Glycosuria in glomerular diseases: histopathology and clinical correlations

There are doubts about the presence of glycosuria and the progress of glomerular disease. Some reports suggest that glycosuria could be an index of a more severe tubulointerstitial lesion. We investigated the presence of glycosuria in 60 patients with primary glomerular diseases: 17 patients (28%) had glycosuria and 43 patients (72%) were glycosuria free. The two groups were similar in age, arterial pressure and sex. Serum creatinine was higher in patients with glycosuria (2.0 ± 1.7 vs 1.3 ± 0.9 mg/dl, P<0.05). The protein excretion rate was 7.5 ± 3.7 vs 5.3 ± 4.2 g/day (P>0.05) in patients with and without glycosuria, respectively, while serum albumin was lower in patients with glycosuria (1.7 ± 0.6 vs 2.7 ± 1.0 g/dl, P<0.05). Several histological forms were present in the group with glycosuria, with membranous glomerulonephritis being the most frequent. Histological evidence of tubular atrophy and interstitial fibrosis prevailed in patients with glycosuria, suggesting a poor prognosis for these patients. We may conclude that the presence of glycosuria in patients with glomerular disease is associated with more pronounced tubular atrophy and interstitial fibrosis and therefore imply a poorer prognosis.

Biology and clinical utilization of mesenchymal progenitor cells

Within the complex cellular arrangement found in the bone marrow stroma there exists a subset of nonhematopoietic cells referred to as mesenchymal progenitor cells (MPC). These cells can be expanded ex vivo and induced, either in vitro or in vivo, to terminally differentiate into at least seven types of cells: osteocytes, chondrocytes, adipocytes, tenocytes, myotubes, astrocytes and hematopoietic-supporting stroma. This broad multipotentiality, the feasibility to obtain MPC from bone marrow, cord and peripheral blood and their transplantability support the impact that the use of MPC will have in clinical settings. However, a number of fundamental questions about the cellular and molecular biology of MPC still need to be resolved before these cells can be used for safe and effective cell and gene therapies intended to replace, repair or enhance the physiological function of the mesenchymal and/or hematopoietic systems.

Extracellular calcium-sensing receptor: structural and functional features and association with diseases

The recently cloned extracellular calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays an essential role in the regulation of extracellular calcium homeostasis. This receptor is expressed in all tissues related to this control (parathyroid glands, thyroid C-cells, kidneys, intestine and bones) and also in tissues with apparently no role in the maintenance of extracellular calcium levels, such as brain, skin and pancreas. The CaR amino acid sequence is compatible with three major domains: a long and hydrophilic aminoterminal extracellular domain, where most of the activating and inactivating mutations described to date are located and where the dimerization process occurs, and the agonist-binding site is located, a hydrophobic transmembrane domain involved in the signal transduction mechanism from the extracellular domain to its respective G protein, and a carboxyterminal intracellular tail, with a well-established role for cell surface CaR expression and for signal transduction. CaR cloning was immediately followed by the association of genetic human diseases with inactivating and activating CaR mutations: familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are caused by CaR-inactivating mutations, whereas autosomal dominant hypoparathyroidism is secondary to CaR-activating mutations. Finally, we will comment on the development of drugs that modulate CaR function by either activating (calcimimetic drugs) or antagonizing it (calcilytic drugs), and on their potential therapeutic implications, such as medical control of specific cases of primary and uremic hyperparathyroidism with calcimimetic drugs and a potential treatment for osteoporosis with a calcilytic drug.

Bone mineral density in young women of the city of São Paulo, Brazil: correlation with both collagen type I alpha 1 gene polymorphism and clinical aspects

Osteoporosis is a multifactorial disease with great impact on morbidity and mortality mainly in postmenopausal women. Although it is recognized that factors related to life-style and habits may influence bone mass formation leading to greater or lower bone mass, more than 85% of the variation in bone mineral density (BMD) is genetically determined. The collagen type I alpha 1 (COLIA1) gene is a possible risk factor for osteoporosis. We studied a population of 220 young women from the city of São Paulo, Brazil, with respect to BMD and its correlation with both COLIA1 genotype and clinical aspects. The distribution of COLIA1 genotype SS, Ss and ss in the population studied was 73.6, 24.1 and 2.3%, respectively. No association between these genotypes and femoral or lumbar spine BMD was detected. There was a positive association between lumbar spine BMD and weight (P<0.0001), height (P<0.0156), and body mass index (BMI) (P<0.0156), and a negative association with age at menarche (P<0.0026). There was also a positive association between femoral BMD and weight (P<0.0001), height (P<0.0001), and BMI (P<0.0001), and a negative correlation with family history for osteoporosis (P<0.041). There was no association between the presence of allele s and reduced BMD. We conclude that a family history of osteoporosis and age at menarche are factors that may influence bone mass in our population.

Reliability and clinical utility of a Portuguese version of the Abnormal Involuntary Movements Scale (AIMS) for tardive dyskinesia in Brazilian patients

The objective of the present study was to evaluate the reliability and clinical utility of a Portuguese version of the Abnormal Involuntary Movements Scale (AIMS). Videotaped interviews with 16 psychiatric inpatients treated with antipsychotic drugs for at least 5 years were evaluated. Reliability was assessed by the intraclass correlation coefficient (ICC) between three raters, two with and one without clinical training in psychopathology. Clinical utility was assessed by the difference between the scores of patients with (N = 11) and without (N = 5) tardive dyskinesia (TD). Patients with TD exhibited a higher severity of global evaluation by the AIMS (sum of scores: 4.2 ± 0.9 vs 0.4 ± 0.2; score on item 8: 2.3 ± 0.3 vs 0.4 ± 0.2, TD vs controls). The ICC for the global evaluation was fair between the two skilled raters (0.58-0.62) and poor between these raters and the rater without clinical experience (0.05-0.29). Thus, we concluded that the Portuguese version of the AIMS shows an acceptable inter-rater reliability, but only between clinically skilled raters, and that it is clinically useful.

Molecular biology and clinical implication of hepatitis C virus

Hepatitis C virus (HCV) was first described in 1989 as the putative viral agent of non-A non-B hepatitis. It is a member of the Flaviviridae family and has been recognized as the major causative agent of chronic liver disease, including chronic active hepatitis, cirrhosis and hepatocellular carcinoma. HCV is a positive RNA virus with a genome containing approximately 9500 nucleotides. It has an open reading frame that encodes a large polyprotein of about 3000 amino acids and is characterized by extensive genetic diversity. HCV has been classified into at least 6 major genotypes with many subtypes and circulates within an infected individual as a number of closely related but distinct variants known as quasispecies. This article reviews aspects of the molecular biology of HCV and their clinical implication.

A conceptual and practical overview of cDNA microarray technology: implications for basic and clinical sciences

cDNA microarray is an innovative technology that facilitates the analysis of the expression of thousands of genes simultaneously. The utilization of this methodology, which is rapidly evolving, requires a combination of expertise from the biological, mathematical and statistical sciences. In this review, we attempt to provide an overview of the principles of cDNA microarray technology, the practical concerns of the analytical processing of the data obtained, the correlation of this methodology with other data analysis methods such as immunohistochemistry in tissue microarrays, and the cDNA microarray application in distinct areas of the basic and clinical sciences.

Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data

Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs). Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686) and hold promise to further boost the median survival of patients with EGFR mutated NSCLC.

Probiotics and oral health: In vitro and clinical studies

Aino Toiviainen Probiotics and oral health: in vitro and clinical studies University of Turku, Faculty of Medicine, Institute of Dentistry, Periodontology, Finnish Doctoral Program in Oral Sciences (FINDOS-Turku), Turku, Finland Annales Universitatis Turkuensis, Sarja – Ser. D, Medica-Odontologica. Painosalama Oy, Turku, Finland, 2015 Probiotics are used, for example, to prevent and treat diarrhea, allergies and respiratory infections, and there is an increasing interest to use probiotics also for oral health purposes. The most commonly used probiotic bacteria are lactobacilli and bifidobacteria, which are acidogenic and aciduric. From the oral point of view, use of these probiotics may, at least in theory, mean an increased risk of caries. In this thesis, the effects of probiotics on oral microbial composition, acid production of dental plaque and gingival health were studied through in vitro studies and two clinical studies. In a randomized, double-blind and crossover study, 13 healthy adults were allocated into two groups. Half of the subjects first consumed Lactobacillus rhamnosus GG tablets twice a day for two weeks, and after the washout period, L. reuteri tablets twice a day for two weeks. The other half of the subjects used the tablets in reverse order. In another controlled, randomized and double-blind study, 62 healthy adults were allocated into two groups. One group used the test tablets containing L. rhamnosus GG and B. lactis BB-12 and the other group used control tablets without probiotics. The recommendation for the use of the tablets was 4 per day for 4 weeks. Probiotic lactobacilli interfered with S. mutans biofilm formation and the adhesion of S. mutans to saliva-coated hydroxyapatite in vitro. No effect was found in S. mutans levels in the three-species biofilms. In clinical studies, the studied probiotics had no effect on the acid production of plaque. The counts of mutans streptococci and the oral microbial composition remained the same. Tablets containing L. rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 did decrease the amount of plaque and gingival bleeding. According to our results, it seems that probiotics have beneficial effects on gingival health. The present results confirmed that probiotics are safe and have beneficial effects on oral health. Since the consumption of probiotics by the general population is steadily increasing, an understanding of the functions of probiotics in the oral cavity has become more important. Keywords: lactobacilli, bifidobacteria, caries, periodontal disease, mutans streptococci, probiotics

BK polyomavirus in Kidney transplant recipients: screening, monitoring and clinical management

BK polyomavirus (BKPyV) is a causal agent of nephropathy, ureteral stenosis and hemorrhagic cystitis in kidney transplant recipients, and is considered an important emerging disease in transplantation. Regular screening for BKPyV reactivation mainly during the first 2 years posttransplant, with subsequent pre-emptive reduction of immunosuppression is considered the best option to avoid disease progression, since successful clearance or reduction of viremia is achieved in the vast majority of patients within 6 months. The use of drugs with antiviral properties for patients with persistent viremia has been attempted despite unclear benefits. Clinical manifestations of BKPyV nephropathy, current strategies for diagnosis and monitoring of BKPyV infection, management of immunosuppressive regimen after detection of BKPyV reactivation and the use of antiviral drugs are discussed in this review.

Promoting Healthy Lifestyles with Personalized, APOE Genotype Based Health Information: The Effects on Psychological-, Health Behavioral and Clinical Factors

There is an increasing demand for individualized, genotype-based health advice. The general population-based dietary recommendations do not always motivate people to change their life-style, and partly following this, cardiovascular diseases (CVD) are a major cause of death in worldwide. Using genotype-based nutrition and health information (e.g. nutrigenetics) in health education is a relatively new approach, although genetic variation is known to cause individual differences in response to dietary factors. Response to changes in dietary fat quality varies, for example, among different APOE genotypes. Research in this field is challenging, because several non-modifiable (genetic, age, sex) and modifiable (e.g. lifestyle, dietary, physical activity) factors together and with interaction affect the risk of life-style related diseases (e.g. CVD). The other challenge is the psychological factors (e.g. anxiety, threat, stress, motivation, attitude), which also have an effect on health behavior. The genotype-based information is always a very sensitive topic, because it can also cause some negative consequences and feelings (e.g. depression, increased anxiety). The aim of this series of studies was firstly to study how individual, genotype-based health information affects an individual’s health form three aspects, and secondly whether this could be one method in the future to prevent lifestyle-related diseases, such as CVD. The first study concentrated on the psychological effects; the focus of the second study was on health behavior effects, and the third study concentrated on clinical effects. In the fourth study of this series, the focus was on all these three aspects and their associations with each other. The genetic risk and health information was the APOE gene and its effects on CVD. To study the effect of APOE genotype-based health information in prevention of CVD, a total of 151 volunteers attended the baseline assessments (T0), of which 122 healthy adults (aged 20 – 67 y) passed the inclusion criteria and started the one-year intervention. The participants (n = 122) were randomized into a control group (n = 61) and an intervention group (n = 61). There were 21 participants in the intervention Ɛ4+ group (including APOE genotypes 3/4 and 4/4) and 40 participants in the intervention Ɛ4- group (including APOE genotypes 2/3 and 3/3). The control group included 61 participants (including APOE genotypes 3/4, 4/4, 2/3, 3/3 and 2/2). The baseline (T0) and follow-up assessments (T1, T2, T3) included detailed measurements of psychological (threat and anxiety experience, stage of change), and behavioral (dietary fat quality, consumption of vegetables, - high fat/sugar foods and –alcohol, physical activity and health and taste attitudes) and clinical factors (total-, LDL- HDL cholesterol, triglycerides, blood pressure, blood glucose (0h and 2h), body mass index, waist circumference and body fat percentage). During the intervention six different communication sessions (lectures on healthy lifestyle and nutrigenomics, health messages by mail, and personal discussion with the doctor) were arranged. The intervention groups (Ɛ4+ and Ɛ4-) received their APOE genotype information and health message at the beginning of the intervention. The control group received their APOE genotype information after the intervention. For the analyses in this dissertation, the results for 106/107 participants were analyzed. In the intervention, there were 16 participants in the high-risk (Ɛ4+) group and 35 in the low-risk (Ɛ4-) group. The control group had 55 participants in studies III-IV and 56 participants in studies I-II. The intervention had both short-term (≤ 6 months) and long-term (12 months) effects on health behavior and clinical factors. The short-term effects were found in dietary fat quality and waist circumference. Dietary fat quality improved more in the Ɛ4+ group than the Ɛ4- and the control groups as the personal, genotype-based health information and waist circumference lowered more in the Ɛ4+ group compared with the control group. Both these changes differed significantly between the Ɛ4+ and control groups (p<0.05). A long-term effect was found in triglyceride values (p<0.05), which lowered more in Ɛ4+ compared with the control group during the intervention. Short-term effects were also found in the threat experience, which increased mostly in the Ɛ4+ group after the genetic feedback (p<0.05), but it decreased after 12 months, although remaining at a higher level compared to the baseline (T0). In addition, Study IV found that changes in the psychological factors (anxiety and threat experience, motivation), health and taste attitudes, and health behaviors (dietary, alcohol consumption, and physical activity) did not directly explain the changes in triglyceride values and waist circumference. However, change caused by a threat experience may have affected the change in triglycerides through total- and HDL cholesterol. In conclusion, this dissertation study has given some indications that individual, genotypebased health information could be one potential option in the future to prevent lifestyle-related diseases in public health care. The results of this study imply that personal genetic information, based on APOE, may have positive effects on dietary fat quality and some cardiovascular risk markers (e.g., improvement in triglyceride values and waist circumference). This study also suggests that psychological factors (e.g. anxiety and threat experience) may not be an obstacle for healthy people to use genotype-based health information to promote healthy lifestyles. However, even in the case of very personal health information, in order to achieve a permanent health behavior change, it is important to include attitudes and other psychological factors (e.g. motivation), as well as intensive repetition and a longer intervention duration. This research will serve as a basis for future studies and its information can be used to develop targeted interventions, including health information based on genotyping that would aim at preventing lifestyle diseases. People’s interest in personalized health advices has increased, while also the costs of genetic screening have decreased. Therefore, generally speaking, it can be assumed that genetic screening as a part of the prevention of lifestyle-related diseases may become more common in the future. In consequence, more research is required about how to make genetic screening a practical tool in public health care, and how to efficiently achieve long-term changes.

Frailty, an Emerging Research and Clinical Paradigm: Issues and Controversies

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The Development, Validation and Implementation of a Broad-Based ADME Genotyping Assay into Research and Clinical Trials

Afin d’adresser la variabilité interindividuelle observée dans la réponse pharmacocinétique à de nombreux médicaments, nous avons créé un panel de génotypage personnalisée en utilisant des méthodes de conception et d’élaboration d’essais uniques. Celles-ci ont pour but premier de capturer les variations génétiques présentent dans les gènes clés impliqués dans les processus d'absorption, de distribution, de métabolisme et d’excrétion (ADME) de nombreux agents thérapeutiques. Bien que ces gènes et voies de signalement sont impliqués dans plusieurs mécanismes pharmacocinétiques qui sont bien connues, il y a eu jusqu’à présent peu d'efforts envers l’évaluation simultanée d’un grand nombre de ces gènes moyennant un seul outil expérimental. La recherche pharmacogénomique peut être réalisée en utilisant deux approches: 1) les marqueurs fonctionnels peuvent être utilisés pour présélectionner ou stratifier les populations de patients en se basant sur des états métaboliques connus; 2) les marqueurs Tag peuvent être utilisés pour découvrir de nouvelles corrélations génotype-phénotype. Présentement, il existe un besoin pour un outil de recherche qui englobe un grand nombre de gènes ADME et variantes et dont le contenu est applicable à ces deux modèles d'étude. Dans le cadre de cette thèse, nous avons développé un panel d’essais de génotypage de 3,000 marqueurs génétiques ADME qui peuvent satisfaire ce besoin. Dans le cadre de ce projet, les gènes et marqueurs associés avec la famille ADME ont été sélectionnés en collaboration avec plusieurs groupes du milieu universitaire et de l'industrie pharmaceutique. Pendant trois phases de développement de cet essai de génotypage, le taux de conversion pour 3,000 marqueurs a été amélioré de 83% à 97,4% grâce à l'incorporation de nouvelles stratégies ayant pour but de surmonter les zones d'interférence génomiques comprenant entre autres les régions homologues et les polymorphismes sous-jacent les régions d’intérêt. La précision du panel de génotypage a été validée par l’évaluation de plus de 200 échantillons pour lesquelles les génotypes sont connus pour lesquels nous avons obtenu une concordance > 98%. De plus, une comparaison croisée entre nos données provenant de cet essai et des données obtenues par différentes plateformes technologiques déjà disponibles sur le marché a révélé une concordance globale de > 99,5%. L'efficacité de notre stratégie de conception ont été démontrées par l'utilisation réussie de cet essai dans le cadre de plusieurs projets de recherche où plus de 1,000 échantillons ont été testés. Nous avons entre autre évalué avec succès 150 échantillons hépatiques qui ont été largement caractérisés pour plusieurs phénotypes. Dans ces échantillons, nous avons pu valider 13 gènes ADME avec cis-eQTL précédemment rapportés et de découvrir et de 13 autres gènes ADME avec cis eQTLs qui n'avaient pas été observés en utilisant des méthodes standard. Enfin, à l'appui de ce travail, un outil logiciel a été développé, Opitimus Primer, pour aider pour aider au développement du test. Le logiciel a également été utilisé pour aider à l'enrichissement de cibles génomiques pour d'expériences séquençage. Le contenu ainsi que la conception, l’optimisation et la validation de notre panel le distingue largement de l’ensemble des essais commerciaux couramment disponibles sur le marché qui comprennent soit des marqueurs fonctionnels pour seulement un petit nombre de gènes, ou alors n’offre pas une couverture adéquate pour les gènes connus d’ADME. Nous pouvons ainsi conclure que l’essai que nous avons développé est et continuera certainement d’être un outil d’une grande utilité pour les futures études et essais cliniques dans le domaine de la pharmacocinétique, qui bénéficieraient de l'évaluation d'une longue liste complète de gènes d’ADME.

Rhythmic Masticatory Muscle Activity during Sleep: Etiology and Clinical Perspectives

L’activité rythmique des muscles masticateurs (ARMM) pendant le sommeil se retrouve chez environ 60% de la population générale adulte. L'étiologie de ce mouvement n'est pas encore complètement élucidée. Il est cependant démontré que l’augmentation de la fréquence des ARMM peut avoir des conséquences négatives sur le système masticatoire. Dans ce cas, l'ARMM est considérée en tant que manifestation d'un trouble moteur du sommeil connue sous le nom de bruxisme. Selon la Classification Internationale des Troubles du Sommeil, le bruxisme est décrit comme le serrement et grincement des dents pendant le sommeil. La survenue des épisodes d’ARMM est associée à une augmentation du tonus du système nerveux sympathique, du rythme cardiaque, de la pression artérielle et elle est souvent en association avec une amplitude respiratoire accrue. Tous ces événements peuvent être décrits dans le contexte d’un micro-éveil du sommeil. Cette thèse comprend quatre articles de recherche visant à étudier i) l'étiologie de l’ARMM pendant le sommeil en relation aux micro-éveils, et à évaluer ii) les aspects cliniques du bruxisme du sommeil, du point de vue diagnostique et thérapeutique. Pour approfondir l'étiologie de l’ARMM et son association avec la fluctuation des micro-éveils, nous avons analysé le patron cyclique alternant (ou cyclic alternating pattern (CAP) en anglais), qui est une méthode d’analyse qui permet d’évaluer l'instabilité du sommeil et de décrire la puissance des micro-éveils. Le CAP a été étudié chez des sujets bruxeurs et des sujets contrôles qui ont participé à deux protocoles expérimentaux, dans lesquels la structure et la stabilité du sommeil ont été modifiées par l'administration d'un médicament (la clonidine), ou avec l'application de stimulations sensorielles (de type vibratoire/auditif) pendant le sommeil. Dans ces deux conditions expérimentales caractérisées par une instabilité accrue du sommeil, nous étions en mesure de démontrer que les micro-éveils ne sont pas la cause ou le déclencheur de l’ARMM, mais ils représentent plutôt la «fenêtre permissive» qui facilite l'apparition de ces mouvements rythmiques au cours du sommeil. Pour évaluer la pertinence clinique du bruxisme, la prévalence et les facteurs de risque, nous avons effectué une étude épidémiologique dans une population pédiatrique (7-17 ans) qui était vue en consultation en orthodontie. Nous avons constaté que le bruxisme est un trouble du sommeil très fréquent chez les enfants (avec une prévalence de 15%), et il est un facteur de risque pour l'usure des dents (risque relatif rapproché, RRR 8,8), la fatigue des muscles masticateurs (RRR 10,5), les maux de tête fréquents (RRR 4,3), la respiration bruyante pendant le sommeil (RRR 3,1), et divers symptômes liés au sommeil, tels que la somnolence diurne (RRR 7,4). Ces résultats nous ont amenés à développer une étude expérimentale pour évaluer l'efficacité d'un appareil d'avancement mandibulaire (AAM) chez un groupe d'adolescents qui présentaient à la fois du bruxisme, du ronflement et des maux de tête fréquents. L'hypothèse est que dans la pathogenèse de ces comorbidités, il y a un mécanisme commun, probablement lié à la respiration pendant le sommeil, et que l'utilisation d'un AAM peut donc agir sur plusieurs aspects liés. À court terme, le traitement avec un AAM semble diminuer l'ARMM (jusqu'à 60% de diminution), et améliorer le ronflement et les maux de tête chez les adolescents. Cependant, le mécanisme d'action exact des AAM demeure incertain; leur efficacité peut être liée à l'amélioration de la respiration pendant le sommeil, mais aussi à l'influence que ces appareils pourraient avoir sur le système masticatoire. Les interactions entre le bruxisme du sommeil, la respiration et les maux de tête, ainsi que l'efficacité et la sécurité à long terme des AAM chez les adolescents, nécessitent des études plus approfondies.