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  • 51.
    Lövgren, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Parvaneh, Hasti
    Academic Centre for Dentistry Amsterdam (ACTA).
    Lobbezoo, Frank
    Academic Centre for Dentistry Amsterdam (ACTA).
    Häggman-Henrikson, Birgitta
    Malmö Högskola.
    Wänman, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Visscher, Corine
    Academic Centre for Dentistry Amsterdam (ACTA).
    Validity of three screening questions in relation to the DC/TMD in a specialized orofacial pain clinicManuscript (preprint) (Other academic)
    Abstract [en]

    Aims: To determine the validity of three screening questions (3Q/TMD) in relation to the

    Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), in a specialized orofacial pain

    clinic.

    Methods: Consecutive patients, >18 years, referred with a TMD complaint to the Orofacial pain

    clinic, Academic Centre for Dentistry Amsterdam, ACTA, the Netherlands, were included in the

    study. The study sample, (n=449) with mean age 44 years (72% females) answered the

    3Q/TMD and the DC/TMD questionnaire before a clinical DC/TMD examination. The 3Q/TMD

    constitutes of two questions on weekly pain from the jaw, face, and temple region, in rest (Q1)

    and on function (Q2), and one function-related question on weekly catching and/or locking of the

    jaw (Q3). Q1 and Q2 were evaluated in relation to a DC/TMD pain diagnosis and Q3 in relation

    to a subgroup of DC/TMD intra-articular diagnosis, referred to as the reference standard.

    Results: In total, 44% of patients received a pain-related DC/TMD diagnosis and 33% an

    intraarticular reference DC/TMD diagnosis. Sensitivity for the two pain screening questions was

    high (0.83-0.94), whereas specificity was low (0.41-0.55). For the function-related question,

    sensitivity was low (0.48), whereas specificity was high (0.96).

    Conclusions: In most TMD-pain patients, the two pain screening questions are positive. The

    high negative predictive values of the two questions on pain (Q1 and Q2) indicate that in

    patients with negative responses, the presence of pain-related TMD is quite unlikely. For the

    functional screening question (Q3), a positive response is indicative for a subgroup of intra-

    articular DC/TMD diagnoses.

  • 52.
    Lövgren, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Parvaneh, Hasti
    Lobbezoo, Frank
    Häggman-Henrikson, Birgitta
    Umeå University, Faculty of Medicine, Department of Odontology. Department of Orofacial Pain and Jaw function, Faculty of Odontology, Malmö University.
    Wänman, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Visscher, Corine Mirjam
    Diagnostic accuracy of three screening questions (3Q/TMD) in relation to the DC/TMD in a specialized orofacial pain clinic2018In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 76, no 6, p. 380-386Article in journal (Refereed)
    Abstract [en]

    Objective: To determine the diagnostic accuracy of three screening questions (3Q/TMD) in relation to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), in a specialized clinic.

    Material and methods: Consecutive patients, >18 years, referred with a possible TMD complaint to the Orofacial Pain and Dysfunction clinic, Academic Centre for Dentistry Amsterdam, the Netherlands, were included in the study. All patients (n = 449; mean age 44 years; 72% females), answered the 3Q/TMD and the DC/TMD questionnaire before a DC/TMD examination. The 3Q/TMD constitutes of two questions on weekly pain from the jaw, face and temple region (Q1), and on function (Q2), and one function-related question on weekly catching and/or locking of the jaw (Q3). Q1 and Q2 were evaluated in relation to a DC/TMD pain diagnosis and Q3 in relation to a subgroup of DC/TMD intra-articular diagnosis, referred to as the reference standard.

    Results: In total, 44% of patients received a pain-related DC/TMD diagnosis and 33% an intra-articular reference DC/TMD diagnosis. Sensitivity for the two pain screening questions was high (0.83–0.94), whereas specificity was low (0.41–0.55). For the function-related question, sensitivity was low (0.48), whereas specificity was high (0.96).

    Conclusions: In a specialized pain clinic, the two pain questions (Q1, Q2) are positive in most patients with pain-related TMD. Therefore, in case of a positive response, further diagnostic procedures for TMD pain are warranted. For the functional screening question (Q3), a positive response is indicative for an intra-articular DC/TMD diagnosis, while in case of a negative outcome, an intra-articular TMD might still be present.

  • 53.
    Lövgren, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Österlund, Catharina
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ilgunas, Aurelija
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lampa, Ewa
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hellström, Fredrik
    A high prevalence of TMD is related to somatic awareness and pain intensity among healthy dental students2018In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 76, no 6, p. 387-393Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Dental students have been identified as a group with high risks of developing both temporomandibular disorders (TMD) and psychosocial conditions. Our primary aim was to evaluate the cross-sectional prevalence of TMD diagnoses, as defined in the Diagnostic Criteria (DC)/TMD, among dental students. The secondary aim was to evaluate the prevalence and association of behavioural and psychosocial factors in relation to DC/TMD diagnoses.

    MATERIALS AND METHODS: The study was conducted among undergraduate dental students during the second semester of their third year at the Department of Odontology, Medical Faculty, Umeå University, Sweden. Three consecutive cohorts were recruited during August in 2013, 2014, 2015. In total, 54 students were included and examined according the DC/TMD procedure.

    RESULTS AND CONCLUSIONS: The prevalence of any DC/TMD diagnosis was 30%. The most prevalent TMD diagnosis was myalgia. Individuals with a TMD-pain diagnosis (i.e. myalgia or arthralgia) reported significantly higher pain intensity levels according to the Graded Chronic Pain Scale (GCPS) as compared to individuals without TMD-pain (Fisher's exact test p < .001, two-sided). In addition, individuals with any TMD scored significantly higher jaw functional limitations according to the Jaw Functional Limitation Scale 20 (JFLS-20, p < .001) and oral parafunctions according to the Oral Behavior Checklist (OBC, p = .005) as compared to individuals without TMD. The psychosocial factors evaluated did not differ between individual with or without a TMD diagnosis. The majority of the dental students reported symptoms that are already identified as risk factors for developing TMD and pain conditions. However, longitudinal data are needed to evaluate how this evolves over time.

  • 54.
    Lövheim, Hugo
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Gilthorpe, Jonathan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Herpes simplex infection and the risk of Alzheimer's disease: a nested case-control study2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 6, p. 587-592Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Herpes simplex virus (HSV) is thought to play an etiological role in the development of Alzheimer's disease (AD).

    METHODS: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years) and 360 age- and sex-matched dementia-free controls, taken on average 9.6 years before AD diagnosis, were analyzed for anti-HSV antibodies (immunoglobulin G, IgG, and immunoglobulin M, IgM) by enzyme-linked immunosorbent assays.

    RESULTS: In the complete sample group, the presence of anti-HSV IgG and IgM antibodies did not increase the risk of AD significantly (odds ratio (OR) 1.636, P = .069 and OR 1.368, P = .299, respectively). In cases with 6.6 years or more between plasma sampling and AD diagnosis (n = 270), there was a significant association between presence of anti-HSV IgG antibodies and AD (OR 2.250, P = .019).

    CONCLUSION: Among persons with a follow-up time of 6.6 years or more, HSV infection was significantly associated with AD.

  • 55.
    Malmbom, Madeleine
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Svahn, Hanna
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Lack of Lipopolysaccharide-induced β-hexosaminidase and TNF-α Release from Human Mast Cells (HMC-1) and Rat Basophilic Cells (RBL-2H3)2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Mast cells are important immune cells that are able to degranulate potent mediators, and participate in infections and inflammatory responses. The process of mast cell degranulation is complex and still partly unknown, especially in bacterial infections caused by endotoxins such as lipopolysaccarides. In this study, we have investigated lipopolysaccharide-induced degranulation of β-hexosaminidase and tumor necrosis factor α in a human mast cell line, HMC-1, and a rat basophilic leukemia cell line, RBL-2H3. We investigated whether the cells expressed the required Toll-like receptor 4 through which lipopolysaccaride activates the mast cell. By using RT-PCR we show that the Toll-like receptor 4 gene is actively transcribed in both cell lines, indicating that the cells could be able to respond to lipopolysaccaride. To analyse the degranulation of β-hexosaminidase, the cells were stimulated with different concentrations of lipopolysaccaride and the extracellular enzyme activity was measured spectrophotometrically. Our results showed that no release could be measured using this method in neither of the cell lines. The release of tumor necrosis factor α was analysed by using enzyme-linked-immunosorbent-assay, and the results indicated that neither lipopolysaccharide, ionomycin, nor 5’-(N-ethylcarboxamido) adenosine had any effect on this process.

    In conclusion, the HMC-1 cell line is not a useful model to study mast cell degranulation in oral infections, and a more reliable in vitro method is needed to investigate the involvement of human mast cells in pathological conditions and to screen for new therapeutic drugs.

  • 56. Mariscal-Munoz, Eduardo
    et al.
    Costa, Carlos A. S.
    Tavares, Hewerson S.
    Bianchi, Jonas
    Hebling, Josimeri
    Machado, João P. B.
    Lerner, Ulf H
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry. Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Souza, Pedro P. C.
    Osteoblast differentiation is enhanced by a nano-to-micro hybrid titanium surface created by Yb:YAG laser irradiation2016In: Clinical Oral Investigations, ISSN 1432-6981, E-ISSN 1436-3771, Vol. 20, no 3, p. 503-511Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to analyze the capacity of a new modified laser surface to stimulate calvarial osteoblasts isolated from neonatal mouse bones to differentiate and form mineralized nodules. Titanium discs were subjectezd or not to laser irradiation according to specific parameters and characterized. Osteoblasts isolated from neonatal mouse calvaria were cultured over the discs, and the capacity of these cells to proliferate (MTT assay), form mineralized nodules (Alizarin red assay), and enhance alkaline phosphatase activity (ALPase activity) was analyzed. Real-time PCR was used for quantification of gene expression. Laser-irradiated titanium discs (L) presented a rough nano-to-micrometric oxidized surface contrasting with the smooth pattern on polished discs (P). The R-a on the micrometric level increased from 0.32 +/- 0.01 mu m on P surfaces to 10.57 +/- 0.39 mu m on L surfaces. When compared with P, L promoted changes in osteoblast morphology, increased mineralized nodule formation in osteoblasts cultured on the surfaces for 14 days, and enhanced ALPase activity at days 7 and 14. Transcription factors triggering osteoblast differentiation (Runx2 and Sp7) and genes encoding the bone extracellular matrix proteins collagen type-1 (Col1a1), osteopontin (Spp1), and osteocalcin (Bglap) were upregulated in cells on L surfaces compared with those on P surfaces at days 1-14. Laser treatment of titanium surfaces created a rough surface that stimulated osteoblast differentiation. Laser treatment of titanium generates a reproducible and efficient surface triggering osteoblast differentiation that can be of importance for osteointegration.

  • 57. Mejàre, Ingegerd A.
    et al.
    Klingberg, Gunilla
    Mowafi, Frida K.
    Stecksén-Blicks, Christina
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Twetman, Svante H. A.
    Tranaeus, Sofia H.
    A Systematic Map of Systematic Reviews in Pediatric Dentistry: What Do We Really Know?2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 2, article id e0117537Article in journal (Refereed)
    Abstract [en]

    Objectives To identify, appraise and summarize existing knowledge and knowledge gaps in practice-relevant questions in pediatric dentistry. Methods A systematic mapping of systematic reviews was undertaken for domains considered important in daily clinical practice. The literature search covered questions in the following domains: behavior management problems/dental anxiety; caries risk assessment and caries detection including radiographic technologies; prevention and non-operative treatment of caries in primary and young permanent teeth; operative treatment of caries in primary and young permanent teeth; prevention and treatment of periodontal disease; management of tooth developmental and mineralization disturbances; prevention and treatment of oral conditions in children with chronic diseases/developmental disturbances/obesity; diagnosis, prevention and treatment of dental erosion and tooth wear; treatment of traumatic injuries in primary and young permanent teeth and cost-effectiveness of these interventions. Abstracts and full text reviews were assessed independently by two reviewers and any differences were solved by consensus. AMSTAR was used to assess the risk of bias of each included systematic review. Reviews judged as having a low or moderate risk of bias were used to formulate existing knowledge and knowledge gaps. Results Out of 81 systematic reviews meeting the inclusion criteria, 38 were judged to have a low or moderate risk of bias. Half of them concerned caries prevention. The quality of evidence was high for a caries-preventive effect of daily use of fluoride toothpaste and moderate for fissure sealing with resin-based materials. For the rest the quality of evidence for the effects of interventions was low or very low. Conclusion There is an urgent need for primary clinical research of good quality in most clinically-relevant domains in pediatric dentistry.

  • 58. Michaud, Dominique S.
    et al.
    Izard, Jacques
    Rubin, Zachary
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Weiderpass, Elisabete
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie Christine
    Clavel-Chapelon, Françoise
    Dossus, Laure
    Kaaks, Rudolf
    Katzke, Verena A.
    Boeing, Heiner
    Foerster, Jana
    Trichopoulou, Antonia
    Naska, Androniki
    Ziara, Giana
    Vineis, Paolo
    Grioni, Sara
    Palli, Domenico
    Tumino, Rosario
    Mattiello, Amalia
    Peeters, Petra H. M.
    Siersema, Peter D.
    Barricarte, Aurelio
    Huerta, José-María
    Molina-Montes, Esther
    Dorronsoro, Miren
    Quirós, J. Ramón
    Duell, Eric J.
    Ohlsson, Bodil
    Jeppsson, Bengt
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Lif, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C.
    Key, Tim J.
    Freisling, Heinz
    Duarte-Salles, Talita
    Stepien, Magdalena
    Riboli, Elio
    Bueno-de-Mesquita, H. Bas
    Lifestyle, dietary factors, and antibody levels to oral bacteria in cancer-free participants of a European cohort study2013In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 24, no 11, p. 1901-1909Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Increasing evidence suggests that oral microbiota play a pivotal role in chronic diseases, in addition to the well-established role in periodontal disease. Moreover, recent studies suggest that oral bacteria may also be involved in carcinogenesis; periodontal disease has been linked to several cancers. In this study, we examined whether lifestyle factors have an impact on antibody levels to oral bacteria.

    METHODS: Data on demographic characteristics, lifestyle factors, and medical conditions were obtained at the time of blood sample collection. For the current analysis, we measured antibody levels to 25 oral bacteria in 395 cancer-free individuals using an immunoblot array. Combined total immunoglobin G (IgG) levels were obtained by summing concentrations for all oral bacteria measured.

    RESULTS: IgG antibody levels were substantially lower among current and former smokers (1,697 and 1,677 ng/mL, respectively) than never smokers (1,960 ng/mL; p trend = 0.01), but did not vary by other factors, including body mass index, diabetes, physical activity, or by dietary factors, after adjusting for age, sex, education, country, and smoking status. The highest levels of total IgG were found among individuals with low education (2,419 ng/mL).

    CONCLUSIONS: Our findings on smoking are consistent with previous studies and support the notion that smokers have a compromised humoral immune response. Moreover, other major factors known to be associated with inflammatory markers, including obesity, were not associated with antibody levels to a large number of oral bacteria.

  • 59.
    Mirzadeh, Sadegh
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    The long-term effect of sinus elevation surgery on the health and thickness of the maxillary sinus membrane. A radiological, retrospective cohort follow up study2015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 60.
    Nemeczek, Hans
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Comparison of Dental Side Effects between Two Oral Appliances for Sleep Apnea - a pilot study2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Oral appliances (OAs) represent a widespread treatment modality for patients with mild to moderate obstructive sleep apnea (OSA). OAs exist in many designs, but it is unknown if there are differences in terms of side effects between the various types. The aim of this pilot study was therefore to evaluate two OA designs, one rigid type of appliance (OAR) and a more flexible one (OAF) regarding increased crowding of the lower front teeth. Six patients with a mean age of 58 years (3 men) who had used OAR and another six patients with a mean age of 63 years (4 men) who had used OAF for at least 2 years were included in the study. The patients responded to a questionnaire and had impressions for plaster casts for analysis of the irregularity in the front teeth using Little's index. The distances between the contacts points between two adjacent teeth were measured in the frontal areas. The OAF group had an increased irregularity of lower front teeth with 0.89 mm (p>0.05) and the OAR group had a reduced irregularity of 0.58 mm (p>0.05). The difference between the groups was significant (p=0.041). There were no changes in crowding of the upper incisors in either group. Patient satisfaction with treatment did not differ between the groups. The present results indicate that a flexible type of OA increase the irregularity of the lower front teeth compared with a more rigid OA. The results should be confirmed in a larger sample.

  • 61.
    Nordstrand, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Larsson, Andreas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lerner, Ulf H
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Inhibition of the insulin-like growth factor-1 receptor enhances effects of Simvastatin on prostate cancer cells in co-culture with bone2013In: Cancer Microenvironment, ISSN 1875-2292, E-ISSN 1875-2284, Vol. 6, no 3, p. 231-240Article in journal (Refereed)
    Abstract [en]

    Prostate cancer (PC) bone metastases show weak responses to conventional therapies. Bone matrix is rich in growth factors, with insulin-like growth factor-1 (IGF-1) being one of the most abundant. IGF-1 acts as a survival factor for tumor cells and we speculate that bone-derived IGF-1 counteracts effects of therapies aimed to target bone metastases and, consequently, that therapeutic effects could be enhanced if given in combination with IGF-1 receptor (IGF-1R) inhibitors. Simvastatin inhibits the mevalonate pathway and has been found to induce apoptosis of PC cells. The aims of this study were to confirm stimulating effects of bone-derived IGF-1 on PC cells and to test if IGF-1R inhibition enhances growth inhibitory effects of simvastatin on PC cells in a bone microenvironment. The PC-3 and 22Rv1 tumor cell lines showed significantly induced cell growth when co-cultured with neonatal mouse calvarial bones. The tumor cell IGF-1R was activated by calvariae-conditioned media and neutralization of bone-derived IGF-1 abolished the calvarium-induced PC-3 cell growth. Treatment of PC-3 and 22Rv1 cells with simvastatin, or the IGF-1R inhibitor NVP-AEW541, reduced tumor cell numbers and viability, and induced apoptosis. Combined simvastatin and NVP-AEW541 treatment resulted in enhanced growth inhibitory effects compared to either drug given alone. Effects of simvastatin involved down-regulation of IGF-1R in PC-3 and of constitutively active androgen receptor variants in 22Rv1 cells. In conclusion, we suggest that IGF-1 inhibition may be a way to strengthen effects of apoptosis-inducing therapies on PC bone metastases; a possibility that needs to be further tested in pre-clinical models.

  • 62. Nyholm, Maria
    et al.
    Lissner, Lauren
    Hörnell, Agneta
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Winkvist, Anna
    Exploring dietary patterns, obesity and sources of bias: the Västerbotten Intervention Programme (VIP)2013In: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 16, no 4, p. 631-638Article in journal (Refereed)
    Abstract [en]

    Objective: Dietary patterns capture the overall diet and thereby provide information on how nutrients are consumed in combinations, and have been suggested to be a better method than studying single nutrients. The present study explored the relationship between dietary patterns at baseline and incidence of obesity at 10-year follow-up in women.

    Design: A longitudinal study using baseline measurements from 1992-1996, including food intake, medication, heredity, socio-economic status, lifestyle and measured body composition, and follow-up data collected in 2002-2006 including measured body composition.

    Setting: Data from the Västerbotten Intervention Programme (VIP) in Sweden.

    Subjects: A total of 6545 initially non-obese women aged 30-50 years.

    Results: Among women reporting plausible energy intakes, the 'Fruit and vegetables cluster' predicted the highest incidence of obesity (OR = 1·76, 95 % CI 1·11, 2·76; P = 0·015) compared with women in the other food pattern groups combined. When adjusting for metabolic factors and BMI at baseline, the risk for obesity in the 'Fruit and vegetables cluster' was attenuated to non-significance. In contrast, high intake of fruit per se was associated with a decreased risk of developing obesity (OR = 0·69, 95 % CI 0·51, 0·91; P = 0·010).

    Conclusions: Dietary pattern groups identified by cluster analysis are likely to reflect characteristics in addition to diet, including lifestyle, previous and current health status and risk factors for future disease, whereas intake of fruit per se was a stable indicator and less affected by baseline characteristics. These results underscore the need for complementary methods in understanding diet-disease relationships.

  • 63.
    Nylander, Åsa
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Structural and functional studies of streptococcal surface adhesins2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The oral cavity is home to an array of microorganisms that are associated with dental plaque. Some Gram-positive bacteria are common inhabitants of the oral cavity and in order to colonize such a unique environment adhesion becomes essential and is accomplish by adhesins expressed on the bacterial surface. Adhesins can interact with host molecules or with structures on the resident oral microbial flora. Members of the antigen I/II (AgI/II) protein family are commonly found on the surface of oral streptococci and have the unique feature that their putative adhesin domain is located in the centre of the primary sequence. Crystal structures representing parts of the C-terminal domains from two AgI/II members, SpaP from Streptococcus mutans and AspA from Streptococcus pyogenes, were determined to 2.2 and 1.8 Å resolution respectively. The structures are very similar and consist of two domains with DEv-IgG folds. The proteins are stabilized by intramolecular isopeptide bonds and tightly coordinated metal ions.

    Another group of surface proteins is the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) that have their putative adhesin domain in the N-terminal, presented on a stalk formed by multiples of repeated C-terminal domains. Sgo0707 from Streptococcus gordonii is an example of this group of proteins and its N-terminal domain was determined to 2.1 Å resolution. The structure consists of two domains, N1 and N2, both of which adopt β-sandwiches. In the Sgo0707 structure no isopeptide bonds or metal ions were detected. A putative binding cleft is present in the N1 domain. Functional studies revealed collagen type-1 and keratinocytes as possible binding partners.

    In order to further characterize the AgI/II protein AspA from S. pyogenes a long form of the protein, AspA-AVPC, was expressed and purified. During the purification process it was observed that the protein fragmented into two major parts. This process could be inhibited by the addition of 0.5 mM EDTA during protein purification.

    In conclusion, these studies have resulted in adding to the knowledge of protein structures and function of streptococcal surface proteins.

  • 64.
    Nylander, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Hall, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jenkinson, H
    Persson, Karina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Expression and purification of Streptococcus pyogenes adhesin AspAManuscript (preprint) (Other academic)
  • 65.
    Näsström, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Fallgren, Jakob
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wänman, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lövgren, Anna
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    The implementation of a decision-tree did not increase decision-making in patients with temporomandibular disorders in the public dental health service2019In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 77, no 5, p. 394-399Article in journal (Refereed)
    Abstract [en]

    Objective: Many patients with temporomandibular disorders (TMD) seem to go undetected within primary dental health care. Primarily we evaluated if the implemented intervention increased the clinical decision-making for TMD patients; secondarily we evaluated if other factors could be identified that predicted performed or recommended TMD treatment.

    Material and Methods: This case–control study was carried out within the Public Dental Health service in Västerbotten County, Sweden. An intervention based on a decision-tree with three screening questions for TMD (3Q/TMD) was implemented during 2015 in four clinics and compared with the remaining county. A total of 400 individuals were selected—200 3Q-positives and 200 3Q-negatives. The 3Q/TMD consists of Q1—frequent jaw pain, Q2—frequent pain on function, and Q3—frequent catching and/or locking of jaw. The 3Q/TMD answers were analyzed in relation to TMD treatment and any TMD related decision that was collected from the digital dental records.

    Results: The intervention did not increase the frequencies of traceable clinical decisions among patients with TMD.

    Conclusions: Despite the implemented intervention aimed, the indicated undertreatment of patients with TMD remains. Future studies are still needed to gain a deeper understanding of the clinical decision-making process for TMD patients in general practice dentistry.

  • 66.
    Peltola, Helen
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Viklund, Magnus
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Behaviour and Knowledge about Dental Caries Prevention among Odontology Students in Sweden2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Dental personnel have an important role in informing the general public about dental care and the positive effect of fluoride. The aim of this study was to investigate how studying at an odontology programme influences knowledge, behaviour and attitudes about dental care and fluoride. A questionnaire was constructed and distributed to odontology students at a basic and an advanced level of their studies at the University of Umeå and at the Karolinska Institute. Students at an Engineering programme at the University of Umeå, 7th semester, functioned as a control group. The questionnaire consisted of questions referring to habits and knowledge about oral care and fluoride. The students at an advanced level of an odontology programme were those who self-estimated their oral care behaviour as highest, followed by students at a basic level and then by students at the engineering programme. The knowledge about the positive and negative effects of fluoride was highest at the advanced level of the odontology programmes while the engineering programme showed the lowest knowledge. In conclusion the way of informing patients about the positive and negative effects of fluoride has to be improved in order to prevent the dental health from declining due to lack of knowledge in the public. But there should always be an individual assessment considering the patient’s age, the risk of developing dental caries and the amount of fluoride in the patient’s drinking water.    

     

  • 67.
    Pettersson, Mattias
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    On titanium release from dental implants and the inflammatory response2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In dentistry, dental implants have become a standard treatment for single tooth loss and partial and total edentulism since their introduction by P-I Brånemark in the 1960s. Long-term follow-up studies have shown that dental implantation is a predictable treatment, with an overall implant survival over ninety-five percent. Mucositis and peri-implantitis are types of inflammation in the peri-implant soft tissue, and the latter occurs with the simultaneous loss of supporting bone. The pathogenesis of mucositis and peri-implantitis is considered a microbial infection in the peri-implant tissue that causes bone loss induced by inflammation. Immune and resident cells are activated by bacterial products and toxins, which induce the release of a cascade of proinflammatory cytokines and chemokines that can activate osteoclasts and cause further bone resorption. Noninfection-induced inflammatory reactions caused by wear particles from an orthopedic implant leading to loss of the prosthesis is a well-known condition in orthopedics. This immune response induced by metal particles has been shown to act by the assembly of a protein complex, i.e., an inflammasome, in macrophages, leading to the release of proinflammatory cytokines, e.g., interleukin 1 beta (IL-1β). Whether metal particles from a dental implant are associated in the pathogenesis of peri-implantitis has not yet been investigated thoroughly. Although titanium dioxide (TiO2) nanoparticles are known to induce a proinflammatory response, the relation between titanium (Ti) and peri-implantitis is not known.

    The overall aim of this thesis was to gain knowledge of the proinflammatory capacity of Ti and its potential association with the pathogenesis of peri-implantitis. The null hypothesis in this thesis is that Ti has no proinflammatory effect.

    To investigate the proinflammatory capacity of Ti, we exposed macrophages derived from a human cell line and monocytes isolated from human blood to Ti. We identified the activation and release of the proinflammatory cytokine IL-1β after the exposure of human macrophages to Ti ions, indicating activation of the inflammasome complex. A five-fold increase in the release of IL-β was found when cells were primed with bacterial products, e.g., Escherichia coli lipopolysaccharide (E. coli LPS) prior to exposure to Ti in culture medium. The proinflammatory effect of Ti was shown to be mediated by metal-protein aggregates formed in the medium and phagocytosed by macrophages. 

    The exposure of macrophages to E. coli LPS mediates the production of intracellular pro-IL-1β, and a second stimulus is needed to cleave the proform of the cytokine, resulting in active IL-1β. Caspase-1, an intracellular protein, is activated through the assembly of the inflammasome complex and is needed for the activation of pro-IL-1β into its active form. Our findings indicate that the Ti-induced activation and release of IL-1β is mediated through the inflammasome complex, as the effect was reduced in the presence of a caspase-1 inhibitor. Peri-implantitis and periodontitis soft tissue samples were investigated chemically and microscopically, and a high content of Ti could be identified in the peri-implantitis tissue samples. The Ti particles identified in the peri-implantitis soft tissue might aggravate the inflammatory response and jeopardize the peri-implant treatment outcome. Transmission electron microscopy (TEM) was used to visualize the formed Ti-protein aggregates, and we discovered that the morphology of the aggregates differed in the presence of cobalt (Co). By microscopy, we could show the uptake of Ti-protein aggregates into macrophage phagolysosomes and that the location of these aggregates differed when Co was present. The origin of the Ti particles found in peri-implantitis soft tissue is unknown, but we could show that Ti is abraded from the implant during insertion into the bone. This abrasion of Ti from the implant surface into the bone is more prominent from an implant with a rough surface than with a smooth surface. 

    We can conclude that Ti can act as a secondary stimulus to macrophages and activate the release of active IL-1β via inflammasome complex assembly. Additionally, Ti forms metal-protein aggregates with a proinflammatory effect that can be inhibited by the presence of Co. Peri-implantitis soft tissue samples contained high concentrations of Ti and metal fragments. Lastly, Ti particles are abraded from the implant during insertion into the bone in amounts that could be proinflammatory. The proinflammatory effect induced by Ti can act in synergy with infection-induced inflammation and cause an imbalance in the host response, leading to the progression of peri-implantitis. The null hypothesis could be rejected.

  • 68.
    Pettersson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Pettersson, Jean
    Department of Chemistry - BMC, Analytical Chemistry, Uppsala, University.
    Molin Thorén, Margareta
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Effect of cobalt ions on the interaction between macrophages and titanium2018In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, no 9, p. 2518-2530Article in journal (Refereed)
    Abstract [en]

    Inflammation and bone reduction around dental implants are described as periimplantitis and can be caused by an inflammatory response against bacterial products and toxins. Titanium (Ti) forms aggregates with serum proteins, which activate and cause release of the cytokine interleukin (IL-1β) from human macrophages. It was hypothesized that cobalt (Co) ions can interact in the formation of pro-inflammatory aggregates, formed by titanium. To test this hypothesis, we differentiated THP-1 cells into macrophages and exposed them to Ti ions alone or in combination with Co ions to investigate if IL-1β release and cytotoxicity were affected. We also investigated aggregate formation, cell uptake and human biopsies with inductively coupled plasma atomic emission spectroscopy (ICP-AES) and electron microscopy. Co at a concentration of 100 μM neutralized the IL-1β release from human macrophages and affected the aggregate formation. The aggregates formed by Ti could be detected in the cytosol of macrophages. In the presence of Co, the Ti-induced aggregates were located in the cytosol of the cultured macrophages, but outside the lysosomal structures. It is concluded that Co can neutralize the Ti-induced activation and release of active IL-1β from human macrophages in vitro. Also, serum proteins are needed for the formation of metal-protein aggregates in cell medium. Furthermore, the structures of the aggregates as well as the localization after cellular uptake differ if Co is present in a Ti solution. Phagocytized aggregates with a similar appearance seen in vitro with Ti present, were also visible in a sample from human peri-implant tissue.

  • 69.
    Ramirez, Eusebio
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Elenius, Jesper
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Indications and Frequency of Orthognathic Surgery in Sweden – a Questionnaire Survey2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Orthognathic surgery is today a standard procedure for improving the intermaxillary relationship by moving either one or both jaws surgically. However, statistics for frequency and indication for orthognathic surgery in Sweden are today non-existent. The purpose of the study is to examine indications, frequency and surgical techniques for orthognathic surgery performed in Swedish Oral and Maxillofacial Surgery (OMFS) clinics.

    A questionnaire survey was performed on all Swedish OMFS clinics for the year 2011 to identify gender and age of the patients, surgical techniques, indications, frequency of operations and whether patients underwent one- or two-jaw surgery. A total of 47 out of 50 clinics responded to the survey. According to it, 894 patients were treated with orthognathic surgery. Slightly more women underwent orthognathic surgery than men and 91% of the patients were 26 years or younger. The most common indication was functional and the most common main jaw discrepancy aimed to correct was of sagittal nature. The survey shows great discrepancies between the counties concerning one- vs. two-jaw surgery.

    The results regarding frequency, age and gender distribution in orthognathic surgery was somewhat expected. However, the spread in frequency regarding one- vs. two-jaw surgery between the counties is concerning. The main indication for performing orthognathic surgery in Sweden is by far functional but there is reason to suggest that aesthetic indication is not negligible.

  • 70. Remen, Kirsten M. Robertson
    et al.
    Lerner, Ulf H.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Gustafsson, Jan-Åke
    Andersson, Göran
    Activation of the liver X receptor-beta potently inhibits osteoclastogenesis from lipopolysaccharide-exposed bone marrow-derived macrophages2013In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 93, no 1, p. 71-82Article in journal (Refereed)
    Abstract [en]

    Bacterial-induced bone diseases, such as periodontitis and osteomyelitis, are chronic inflammatory diseases characterized by increased bone destruction as a result of enhanced osteoclastogenesis. The LXR alpha and -beta are important modulators of inflammatory signaling and can potently inhibit RANKL-induced osteoclast differentiation. Here, we investigated the effects of the LXR agonist GW3965 on LPS-induced osteoclast differentiation. Mouse BMMs primed with RANKL for 24 h, then exposed to LPS in the presence of GW3965 for 4 days, formed significantly fewer and smaller TRAP(+)-multinucleated osteoclasts with reduced expression of osteoclast markers (Acp5, Ctsk, Mmp-9, Dc-stamp, and Itg beta 3), along with inhibition of actin ring development. GW3965 was able to repress proinflammatory cytokine (TNF-alpha, IL-1 beta, IL-6, and IL-12p40) expression in BMMs exposed to LPS alone; however, once BMMs entered the osteoclast lineage following RANKL priming, GW3965 no longer inhibited cytokine expression. The inhibitory action of GW3965 involved the Akt pathway but seemed to be independent of MAPKs (p38, ERK, JNK) and NF-kappa B signaling. GW3965 acted in a LXR beta-dependent mechanism, as osteoclast differentiation was not inhibited in BMMs derived from LXR beta-/- mice. Finally, activation of LXR also inhibited differentiation in LPS-exposed mouse RAW264.7 cells. In conclusion, GW3965 acts through LXR beta to potently inhibit osteoclast differentiation from RANKL-primed BMMs in a LPS environment. In this respect, activation of the LXR could have a beneficial, therapeutic effect in the prevention of bacterial-induced bone erosion. 

  • 71.
    Romani Vestman, Nelly
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Chen, Tsute
    Department of Microbiology, The Forsyth Institute, .
    Lif Holgersson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Öhman, Carina
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    454 pyrosequencing characterization of the oral microbiota after 12-week supplementation with lactobacillus reuteri DSM 17938 and PTA 5289Manuscript (preprint) (Other academic)
  • 72.
    Sjöholm, Billie
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Bahrami, Babak
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Prevalence and Identification of Lactobacillus Species Isolated from Infected Root Canals by MALDI-TOF Mass Spectrometry, 16S rRNA Gene Sequencing and API 50 CHL2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Lactobacillus, a part of the commensal oral microflora, is frequently found in infected root canals but is not considered to be an endodontic pathogen. Lactobacilli have proven to be difficult to identify on species level with biochemical and gene sequencing methods. MALDI-TOF is a new identification method and to our knowledge it has not been used on lactobacilli from infected root canals.

    The aims of this study were to evaluate the prevalence of lactobacilli in infected root canals and to examine if MALDI-TOF is a suitable method for identifying lactobacilli species. In the retrospective study, we evaluated 449 microbial samples obtained from 361 patients. In the prospective study, 100 consecutive microbial samples were collected from 93 patients with infected root canals. Twelve clinical isolates from eight patients were obtained and six selected reference strains were included in the study. MALDI-TOF, 16S rRNA gene sequencing and API 50 CHL identification methods were used to identify lactobacilli isolates and reference strains on species level. In conclusion, the prevalence of lactobacilli in infected root canals was 22% in our material. Molars were the most frequent tooth group infected with lactobacilli. For identification of the reference strains, MALDI-TOF performed slightly better than the other methods. The identification of clinical isolates was inconclusive. MALDI-TOF is an inexpensive, simple and rapid method for identification of lactobacilli and performs well in comparison with conventional methods. However, all of the three identification methods used in this study have limitations when differentiating between closely related lactobacilli species.

  • 73. Sundström, Johan
    et al.
    Björkelund, Cecilia
    Giedraitis, Vilmantas
    Hansson, Per-Olof
    Högman, Marieann
    Janson, Christer
    Koupil, Ilona
    Kristenson, Margareta
    Lagerros, Ylva Trolle
    Leppert, Jerzy
    Lind, Lars
    Lissner, Lauren
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Ludvigsso, Jonas F.
    Nilsson, Peter M.
    Olsson, Håkan
    Pedersen, Nancy L.
    Rosenblad, Andreas
    Rosengren, Annika
    Sandin, Sven
    Snackerstrom, Tomas
    Stenbeck, Magnus
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Heart Center, Umeå University, Umeå.
    Weiderpass, Elisabete
    Wanhainen, Ers
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Fortier, Isabel
    Heller, Susanne
    Storgards, Maria
    Svennblad, Bodil
    Rationale for a Swedish cohort consortium2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.

  • 74.
    Svensson, Fabio
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Seifaldin, Ziad
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Are gingivitis, periodontitis and peri- implantitis associated with autoantibodies- A litterature review2018Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction: Periodontal disease is one of the most common inflammatory diseases in the world. A possible autoimmune aspect behind the local tissue destruction in periodontal disease, as a result of the invasion of oral pathogens over time has been reported in previous studies, but the correlation is yet unclear. Purpose: The aim of this literature review was to shed light on the topic if autoantibodies and autoimmune reactions are associated with gingivitis, periodontitis or peri-implantitis and the progression of these inflammatory diseases. Material and methods: A search in the Pubmed database was done resulting in 138 hits. To follow a systematic approach for selecting the studies to include, we used predefined inclusion and exclusion criteria Results: 26 articles studying a broad variety of different autoantibodies was included for this literature review. A vast majority of the included studies were of case-control design and, because of the broad variety and different variables and data, we decided that a meta-analysis could not be performed. Conclusion: Many studies where results could be compared due to similar comparisons, regarding the incidence of periodontal disease and the prevalence of certain autoantibodies, showed opposite results which makes it hard to reach a conclusion. The main part of the included studies were of small size and therefore more comparable studies are needed to clarify the possible association between periodontal disease and an autoimmune reaction mediated by autoantibodies.

  • 75.
    Tahmasebi, Ava
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Skytén, Jennifer
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    An in vitro Study of Drug-induced Degranulation of Human HMC-1 Mast Cells and Rat RBL-2H3 Cells2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Mast cells and basophils participate in biological responses such as inflammation and allergic reactions and contain potent mediators such as histamine and cytokines. Some drugs, for example opioids, are known to trigger mast cell degranulation with the release of immunogenic mediators that may cause severe side effects.

    The aim of this study was to investigate if the human mast cell line HMC-1 is a useful model to study codeine-induced degranulation in vitro. The rat basophilic leukemia RBL-2H3 cell line was used as a reference. Time- and concentration-dependent effects of codeine, compound 48/80, and A23187 on the degranulation of HMC-1 cells and RBL-2H3 cells were investigated by measuring extracellular levels of β-hexosaminidase and [3H]serotonin.

    Neither codeine nor compound 48/80 produced any significant basophil or mast cell degranulation, whereas the calcium ionophore A23187 triggered a degranulation of both cell lines.

    In conclusion, none of the cell lines are useful as relevant, robust and reproducible in vitro models to study drug-induced mast cell degranulation.

  • 76.
    Thulin, Tamara
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Mosally, Kristina
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Bone Formation after Sinus Membrane Elevation and Simultaneous Placement of Implants without Grafting Materials – A Systematic Review2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Background: Rehabilitation of the atrophied edentulous maxilla is complicated. Often the residual bone height is insufficient for implant placement due to crestal bone resorption and pneumatization of the sinus. The most common treatment has been a two-stage surgery using autogenous or synthetic grafting materials placed in the maxillary sinus before implant therapy. The sinus lift technique was introduced by Boyne et al. (1980) and much research has been done to evaluate this technique where the implants have been placed emerging into the sinus without grafting.

    This paper consists of a review of the literature available on sinus membrane elevation with simultaneous implant placement without the use of grafting materials and a comparison between lateral approach sinus floor elevation (LASFE) and osteotome sinus floor elevation (OSFE).

    Materials & Methods: PubMed was used as database to search for articles. Also, relevant journals and systematic reviews were evaluated. Clinical studies with sinus lift without grafting materials with simultaneous implant placement were included. A minimum of 6 months follow-up was an inclusion criteria. Experimental studies and studies with less than ten implants were excluded.

    Results: 22 articles were included, nine studies using LASFE and 13 using OSFE. The implant survival rate was 98.9% and 97.9% respectively. The MBL was 0.4 – 2.1±0.5 mm for LASFE and 0.2±0.8 – 1.4±0.2 mm for OSFE. New bone formation was 1.7±2.0 – 7.9±3.6 mm and 2.2±1.7 – 4.5±1.9 mm respectively.

    Conclusion: This review shows that grafting materials are not necessary to achieve a high implant survival rate. Some advantages with the less invasive non-grafting method are a decreased patient discomfort and a shorter treatment time.

    Both LASFE and OSFE without grafting have good outcomes. The surgeon should choose technique considering personal experience and the individual patient situation.

  • 77.
    Tyler, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Karlsson, Terese
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kumar Gudey, Shyam
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Behnam-Motlagh, Parviz
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Targeting glucosylceramide synthase induction of cell surface globotriaosylceramide (Gb3) in acquired cisplatin-resistance of lung cancer and malignant pleural mesothelioma cells2015In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 336, no 1, p. 23-32Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Acquired resistance to cisplatin treatment is a caveat when treating patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Ceramide increases in response to chemotherapy, leading to proliferation arrest and apoptosis. However, a tumour stress activation of glucosylceramide synthase (GCS) follows to eliminate ceramide by formation of glycosphingolipids (GSLs) such as globotriaosylceramide (Gb3), the functional receptor of verotoxin-1. Ceramide elimination enhances cell proliferation and apoptosis blockade, thus stimulating tumor progression. GSLs transactivate multidrug resistance 1/P-glycoprotein (MDR1) and multidrug resistance-associated protein 1 (MRP1) expression which further prevents ceramide accumulation and stimulates drug efflux. We investigated the expression of Gb3, MDR1 and MRP1 in NSCLC and MPM cells with acquired cisplatin resistance, and if GCS activity or MDR1 pump inhibitors would reduce their expression and reverse cisplatin-resistance.

    METHODS: Cell surface expression of Gb3, MDR1 and MRP1 and intracellular expression of MDR1 and MRP1 was analysed by flow cytometry and confocal microscopy on P31 MPM and H1299 NSCLC cells and subline cells with acquired cisplatin resistance. The effect of GCS inhibitor PPMP and MDR1 pump inhibitor cyclosporin A for 72h on expression and cisplatin cytotoxicity was tested.

    RESULTS: The cisplatin-resistant cells expressed increased cell surface Gb3. Cell surface Gb3 expression of resistant cells was annihilated by PPMP whereas cyclosporin A decreased Gb3 and MDR1 expression in H1299 cells. No decrease of MDR1 by PPMP was noted in using flow cytometry, whereas a decrease of MDR1 in H1299 and H1299res was indicated with confocal microscopy. No certain co-localization of Gb3 and MDR1 was noted. PPMP, but not cyclosporin A, potentiated cisplatin cytotoxicity in all cells.

    CONCLUSIONS: Cell surface Gb3 expression is a likely tumour biomarker for acquired cisplatin resistance of NSCLC and MPM cells. Tumour cell resistance to MDR1 inhibitors of cell surface MDR1 and Gb3 could explain the aggressiveness of NSCLC and MPM. Therapy with GCS activity inhibitors or toxin targeting of the Gb3 receptor may substantially reduce acquired cisplatin drug resistance of NSCLC and MPM cells.

  • 78.
    Tyler, Andreas
    et al.
    Klinisk Kemi.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Karlsson, Terese
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rodsand, Pouria
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Behnam-Motlagh, Parviz
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    The role of exosomes in transferal of acquired cisplatin resistanceManuscript (preprint) (Other academic)
    Abstract [en]

    Background: A major obstacle when treating cancer patients with cisplatin is that cancer often acquires cisplatin resistance during treatment, resulting in poor patient survival time. One important mechanism of cisplatin resistance is thought to be transferal of pro-survival characteristics, such as increased expression of the anti-apoptotic heat shock protein 70 (HSP70) through release and uptake of exosomes, small bioparticles that contain proteins, messenger RNA (mRNA) or micro RNA (miR).

    Methods: We studied the morphology and size distribution of exosomes released by malignant pleural mesothelioma (MPM) and non-small cell lung cancer cells through confocal microscopy and nanoparticle tracking analysis. We assessed whether exosomes extracted from cells of the studied cell lines could fuse with the plasma membrane and introduce HSP70 to the cell surface through confocal microscopy.

    Results: Exosomes secreted from cisplatin-resistant P31res cells and H1299res cells were able to fuse with the plasma membrane and present HSP70 on the surface of cells from the corresponding cell line (P31 and H1299) as well as the cells they originated from.

    Conclusions: Cisplatin resistance transferal through exosomes may lead to better future treatment alternatives.

  • 79.
    Tyler, Andreas
    et al.
    Klinisk Kemi.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rodsand, Pouria
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Karlsson, Terese
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Behnam-Motlagh, Parviz
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Cell membrane expression of HSP70 in cisplatin resistant tumour cells may be targeted through the co-localized glycosphingolipid Gb3Manuscript (preprint) (Other academic)
    Abstract [en]

    Globotriaosylceramide (Gb3) and heat-shock protein 70 (HSP70) are often co-localized on the cell surface of tumours and facilitates metastasis and cisplatin resistance. We hypothesized that targeting Gb3 could also inhibit HSP70 expression in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM).

    Gb3 and HSP70 were co-localized on the cell surface. The glucosylceramide synthaseinhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP), Gb3 synthase siRNA and VT-1 reduced Gb3 and HSP70 expression, while HSP90-inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) increased Gb3 and HSP70. The combination of 17-AAG and VT-1 had a synergistic cytotoxic effect.

    Cell membrane HSP70 expression in cisplatin-resistant tumour cells may be targeted through co-localized Gb3. 

  • 80.
    Tyler, Andreas
    et al.
    Klinisk Kemi.
    Sandberg, Camilla
    Blom, Amanda
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Behnam-Motlagh, Parviz
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Rondahl, Veronica
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Department of Pathology and Wildlife Diseases, National Veterinary Institute, Uppsala, Sweden.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Acquired cisplatin resistance in malignant pleural mesothelioma cells is reversed by both BH3-mimetic obatoclax and IAP-inhibitor AT-406Manuscript (preprint) (Other academic)
    Abstract [en]

    Treatment of malignant pleural mesothelioma (MPM) with cisplatin often leads to acquired resistance with ensuing therapy failure, which may be the consequence of decreased apoptosis due overexpression of anti-apoptotic Bcl-2 family proteins or inhibitor of apoptosis (IAP) family proteins. Pro-apoptotic BH3-mimetics that antagonize the anti-apoptotic Bcl-2 protein family members and IAP inhibitors, which target the IAP family, could re-sensitize resistant MPM cells to cisplatin. We studied the effects of cisplatin, IAP inhibitor AT-406 and the BH3-mimetics ABT-737 and obatoclax on apoptosis and cytotoxicity in a cisplatin-resistant subline of MPM (P31res) and its parental cell line (P31). We used protein arrays and Western blot to study the differences between P31 and P31res cells in apoptosis signal transduction as well as the effects of cisplatin and obatoclax . P31res cells displayed changes in the Bcl-2 family protein expression in response to cisplatin and a massive inhibition of Bcl-x expression by obatoclax. The IAP-binding proteins Smac/Diablo and Htra2 were downregulated in P31res cells and cisplatin further downregulated Htra2. This suggested that Bcl-2 family proteins and IAP-related proteins may play a role in cisplatin resistance in the studied cell lines. Obatoclax decreased IAP protein expression in both P31 and P31res subline cells but addition of cisplatin abolished this effect in P31res cells. The IAP inhibitor AT-406 and BH3-mimetic obatoclax increased cisplatin cytotoxicity and apoptosis. Combined use of obatoclax with IAP inhibition only had a slight additive effect. This warrants further studies of targeting anti-apoptotic Bcl-2 family proteins and IAPs in malignant pleural mesothelioma. 

  • 81.
    van Dijken, Jan W V
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Lindberg, Anders
    A 15-year randomized controlled study of a reduced shrinkage stress resin composite2015In: Dental Materials, ISSN 0109-5641, E-ISSN 1879-0097, Vol. 31, no 9, p. 1150-1158Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this randomized controlled study was to evaluate the long term effectiveness of a reduced shrinkage stress resin composite in Class II restorations. The material was compared intra-individually with a microhybrid resin composite.

    MATERIALS AND METHODS: Each of 50 patients with at least one pair of two similar sized Class II cavities participated (22 female, 28 male, mean age 43 years, range 18-64). Each participant received in each pair, in a randomized way, one Class II restoration performed with a reduced shrinkage stress resin composite (InTen-S) and the other restoration with a microhybrid resin composite restoration (Point 4). Both restorations were placed with an etch-and-rinse bonding system and an oblique layering technique. A total of 106 restorations, 33 premolar and 73 molars, were placed. The restorations were evaluated blindly each year using modified USPHS criteria. The overall performance of the experimental restorations was tested after intra-individual comparison using the Friedmańs two-way analysis of variance test. The hypothesis was rejected at the 5% level.

    RESULTS: At 15 years, 91 restorations were evaluated. The drop out frequency was 15 restorations (5 male, 3 female participants; 2 premolar and 13 molar restorations). Except for 2 participants, who reported slight symptoms during a few weeks after placement, no post-operative sensitivity was observed at the recalls. The overall success rate at 15 years was 77%. Twenty-one non acceptable restorations were observed during the 15 years follow up, 10 InTen-S (21.7%) and 11 Point 4 (24.4%) restorations (p>0.05). Annual failure rates for the resin composites were 1.5% and 1.6%, respectively. The main reasons for failure were secondary caries (8) and resin composite fracture (7). The differences between premolar vs. molar restorations and between restorations in male vs. female participants were not significant. Significant differences were observed between 2-surface vs. 3-surface restorations.

    SIGNIFICANCE: During the 15-year follow up, the reduced shrinkage stress resin composite showed a good clinical durability in Class II cavities, but not significantly better than the control microhybrid resin composite. Secondary caries and material fracture were the main reasons of failure.

  • 82. Vergnaud, Anne-Claire
    et al.
    Romaguera, Dora
    Peeters, Petra H.
    van Gils, Carla H.
    Chan, Doris S. M.
    Romieu, Isabelle
    Freisling, Heinz
    Ferrari, Pietro
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Dartois, Laureen
    Li, Kuanrong
    Tikk, Kaja
    Bergmann, Manuela M.
    Boeing, Heiner
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Dahm, Christina C.
    Luisa Redondo, Maria
    Agudo, Antonio
    Sanchez, Maria-Jose
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Khaw, Kay-Tee
    Wareham, Nick J.
    Crowe, Francesca
    Trichopoulou, Antonia
    Orfanos, Philippos
    Trichopoulos, Dimitrios
    Masala, Giovanna
    Sieri, Sabina
    Tumino, Rosario
    Vineis, Paolo
    Panico, Salvatore
    Bueno-de-Mesquita, H. Bas
    Ros, Martine M.
    May, Anne
    Wirfalt, Elisabet
    Sonestedt, Emily
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Hallmans, Goran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lund, Eiliv
    Weiderpass, Elisabete
    Parr, Christine L.
    Riboli, Elio
    Norat, Teresa
    Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe: results from the European Prospective Investigation into Nutrition and Cancer cohort study2013In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 97, no 5, p. 1107-1120Article in journal (Refereed)
    Abstract [en]

    Background: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. Objective: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. Design: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. Results: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. Conclusion: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.

  • 83. Vermeulen, Esther
    et al.
    Zamora-Ros, Raul
    Duell, Eric J
    Lujan-Barroso, Leila
    Boeing, Heiner
    Aleksandrova, Krasimira
    Bueno-de-Mesquita, H Bas
    Scalbert, Augustin
    Romieu, Isabelle
    Fedirko, Veronika
    Touillaud, Marina
    Fagherazzi, Guy
    Perquier, Florence
    Molina-Montes, Esther
    Chirlaque, Maria-Dolores
    Argueelles, Marcial Vicente
    Amiano, Pilar
    Barricarte, Aurelio
    Pala, Valeria
    Mattiello, Amalia
    Saieva, Calogero
    Tumino, Rosario
    Ricceri, Fulvio
    Trichopoulou, Antonia
    Vasilopoulou, Effie
    Ziara, Gianna
    Crowe, Francesca L
    Khaw, Kay-Thee
    Wareham, Nicholas J
    Lukanova, Annekatrin
    Grote, Verena A
    Tjonneland, Anne
    Halkjaer, Jytte
    Bredsdorff, Lea
    Overvad, Kim
    Siersema, Peter D
    Peeters, Petra HM
    May, Anne M
    Weiderpass, Elisabete
    Skeie, Guri
    Hjartaker, Anette
    Landberg, Rikard
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Sonestedt, Emily
    Ericson, Ulrika
    Riboli, Elio
    Gonzalez, Carlos A
    Dietary flavonoid intake and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition Cohort2013In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 178, no 4, p. 570-581Article in journal (Refereed)
  • 84.
    Vestman, Nelly Romani
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Hasslöf, Pamela
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Keller, Mette K
    Granström, Elisabeth
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Roos, Stefan
    Twetman, Svante
    Stecksen-Blicks, Christina
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Lactobacillus reuteri influences regrowth of mutans streptococci after full-mouth disinfection: a double-blind, randomised controlled trial2013In: Caries Research, ISSN 0008-6568, E-ISSN 1421-976X, Vol. 47, no 4, p. 338-345Article in journal (Refereed)
    Abstract [en]

    This study assessed whether the persistence of Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 in saliva could delay the regrowth of mutans streptococci (MS) after a full-mouth disinfection with chlorhexidine (CHX). A randomised, double-blind, placebo-controlled study with a 6-week intervention period and 3- and 6-month follow-up was performed. 62 healthy subjects with moderate to high counts of MS were randomly assigned to a test group (n = 32) or a placebo group (n = 30). Before onset of the intervention, subjects received two sessions of professional cleaning, flossing, and application of CHX varnish and rinsed their mouth with a CHX solution between the sessions (2 days). Thereafter, the test group used probiotic lozenges (2/day) containing L. reuteri (DSM 17938 and ATCC PTA 5289; 1 × 108 CFU of each strain), and the placebo group used identical lozenges lacking the lactobacilli. Saliva samples were collected and cultured onto selective media, and isolates of L. reuteri as well as DNA directly extracted from saliva were tested by polymerase chain reaction (PCR) with specific primers. Presence of salivary MS was analysed with a chair-side test. L. reuteri was frequently detected by culture during the intervention period but in only 3 test group subjects at follow-ups. Regrowth of MS statistically significantly differed depending on the presence or absence of L. reuteri DSM 17938 detected by PCR. We conclude that cultivable L. reuteri strains may only sporadically be confirmed after termination of the intervention, but subjects with PCR-detected L. reuteridemonstrated slower regrowth of MS.

  • 85.
    Vestman, Nelly Romani
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Timby, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Holgerson, Pernilla Lif
    Umeå University, Faculty of Medicine, Department of Odontology.
    Kressirer, Christine A
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Öhman, Carina
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Tanner, Anne CR
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Characterization and in vitro properties of oral lactobacilli in breastfed infants2013In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 13, p. 193-Article in journal (Refereed)
    Abstract [en]

    Background: Lactobacillus species can contribute positively to general and oral health and are frequently acquired by breastfeeding in infancy. The present study aimed to identify oral lactobacilli in breast and formula-fed 4 month-old infants and to evaluate potential probiotic properties of the dominant Lactobacillus species detected. Saliva and oral swab samples were collected from 133 infants who were enrolled in a longitudinal study (n=240) examining the effect of a new infant formula on child growth and development. Saliva was cultured and Lactobacillus isolates were identified from 16S rRNA gene sequences. Five L. gasseri isolates that differed in 16S rRNA sequence were tested for their ability to inhibit growth of selected oral bacteria and for adhesion to oral tissues. Oral swab samples were analyzed by qPCR for Lactobacillus gasseri.

    Results: 43 (32.3%) infants were breastfed and 90 (67.7%) were formula-fed with either a standard formula (43 out of 90) or formula supplemented with a milk fat globule membrane (MFGM) fraction (47 out of 90). Lactobacilli were cultured from saliva of 34.1% breastfed infants, but only in 4.7% of the standard and 9.3% of the MFGM supplemented formula-fed infants. L. gasseri was the most prevalent (88% of Lactobacillus positive infants) of six Lactobacillus species detected. L. gasseri isolates inhibited Streptococcus mutans binding to saliva-coated hydroxyapatite, and inhibited growth of S. mutans, Streptococcus sobrinus, Actinomyces naeslundii, Actinomyces oris, Candida albicans and Fusobacterium nucleatum in a concentration dependent fashion. L. gasseri isolates bound to parotid and submandibular saliva, salivary gp340 and MUC7, and purified MFGM, and adhered to epithelial cells. L. gasseri was detected by qPCR in 29.7% of the oral swabs. Breastfed infants had significantly higher mean DNA levels of L. gasseri (2.14 pg/uL) than infants fed the standard (0.363 pg/uL) or MFGM (0.697 pg/uL) formula.

    Conclusions: Lactobacilli colonized the oral cavity of breastfed infants significantly more frequently than formulafed infants. The dominant Lactobacillus was L. gasseri, which was detected at higher levels in breastfed than formula-fed infants and displayed probiotic traits in vitro.

  • 86.
    Yacub Natek, Zena
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Gabro, Vivian
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Induced Secretion of IL-1β from THP-1 Cells after Titanium Exposure2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Within the orthopedic field, a post-installation complication such as aseptic inflammation occurs around orthopedic prosthetic implants. Immunological studies within the field have so far been correlating the aseptic osteolytic process to activated macrophages due to phagocytosis of implant wear debris. The activated macrophages respond with an inflammasome mediated secretion of pro-inflammatory mediators Macrophage-polarization is another theory behind the mechanism of aseptic inflammation induced by orthopedic prosthetic implants, leading to a higher ratio of the pro-inflammatory subtype M1-macrophage in the local peri-implant tissue.

    Together with the lack of a true definition of peri-implantitis of dental implants, the mechanisms involved in the pathogenesis remain unravelled. Hence, the aim of our study was to investigate if mechanisms previously mentioned could be correlated to factors involved in pathogenesis of peri-implantitis. We hypothesized that samples of solid titanium and titanium-ions in combination with microbial stimuli could induce an enhanced pro-inflammatory interleukin-1β (IL-1β) secretion from macrophages. This hypothesis was tested in our in vitro experiments, where THP-1 cells (human monocyte cancer cell line) and freshly isolated human macrophages were exposed to solid titanium samples and titanium-ions in the presence of microbial stimuli (Escherichia coli LPS). Results showed that a pro-inflammatory response could be induced from THP-1 cells, due to exposure of titanium-metal and titanium-ions, dependent on the dose/purity of titanium. This indicates that a bacteria-induced inflammatory response could be further enhanced in vicinity to titanium implants.

  • 87. Zamora-Ros, Raul
    et al.
    Rothwell, Joseph A.
    Scalbert, Augustin
    Knaze, Viktoria
    Romieu, Isabelle
    Slimani, Nadia
    Fagherazzi, Guy
    Perquier, Florence
    Touillaud, Marina
    Molina-Montes, Esther
    Maria Huerta, Jose
    Barricarte, Aurelio
    Amiano, Pilar
    Menendez, Virginia
    Tumino, Rosario
    Santucci de Magistris, Maria
    Palli, Domenico
    Ricceri, Fulvio
    Sieri, Sabina
    Crowe, Francesca L.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Grote, Verena
    Li, Kuanrong
    Boeing, Heiner
    Foerster, Jana
    Trichopoulou, Antonia
    Benetou, Vassiliki
    Tsiotas, Konstantinos
    Bueno-de-Mesquita, H. Bas
    Ros, Martine
    Peeters, Petra H. M.
    Tjonneland, Anne
    Halkjaer, Jytte
    Overvad, Kim
    Ericson, Ulrika
    Wallstrom, Peter
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Landberg, Rikard
    Weiderpass, Elisabete
    Engeset, Dagrun
    Skeie, Guri
    Wark, Petra
    Riboli, Elio
    Gonzalez, Carlos A.
    Dietary intakes and food sources of phenolic acids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2013In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, no 8, p. 1500-1511Article in journal (Refereed)
    Abstract [en]

    Phenolic acids are secondary plant metabolites that may have protective effects against oxidative stress, inflammation and cancer in experimental studies. To date, limited data exist on the quantitative intake of phenolic acids. We estimated the intake of phenolic acids and their food sources and associated lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Phenolic acid intakes were estimated for 36 037 subjects aged 35-74 years and recruited between 1992 and 2000 in ten European countries using a standardised 24 h recall software (EPIC-Soft), and their food sources were identified. Dietary data were linked to the Phenol-Explorer database, which contains data on forty-five aglycones of phenolic acids in 452 foods. The total phenolic acid intake was highest in Aarhus, Denmark (1265.5 and 980.7 mg/d in men and women, respectively), while the intake was lowest in Greece (213.2 and 158.6 mg/d in men and women, respectively). The hydroxycinnamic acid subclass was the main contributor to the total phenolic acid intake, accounting for 84.6-95.3% of intake depending on the region. Hydroxybenzoic acids accounted for 4.6-14.4%, hydroxyphenylacetic acids 0.1-0.8% and hydroxyphenylpropanoic acids <= 0.1% for all regions. An increasing south-north gradient of consumption was also found. Coffee was the main food source of phenolic acids and accounted for 55.3-80.7% of the total phenolic acid intake, followed by fruits, vegetables and nuts. A high heterogeneity in phenolic acid intake was observed across the European countries in the EPIC cohort, which will allow further exploration of the associations with the risk of diseases.

  • 88.
    Zanbil, Angela
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Age Related Differences in Muscle Fiber Composition and Capillary Supply of the Human Masseter Muscle2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of the study was to test the hypothesis that aging causes changes in fiber composition and vascular supply in the human masseter muscle that contribute to impaired jaw function in elderly. The myosin heavy chain (MyHC) composition and capillary supply of muscle fibers in functionally different parts of the masseter muscle of six elderly and six young subjects (mean age 74 and 22 years) were analyzed with immunohistochemical and morphological methods.

    The mean muscle fiber area in the old masseter was decreased by 27% compared to the young subjects (1100 vs. 1507 m2, p=0.038). Smaller mean fiber area was observed for all fibers containing only slow MyHCI or fast MyHCII isoforms, but not for fibers co-expressing slow and fast MyHCs. There were no significant differences in the numbers of capillaries around fiber (CAF 1.85 vs. 1.92). When CAF was related to individual fiber area, capillaries around fiber area (CAFA), the capillary supply was significantly higher in elderly (CAFA 1.10 vs. 1.65, p=0.004). This was reflected by a higher capillary density in the old masseter (CD 574 vs. 794, cap/mm2, p=0.002).

    The loss of muscle mass without any reduction in capillary supply, suggests that the capillary network in the human masseter muscle is rather stable against degradation during aging. This finding is in contrast to previous findings in human limbs, where aging has been reported to decrease both fiber size and capillary network in muscles. We conclude that the ageing process might have different impact on jaw and limb muscles.

  • 89. Zheng, Jiaojiao
    et al.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Santoni, Giola
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Xie, Shao-Hua
    Lagergren, Jesper
    Prediabetes and diabetes in relation to risk of gastric adenocarcinoma2019In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 120, no 12, p. 1147-1152Article in journal (Refereed)
    Abstract [en]

    Background: Whether prediabetes or diabetes increases the risk of gastric adenocarcinoma is not clear.

    Methods: This cohort study included 111,198 participants in the Northern Swedish Health and Disease Study. The participants were followed up from November 1985 to April 2017. The exposure to prediabetes or diabetes was assessed by oral glucose tolerance tests and self-reports. The incidence of the outcome gastric adenocarcinoma was identified from the Swedish Cancer Registry. Multivariable Cox regressions were used to analyse the associations between prediabetes or diabetes and the risk of gastric adenocarcinoma, providing hazard ratios (HR) with 95% confidence intervals (CI), with adjustment for sex, age, calendar year, body mass index, tobacco smoking and education level.

    Results: Compared with normoglycaemic participants, the risk of gastric adenocarcinoma was not increased among participants with prediabetes (HR 1.07, 95% CI 0.79–1.44), diabetes (HR 0.77, 95% CI 0.46–1.29) or any of these exposures (HR 0.96, 95% CI 0.73–1.27). No associations were identified between prediabetes or diabetes and the risk of gastric adenocarcinoma in stratified analyses or in analyses separating cardia and non-cardia gastric adenocarcinoma.

    Conclusions: This study does not support the hypothesis that prediabetes or diabetes increases the risk of gastric adenocarcinoma.

12 51 - 89 of 89
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