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  • 101.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Enroth, Helena
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Claesson, Berndt E. B.
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Ovemyr, Ida
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Karlsson, Jesper
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Fröberg, Berit
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Brodin, Anna-Karin
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jacobsson, Gunnar
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Rune
    Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden..
    Karlsson, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, no 1, article id 199Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis.

    METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity.

    RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results.

    CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis.

  • 102.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital / The swedish strategic program against antibiotic resistance.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    The diagnostic value of PCT as biomarker in patients suspected with community-onset bacterial sepsis2017Conference paper (Refereed)
  • 103.
    Ljungström, Lars
    et al.
    Skaraborg Hospital Skövde, Sweden.
    Karlsson, Diana
    Skaraborg Hospital Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Andersson, R.
    Institute of Biosciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Jacobsson, Gunnar
    Skaraborg Hospital Skövde, Sweden.
    Neutrophil to lymphocyte count ratio performs better than procalcitonin as a biomarker for bacteremia and severe sepsis in the emergency department2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no Suppl 1, article id P66Article in journal (Refereed)
  • 104.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden / CARe–Center for Antibiotic Resistance Research, Gothenburg University, Gothenburg, Sweden.
    Andersson, Rune
    CARe–Center for Antibiotic Resistance Research, Gothenburg University, Gothenburg, Sweden / Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University and Sahlgrenska University Hospital, Gothenburg, Sweden.
    Usener, Barbara
    Department of Clinical Chemistry, Unilabs AB, Skövde, Sweden.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, article id e018704Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Early recognition is a key factor to achieve improved outcomes for septic patients. Combinations of biomarkers, as opposed to single ones, may improve timely diagnosis and survival. We investigated the performance characteristics of sepsis biomarkers, alone and in combination, for diagnosis of verified bacterial sepsis using Sepsis-2 and Sepsis-3 criteria, respectively.

    METHODS:

    Procalcitonin (PCT), neutrophil-lymphocyte count ratio (NLCR), C-reactive protein (CRP), and lactate were determined in a total of 1,572 episodes of adult patients admitted to the emergency department on suspicion of sepsis. All sampling were performed prior to antibiotic administration. Discriminant analysis was used to construct two composite biomarkers consisting of linear combinations of the investigated biomarkers, one including three selected biomarkers (i.e., NLCR, CRP, and lactate), and another including all four (i.e., PCT, NLCR, CRP, and lactate). The diagnostic performances of the composite biomarkers as well as the individual biomarkers were compared using the area under the receiver operating characteristic curve (AUC).

    RESULTS:

    For diagnosis of bacterial sepsis based on Sepsis-3 criteria, the AUC for PCT (0.68; 95% CI 0.65-0.71) was comparable to the AUCs for the both composite biomarkers. Using the Sepsis-2 criteria for bacterial sepsis diagnosis, the AUC for the NLCR (0.68; 95% CI 0.65-0.71) but not for the other single biomarkers, was equal to the AUCs for the both composite biomarkers. For diagnosis of severe bacterial sepsis or septic shock based on the Sepsis-2 criteria, the AUCs for both composite biomarkers were significantly greater than those of the single biomarkers (0.85; 95% CI 0.82-0.88 for the composite three-biomarker, and 0.86; 95% CI 0.83-0.89 for the composite four-biomarker).

    CONCLUSIONS:

    Combinations of biomarkers can improve the diagnosis of verified bacterial sepsis in the most critically ill patients, but in less severe septic conditions either the NLCR or PCT alone exhibit equivalent performance.

  • 105.
    Ljungström, Lars R.
    et al.
    Department of Infectious Diseases, Skaraborg Hospital / CARe (Center for Antibiotic Resistance Research), Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital, Skövde / CARe (Center for Antibiotic Resistance Research), Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg.
    Claesson, Berndt E. B.
    Department of Clinical Microbiology, Unilabs, Skaraborg Hospital, Skövde.
    Andersson, Rune
    CARe (Center for Antibiotic Resistance Research), Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Enroth, Helena
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Molecular Microbiology, Unilabs, Skaraborg Hospital, Skövde.
    Respiratory viral infections are underdiagnosed in patients with suspected sepsis2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 10, p. 1767-1776Article in journal (Refereed)
    Abstract [en]

    The study aim was to investigate the prevalence and clinical relevance of viral findings by multiplex PCR from the nasopharynx of clinically septic patients during a winter season. During 11 weeks of the influenza epidemic period in January-March 2012, consecutive adult patients suspected to be septic (n = 432) were analyzed with cultures from blood and nasopharynx plus multiplex PCR for respiratory viruses on the nasopharyngeal specimen. The results were compared with those from microbiology analyses ordered as part of standard care. During the winter season, viral respiratory pathogens, mainly influenza A virus, human metapneumovirus, coronavirus, and respiratory syncytial virus were clinically underdiagnosed in 70% of patients positive by the multiplex PCR assay. During the first four weeks of the influenza epidemic, few tests for influenza were ordered by clinicians, indicating low awareness that the epidemic had started. Nasopharyngeal findings of Streptococcus pneumoniae and Haemophilus influenzae by culture correlated to pneumonia diagnosis, and in those patients laboratory signs of viral co-infections were common but rarely suspected by clinicians. The role of respiratory viral infections in patients presenting with a clinical picture of sepsis is underestimated. Specific antiviral treatment might be beneficial in some cases and may reduce spread in a hospital setting. Diagnosing viral infections may promote reduction of unnecessary antibiotic use. It can also be a tool for decisions concerning patient logistics, in order to minimize exposure of susceptible patients and personnel.

  • 106.
    Lossos, Alexander
    et al.
    Department of Neurology, Hebrew University-Hadassah Medical Centre, Jerusalem, Israel.
    Oldfors, Anders
    Department of Pathology, University of Gothenburg, Sahlgrenska Hospital, Gothenburg, Sweden.
    Fellig, Yakov
    Department of Pathology, Hebrew University-Hadassah Medical Centre, Jerusalem, Israel.
    Meiner, Vardiella
    Department of Genetics, Hebrew University-Hadassah Medical Centre, Jerusalem, Israel.
    Argov, Zohar
    Department of Neurology, Hebrew University-Hadassah Medical Centre, Jerusalem, Israel.
    Tajsharghi, Homa
    Department of Pathology, University of Gothenburg, Sahlgrenska Hospital, Gothenburg, Sweden.
    MYH2 mutation in recessive myopathy with external ophthalmoplegia linked to chromosome 17p13.1-p122013In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 136, no 7, article id e238Article in journal (Refereed)
  • 107.
    Lundh, Dan
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Coleman, Scott
    Motion and Sports Lab, Baylor University Medical Center, Dallas, TX, USA.
    Riad, Jacques
    Orthopaedic Department, Skaraborg Hospital Skövde, Sweden / Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
    Movement deviation and asymmetry assessment with three dimensional gait analysis of both upper- and lower extremity results in four different clinical relevant subgroups in unilateral cerebral palsy2014In: Clinical Biomechanics, ISSN 0268-0033, E-ISSN 1879-1271, Vol. 29, no 4, p. 381-386Article in journal (Refereed)
    Abstract [en]

    Background

    In unilateral cerebral palsy, movement pattern can be difficult to define and quantify. The aim was to assess the degree of deviation and asymmetry in upper and lower extremities during walking.

    Methods

    Forty-seven patients, 45 Gross Motor Function Classification Scale (GMFCS) I and 2 patients GMFCS II, mean age 17.1 years (range 13.1 to 24.0) and 15 matched controls were evaluated. Gait profile score (GPS) and arm posture score (APS) were calculated from three-dimensional gait analysis (GA). Asymmetry was the calculated difference in deviation between affected and unaffected sides.

    Findings

    The GPS was significantly increased compared to the control group on the affected side (6.93 (2.08) versus 4.23 (1.11) degrees) and on the unaffected side (6.67 (2.14)). The APS was also significantly increased on the affected side (10.39 (5.01) versus 5.52 (1.71) degrees) and on the unaffected side (7.13 (2.23)). The lower extremity asymmetry increased (significantly) in comparison with the control group (7.89 (3.82) versus 3.90 (1.01)) and correspondingly in the upper extremity (9.75 (4.62) versus 5.72 (1.84)). The GPS was not different between affected and unaffected sides, however the APS was different (statistically significant).

    Interpretation

    We calculated deviation and asymmetry of movement during walking in unilateral CP, identifying four important clinical groups: close to normal, deviations mainly in the leg, deviations mainly in the arm and those with deviation in the arm and leg. This method can be applied to any patient group, and aid in diagnosing, planning treatment, and prognosis.

  • 108.
    Lööf, Jasmine
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Rosell, Johan
    Department of Oncology, Linköping University Hospital, S-58185 Linköping, Sweden.
    Bratthäll, Charlotte
    Department of Oncology, Linköping University Hospital, S-58185 Linköping, Sweden.
    Doré, Siv
    Department of Pathology, Linköping University, Linköping, Sweden.
    Starkhammar, Hans
    Department of Oncology, Linköping University Hospital, S-58185 Linköping, Sweden.
    Zhang, Hong
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Sun, Xiao-Feng
    Department of Oncology, Linköping University, Linköping, Sweden.
    Impact of PINCH expression on survival in colorectal cancer patients2011In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 11, p. Artikelnr 103-Article in journal (Refereed)
    Abstract [en]

    Background: The adaptor protein PINCH is overexpressed in the stroma of several types of cancer, and is an independent prognostic marker in colorectal cancer. In this study we further investigate the relationship of PINCH and survival regarding the response to chemotherapy in colorectal cancer. Results: Paraffin-embedded tissue sections from 251 primary adenocarcinomas, 149 samples of adjacent normal mucosa, 57 samples of distant normal mucosa and 75 lymph node metastases were used for immunohistochemical staining. Stromal staining for PINCH increased from normal mucosa to primary tumour to metastasis. Strong staining in adjacent normal mucosa was related to worse survival independently of sex, age, tumour location, differentiation and stage (p = 0.044, HR, 1.60, 95% Cl, 1.01-2.52). PINCH staining at the invasive margin tended to be related to survival (p = 0.051). In poorly differentiated tumours PINCH staining at the invasive margin was related to survival independently of sex, age and stage (p = 0.013, HR, 1.90, 95% Cl, 1.14-3.16), while in better differentiated tumours it was not. In patients with weak staining, adjuvant chemotherapy was related to survival (p = 0.010, 0.013 and 0.013 in entire tumour area, invasive margin and inner tumour area, respectively), but not in patients with strong staining. However, in the multivariate analysis no such relationship was seen. Conclusions: PINCH staining in normal adjacent mucosa was related to survival. Further, PINCH staining at the tumour invasive margin was related to survival in poorly differentiated tumours but not in better differentiated tumours, indicating that the impact of PINCH on prognosis was dependent on differentiation status.

  • 109.
    Magnusson Hanson, Linda L.
    et al.
    Stress Research Institute, Stockholm University, Sweden.
    Rod, Naja Hulvej
    Section of Epidemiology, Department of Public Health, University of Copenhagen, Social Medicine Section, Copenhagen, Denmark / National Research Centre for the Working Environment, Copenhagen, Denmark.
    Vahtera, Jussi
    Department of Public Health, University of Turku, Finland / Turku University Hospital, Finland.
    Peristera, Paraskevi
    Stress Research Institute, Stockholm University, Sweden.
    Pentti, Jaana
    Department of Public Health, University of Turku, Finland.
    Rugulies, Reiner
    Section of Epidemiology, Department of Public Health, University of Copenhagen, Social Medicine Section, Copenhagen, Denmark / National Research Centre for the Working Environment, Copenhagen, Denmark / Department of Psychology, University of Copenhagen, Denmark.
    Madsen, Ida Elisabeth Huitfeldt
    National Research Centre for the Working Environment, Copenhagen, Denmark.
    Lamontagne, Anthony D.
    McCaughey Centre, Centre for Health Equity, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia / Population Health Strategic Research Centre, School of Health and Social Development, Deakin University, Burwood, Victoria, Australia.
    Milner, Allison
    Disability and Health Unit, Centre for Health Equity, Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia.
    Lange, Theis
    Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark.
    Suominen, Sakari
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Public Health, University of Turku, Finland.
    Stenholm, Sari
    Department of Public Health, University of Turku, Finland.
    Xu, Tianwei
    Section of Epidemiology, Department of Public Health, University of Copenhagen, Social Medicine Section, Copenhagen, Denmark / National Research Centre for the Working Environment, Copenhagen, Denmark.
    Kivimäki, Mika
    Clinicum, Faculty of Medicine, University of Helsinki, Finland / Department of Epidemiology and Public Health, University College London, UK.
    Westerlund, Hugo
    Stress Research Institute, Stockholm University, Sweden.
    Multicohort study of change in job strain, poor mental health and incident cardiometabolic disease2019In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 76, p. 785-792Article in journal (Refereed)
    Abstract [en]

    Objectives: Several recent large-scale studies have indicated a prospective association between job strain and coronary heart disease, stroke and diabetes. Job strain is also associated with poorer mental health, a risk factor for cardiometabolic disease. This study investigates the prospective relationships between change in job strain, poor mental health and cardiometabolic disease, and whether poor mental health is a potential mediator of the relationship between job strain and cardiometabolic disease. Methods: We used data from five cohort studies from Australia, Finland, Sweden and UK, including 47 757 men and women. Data on job strain across two measurements 1-5 years apart (time 1 (T1)-time 2 (T2)) were used to define increase or decrease in job strain. Poor mental health (symptoms in the top 25% of the distribution of the scales) at T2 was considered a potential mediator in relation to incident cardiometabolic disease, including cardiovascular disease and diabetes, following T2 for a mean of 5-18 years. Results: An increase in job strain was associated with poor mental health (HR 1.56, 95% CI 1.38 to 1.76), and a decrease in job strain was associated with lower risk in women (HR 0.70, 95% CI 0.60-0.84). However, no clear association was observed between poor mental health and incident cardiometabolic disease (HR 1.08, 95% CI 0.96-1.23), nor between increase (HR 1.01, 95% CI 0.90-1.14) and decrease (HR 1.08, 95% CI 0.96-1.22) in job strain and cardiometabolic disease. Conclusions: The results did not support that change in job strain is a risk factor for cardiometabolic disease and yielded no support for poor mental health as a mediator.

  • 110.
    Magnusson, Maria K.
    et al.
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Brynjólfsson, Siggeir F.
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Dige, Anders
    Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Uronen-Hansson, Heli
    Immunology Section, Department of Experimental Medical Science, Lund University, Lund, Sweden.
    Börjesson, Lars G.
    Department of Surgery, Sahlgrenska University Hospital, Gotenburg, Sweden.
    Bengtsson, Jonas L.
    Department of Surgery, Sahlgrenska University Hospital, Gotenburg, Sweden.
    Gudjonsson, Sigurdur
    Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Öhman, Lena
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Agnholt, Jørgen
    Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Sjövall, Henrik
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Agace, William W.
    Immunology Section, Department of Experimental Medical Science, Lund University, Lund, Sweden / Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
    Wick, Mary Jo
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation2016In: Mucosal Immunology, ISSN 1933-0219, E-ISSN 1935-3456, Vol. 9, no 1, p. 171-182Article in journal (Refereed)
    Abstract [en]

    Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14(+)DR(int) MQs characterized inflamed intestinal mucosa while total CD141(+) or CD1c(+) DCs numbers were unchanged. However, CD103(+) DCs, including CD141(+)CD103(+) and CD1c(+)CD103(+) DCs, were reduced in inflamed intestine. In MLNs, two CD14(-) DC populations were identified: CD11c(int)HLADR(hi) and CD11c(hi)HLADR(int) cells. A marked increase of CD11c(hi)HLADR(int) DC, particularly DR(int)CD1c(+) DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn's colon. In contrast, no difference in the frequency of ALDH(+) cells among blood precursors was detected between UC patients and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.

  • 111.
    Magnusson, Maria K.
    et al.
    Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Strid, Hans
    Department of Internal Medicine, Södra Älvsborg Hospital, Borås, Sweden.
    Isaksson, Stefan
    Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Simrén, Magnus
    Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Öhman, Lena
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Swede.
    The Mucosal Antibacterial Response Profile and Fecal Microbiota Composition Are Linked to the Disease Course in Patients with Newly Diagnosed Ulcerative Colitis2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 6, p. 956-966Article in journal (Refereed)
    Abstract [en]

    Background: The clinical disease course of ulcerative colitis (UC) varies substantially between individuals and can currently not be reliably predicted. The gut microbiota and the host's immune defense are key players for gut homeostasis and may be linked to disease outcome. The aim of this study was to determine fecal microbiota composition and mucosal antibacterial response profile in untreated patients with newly diagnosed UC and the impact of these factors on disease course. Methods: Stool samples and intestinal biopsies were obtained from therapy-naive newly diagnosed patients with UC. Patients were defined to have mild or moderate/severe disease course assessed by disease activity during the 3 years follow-up. Fecal microbiota was analyzed by the GA-map Dysbiosis test (n = 18), and gene expression in intestinal biopsies was analyzed by RT2 Profiler polymerase chain reaction array (n = 13) and real-time polymerase chain reaction (n = 44). Results: At the time of diagnosis of UC, the fecal microbiota composition discriminated between patients with mild versus moderate/severe disease course. Also, the mucosal antibacterial gene expression response profile differed between patients with mild versus moderate/severe disease course with bactericidal/permeability-increasing protein (BPI) being most important for the discrimination. Mucosal bactericidal/permeability-increasing protein gene expression at diagnosis was higher in patients with mild versus moderate/severe disease course when confirmed in a larger patient cohort (P = 0.0004, n = 44) and was a good predictor for the number of flares during the 3 years follow-up (R-2 = 0.395, P < 0.0001). Conclusions: In patients with newly diagnosed UC, fecal microbiota composition and mucosal antibacterial response profile, especially bactericidal/permeability-increasing protein, are linked to disease course.

  • 112.
    Magnusson, Maria K.
    et al.
    Department of Microbiology and Immunology, University of Gothenburg, Institute for Biomedicine, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden.
    Strid, Hans
    Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden / Södra Älvsborg Hospital, Department of Internal Medicine, Borås, Sweden.
    Sapnara, Maria
    Department of Microbiology and Immunology, University of Gothenburg, Institute for Biomedicine, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden.
    Lasson, Anders
    Södra Älvsborg Hospital, Department of Internal Medicine, Borås, Sweden.
    Bajor, Antal
    Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden / Södra Älvsborg Hospital, Department of Internal Medicine, Borås, Sweden .
    Ung, Kjell-Arne
    Kärnsjukhuset, Department of Internal Medicine, Skövde, Sweden.
    Öhman, Lena
    University of Skövde, School of Health and Education. Department of Microbiology and Immunology, University of Gothenburg, Institute for Biomedicine, Gothenburg, Sweden / Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Institute for Medicine, Gothenburg, Sweden.
    Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 8, p. 943-952Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome.

    METHODS: Serum and biopsies were obtained from UC patients naïve to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12-14 weeks after baseline.

    RESULTS: At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders.

    CONCLUSIONS: Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.

  • 113.
    Malmrot, Gustav
    et al.
    University of Skövde, School of Life Sciences.
    Ulver, Erika
    University of Skövde, School of Life Sciences.
    Ett sviktande hjärta: patientupplevelser av att leva med en kronisk hjärtsvikt2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    As the occurrence of obesity increases amongst young people, so increases the risk of more people suffering from heart failure as early as during middle age. The aim is to describe the life experiences of middle aged persons living with chronic heart failure. The literature study is based on twelve published, qualitative, and scientifically proved articles derived from MedLine and Cinahl using queries representing the subject, as well as from manual searching in ScienceDirect and LIBRIS. These articles have been analyzed from a life world perspective. Four main themes and four sub themes were identified from the articles' results. The main themes are "The social life", "Quality of life", "Body failing", and "the Economical impact of chronic heart failure". These represent the main areas where the patients feel the greatest loss due to their condition. The discussion reveals the importance of informing the patients of the common prevalence of the feelings described in this study. Also, the nurse should function as a coach for self-care with continuous follow-ups. The result of this study will hopefully increase the understanding of the heart diseased patients' life situations.

  • 114.
    Marcišauskas, Simonas
    et al.
    Division of Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
    Ulfenborg, Benjamin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Kristjansdottir, Björg
    Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
    Waldemarson, Sofia
    Department of Immunotechnology, Lund University, Medicon Village, Lund, Sweden.
    Sundfeldt, Karin
    Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
    Univariate and classification analysis reveals potential diagnostic biomarkers for early stage ovarian cancer Type 1 and Type 22019In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 196, p. 57-68Article in journal (Refereed)
    Abstract [en]

    Biomarkers for early detection of ovarian tumors are urgently needed. Tumors of the ovary grow within cysts and most are benign. Surgical sampling is the only way to ensure accurate diagnosis, but often leads to morbidity and loss of female hormones. The present study explored the deep proteome in well-defined sets of ovarian tumors, FIGO stage I, Type 1 (low-grade serous, mucinous, endometrioid; n = 9), Type 2 (high-grade serous; n = 9), and benign serous (n = 9) using TMT–LC–MS/MS. Data are available via ProteomeXchange with identifier PXD010939. We evaluated new bioinformatics tools in the discovery phase. This innovative selection process involved different normalizations, a combination of univariate statistics, and logistic model tree and naive Bayes tree classifiers. We identified 142 proteins by this combined approach. One biomarker panel and nine individual proteins were verified in cyst fluid and serum: transaldolase-1, fructose-bisphosphate aldolase A (ALDOA), transketolase, ceruloplasmin, mesothelin, clusterin, tenascin-XB, laminin subunit gamma-1, and mucin-16. Six of the proteins were found significant (p <.05) in cyst fluid while ALDOA was the only protein significant in serum. The biomarker panel achieved ROC AUC 0.96 and 0.57 respectively. We conclude that classification algorithms complement traditional statistical methods by selecting combinations that may be missed by standard univariate tests. Significance: In the discovery phase, we performed deep proteome analyses of well-defined histology subgroups of ovarian tumor cyst fluids, highly specified for stage and type (histology and grade). We present an original approach to selecting candidate biomarkers combining several normalization strategies, univariate statistics, and machine learning algorithms. The results from validation of selected proteins strengthen our prior proteomic and genomic data suggesting that cyst fluids are better than sera in early stage ovarian cancer diagnostics. 

  • 115.
    Marcondes, Rodrigo R.
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Disciplina de Ginecologia, Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
    Maliqueo, Manuel
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Endocrinology and Metabolism Laboratory, Department of Medicine, West Division, University of Chile, Santiago, Chile.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Benrick, Anna
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Hu, Min
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ivarsson, Niklas
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Carlström, Mattias
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Cushman, Samuel W.
    Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
    Stenkula, Karin G.
    Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
    Maciel, Gustavo A. R.
    Disciplina de Ginecologia, Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Exercise differentially affects metabolic functions and white adipose tissue in female letrozole-and dihydrotestosterone-induced mouse models of polycystic ovary syndrome2017In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 448, p. 66-76Article in journal (Refereed)
    Abstract [en]

    Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue. 

  • 116.
    Mijwel, Sara
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Backman, Malin
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden / Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Bolam, Kate A.
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden / School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Australia.
    Jervaeus, Anna
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Sundberg, Carl Johan
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.
    Margolin, Sara
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden / Department of Oncology, Stockholm South General Hospital, Stockholm, Sweden.
    Browall, Maria
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Rundqvist, Helene
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
    Wengström, Yvonne
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden / Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Adding high-intensity interval training to conventional training modalities: optimizing health-related outcomes during chemotherapy for breast cancer: the OptiTrain randomized controlled trial2018In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 168, no 1, p. 79-93Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Exercise training is an effective and safe way to counteract cancer-related fatigue (CRF) and to improve health-related quality of life (HRQoL). High-intensity interval training has proven beneficial for the health of clinical populations. The aim of this randomized controlled trial was to compare the effects of resistance and high-intensity interval training (RT-HIIT), and moderate-intensity aerobic and high-intensity interval training (AT-HIIT) to usual care (UC) in women with breast cancer undergoing chemotherapy. The primary endpoint was CRF and the secondary endpoints were HRQoL and cancer treatment-related symptoms.

    METHODS: Two hundred and forty women planned to undergo chemotherapy were randomized to supervised RT-HIIT, AT-HIIT, or UC. Measurements were performed at baseline and at 16 weeks. Questionnaires included Piper Fatigue Scale, EORTC-QLQ-C30, and Memorial Symptom Assessment Scale.

    RESULTS: The RT-HIIT group was superior to UC for CRF: total CRF (p = 0.02), behavior/daily life (p = 0.01), and sensory/physical (p = 0.03) CRF. Role functioning significantly improved while cognitive functioning was unchanged for RT-HIIT compared to declines shown in the UC group (p = 0.04). AT-HIIT significantly improved emotional functioning versus UC (p = 0.01) and was superior to UC for pain symptoms (p = 0.03). RT-HIIT reported a reduced symptom burden, while AT-HIIT remained stable compared to deteriorations shown by UC (p < 0.01). Only RT-HIIT was superior to UC for total symptoms (p < 0.01).

    CONCLUSIONS: 16 weeks of resistance and HIIT was effective in preventing increases in CRF and in reducing symptom burden for patients during chemotherapy for breast cancer. These findings add to a growing body of evidence supporting the inclusion of structured exercise prescriptions, including HIIT, as a vital component of cancer rehabilitation.

    TRIAL REGISTRATION: Clinicaltrials.gov Registration Number: NCT02522260.

  • 117.
    Mohammad, Sameh
    University of Skövde, School of Life Sciences.
    Long-term depression in the rat hippocampus as a memory model: Interrogating the role of protein synthesis in NMDA- and mGluR-dependent synaptic plasticity2010Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Long-term potentiation (LTP) and depression (LTD) are important forms of activity-dependent synaptic plasticity believed to play a role in memory at the cellular level. It has previously been described that synthesis of new proteins is needed to maintain LTP longer than a few hours. Other reports argue that sufficient proteins for stable LTP are already available. The present study aims to examine the role of protein synthesis in LTD, the presumed mirror mechanism of LTP.

    Experiments were carried out in hippocampal slices from young (12-45 days) and old (12-18 weeks) Sprague-Dawley rats. Extracellular techniques were used to study synaptic responses in the Schaffer-collateral-commissural pathway. Plasticity was induced electrically by low frequency stimulation (2-3 trains at 1 Hz for 15 min) or chemically by brief exposure to certain glutamate receptor agonists (NMDA at 20 µM for 3 min or DHPG at 100 µM for 10 min). Whole slice protein synthesis was quantified by assessing 3H-leucine incorporation.

    Stable LTD (> 8 h) was be obtained by either electrical or chemical activation. Protein synthesis inhibitors anisomycin (40 uM) and cycloheximide (100 uM) both failed to influence the magnitude of LTD. Moreover, no age difference was found, in terms of stable LTD in both young and old rats under inhibition of protein synthesis. The potency of the inhibitors was found to be high, depressing synthesis down to a few percent. It is concluded that sufficient proteins for generating stable LTD are normally present in the brain, implying a large safety-margin for cellular memory.

  • 118.
    Moslemi, Ali-Reza
    et al.
    Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Lindberg, Christopher
    Department of Neurology, Institute of Physiology and Neurological Sciences, University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Johanna
    Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Tajsharghi, Homa
    Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Andersson, Bert
    Department of Cardiology, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Oldfors, Anders
    Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Glycogenin-1 deficiency and inactivated priming of glycogen synthesis2010In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 362, no 13, p. 1203-1210Article in journal (Refereed)
    Abstract [en]

    Glycogen, which serves as a major energy reserve in cells, is a large, branched polymer of glucose molecules. We describe a patient who had muscle weakness, associated with the depletion of glycogen in skeletal muscle, and cardiac arrhythmia, associated with the accumulation of abnormal storage material in the heart. The skeletal muscle showed a marked predominance of slow-twitch, oxidative muscle fibers and mitochondrial proliferation. Western blotting showed the presence of unglucosylated glycogenin-1 in the muscle and heart. Sequencing of the glycogenin-1 gene, GYG1, revealed a nonsense mutation in one allele and a missense mutation, Thr83Met, in the other. The missense mutation resulted in inactivation of the autoglucosylation of glycogenin-1 that is necessary for the priming of glycogen synthesis in muscle.

  • 119.
    Mårtensson, Lena
    University of Skövde, School of Life Sciences.
    Sterile water injections and acupuncture as treatment for labour pain2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Most women experience pain during labour. Complementary pain relief methods such as sterile water injections and acupuncture are two alternatives for the child birthing women. The lack of knowledge about the use of these methods in clinical practice creates the need to develop and evaluate them.

    Aims and methods: To elucidate whether the new subcutaneous method of administering sterile water, as well as the previously described intracutaneous injection method, were effective for the relief of labour pain. Ninety-nine women in labour were randomized to either intracutaneous- , subcutaneous injections of sterile water or to placebo (Paper I). To investigate if there was any difference in perceived pain between the intracutaneous and subcutaneous techniques during injection of sterile water. One hundred female volunteers were given injections with both techniques in a cross-over trial (Paper II). To elucidate the clinical use of acupuncture and sterile water injections as pain relief and relaxation during childbirth in Swedish delivery wards. Five hundred and sixty-five midwives answered a questionnaire about their use of these methods (Paper III). To elucidate if there were any differences between acupuncture and sterile water injections in terms of pain relief and relaxation during labour. One hundred and twenty-eight pregnant women in childbirth were randomized to either sterile water injections or acupuncture (Paper IV).

    Results: Paper I: VAS pain scores were significantly lower in both treatment groups 10 minutes (p=0.001) and 45 minutes (p=0.005) after treatment, compared with the placebo group. Paper II: subcutaneous injections were still perceived as less painful than intracutaneous injections after trial, day and injection location were taken into consideration (p<0.001). Paper III: the midwives’ estimated frequency of administration of acupuncture was much higher than that of sterile water injections, 25 % versus 2 %. The intracutaneous injection technique was more common in clinical practice than the subcutaneous technique. Sterile water injections were used exclusively for pain relief during labour while acupuncture was used for both pain relief and relaxation during labour. Paper IV: women given sterile water injections experience significantly less labour pain and a higher degree of relaxation in labour, compared to women given acupuncture (p<0.001).

    Conclusions: The results indicate that the subcutaneous injection technique is preferable when using sterile water injections for low back pain during labour. Sterile water injections seem to provide more pain relief and a higher degree of relaxation, compared to acupuncture. However, acupuncture is a more common pain relief method in clinical practice.

  • 120.
    Mårtensson, Lena B.
    et al.
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Ek, Kristina
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Ekström, Anette
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Bergh, Ingrid H. E.
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Midwifery students' conceptions of worst imaginable pain2014In: Women and Birth, ISSN 1871-5192, E-ISSN 1878-1799, Vol. 27, no 2, p. 104-107Article in journal (Refereed)
    Abstract [en]

    Background: The Visual Analogue Scale (VAS) is one of the most widely used pain assessment scales in clinical practice and research. However, the VAS is used less frequently in midwifery than in other clinical contexts. The issue of how people interpret the meaning of the VAS endpoints (i.e. no pain and worst imaginable pain) has been discussed. The aim of this study was to explore midwifery students' conceptions of 'worst imaginable pain'. Methods: A sample of 230 midwifery students at seven universities in Sweden responded to an open-ended question: 'What is the worst imaginable pain for you?' This open-ended question is a part of a larger study. Their responses underwent manifest content analysis. Results: Analysis of the midwifery students' responses to the open-ended question revealed five categories with 24 sub-categories. The categories were Overwhelming pain, Condition-related pain, Accidents, Inflicted pain and Psychological suffering. Conclusions: The midwifery students' conceptions of 'worst imaginable pain' are complex, elusive and diverse. © 2014 Australian College of Midwives.

  • 121.
    Mårtensson, Lena
    et al.
    University of Skövde, School of Life Sciences.
    Nyberg, Karin
    Department of Health Sciences, University of Göteborg, Sweden.
    Wallin, Gunnar
    Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Sweden.
    Subcutaneous versus intracutaneous injections of sterile water for labour analgesia: a comparison of perceived pain during administration2000In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 107, no 10, p. 1248-1251Article in journal (Refereed)
    Abstract [en]

    Objective To investigate whether, during injections of sterile water, there is any difference in perceived pain between intracutaneous and subcutaneous injections.

    Design Blind controlled trial with cross-over design.

    Setting Göteborg and Skövde, Sweden.

    Participants One hundred healthy female volunteers.

    Methods The women were randomised into two groups and subjected to two trials, within one week of each other. During the first trial one group ( n= 50 ) received the intracutaneous injection first, followed by the subcutaneous injection. The second group ( n= 50 ) was given the subcutaneous injection first, followed by intracutaneous injection. In both groups all the injections were given in reverse order during the second trial.

    Main outcome measures Experienced pain during the administration of sterile water injections, measured by visual analogue scale.

    Results The analysis showed intracutaneous injections to be significantly more painful than subcutaneous injections, even after adjusting for injection day and for left/right site of injection (mean 60.8 vs 41.3,  P < 0.001 ).

    Conclusions The findings suggest that the less painful subcutaneous injection technique should be used.

  • 122.
    Mårtensson, Lena
    et al.
    University of Skövde, School of Life Sciences.
    Stener-Victorin, Elisabet
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci Physiol Endocrinol, Gothenburg, Sweden.
    Wallin, Gunnar
    Univ Gothenburg, Sahlgrenska Acad, Dept Obstet & Gynecol, Gothenburg, Sweden.
    Acupuncture versus subcutaneous injections of sterile water as treatment for labour pain2008In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 87, no 2, p. 171-177Article in journal (Refereed)
    Abstract [en]

    Two methods for pain relief and relaxation during labour are sterile water injections and acupuncture. In several studies, sterile water injections have been shown to provide good pain relief, particularly for low back pain during labour. The acupuncture studies for pain relief during labour are not as concordant. Therefore, the aim of this study was to explore if there were any differences between acupuncture and sterile water injections regarding pain relief and relaxation during labour. METHODS: A randomised controlled trial. Some 128 pregnant women at term were randomly assigned to receive acupuncture (n=62) or sterile water injections (n=66). The primary endpoint was to compare the differences between pre-treatment pain levels and maximum pain in the 2 groups. RESULTS: The main results of this study were that sterile water injections yielded greater pain relief (p<0.001) during childbirth compared to acupuncture. The secondary outcome showed that women in the sterile water group had a higher degree of relaxation (p<0.001) compared to the acupuncture group. The women's own assessment of the effects also favoured sterile water injections (p<0.001). There were no significant differences regarding requirements for additional pain relief after treatment between the 2 groups. CONCLUSIONS: Women given sterile water injection experience less labour pain compared to women given acupuncture.

  • 123.
    Mårtensson, Lena
    et al.
    University of Skövde, School of Life Sciences.
    Wallin, Gunnar
    Dept. of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Labour pain treated with cutaneous injections of sterile water: a randomised controlled trial1999In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 106, no 7, p. 633-637Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate the relief of pain in labour with subcutaneous and intracutaneous injections of sterile water, compared with placebo.

    Design Randomised controlled trial.

    Setting Labour ward with approximately 3000 deliveries annually in a suburban area near Gothenburg, Sweden.

    Participants Ninety-nine pregnant women at term, requiring pain relief for severe lower back pain during the first stage of labour. The women were randomised to receive four injections of 0.1 mL sterile water (without salt) intracutaneously ( n= 33 ), four injections of 0.5 mL sterile water subcutaneously ( n= 33 ) or placebo treatment ( n= 33 ).

    Main outcome measures Reduction of labour pain measured by visual analogue scale.

    Results The median visual analogue scale pain score for labour pain was significantly lower compared with initial values in the two study groups and compared with placebo at 10 and 45 minutes after treatment. The median reductions in visual analogue scores after 10 minutes were 5.0 cm and 4.5 cm in the intracutaneous and subcutaneous injection groups, respectively; women in the placebo group scored a median reduction of 1.7 cm. After 45 minutes the median reductions in the visual analogue scores were 4.9 cm and 4.0 cm in the intracutaneous and subcutaneous injection groups, respectively, compared with 1.0 cm for women in the placebo group. No significant differences in analgesic effect or pain experienced during administration were found between the two study groups.

    Conclusion The new subcutaneous method of administering sterile water, as well as the earlier described intracutaneous injection method, were effective for the relief of pain in labour.

  • 124.
    Nematollahi Mahani, Seyed Alireza
    University of Skövde, School of Health and Education.
    Human placental trophoblast infection with rift valley fever virus and the cell cytokine response to infection2017Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Rift Valley Fever Virus (RVFV) is a Mosquito borne virus (Bunyaviridae family) associated withhemorrhagic fever and abortion in ruminants and humans. Geographic distribution of the virus has expanded to most countries in African continent and in 2001 to Arabian Peninsula resulting in repeated epidemic and epizootic events. With abortion being the hallmark of RVFV infection,Understanding RVFV infection in human placental tissue can provide better insight into disease pathobiology.

    In this study, three human trophoblast cell lines (A3, Jar & BeWo) were evaluated for permissiveness to RVFV infection. Furthermore, the viral capacity to spread by producing progeny viruses in trophoblasts was evaluated. The trophoblast response to infection was additionally assessed by measuring expression levels of important inflammatory cytokines in the cells (IL-1 β, IL-6, IL-8, IL-10, IL15, CSF-2, IFN-g, Fas-L). Finaly, two viral entrance mechanisms suggested for this virus were investigated in these cell models.

    Results suggested high permissiveness of studied trophoblasts cell lines to RVFV, leading to severe cytokine response (IL-8 and IL-1β in Jar and increase in CSF-2, IL-1β, IL-6 and IL-8 in A3 cell line). Since these cytokines are vital in embryonic regulation and development, the severe effect of infection could potentially be part of pathogenesis of virus-induced abortion. When viral entry routes were investigated, heparan sulfate proved to be the main cell entry membrane protein used by RVFV. However removal of all galactosylamintransferases resulted in higher infection rate suggesting presence of other entry mechanisms in absence of galactosylamin transferase. Considering these results and the nature of primary trophoblasts in resisting infection, it is important to evaluate if the primary trophoblasts show the same or similar pattern of sensitivity to RVFV infection with both wild type and mutated viral strains.These findings merit further investigations regarding pregnancy response to infection, vaccination and treatment.

  • 125.
    Nilipour, Yalda
    et al.
    Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Iran.
    Nafissi, Shahriar
    Tehran University of Medical Sciences, Iran.
    Tjust, Anton E.
    Umeå University, Sweden.
    Ravenscroft, Gianina
    The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia.
    Hossein-Nejad Nedai, Hamid
    Shahid Beheshti University of Medical Sciences, Iran.
    Taylor, Rhonda L.
    The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia.
    Varasteh, Vahid
    Shahid Beheshti University of Medical Sciences, Iran.
    Pedrosa Domellöf, Fatima
    Umeå University, Sweden.
    Zangi, Mahdi
    National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Iran.
    Tonekaboni, Seyed Hassan
    Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Iran.
    Olivé, M.
    IDIBELL-Hospital de Bellvitge, Barcelona, Spain.
    Kiiski, Kirsi
    Folkhälsan Institute of Genetics, Medicum, University of Helsinki, Finland.
    Sagath, L.
    Folkhälsan Institute of Genetics, Medicum, University of Helsinki, Finland.
    Davis, Mark R.
    Pathwest, QEII Medical Centre, Nedlands, Western Australia.
    Laing, Nigel G.
    The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia.
    Tajsharghi, Homa
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia.
    Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 6, p. 841-847Article in journal (Refereed)
    Abstract [en]

    Background: Nemaline myopathy has been associated with mutations in twelve genes to date. However, for some patients diagnosed with nemaline myopathy, definitive mutations are not identified in the known genes, suggesting there are other genes involved. This study describes compound heterozygosity for rare variants in RYR3 in one such patient.

    Results: Clinical examination of the patient at 22 years of age revealed a long-narrow face, high arched palate and bilateral facial weakness. She had proximal weakness in all four limbs, mild scapular winging but no scoliosis. Muscle biopsy revealed wide variation in fibre size with type 1 fibre predominance and atrophy. Abundant nemaline bodies were located in perinuclear areas, subsarcolemmal and within the cytoplasm. No likely pathogenic mutations in known nemaline myopathy genes were identified. Copy number variation in known nemaline myopathy genes was excluded by nemaline myopathy targeted array-CGH. Next generation sequencing revealed compound heterozygous missense variants in the ryanodine receptor type 3 gene (RYR3).  RYR3 transcripts are expressed in human fetal and adult skeletal muscle as well as in human brain or cauda equina samples. Immunofluorescence of human skeletal muscle revealed a "single-row" appearance of RYR3, interspaced between the "double-rows" of RYR1 at each A-I junction.

    Conclusion: The results suggest that variants in RYR3 may cause a recessive muscle disease with pathological features including nemaline bodies. We characterize the expression pattern of RYR3 in human skeletal muscle and brain and the subcellular localization of RYR1 and RYR3 in human skeletal muscle.

  • 126.
    Nilsson, J.
    et al.
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Tajsharghi, Homa
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Beta-tropomyosin mutations alter tropomyosin isoform composition2008In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 15, no 6, p. 573-578Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Tropomyosin (TM) is an actin-binding protein, which is localized head to tail along the length of the actin filament. There are three major TM isoforms in human striated muscle. Mutations in beta-tropomyosin (TPM2) have recently been identified as an important cause of neuromuscular disorders.

    MATERIALS AND METHODS: The expression of TM isoforms in patients carrying mutations in TPM2 was detected using a combination of SDS-PAGE, Western blotting, and a new method to measure the relative abundance of the various TM transcripts.

    RESULTS: The level of gamma-TM is reduced in patients with mutations in TPM2. Beta-tropomyosin was expressed at high levels in muscle specimens of the patients.

    DISCUSSION: Our study indicates that beta-TM gene mutations can alter the expression of other sarcomeric TM isoforms and that the perturbation of TM isoform levels may affect the dimer preference within the thin filaments, which may contribute to muscle weakness as a result of both functional and structural changes in muscle.

  • 127.
    Nolskog, Peter
    et al.
    Department of Communicable Disease Control and Prevention, Region of Västra Götaland, Skaraborg Hospital, Skövde, Sweden.
    Backhaus, Erik
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Nasic, Salmir
    Research and Development Centre, Skaraborg Hospital, Skövde, Sweden.
    Enroth, Helena
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Clinical molecular microbiology, Laboratory Medicine, Unilabs, Skövde, Sweden.
    STI with Mycoplasma genitalium: More common than Chlamydia trachomatis in patients attending youth clinics in Sweden2019In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, no 1, p. 81-86Article in journal (Refereed)
    Abstract [en]

    The prevalence of Chlamydia trachomatis in Sweden is well known, whereas the prevalence of Mycoplasma genitalium is less well documented. Youth clinics offer free contraception advice, sexually transmitted infection (STI) testing and/or contact tracing for the age group 15–25 years. The main objective of this study was to determine the prevalence of STIs, the presence of symptoms and the role of contact tracing. From July 2013 to March 2014, 1001 persons, 509 women and 492 men, were included in this study of six youth clinics in the Region of Västra Götaland. Symptoms were registered and whether the patient was tested because of contract tracing. Collection of urine samples, testing, treatment and disease registration were performed according to clinical routines. Urine samples were analysed for C. trachomatis/N. gonorrhoeae on the Cobas 4800 system (Roche). M. genitalium was analysed by lab-developed PCR. Genital infection was present in 16.8%. The prevalence of M. genitalium was higher than for C. trachomatis (9.6% and 7.1%). Men with symptoms have a significantly higher relative risk for infection with M. genitalium or C. trachomatis compared to asymptomatic men, while there is no increase for women. Contact tracing is important since positive outcome has a high relative risk for both infections. The prevalence of M. genitalium was higher than C. trachomatis in this study population. Initial testing for both C. trachomatis and M. genitalium should at least be considered for young men presenting with symptoms of genital infection. In finding positive cases, contact tracing is of great importance. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

  • 128.
    Nygren, Maria
    et al.
    University of Skövde, School of Life Sciences.
    Trojette, Faten
    University of Skövde, School of Life Sciences.
    KVINNORS UPPLEVELSER AV STÖD VID MISSFALL: En litteraturöversikt2009Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    A miscarriage is a big and chaotic event in a woman's life. During this time caregiver has an important role in how women cope with their situation and how they move forward. The purpose of this literature review was to highlight women’s experiences of support at miscarriage. This can help nurses to better understand the woman in her situation in a miscarriage. The method was a literature review according to Friberg (2006). Nine scientific articles formed the base of the review. The results revealed two main areas: emotional support and practical assistance with five different sub-areas: social assistance, professional support, treatment and attitude, follow up and information. It appeared both positive and negative experiences of the provided care. The support and care provided by nurses at an miscarriage should be as good as possible with the idea that each case is individual and unique. This by listening to what the women need and shaping health care for her.

  • 129.
    Ochala, Julien
    et al.
    Department of Clinical Neurophysiology, Uppsala University Hospital, Uppsala, Sweden.
    Li, Mingxin
    Department of Clinical Neurophysiology, Uppsala University Hospital, Uppsala, Sweden / Department of Neurology, Qilu Hospital, Shandong University, Shandong, China.
    Tajsharghi, Homa
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Kimber, Eva
    Department of Neuropaediatrics, Uppsala University Children's Hospital, Sweden.
    Tulinius, Mar
    The Queen Silvia Children's Hospital, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
    Oldfors, Anders
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Larsson, Lars
    Department of Clinical Neurophysiology, Uppsala University Hospital, Uppsala, Sweden / Center for Development and Health Genetics, Pennsylvania State University, University Park, PA, United States.
    Effects of a R133W beta-tropomyosin mutation on regulation of muscle contraction in single human muscle fibres2007In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 581, no 3, p. 1283-1292Article in journal (Refereed)
    Abstract [en]

    A novel R133W beta-tropomyosin (beta-Tm) mutation, associated with muscle weakness and distal limb deformities, has recently been identified in a woman and her daughter. The muscle weakness was not accompanied by progressive muscle wasting or histopathological abnormalities in tibialis anterior muscle biopsy specimens. The aim of the present study was to explore the mechanisms underlying the impaired muscle function in patients with the beta-Tm mutation. Maximum force normalized to fibre cross-sectional area (specific force, SF), maximum velocity of unloaded shortening (V0), apparent rate constant of force redevelopment (ktr) and force-pCa relationship were evaluated in single chemically skinned muscle fibres from the two patients carrying the beta-Tm mutation and from healthy control subjects. Significant differences in regulation of muscle contraction were observed in the type I fibres: a lower SF (P<0.05) and ktr (P<0.01), and a faster V0 (P<0.05). The force-pCa relationship did not differ between patient and control fibres, indicating an unaltered Ca2+ activation of contractile proteins. Collectively, these results indicate a slower cross-bridge attachment rate and a faster detachment rate caused by the R133W beta-Tm mutation. It is suggested that the R133W beta-Tm mutation induces alteration in myosin-actin kinetics causing a reduced number of myosin molecules in the strong actin-binding state, resulting in overall muscle weakness in the absence of muscle wasting.

  • 130.
    Ohlsson, M.
    et al.
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Quijano-Roy, S.
    AP-HP, Service de Pédiatrie, Centre National de Référence des Maladies Neuromusculaires GNMH, Garches, France.
    Darin, N.
    Department of Pediatrics, Sahlgrenska University Hospital, Göteborg, Sweden.
    Brochier, G.
    Institut de Myologie, Groupe Hospitalier Pitie-Salpêtrière, Paris, France.
    Lacène, E.
    Institut de Myologie, Groupe Hospitalier Pitie-Salpêtrière, Paris, France.
    Avila-Smirnow, D.
    AP-HP, Service de Pédiatrie, Centre National de Référence des Maladies Neuromusculaires GNMH, Garches, France.
    Fardeau, M.
    Institut de Myologie, Groupe Hospitalier Pitie-Salpêtrière, Paris, France.
    Oldfors, Anders
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Tajsharghi, Homa
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    New morphologic and genetic findings in cap disease associated with beta-tropomyosin (TPM2) mutations2008In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, no 23, p. 1896-1901Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Mutations in the beta-tropomyosin gene (TPM2) are a rare cause of congenital myopathies with features of nemaline myopathy and cap disease and may also cause distal arthrogryposis syndromes without major muscle pathology. We describe the muscle biopsy findings in three patients with cap disease and novel heterozygous mutations in TPM2.

    METHODS: Three unrelated patients with congenital myopathy were investigated by muscle biopsy and genetic analysis.

    RESULTS: All three patients had early-onset muscle weakness of variable severity and distribution. Muscle biopsy demonstrated in all three patients near uniformity of type 1 fibers and an unusual irregular and coarse-meshed intermyofibrillar network. By electron microscopy, the myofibrils were broad and partly split, and the Z lines appeared jagged. In one of the patients caps structures were identified only by electron microscopy, and in one patient they were identified only in a second biopsy at adulthood. Three novel, de novo, heterozygous mutations in TPM2 were identified: a three-base pair deletion in-frame (p.Lys49del), a three-base pair duplication in-frame (p.Gly52dup), and a missense mutation (p.Asn202Lys).

    CONCLUSIONS: Mutations in TPM2 seem to be a frequent cause of cap disease. Because cap structures may be sparse, other prominent features, such as a coarse-meshed intermyofibrillar network and jagged Z lines, may be clues to correct diagnosis and also indicate that the pathogenesis involves defective assembly of myofilaments.

  • 131.
    Ohlsson, M.
    et al.
    Department of Pathology, Göteborg Neuromuscular Center, Sahlgrenska University Hospital, Göteborg, Sweden.
    Tajsharghi, Homa
    Department of Pathology, Göteborg Neuromuscular Center, Sahlgrenska University Hospital, Göteborg, Sweden.
    Darin, N.
    Department of Pediatrics, Göteborg Neuromuscular Center, Sahlgrenska University Hospital, Göteborg, Sweden.
    Kyllerman, M.
    Department of Pediatrics, Göteborg Neuromuscular Center, Sahlgrenska University Hospital, Göteborg, Sweden.
    Oldfors, Anders
    Department of Pathology, Göteborg Neuromuscular Center, Sahlgrenska University Hospital, Göteborg, Sweden.
    Follow-up of nemaline myopathy in two patients with novel mutations in the skeletal muscle alpha-actin gene (ACTA1)2004In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 14, no 8-9, p. 471-475Article in journal (Refereed)
    Abstract [en]

    Nemaline myopathy has been associated with mutations in five different genes, which all encode protein components of the sarcomeric thin filaments. We report follow-up studies in two children with mutations not previously described in skeletal muscle alpha-actin (ACTA1). Case 1 was a male patient who after birth suffered from pronounced muscle weakness and hypotonia. Muscle biopsy showed small fibers with numerous rods. He failed to achieve any motor milestones. At the age of 17 he required 24 h ventilator support. He could not lift his arms against gravity, but he could use his hands to control his electric wheelchair. The muscle biopsy showed marked replacement of muscle tissue by fat and connective tissue. Only few fibers showed nemaline rods. He had a de novo, heterozygous mutation, G268D in ACTA1. Case 2 was a female patient with feeding difficulties and mild hypotonia in the neonatal period. Muscle biopsy showed hypoplastic muscle fibers and numerous rods. At 11 years of age she walked and moved unhindered and could run fairly well. She had a de novo, heterozygous mutation, K373E, in ACTA1. These two patients illustrate the marked variability in the clinical features of nemaline myopathy in spite of similar muscle pathology in early childhood. The severe muscle atrophy with replacement of fat and connective tissue in case 1 demonstrates the progressive nature of nemaline myopathy in some cases. The described two mutations add to the previously reported mutations in ACTA1 associated with nemaline myopathy.

  • 132.
    Ohlsson, Monica
    et al.
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Hedberg, Carola
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Brådvik, Björn
    Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden.
    Lindberg, Christopher
    Department of Neurology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Tajsharghi, Homa
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Danielsson, Olof
    Division of Neurology, Department of Clinical and Experimental Medicine, University Hospital Linköping, Linköping, Sweden.
    Melberg, Atle
    Department of Neuroscience, Neurology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
    Udd, Bjarne
    Neuromuscular Centre, Tampere University and Hospital, Tampere, Finland / Department of Neurology, Vasa Central Hospital, Vasa, Finland / Folkhälsan Genetic Institute, Department of Medical Genetics, Helsinki University, Helsinki, Finland.
    Martinsson, Tommy
    Department of Clinical Genetics, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Oldfors, Anders
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Hereditary myopathy with early respiratory failure associated with a mutation in A-band titin2012In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 135, no 6, p. 1682-1694Article in journal (Refereed)
    Abstract [en]

    Hereditary myopathy with early respiratory failure and extensive myofibrillar lesions has been described in sporadic and familial cases and linked to various chromosomal regions. The mutated gene is unknown in most cases. We studied eight individuals, from three apparently unrelated families, with clinical and pathological features of hereditary myopathy with early respiratory failure. The investigations included clinical examination, muscle histopathology and genetic analysis by whole exome sequencing and single nucleotide polymorphism arrays. All patients had adult onset muscle weakness in the pelvic girdle, neck flexors, respiratory and trunk muscles, and the majority had prominent calf hypertrophy. Examination of pulmonary function showed decreased vital capacity. No signs of cardiac muscle involvement were found. Muscle histopathological features included marked muscle fibre size variation, fibre splitting, numerous internal nuclei and fatty infiltration. Frequent groups of fibres showed eosinophilic inclusions and deposits. At the ultrastructural level, there were extensive myofibrillar lesions with marked Z-disc alterations. Whole exome sequencing in four individuals from one family revealed a missense mutation, g.274375T>C; p.Cys30071Arg, in the titin gene (TTN). The mutation, which changes a highly conserved residue in the myosin binding A-band titin, was demonstrated to segregate with the disease in all three families. High density single nucleotide polymorphism arrays covering the entire genome demonstrated sharing of a 6.99 Mb haplotype, located in chromosome region 2q31 including TTN, indicating common ancestry. Our results demonstrate a novel and the first disease-causing mutation in A-band titin associated with hereditary myopathy with early respiratory failure. The typical histopathological features with prominent myofibrillar lesions and inclusions in muscle and respiratory failure early in the clinical course should be incentives for analysis of TTN mutations.

  • 133.
    Oldfors, Anders
    et al.
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Tajsharghi, Homa
    Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Darin, Niklas
    Department of Paediatrics, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lindberg, Christopher
    Department of Neurology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Myopathies associated with myosin heavy chain mutations2004In: Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases, ISSN 1128-2460, Vol. 23, no 2, p. 90-96Article in journal (Refereed)
    Abstract [en]

    Myosin, a molecular motor, converts chemical energy into mechanical force. The motor domain of myosin heavy chain (MyHC) includes an ATP binding region with ATPase activity and an actin-binding region. Motor function is achieved by conformational changes, at hydrolysis, of ATP causing a shift in the angle between the actin binding head and the rod region of the molecule. The elongated alpha-helical coiled-coil rod region of MyHC molecules constitutes the major part of the thick filaments of the sarcomere. Three major MyHC isoforms are expressed in human skeletal muscle (type I, MYH7, expressed in type 1 fibres; IIa, MYH2, expressed in 2A fibres; IIx, MYH1, expressed in 2B fibres). While mutations in slow/beta cardiac MyHC (MYH7) are a common cause of familial hypertrophic cardiomyopathy, no skeletal myopathies have, until recently, been associated with mutations in MyHC. A heterozygous mutation, Glu706Lys, in the core of the head of MyHC IIa is associated with a familial congenital myopathy, which, in most instances, has shown mild phenotypic expression in children but progressive course in some adults. There is a relationship between the level of expression of mutated MyHC IIa and muscle pathology. Some adults with a progressive course show muscle fibres with rimmed vacuoles and filaments of the type seen in inclusion body myositis/myopathy (IBM). Endurance training in a group of affected patients caused a shift in the expression of myosin from fast (IIx) to slow (I) isoforms but no reduction in the expression of MyHC IIa. A heterozygous mutation, Arg1845Trp, in the distal rod region of slow myosin (type I, MYH7) is associated with familial congenital myopathy, with large deposits of MyHC I in the subsarcolemmal region of type 1 muscle fibres, "Myosin storage myopathy". These patients showed slowly progressive muscle weakness but no overt cardiomyopathy. These two muscle diseases, which are caused by mutations in MyHC, form the basis of a novel entity: "Myosin myopathies".

  • 134.
    Oldfors, Anders
    et al.
    Göteborg, Sweden.
    Tajsharghi, Homa
    Göteborg, Sweden.
    Thornell, L. E.
    Mutation of the slow myosin heavy chain rod domain underlies hyaline body myopathy2005In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 64, no 3, p. 580-581Article in journal (Refereed)
  • 135.
    Olivé, Montse
    et al.
    Institute of Neuropathology, Department of Pathology and Neuromuscular Unit, Department of Neurology, Barcelona, Spain / CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Barcelona, Spain.
    Abdul-Hussein, Saba
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Oldfors, Anders
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    González-Costello, José
    Department of Cardiology, Barcelona, Spain.
    van der Ven, Peter F. M.
    Department of Molecular Cell Biology, Institute for Cell Biology, University of Bonn, Bonn, Germany.
    Fürst, Dieter O.
    Department of Molecular Cell Biology, Institute for Cell Biology, University of Bonn, Bonn, Germany.
    González, Laura
    Institute of Neuropathology, Department of Pathology and Neuromuscular Unit, Department of Neurology.
    Moreno, Dolores
    Institute of Neuropathology, Department of Pathology, Barcelona, Spain.
    Torrejón-Escribano, Benjamín
    Scientific and Technical Services Facility, Biology Unit, CCiTUB, IDIBELL-University of Barcelona, Barcelona, Spain.
    Alió, Josefina
    Department of Cardiology, Barcelona, Spain.
    Pou, Adolf
    Department of Neurology, Hospital del Mar, Barcelona, Spain.
    Ferrer, Isidro
    Institute of Neuropathology, Department of Pathology, Barcelona, Spain / CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto Carlos III, Barcelona, Spain.
    Tajsharghi, Homa
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    New cardiac and skeletal protein aggregate myopathy associated with combined MuRF1 and MuRF3 mutations: [Human Molecular Genetics, 24, 13, (2015) 3638-3650] DOI: 10.1093/hmg/ddv108 [Erratum]2015In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, no 21, p. 6264-6264Article in journal (Refereed)
  • 136.
    Olofsson, Peder S.
    et al.
    Center for Bioelectronic Medicine, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden / Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Steinberg, Benjamin E.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA / The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
    Sobbi, Roozbeh
    Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
    Cox, Maureen A.
    The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
    Ahmed, Mohamed N.
    Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Oswald, Michaela
    Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Szekeres, Ferenc
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Hanes, William M.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Introini, Andrea
    Department of Medicine, Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Liu, Shu Fang
    Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Holodick, Nichol E.
    Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Rothstein, Thomas L.
    Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Lövdahl, Cecilia
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Chavan, Sangeeta S.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Yang, Huan
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Pavlov, Valentin A.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Broliden, Kristina
    Department of Medicine, Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Andersson, Ulf
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Diamond, Betty
    The Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Miller, Edmund J.
    Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Arner, Anders
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Gregersen, Peter K.
    Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Backx, Peter H.
    Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada / Department of Biology, York University, Toronto, Ontario, Canada.
    Mak, Tak W.
    The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
    Tracey, Kevin J.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Blood pressure regulation by CD4lymphocytes expressing choline acetyltransferase2016In: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 34, no 10, p. 1066-1071Article in journal (Refereed)
    Abstract [en]

    Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4(+) T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals(1). Here we show that these CD4(+)CD44(hi)CD62L(Io) T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T-ChAT). Mice lacking ChAT expression in CD4(+) cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JT(ChAT)) decreased blood pressure when infused into mice. Co-incubation of JT(ChAT) and endothelial cells increased endothelial cell levels of phosphorylated endothelial nitric oxide synthase, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasorelaxant nitric oxide. The isolation and characterization of CD4 T-ChAT cells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.

  • 137.
    Owemyr, Ida
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Enroth, Helena
    Unilabs AB, Skövde, Sweden.
    Ljungström, Lars
    Skaraborg Hospital, Skövde, Sweden.
    Jacobsson, Gunnar
    Skaraborgs Sjukhus, Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Karlsson, Diana
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Evaluation of microarray-based assay for identification of bloodstream bacteria in patients with suspected sepsis2013Conference paper (Refereed)
  • 138.
    Pendharkar, Sonal
    et al.
    Karolinska institutet, Stockholm, Sweden.
    Brandsborg, Erik
    Bifodan AS, Hundested, Denmark.
    Hammarström, Lennart
    Karolinska Institutet, Stockholm, Sweden.
    Marcotte, Harold
    Karolinska Institutet, Stockholm, Sweden.
    Larsson, Per-Göran
    University of Skövde, School of Bioscience. Department of Obstetrics and Gynaecology Kärnsjukhuset, Skaraborg hospital, Skövde, Sweden.
    Vaginal colonisation by probiotic lactobacilli and clinical outcome in women conventionally treated for bacterial vaginosis and yeast infection2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, p. 1-12, article id 255Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to investigate the colonisation by lactobacilli and clinical outcome in women with bacterial vaginosis (BV) and recurrent vulvovaginal candidiasis (R-VVC) receiving antibiotic or anti-fungal treatment in combination with the probiotic EcoVag(R) capsules. Methods: A total of 40 Scandinavian women diagnosed with BV or VVC on the basis of Amsel's criteria or clinical symptoms were consecutively recruited in two pilot open label clinical trials. In trial I, women with BV were treated with clindamycin and metronidazole followed by vaginal EcoVag(R) capsules, containing Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869, for 5 consecutive days after each antibiotic treatment. In trial II, women were recruited in three groups as follows: women with BV receiving clindamycin and metronidazole treatment together with a prolonged administration of EcoVag(R) (10 consecutive days after each antibiotic treatment followed by weekly administration of capsules for next four months), women with R-VVC receiving extended fluconazole and EcoVag(R) treatment, and women receiving extended fluconazole treatments only. The difference in frequency of isolation of EcoVag(R) strains or other lactobacilli between groups was compared by Fisher's exact test. Results: The 6-month cure rate for BV was 50 % in trial I while both the 6- and 12-month cure rates were 67 % in trial II. The 6- and 12-month cure rates for VVC were 100 % and 89 % in women receiving fluconazole and EcoVag(R), and 100 % and 70 % in women receiving fluconazole only. The frequency of isolation of any Lactobacillus species during the course of the study was associated with cure of BV in trial I and II, whereas the frequency of isolation of EcoVag(R) strains was significantly associated with the cure of BV in trial II only. As previously observed, a change in sexual partner was associated with relapse of BV with an Odds ratio of 77 (95 % CI: 2.665 to 2225). Conclusions: The study suggests that the treatment with antibiotics or anti-fungal medication in combination with EcoVag(R) capsules provide long-term cure against BV and R-VVC as compared to previous reports.

  • 139.
    Pokrzywa, Malgorzata
    et al.
    Department of Clinical and Medical Genetics, University of Gothenburg, Sweden.
    Norum, Michaela
    Department of Clinical and Medical Genetics, University of Gothenburg, Sweden.
    Lengqvist, Johan
    Proteomic Core Facility, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Ghobadpour, Mehrnaz
    Department of Clinical and Medical Genetics, University of Gothenburg, Sweden.
    Abdul-Hussein, Saba
    Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Moslemi, Ali-Reza
    Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Tajsharghi, Homa
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Developmental MYH3 Myopathy Associated with Expression of Mutant Protein and Reduced Expression Levels of Embryonic MyHC2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0142094Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    An essential role for embryonic MyHC in foetal development has been found from its association with distal arthrogryposis syndromes, a heterogeneous group of disorders characterised by congenital contractions. The latter probably result from severe myopathy during foetal development. Lack of embryonic muscle biopsy material and suitable animal models has hindered study of the pathomechanisms linking mutations in MYH3 to prenatal myopathy.

    METHODS AND RESULTS:

    We determined the pathomechanisms of developmental myopathy caused by recurrent p.Thr178Ile MYH3 heterozygosity, using patient-derived skeletal muscle cells in culture as an experimental disease model to emulate early embryonic development. These cultured cells were processed for discrimination and quantitative analysis of mutant and wild-type MYH3 alleles and MyHC transcripts, real-time RT-qPCR, sequence analysis, immunofluorescence microscopy, immunoblot, and proteomic assessments. Involvement of the ubiquitin proteasome system was investigated in patients with p.Thr178Ile mutations in MYH3 and MYH2. We found equal overall expression of mutant and wild-type MyHC mRNAs and proteins. Compared to the controls, however, expression of embryonic MyHC transcripts and proteins was reduced whereas expression of myosin-specific E3 ubiquitin ligase (MuRF1) was increased. We also found delayed myofibrillogenesis and atrophic myotubes but structured sarcomeres.

    CONCLUSION:

    In conclusion, this study suggests that developmental p.Thr178Ile MYH3 myopathy is associated with a combined pathomechanism of insufficient dosage of functional embryonic MyHC and production of mutant protein.

  • 140.
    Rafi, Ali
    University of Skövde, School of Life Sciences.
    Estrogen action in growth plate cartilage2011Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
  • 141.
    Retz, Karolina
    et al.
    Department of Clinical Microbiology, Unilabs AB, Skövde.
    Andersson, Sofie
    Department of Clinical Microbiology, Unilabs AB, Skövde .
    Andersson, Carl
    University of Skövde.
    Svensson, Kristina
    Department of Clinical Microbiology, Unilabs AB, Skövde .
    Ljungström, Lars
    The Skaraborg Hospital, Skövde, Sweden .
    Enroth, Helena
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Microbiology, Unilabs AB, Skövde .
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Evaluation of the QuickFISH and the Sepsityper assays for early identification of etiological agents in bloodstream infection in a clinical routine setting2017Conference paper (Refereed)
  • 142.
    Russo, Marika D.
    et al.
    Institute of Food Sciences, CNR, Avellino, Italy.
    Ahrens, Wolfgang
    Leibniz Institute for Prevention Research and Epidemiology BIPS, Bremen, Germany / Institute of Statistics, University of Bremen, Germany.
    De Henauw, Stefaan
    Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Belgium.
    Eiben, Gabriele
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Hebestreit, Antje
    Leibniz Institute for Prevention Research and Epidemiology BIPS, Bremen, Germany.
    Kourides, Yannis
    Research and Education Institute of Child Health, Cyprus.
    Lissner, Lauren
    Section for Epidemiology and Social Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Molnar, Denes
    Department of Paediatrics, University of Pécs, Hungary.
    Moreno, Luis A.
    GENUD (Growth, Exercise, Nutrition and Development) Research Group, University of Zaragoza, Spain.
    Pala, Valeria
    Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
    Veidebaum, Toomas
    National Institute for Health Development, Tallinn, Estonia.
    Siani, Alfonso
    Institute of Food Sciences, CNR, Avellino, Italy.
    Russo, Paula
    Institute of Food Sciences, CNR, Avellino, Italy.
    The impact of adding sugars to milk and fruit on adiposity and diet quality in children: A cross-sectional and longitudinal analysis of the identification and prevention of dietary-and lifestyle-induced health effects in children and infants (IDEFICS) study2018In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, no 10, article id 1350Article in journal (Refereed)
    Abstract [en]

    Sugar, particularly as free sugars or sugar-sweetened beverages, significantly contributes to total energy intake, and, possibly, to increased body weight. Excessive consumption may be considered as a proxy of poor diet quality. However, no previous studies evaluated the association between the habit of adding sugars to “healthy” foods, such as plain milk and fresh fruit, and indicators of adiposity and/or dietary quality in children. To answer to these research questions, we Panalysed the European cohort of children participating in the IDEFICS study. Anthropometric variables, frequency of consumption of sugars added to milk and fruit (SAMF), and scores of adherence to healthy dietary pattern (HDAS) were assessed at baseline in 9829 children stratified according to age and sex. From this cohort, 6929 children were investigated again after two years follow-up. At baseline, a direct association between SAMF categories and adiposity indexes was observed only in children aged 6–<10 years, while the lower frequency of SAMF consumption was significantly associated with a higher HDAS. At the two year follow-up, children with higher baseline SAMF consumption showed significantly higher increases in all the anthropometric variables measured, with the exception of girls 6–<10 years old. The inverse association between SAMF categories and HDAS was still present at the two years follow-up in all age and sex groups. Our results suggest that the habit to adding sugars to foods that are commonly perceived as healthy may impact the adherence to healthy dietary guidelines and increase in adiposity risk as well. 

  • 143.
    Saafan, Tamer
    et al.
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Bashah, Moataz
    Department of Bariatric Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    El Ansari, Walid
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar / College of Medicine, Doha, Qatar.
    Karam, Mohsen
    Department of Bariatric Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
    Histopathological Changes in Laparoscopic Sleeve Gastrectomy Specimens: Prevalence, Risk Factors, and Value of Routine Histopathologic Examination2017In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 27, no 7, p. 1741-1749Article in journal (Refereed)
    Abstract [en]

    Laparoscopic sleeve gastrectomy (LSG) is a common surgical therapeutic option for obese patients, with debate about the value of routine histopathologic examination of LSG specimens. We assessed the following: prevalence of different histopathologic changes in LSG specimens, risk factors associated with premalignant and with frequent histopathologic changes, and whether routine histopathologic examination is warranted for LSG patients with nonsignificant clinical history. Retrospective review of records of all LSG patients operated upon at Hamad General Hospital, Qatar (February 2011-July 2014, n = 1555), was conducted. Risk factors (age, BMI, gender, and Helicobacter pylori) were assessed in relation to specific abnormal histopathologic changes. Mean age and BMI of our sample were 35.5 years and 46.8, respectively. Females comprised 69.7% of the sample. Normal histopathologic specimens comprised 52% of the sample. The most common histopathologic changes were chronic inactive gastritis (33%), chronic active gastritis (6.8%), follicular gastritis (2.7%), and lymphoid aggregates (2.2%). We observed rare histopathology in 3.3% of the sample [e.g., intestinal metaplasia and gastrointestinal stromal tumor (GIST)]. Older age was associated with GIST and intestinal metaplasia (P = 0.001 for both). Females were associated with chronic active gastritis (P = 0.003). H. pylori infection was associated with follicular gastritis, lymphoid aggregates, GIST, intestinal metaplasia, and chronic active gastritis (P < 0.001 for each). Older age, H. pylori, and female gender are risk factors for several abnormal histopathologic changes. Histopathologic examination of LSG specimens might harbor significant findings; however, routine histopathologic examination of all LSG specimens, particularly in the absence of suggestive clinical symptoms, is questionable. The association between female gender and chronic active gastritis; and the association between H. pylori infection and GIST are both novel findings that have not been previously reported in the published literature.

  • 144.
    Saafan, Tamer
    et al.
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, 3050, Qatar.
    El Ansari, Walid
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, 3050, Qatar ; College of Medicine, Qatar University, Doha, 2713, Qatar.
    Al-Yahri, Omer
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, 3050, Qatar.
    Eleter, Ammar
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, 3050, Qatar.
    Eljohary, Hisham
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, 3050, Qatar.
    Alfkey, Rashad
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, 3050, Qatar.
    Hajjar, Mustafa
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, 3050, Qatar.
    Toffaha, Ali
    Department of General Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, 3050, Qatar.
    El Osta, Abdelrahman
    Department of Surgery, AlWakra Hospital, AlWakra, Qatar.
    Assessment of PULP score in predicting 30-day perforated duodenal ulcer morbidity, and comparison of its performance with Boey and ASA, a retrospective study2019In: Annals of Medicine and Surgery, ISSN 2049-0801, Vol. 42, p. 23-28Article in journal (Refereed)
    Abstract [en]

    Background: /aim: Scores commonly employed to risk stratify perforated peptic ulcer patients include ASA (American Society of Anesthesiologists), Boey and peptic ulcer perforation score (PULP). However, few studies assessed and compared the accuracy indices of these three scores in predicting post PPU repair 30-day morbidity. We assessed accuracy indices of PULP, and compared them to Boey and ASA in predicting post perforated duodenal (PDU) ulcer repair 30-day morbidity. Methods: Retrospective chart review of all PDU patients (perforated duodenal ulcers only) at the largest two hospitals in Qatar (N = 152). Data included demographic, clinical, laboratory, operative, and post repair 30-day morbidity. Area under the Curve (AUC), sensitivity and specificity were computed for each of the 3 scores. Multivariate logistic regression assessed the accuracy indices of each score. Results: All patients were males (M age 37.41 years). Post PDU repair 30-day morbidity was 10.5% (16 morbidities). Older age, higher ASA (≥3), Boey (≥1) or PULP (≥8) scores, shock on admission and preoperative comorbidities; and conversely, lower hemoglobin and albumin were all positively significantly associated with higher post PDU 30-day morbidity. PULP displayed the largest AUC (72%), and was the only score to significantly predict 30-day morbidity. The current study is the first to report the sensitivity and specificity of these three scores for post PDU repair 30-day morbidity; and first to assess accuracy indices for PULP in predicting post PDU repair 30-day morbidity. Conclusion: PULP score had the largest AUC and was the only score to significantly predict post PDU repair 30-day morbidity. © 2019 The Author(s)

  • 145.
    Sandman, Nils
    et al.
    Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland / Department of Psychology and Speech Language Pathology, Centre for Cognitive Neuroscience, Turku Brain and Mind Centre, University of Turku, Turku, Finland.
    Merikanto, Ilona
    Department of Health, National Institute for Health and Welfare, Helsinki, Finland / Department of Biosciences, University of Helsinki, Helsinki, Finland.
    Määttänen, Hanna
    Department of Psychology and Speech Language Pathology, Centre for Cognitive Neuroscience, Turku Brain and Mind Centre, University of Turku, Turku, Finland.
    Valli, Katja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Psychology and Speech Language Pathology, Centre for Cognitive Neuroscience, Turku Brain and Mind Centre, University of Turku, Turku, Finland.
    Kronholm, Erkki
    Department of Health, National Institute for Health and Welfare, Turku, Finland.
    Laatikainen, Tiina
    Department of Health, National Institute for Health and Welfare, Helsinki, Finland / Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland / Hospital District of North Karelia, Joensuu, Finland .
    Partonen, Timo
    Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
    Paunio, Tiina
    Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland / Department of Psychiatry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
    Winter is coming: nightmares and sleep problems during seasonal affective disorder2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, no 5, p. 612-619Article in journal (Refereed)
    Abstract [en]

    Sleep problems, especially nightmares and insomnia, often accompany depression. This study investigated how nightmares, symptoms of insomnia, chronotype and sleep duration associate with seasonal affective disorder, a special form of depression. Additionally, it was noted how latitude, a proxy for photoperiod, and characteristics of the place of residence affect the prevalence of seasonal affective disorder and sleep problems. To study these questions, data from FINRISK 2012 study were used. FINRISK 2012 consists of a random population sample of Finnish adults aged 25–74 years (n = 4905) collected during winter from Finnish urban and rural areas spanning the latitudes of 60°N to 66°N. The Seasonal Pattern Assessment Questionnaire was used to assess symptoms of seasonal affective disorder. Participants with symptoms of seasonal affective disorder had significantly increased odds of experiencing frequent nightmares and symptoms of insomnia, and they were more often evening chronotypes. Associations between latitude, population size and urbanicity with seasonal affective disorder symptoms and sleep disturbances were generally not significant, although participants living in areas bordering urban centres had less sleep problems than participants from other regions. These data show that the prevalence of seasonal affective disorder was not affected by latitude. 

  • 146.
    Sandman, Nils
    et al.
    National Institute for Health and Welfare, Public Health Genomics Unit and Institute for Molecular Medicine FIMM, Helsinki, Finland / University of Turku, Centre for Cognitive Neuroscience, Turku Brain and Mind Center, Department of Psychology, Turku, Finland.
    Valli, Katja
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. University of Turku, Centre for Cognitive Neuroscience, Turku Brain and Mind Center, Department of Psychology, Turku, Finland.
    Kronholm, Erkki
    National Institute for Health and Welfare, Department of Health, Unit of Chronic Disease Prevention, Turku, Finland.
    Revonsuo, Antti
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. University of Turku, Centre for Cognitive Neuroscience, Turku Brain and Mind Center, Department of Psychology, Turku, Finland.
    Laatikainen, Tiina
    National Institute for Health and Welfare, Department of Health, Unit of Chronic Disease Prevention, Turku, Finland / University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, Finland / Hospital District of North Karelia, Joensuu, Finland.
    Paunio, Tiina
    National Institute for Health and Welfare, Public Health Genomics Unit and Institute for Molecular Medicine FIMM, Helsinki, Finland / Helsinki University and University Hospital, Department of Psychiatry, Helsinki, Finland.
    Nightmares: Risk factors among the Finnish general adult population2015In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 38, no 4, p. 507-514Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: To identify risk factors for experiencing nightmares among the Finnish general adult population. The study aimed to both test whether previously reported correlates of frequent nightmares could be reproduced in a large population sample and to explore previously unreported associations.

    DESIGN: Two independent cross-sectional population surveys of the National FINRISK Study.

    SETTING: Age- and sex-stratified random samples of the Finnish population in 2007 and 2012.

    PARTICIPANTS: A total of 13,922 participants (6,515 men and 7,407 women) aged 25-74 y.

    INTERVENTIONS: N/A.

    MEASUREMENTS AND RESULTS: Nightmare frequency as well as several items related to socioeconomic status, sleep, mental well-being, life satisfaction, alcohol use, medication, and physical well-being were recorded with a questionnaire. In multinomial logistic regression analysis, a depression-related negative attitude toward the self (odds ratio [OR] 1.32 per 1-point increase), insomnia (OR 6.90), and exhaustion and fatigue (OR 6.86) were the strongest risk factors for experiencing frequent nightmares (P < 0.001 for all). Sex, age, a self-reported impaired ability to work, low life satisfaction, the use of antidepressants or hypnotics, and frequent heavy use of alcohol were also strongly associated with frequent nightmares (P < 0.001 for all).

    CONCLUSIONS: Symptoms of depression and insomnia were the strongest predictors of frequent nightmares in this dataset. Additionally, a wide variety of factors related to psychological and physical well-being were associated with nightmare frequency with modest effect sizes. Hence, nightmare frequency appears to have a strong connection with sleep and mood problems, but is also associated with a variety of measures of psychological and physical well-being.

  • 147.
    Saxenborn, Patricia
    University of Skövde, School of Health and Education.
    Investigating the Effect of 1,25-Dihydroxyvitamin D3 and Retinoic acid on Viability, Differentiation and Migration in NB69 and T47D cells.2016Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Cancer is a well-known disease that many people encounter in their lifetime. There is constantly research being performed on cancer to find treatments for those types where none has been found, or even find better or more efficient treatments for those cancer types where there already is treatment available. Two types of cancer that have been studied in this thesis are neuroblastoma, which is a form of cancer that affects children and infants, and breast cancer. The 13-cis retinoic acid is presently used as treatment for neuroblastoma post-surgery and post-chemo therapy, but the treatment is quite invasive. It has been shown that 1,25-dihydroxyvitamin D3 is a good candidate for cancer treatment, and the aim of this study was to investigate whether a combination of 1,25-dihydroxyvitamin D3 and two forms of retinoic acid, all-trans and 13-cis, could cause synergistic effects on cell viability, invasion, and differentiation of the cells. The two vitamins were combined at different concentrations and ratios to make the different treatments. A proliferation assay with absorbance measurement was performed to determine cell viability, and a migration assay was performed to observe the migratory properties of the cells after treatment. The results concluded that the combined treatments had greater effect than the single treatments on cell viability in both neuroblastoma and breast cancer cells. The results showed that single treatment of 13-cis retinoic acid and combined treatments had the highest effect on invasion and differentiation on neuroblastoma cells.

  • 148.
    Scheynius, Hanna
    et al.
    University of Skövde, School of Life Sciences.
    Lager, Josefin
    University of Skövde, School of Life Sciences.
    Kvinnors upplevelser av stöd från barnmorskor i samband medmedicinsk hemabort: en kvalitativ studie2010Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Medical abortion means termination of pregnancy in a pharmacological way, it can beperformed until the ninth week of pregnancy. Abortion at home means that women completea medical abortion in their homes, it has been allowed in Sweden since 2004. Previous studiesillustrate that women experience abortion at home as more natural than abortion performed athospital. Support can be seen from four different dimensions; informational, instrumental,emotional and appraisal. The aim of the study was to describe women’s experiences ofsupport from midwives in connection to induced medical abortion at home. The method usedis qualitative content analysis with an inductive approach. The collecting of data has beenmade through a questionnaire with open questions. Six women chose to participate in thestudy. The result was divided into six categories and one theme. The result shows that eventhough the women feel vulnerable, they are satisfied with the support they are offered. Thewomen feel that they are well informed, involved and safe; they appreciate the call from themidwife during the day of the abortion, also that the hospital can be reached day and night.

  • 149.
    Scholtes, Rosalie A.
    et al.
    Diabetes Centre, Department of Internal Medicine, Amsterdam University Medical Centres, location VUmc, Amsterdam, Netherlands.
    van Raalte, Daniël H.
    Diabetes Centre, Department of Internal Medicine, Amsterdam University Medical Centres, location VUmc, Amsterdam, Netherlands.
    Correa-Rotter, Ricardo
    Nephrology and Mineral Metabolism, National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City, Mexico.
    Toto, Robert D.
    University of Texas Southwestern Medical Center, Dallas, TX, United States.
    Heerspink, Hiddo J. L.
    Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Netherlands.
    Cain, Valerie
    Bogier Clinical and IT Solutions Inc., Raleigh, NC, United States.
    Sjöström, C. David
    AstraZeneca, Gothenburg, Sweden.
    Sartipy, Peter
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. AstraZeneca, Gothenburg, Sweden.
    Stefánsson, Bergur V.
    AstraZeneca, Gothenburg, Sweden.
    The effects of dapagliflozin on cardio-renal risk factors in patients with type 2 diabetes with or without renin-angiotensin system inhibitor treatment: a post hoc analysis2019In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326Article in journal (Refereed)
    Abstract [en]

    Aims: Renin-angiotensin system inhibitors (RASi) are the most effective treatments for diabetic kidney disease but significant residual renal risk remains, possibly because of other mechanisms of kidney disease progression unrelated to RAS that may be present. Sodium-glucose co-transporter-2 inhibitors reduce albuminuria and may complement RASi by offering additional renal protection. This post hoc analysis investigated the effects of dapagliflozin on cardio-renal risk factors in patients with type 2 diabetes (T2D) with increased albuminuria treated with or without RASi at baseline. Materials and methods: We evaluated the effects of dapagliflozin 10 mg/day over 12–24 weeks across 13 placebo-controlled studies in patients with T2D with a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g at baseline. Patients were divided into two subgroups based on treatment with or without RASi at baseline. Results: Compared with patients with RASi at baseline (n = 957), patients without RASi (n = 302) were younger, had a shorter duration of diabetes (7 vs. 12 years), higher estimated glomerular filtration rate (eGFR) and lower UACR, serum uric acid (sUA), body weight and systolic blood pressure. Placebo-adjusted treatment effects of dapagliflozin on UACR, eGFR, glycated haemoglobin and haematocrit over 24 weeks were similar across groups. Mean reductions in body weight and sUA were more distinct in patients without RASi treatment at baseline. Conclusions: Treatment with dapagliflozin over 24 weeks provides similar clinically relevant improvements in metabolic and haemodynamic parameters, and similar reductions in UACR, in patients with T2D with elevated albuminuria treated with or without RASi at baseline. © 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  • 150.
    Sedghi, Maryam
    et al.
    Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
    Salari, Mehri
    Department of Neurology, Shahid Beheshti University of Medical Science, Tehran, Iran.
    Moslemi, Ali-Reza
    Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Sweden.
    Kariminejad, Ariana
    Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
    Davis, Mark
    Department of Diagnostic Genomics, Pathwest, QEII Medical Centre, Australia.
    Goullée, Hayley
    Centre for Medical Research, University of Western Australia / Harry Perkins Institute for Medical Research, Nedlands, Australia.
    Olsson, Björn
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Laing, Nigel
    Centre for Medical Research, University of Western Australia / Harry Perkins Institute for Medical Research, Nedlands, Australia.
    Tajsharghi, Homa
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. Centre for Medical Research, University of Western Australia / Harry Perkins Institute for Medical Research, Nedlands, Australia.
    Ataxia-telangiectasia-like disorder in a family deficient for MRE11A, caused by a MRE11 variant2018In: Neurology: Genetics, ISSN 2376-7839, Vol. 4, no 6, article id e295Article in journal (Refereed)
    Abstract [en]

    Objective We report 3 siblings with the characteristic features of ataxia-telangiectasia-like disorder associated with a homozygous MRE11 synonymous variant causing nonsense-mediated mRNA decay (NMD) and MRE11A deficiency. Methods Clinical assessments, next-generation sequencing, transcript and immunohistochemistry analyses were performed. Results The patients presented with poor balance, developmental delay during the first year of age, and suffered from intellectual disability from early childhood. They showed oculomotor apraxia, slurred and explosive speech, limb and gait ataxia, exaggerated deep tendon reflex, dystonic posture, and mirror movement in their hands. They developed mild cognitive abilities. Brain MRI in the index case revealed cerebellar atrophy. Next-generation sequencing revealed a homozygous synonymous variant in MRE11 (c.657C>T, p.Asn219=) that we show affects splicing. A complete absence of MRE11 transcripts in the index case suggested NMD and immunohistochemistry confirmed the absence of a stable protein. Conclusions Despite the critical role of MRE11A in double-strand break repair and its contribution to the Mre11/Rad50/Nbs1 complex, the absence of MRE11A is compatible with life. 

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