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- Associação dos polimorfismos dos genes da IL-1 e do IL-1RA com a peri-implantitePublication . Cardoso, José Maria Correia Gonçalves Neves; Alves, Ricardo Castro; Ribeiro, Ana Clara; Noronha, Susana do CantoDental implants are currently an increasingly predictable and effective modality for the rehabilitation of partially or totally edentulous patients, contributing to the patient's quality of life. This type of rehabilitation has high success and survival rates, however biological complications may arise. Such complications mainly refer to inflammatory conditions associated with bacterial challenge, and two clinical variants can be distinguished: peri-implant mucositis and peri-implantitis. While the presence of an inflammatory lesion is a common feature of both conditions, only the latter is associated with loss of supporting bone. Mucositis is thought to precede peri-implantitis. With the massive increase in the number of patients with dental implants, the prevalence of inflammatory conditions around implants is also intensifying. Peri-implantitis is becoming a scourge and a serious public health problem, being their management challenging, and being associated with significant morbidity. The treatment of peri-implantitis involves high costs for the community and often fails to control the progression of the disease, leading to loss of the implant. This situation of implant loss is associated with bone loss, which in some cases may require complex bone grafting procedures for a new implant placement or, as a last resort, may make a new implant placement impossible. The impossibility of replacing an implant has consequences for the patient in terms of health, function and esthetics. There is currently no test that can determine the susceptibility of a patient to peri-implantitis who will receive a dental implant. At the end of the last century, the hypothesis was generated that the genetic background of an individual may modulate the severity and progressive character of oral inflammations through expression of cytokines and their modulators. Interleukin-1 (IL-1) is a multifunctional cytokine playing a key role in the pathogenesis of inflammatory diseases with a large number of diverse activities and functions in immune response, inflammation, tissue breakdown, and tissue homeostasis. The IL-1 family includes 11 cytokines, whose coding genes are located on the long arm of chromosome 2q. The two most extensively studied members are the IL-1A, IL-1B genes, which encode IL-1α and IL-1β, respectively. Within the IL-1 family of proteins, there is also the IL-1 receptor antagonist (IL-1Ra), which is encoded by the IL-1RN gene. IL-1Ra plays an anti inflammatory role by preventing the transmission of proinflammatory signals and preventing the immune response by using the same receptor as proinflammatory IL-1. Scientific evidence indicates that biological complications in dental implants tend to be concentrated in a subset of individuals, which seems to imply that the host response may play a determining role in implant success. Even when exposed to similar risk factors, not all patients develop peri-implantitis, a situation that highlights the importance of genetic predisposition and differences between populations. Given the crucial role of IL-1 and IL-1Ra in inflammation, the genes IL-1A, IL-1B and IL1RN are potential candidates for genetic markers in peri-implantitis. However, studies that analyzed the relationship between these polymorphisms and peri-implantitis have shown conflicting results. Therefore, a systematic review and meta-analysis was performed, before the experimental work, to quantitatively synthesize existing studies to evaluate the association of common functional polymorphisms in the IL-1 and IL-1RN genes with susceptibility to periimplantitis (Chapter 2). This review attempted to overcome the existing limitations of published systematic reviews and meta-analyses. No robust conclusions could be drawn from the current literature about the possible link between genetic variations and the occurrence of peri-implantitis. The inequality of the design of the studies requires more studies to be carried out using larger population samples and from different ethnic groups. Studies have reported that the frequency of gene polymorphisms associated with genetic susceptibility to a particular disease can be influenced by ethnic and racial variations. There are few studies that try to evaluate this possible relationship in southern Europe. In this sense our main purpose was to investigate whether the three genetic variants (IL-1A - 889C/T, IL-1B + 3954C/T and IL-1RN (Variable Number of Tandem Repeats (VNTR)) were associated with the occurrence of peri-implantitis in a Portuguese Caucasian population. Prior to the main study, a pilot study was conducted with twenty participants (Chapter 4) to test the feasibility of the study and to calculate the sample size. Subsequently, a cross-sectional analytical study was carried out (Chapter 5), involving a total of 102 Portuguese Caucasian individuals. Participants were categorized into two groups: 59 with healthy implants and 43 individuals with periimplantitis. Buccal mucosa samples were swabbed and genetic analysis was performed at the Molecular Biology Laboratory of the Egas Moniz School of Health and Science, using the real-time polymerase chain reaction (PCR) technique for IL-1A and IL-1B and using PCR for IL-1RN. The IL-1A -889 C/T polymorphism showed a higher prevalence of the altered allele (T allele) in cases of peri-implantitis than in healthy cases (27.9% vs 16.9% respectively), although without statistically significant differences (p = 0.060). For the IL-1B +3954 C/T and IL-1RN (VNTR) polymorphisms, the analysis revealed that the frequencies of the different alleles and different genotypes did not differ significantly between the groups. Although there are studies that attempt to link the existence of certain genetic polymorphisms and the presence of peri-implantitis, with contradictory results, the scientific evidence on the possible relationship between genetic alterations and biochemical alterations in the peri-implant crevicular fluid (PICF) is very scarce. The possible association between genetic polymorphisms and periimplantitis must be based on a change in the individual's immune-inflammatory. In this way the aim of our investigation was also to evaluate the levels of the inflammatory response markers IL-1β, PGE2 and TNF-α in the PICF of patients with healthy dental implants and individuals with peri-implantitis, under consideration of the patients´ individual IL-1 and IL-1RN genotypes. Biochemical analysis was performed on 51 of the 102 patients who underwent genetic analysis (Chapter 6). For the biochemical analysis, the concentrations of PICF inflammatory mediators IL-1b and TNF-a were analyzed using multiplexed fluorescent sphere immunoassays and PGE2 by enzyme-linked immunosorbent assay (ELISA). In patients where the presence of the polymorphism in the IL-1RN was detected, there was an increase in the concentration of the three inflammatory mediators with statistically significant differences for TNF-a and PGE2 mean values, regardless of peri-implant health status (p = 0.002 and p = 0.049, respectively). Based on the results obtained in this work, it could be concluded that there was no correlation between IL-1A -889, IL-1B +3954 and IL-1RN polymorphisms and peri-implantitis, on the studied population. On the other hand, it was observed that the prevalence of these polymorphisms in the population evaluated was lower than in other European countries. This situation may hypothetically explain the absence of differences between groups regarding the role of these polymorphisms in the occurrence of peri-implantitis. This situation emphasizes how important it is to develop this type of studies in different ethnic groups. It was observed that individuals with the IL-1RN gene polymorphism, regardless of their peri-implant health status, have higher levels of TNF-α and PGE2 in the PICF compared to patients without the polymorphism, which could put them at greater risk of peri-implant inflammatory complications. These results should be confirmed in studies with larger samples and ideally with a longitudinal character, as this will allow better control of the various factors that may influence the onset and progression of a disease with a multifactorial etiology such as periimplantitis. Among the patients with the positive composite genotype (at least one allele with nucleotide sequence changed in IL-1A and IL-1B genes), it was observed that those with peri-implantitis had a greater volume of PICF and a higher concentration of PGE2.
- Comparison between osseodensification and conventional osteotomy protocol for implant site preparationPublication . Gaspar, João Rui Carvalho; Mendes, José João; Neiva, RodrigoOral rehabilitation with endosseous implants is a safe and effective treatment option which is associated with high success rates. Implant stability is a critical factor for the clinical success of rehabilitation and includes primary stability (mechanical engagement obtained upon insertion into the bone, holding the implant in place), and secondary stability (biological fixation that occurs due to the new bone formation during healing, resulting in osseointegration). It has been shown in the literature that implant micromotion exceeding 50 to 150 μm during healing period can lead to fibrous tissue interposition at the boneimplant interface and consequent failure in the osseointegration process. Therefore, according to several authors, high degrees of primary stability are associated in the literature with superior and higher probability of osseointegration. Furthermore, there are several parameters that must be considered during the implant site preparation, which should be as atraumatic as possible to maintain cell viability. The preservation of the bone structure and collagen matrix, together with the increase in primary stability, also demonstrated the potential to accelerate the post-surgery healing process. In 2015, a novel surgical technique for implant site preparation termed osseodensification (OD) has been introduced. It is a non-subtractive drilling technique that preserves bone by using specially designed burs in counterclockwise (CCW; noncutting motion) with copious irrigation. Contrary to conventional drilling techniques, OD promotes bone compaction along the osteotomy walls and into the trabecular spaces, increasing the bone density at the site. Several authors reported that this technique can help to obtain higher values of primary stability and implant insertion torque, especially in less dense bone. However, these drills have a dual-mode action since they may also be used in clockwise direction (CW) in which they have cutting capacity like any other system. Since it pushes the bone instead of removing it, OD has enormous potential in the field of oral implantology in different indications, namely in ridge expansion, post-extraction implant placement or maxillary sinus floor elevation (SFE) by crestal approach with high predictability and reduced morbidity, compared to alternative techniques.The main objective of this doctoral project was to contribute to advance knowledge regarding the OD technique and to validate its versatility and application in different clinical situations. In this sense, we decided to perform a systematic review and meta-analysis, with the aim of comparing implant stability between site preparation with OD compared to the conventional osteotomy protocol. This review was the first to exclusively analyze human data and demonstrated that OD consistently achieved higher values of primary and secondary stability (4-6 months after implant placement) compared with conventional drilling (Chapter 3). In addition, we had the opportunity to participate in an international multicenter retrospective clinical study, with colleagues from five nationalities, which confirmed the ability of OD to expand the interradicular septum for the post-extraction implant placement in molars. Furthermore, this study also allowed the introduction of a new molar socket classification, which can be used by the scientific community and facilitate communication between peers (Chapter 4). Finally, according to the current evidence, OD appears to have, in fact, enormous potential for SFE. However, there is still a lack of scientific studies with adequate methodology that effectively allow the OD technique to be considered as a valid alternative to the classic lateral window technique (LW), especially in highly resorbed posterior maxilla in which it continues to be considered the gold standard. Therefore, we decided to conduct a randomized clinical trial with the aim of comparing the effectiveness and impact on patients' quality of life of SFE with OD versus LW, both with simultaneous implant placement when residual bone height (RBH) < 4 mm. The results showed that, although both techniques were similarly effective, OD significantly outperformed LW in pain experience, impact on self-perceived quality of life, surgery duration, postoperative edema and analgesics intake (Chapter 5). In conclusion, OD represents a paradigm shift in implantology in terms of implant site preparation. This thesis confirms its clinical potential and versatility in different situations, from optimizing the implant site alone to bone expansion or SFE by crestal approach. Furthermore, our results position OD as a real and valid alternative to the LW technique in extreme cases with reduced RBH, with a significant improvement in patient experience.
- Dentify : virtual reality and haptics in teaching dental implantology and operative dentistry: an approach to multimodal simulationPublication . Rodrigues, Pedro Miguel da Silva; Mendes, José João; Lopes, Daniel Simões; Ribeiro, Carlos ZagaloThe technological revolution is no longer imminent, but, instead, a reality. Technology has consolidated, in societies, the emergence of rapid change in the qualifications of the population and, consequently, the economy. In general, accessibility to information has expanded educational needs and demands. Particularly on the teaching and student population, the universalization of information technology has irreversibly imposed the appropriate pressure for the benefits of digital transformation and this, in turn, is directly dependent on the skill-set of its population. The real benefits of technological transformation can only be felt by a population, in the medium and long term, by placing these platforms in the integrated scheme of Education. The introduction of Virtual Reality (VR) and Haptic Technology (HT) have added new dimensions to education and the way we approach daily professional challenges. If, on the one hand, it is legitimate to say that necessity creates technology, on the other hand, it is equally valid to infer that technology imprints an irreversible need to reevaluate preexisting conventional methodologies, with an objectively critical and constructive sense. When applied to teaching, this strategy tends to provoke qualitative and quantitative changes on pedagogy with the purpose of improving the student. In Health teaching, its application has changed the approach paradigm to both the patient and the disease. It is unequivocally intended for a training process that is closer to the real thing and allows for a greater number of simulation repetitions prior to the medical act, to reduce the number of complications resulting from the act itself, enable greater predictability, and lower morbidity. Pre- and post-graduate education in Dentistry require an evolutionary break; a qualitative leap in line with the real technological potential that we currently have. More predictable results are desired from students with more training hours and with the constancy of competence that arises from repetition. This presents a real need and opportunity in Teaching. In dental training, the transition from preclinical pre- and post-graduate teaching to clinical teaching are moments of central importance for the student. It is in the preclinical stage that the student begins to develop the manual dexterity that will allow him/her to perform the fine and delicate movements and tactile perception necessary for the execution of the protocols inherent to treatment in such delicate tissues as oral tissues. It is also at this stage that the student is most likely to acquire the criteria of rigour and evaluation for the execution of such procedures. Traditionally, pre-clinical teaching occurs through simulation in synthetic and/or human or non-human non-living models, not considering patient motivation, expectations, pain and emergency situations that involve the treatments of real patients. Clear communication of the aforementioned evaluation criteria will allow the student to learn and define his own execution criteria, which is in line with the overarching goal of improving simulation to ease the transition to clinical life, thus reducing the anxiety associated with this transition as well as reducing iatrogenesis. Given the irreversibility of clinical protocols in Dentistry in general, and particularly in Operative Dentistry and Implantology, teaching in these areas presents, in the practical side of training, a fundamental vector in skill acquisition. The purpose of this research is to amplify Operative Dentistry and Dental Implantology teaching through the creation of a simulator with VR and haptic technology, centered on the student's self-assessment by exposing him/herself to simulated scenarios with virtual reality and haptic technology. Having identified the limitations inherent not only to conventional teaching in Implant Dentistry and Operative Dentistry, but also to available simulators, an immersive and multimodal simulator using virtual reality and haptic technology was developed, based on the student’s educational and pedagogical self-perception, allowing the transposition of the aforementioned limitations. The absence of universal evaluation systems, along with consistent simulation on artificial models with little pathological reality, distances conventional simulation from clinical reality. The project aims to validate the use of haptic technologies and virtual reality as methods to improve teaching in Dentistry and Implantology, with proven applicability in preclinical scenarios. The simulator could never be built without a collaborative strategy between pedagogy and programming. The contribution of educational sensitivity in Dentistry would first be introduced by testing the simulator prototype with experienced Dentistry professionals and professors at the Instituto Universitário Egas Moniz (IUEM), Egas Moniz School of Health and Science, in the areas of Dental Implantology and Operative Dentistry, in the context of collaborative work and co-design of the simulator. It was determined that tests with students would only take place after 1) validation of the prototypes through tests with professionals and their publication; and the introduction of changes suggested by the tests with professionals in a more definitive and elaborated version of the prototypes prior to testing with students. The development of the simulator was therefore subdivided into 2 vectors corresponding to the proposed areas: Dental Implantology (IMMPLANT) and Operative Dentistry (DENTIFY OD). IMMPLANT consists of a tech probe that combines a VR head-mounted display, a small hand tracking device placed in the front side of the VR headset and a smartphone, all connected to a laptop. User interaction with the virtual scenarios follows a bi-manual approach where the free (dominant) hand directly manipulates all 6 or 5 degrees-of-freedom of either the mandible or implant, respectively, while the other (non-dominant) hand operates a smartphone for more fine-tuned manipulation. DENTIFY OD is a multimodal simulator that resorts to VR and haptic pen technology. It places the student/user in an immersive virtual environment, composed of visual, auditory and haptic stimuli. It combines a haptic pen, VR goggles with audio output, turbine and drilling sounds, virtual dental models of isolated teeth and complete dental arches. To promote realism of the virtual environment immersion, the haptic pen grip has been replaced by a printed model of a dental turbine. It is intended to be a pedagogical tool for training and teaching the cavity preparation phase in OD, aimed at students in preclinical training for the purposes of improving the student's manual dexterity and three-dimensional spatial manipulation, increasing the number of repetitions per training session, and, additionally, providing a set of metrics corresponding to each use, per user. The simulator also allows for users to save their data per user and per simulation, thus allowing the user to compile a graphical progressive evaluation. Exposing the student to DENTIFY's metrics results aims to stimulate self-assessment and self-criticism, as well as the perception of the user's own learning curve on the grounds of objective and numerically measurable parameters. The tests performed by dental professionals with the IMMPLANT and DENTIFY OD prototypes were very encouraging to the progressive development of DENTIFY. Preliminary tests of IMMPLANT with professionals involved guided interviews, as well as usability and workload questionnaires, whose results allowed us to conclude that it constitutes a versatile virtual reality tool suitable for education in Dental Implantology. The co-design strategy mentioned above was extended to DENTIFY OD, using questionnaires on workload; cybersickness; system usability; and guided interviews. The user acceptance results allowed for the conclusion that DENTIFY OD shows potential in improving its teaching, promotes self-assessment, and provides a real multimodal immersion. It showed pedagogical potential in Operative Dentistry. Regarding of the Dental Implantology’s evolution, it was a conscious choice to not run the tests with students at this stage since, in development meetings, it was concluded that it was mandatory to explore more of its pedagogical potential, lest this tool be underutilized. Regarding DENTIFY OD, tests were performed with students on a renewed simulator, which included, in its reprogramming, results obtained from the previous tests, leading to software changes regarding its aesthetics, handling and usability. Tests with 3rd year Dental Medicine Integrated Master students at the IUEM took place in different sessions and focused on measuring self-assessment and usability by the users (undergraduates). Again, the results can be considered very positive. Students adhered very positively to sessions with the simulator, presenting indistinct performance metrics between users with and without previous experience with Virtual Reality, as well as similar results between gamers and non-gamers. The possibility of instant evaluation and, thus, helping in creating self-criticism in performance standards were considered fundamental in DENTIFY OD’s pedagogical attributes. The inherent potential of Virtual Reality and Haptic Technology suggests that these should be included in the pedagogical reality of pre-clinical teaching in Dentistry, in a definitive, gradual, and consistent manner while presenting measurable performance metrics that reflect the student’s evolutionary curve, numerically and without subjectivity. This work is in conformity with the following UNESCO Objectives for Sustainable Development: ODS 4 – Ensure inclusive and equitable quality education and promote lifelong learning opportunities for all – by universalizing and allowing teaching by cost reduction of the available technology and, therefore, allowing accessibility. ODS 9 – to promote and foster innovation – by further enabling haptic technology and virtual reality in teaching Dental Medicine. To promote better oral health care services to the general community by improving dental teaching.
- 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.