| 1. |
- Sundell, Anna Lena, 1970-
(författare)
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Children with orofacial clefts : dental caries and health-related quality of life
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. The current understanding on caries and enamel developmental defects prevalence and frequency, caries risk, health-related quality life (HRQoL) and stress response in young children with cleft lip and/or palate (CL/P) are sparse. In this thesis these aspects were investigated in 5- and 10- year-old children with CL/P in comparison to non-cleft children in the same ages.Design. The studies in this thesis have a cross-sectional case-control design. Participants. The study group consisted of 139 children with CL/P (80 children aged 5 years and 59 aged 10 years) and 313 non-cleft controls (144 children aged 5 years and 169 aged 10 years).Method. Caries was scored according to International Caries Detection and Assessment System (ICDAS II) and developmental enamel defects were measured as presence and frequency of hypoplasia and hypomineralization. Oral hygiene was assessed using Quigley-Hein plaque index. Stimulated saliva samples were analyzed for mutans streptococci, lactobacilli, buffering capacity and secretion rates. Information regarding children’s oral hygiene routines, dietary habits and fluoride exposure were collected with questionnaires. Caries risk was evaluated with algorithm-based software, Cariogram while HRQoL was perceived with KIDSCREEN-52. Stress response was analyzed with cortisol concentration in saliva at three different time points using a commercial competitive radioimmunoassay.Results. Caries prevalence (36% versus 18%) and caries frequency (1.2 dmfs versus 0.9 dmfs) was significantly higher in 5-year-old children with CL/P in comparison to non-cleft controls. In 10-yearolds no significant difference was found between children with CL/P and non-cleft controls in caries prevalence (47% versus 38%) or in caries frequency (0.7 DMFS versus 0.5 DMFS). Children with CL/P had significantly higher prevalence of enamel defects, higher counts of salivary lactobacilli and less good oral hygiene. The odds of being categorized with high caries risk were elevated in children with CL/P. Children with CL/P had similar HRQoL and salivary cortisol concentrations as non-cleft controls. However, 10-year-old boys with CL/P had significantly higher cortisol concentrations in the evening than non-cleft boys.Conclusions. Preschool children with CL/P seem to have more caries in the primary dentition than non-cleft controls. Children with CL/P had increased odds of being categorized as high caries risk individuals compared to controls. Some of the contributing factors seem to be higher prevalence of enamel defects, impaired oral hygiene and elevated salivary lactobacilli. Furthermore, as measured with the help of cortisol concentrations in saliva, children with CL/P were not more stressed than noncleft controls and their HRQoL was comparable to a European norm population. It appears that regular comprehensive preventive oral care in children with CL/P is effective in preventing caries development in permanent teeth. However, children with CL/P are at risk of caries development and preventive oral care should be implemented and started earlier than today.
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| 2. |
- Wilms, Torben, 1973-
(författare)
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Squamous cell carcinoma of the head and neck, focusing on Epstein-Barr-virus, programmed cell death ligand 1 and serum lipoproteins
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Squamous cell carcinoma of the head and neck (SCCHN)comprises a large group of tumours including the oral cavity and nasopharyngealarea, and typically affects older males in association with alcohol/tobacco usage.Within the oral cavity, the mobile tongue is the most common site for tumourdevelopment. The incidence of squamous cell carcinoma of the oral tongue(SCCOT) is increasing in younger people, which has been suggested to associatewith other than the traditional risk factors for this disease. Two common humanoncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV)are connected to certain types of SCCHN, in oropharynx and nasopharynxrespectively. The receptor programmed cell death 1 (PD)-1 and its ligandprogrammed cell death ligand 1 (PD-L1) are particularly relevant in immunecheckpoint control, and elevated levels have been seen in various cancer types. Alink between hyperlipidemia and cancer risk has previously been suggested. Theaim of this thesis was to investigate risk factors and prognostic features forSCCHN, by focusing on EBV, PD-L1 and serum lipoproteins.Materials and methods: Ninety-eight cases of SCCOT and 15 cases of tonsillarsquamous cell carcinoma were examined for the presence of EBV-encodedribonucleic acids (EBERs), EBV deoxyribonucleic acid (DNA) and the proteinEBV-encoded nuclear antigen-1 (EBNA-1), using in situ hybridisation,polymerase chain reaction (PCR) and immunohistochemistry respectively. Onehundred and one cases of SCCOT were examined for expression of PD-L1 intumour and surrounding immune cells using Ventana SP263immunohistochemistry assay and a QuickScore (QS) method. An estimation oftumour-infiltrating immune cells was also performed in 25 of the patients.Circulating levels of PD-L1 were measured using an electrochemiluminescenceassay platform in serum from 30 patients. Finally, serum samples from 106patients and 28 healthy controls were investigated for levels of total cholesterol,low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides andlipoprotein(a).Results: In the first study, using an in situ hybridisation kit no EBER transcriptswere detected. No EBV DNA was identified with PCR analysis, andimmunohistochemistry for EBNA-1 was also negative. In the second study, highertumour cell PD-L1 levels were found in females than males (p = 0.019). Forpatients with low PD-L1 in tumour cells, better survival was shown in males thanfemales (overall survival p = 0.021, disease-free survival p = 0.020). Tumourinfiltrating natural killer (NK) T cells, immature dendritic cells (DCs) and M1macrophages correlated positively with tumour cell PD-L1 (p < 0.05). In the laststudy, the only lipoprotein showing significant difference in concentration iiibetween healthy controls and patients was HDL (p = 0.012). Kaplan-Meiersurvival curves showed that patients with high levels of total cholesterol or LDLhad better survival than patients with normal levels (p = 0.028 and p = 0.007respectively). Adjusting for the effects of age at diagnosis, TNM stage and weightchange, multivariate Cox regression models showed LDL to be an independentprognostic factor for both overall (p = 0.010) and disease-free survival (p =0.018).Conclusion: We excluded EBV as a potential player in SCCOT in both old andyoung patients and highlight the importance of appropriate controls for EBVencoded RNA in-situ hybridization (EBER-ISH) when investigating EBV inhuman diseases. Regarding PD-L1, our data supported the significance of genderon tumour cell PD-L1 expression and demonstrated combined effects of genderand PD-L1 levels on clinical outcome in patients with SCCOT. Data also indicatedthe involvement of specific immune cell types in PD-L1-regulated immuneevasion. Looking at serum lipoproteins, we found high LDL levels to be beneficialfor survival outcome in patients with SCCHN. Furthermore, the use of cholesterollowering medicine for prevention or management of SCCHN needs to be carefullyevaluated.
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| 3. |
- Wahlqvist, Moa, 1979-
(författare)
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Health and People with Usher syndrome
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis concerns people with Usher syndrome (USH) and their health. People with USH have a congenital hearing loss of various degrees and an eye disease with a progressive course; for some, the balance is also affected. Three clinical groups have been identified 1, 2 and 3, and 13 genes have currently been identified. USH is the most common cause of deafblindness. Clinical knowledge and the limited research that exists have shown that people with deafblindness can experience difficulties in everyday life. Depression, anxiety and social withdrawal have been described.The general aim of the present thesis was to describe the health of people with USH. The empirical material employed was based on an extensive survey in which people with USH answered two questionnaires concerning health, anxiety, depression, social trust, work, health-care, financial situation, and alcohol and drug use. The focus of the present thesis is on general health, physical health and psychological health, social trust and finance. Three studies in the present theses focus on USH1, 2 and 3, respectively; finally, the fourth study provides an in-group comparison of people with USH. The results of studies I and III are compared with a crosssection of the Swedish population. The results revealed poor physical and psychological health, a lack of social trust and a strained financial situation regardless of clinical diagnosis. The discussion stresses the importance of taking a biopsychosocial approach when describing the health of people with USH, in which previous research is lacking. Additional research should focus on the mechanisms at different levels that affect people with USH and their health from a life- course perspective. Furthermore, research should include a salutogenic perspective to explore the resources and strengths of people with USH.
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| 4. |
- Bruce, Barbro
(författare)
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Problems of language and communication in children; Identification and intervention
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis addresses identification and intervention of language and communication problems in children. The issue of identification is addressed in study I by investigating communicative ability in 18-month-old children, and in study II by exploring the prevalence of language and communication problems in children with complex problems, such as attention deficit hyperactivity disorder (ADHD). The issue of intervention is addressed in studies III and IV by analysing verbal interaction in conversations, in which one of the participants is a child with specific language impairment (SLI). Study III explores how dialogues between children with SLI and typically developing peers (TLD) representing the same age (age peers), and the same language level (language peers) respectively, differ with respect to responsiveness, assertiveness and reciprocity. Study IV investigates interactional style and elicitation strategies of speech/language pathologists (SLP) during intervention, and how these factors influence the child with SLI. The results from study I show that receptive skills and symbolic play at 18 months of age are significantly associated with language ability three years later. Study II, in which language skills in children with ADHD were explored, indicates that language ability plays an important role for all other aspects of children's development and behaviour, with the exception of motor skills. Use of language and language comprehension caused these children many more problems than structural aspects of language production. Furthermore, reading and writing problems were found to be very frequent. Study III shows that dialogues between children with SLI and TLD age peers are characterized by more responsiveness and topic coherence than dialogues between children with SLI and TLD language peers. However, the children with SLI were more assertive, i.e., introduced more topics, in dialogues with language peers. Study IV indicates that the children with SLI talked more and had a higher mean length of utterance (MLU) in the free conversational context, whereas the individually selected grammatical targets occurred more often in the training context. In the conversational context the SLPs linked, i.e., attended, more to the child's focus and gave more feedback, while in the training context the individually selected grammatical targets occurred more often and the children were more frequently asked to follow instructions. The results have important clinical implications. First; screening procedures at Child Health Care (CHC) centres should be recommended to focus on receptive language skills and play behaviour, and not only on size of vocabulary at 18 months of age. Second; language skills, in particular language comprehension, language use and literacy skills were found to cause children with ADHD problems, and should therefore be assessed. Third; it is of great value for children with SLI to be in mixed groups with peers representing different ages and language levels, and to avoid the risk of not being selected as playmates. Fourth; increased awareness of how interactional style and elicitation strategies influence the developing language skills in children with SLI can be used in intervention planning, depending on the goals of the specific intervention procedures for the individual child.
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| 5. |
- Holmberg, Johan
(författare)
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Dizziness and fear of falling: A behavioural and physiological approach to Phobic Postural Vertigo
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dizziness is a common problem and it often co-exists with anxiety. Level of anxiety is the best predictor of handicap for dizzy patients. There is diagnostic controversy and few treatment programs for such patients. These patients can be labeled as panic disorder with agoraphobia or by the concept of Phobic Postural Vertigo which is characterized by dizziness or imbalance in standing or walking despite normal clinical balance tests and avoidance behaviours. This thesis aimed to investigate the benefits and shortcomings of the concept of Phobic Postural Vertigo and to develop treatment methods. We compared posturography results of patients with Phobic Postural Vertigo with healthy subjects. Patients with Phobic Postural Vertigo had more sway in frequencies above 0.1 Hz. Vibratory proprioceptive stimulation increased differences between populations. Patients were less able to use vision to compensate for vibratory stimulation. We compared results in questionnaires for patients with Phobic Postural Vertigo with unselected patients with dizziness. Patients with Phobic Postural Vertigo, and especially women, experienced higher degree of handicap, anxiety and dizziness severity. During cognitive behavioural therapy for those patients it was found that a fear of falling was provoked by standing and by misinterpretation of spontaneous body sway. Patients restricted their body sway area by co-contracting postural muscles. It is hypothesized that this behaviour leads to muscular fatigue, pain problems and distorted proprioception. There are however also other factors behind patients dizziness. Treatment methods were developed, mainly targeting the misinterpretaton of spontaneous body sway, fear of falling and fear regulating postural responses including exposure to standing in specific situations. One group of patients with Phobic Postural Vertigo had Cognitive Behavioural Therapy while another group underwent a self treatment procedure. Patients who had the additional Cognitive Behavioural Therapy fared considerably better in degree of handicap, anxiety and depression. In a one year follow up, treatment results deteriorated to pre-treatment levels. Men seemed to benefit more from the treatment. Phobic Postural Vertigo is a relevant concept to describe the fear of falling and subsequent postural behaviours. As treatment results were not maintained future approaches might also includ physiotherapy and pharmacological treatment.
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| 6. |
- Shen, Yue, 1981-
(författare)
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Plasminogen : a novel inflammatory regulator that promotes wound healing
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The plasminogen activator (PA) system has been shown to be intimately involved in wound healing. However, the role of this system in the initiation and resolution of inflammation during healing process remained to be determined. The aims of this thesis were to investigate the molecular mechanism underlying the interaction between the PA system and the inflammatory system during wound healing and to explore the therapeutic potential of plasminogen in various wound-healing models.The role of plasminogen in the inflammatory phase of the healing process of acute and diabetic wounds was studied first. Our data showed that administration of additional plasminogen to wild-type mice accelerates the healing of acute wounds. After injury, both endogenous and exogenous plasminogen are bound to inflammatory cells and are transported to the wound site, which leads to activation of inflammatory cells. In diabetic db/db mice, wound-specific accumulation of plasminogen does not take place and the inflammatory response is impaired. However, when additional plasminogen is injected, plasminogen accumulates in the wound, the inflammatory response is enhanced, the signal transduction cascade is activated and the healing rate is significantly increased. These results indicate that administration of plasminogen may be a novel therapeutic strategy to treat different types of wounds, especially chronic wounds in diabetes.The role of plasminogen at the later stage of wound healing was also studied in plasminogen-deficient mice. Our data showed that even if re-epithelialization is achieved in these mice, a prolonged inflammatory phase with abundant neutrophil accumulation and persistent fibrin deposition is observed at the wound site. These results indicate that plasminogen is also essential for the later phases of wound healing by clearing fibrin and resolving inflammation.The functional role of two physiological PAs during wound healing was further studied in a tympanic membrane (TM) wound-healing model. Our data showed that the healing process was clearly delayed in urokinase-type PA (uPA)-deficient mice but not in tissue-type PA (tPA)-deficient mice. Less pronounced keratinocyte migration, abundant neutrophil accumulation and persistent fibrin deposition were observed in uPA-deficient mice. These results indicate that uPA plays a central role in the generation of plasmin during the healing of TM perforations.Finally the therapeutic potential of plasminogen in the TM wound-healing model was studied. Our data showed that local injection of plasminogen restores the ability to heal TM perforations in plasminogen-deficient mice in a dose-dependent manner. Plasminogen supplementation also potentiates healing of acute TM perforations in wild-type mice, independent of the administration method used. A single local injection of plasminogen in plasminogen-deficient mice can initiate healing of chronic TM perforations resulting in a closed TM with a continuous but rather thick outer keratinocyte layer. Three plasminogen injections lead to a completely healed TM with a thin keratinizing squamous epithelium covering a connective tissue layer that can start to reorganize and further mature to its normal appearance. In conclusion, our results suggest that plasminogen is a promising drug candidate for the treatment of chronic TM perforations in humans. Taken together, our data indicate that plasminogen is a novel inflammatory regulator that promotes wound healing.
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| 7. |
- Petersen, Eline Borch, 1986-
(författare)
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Neural and Cognitive Effects of Hearing Loss on Speech Processing
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Understanding speech in the presence of noise can be difficult, especially when suffering from a hearing loss. This thesis examined behavioural and electrophysiological measures of speech processing with the aim of establishing how they were influenced by hearing loss (internal degradation) and listening condition (external degradation). The hypothesis that more internal and external degradation of a speech signal would result in higher working memory (WM) involvement was investigated in four studies. The behavioural measure of speech recognition consistently decreased with worse hearing, whereas lower WM capacity only resulted in poorer speech recognition when sound were spatially co-located. Electrophysiological data (EEG) recorded during speech processing, revealed that worse hearing was associated with an increase in inhibitory alpha activity (~10 Hz). This indicates that listeners with worse hearing experienced a higher degree of WM involvement during the listening task. When increasing the level of background noise, listeners with poorer hearing exhibited a breakdown in alpha activity, suggesting that these listeners reached a ceiling at which no more WM resources could be released through neural inhibition. Worse hearing was also associated with a reduced ability to selectively attend to one of two simultaneous talkers, brought on by a reduced neural inhibition of the to-be-ignored speech. Increasing the level of background noise reduced the ability to neurally track the to-be-attended speech. That internal and external degradation affected the tracking of ignored and attended speech, respectively, indicates that the two speech streams were neurally processed as independent objects. This thesis demonstrates for the first time that hearing loss causes changes in the induced neural activity during speech processing. In the last paper of the thesis, it is tentatively suggested that neural activity can be utilized from electrodes positioned in the ear canal (EarEEG) for adapting hearing-aid processing to suite the individual listeners and situation.
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| 8. |
- Hansson, Kristina
(författare)
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Specific Language Impairment in Swedish: Grammar and Interaction
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main purpose of this work was to explore grammar in Swedish children with Specific Language Impairment (SLI), that is children with impaired language development in the presence of normal hearing and otherwise normal development. In four differents studies, spontaneous data from six children with SLI were analysed and compared with data from either younger children with phonological impairment but normal grammar (PI), or from younger controls with typical development. The children with SLI were matched to their controls on the basis of mean length of utterance (MLU). One of the studies also includes longitudinal data. A fifth study includes experimental data from 10 children with SLI and 10 younger language matched controls. The results showed that in particular word order, verb forms requiring an auxiliary or a modal, and subordination were structures where the Swedish children with SLI differed from their controls. The children with SLI were further found to have a higher amount of hesitation phenomena than children with PI. These two groups also differed with respect to qualitative aspects of their maze behaviour. The conversational partner was not found to influence structural aspects of the language production of children with SLI or PI. The conversational partner did, however, influence the interactive behavior and the productivity of the children. Clinically, the pinpointing of vulnerable structures have important implications for the assessment of children with language impairment in Sweden. The analysis of the influence of the conversational partner can have implications for therapy, if further developed. The results point to the importance of investigating SLI in different languages.
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| 9. |
- Reuterskiöld, Christina
(författare)
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Language Processing and Contextual Influence. A study of Swedish preschool children with language impairment.
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Language Processing and Contextual Influence A Study of Swedish Preschool Children with Language Impairment The aim of the present work was to study different types of contextual influence on language performance in a variety of tasks: repetition of nonwords, narration, understanding of idioms and picture naming in a group of Swedish preschool children with language impairment (LI). The stress pattern of words and nonwords was found to have an impact on the repetition performance of the participants. Furthermore, nonword repetition was found to be linked to expressive language skills, particularly phonological developmental level. Different types of genres, that is conversation and narration, led to differences in aspects of language production such as fluency and grammatical structure. We also found that the relative level of language comprehension was important for the ability to provide a story with several content units as well as to only include aspects considered relevant for the listener and the task. It was shown that preschool children with LI do not interpret idioms literally but they have difficulties defining them. Idiom understanding was linked to performance on a theory of mind task, measures of semantic-lexical skills as well as receptive grammar. In the final study a sentence prime significantly increased naming speed in children with LI. There was a tendency that children who benefitted from the prime were the individuals with relatively good scores on some of the verbal measures. Assessment tools that incorporate dynamic aspects of processing need to be developed for clinical use. A dialogistic perspective could provide additional information when assessing children with LI.
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| 10. |
- Samuelsson, Christina
(författare)
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Prosody in Swedish Children with Language Impairment. Perceptual, Acoustic and Interactional Aspects
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to explore prosodic problems in Swedish children with language impairment (LI). In the first study, 29 children with LI participated. They were assessed with an assessment procedure for prosody at the word, phrase and discourse levels, developed within this thesis. The results showed that 41% of the children had prosodic problems to some extent. In addition, reliability and validity of the newly developed assessment procedure were evaluated. The procedure was found to be sufficiently reliable and also a valid instrument to assess prosodic problems. In study II data from 25 children with LI in combination with prosodic problems as assessed by their clinician, were compared to data from 25 children with typically developing language matched to age, gender and regional dialect. Results from this study showed that the children with LI in combination with prosodic problems scored significantly lower on all aspects of prosody. Moreover, the results indicated that there were at least two subgroups of prosodic problems; one with prosodic problems related to linguistic/phonetic problems and the other with prosodic problems related to pragmatic problems. Contrast of tonal word accents was one of the most difficult prosodic features to acquire for children with LI in combination with prosodic problems. The ability to produce this contrast was investigated with perceptual as well as acoustic evaluations in study III. Both the perceptual and the acoustic evaluation verified that children with LI in combination with prosodic problems had significant problems in producing the contrasts of tonal word accents. The results also indicated that the problems are a lack of contrast rather than an overgeneralization of accent II, which has previously been suggested. Study IV is a case study of two children with prosodic problems at the discourse level. In this study it was shown that prosodic problems at the discourse level may be related to pragmatic problems. The results of this thesis have important clinical implications and implications for future research.
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