Cuidados dentários no âmbito do tratamento de radioterapia da cabeça e do pescoço : revisão narrativa

Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas MonizHoje em dia a prevalência do cancro da cabeça e do pescoço é elevada, sendo o sétimo tipo de cancro mais prevalente a nível mundial, que abrange diversos órgãos da parte superior do corpo. Em 2016, houve 1.1 milhões de casos novos e 4.1 milhões de casos prevalentes de cancro da cabeça e do pescoço, resultando em cerca de 500 000 mortes. Cabe ao profissional de saúde oral a responsabilidade de preconizar estratégias de prevenção primária, secundária e terciária nos pacientes com cancro da cabeça e do pescoço. Estes tipos de cancro são frequentemente descobertos pelo Médico Dentista ou pelo médico, por isso o Médico Dentista tem um papel fundamental na deteção precoce destes cancros, bem como na prevenção e intervenção antes, durante e após o tratamento. Por conseguinte, é necessário fundamentar os critérios e guidelines relativamente as estratégias em todas as fases de prevenção no tratamento da radioterapia da cabeça e do pescoço. “A maioria dos cancros de cabeça e pescoço são tratados com cirurgia, radioterapia, quimioterapia ou uma combinação destas modalidades.” Nesta revisão narrativa, analisaremos especificamente os cuidados prestados aos pacientes submetidos a radioterapia para o cancro da cabeça e do pescoço. Vários efeitos secundários e reações adversas podem ocorrer ao longo da radioterapia de forma precoce ou a longo prazo. O papel do Médico Dentista será adotar medidas preventivas de forma a melhorar a qualidade de vida e a saúde oral do paciente. O objetivo desta revisão narrativa é fornecer um resumo objetivo, fiável e atualizado dos cuidados fornecidos ao paciente antes, durante e após o tratamento com radioterapia da cabeça e do pescoço. Esta investigação fornecerá uma indicação do protocolo para os Médicos Dentistas que enfrentam esta situação no seu consultório.Nowadays the prevalence of head and neck cancer is high, and it is the seventh most prevalent type of cancer worldwide, covering various organs in the upper body. In 2016, there were 1.1 million new cases and 4.1 million prevalent cases of head and neck cancer, resulting in around 500,000 deaths. Oral health professionals are responsible for advocating primary, secondary and tertiary prevention strategies for patients with head and neck cancer. These types of cancer are often discovered by the dentist or doctor, so the dentist has a fundamental role to play in the early detection of these cancers, as well as in prevention and intervention before, during and after treatment. Therefore, it is necessary to substantiate the criteria and guidelines for strategies at all stages of prevention in the treatment of head and neck radiotherapy. "Most head and neck cancers are treated with surgery, radiotherapy, chemotherapy or a combination of these modalities." In this narrative review, we will specifically analyze the care provided to patients undergoing radiotherapy for head and neck cancer. Various side effects and adverse reactions can occur during radiotherapy in the early or long term. The role of the dentist will be to adopt preventive measures in order to improve the patient's quality of life and oral health. The aim of this narrative review is to provide an objective, reliable and up-to-date summary of the care provided to patients before, during and after head and neck radiotherapy treatment. This research will provide an indication of protocol for dentists facing this situation in their practice

How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements

Les espaces en creux de la protection environnementale, nouveaux terrains de recherche et d’action à explorer ?

Le texte propose d’esquisser les problématiques associées aux espaces en creux de la protection environnementale. Ceux-ci posent question à divers égards aux géographes, tant dans leur définition, que dans les méthodologies adoptées pour leur analyse. La mobilisation spécifique des acteurs de ces zones en fait des espaces novateurs du point de vue de la gouvernance des milieux. Enfin, les modalités spatiales de structuration des demandes sociales développées dans ces zones constituent aujourd’hui une piste de travail non négligeable pour les géographes. Entre espaces protégés et espaces non spécifiquement reconnus d’un point de vue environnemental, quels modèles peut-on voir émerger ?This text outlines the main issues related with the hollow spaces of environmental protection; without any particular spatial status of protected area, these spaces generate specific problems of definition, but also methodological difficulties. The mobilization of local stakeholders defines these places as spaces of innovative environmental governance. The spatial modalities of restructuring of social demands developed in these areas are an interesting field of study for some geographers. The possibility to determinate some associated spatial models is also a new research field to explore. Between protected spaces and non-specifically recognized environmental spaces, what models can be expected to emerge

Retourner en forêt quinze ans après sa thèse : quelle place nouvelle pour le paysage dans la gestion forestière depuis le début des années 2000 ?

L’article propose de réexaminer la place du paysage dans deux corpus de textes forestiers, entre 2006 et 2018, dans la continuité d’une thèse antérieure. Au travers des publications récentes de la Revue forestière française et des chartes forestières de territoire signées en région Provence-Alpes-Côte d’Azur (Paca), la définition et l’application de la notion de paysage par les acteurs du monde forestier sont analysées. De plus en plus sollicitée d’un point de vue théorique comme outil d’analyse du territoire et de ses évolutions, la notion de paysage ne semble guère gagner en dimension opérationnelle. Les références au paysagisme d’aménagement, omniprésentes dans la décennie 1980-1990, se raréfient, tandis que l’écologie du paysage, mobilisée dans les travaux scientifiques sur la forêt, n’apparaît guère dans les documents plus opérationnels. En ce sens, les corpus étudiés apparaissent cohérents avec l’évolution plus large de la prise en compte du paysage dans les champs scientifiques et de l’aménagement des territoires. L’ensemble témoigne d’une évolution à bas bruit et sur le temps long, justifiant d’un point de vue méthodologique le « retour sur terrain » ou plus précisément sur « objet » à intervalles réguliers.Following up on a thesis, this article re-examines the role of the landscape in two bodies of forestry documents dating from 2006 to 2018. Based on recent publications of the review Revue forestière française and forestry charters signed in the Provence-Alpes-Côte d’Azur (PACA) region, the definition and implementation of the notion of the landscape by forestry stakeholders is examined. This notion of the landscape is increasingly employed as a theoretical tool for analysing a territory and its evolution, however it does not seem to have acquired an operational dimension. References to landscape management, which were prevalent in the 1980s and 1990s, are becoming rarer, whereas landscape ecology, which is used in scientific research on forests, is hardly ever referred to in the more operational documents. In this sense, the documents studied appear to be consistent with the broader changes in the way the landscape is considered in scientific research and land use planning. The literature bears witness to gradual change over a long period of time which, from a methodological point of view, justifies going back into the “field" or more precisely re-examining the research "object" at regular intervals

Using Clinical Trial Simulators to Analyse the Sources of Variance in Clinical Trials of Novel Therapies for Acute Viral Infections.

BACKGROUND:About 90% of drugs fail in clinical development. The question is whether trials fail because of insufficient efficacy of the new treatment, or rather because of poor trial design that is unable to detect the true efficacy. The variance of the measured endpoints is a major, largely underestimated source of uncertainty in clinical trial design, particularly in acute viral infections. We use a clinical trial simulator to demonstrate how a thorough consideration of the variability inherent in clinical trials of novel therapies for acute viral infections can improve trial design. METHODS AND FINDINGS:We developed a clinical trial simulator to analyse the impact of three different types of variation on the outcome of a challenge study of influenza treatments for infected patients, including individual patient variability in the response to the drug, the variance of the measurement procedure, and the variance of the lower limit of quantification of endpoint measurements. In addition, we investigated the impact of protocol variation on clinical trial outcome. We found that the greatest source of variance was inter-individual variability in the natural course of infection. Running a larger phase II study can save up to $38 million, if an unlikely to succeed phase III trial is avoided. In addition, low-sensitivity viral load assays can lead to falsely negative trial outcomes. CONCLUSIONS:Due to high inter-individual variability in natural infection, the most important variable in clinical trial design for challenge studies of potential novel influenza treatments is the number of participants. 100 participants are preferable over 50. Using more sensitive viral load assays increases the probability of a positive trial outcome, but may in some circumstances lead to false positive outcomes. Clinical trial simulations are powerful tools to identify the most important sources of variance in clinical trials and thereby help improve trial design

Cation–π interactions in protein–ligand binding: theory and data-mining reveal different roles for lysine and arginine

We have studied the cation–p interactions of neutral aromatic ligands with the cationic amino acid residues arginine, histidine and lysine using ab initio calculations, symmetry adapted perturbation theory (SAPT), and a systematic meta-analysis of all available Protein Data Bank (PDB) X-ray structures. Quantum chemical potential energy surfaces (PES) for these interactions were obtained at the DLPNO-CCSD(T) level of theory and compared against the empirical distribution of 2012 unique protein–ligand cation–π interactions found in X-ray crystal structures. We created a workflow to extract these structures from the PDB, filtering by interaction type and residue pKa. The gas phase cation–π interaction of lysine is the strongest by more than 10 kcal mol^-1, but the empirical distribution of 582 X-ray structures lies away from the minimum on the interaction PES. In contrast, 1381 structures involving arginine match the underlying calculated PES with good agreement. SAPT analysis revealed that underlying differences in the balance of electrostatic and dispersion contributions are responsible for this behavior in the context of the protein environment. The lysine–arene interaction, dominated by electrostatics, is greatly weakened by a surrounding dielectric medium and causes it to become essentially negligible in strength and without a well-defined equilibrium separation. The arginine–arene interaction involves a near equal mix of dispersion and electrostatic attraction, which is weakened to a much smaller degree by the surrounding medium. Our results account for the paucity of cation–π interactions involving lysine, even though this is a more common residue than arginine. Aromatic ligands are most likely to interact with cationic arginine residues as this interaction is stronger than for lysine in higher polarity surroundings

The effect of microhydration on ionization energies of thymine

A combined theoretical and experimental study of the effect of microhydration on ionization energies (IEs) of thymine is presented. The experimental IEs are derived from photoionization efficiency curves recorded using tunable synchrotron VUV radiation. The onsets of the PIE curves are 8.85+-0.05, 8.60+-0.05, 8.55+-0.05, and 8.40+-0.05 eV for thymine, thymine mono-, di-, and tri-hydrates, respectively. The computed (EOM-IP-CCSD/cc-pVTZ) AIEs are 8.90, 8.51, 8.52, and 8.35 eV for thymine and the lowest isomers of thymine mono-, di-, and tri-hydrates. Due to large structural relaxation, the Franck-Condon factors for the 0<-- 0 transitions are very small shifting the apparent PIE onsets to higher energies. Microsolvation strongly affects IEs of thymine -- addition of each water molecule reduces the first vertical IE by 0.10-0.15 eV. The adiabatic IE decreases even more (up to 0.4 eV). The magnitude of the effect varies for different ionized states and for different isomers. For the ionized states that are localized on thymine the dominant contribution to the IE reduction is the electrostatic interaction between the delocalized positive charge on thymine and the dipole moment of the water molecule

Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules

Enhancing the robustness of functional biomacromolecules is a critical challenge in biotechnology, which if addressed would enhance their use in pharmaceuticals, chemical processing and biostorage. Here we report a novel method, inspired by natural biomineralization processes, which provides unprecedented protection of biomacromolecules by encapsulating them within a class of porous materials termed metal-organic frameworks. We show that proteins, enzymes and DNA rapidly induce the formation of protective metal-organic framework coatings under physiological conditions by concentrating the framework building blocks and facilitating crystallization around the biomacromolecules. The resulting biocomposite is stable under conditions that would normally decompose many biological macromolecules. For example, urease and horseradish peroxidase protected within a metal-organic framework shell are found to retain bioactivity after being treated at 80 °C and boiled in dimethylformamide (153 °C), respectively. This rapid, low-cost biomimetic mineralization process gives rise to new possibilities for the exploitation of biomacromolecules.Kang Liang, Raffaele Ricco, Cara M. Doherty, Mark J. Styles, Stephen Bell, Nigel Kirby, Stephen Mudie, David Haylock, Anita J. Hill, Christian J. Doonan, Paolo Falcar

Understanding the within-host dynamics of influenza A virus: from theory to clinical implications

Mathematical models have provided important insights into acute viral dynamics within individual patients. In this paper, we study the simplest target cell-limited models to investigate the within-host dynamics of influenza A virus infection in humans. Despite the biological simplicity of the models, we show how these can be used to understand the severity of the infection and the key attributes of possible immunotherapy and antiviral drugs for the treatment of infection at different times post infection. Through an analytic approach, we derive and estimate simple summary biological quantities that can provide novel insights into the infection dynamics and the definition of clinical endpoints. We focus on nine quantities, including the area under the viral load curve, peak viral load, the time to peak viral load and the level of cell death due to infection. Using Markov chain Monte Carlo methods, we fitted the models to data collected from 12 untreated volunteers who participated in two clinical studies that tested the antiviral drugs oseltamivir and zanamivir. Based on the results, we also discuss various difficulties in deriving precise estimates of the parameters, even in the very simple models considered, when experimental data are limited to viral load measures and/or there is a limited number of viral load measurements post infection