907 research outputs found

    Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea

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    ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK

    Immune contexture monitoring in solid tumors focusing on Head and Neck Cancer

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    Forti evidenze dimostrano una stretta interazione tra il sistema immunitario e lo sviluppo biologico e la progressione clinica dei tumori solidi. L'effetto che il microambiente immunitario del tumore può avere sul comportamento clinico della malattia è indicato come "immunecontexture". Nonostante ciò, l'attuale gestione clinica dei pazienti affetti da cancro non tiene conto di alcuna caratteristica immunologica né per la stadiazione né per le scelte terapeutiche. Il tumore della testa e del collo (HNSCC) rappresenta il 7° tumore più comune al mondo ed è caratterizzato da una prognosi relativamente sfavorevole e dall'effetto negativo dei trattamenti sulla qualità della vita dei pazienti. Oltre alla chirurgia e alla radioterapia, sono disponibili pochi trattamenti sistemici, rappresentati principalmente dalla chemioterapia a base di platino-derivati o dal cetuximab. L'immunoterapia è una nuova strategia terapeutica ancora limitata al setting palliativo (malattia ricorrente non resecabile o metastatica). La ricerca di nuovi biomarcatori o possibili nuovi meccanismi target è molto rilevante quindi nel contesto clinico dell'HNSCC. In questa tesi ci si concentrerà sullo studio di tre possibili popolazioni immunitarie pro-tumorali studiate nell'HNSCC: i neutrofili tumore-associati (TAN), le cellule B intratumorali con fenotipo immunosoppressivo e i T-reg CD8+. Particolare attenzione è data all'applicazione di moderne tecniche biostatistiche e bioinformatiche per riassumere informazioni complesse derivate da variabili cliniche e immunologiche multiparametriche e per validare risultati derivati ​​in situ, attraverso dati di espressione genica derivati da dataset pubblici. Infine, la seconda parte della tesi prenderà in considerazione progetti di ricerca clinica rilevanti, volti a migliorare l'oncologia di precisione nell'HNSCC, sviluppando modelli predittivi di sopravvivenza, confrontando procedure oncologiche alternative, validando nuovi classificatori o testando l'uso di nuovi protocolli clinici come l'uso dell'immunonutrizione.Strong evidences demonstrate a close interplay between the immune system and the biological development and clinical progression of solid tumors. The effect that the tumor immune microenvironment can have on the clinical behavior of the disease is referred as the immuno contexture. Nevertheless, the current clinical management of patients affected by cancer does not take into account any immunological features either for the staging or for the treatment choices. Head and Neck Cancer (HNSCC) represents the 7th most common cancer worldwide and it is characterized by a relatively poor prognosis and detrimental effect of treatments on the quality of life of patients. Beyond surgery and radiotherapy, few systemic treatments are available, mainly represented by platinum-based chemotherapy or cetuximab. Immunotherapy is a new therapeutical strategy still limited to the palliative setting (recurrent not resectable or metastatic disease). The search for new biomarkers or possible new targetable mechanisms is meaningful especially in the clinical setting of HNSCC. In this thesis a focus will be given on the study of three possible pro-tumoral immune populations studied in HNSCC: the tumor associated neutrophils (TAN), intratumoral B-cells with a immunosuppressive phenotype and the CD8+ T-regs. Biostatistical and bioinformatical techniques are applied to summarize complex information derived from multiparametric clinical and immunological variables and to validate in-situ derived findings through gene expression data of public available datasets. Lastly, the second part of the thesis will take into account relevant clinical research projects, aimed at improving the precision oncology in HNSCC developing survival prediction models, comparing alternative oncological procedures, validating new classifiers or testing the use of novel clinical protocols as the use of immunnutrition

    Prognostic biomarkers for stage II and III colon cancer

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    As we learn more and more about the underlying biology of colon cancer, biomarkers will play a prominent role in the improvement of the identification of patients with high risk of recurrence. Once the identification of the prognostic tumour characteristics has been optimized an appropriate therapy can be advised, whereas others may safely choose to refrain from adjuvant therapy. In this thesis we tried to optimize the process of identification of patients with poor prognosis, the efficacy, the safety and the cost-effectiveness of adjuvant therapies need to be addressed separately, and was beyond the scope of this thesis. In Chapter 2 we described the prognostic value of microvessel density (MVD) as a surrogate marker for angiogenesis, one of the hallmarks of cancer. As angiogenesis itself remains difficult to measure directly, MVD may provide insight in this microenvironmental process. This computerized morphological study showed that MVD increases with stage, which may explain the observation that stage II patients with high MVD had poor prognosis, biologically being a kind of pre-stage III. Actual stage III patients with high MVD, that were all treated with adjuvant 5-FU based chemotherapy, showed better prognosis on the contrary. We hypothesized that residual or recurrent tumour tissue in stage III patients, from primary tumours with high MVD, were better penetrable for chemotherapy, explaining the improved survival. In Chapter 3 we tried to validate CDX2 immunohistochemically, being a promising biomarker published in a high-impact journal by Dalerba et al. Our study showed the practical hurdles involved in validating biomarkers in other cohorts. For disease free survival we were not able to find significant differences between high and low expression of CDX2. However, for disease specific survival we did find comparable results. For a subset of 41 patients we analysed expression of CDX2 by both immunohistochemistry and mass spectrometry. Interestingly, discriminatory power of CDX2 as a prognostic biomarker detected by mass spectrometry outperformed the immunohistochemical detection method. This observation shows that in some cases the biomarker itself may be promising, but the method ought to be fine-tuned to benefit from that marker’s full potential. In chapter 4 we presented a new biomarker, obtained from promising research in mice. Expression of KCNQ1 and CD44, both regulated by Wnt-signalling, was analysed immunohistochemically in 386 stage II and III patients, and on mRNA in an external cohort of 90 patients. We concluded that KCNQ1 was a strong prognostic biomarker for disease recurrence. KCNQ1 may be particularly useful in stage II MSS patients, where the question remains which patients are at risk for recurrence and might benefit from adjuvant chemotherapy. In Chapter 5 MACROD2 was discussed, a relatively unknown gene, although a tumour suppressing function by activating PARP1 and DNA repair is suspected. We indeed found that low nuclear expression was associated with poor prognosis in stage III MSS colon cancer patients, treated with 5-FU based ACT. Even more, high expression of MACROD2 may serve as a predictive biomarker in stage III MSS tumours, favouring adjuvant treatment with 5-FU compared to no adjuvant treatment at all. In the final chapter, Chapter 6, we describe an ultimate attempt to improve the identification of high risk patients. Several biomarkers have been studied on our cohort over the years, some with promising and some with disappointing results. For this study we intended to analyse all these markers combined, to find out which (combination of) biomarkers was able to estimate prognosis best, and whether or not previous less important biomarkers became more interesting. Although other techniques were also used on (some subsets of) this cohort, i.e. mass spectrometry, next generation sequencing and morphological analysis (MVD), for this study we chose for a feasible and widely applicable technique like immunohistochemistry. Therefore, all immunohistochemical biomarkers examined previously on tissue micro arrays were included, in addition to all common clinical and pathological parameters available in our cohort. These were all included in a Classification and Regression Tree (CART) analysis, which showed that both lymphovascular invasions (LVI) and KCNQ1 were the key features for estimating prognosis in stage II and III colon cancer

    Identifying therapeutic targets against viral hepatitis and liver cancer

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    Oral health in children and adolescents with juvenile idiopathic arthritis : Caries, plaque, gingival bleeding, and oral health-related quality of life

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    Munnhelsen blant norske barn og unge med juvenil idiopatisk artritt (JIA) er ukjent. Internasjonale studier som fokuserer på munnhelsen hos denne pasientgruppen, viser motstridende resultater, samtidig som kvaliteten på forskningen som er utført spriker. JIA omfatter ulike sykdomskategorier med distinkte egenskaper, noe som medfører at forebyggende tiltak rettet mot denne pasientgruppen er avhengig av mer kunnskap. Det overordnede målet med avhandlingen var å undersøke mulige forskjeller når det gjelder karies, plakk, gingival blødning og munnhelserelatert livskvalitet mellom unge individer med JIA og en kontrollgruppe uten JIA. I tillegg var delmål å vurdere om sosiale-, adferdsmessige - og munnhulefaktorer påvirket de observerte forskjellene i tannhelse, vurdere effekten av klynge data og evaluere variasjonen i karies og periodontale tilstander på flate-nivå. Et ytterligere delmål var å måle variasjoner i tannhelse etter JIA spesifikke karakteristika. Hypotesen var at unge individer med JIA har dårligere munnhelse og opplever dårligere munnhelserelatert livskvalitet enn jevnaldrende uten JIA. Deltakerne, 4-16 år gamle med JIA (n=224) og matchete kontroller (n=224), fikk indekstenner undersøkt mellom 2015-2018 av kalibrerte tannleger ved hjelp av anerkjente måleinstrumenter. JIA-spesifikke karakteristika ble vurdert av barnerevmatologer, og sosiodemografiske, adferdsmessige og selv-rapporterte munnhelseopplysninger ble innsamlet ved hjelp av spørreskjema og intervju. Flernivå analyser viste signifikant sammenheng mellom JIA status og plakk, og gingival blødning, men ikke for karies. Forskjeller mellom JIA- og kontrollgruppen med hensyn til munnhelserelatert livskvalitet var avhengig av type analyse og gav ikke entydige resultater. Lav utdanning blant mødre økte signifikant risikoen for karies. Jenter 12-16 år gamle med JIA hadde økt sannsynlighet for å rapportere om påvirket livskvalitet. Signifikant interaksjon mellom karies og plakk på flate-nivå og gruppetilhørighet ble påvist i det permanente tannsettet. Økt sannsynlighet for approksimal-karies (i.e., mesial) var merkbar blant JIA gruppen i det permanente tannsettet. Klynge-effektene demonstrerte behovet for flernivå analyser. Visse JIA spesifikke karakteristika, ofte forenelig med et mer alvorlig sykdomsforløp, indikerte økt risiko for påvirket munnhelse. Det kan konkluderes med at hypotesen om dårligere munnhelse blant unge med JIA sammenlignet med jevnaldrende, bekreftes for de periodontale tilstandene, men ikke for karies og munnhelserelatert livskvalitet målt ved generiske instrumenter. Forebyggende tiltak har stort potensiale blant barn og unge med JIA; økt fokus er nødvendig på flere plan, også blant de som ikke er tannhelsepersonell, for å oppnå best mulig helse blant unge individer med JIA.Oral health in Norwegian children and adolescents with juvenile idiopathic arthritis (JIA) is undetermined. International studies report inconsistent findings, and high-quality research is called for. JIA encompasses a heterogeneous group of disease categories, and the distinct characteristics must be accounted for when evaluating this group of patients. The main objective of this multicenter cross-sectional study was to explore whether the outcome variables caries, plaque, gingival bleeding, and oral health-related quality of life (OHRQoL) differ between young individuals with JIA compared to controls without JIA. Additionally, explore whether socio-behavioral and intraoral characteristics affect the outcomes and whether these covariates vary according to group affiliation on impacted OHRQoL. Multilevel modeling facilitated caries and periodontal exploration at surface-level and cluster effect measures. Association between JIA-specific features and the outcomes was evaluated. We hypothesized that young individuals with JIA have poorer oral health than their peers. Participants, 4-16-year-olds with JIA (n=224) and their matched controls (n=224), were assessed, according to index-teeth and internationally acknowledged indices, during 2015-2018 by calibrated dentists. Pediatric rheumatologists evaluated JIA-specific characteristics, and socio-demographic, behavioral, and self-reported oral health information was collected through questionnaires and personal interviews. Adjusted mixed effects logistic regression showed a significant association between JIA status and plaque, and gingival bleeding, but not for caries. JIA status was significantly associated with impacted OHRQoL by application of negative binomial regression amongst the youngest (4-11 years) but not amongst the participants from 12 years; ordinary logistic regression did not show any significant associations in any age groups. Low maternal educational level was significantly associated with caries. Female adolescents (12-16 years) with JIA were more likely to report OHRQoL impacts. Surface-specific caries and plaque in the permanent dentition varied among the two groups. A trend of increased caries susceptibility on approximal surfaces (i.e., mesial) of permanent molars was apparent in the JIA group. Cluster effects warranted the application of multilevel modeling. Some JIA-specific features, often consistent with a more severe disease course, are suggested to increase susceptibility to impaired oral health. In conclusion, the hypothesis of poorer oral health in young individuals with JIA compared to peers was confirmed for the periodontal outcomes but not for caries and OHRQoL measured by generic instruments. The potential of preventive strategies among young individuals with JIA is considerable; increased focus beyond the dental disciplines is needed to achieve the best possible outcomes.Doktorgradsavhandlin
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