and resources related to the team-based approach to diabetes management. For the qualitative studies, five public purposely-selected PHCCs were approached. The diabetes consultations conducted by the core members and other supportive members involved in diabetes management were observed and later the Primary Health Care Providers (PHCPs) were interviewed. The different approaches explored challenges related to diabetes management and the most preferable HRH mechanism by PHCPs. Seven type 2 diabetes patients with different gender, employment status, and education were consequently interviewed to explore their perceptions towards the current diabetes management service and their opinions towards nurse-led clinics.

    Results: The survey provided significant and diverse perceptions of PHCPs towards their competencies, values, skills, and resources related to diabetes management. Physicians considered themselves to have better competencies than nurses and dieticians. Physicians also scored higher on team-related skills and values compared with health educators. In terms of team-related skills, the difference between physicians and nurses was statistically significant and showed that physicians perceived themselves to have better skills than nurses. Confusion about the leadership concept among PHCPs with a lack of pharmacological, technical, and human resources was also reported. The observations and interviews with PHCPs disclosed three different models of service delivery at diabetes management clinics. The challenges explored involved PHCCs’ infrastructure, nurses’ knowledge, skills, and non-availability of technical and pharmaceutical support. Other challenges that evolved into the community were cultural beliefs, traditions, health awareness, and public transportation. Complete implementation of task-sharing mechanisms within the team-based approach was selected by all PHCPs as the most preferable HRH mechanism. The selection was discussed in the context of positive outcomes, worries, and future requirements. The physicians stated that nurses’ weak contribution to the team within the selected mechanism could be the most significant aspect. Other members supported the task-sharing mechanism between physicians and nurses. However, type 2 diabetes patients’ non-acceptance of a service provided by the nurses created worries for the nurses. The interviews with type 2 diabetes patients disclosed positive perceptions towards the current diabetes management visits; however, opinions towards nurse-led clinics varied among the patients.

    Conclusions and recommendations: The team-based approach at diabetes management clinics in public PHCCs in Oman requires thoughtful attention. Diverse presence of the team members can form challenges during service delivery. Clear roles for team members must be outlined through a solid HRH management mechanism in the context of a sharp leadership concept. Nurse-led clinics are an important concept within the team; however, their implementation requires further investigation. The concept must involve clear understandings of independence and interdependence by the team members, who must be educated to provide a strong gain for team-based service delivery.

  • 305.
    Al-Alawi, Kamila
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa. Department of Training and Studies, Royal Hospital, Ministry of Health, Muscat, Oman.
    Al Mandhari, Ahmed
    Johansson, Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Care providers' perceptions towards challenges and opportunities for service improvement at diabetes management clinics in public primary health care in Muscat, Oman: a qualitative study2019Inngår i: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 19, artikkel-id 18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundThe literature has described several challenges related to the quality of diabetes management clinics in public primary health care centres in Oman. These clinics continue to face challenges due to the continuous growth of individuals diagnosed with type 2 diabetes. We sought to explore the challenges faced in these clinics and discuss opportunities for improvement in Oman.MethodsThis qualitative study was designed to include non-participant observations of diabetic patients and care providers during service provision at diabetes management clinics, as well as semi-structured interviews with care providers, at five purposively selected public primary health care centres. Care providers included physicians, nurses, dieticians, health educators, pharmacists, an assistant pharmacist, a psychologist, and a medical orderly. The data were analysed using qualitative content analysis.ResultsThe study disclosed three different models of service delivery at diabetes management clinics, which, to varying degrees, face challenges related to health centre infrastructure, technical and pharmaceutical support, and care providers' interests, knowledge, and skills. Challenges related to the community were also found in terms of cultural beliefs, traditions, health awareness, and public transportation.ConclusionThe challenges encountered in diabetes management clinics fall within two contexts: health care centres and community. Although many challenges exist, opportunities for improvement are available. However, improvements in the quality of diabetic clinics in primary health care centres might take time and require extensive involvement, shared responsibilities, and implications from the government, health care centres, and community.

  • 306.
    Al-Alawi, Kamila
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Johansson, Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Perceptions of type-two diabetes patients towards diabetes management visits at public primary health care centres with diverse opinions towards nurse-led clinics in Muscat, Oman: a pilot qualitative studyManuskript (preprint) (Annet vitenskapelig)
  • 307.
    Al-Alawi, Kamila
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Johansson, Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    The question is not what we want; the question is, are we ready?: a qualitative study exploring primary health care providers`perceptions towards different human resources for health management mechanisms at diabetes management clinics in primary health care centres in Muscat, OmanManuskript (preprint) (Annet vitenskapelig)
  • 308.
    Al-Alawi, Kamila
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Department of Training and Studies, Royal Hospital, Ministry of Health, Muscat, Oman.
    Johansson, Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Al Mandhari, Ahmed
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Are the resources adoptive for conducting team-based diabetes management clinics?: An explorative study at primary health care centers in Muscat, Oman2018Inngår i: Primary Health Care Research and Development, ISSN 1463-4236, E-ISSN 1477-1128, Vol. 20, s. 1-28, artikkel-id E3Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: The aim of this study is to explore the perceptions among primary health center staff concerning competencies, values, skills and resources related to team-based diabetes management and to describe the availability of needed resources for team-based approaches.

    BACKGROUND: The diabetes epidemic challenges services available at primary health care centers in the Middle East. Therefore, there is a demand for evaluation of the available resources and team-based diabetes management in relation to the National Diabetes Management Guidelines.

    METHOD: A cross-sectional study was conducted with 26 public primary health care centers in Muscat, the capital of Oman. Data were collected from manual and electronic resources as well as a questionnaire that was distributed to the physician-in-charge and diabetes management team members.

    FINDINGS: The study revealed significant differences between professional groups regarding how they perceived their own competencies, values and skills as well as available resources related to team-based diabetes management. The perceived competencies were high among all professions. The perceived team-related values and skills were also generally high but with overall lower recordings among the nurses. This pattern, along with the fact that very few nurses have specialized qualifications, is a barrier to providing team-based diabetes management. Participants indicated that there were sufficient laboratory resources; however, reported that pharmacological, technical and human resources were lacking. Further work should be done at public primary diabetes management clinics in order to fully implement team-based diabetes management.

  • 309.
    Alam, Athar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Golovliov, Igor
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Javed, Eram
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    ClpB mutants of Francisella tularensis subspecies holarctica and tularensis are defective for type VI secretion and intracellular replication2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 11324Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Francisella tularensis, a highly infectious, intracellular bacterium possesses an atypical type VI secretion system (T6SS), which is essential for the virulence of the bacterium. Recent data suggest that the HSP100 family member, ClpB, is involved in T6SS disassembly in the subspecies Francisella novicida. Here, we investigated the role of ClpB for the function of the T6SS and for phenotypic characteristics of the human pathogenic subspecies holarctica and tularensis. The Delta clpB mutants of the human live vaccine strain, LVS, belonging to subspecies holarctica, and the highly virulent SCHU S4 strain, belonging to subspecies tularensis, both showed extreme susceptibility to heat shock and low pH, severely impaired type VI secretion (T6S), and significant, but impaired intracellular replication compared to the wild-type strains. Moreover, they showed essentially intact phagosomal escape. Infection of mice demonstrated that both Delta clpB mutants were highly attenuated, but the SCHU S4 mutant showed more effective replication than the LVS strain. Collectively, our data demonstrate that ClpB performs multiple functions in the F. tularensis subspecies holarctica and tularensis and its function is important for T6S, intracellular replication, and virulence.

  • 310.
    Al-ameri, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Effektskillnad mellanmåldos och lågdos vidhjärtsviktsbehandling2018Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 311.
    Al-Ameri, Mona
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Normark, Theresia
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Rhythmical Jaw Opening-Closing Patterns in Healthy Individuals2015Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    Pain affects movements, hampers normal function and may induce dysfunction in jaw system. The aim of this study was to examine if the pattern and stability of a rhythmical jaw opening- closing task changed during a five minute session, in healthy individuals. The analyses included nine men and nine women (mean age 26.7 years; SD 5.3). The participants were instructed to perform rhythmical jaw opening-closing movements with a pace of one per second and amplitude of approximately 20 mm during a five minutes period. The jaw movements were recorded with a 3D optoelectronic recording system. The parameters’ analyses were jaw opening-closing amplitudes and cycle times, to analyze if these parameters differed between men and women and to evaluate if the task evoked tiredness or pain in the jaws. The ten first jaw opening-closing amplitudes and cycle times at each sequence were analysed and compared within individuals and between the groups. Non-parametrical statistics were used. A P-value <0.05 was considered statistically significant. The results showed for both men and women a significant decrease in amplitude and cycle time between the first and the other sequences. The results showed for both men and women that the rhythmical jaw opening-closing task induces self-reported tiredness in the jaws. In conclusion, individuals seem to adhere to pace by reducing amplitude and cycle time during continuous jaw opening-closing tasks. When used as exercise for rehabilitation of the jaw function both patients and dentists should be aware of this behavior.

  • 312.
    Al-Amiry, Bariq
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Radiological measurements in total hip arthroplasty2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Every year, about 1 million patients worldwide and 20000 patients in Sweden undergo total hip arthroplasty (THA). This type of operation is considered a successful, safe and cost-effective procedure to regain mobility and restore hip joint function in patients suffering from severe hip joint disease or trauma. The main goals of the operation are to relief the pain, improve quality of life (QoL) and to restore the biomechanical forces around the hip with appropriate femoral offset (FO), leg length and proper component position and orientation. The radiographic preoperative planning and postoperative evaluation of these parameters require good validity, interobserver reliability and intraobserver reproducibility. Most patients are satisfied after THA, although this treatment still has its complications. About 10 % of THA patients report persistent pain and suboptimal functional outcome and QoL at long-term follow-up. The absolute number of dissatisfied patients is expected to rise given the increase in the annual number of THA performed. Therefore, every effort should be made to investigate factors that possibly influence THA outcome. The data available about the influence of preoperative radiological severity and symptom duration of OA on the outcome of THA are scarce and contradictory. Further studies even needed to evaluate the effect of obesity on post-operative THA radiological measurements

  • 313.
    Al-Amiry, Bariq
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden.
    Mahmood, Sarwar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Krupic, Ferid
    Sayed-Noor, Arkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Leg lengthening and femoral-offset reduction after total hip arthroplasty: where is the problem - stem or cup positioning?2017Inngår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 58, nr 9, s. 1125-1131, artikkel-id UNSP 0284185116684676Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Restoration of femoral offset (FO) and leg length is an important goal in total hip arthroplasty (THA) as it improves functional outcome. Purpose: To analyze whether the problem of postoperative leg lengthening and FO reduction is related to the femoral stem or acetabular cup positioning or both. Material and Methods: Between September 2010 and April 2013, 172 patients with unilateral primary osteoarthritis treated with THA were included. Postoperative leg-length discrepancy (LLD) and global FO (summation of cup and FO) were measured by two observers using a standardized protocol for evaluation of antero-posterior plain hip radiographs. Patients with postoperative leg lengthening >= 10mm (n = 41) or with reduced global FO >5mm (n = 58) were further studied by comparing the stem and cup length of the operated side with the contralateral side in the lengthening group, and by comparing the stem and cup offset of the operated side with the contralateral side in the FO reduction group. We evaluated also the inter-observer and intra-observer reliability of the radiological measurements. Results: Both observers found that leg lengthening was related to the stem positioning while FO reduction was related to the positioning of both the femoral stem and acetabular cup. Both inter-observer reliability and intra-observer reproducibility were moderate to excellent (intra-class correlation co-efficient, ICC >= 0.69). Conclusion: Post THA leg lengthening was mainly caused by improper femoral stem positioning while global FO reduction resulted from improper positioning of both the femoral stem and the acetabular cup.

  • 314.
    Al-Amiry, Bariq
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Pantelakis, Georgios
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Mahmood, Sarwar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Kadum, Bakir
    Brismar, Torkel B.
    Sayed-Noor, Arkan S.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Does body mass index affect restoration of femoral offset, leg length and cup positioning after total hip arthroplasty?: A prospective cohort study2019Inngår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 20, artikkel-id 422Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In obese patients, total hip arthroplasty (THA) can be technically demanding with increased perioperative risks. The aim of this prospective cohort study is to evaluate the effect of body mass index (BMI) on radiological restoration of femoral offset (FO) and leg length as well as acetabular cup positioning.

    Methods: In this prospective study, patients with unilateral primary osteoarthritis (OA) treated with THA between September 2010 and December 2013 were considered for inclusion. The perioperative plain radiographs were standardised and used to measure the preoperative degree of hip osteoarthritis, postoperative FO, leg length discrepancy (LLD), acetabular component inclination and anteversion.

    Results: We included 213 patients (74.5% of those considered for inclusion) with a mean BMI of 27.7 (SD 4.5) in the final analysis. The postoperative FO was improper in 55% and the LLD in 15%, while the cup inclination and anteversion were improper in 13 and 23% of patients respectively. A multivariable logistic regression model identified BMI as the only factor that affected LLD. Increased BMI increased the risk of LLD (OR 1.14, 95% CI 1.04 to 1.25). No other factors included in the model affected any of the primary or secondary outcomes.

    Conclusion: Increased BMI showed a negative effect on restoration of post-THA leg length but not on restoration of FO or positioning of the acetabular cup. Age, gender, OA duration or radiological severity and surgeon’s experience showed no relation to post-THA restoration of FO, leg length or cup positioning.

  • 315.
    Al-Amiry, Bariq Sh.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Gaber, John F.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Kadum, Bakir K.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Brismar, Torkel B.
    Sayed-Noor, Arkan S.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    The Influence of Radiological Severity and Symptom Duration of Osteoarthritis on Postoperative Outcome After Total Hip Arthroplasty: A Prospective Cohort Study2018Inngår i: The Journal of Arthroplasty, ISSN 0883-5403, E-ISSN 1532-8406, Vol. 33, nr 2, s. 436-440Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: We aimed to investigate the influence of preoperative radiological severity and symptom duration of hip osteoarthritis (OA) on the postoperative functional outcome, quality of life, as well as abductor muscle strength after total hip arthroplasty (THA). Methods: In this prospective cohort study, we studied 250 patients. Preoperatively, we evaluated the function with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and quality of life with euroqol-5D (EQ-5D). At 1 year after THA, the same scores and also hip abductor muscle strength were measured in 222 patients. We divided the cohort twice, first according to the radiological OA severity [Kellgren-Lawrence classification (KL)] and then according to the OA symptom duration. We investigated whether the preoperative KL class and symptom duration influenced the 1-year WOMAC (primary outcome measure) or EQ-5D and abductor muscle strength (secondary outcome measures). Results: The crude results showed that KL class and symptom duration had no influence (P = .90 and P = .20, respectively) on the 1-yearWOMAC. Younger age, male gender, and lower body mass index were associated with a better function. Regarding 1-year EQ-5D, the crude results showed that body mass index and KL class had no influence (P = .83 and P = .39, respectively). The adjusted results showed that only age and gender influenced the postoperative EQ-5D. No influence of the tested factors was found on the 1-year abductor muscle strength. Conclusion: Preoperative radiological OA severity and symptom duration had no influence on the outcome of THA and should probably not affect the decision about timing the operative intervention. 

  • 316. Al-Anati, Lauy
    et al.
    Viluksela, Matti
    Strid, Anna
    Bergman, Åke
    Andersson, Patrik L
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Stenius, Ulla
    Högberg, Johan
    Hydroxyl metabolite of PCB 180 induces DNA damage signaling and enhances the DNA damaging effect of benzo[a]pyrene2015Inngår i: Chemico-Biological Interactions, ISSN 0009-2797, E-ISSN 1872-7786, Vol. 239, s. 164-173Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) and their hydroxyl metabolites (OH-PCBs) are ubiquitous environmental contaminants in human tissues and blood. The toxicological impact of these metabolites is poorly understood. In this study rats were exposed to ultrapure PCB180 (10-1000 mg/kg bw) for 28 days and induction of genotoxic stress in liver was investigated. DNA damage signaling proteins (pChk1Ser317 and gamma H2AXSer319) were increased dose dependently in female rats. This increase was paralleled by increasing levels of the metabolite 3'-OH-PCB180. pChk1 was the most sensitive marker. In in vitro studies HepG2 cells were exposed to 1 mu M of PCB180 and 3'-OH-PCB180 or the positive control benzo[a]pyrene (BaP, 5 mu M). 3'-OH-PCB180, but not PCB180, induced CYP1A1 mRNA and gamma H2AX. CYP1A1 mRNA induction was seen at 1 h, and gamma H2AX at 3 h. The anti-oxidant N-Acetyl-L-Cysteine (NAC) completely prevented, and 17 beta-estradiol amplified the gamma H2AX induction by 3'-OH-PCB180. As 3'-OH-PCB180 induced CYP1A1, a major BaP-metabolizing and activating enzyme, interactions between 3'-OH-PCB180 and BaP was also studied. The metabolite amplified the DNA damage signaling response to BaP. In conclusion, metabolism of PCB180 to its hydroxyl metabolite and the subsequent induction of CYP1A1 seem important for DNA damage induced by PCB180 in vivo. Amplification of the response with estradiol may explain why DNA damage was only seen in female rats.

  • 317.
    Alanentalo, Tomas
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Hörnblad, Andreas
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Mayans, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Nilsson, Anna Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sharpe, James
    Larefalk, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Ahlgren, Ulf
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Holmberg, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Quantification and 3-D imaging of the insulitis-induced destruction of β-cells in murine type 1 diabetes2010Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, nr 7, s. 1756-1764Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining beta-cell volume during the progression of type 1 diabetes in the NOD mouse model of the disease.

    Research design and methods: Using an ex vivo technique, optical projection tomography (OPT), we quantified and assessed the 3D spatial development and progression of insulitis and beta-cell destruction in pancreas from diabetes prone NOD and non-diabetes prone congenic NOD.H-2b mice between 3 and 16 weeks of age.

    Results: Together with results showing the spatial dynamics of the insulitis process we provide data of beta-cell volume distributions down to the level of the individual islets and throughout the pancreas during the development and progression of type 1 diabetes. Our data provide evidence for a compensatory growth potential of the larger insulin(+) islets during the later stages of the disease around the time point for development of clinical diabetes. This is in contrast to smaller islets, which appear less resistant to the autoimmune attack. We also provide new information on the spatial dynamics of the insulitis process itself, including its apparently random distribution at onset, the local variations during its further development, and the formation of structures resembling tertiary lymphoid organs at later phases of insulitis progression.

    Conclusions: Our data provides a powerful tool for phenotypic analysis of genetic and environmental effects on type 1 diabetes etiology as well as for evaluating the potential effect of therapeutic regimes.

  • 318. Alarcon, Flora
    et al.
    Plante-Bordeneuve, Violaine
    Olsson, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Norrlands university hospital, NUS M31, Umeå, Sweden.
    Nuel, Gregory
    Non-parametric estimation of survival in age-dependent genetic disease and application to the transthyretin-related hereditary amyloidosis2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 9, artikkel-id e0203860Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In genetic diseases with variable age of onset, survival function estimation for the mutation carriers as well as estimation of the modifying factors effects are essential to provide individual risk assessment, both for mutation carriers management and prevention strategies. In practice, this survival function is classically estimated from pedigrees data where most genotypes are unobserved. In this article, we present a unifying Expectation-Maximization (EM) framework combining probabilistic computations in Bayesian networks with standard statistical survival procedures in order to provide mutation carrier survival estimates. The proposed approach allows to obtain previously published parametric estimates (e.g. Weibull survival) as particular cases as well as more general Kaplan-Meier non-parametric estimates, which is the main contribution. Note that covariates can also be taken into account using a proportional hazard model. The whole methodology is both validated on simulated data and applied to family samples with transthyretin-related hereditary amyloidosis (a rare autosomal dominant disease with highly variable age of onset), showing very promising results.

  • 319. Alaridah, Nader
    et al.
    Hallbäck, Erika Tång
    Tångrot, Jeanette
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). National Bioinformatics Infrastructure Sweden (NBIS), SciLifeLab, Computational Life Science Cluster, Umeå University, Umeå, Sweden.
    Winqvistz, Niclas
    Sturegard, Erik
    Floren-Johanssons, Kerstin
    Jonsson, Bodil
    Tenland, Erik
    Welinder-Olssons, Christina
    Medstrand, Patrik
    Kaijser, Bertil
    Godaly, Gabriela
    Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 4931Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.

  • 320.
    Alasalmi, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Spirometry in medical surveillance of asbestosis and silicosis: Sensitivity, specificity and predictive values2017Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 321.
    Alastalo, Pihla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Mörfelt, Isabella
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Arbetsterapeutiska interventioner i förskole- och skolmiljö för barn med autismspektrumtillstånd: En litteraturstudie2014Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Autismspektrumtillstånd (AST) sammanfattar olika diagnoser som innebär svårigheter inom social interaktion, kommunikation och föreställningsförmåga. Barn med AST ställs inför många utmaningar i förskole- och skolmiljö och är i behov av anpassningar och stöd i sina studier. Syftet med denna litteraturstudie var att beskriva arbetsterapeutiska interventioner i förskole- och skolmiljö för barn med autismspektrumtillstånd. En beskrivande litteraturöversikt genomfördes genom att granska vetenskapliga artiklar. Litteraturstudiens resultat omfattar nio vetenskapliga artiklar publicerade mellan åren 2006-2012 och beskriver arbetsterapeutiska interventioner för barn mellan tre och tjugo år med diagnos inom AST. Analysen av de utvalda studierna resulterade i tre kategorier: Kompensatoriska interventioner för att möjliggöra delaktighet i klassrummet, Interventioner riktade mot träning av sociala färdigheter och Interventioner riktade mot modifiering av beteenden. För att öka barnens kommunikation och sociala interaktion med omvärlden kan till exempel rollspel, yoga och interventioner med djur vara till hjälp. Kompensatoriska interventioner som bollstolar och tyngdvästar kan utgöra ett stöd för vissa barn men för andra barn påverkas koncentrationsförmågan negativt. Arbetsterapeutiska interventioner har potential att underlätta skolsituationen för barn och unga vuxna med AST. Det finns ett behov av att utveckla arbetsterapeutiska interventioner och undersöka dess effekter.

     

     

    Sökord: arbetsterapi, elev, åtgärd, autismspektrum, klassrum

  • 322.
    Alattar, Hiba
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Läkemedelsbehandling hos för tidigt födda barn: Läkemedelsbehandling och biverkningar hos barn med lungproblem2013Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 323. Alavi, Y.
    et al.
    Arai, M.
    Mendoza, J.
    Tufet-Bayona, M.
    Sinha, R.
    Fowler, K.
    Billker, Oliver
    Department of Biological Sciences, Imperial College London, London SW7 2AZ, UK.
    Franke-Fayard, B
    Janse, C J
    Waters, A
    Sinden, R E
    The dynamics of interactions between Plasmodium and the mosquito: a study of the infectivity of Plasmodium berghei and Plasmodium gallinaceum, and their transmission by Anopheles stephensi, Anopheles gambiae and Aedes aegypti2003Inngår i: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 33, nr 9, s. 933-943Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Knowledge of parasite–mosquito interactions is essential to develop strategies that will reduce malaria transmission through the mosquito vector. In this study we investigated the development of two model malaria parasites, Plasmodium berghei and Plasmodium gallinaceum, in three mosquito species Anopheles stephensi, Anopheles gambiae and Aedes aegypti. New methods to study gamete production in vivo in combination with GFP-expressing ookinetes were employed to measure the large losses incurred by the parasites during infection of mosquitoes. All three mosquito species transmitted P. gallinaceumP. berghei was only transmitted by Anopheles spp. Plasmodium gallinaceum initiates gamete production with high efficiency equally in the three mosquito species. By contrast P. berghei is less efficiently activated to produce gametes, and in Ae. aegypti microgamete formation is almost totally suppressed. In all parasite/vector combinations ookinete development is inefficient, 500–100,000-fold losses were encountered. Losses during ookinete-to-oocyst transformation range from fivefold in compatible vector parasite combinations (P. berghei/An. stephensi), through >100-fold in poor vector/parasite combinations (P. gallinaceum/An. stephensi), to complete blockade (>1,500 fold) in others (P. berghei/Ae. aegypti). Plasmodium berghei ookinetes survive poorly in the bloodmeal of Ae. aegypti and are unable to invade the midgut epithelium. Cultured mature ookinetes of P. berghei injected directly into the mosquito haemocoele produced salivary gland sporozoites in An. stephensi, but not in Ae. aegypti, suggesting that further species-specific incompatibilities occur downstream of the midgut epithelium in Ae. aegypti. These results show that in these parasite–mosquito combinations the susceptibility to malarial infection is regulated at multiple steps during the development of the parasites. Understanding these at the molecular level may contribute to the development of rational strategies to reduce the vector competence of malarial vectors.

  • 324.
    Albadi, Danial
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Changes in the treatment of cervical hip fractures at Umeå University Hospital2018Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 325.
    Albadran, Nadia
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Små molekyler från bakterier i kampen mot antibiotikaresistens: Marina aktinomyceter som en lovande källa mot multiläkemedelsresistent Staphylococcus aureus2013Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 326.
    Albagha, O M E
    et al.
    University of Aberdeen.
    Pettersson, Ulrika
    University of Aberdeen .
    Stewart, A
    University of Aberdeen.
    McGuigan, F E A
    University of Aberdeen.
    MacDonald, H M
    University of Aberdeen.
    Reid, D M
    University of Aberdeen.
    Ralston, S H
    University of Aberdeen.
    Association of oestrogen receptor alpha gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone.2005Inngår i: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 42, nr 3, s. 240-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The gene encoding oestrogen receptor alpha (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk.

    OBJECTIVE: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women.

    RESULTS: There was a significant association between a common haplotype "px", defined by the PvuII and XbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were approximately 14% higher in subjects who carried one copy of px and 22% higher in those who carried two copies, compared with those who did not carry the px haplotype. The px haplotype was associated with lower femoral neck BMD in the postmenopausal women (p = 0.02), and with reduced calcaneal broadband ultrasound attenuation (BUA) values in the whole study population (p = 0.005). There was no association between a TA repeat polymorphism in the ESR1 promoter and any phenotype studied, though on long range haplotype analysis subjects with a smaller number of TA repeats who also carried the px haplotype had reduced BUA values.

    CONCLUSIONS: The ESR1px haplotype is associated with reduced hip BMD values and increased rates of femoral neck bone loss in postmenopausal women. An association with BUA may explain the fact that ESR1 intron 1 alleles predict osteoporotic fractures by a mechanism partly independent of differences in BMD.

  • 327. Alberto Diaz-Sanchez, Adrian
    et al.
    Corona-Gonzalez, Belkis
    Meli, Marina L.
    Obregon Alvarez, Dasiel
    Vega Canizares, Ernesto
    Fonseca Rodriguez, Osvaldo
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa. Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Centro Nacional de Sanidad Agropecuaria (CENSA), San José de las Lajas, Mayabeque, Cuba.
    Lobo Rivero, Evelyn
    Hofmann-Lehmann, Regina
    First molecular evidence of bovine hemoplasma species (Mycoplasma spp.) in water buffalo and dairy cattle herds in Cuba2019Inngår i: Parasites & Vectors, ISSN 1756-3305, E-ISSN 1756-3305, Vol. 12, artikkel-id 78Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Hemotropic mycoplasmas (aka hemoplasmas) are small bacteria which cause infectious anemia in several mammalian species including humans. Information on hemoplasma infections in Cuban bovines remains scarce and no studies applying molecular methods have been performed so far. The aim of the present study was to utilize real-time PCR and sequence analysis to investigate dairy cattle and buffalo from Cuba for the presence of bovine hemoplasma species.

    Results: A total of 80 blood samples from 39 buffalo and 41 dairy cattle were investigated for the presence of Mycoplasma wenyonii and Candidatus Mycoplasma haemobos using two species-specific real-time TaqMan PCR assays. PCR results revealed overall 53 (66.2%; 95% CI: 55.3-75.7%) positive animals for M. wenyonii and 33 (41.2%; 95% CI: 31.1-52.2%) for Ca. M. haemobos; the latter were all co-infections with M. wenyonii. The sample prevalences were similar in cattle and buffalo. Based on the sequence analysis of the nearly full-length 16S rRNA gene from two cattle and two buffalo, the presence of M. wenyonii and Ca. M. haemobos was confirmed. Statistical analysis revealed that buffalo and cattle one year of age or older were more frequently infected with M. wenyonii or Ca. M. haemobos than younger animals. PCR-positivity was not associated with anemia; however, the infection stage was unknown (acute infection versus chronic carriers).

    Conclusions: The high occurrence of bovine hemoplasma infections in buffalo and dairy cattle may have a significant impact on Cuban livestock production. To the best of our knowledge, this is the first molecular evidence of bovine hemoplasma species infection in dairy cattle and buffalo from Cuba and the Caribbean.

  • 328. Alberts, Marianne
    et al.
    Dikotope, Sekgothe A
    Choma, Solomon R
    Masemola, Matshane L
    Modjadji, Sewela EP
    Mashinya, Felistas
    Burger, Sandra
    Cook, Ian
    Brits, Sanette J
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, University of the Witwatersrand, Johannesberg, South Africa.
    Health & Demographic Surveillance System Profile: The Dikgale Health and Demographic Surveillance System.2015Inngår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, nr 5, s. 1565-1571Artikkel i tidsskrift (Fagfellevurdert)
  • 329.
    Albertsson, Jakob
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Effekt av förbehandling vid detektion av muterat superoxiddismutas-1 protein: Immunohistokemisk detektion av SOD1 aggregat hos G93A transgena möss2016Independent thesis Basic level (professional degree), 180 hpOppgave
  • 330.
    Albertsson, Jakob
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Effekt av förbehandling vid detektion av muterat superoxiddismutas-1 protein: Immunohistokemisk detektion av SOD1 aggregat hos G93A transgena möss2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 331.
    Albertsson, Katarina Wikén
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    van Dijken, Jan W V
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Awareness of toothbrushing and dentifrice habits in regularly dental care receiving adults2010Inngår i: Swedish Dental Journal, ISSN 0347-9994, Vol. 34, nr 2, s. 71-78Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to investigate toothbrushing and dentifrice habits in a Swedish adult population with relatively high caries frequency, which received regularly dental care and to evaluate the awareness of their toothbrush technique. Sixty adult participants with high caries frequency, 29 woman and 31 men, answered a self-reporting questionnaire with 42 questions concerning their oral care, brushing technique and -habits.The responses were related to their clinical behaviour observed during a customary toothbrushing session. Fifty-three participants fulfilled both the questionnaire and the clinical observation. Half of these used toothpaste containing 1450-1500 ppm fluoride but only one of all participants was aware of the fluoride concentration used. The majority used a manual toothbrush and 95% brushed their teeth twice a day using 0.9 g toothpaste. A wide range of brushing methods and habits was observed. Sixty percent did not brush systematically. Spitting of toothpaste-saliva during brushing was performed by 60% and after brushing by 15%.The observed brushing times were significantly higher than the self reported. The observed brushing times were <1 min: 3.4%, 1-2 min: 36.7% and >2 min: 47.0%. There was a significant correlation between observed brushing time and caries activity. Rinsing with water after brushing was performed once (32%) or twice (44%) during the observations. Only 9% rinsed with toothpaste slurry after brushing. It can be concluded that the awareness of the individual toothbrushing, post-brushing behaviour and the use of fluoride toothpaste was non-optimal in the adult participants. Oral health promotion by optimalized use of fluoride toothpaste and improved post-brushing behaviour should be recommended.

  • 332.
    Albertsson, Pontus
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap.
    Occupant casualties in bus and coach traffic: injury and crash mechanisms2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: The relevance of conducting this thesis is evident by the fact that bus and coach casualties have been “stubbornly stable” in Europe recent years and a need for investigating if a similar trend could be found in Sweden is therefore obvious. It was also important to add new knowledge to the bus and coach research in Sweden, since many areas were scarcely addressed.

    Aims: To describe bus and coach occupants’ injuries, crash and injury mechanisms generated in a traffic environment based on data from the medical sector. Additional aims were to investigate the injury reducing effect of a 3-point belt, the effect of cross-winds, and crucial factors in the emergency- and rescue response.

    Material and methods: Injury data analyses were based on a complete ten-year medical data set from a catchment-area with about 130,000 inhabitants. A number of crash studies with the scope in different crash phases were conducted by applying and elaborating the Haddon matrix as a framework. An additional framework, Protocol for Major Incidents was used in order to investi-gate the emergency- and rescue response to a severe coach crash.

    Results: Between the first and second five-year period, the incidence of injured in non-crash in-cidents was increased by 24%. In non-crash incidents, 54% were injured; 2/3 while alighting from a bus or coach. The pre-crash factor cross-wind, in addition to vehicle design, vehicle speed and road friction, was investigated in ten crashes. It was confirmed that cross-wind, in relation to vehicle speed and slippery road conditions, needs more attention. The importance of goods load-ing and passengers’ position in the bus, was indicated by the fact that a displacement of the cen-tre of mass rearwards with 10% increased the necessary coefficient of friction with, on average 45%, which in many cases corresponded to dry road conditions. Three Swedish rollover crashes were analysed with regard to the injury outcome, mechanisms and the possible injury reduction for occupants using a safety belt. A considerable increase in safety for occupants belted with 3-point belts was shown through limiting interior contacts, occupant interaction and the possibility of ejection. Crucial post-crash factors in the emergency- and rescue response showed that ordi-nary ways of working and equipment are not always useful and proper equipment for lifting a coach body is essential in the case of a rollover. Finally, the communication between the hospitals is important, and the telephone systems may be overloaded by calls from worried relatives and media.

    Conclusions: In non-crash events: Non-crash events constitute a majority of all bus and coach casualties with a high proportion of elderly female occupants among the MAIS 2+ injury cases. Boarding and, especially alighting causes many injuries to the lower extremities.

    In the pre-crash phase: Cross-winds do affect the safety of buses and coaches and requires more at-tention. Seat belt usage among bus and coach occupants has to be increased.

    In the crash phase: Rollover and ejection are the major causes behind serious and fatal injuries to bus and coach occupants, consequently, retentive glazing, pillars or rails need more attention. An upgrade from 2-point seat belts to 3-point seat belts yields an increase in the estimated injury re-duction from approximately 50% up to 80% for the MAIS 2+ casualties in a rollover crash.

    In the post-crash phase: In order to be able to lift a coach body proper equipment originated from experience and development is essential in a rescue operation of a crashed bus or coach. Fur-thermore, to improve the emergency response inside crashed coaches proper methods originated from experience need to be developed.

    Euro NBAP: Based on the results and conclusions generated in this thesis, a European New Bus and Coach Assessment Programme is suggested, which would provide bus and coach occupants with a assessment programme similar to the Euro NCAP.

  • 333.
    Albertsson, Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Juntunen, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Styrketräningsadaption: Aminosyrafördelning och intracellulär signalering2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Muscle mass regulation is responsive to a variety of stimuli, whereas amino acids and resistance exercise are two major regulators. Protein accretion occurs when the rate of protein synthesis exceeds the rate of protein degradation. It has long been recognized that both amino acid and resistance exercise effect protein synthesis and protein degradation, although the effect of varying distribution of amino acids remain unknown. The intracellular pathways by which protein synthesis are activated is complex. The purpose of this essay is to elucidate if there exist any scientific rationale to spread the amino acid intake over the day, with the purpose to maximize muscle protein accretion in response to resistance exercise. Furthermore , we intend to describe how amino acids and resistance exercise effect the molecular pathways that regulate protein synthesis, with the main focus on pathways that activate and are activated by mTOR.

    Studies that examine acute effects on protein synthesis or protein balance after resistance exercise and amino acid intake support the notion that there may be an advantage to spread the amino acid intake over the day, since the synthetic response to amino acids are transient. However, studies examining the effect of different meal frequencies on protein accretion and /or training results fail to support this notion. Both amino acids and resistance exercise seems to independently activate the intracellular pathways that regulate protein synthesis, with the effect being greatest when both are combined. The regulation also seems to be dependent on exercise intensity and volume, age of test subjects, contraction type and muscle fiber type. Furthermore, some researchers have found correlations between activation of these pathways and resistance exercise-induced muscle gain and strength gain.

  • 334. Albertsson-Wikland, Kerstin
    et al.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jonsson, Björn
    Hochberg, Zeʼev
    Long-term response to growth hormone (GH) therapy in short children with a delayed infancy childhood transition (DICT)2011Inngår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 69, s. 504-510Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transition of growth from infancy to childhood is associated with activation of the GH-IGF-I axis. Children with a delayed infancy-childhood-transition (ICT) are short as adults. Thus, age at ICT may impact on growth response to GH. The objective was to investigate associations between growth response to GH-treatment and ICT-timing in children with idiopathic short stature (ISS) in a randomized, controlled, multicenter trial, TRN 88-080. 147 pre-pubertal children (mean age, 11.5±1.4 yrs) were randomized to receive GH 33μg/kg/d (GH33, n=43), GH 67μg/kg/d (GH67, n=61) or no treatment (n=43). Data on growth to final height (FH) were analyzed after categorization into those with normal (n=76) or delayed ICT (n=71). Within the GH33 group, significant height gain at FH was only observed in children with a delayed ICT (p<0.001) with each month of delay corresponding to gain of 0.13 standard deviation score (SDS). For the GH67 group, the timing of the onset of the ICT had no impact on growth response. In conclusion, ISS children with a delayed ICT responded to standard-GH-dose (better responsiveness), whereas those with a normal ICT required higher doses to attain a significant height gain to FH.

  • 335. Albertsson-Wikland, Kerstin
    et al.
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. berit.kristrom@umu.se.
    Lundberg, Elena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Aronson, A. Stefan
    Gustafsson, Jan
    Hagenäs, Lars
    Ivarsson, Sten-A.
    Jonsson, Bjorn
    Ritzen, Martin
    Tuvemo, Torsten
    Westgren, Ulf
    Westphal, Otto
    Åman, Jan
    Growth Hormone Dose-Dependent Pubertal Growth: A Randomized Trial in Short Children with Low Growth Hormone Secretion2014Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, nr 3, s. 158-170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i. e. idiopathic isolated GH deficiency. Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH(33) mu g/kg/day for >= 1 year. They were randomized to receive 67 mu g/kg/day (GH(67)) given as one (GH(67x1); n = 35) or two daily injections (GH(33x2); n = 36), or to remain on a single 33 mu g/kg/day dose (GH(33x1); n = 40). Growth was assessed as height SDS gain for prepubertal, pubertal and total periods, as well as AH SDS versus the population and the midparental height. Results: Pubertal height SDS gain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33x1), 0.41, p < 0.05). AH(SDS) was greater on GH(67) (GH(67x1), -0.84; GH(33x2), -0.83) than GH(33) (-1.25, p < 0.05), and height SDS gain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height SDS. Conclusion: Pubertal height SDS gain and AH SDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once-and twice-daily GH(67) regimens. (C) 2014 S. Karger AG, Basel.

  • 336. Albertsson-Wikland, Kerstin
    et al.
    Martensson, Anton
    Savendahl, Lars
    Niklasson, Aimon
    Bang, Peter
    Dahlgren, Jovanna
    Gustafsson, Jan
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Norgren, Svante
    Pehrsson, Nils-Gunnar
    Oden, Anders
    Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics2016Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, nr 5, s. 2149-2159Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment.

    Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA).

    Participants: The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010).

    Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982).

    Main Outcome Measures: Death.

    Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations.

    Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95.

    Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001).

    Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

  • 337. Albertsson-Wikland, Kerstin
    et al.
    Mårtensson, Anton
    Sävendahl, Lars
    Niklasson, Aimon
    Bang, Peter
    Dahlgren, Jovanna
    Gustafsson, Jan
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Norgren, Svante
    Pehrsson, Nils-Gunnar
    Oden, Anders
    Birth Characteristics Explain One Third of Expected Deaths in rhGH-treated Patients Diagnosed with IGHD, ISS & SGA2016Inngår i: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 86, s. 49-49Artikkel i tidsskrift (Annet vitenskapelig)
  • 338. Albiges, Laurence
    et al.
    Powles, Tom
    Staehlerr, Michael
    Bensalan, Karim
    Giles, Rachel H.
    Horag, Milan
    Kuczyk, Markus A.
    Lam, Thomas B.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Marconi, Lorenzo
    Merseburger, Axel S.
    Volpe, Alessandro
    Abu-Ghanem, Yasmin
    Dabestani, Saeed
    Fernndez-Pello, Sergio
    Hofmann, Fabian
    Kuusk, Teele
    Tahbaz, Rana
    Bex, Axel
    Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma2019Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 2, s. 151-156Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma. The European Association of Urology Guidelines Panel has updated its recommendations based on these studies.

    Patient summary: Pembrolizumab plus axitinib is a new standard of care for patients diagnosed with kidney cancer spread outside the kidney and who did not receive any prior treatment for their cancer (treatment naive). This applies to all risk groups as determined by the International Metastatic Renal Cell Carcinoma Database Consortium criteria.

  • 339.
    Albiin, Nils
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Middle ear structure in relation to function: the rat in middle ear research1985Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The present study was undertaken to evaluate the rat as a model for middle ear re­search. The rat was chosen primarily because the gross structure of its middle ear shows several similarities to that of man. It was considered of great importance to make a thorough structural study of the rat middle ear and to compare the results with those reported for the human middle ear. The thesis therefore includes indepen­dent studies on various aspects of rat middle ear structure and function as well as a review of the literature. The most pertinent findings in the experimental part of this study were the following.

    The rat Eustachian tube consists of a nasopharyngeal, and a cartilaginous and bony portion. The orifice of the nasopharyngeal portion is composed of two soft tissue lips, which appear to be opened mainly by the action of the salpingopharyngeal mus­cle, but also by the levator and tensor veli palatini muscles. The cartilaginous por­tion appears to be opened solely by the tensor veli palatini muscle. The tensor tympani muscle seems to have no effect on the tube.

    A ciliated and secretory epithelium lines the inferomedial walls of the tube throughout its length. In the tympanic cavity these thelial cell types extend as two tracts - one anterior and the other inferoposterior to  the promontory - which communicate with the epitympanic/attic compartments. The remaining parts of the tube and the tympanic cavity are covered by a squamous/cuboidal, non-ciliated epithelium. The subepithelial loose connective tissue contains vessels, nerves, and connective tissue cells, among these mast cells. The mast cells are confined to areas covered by the ciliated epithelium, and in the floor of the bulla, in the pars flaccida, and along the manubrial vessels. Glands are restricted to the Eustachian tube.

    In the clearance/transport of serum-like material, from the epitympanum towards the tube, hydrostatic forces appear to be important.

    The tympanic membrane is vascularized from meatal and tympanal vessels. Meatal ves­sels branch in the pars flaccida and along the handle of the malleus, where they are localized directly beneath the outer, keratinizing, stratified, squamous epithelium. Furthermore, meatal vessels form a vascular network at the junction between the fi­brocartilaginous annulus and the tympanic sulcus. Tympanal vessels send branches to the periphery of the pars tensa, where they run immediately beneath the tympanal, simple, squamous epithelium. In the major portion of the pars tensa, no blood vessels were found.

    The rat stapedial artery is a thin-walled vessel with a wide lumen. Without branch­ing, it runs through the tympanic cavity to the extratympanal regions it supplies. In contrast to the corresponding artery in man, the rat stapedial artery persists throughout life. The artery does not seem to be affected by the fluid produced during experimentally induced otitis media with effusion.

    The middle ear structure in the rat and in man show both similarities and differ­ences. If the differences are kept in mind and considered, it would seem that the rat is indeed a suitable model for experimental middle ear research.

  • 340.
    Albinsson, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Nordlander, Anna-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Sjuksköterskors upplevelser och erfarenheter av samtal med äldre personer som vårdas i livets slutskede2017Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Bakgrund. Att säkra god vård i livets slutskede är en mångfacetterad uppgift. Fokus tenderar ofta vara farmakologiskt och stor vikt läggs vid att lindra fysiska symtom som smärta. För en personcentrerad vård utifrån en helhetssyn är sjuksköterskans samtal med patienten betydelsefulla.

    Syftet med denna studie var att beskriva sjuksköterskors upplevelser och erfarenheter av samtal med äldre personer som vårdas i livets slutskede.

    Design. Denna studie har en kvalitativ deskriptiv design och är baserad på intervjuer.

    Metod. Totalt tio sjuksköterskor deltog i semistrukturerade intervjuer under början av året 2017. Materialet analyserades med kvalitativ innehållsanalys.

    Resultat. Åtta kategorier framkom vid analysen. Studien visar att sen insikt och ett förnekande förhållningssätt till livets slutskede hos den äldre upplevs som hindrande omständigheter för samtal. En rad andra hindrande omständigheter som tidsbrist, språkliga hinder, brist på kunskap och erfarenhet samt anhörigas närvaro framkommer även i studien. Som stödjande förhållanden för samtal framkommer sjuksköterskans närhet i neutral relation, patientens upplevelse av acceptans och sjuksköterskans förmåga till balans mellan professionalitet och förtroendefullt engagemang. Ett enigt palliativt fokus kring patienten skapar bättre möjligheter till samtal och stöd för patientens bearbetning och acceptans i livets slutskede.

    Slutsats. Resultatet visar att förtroendefulla samtal är meningsfulla både för patienten och för sjuksköterskan. Sjuksköterskan upplever att möten genom samtal är betydelsefulla och nödvändiga förutsättningar för utformning av en personcentrerad vård. Samtalen behöver därmed lyftas som självklara och prioriterade delar vid omvårdnad av den äldre personen i livets slutskede.

    Nyckelord: livets slutskede, samtal, äldre, omvårdnad, sjuksköterskors upplevelser, personcentrerad vård.

  • 341. Albrecht, Letusa
    et al.
    Moll, Kirsten
    Blomqvist, Karin
    Normark, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Chen, Qijun
    Wahlgren, Mats
    var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.22011Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 10, artikkel-id 17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra- vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of approximate to 60 var genes. Methods: The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results: Transcripts from var1 (FCR3S1.2(var1); IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1a of var2 produced in E. coli completely and dosedependently disrupted rosettes (approximate to 95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion: The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1a of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1 alpha of the var2 encoded PfEMP1.

  • 342. Albrechtsen, A.
    et al.
    Grarup, N.
    Li, Y.
    Sparso, T.
    Tian, G.
    Cao, H.
    Jiang, T.
    Kim, S. Y.
    Korneliussen, T.
    Li, Q.
    Nie, C.
    Wu, R.
    Skotte, L.
    Morris, A. P.
    Ladenvall, C.
    Cauchi, S.
    Stancakova, A.
    Andersen, G.
    Astrup, A.
    Banasik, K.
    Bennett, A. J.
    Bolund, L.
    Charpentier, G.
    Chen, Y.
    Dekker, J. M.
    Doney, A. S. F.
    Dorkhan, M.
    Forsen, T.
    Frayling, T. M.
    Groves, C. J.
    Gui, Y.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hattersley, A. T.
    He, K.
    Hitman, G. A.
    Holmkvist, J.
    Huang, S.
    Jiang, H.
    Jin, X.
    Justesen, J. M.
    Kristiansen, K.
    Kuusisto, J.
    Lajer, M.
    Lantieri, O.
    Li, W.
    Liang, H.
    Liao, Q.
    Liu, X.
    Ma, T.
    Ma, X.
    Manijak, M. P.
    Marre, M.
    Mokrosinski, J.
    Morris, A. D.
    Mu, B.
    Nielsen, A. A.
    Nijpels, G.
    Nilsson, P.
    Palmer, C. N. A.
    Rayner, N. W.
    Renstrom, F.
    Ribel-Madsen, R.
    Robertson, N.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rossing, P.
    Schwartz, T. W.
    Slagboom, P. E.
    Sterner, M.
    Tang, M.
    Tarnow, L.
    Tuomi, T.
    van't Riet, E.
    van Leeuwen, N.
    Varga, T. V.
    Vestmar, M. A.
    Walker, M.
    Wang, B.
    Wang, Y.
    Wu, H.
    Xi, F.
    Yengo, L.
    Yu, C.
    Zhang, X.
    Zhang, J.
    Zhang, Q.
    Zhang, W.
    Zheng, H.
    Zhou, Y.
    Altshuler, D.
    't Hart, L. M.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Balkau, B.
    Froguel, P.
    McCarthy, M. I.
    Laakso, M.
    Groop, L.
    Christensen, C.
    Brandslund, I.
    Lauritzen, T.
    Witte, D. R.
    Linneberg, A.
    Jorgensen, T.
    Hansen, T.
    Wang, J.
    Nielsen, R.
    Pedersen, O.
    Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes2013Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, nr 2, s. 298-310Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

  • 343. Al-Chalabi, Ammar
    et al.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Chandran, Siddharthan
    Chio, Adriano
    Corcia, Philippe
    Couratier, Philippe
    Danielsson, Olof
    de Carvalho, Mamede
    Desnuelle, Claude
    Grehl, Torsten
    Grosskreutz, Julian
    Holmøy, Trygve
    Ingre, Caroline
    Karlsborg, Merete
    Kleveland, Grethe
    Christoph Koch, Jan
    Koritnik, Blaz
    KuzmaKozakiewicz, Magdalena
    Laaksovirta, Hannu
    Ludolph, Albert
    McDermott, Christopher
    Meyer, Thomas
    Ropero, Bernardo Mitre
    Pardina, Jesus Mora
    Nygren, Ingela
    Petri, Susanne
    Povedano Panades, Mónica
    Salachas, Francois
    Shaw, Pamela
    Silani, Vincenzo
    Staaf, Gert
    Svenstrup, Kirsten
    Talbot, Kevin
    Tysnes, Ole-Bjørn
    Van Damme, Philip
    van der Kooi, Anneke
    Weber, Markus
    Weydt, Patrick
    Wolf, Joachim
    Hardiman, Orla
    van den Berg, Leonard H.
    July 2017 ENCALS statement on edaravone2017Inngår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 7-8, s. 471-474Artikkel i tidsskrift (Annet vitenskapelig)
  • 344. Alcocer, Marcos
    et al.
    Rundqvist, Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ber e 1 protein: the versatile major allergen from Brazil nut seeds.2012Inngår i: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 34, nr 4, s. 597-610Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Due mainly to its extremely high content of sulphur amino acids, Ber e 1 protein, the major allergen from Brazil nut, has attracted much scientific and press attention. Ber e 1 was the main target protein in early biotechnology transgenic work, in early processing studies of plant storage proteins, in plant vacuolar targeting studies and as the main protein in early nutritional supplementation experiments. Ber e 1 was also one of the first food allergens to be unintentionally transferred from one plant to another and was involved in the first reported case of systemic allergic reaction caused by a food allergen transferred in semen. In this review, many of the Ber e 1 unique biotechnological and structural functions are discussed with a particular emphasis on its use as model protein for studies of intrinsic allergenicity of food proteins.

  • 345. Aldick, Thomas
    et al.
    Bielaszewska, Martina
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Humpf, Hans-Ulrich
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Karch, Helge
    Vesicular stabilization and activity augmentation of enterohaemorrhagic Escherichia coli haemolysin2009Inngår i: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 71, nr 6, s. 1496-508Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Haemolysin from enterohaemorrhagic Escherichia coli (EHEC-Hly), a putative EHEC virulence factor, belongs to the RTX (repeat-in-toxin) family whose members rapidly inactivate themselves by self-aggregation. By investigating the status of EHEC-Hly secreted extracellularly, we found the toxin both in a free, soluble form and associated, with high tendency and independently of its acylation status, to outer membrane vesicles (OMVs) extruded by EHEC. We compared the interaction of both toxin forms with erythrocytes using scanning electron microscopy and binding assays. The OMV-associated toxin was substantially (80 times) more stable under physiological conditions than the free EHEC-Hly as demonstrated by prolonged haemolytic activity (half-life time 20 h versus 15 min). The haemolysis was preceded by calcium-dependent binding of OMVs carrying EHEC-Hly to erythrocytes; this binding was mediated by EHEC-Hly. We demonstrate that EHEC-Hly is a biologically active cargo in OMVs with dual roles: a cell-binding protein and a haemolysin. These paired functions produce a biologically potent form of the OMV-associated RTX toxin and augment its potential towards target cells. Our findings provide a general concept for stabilization of RTX toxins and open new insights into the biology of these important virulence factors.

  • 346. Aldrich, Rosemary
    et al.
    Mahoney, Mary
    Harris, Elizabeth
    Simpson, Sarah
    Stewart-Williams, Jenny
    Newcastle Institute of Public health, University of Newcastle, New South Wales, Australia.
    Building an equity focus in health impact assessment2005Inngår i: New South Wales Public Health Bulletin, ISSN 1034-7674, Vol. 16, nr 7-8, s. 118-119Artikkel i tidsskrift (Fagfellevurdert)
  • 347.
    Aledahl, Adam
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Följs riktlinjerna för remittering till MRT vid ländryggssmärta?2018Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [sv]

    Introduktion: Idag finns inga uppgifter om att medicinsk personal i Sverige följer riktlinjer för remittering till magnetresonanstomografi (MRT) vid ländryggssmärta. Det har tidigare förts fram att män och kvinnor bemöts olika vid behandling av ryggbesvär men saknas uppgifter kring skillnader i kön, ålder eller symptomduration vid remittering till MRT. Denna information är nödvändig för att säkerställa att patienter får adekvat undersökning och bedömning.

    Syfte: Studera remisser för att utvärdera om remissens frågeställning följer gällande riktlinjer samt att undersöka om det finns samband mellan kön, ålder, smärtduration och om riktlinjerna följs samt om riktlinjerna ger ökad överensstämmelse mellan frågeställning och svar på MRT.

    Metod: Retrospektiv studie där samtliga remisser till MRT ländrygg inom Västerbottens Läns landsting (VLL) under 2016 granskades. Remisser och remissvar granskades och kodades under januari-juli 2018. Data gällande ålder, kön, följer riktlinjer, symptomduration, nämnd patoanatomisk frågeställning (PAD) i remiss och om PAD identifierades samlades in. För att beskriva samband mellan kön, ålder, symptomduration och efterföljda riktlinjer gjordes logistisk regression. För att beskriva skillnad mellan remisser där riktlinjer följs inte följs gällande antal PAD gjordes ett chi2-test. 

    Resultat: 62% av de inkluderade remisserna följde aktuella riktlinjer. Det fanns ett signifikant positivt samband mellan ålder och följda riktlinjer (p≤0.001). Det var ett signifikant positivt samband mellan subakuta besvär (p<0.05), kroniska besvär (p≤0.001) och besvär >5 år och följda riktlinjer (p<0.05). Inget samband mellan kön och följda riktlinjer påvisades.

    Slutsats: Totalt 38 % av remisserna kunde inte anses ingå inom ramen för aktuella riktlinjer. Det finns inget samband mellan kön, men ett positivt samband mellan följda riktlinjer, ökad ålder och längre tid med besvär. 

  • 348. Aleksandrova, Krasimira
    et al.
    Bamia, Christina
    Drogan, Dagmar
    Lagiou, Pagona
    Trichopoulou, Antonia
    Jenab, Mazda
    Fedirko, Veronika
    Romieu, Isabelle
    Bueno-de-Mesquita, H. Bas
    Pischon, Tobias
    Tsilidis, Kostas
    Overvad, Kim
    Tjønneland, Anne
    Bouton-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Kaaks, Rudolf
    Kuehn, Tilman
    Tsironis, Christos
    Papatesta, Eleni-Maria
    Saitakis, George
    Palli, Domenico
    Panico, Salvatore
    Grioni, Sara
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H.
    Weiderpass, Elisabete
    Lukic, Marko
    Braaten, Tonje
    Ramon Quiros, J.
    Lujan-Barroso, Leila
    Sanchez, Mara-Jose
    Chilarque, Maria-Dolores
    Ardanas, Eva
    Dorronsoro, Miren
    Nilsson, Lena Maria
    Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wallström, Peter
    Ohlsson, Bodil
    Bradbury, Kathryn E.
    Khaw, Kay-Tee
    Wareham, Nick
    Stepien, Magdalena
    Duarte-Salles, Talita
    Assi, Nada
    Murphy, Neil
    Gunter, Marc J.
    Riboli, Elio
    Boeing, Heiner
    Trichopoulos, Dimitrios
    The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition2015Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 102, nr 6, s. 1498-1508Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having >= 4 cups (600mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.

  • 349. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Jenab, Mazda
    Bas Bueno-de-Mesquita, H
    Jansen, Eugene
    van Duijnhoven, Fränzel J B
    Fedirko, Veronika
    Rinaldi, Sabina
    Romieu, Isabelle
    Riboli, Elio
    Romaguera, Dora
    Overvad, Kim
    Ostergaard, Jane Nautrup
    Olsen, Anja
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Masala, Giovanna
    Agnoli, Claudia
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Trichopoulou, Antonia
    Naska, Androniki
    Bamia, Christina
    Peeters, Petra H
    Rodríguez, Laudina
    Buckland, Genevieve
    Sánchez, María-José
    Dorronsoro, Miren
    Huerta, Jose-María
    Barricarte, Aurelio
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Allen, Naomi E
    Tsilidis, Konstantinos K
    Pischon, Tobias
    Metabolic syndrome and risks of colon and rectal cancer: the European prospective investigation into cancer and nutrition study.2011Inngår i: Cancer prevention research (Philadelphia, Pa.), ISSN 1940-6215, Vol. 4, nr 11, s. 1873-83Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Metabolic syndrome (MetS) is purportedly related to risk of developing colorectal cancer; however, the association of MetS, as defined according to recent international criteria, and colorectal cancer has not been yet evaluated. In particular, it remains unclear to what extent the MetS components individually account for such an association. We addressed these issues in a nested case-control study that included 1,093 incident cases matched (1:1) to controls by using incidence density sampling. Conditional logistic regression was used to estimate relative risks (RR) and 95% CIs. MetS was defined according to the criteria of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII), the International Diabetes Federation (IDF), and the 2009 harmonized definition. Among individual components, abdominal obesity (RR = 1.51; 95% CI: 1.16-1.96) was associated with colon cancer, whereas abnormal glucose metabolism was associated with both colon (RR = 2.05; 95% CI: 1.57-2.68) and rectal cancer (RR = 2.07; 95% CI: 1.45-2.96). MetS, as defined by each of the definitions, was similarly associated with colon cancer (e.g., RR = 1.91; 95% CI: 1.47-2.42 for MetS by NCEP/ATPIII), whereas MetS by NCEP/ATPIII, but not IDF or harmonized definition, was associated with rectal cancer (RR = 1.45; 95% CI: 1.02-2.06). Overall, these associations were stronger in women than in men. However, the association between MetS and colorectal cancer was accounted for by abdominal obesity and abnormal glucose metabolism such that MetS did not provide risk information beyond these components (likelihood ratio test P = 0.10 for MetS by NCEP/ATPIII). These data suggest that simple assessment of abnormal glucose metabolism and/or abdominal obesity to identify individuals at colorectal cancer risk may have higher clinical utility than applying more complex MetS definitions. Cancer Prev Res; 4(11); 1873-83. ©2011 AACR.

  • 350. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Jenab, Mazda
    Bueno-de-Mesquita, H. Bas
    Jansen, Eugene
    van Duijnhoven, Franzel J. B.
    Rinaldi, Sabina
    Fedirko, Veronika
    Romieu, Isabelle
    Riboli, Elio
    Gunter, Marc J.
    Westphal, Sabine
    Overvad, Kim
    Tjonneland, Anne
    Halkjaer, Jytte
    Racine, Antoine
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Mattiello, Amalia
    Pala, Valeria
    Palli, Domenico
    Tumino, Rosario
    Vineis, Paolo
    Buckland, Genevieve
    Sanchez, Maria-Jose
    Amiano, Pilar
    Maria Huerta, Jose
    Barricarte, Aurelio
    Menendez, Virginia
    Peeters, Petra H.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Allen, Naomi E.
    Crowe, Francesca L.
    Khaw, Kay-Tee
    Wareham, Nickolas
    Pischon, Tobias
    Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into Cancer and nutrition cohort2012Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 72, nr 20, s. 5328-5337Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; P-trend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P-trend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P-trend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, P-trend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 5328-37. (C) 2012 AACR.

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