| 1. |
- Afzelius, Maria
(author)
-
Families with parental mental illness : supporting children in psychiatric and social services
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Children living with a parent with a mental illness can face difficulties. Parentalmental illness may influence the parents’ ability to cope with family life, where theparents’ awareness of their illness plays an important role. Family interventionsprovided by psychiatric and children’s social care services can be a way to supportthese children, making them feel less burdened, and improving the relationshipswithin the family. The aim of this thesis was to illuminate how children infamilies with a parent with a mental illness are supported in psychiatric and socialservices, especially by means of family interventions, and how families experiencethe support. Study I explored how professionals in adult psychiatric outpatient servicesdeal with children and families when a parent has a mental illness. The findingsshowed that professionals balanced between establishing, and maintaining,a relationship with the patient and fulfilling the legal obligations towards thepatient’s children. Asking the patient about their children could be experiencedas intrusive, and involving the patient’s family in the treatment could be seen asa dilemma, in relation to the patient. Efforts were made to enhance the familyperspective, and when the patient’s family and children joined the treatment thisrequired flexibility from the professional. Study II examined how professionals in children’s social care services experienceworking with children and families when a parent has a mental illness. The socialworkers’ objective was to identify the needs of the children. No specific attentionwas paid to families with parental mental illness; they were supported in thesame way as other families. When the parental mental illness became difficult tohandle both for the parent and the social worker, the latter had to set the child’sneeds aside in order to support the parent. Interagency collaboration seemed likea successful way to support these families, but difficult to achieve. Study III investigated if patients in psychiatric services that are also parentsof underage children, are provided with child-focused interventions or involvedin interagency collaboration between psychiatric and social services and childand adolescent psychiatry. The findings showed that only 12.9% of the patientsregistered as parents in Psykiatri Skåne had registered children under the ageof 18 years. One fourth of these patients had been provided with child-focusedinterventions in psychiatric service, and 13% of them were involved in interagencycollaboration. If a patient received child-focused interventions from the psychiatricservices, the likelihood of being involved in interagency collaboration was fivetimes greater as compared to patients receiving no child-focused intervention.Study IV explored how parents and their underage children who were supportedwith family interventions experienced these interventions. The results showedthat parents experiencing mental illness were eager to find support in explainingto and talking with their children about their mental illness, although the supportfrom the psychiatric service varied. Both children and other family membersappreciated being invited to family interventions. After such an intervention, theyexperienced the atmosphere in the family as less strained and found it easier tocommunicate with each other about difficulties. Unfortunately, the participatingpartners felt that they were left without support specifically targeted at them. The thesis showed that there is a gap between how professionals deal withquestions concerning these families and their support, and the parents’ and thefamilies’ needs to receive support in handling the parental mental illness in thefamily. The psychiatric and social services need to expand their approach andwork with the whole family, in order to meet the needs of the child and otherfamily members involved.
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| 2. |
- Al-Okshi, Ayman
(author)
-
Maxillofacial cone beam computed tomography (CBCT) : aspetcs on optimisation
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Inom odontologisk såväl som inom medicinsk radiologi sker en snabb utveckling av nya tekniker. Nya metoder för att kunna diagnosticera och följa sjukdomsförlopp över tid introduceras. Cone-Beam Computed Tomography (CBCT) är en sådan ny teknik, som introducerades inom odontologin under sent 1990-tal. Tekniken innebär att man får en avbildning av kroppen i genomskärning i tre mot varandra vinkelräta plan. Efter en långsam start med få fabrikanter och typer av CBCT-maskiner har antalet tillverkare och modeller ökat och en snabb spridning av tekniken har skett. CBCT kan ge en utökad och bättre diagnostisk information än konventionell röntgenteknik, men till priset av högre stråldos. Eftersom utveckling av nya tekniker liksom försäljning av ny apparatur går snabbare än forskning som undersöker nyttan med de nya teknikerna, är det angeläget att vetenskapligt utvärdera i vilken utsträckning nya tekniker är till nytta för de patienter som undersöks. Alla undersökningar som görs med röntgenstrålning ska vara berättigade och optimerade dvs utföras med lägsta möjliga stråldos för en specifik klinisk frågeställning. Därför är det viktigt att forskning som rör nya tekniker beaktar olika aspekter av optimering av undersökningar som utförs vid olika kliniska indikationer. Denna avhandling behandlar några aspekter av hur undersökningar med CBCT kan optimeras. I det första delarbetet gjordes en systematisk granskning av den vetenskapliga litteratur som publicerats då det gäller hur stora stråldoser som en undersökning med CBCT av tänder, käkar och ansiktsskelett ger upphov till, samt hur dessa stråldoser beräknas. För att hitta all relevant litteratur gjordes en sökning i tre databaser vilket resulterade i att över 700 publikationer identifierades. Efter en första genomgång kvarstod 38 publikationer som handlade om dosmätningar vid CBCT undersökningar av tänder, käkar och ansiktsskelett. Få studier beskrev i tillräcklig omfattning hur stråldoser beräknats, vilka protokoll och mätmetoder som använts. Likaså var beskrivningen av hur stråldoser relateras till kvalitén på de röntgenbilder som undersökningen resulterade i, mestadels knapphändig. Det behövs mer forskning som beskriver hur beräkningar av stråldoser sker samt hur man kan använda den lägsta möjliga stråldosen för att uppnå den kvalitén på röntgenbilderna som är optimal för en given klinisk frågeställning. En modell för vilka parametrar som är nödvändiga vid rapportering av uppmätt stråldos för CBCT undersökningar av tänder, käkar och ansiktsskelett föreslås. Syftet med det andra delarbetet var att testa en metod för att beräkna stråldos, som inte tidigare använts i nämnvärd utsträckning för odontologiska undersökningar. Denna metod innebär att en röntgenkänslig film placeras i ett fantom som är sammansatt av material vilka simulerar biologisk vävnad. Stråldosen från tre CBCT apparater från olika tillverkare beräknades för tre olika kliniska frågeställningar. Därutöver jämfördes de uppmätta stråldoserna från de tre CBCT apparaterna med doser från tre konventionella röntgenapparater som ger två dimensionella bilder av tänder och käkar sk panoramaröntgenbilder. Stråldoserna från CBCT apparaterna varierade beroende på strålfält, samt energi och mängd av röntgenstrålning för de olika undersökningarna och var generellt högre än de uppmätta stråldoserna från panoramaröntgenapparaterna. I det tredje delarbetet var målet att relatera stråldos till bildkvalitet för en specifik klinisk frågeställning och en specifik CBCT apparat. Stråldoser uppmättes med en DAP-meter och bildkvalité utvärderades såväl fysikaliskt (objektivt) som subjektivt. För beräkning av den objektiva bildkvalitén användes ett fantom som tagits fram i ett tidigare EU-finansierat projekt (SEDENTEXCT) och för bedömning av den subjektiva bildkvalitén användes att fantom som var sammansatt av material liknande biologisk vävnad. Från resultaten av denna studie kunde ett undersökningsprotokoll föreslås för undersökning av tänder och omgivande vävnad som ger den bästa bildkvalitén med lägsta möjliga stråldos. I det fjärde delarbetet användes röntgenbilder tagna på unga individer som skulle genomgå behandling för att korrigera snedställda tänder. En sådan tandreglerings behandling kan ge upphov till vissa icke önskvärda sidoeffekter så som förkortade tandrötter och/eller att den benvävnad som omger tänderna till viss del blir förstörd. Det kan därför vara viktigt att utföra röntgenundersökningar på denna patientgrupp både innan behandlingen påbörjas och vid uppföljningar av behandlingen. Syftet med denna studie var att undersöka hur olika bedömare identifierar och mäter anatomiska strukturer (tandrötter och den benvävnad som omger tänderna) i röntgenbilder från CBCT undersökningar och jämföra med mätningar i röntgenbilder från två konventionella tekniker. Sex bedömare granskade röntgenbilderna och utförde mätningarna. Resultatet visar att i röntgenbilder från CBCT undersökningen var det lättare att identifiera de anatomiska strukturerna än i röntgenbilderna från de konventionella teknikerna. Likaså var samstämmigheten mellan och inom bedömare högst för CBCT undersökningen då det gäller mätning av rötternas längd. Då det gäller mätning av benvävnaden runt tänderna fanns ingen skillnad mellan de olika teknikerna. Sammanfattningsvis visar denna avhandling att det saknas studier av hög kvalitet då det gäller mätning av stråldos relaterat till optimal objektiv och subjektiv bildkvalitet för givna kliniska frågeställningar. Vidare förslås en modell som innehåller nödvändiga parametrar för att rapportera uppmätt stråldos vid undersökning med CBCT av tänder, käkar och ansiktsskelett. Ett protokoll för CBCT undersökning av tänder och omgivande benvävnad som ger bästa möjliga bildkvalitet med minsta möjliga stråldos föreslås liksom vilka aspekter som bör beaktas i vetenskapliga studier för röntgenologisk kartläggning av icke-önskvärda effekter av tandregleringsbehandling.
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| 3. |
- Chrcanovic, Bruno
(author)
-
On failure of oral implants
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- Introduktion: Behandling med orala implantat är idag en effektiv och fungerande metod att ersätta bettfunktion vid partiell eller hel tandlöshet. Trots höga överlevnads- och lyckandesiffror finns ändå riskfaktorer som för vissa patienter kan resultera i implantatförlust. Man behöver noggrant utreda olika faktorer som kan påverka benförankringen, osseointegrationen, av implantaten för att ytterligare förbättra lyckandesiffrorna. Om faktorer som leder till ökad implantatförlust kan identifieras, skulle det underlätta för såväl tandläkare som för patienten genom att man då får möjlighet att undvika eller kompensera för individuella risker. Den här avhandlingen har haft som syfte att presentera kända riskfaktorer bakom implantatförluster.Material och metodik: Artiklarna som ingår i denna avhandling kan indelas i tre olika sorters studier. Först gjordes en allmän översikt om kända faktorer bakom implantatproblem (arbete I). Därefter utfördes en meta-analys innebärande en genomgång av relevant litteratur för att mer djupgående kunna analysera en selekterad riskfaktor, nämligen att patienter som röker kan påverka såväl benförlust runt implantatet som postoperativ infektionsrisk och implantatförlust.(Arbete II). Därefter utfördes sju retrospektiva (tillbakablickande) studier(Arbeten III-IX) baserat på 10.096 implantat, konsekutivt insatta på tillsammans 2670 patienter på en klinik – folktandvården i Skåne, specialisttandvården Malmö under tiden 1980 till 2014. Efter godkännande från etisk nämnd har det blivit möjligt att datorbehandla tandläkarjournaler från detta patientmaterial. Data införs på en SPSS fil (SPSS software, version 23, SPSS Inc, Chicago, USA). Anatomiska-, patient-, hälso- och implantatrelaterade faktorer registrerades. De kliniska studier som ingår i avhandlingen har fokuserats kring frågeställningar som implantatförlust och bruxism(tandgnissling), medikamentell behandling med protonpumpsinhibitorer(magsårsmedicin) eller serotonin(antidepressivt medel), lyckandedata för implantat insatta av olika kirurger, tidiga förluster och s k clusterbeteende. Klusterbeteende avser att implantatförluster inte är jämnt fördelade bland patienterna, utan att det rör sig främst om ett fåtal patienter som har många misslyckanden. Därtill utfördes röntgenologiska beräkningar av benförlust runt implantat som varit insatta under mer än 20 års tid. Olika statistiska modeller användes för att testa om erhållna data var signifikant skilda åt i jämförelse med relevanta kontroller.Resultat och Diskussion: Den systematiskta genomgången av litteraturen antydde att det fanns en serie faktorer som kunde påverka implantatutgången; t ex lågt vridmoment vid implantatinsättningen om man samtidigt avsåg belasta implantaten snabbt; att oerfarna eller dåligt skolade kirurger har sämre kliniskt resultat än mer skolade kollegor; implantatinsättning i överkäken; implantatinsättning i bakre delen av käkarna eller i ben av dålig kvalitet/kvantitet; rökande patienter; användning av korta implantat eller för många implantat; insättning av icke gängade implantat eller användande av s k täckprotes. Därtill fanns antydningar om andra faktorer som möjligen skulle kunna påverka implantatframgången negativt, som att låta implantaten ha direkt genomgång i slemhinnan utan tidigare vilofas, som direktbelastning av implantaten, som insättning av implantat direkt efter tandutdragning, som implantat med liten diameter. En del senare studier antydde att moderna moderat råa implantatytor kunde kompensera för risker med en del faktorer som insättning i överkäken, användande av korta implantat eller vid direktbelastning (Studie I). Den mer systematiska analysen av rökande patienter fann en ökning av implantatförlusterna hos rökare och därtill påverkades infektionsrisken efter implantatinsättningen och man fick ökad benförlust runt implantaten när patienten rökte (Studie II).Rökning kunde verifieras som riskfaktor i den kliniska analysen och även om patienten åt antidepressiva tabletter av serotonin-typ, så ökade i vart fall de tidiga implantatförlusterna (Studie III). Patienter som gnisslade tänder hade signifikant ökning av implantatförluster och fick därtill ökning av implantatfrakturer och brott på tandbroar (Studie IV). Resultaten visade också att en vanlig typ av magsårsmedicin; s k proton pumphämmare, resulterade i ökning av antalet implantatförluster (Studie V). Man fann däremot inga säkra tecken på ökad implantatförlust vad gällde sena resultat för de som åt antidepressiva mediciner av serotonintyp (Studie VI). Vidare fanns klara antydningar att vissa kirurger hade fler implantatförluster än andra, något som kan ha att göra med vald kirurgisk teknik, kirurgisk förmåga, kirurgiskt omdöme(vissa tänkta implantatpatienter skall kanske inte operas utan få annan behandling) (Studie VII). Vissa patienter med specifika karaktäristika som pekats på i studie I förlorade klart fler implantat än medelpatienten (Studie VIII). Slutligen noterades en mycket klar övervikt för tidiga implantatförluster under de första två åren efter implantatinsättningen, varefter ytterliga implantatförluster förekom men var långt mer ovanliga. En särskild faktor som antytts ställa till stora kliniska problem, som benförlust runt implantaten, visade sig i verkligheten sällan leda till implantatförlust. De flesta implantat som uppvisade benförlust fungerade trots detta utmärkt kliniskt (Studie IX). Den övergripande målsättningen med denna avhandling har varit att öka kunskapen om olika faktorer bakom implantatförlust för att på så sätt kunna bidra till ytterligare förbättring av kliniska resultat i framtiden.
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| 4. |
- Christell, Helena
(author)
-
Cost and benefits of cone beam computed tomography : for maxillary canines with eruption disturbance
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- I tandvården finns allt fler metoder för prevention, diagnostik och behandling. Eftersom resurserna är begränsade bör den metod väljas där nyttan uppväger kostnaden. Idag saknas dock vetenskapliga belägg gällande kostnadseffektivitet för undersökning med Cone Beam Computed Tomography (CBCT). En systematisk översikt i Studie I identifierade 160 hälsoekonomiska utvärderingar inom tandvård varav 12 gällande diagnostiska metoder. Översikten kunde inte identifiera någon kostnadsanalys på patientnivå för diagnostiska metoder. Därför konstruerades i Studie II ett ramverk för analys av kostnader förknippade med diagnostiska metoder i tandvården. Applicering av ramverket visade att CBCT och panoramaröntgen hade en signifikant högre kostnad (128,80€) jämfört med intraoral och panoramaröntgen (81,80€). I Studie III jämfördes kostnader för CBCT undersökning av patienter med olika kliniska tillstånd på kliniker i Cluj -Rumänien, Leuven -Belgien, Malmö -Sverige och Vilnius -Litauen. Klinikrelaterade kostnader varierade mellan sjukvårdssystemen vilket främst berodde på olika höga inköpskostnader för CBCT-apparaterna. I enkätundersökning i Studie IV ombads specialister i tandreglering att ta beslut om behandling gällande patienter med misstanke om eruptionsstörning av överkäkshörntanden. Majoriteten av behandlingsvalen var samma oavsett om de hade tillgång till CBCT och panorama eller till intraoral röntgen och panorama.Sammanfattningsvis kan sägas att det finns ett stort behov av hälsoekonomiska studier med god kvalitet gällande diagnostiska metoder inom tandvård. Undersökning med CBCT medför en högre kostnad än konventionella röntgenmetoder och för majoriteten av patienter med misstanke om eruptionsstörning av överkäkshörntänderna medför den ingen extra nytta avseende behandlingsbeslut.
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| 5. |
- Erovic Ademovski, Seida
(author)
-
Treatment of intra-oral halitosis
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Intra -oral halitosis (bad breath) is reported to affect 15 -83 % of the adult population. Having intra- oral halitosis is a social and psycho- logical handicap, and may cause people in the person’s social circle to increase the physical distance or to turn their faces in another di- rection to avoid the unpleasant smell from the exhaled air. Such be- haviours may affect the individual’s self -confidence resulting in ins e- curity in social and inti mate relations. The oral health -related quality of life status has also been reported to be lower in individuals with halitosis. Approximately 90% of what is considered as bad breath is the result of the degradation of organic substrates (proteins) by an- aerobic bacteria of the oral cavity. Intra -oral halitosis can be as- sessed using both subjective and objective methods to evaluate the subject’s exhaled air. The most common one and the one often r e- ferred to as the ” gold standard”, is the organoleptic scoring system (OLS). OLS is a subjective method evaluating the strength of halit o- sis in exhaled air using a scale from 0- 5. One objective method to assess the presence of volatile sulphur compounds in exhaled air is to use a sulphide monitor measuring the total sum of the volatile sul- phur compounds (T -VSC) in exhaled air. The three gases (hydrogen sulphide (H 2 S), methyl mercaptan (MM) and dimethyl sulphide (DMS)) in exhaled air related to intra- oral halitosis can be assessed separately using a simplified gas chromatograph. Different treatment models such as periodontal treatment, tongue scraping and rinsing with Zn ion containing products have been used to reduce intra -oral halitosis. The present thesis has evaluated the efficacy of different treatment models in t he treatment of intra -oral halitosis.
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| 6. |
- Johansson, Pär
(author)
-
On hydroxyapatite modified peek implants for bone applications
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- People are living longer today than ever before, and the number of older adults will increase exponentially over the next coming years. However, that does not necessarily mean that they are living healthier. An aging population presents many opportunities but also challenges in the public health care with a sharp increase in incidence of many diseases associated to the bone, teeth and joint systems. Orthopedic and dental implants commonly used mostly consist of metals, composites, polymers and ceramics. Titanium has been widely used in the orthopedic and dental field to replace or support mineralized structures. Titanium possesses good mechanical, physical and biologic properties. However, titanium has in the clinic presented some critical drawbacks. The modulus of elasticity is higher than that of bone which may cause stress shielding and bone resorption ultimately jeopardizing the implant retention. In addition, with rare cases of titanium allergy and patient desires for non-metallic treatments, alternatives to titanium are being studied. Furthermore, the radiopacity of titanium causes interference with the radiographic evaluation and the non-esthetic color may discolor the gingiva of thin biotypes. Recently, advanced polymeric implantable materials have been introduced into the medical field. Polyetherether ketone (PEEK) is widely used in various orthopedic applications, such as spine implants, joint replacements and fracture fixations. In dentistry, PEEK can be manufactured as prosthetic components, fixed and removable bridges and dentures. PEEK is a thermoplastic polymer with mechanical properties that are close to those of human bone, for example the elastic modulus. This will minimize the stress shielding upon loading and stress distribution. Besides, PEEK holds excellent biocompatibility with no toxic or mutagenic effects in vitro and in vivo. However, unmodified PEEK is biologically inert with limited pro-tein and cell adhesion to the surface. Therefore, improving the bio-activity of PEEK is a significant challenge and a prerequisite to possess all of its potentials as a biomaterial. There are currently 2 methods to improve the bioactivity of PEEK; surface modification and composite preparation. Hydroxyapatite (HA) is the most widely used material due to its biocompatibility and osteoconductive potential in association with biomaterials. There are many developed and evaluated methods to deposit HA on metallic implants, but the only commercially used one is plasma spraying. However, the technique has some severe disadvantages such as irregular coating thickness with deficient adherence to the implant surface. Clinical complications have been confirmed with inflammation caused by fragments of delaminated coating. To challenge these disadvantages, several alternative coating techniques have been introduced. The aim of this thesis was to evaluate a novel surface modification of bioactive hydroxyapatite deposited by a spincoating technique. The technique generates a crystalline, nanosized coating homogenously distributed over the implant surface. In particular, the thesis encompasses a comprehensive topographic analysis to evaluate the coating properties. In addition, the HAPEEK implant will be compared in vivo with an unmodified control with respect to its oste-oconductive and bioactive properties. In study I, the surface topography was characterized using interferometry (IFM), scanning electron microscopy (SEM) and atomic force microscopy (AFM) of the same types of implants that were evaluated in the experimental animal models. The chemical characterization before and after the coating procedure was evaluated with X-ray photon spectroscopy (XPS). Mechanical testing of implants were completed in accordance with the tensile testing standard (ISO 527-2). Furthermore, the hydrophilic appearance after coating was estimated by measuring the contact angle. The results from the ma-terial characterization reveal a hydrophilic coating with a minimally rough surface which preserved its mechanical properties after the coating procedure. The chemical analysis revealed that only Ca, P, C and O were present at the surface of HA-PEEK with a proportion as that of human bone. In study I and IV, PEEK implants were implanted in the rabbit tibia and femur and retrieved after 3, 12 and 20 weeks of submerged heal-ing and subjected to biomechanical analysis using a removal torque device. The removal torque required to unscrew the implants was significantly higher for HA-PEEK after the 3 and 12 week retrieval time points. However, the absolute torque values were lower at 12 weeks compared to earlier time points, presumably caused by absence of primary stability and dissolution of the HA-coating. After 20 weeks of healing the absolute values were even lower than for the implants recovered at 3 and 12 weeks. However, the retention was still significantly increased for the HA-PEEK implants. In study II, III and IV, the osseointegration was histologically evaluated with respect to boneimplant contact (BIC) and bone area (BA) after the same healing time points as aforementioned. The performance of the HA-coating was most significant 3 weeks after implantation. However, after 12 and 20 weeks, the BIC turned out to be comparable between the groups. Furthermore, the implants implanted in femur were designed with an apical perforation to evalu-ate the osteoconductivity in terms of area of bone. After 3 and 12 weeks the results revealed a significant improvement on the HA-PEEK. However, after an extended healing period of 20 weeks, the unmodified implants were presenting comparable results as the HA-PEEK group. A more comprehensive description of the osseointegration can be achieved using computed microtomography. Three different diameters around the implant and inside the apical perforation were evaluated with respect to bone density and trabecular properties. However, there were no detectable differences between the PEEK and HA-PEEK. The outcome was limited to the resolution of X-rays. There was a minor contrast between resin and PEEK. The implant surface, particularly the thread edges are subjected to mechanical forces during implant placement and removal. The stability of the coating was evaluated in study II. The coating was wellpreserved in deformities of the surface, but on the flat edges of the threads there were signs of deformation and absence of HA crystals. This thesis demonstrated that a nanosized HA-coating can be pro-cessed using a spin-coating technique with nanostructures and suffi-cient adhesion to the substrate. Furthermore, the performance of the HA-coating was found to improve the surface osteoconductivity by increasing the level and speed of osseointegration. However, the effect was most prominent in the early stages of healing whereas the implants from the extended time points showed osteoconductive properties comparable to unmodified PEEK. In addition, the ability of HA-coating to improve bone fusion inside a perforation was the most clinical relevant outcome. Unmodified PEEK implants are today widely used in spine surgery and the present surface modifications may improve the clinical outcomes where a rapid bone formation is essential.
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| 7. |
- Möllerberg, Marie-Louise
(author)
-
Families' life situation when living with cancer : aspects of health and family sense of coherence
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Aim: To investigate families’ perceived life situation when living with cancer, with a focus on health and family sense of coherence.Methods: Study I is a population-based register study that explored how cancer influenced the health of cohabitating partners of persons with cancer in Sweden by examining the onset of new diagnoses, health care use, and health care costs among the partners. Study II focused on familial interaction patterns for families living with cancer in a palliative phase, based on family interviews, and analysed using Gadamerian hermeneutics. In study III, Family Sense of Coherence scale (S-FSOC-S) was culturally adapted and evaluated for reliability and validity, using psychometric analyses. Study IV explored associations between family sense of coherence and hope, anxiety, and symptoms of depression using descriptive statistics and nested linear regression.Results: Study I showed that the partners of persons with cancer had significantly increased health care use and health care costs both one and two years after the cancer diagnosis, and that use patterns and costs varied according to the type of cancer that had been diagnosed. Study II revealed that the familial interaction patterns were adjusted in response to changes in family life - changes which encompassed three different, but interrelated, patterns: power dynamics in the family, the “secret game” in the family, and multifaceted closeness and distance in the family. Study III suggested that S-FSOC-S is useful for assessing familial coherence and shows satisfactory reliability and validity. Study IV showed that stronger family sense of coherence was associated with higher hope and lower anxiety and symptoms of depression levels in both persons with cancer and their family members.Conclusions: Families’ life situation was affected by the cancer diagnosis, which had an impact on both individual family members and the family as a unit. The type of cancer may help to determine partners’ risk of ill health. The changed familial interaction patterns increased the families’ ability to deal with family life without hurting each other. The S-FSOC-S is a useful instrument for assessing family sense of coherence and can help identify families with weak family sense of coherence, who may need professional support.
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| 8. |
- Prgomet, Zdenka
(author)
-
The role of WNT5A in oral squamous cell carcinoma
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Cancer is one of the leading causes of death worldwide and furtherresearch into the cancer biology is required to improve treatment andsurvival. Cancer can start in all sites of the body and is characterizedby uncontrolled cell growth and capability of invading surroundingtissue and spreading to other sites of the body. The most commontype of cancer occurring in the oral cavity is oral squamous cellcarcinoma (OSCC). Tobacco, including the betel quid and othertypes of smokeless tobacco, is the main risk factor for developmentof OSCC. Even though therapeutic treatment of OSCC has beenimproved, the prognosis is still poor, and the 5-year survival remainsaround 50%. The ongoing research have shown that proteins involvedin signaling pathways play an important role in the progression ofcancer, however, no reliable biomarkers have yet been identified aspredictors of OSCC progression.Over the past years, a protein named WNT5A, has been shownto be involved in different types of cancer, either by promoting orsuppressing cancer progression. However, its role in OSCC is stillambiguous. This thesis aimed to provide an insight into the role ofWNT5A signaling in OSCC.We started by investigating the functional role of WNT5A in OSCCcells. Due to the lack of the endogenous WNT5A expression, wetreated the cells with recombinant WNT5A (rWNT5A) and observedactivation of the non-canonical WNT/Ca2+/PKC signaling in OSCCcells. This rWNT5A-induced signaling enhanced migration andinvasion of OSCC cells, which was ascertained by different WNT5Ainhibitors. These inhibitors eliminated the rWNT5A-induced WNT/Ca2+/PKC signaling and migration of OSCC cells indicating apromoting role of WNT5A in OSCC cells.Before investigating the expression of WNT5A in human OSCCtissues, we evaluated four commercially available WNT5A antibodiesfor use in immunohistochemistry (IHC) and western blot analysis(WB). Cytoplasmic WNT5A immunostaining pattern was observedwith all four antibodies but only the polyclonal AF645 antibody wasable to detect WNT5A protein in WNT5A-positive cell lysates. Preabsorptiontests revealed that the polyclonal AF645 antibody is thebest antibody for detection of WNT5A by WB while the monoclonal3A4 antibody is the most suitable for use in IHC. Using the monoclonal 3A4 antibody, we investigated the expressionof WNT5A in human OSCC tissues. No expression of WNT5A wasobserved in normal oral epithelium or in mild grade of dysplasia.However, cytoplasmic WNT5A immunostaining was found in 38%of dysplastic tissues and in 81% of the OSCCs. We also noticedthat WNT5A was more expressed in advanced OSCCs than in earlyinvasive OSCCs. Furthermore, we did not observe any correlationbetween expression of WNT5A and two adhesion-proteins, β-cateninand E-cadherin, either in OSCC tissues or in OSCC cells. Thesefindings suggest that WNT5A does not affect the canonical WNT/β-catenin pathway or downregulation of E-cadherin in OSCC.At last, we investigated if the rWNT5A-induced WNT/Ca2+/PKCsignaling affected secretion and activation of matrix metalloproteinases(MMPs) in OSCC cells. We found that rWNT5A-induced activationof MMP2 is not dependent on activation of either β-catenin, ERK1/2,or p38-MAPK, but could instead be induced by WNT5A/Ca2+/PKCpathway. In conclusion, these findings suggest that WNT5A acts as a cancerpromoter in OSCC by facilitating cell migration and invasion via theWNT5A/Ca2+/PKC signaling and activation of MMP2.
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| 9. |
- Senneby, Anna
(author)
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Re-evaluation of methods to identify individuals with increased risk of caries
- 2017
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Doctoral thesis (other academic/artistic)abstract
- The overall aim of this thesis was to evaluate methods used to identify individuals with increased risk of coronal caries lesion development. The specific aims were to:•evaluate the accuracy of different methods used to identify individuals with increased risk of developing dental coronal caries lesions (study I)•design and pilot a novel classification system for the assessment of caries lesion progression in bitewing radiography and to report rater agreement of the system (study II)•assess intra-individual differences in biofilm acid-tolerance between different tooth surfaces and inter-individual variation as well as stability of acid tolerance over time (study III)•assess diagnostic accuracy of two established methods and a candidate method to identify adolescents with increased risk of dental coronal caries lesion development (study IV).Study I comprised a systematic review of caries risk assessment methods, following methods were included for final analysis: previous caries experience, tests using microbiota, buffering capacity, salivary flow rate, dental plaque, dietary habits and sociodemographic variables. Assessment of risk of bias with the aid of Quadas-2 resulted in identification of methodological limitations concerning study design, test technology and reporting. Evidence for methods using previous caries experience and salivary mutans streptococci was low and evidence regarding other methods was lacking. The overall evidence on the validity of analysed methods used for caries risk assessment is limited. As methodological quality was low, there is a need to improve study design. In study II a classification system with drawings and text was designed to assess caries lesion progression in bitewing radiographs. Guidelines for Reporting Reliability and Agreement Studies, GRRAS were used to design and report the study. Pairs of posterior bitewing radiographs (baseline and 1-year follow-up) with different status concerning caries lesion progression were selected and 10 raters assessed the radiographs with the aid of the classification system. Seven raters repeated their assessments. Kappa for the interrater agreement of 10 raters assessing progression was 0.61, indicating substantial agreement. Corresponding intrarater agreement was substantial (kappa 0.66–0.82). This system can provide a common framework for clinical decision-making on caries interventional methods and patient visiting intervals. Scientifically, the system allows for a comparative analysis of different methods of prevention and treatment of caries as well as of different caries risk assessment methods.In study III dental biofilms were collected from supragingival approximal surfaces of canines and first premolars, second premolar and first molars, and between the central incisors of both jaws in adolescents at baseline, day 3, after 1 month as well as after 6- and 12 months for the approximal surfaces of second molars and first molars. After exposure to pH 3.5 for 2 hours, biofilm cells were visualized using LiveDead® BacLightTM staining and each sample was examined using an inverted confocal scanning laser microscope. Live bacteria (acid-tolerant) appeared green while dead (non acid-tolerant) bacteria appeared red. Images of the biofilm were compared with a scale (score 1-5) to assess the proportion acid-tolerant bacteria in each sample. A majority of the adolescents were assessed with low scores of biofilm acid tolerance. In 14 of 20 individuals, no differences were seen between the three dental sites. At 51 of total 60 sites, assessed score of acid tolerance at baseline was unchanged after one month. However, scores for acid tolerance changed over a 1-year period in 50% of the individuals. Results should be interpreted with caution because of the limitation in sample size. Acid tolerance of dental biofilm is a candidate method that may be implement in caries risk assessment methods. It needs to be scientifically evaluated in clinical prospective studies as a biomarker for caries development. For the purpose of study IV, the STARD-statement “Standards for Reporting of Diagnostic Accuracy” was implemented for design and reporting of the study. Adolescents, aged 12, visiting two public dental clinics were examined by visual/tactile examination and bitewing radiography of posterior teeth at baseline and after 1 year. Two established methods (previous caries experience and dentists’ risk assessment) and one candidate method (acid tolerance in dental biofilm) were applied with pre-specified thresholds. The reference standard comprised coronal caries lesion development after 1 year. Caries lesion progression occurred in 29% of the adolescents, mainly approximal lesions within enamel. Diagnostic test accuracy varies with thresholds of the index tests, reference standard and with different caries status and caries lesion progression. Most positive likelihood ratios for the methods were
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| 10. |
- Wahlin, Åsa
(author)
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Periodontal health and disease in two adult populations in Sweden
- 2017
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Doctoral thesis (other academic/artistic)abstract
- This thesis deals with epidemiological data regarding periodontaldisease from two different Swedish populations (Jönköping andSkåne).BackgroundThe studies focus on periodontal disease, a disease affecting a largepart of the adult population. Periodontitis is a complex inflammatorydisease, often chronic, which affects the tissues supporting the teeth– the periodontium. The biofilm that adheres to the hard surfaces of the teeth initiate an inflammation in the supporting tissues. Insusceptible individuals, the inflammation may cause the destructionof the periodontium (periodontitis). Individuals with severeperiodontitis – between 5-15% in different populations – show arange of clinical signs and symptoms, such as bleeding gums, mobileand drifting teeth, the loss of interdental papillae, and eventually theloss of teeth. This may affect the function of the dentition and theaesthetic appearance of the individual. Despite this, the disease isoften considered to be silent. AimsThe overall aim was to study periodontitis prevalence and severityin two Swedish adult populations, and to describe the changes overtime. Further aims were to examine the effect of an individual’ssense of coherence on periodontitis and to analyse the impact ofperiodontitis on oral health-related quality of life.In order to examine this, a series of four different studies wereperformed with the following specific aims: I) to investigate the prevalence, severity, extent of marginal bone loss and subjectcharacteristics in the adult population in the county of Skåne, Sweden;II) to assess trends over 40 years regarding the prevalence and severityof periodontitis in an adult Swedish population; III) to investigatethe impact of periodontal disease experience on quality of life, inan adult Swedish population, using the OHIP-14 questionnaire;and finally IV). To investigate how an individual’s level of senseof coherence correlates with their periodontitis experience, in twodifferent random samples, ten years apart. MethodsOne cross-sectional clinical study in Skåne and five cross-sectionalclinical studies in Jönköping, repeated every ten years, were performedwith random samples of the adult populations. Both study protocolsincluded questionnaires regarding demographic as well as healthand oral health-related factors, as well as patient-related outcomemeasures, such as oral health related quality of life and sense ofcoherence.ResultsThe prevalence of severe periodontitis experience was elevenpercent across the two study populations. There was no differencein periodontitis prevalence according to gender. It was also shownthat subjects with severe periodontitis suffered from worse quality oflife compared to subjects without periodontitis. Regarding the senseof coherence, no difference could be observed between the differentdegrees of periodontitis experience. ConclusionThe main findings over time were the increase of periodontally healthyindividuals and the retention of more teeth among subjects with severeperiodontal disease. Also, individuals with advanced periodontitisexperience worse quality of life compared to periodontally healthyindividuals.
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| 11. |
- Wierzbicka, Celina
(author)
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New fractionation tools targeting elusive post-translational modifications
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Protein phosphorylation is a reversible post-translational modification (PTM)playing a central role in numerous biological events including disease pathogenesis.Thus, the analysis of phosphoproteome is crucial for understandingcellular regulation processes and can facilitate the development of new diagnosticand therapeutic tools.Phosphoproteins are typically analyzed using liquid chromatography coupledwith mass spectrometry (LC-MS) after proteolytic processing. However,phosphopeptides are notoriously difficult to analyze by LC-MS due their lowabundance and transient nature. This creates a need for effective enrichmenttools for phosphorylated proteins and peptides prior to mass spectrometryanalysis.The work presented in this thesis is focused on development and validationof methods and tools for enrichment of phosphopeptides with the use of molecularimprinting technology. In particular, the targeted PTMs include phosphorylationon tyrosine (pTyr) and histidine (pHis).The key recognition element employed in developed synthetic receptors was1,3-diaryl urea functional monomer FM1. This monomer is a potent hydrogenbond donor forming strong cyclic hydrogen bonds with oxyanions such asphosphates. The bias of the imprinted urea-based receptor towards differentphosphorylated residues can be programmed by selection of the template. Thus, the N, C-protected phosphotyrosine and phosphonotriazolylalaninewere used as templates to generate phosphotyrosine (pTyr MIP) and phosphohistidine(pHis MIP) selective molecularly imprinted polymers, respectively.The application of previously reported pTyr MIP for phosphoproteomicstudies was validated on complex biological samples of the mouse brain lysatedigest spiked with standard peptides and HeLa cells digested proteins. Furthermore,the pTyr MIP was developed in the format of microspherical porous beads characterized by uniformly sized and shaped particles with increasedsurface area and pore size as well as improved binding affinity and selectivityfor larger pTyr peptides (2-3 kDa). This opens the way to generation of capturematerials suitable for middle-down phosphoproteomics.In response to the lack of adequate tools and methods for enrichment of acid-labile phosphohistidine peptides a pHis MIP-based approach is proposed asa solution. The method involving selective dephosphorylation ofphosphoserine (pSer) peptide by alkali treatment of the sample, followed byextraction of base-stable pHis peptides with MIP was demonstrated on thesample of bovine serum albumin digest spiked with standard pSer and pHispeptides.The last part of this thesis is focused on improving the recognition ofphosphopeptides in aqueous media – the natural environment of biologicalsamples. Guided by the principles of supramolecular chemistry, novel cationichost monomers were introduced for binding phosphates by ionic hydrogenbonds. These were used to synthesize MIPs showing enhanced binding ofphosphopeptides in aqueous media.
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