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    Infection and disinfection of transmucosal implant surfaces "in vitro"

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    Peri-implantitis is an inflammatory process, which is initiated by a biofilm-induced pathway causing a reversible inflammatory reaction in the soft tissues surrounding the implant; however, it may progress into irreversible damage in the surrounding alveolar bone and result in loss of attachment. Modelling any kind of oral biofilm is challenging as up to 700 species have been identified on various surfaces within the mouth. Thus, also data on bacterial colonization and biofilm formation on dental implant surfaces is limited and mostly based on identification of species. However, knowledge about this process, in particular in its early stages, is essential for the development of strategies to prevent and control microbial adherence and biofilm formation. The aims of this study were (i) to develop and validate a flow chamber model to assess peri-implantitis related multispecies biofilm formation; (ii) to test antimicrobial susceptibility of this biofilm; (iii) to evaluate the reliability of commonly used methods and novel isothermal microcalorimetry (IMC) analyses for vitality testing of adherent microorganisms in vitro. An in vitro flow chamber model was developed to study single- and multispecies adhesion to protein-coated surface in reduced nutrient conditions that mimic the clinical situation of peri-implant disease. Adherent single-species model with S. sanguinis was used for antimicrobial susceptibility testing (Original study 1 in Chapter 4) to answer two questions: firstly, how efficient is disinfectant treatment and secondly, to identify discrepancies between the results revealed by different vitality detection methods (commonly applied: staining by Live/dead Baclight kit, conventional culturing; and a novel approach by IMC). Chlorhexidine has been considered for many years the standard in oral infection control, however, the three other disinfectants (povidone-iodine, octenidine dihydrochloride, polyhexanide) showed comparable efficacy against the adherent microorganism. The interpretation of the results of staining and traditional culturing is difficult as major discrepancies were present. The disagreement between the results of the methods can be attributed to different aspects: (i) staining is based on the destruction or integrity of the cell wall; (ii) conventional culturing requires bacteria to be re-suspended prior to cultivation and subsequent quantification of colony-forming units. However, several factors – such as physical damage to the cells by re-suspension or lack of growth due to suboptimal culture conditions – may cause false negative results; (iii) the population of cells that are viable but not cultivable (VBNC), but are still present by staining and microscopy. The IMC is a very sensitive method, which detects heat-flow from all metabolic processes in any living microorganism. The principle of the method is that all living systems produce heat and heat release can be measured calorimetrically without any interference with the processes. In other words, IMC measures heat production or consumption, which is proportional to the rate at which any given chemical, physical or biological process is taking place (i.e., metabolic heat from bacterial growth). Our results on adherent disinfectant-treated S. sanguinis indicate that IMC is a useful tool to avoid the problem with VBNC cells and provides a novel approach in oral microbiology that detects reliably all the cells that are able to resuscitate after disinfectant treatment and thereby may lead to the expression of virulence factors in the colonized sites. In order to study antimicrobial efficacy on a more complex system, a 72-hour biofilm model including S. sanguinis, F. nucelatum and P. gingivalis was created (Original study 2 in Chapter 5). After 72 h, the three species were always detected with similar proportions throughout experiments by microscopic methods. Even, when such stability in the proportions and structure was found, the metabolic activity of biofilms in IMC revealed high heterogeneity. Thus, this heterogeneity suggests that bacteria appear to have intra-species variance affecting their behaviour in biofilms, which is dependent on different factors that are hitherto not well understood. IMC analysis of the behaviour of the three-species biofilm provided a novel opportunity to observe how an intact biofilm acts as an entity when exposed to antibiotics (Original study 3 in Chapter 6). The clinical efficacy of adjuvant antibiotic therapy in the periimplantitis treatment is unclear; in order to gain better understanding the most frequently used antibiotics: amoxicillin, metronidazole and their combination were tested. Additionally, in order to obtain comparable data to the previously published information (Chapter 4), the vitality of adherent single-species of S. sanguinis and P. gingivalis after antibiotic treatment was assessed by vitality staining, conventional culturing and IMC. The results of staining and culturing correlated poorly. This can be due to reasons mentioned earlier, such as limitations of the methods and VBNC cells, but can also be due to the bacteriostatic effects of antibiotics that cannot be reliably detected by staining. Although amoxicillin and metronidazole are considered bactericidal, IMC results suggest that when applied alone, the antibiotics seem to work primarily through bacteriostatic effects; when combined, the efficacy is increased by their synergistic bactericidal action. Furthermore, this indicates that it might not be possible to strictly divide the effects of antibiotics into bacteriostatic and bactericidal, as the results here imply that the effect seems to be dependent on their concentration and combination plus the nature of targeted cells. In conclusion, this study emphasises the need to critically evaluate the results of live/dead staining and conventional culturing as many aspects can affect the outcome of these methods leading to miscalculations on the proportion of cells that are able to resuscitate and express virulence factors on treated sites. Thus, as a novel alternative in oral biofilm research IMC gives new insights helping to monitor the efficacy and dynamics of biofilms and their antimicrobial susceptibility in vitro

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Oral health of patients with severe haematological malignancies and disorders before and after haematopoietic stem cell transplantation

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    ABSTRACT Introduction and objectives: Potentially lethal haematological disorders and malignancies – such as myelodysplastic syndromes, acute and chronic leukaemias, severe aplastic anaemias and lymphomas – represent a heterogeneous group of diseases characterised by alterations in the proliferation and function of blood cells. It was reported decades ago that patients with acute leukaemia (AL) have signs of specific leukaemia-related oral lesions, such as petechias, gingival bleeding, and gingival swelling. Previous studies have also concluded that general dental treatment needs to be high among haematological cancer patients at the time of diagnosis and before cancer treatments, but the data are sparse. Thus, there is a need to gather contemporary information on the state of oral health of these patients. Poor oral health is considered a risk factor for several diseases, including specific cancers, but the associations between oral health and severe haematological malignancies and disorders are unclear. The existing knowledge is based on a limited number of studies and the results are contradictory. Treatments of these disorders and malignancies are often intensive and may include chemotherapy, radiation therapy, and haematopoietic stem cell transplantation (HSCT). Thus, the elimination of possible oral foci has been suggested in oral health protocols for such patients. As well as the disorders and malignancies themselves, their treatments are known to affect oral health. As HSCT procedures and success rates have increased, a growing number of patients have experienced serious short- and long-term side effects and comorbidities. Due to the toxic effects of chemotherapies, total body irradiation, and immunosuppression, HSCT recipients are at risk of oral side effects during and after HSCT. Side effects of the therapy in the oral cavity are common and approximately 80% of patients are affected by comorbidities such as mucositis, hyposalivation, and graft versus host disease (GvHD). The purpose of this thesis was to investigate the oral health parameters of adult patients with severe haematological malignancy or disorder before HSCT and the progression of the oral health parameters post-HSCT. The results were compared with controls of normal population. Additionally, the associations between oral health parameters and hyposalivation with survival were investigated. Methods: A group of 572 adult patients referred for dental examination to University Center for Dental Medicine Basel from Hematological Department of University Hospital Basel between 2008 and 2018 was included in the sub-studies of this thesis. From 2008 to 2016, the data collection was retrospective, and for 2018 prospective. A dental examination conducted included the following: decayed, missing, and filled teeth (DMFT) index; calculation of number of teeth; stimulated salivary flow rate (SSFR); presence of periodontitis; presence of acute infections; panoramic radiographs and if needed, additional radiographs. After HSCT, the presence of oral GvHD was additionally examined. In the longitudinal part of the study, the patients were examined six, 12, and 24 months post-HSCT. The changes in SSFR and influence of SSFR on other oral health parameters and on six-month survival were examined. The control group consisted of 289 adults recruited from the Swiss Bone Marrow Donor Registry of the Blood Transfusion Service SRC Basel, Switzerland. Oral examination was performed for the controls in University Center for Dental Medicine Basel, in a process similar to that previously described – with the exception that radiographs were not taken and, instead, a clinical periodontal status was performed. In the first sub-study (8.1), the final study population included 143 allogeneic HSCT recipients matched with controls by age and sex. In the second sub-study (8.2), a total of 149 patients who had got their haematological diagnosis not more than six months ago were included and compared with a control group of 154 subjects of same mean age. For the longitudinal part of the study (8.3), 269 allogeneic HSCT recipients were included. Results: In the first sub-study (8.1), the mean SSFR and mean DMFT index and number of caries lesions were observed to be poorer among HSCT recipients than controls (all p-values < 0.05). Acute symptomatic infections were observed in nine HSCT recipients (6.3%) and none of the controls. The number of teeth was lower among the HSCT recipients, but no statistically significant difference was observed. Statistically significant differences in the measures of current or previous periodontitis were not observed. In the second sub-study (8.2), where patients with newly diagnosed severe haematological malignancy or disorder were compared with controls, the mean SSFR of the patients was significantly lower than the mean SSFR of the controls (p < 0.005). Additionally, the number of caries lesions was significantly higher in the patient group than in the control group (p < 0.005). There were fewer teeth and a higher DMFT index in the patient group compared to the control group, but the differences were not statistically significant. Acute symptomatic infections were observed in eight (5.4%) patients and in none of the controls (p < 0.01). In the third longitudinal study (8.3), 40 HSCT recipients (14.8%) died within six months after HSCT. Among the deceased recipients, hyposalivation and caries were more common pre-HSCT than in recipients who survived more than six months (p < 0.05). HSCT recipients with hyposalivation pre-HSCT had a higher risk of death (HR: 1.90, 95% CI: 1.00-3.60; p = 0.044) within six months post-HSCT compared to recipients without hyposalivation. Additionally, hyposalivation pre-HSCT was associated with a higher DMFT index score (p < 0.05) and a lower number of teeth (p < 0.005) 24 months post-HSCT in comparison to those without hyposalivation. Conclusions and clinical relevance: Patients with severe haematological disease demonstrated a high prevalence of oral disorders at the time of diagnosis and at the time of pre-HSCT. Hyposalivation and caries were associated with a lower rate of survival in HSCT recipients. In addition, hyposalivation predisposed patients to deterioration of oral health post-HSCT. These findings support the recommendations for early dental examination at the time of diagnosis. Efficient preventive strategies are important to maintain the oral health of these patients

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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