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- The impact of periodontal infection and its treatment on alpha-synuclein levels and inflammationPublication . Lyra, Patrícia Soares; Mendes, José João; Botelho, João; Chaudhuri, Kallol RayPeriodontitis - a chronic inflammatory disease of tooth-supporting tissues, that can lead to tooth loss - is a major source of inflammation and can have a disruptive effect on systemic health. On the one hand, an untreated periodontal infection may result in the dissemination of periodontal bacteria and their products to distant tissues with pathological implications; and on the other hand, there is the hypothesis of a periodontitis-induced systemic inflammatory burden, through the haematological dissemination of inflammatory mediators. The resulting state of peripheral chronic inflammation supports the association of periodontal infection with several extra-oral inflammation-driven pathologies, namely diabetes mellitus, cardiovascular disease, cancer, rheumatoid arthritis, adverse pregnancy outcomes or even neurodegenerative conditions such as Alzheimer’s disease (AD) and, more recently, Parkinson’s disease (PD). In fact, there is a clear association between periodontitis and α-synucleinopathies - a group of neurodegenerative disorders characterised by abnormal intracellular aggregation of α-synuclein (α-Syn) - such as PD, due to the inherent motor and cognitive impairments and the consequent impact on the oral health of PD patients. To date, the biological and pathological mechanisms of protein α-Syn remain unclear, and the contributing effect of environmental influences such as systemic chronic inflammation and dysbiotic disturbances in commensal gut and/or periodontal microflora are not discarded as one of the key multifactorial mechanisms of PD onset and progression. In this context, there is also a potential for the indirect prevention and/or management of α-synucleinopathies through the treatment of peripheral chronic, inflammatory, and dysbiotic pathologies, such as periodontitis. All in all, the evidence linking PD and periodontitis remains inconclusive due to the lack of intervention studies focusing on relevant biological pathways. In today's context of an ageing population, there is real concern about the growing prevalence of neurodegenerative diseases, whose risk usually increases with age; as well for the deleterious systemic impact of periodontitis – the most common chronic inflammatory non-communicable illness worldwide. To this end, this study aimed to investigate whether the chronic pattern of periodontitis may be responsible for persistent inflammatory states with unknown consequences in PD and other α-synucleinopathies. In addition, the aim was to help establish the basis for a potential biological mechanism linking periodontal infection (and its treatment) with PD through its keystone marker, α-Syn, which has never been investigated. For this purpose, we initiated this research project with an extensive review of the available evidence to date on the mechanistic pathways of α-Syn to inflammation, as well as the potential role of microbial dysbiosis and systemic inflammatory mitigation on α-Syn, as presented in Paper I (Chapter 3). Overall, microbiota and inflammation seem to have a significant role in the pathogenesis of α-synucleinopathies. Alongside intestinal dysbiosis, oral microbiota dysbiosis ought to be considered in α-Syn pathology. Finally, the therapeutic management of chronic inflammatory pathologies, such as periodontitis, may yield beneficial results for the clinical outcome of α-synucleinopathies. Furthermore, the publication of Paper II (Chapter 4) allowed for the observation of the systemic burden of periodontitis in PD patients by comparing the highsensitivity C-reactive protein (hs-CRP) levels of self-reported periodontitis cases with periodontally healthy counterparts in a PD population, using available data from the American database National Health and Nutrition Examination Survey (NHANES) and following eligibility criteria. Through this study, we were able to strengthen the existing hypothesis that PD patients with periodontitis carry a systemic inflammatory burden, which can be translated into higher circulating hs-CRP levels. This study provided a reasonable basis for further investigation of the systemic inflammatory burden associated with periodontitis and its treatment using α-Syn levels in people otherwise free of neurological impairment, which we subsequently did in Paper IV (Chapter 6). In order to achieve the most effective strategies for patient identification, in our third study, Paper III (Chapter 5), we cross-culturally adapted and validated a self-report strategy for predicting periodontitis prevalence in a Portuguese population. Our results showed that self-report measures of periodontitis combined with risk factors (such as smoking status and diabetes mellitus) had predictive validity for periodontitis and its severe form in the Portuguese population, using both the 2018 and 2012 case definitions. Finally, in Paper IV (Chapter 6), baseline salivary and blood levels of α-Syn, Interleukin (IL)-6 and IL1-β were analyzed according to the periodontal status and 30 days following standard periodontal therapy. We found no linear association between the saliva and plasma α-Syn levels at baseline, indicating that the bioavailability of both markers seems to function independently. Also, periodontal diagnosis does not seem to alter baseline α-Syn levels in both biological fluids. When analysing the effects of non-surgical periodontal therapy (NSPT) on α-Syn levels, our results show no significant variations in plasma, but salivary α-Syn levels showed a decrease at the 30-day of follow-up, especially in periodontitis patients. The present thesis confirmed that NSPT appears to have an effect on salivary α-Syn levels. These results present clinical relevance when using salivary α-Syn as a biomarker in the in diagnosis or clinical management of α-synucleinopathies, with periodontal therapy being a confounding factor if performed at least up to one month prior to the analysis. However, these preliminary findings require further confirmation in future larger and prospective studies.
- Sex and age prediction through dental and radiographic measurements : elaboration and validation of forensic models for the portuguese populationPublication . Neves, João Albernaz Santos Coelho das; Mendes, José João; Botelho, JoãoAge estimation interest has grown in recent years, both because of the increasing number of unidentified corpses and because of the existence of living people without validated birth dates. There are two types of dental age estimation: developmental changes, which occur in human dentition during eruption, and degenerative changes, which occur during attrition. The eruption of the third molar occurs between the ages of 17 and 19 years. The tooth may be fully developed yet displaced, fully or partly displaced, or missing altogether. Only radiographs can provide accurate documentation of its status. Sex determination is important in forensic dentistry to help identify unknown persons. There are four ways to do this: skull analysis, DNA analysis of oral tissue, dental morphology, and measurement of mesiodistal and lingual vestibular dimensions, the latter being the easiest way to determine sex. Evidence is synthesized and evaluated through systematic reviews and metaanalyses. They can guide clinical practice by providing information on the effectiveness of treatments or the diagnostic and prognostic accuracy. However, the relationships between individual exposures and outcomes are the focus of systematic reviews and meta-analyses. They may not capture all potentially relevant exposures or effects in a whole study area. Ongoing efforts have identified significant deficiencies in the reporting of narrative syntheses, and the quality of conducting and reporting systematic reviews continues to be low. Clinicians and policy makers need guidance on the quality of systematic reviews, but the existing literature does not provide it adequately.