Ancora sul problema degli ossi scolpiti del Museo di Alessandria

Analisi iconografica e stilistica di ossi scolpiti conservati nel Museo greco- romano di Alessandria in Egitto, provenienti da scavi urbani e dalle necropoli. Produzione di ateliers alessandrini attivi dal II al VI secolo

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.Approximately 60% of the general adult population experiences rhythmic masticatory muscle activity (RMMA) during sleep. The etiology of this movement is not yet understood. However, it has been demonstrated that an increased frequency of RMMA may have detrimental consequences on the stomatognathic system. In this case, RMMA is considered the manifestation of a sleep-related motor disorder known as sleep bruxism (SB). According to the definition of the International Classification of Sleep Disorders, SB is the activity of tooth grinding and clenching during sleep. The occurrence of SB-related activity, i.e., RMMA, is associated with rises of sympathetic tone, heart rate, blood pressure, and it is frequently concomitant with larger respiratory breaths. All these events can be described within a sleep arousal. The present thesis includes four research articles aimed to study i) the etiology of RMMA during sleep in relation to sleep arousal; and ii) the clinical perspectives of SB assessment and management. To further investigate the etiology of RMMA and its association with sleep arousal fluctuations we analyzed the cyclic alternating pattern (CAP), a scoring method to assess sleep instability and describe sleep arousal pressure. CAP was scored in SB subjects and controls that participated in two experimental protocols in which sleep architecture and stability were altered by either a medication (i.e., clonidine), or sensory stimulations (i.e., vibratory/auditory). Under these experimental conditions known to increase sleep instability, we were able to show that sleep arousal is not the trigger or cause of RMMA, rather the “permissive window” that facilitates the occurrence of RMMA during sleep. To evaluate the clinical relevance of SB, we conducted a survey on a 7-17 year old orthodontic population to investigate the prevalence and risk factors associated with SB. It appeared that SB is a highly prevalent sleep disorders in children (15% of prevalence), and is a risk factor for tooth wear (odds ratio, OR 8.8), jaw muscle fatigue (OR 10.5), frequent headache (OR 4.3), loud breathing during sleep (OR 3.1), and several sleep complaints, such as daytime sleepiness (OR 7.4). These findings led us to design an experimental trial using a mandibular advancement appliance (MAA) in adolescents in order to investigate the possible relationship between SB, snoring, and headache. We hypothesized that a common underlying mechanism related to breathing during sleep may be responsible for all concomitant conditions. The short-term use of an MAA appeared to reduce SB (up to 60%), and improve snoring and headache complaints in adolescents. However, the precise mechanism of action of MAA remains under debate; its effectiveness can be either related to the improvement of breathing during sleep, or its influence on the masticatory system. The interactions between SB, breathing, and headache as well as the long-term effectiveness and safety of the MAA in adolescents need further investigations.L’attività ritmica dei muscoli masticatori (ARMM) durante il sonno si osserva in circa il 60% della popolazione generale adulta. L'eziologia di questo movimento non è stata ancora del tutto compresa. Tuttavia, è dimostrato che un’aumentata frequenza di ARMM può avere conseguenze negative sul sistema stomatognatico. In questo caso, l’ARMM è considerato la manifestazione di un disturbo motorio del sonno noto come bruxismo. Secondo la Classificazione Internazionale dei Disturbi del Sonno, il bruxismo è l'attività di digrignamento e serramento dei denti durante il sonno. La comparsa di episodi di ARMM durante il sonno è associata a un aumento del tono del sistema nervoso simpatico, della frequenza cardiaca, della pressione arteriosa, ed è spesso in concomitanza con un aumentato volume inspiratorio. Le variazioni di questi parametri fisiologici sono compresi nel contesto di un arousal (micro risveglio) del sonno. Questa tesi comprende quattro articoli di ricerca volti a studiare i) l'eziologia dell’ARMM durante il sonno in relazione all’arousal, ed a valutare ii) l’inquadramento clinico del bruxismo nel sonno. Per approfondire l'eziologia dell’ARMM e l’associazione con l’arousal nel sonno, abbiamo analizzato il cyclic alternating pattern (CAP), che permette di valutare l'instabilità del sonno e descrivere la potenza degli arousals. Il CAP è stato esaminato in soggetti con bruxismo e soggetti controllo che hanno partecipato in due protocolli sperimentali, in cui la struttura e la stabilità del sonno sono stati modificati con la somministrazione di un farmaco (la clonidina), o con l’applicazione di stimolazioni sensoriali (di tipo vibratorio/uditivo) durante il sonno. In queste condizioni sperimentali caratterizzate da un’aumentata instabilità del sonno, siamo stati in grado di dimostrare che l’arousal non è la causa o il generatore dell’ARMM, ma piuttosto la "finestra permissiva" che facilita il verificarsi di questi movimenti ritmici durante il sonno. Per valutare la rilevanza clinica del bruxismo, abbiamo condotto uno studio epidemiologico in una popolazione pediatrica afferente alla clinica di ortodonzia per studiare la prevalenza e i fattori di rischio associati al bruxismo. Questa ricerca ha evidenziato che il bruxismo è un comune disturbo del sonno nei bambini (con una prevalenza del 15%), ed è un fattore di rischio per usura dentale (odds ratio, OR 8.8), fatica dei muscoli masticatori (OR 10.5), mal di testa frequenti (OR 4.3), respirazione rumorosa durante il sonno (OR 3.1), e diversi sintomi legati al sonno, quali la sonnolenza diurna (OR 7.4). Questi risultati ci hanno portato a progettare uno studio sperimentale per valutare l’efficacia di un apparecchio di avanzamento mandibolare (AAM) in un gruppo di adolescenti che presentavano al contempo bruxismo, russamento e frequenti cefalee. L’ipotesi è che nella patogenesi di tali comorbidità, vi sia un meccanismo comune, probabilmente legato alla respirazione durante il sonno, e che l’utilizzo di un AAM possa quindi avere un beneficio multiplo. Il trattamento a breve termine con un AAM sembra diminuire l’ARMM (fino al 60%) e migliorare il russamento e i mal di testa negli adolescenti. Tuttavia, l'esatto meccanismo di azione degli AAM rimane incerto; la loro efficacia può essere correlata sia al miglioramento della respirazione durante il sonno, ma anche all’influenza che questi apparecchi svolgono sul sistema masticatorio. Le interazioni tra il bruxismo nel sonno, la respirazione, e le cefalee, così come l'efficacia e la sicurezza a lungo termine degli AAM negli adolescenti, necessitano di ulteriori studi clinici

Le risposte delle cellule mesenchimali esposte alla topografia di superfici di titanio: il ruolo di β-catenina

La topografia delle superfici in titanio è considerata uno dei fattori più importanti per il successo degli impianti ossei. E’ noto, infatti, che il grado di rugosità delle superfici influenza il comportamento dei precursori mesenchimali delle cellule ossee, modulandone la proliferazione, il differenziamento e la commissione verso il fenotipo osteoblastico. Tuttavia i meccanismi molecolari alla base delle risposte cellulari nei confronti della topografia di superficie sono ancora poco chiari. L’obiettivo del lavoro è stato quello di studiare il comportamento delle cellule mesenchimali murine cresciute a contatto con differenti superfici in titanio. Si è inoltre analizzato l’effetto di tali superfici sulla crescita cellulare in presenza di stress ossidativo. A tale scopo, cellule C2C12 sono state transfettate con il plasmide per il Wnt3a o per la β-catenina e con un costrutto reporter per TCF basato sull’attività dell’enzima Luciferasi. La stimolazione della via di segnalazione di Wnt, analizzata mediante lettura al luminometro, risulta aumentata in cellule cresciute su superfici rugose (SLA) rispetto a quelle lisce (polished). Inoltre quando le cellule vengono trasfettate con la forma costitutivamente attiva di β-catenina (SS33Y), le differenze tra le due superfici non sono più apprezzabili. Si è poi proceduto ad analizzare mediante RealTime-PCR i livelli di espressione di geni target della via di segnalazione del Wnt in cellule transfettate con Wnt3a. Cellule a contatto con titanio SLA, in seguito a stimolazione con Wnt3a, mostrano livelli di mRNA dei geni ALP, OPG e Wisp-2 significativamente più elevati rispetto alle cellule cresciute su titanio liscio, mentre i livelli dei geni CX43 e COX-2 sono più elevati su superfici rugose già allo stato basale. Inoltre l’espressione del gene Axin-2, coinvolto nel processo di degradazione di β-catenina, appare ridotta sulle superfici rugose. Allo scopo di analizzare l’influenza della rugosità di superficie sul comportamento cellulare in presenza di uno stato di stress ossidativo, le cellule sono state transfettate con un costrutto reporter per il fattore FoxO. La via molecolare dipendente dall’attivazione del complesso di trascrizione FoxO/β-catenina risulta significativamente più attiva in C2C12 cresciute su superfici SLA sia in assenza di stress ossidativo che dopo stimolazione con 0.1 mM di H2O2, e l’espressione dei geni target di FoxO, quali Catalasi e Superossido Dismutasi, enzimi con funzione di difesa nei confronti dell’azione lesiva delle specie reattive all’ossigeno, risulta aumentata sulle superfici rugose. Questi risultati sono coerenti con l’osservazione che il danno da stress ossidativo è minore in cellule cresciute su titanio SLA rispetto a quelle cresciute sul titanio pulished. In conclusione, si può affermare che la topografia delle superfici in titanio influenza in maniera importante il comportamento e la sopravvivenza delle cellule, controllando il bilancio tra i meccanismi molecolari che regolano da un lato la crescita e dall’altro le difese cellulari nei confronti dei radicali liberi dell’ossigeno. Questi risultati mostrano inoltre come la rugosità di superficie influenzi sia il pathway di Wnt sia la via di segnalazione di FoxO attraverso il controllo della degradazione di β-catenina, fornendo così la spiegazione per il comportamento delle cellule cresciute a contatto con superfici ruvide

Asthma control, lung function, nutritional status, and health-related quality of life : differences between adult males and females with asthma

Objective: To evaluate health-related quality of life in asthma patients treated at a referral center in southern Brazil, identifying differences between male and female patients, as well as to evaluate differences between the males and females in terms of asthma control, lung function, and nutritional status. Methods: This was a cross-sectional study involving patients ≥ 18 years of age treated at an asthma outpatient clinic. We evaluated clinical parameters, lung function, nutritional status, and quality of life. Results: A total of 198 patients completed the study. The mean age was 56.2 ± 14.8 years, and 81.8% were female. The proportion of patients with uncontrolled asthma was higher among females than among males (63.0% vs. 44.4%; p = 0.041). The body mass index (BMI) and percentage of body fat were higher in females than in males (30.2 ± 5.8 kg/m2 vs. 26.9 ± 4.5 kg/m2 and 37.4 ± 6.4% vs. 26.5 ± 7.4%; p = 0.002 and p < 0.001, respectively). Quality of life was lower in females than in males in the following domains: symptoms (3.8 ± 1.5 vs. 4.6 ± 1.7; p = 0.006); activity limitation (3.6 ± 1.3 vs. 4.4 ± 1.5; p = 0.001); emotional function (3.6 ± 1.9 vs. 4.5 ± 1.7; p = 0.014); and environmental stimuli (3.2 ± 1.6 vs. 4.3 ± 1.9; p = 0.001). Conclusions: Male asthma patients appear to fare better than do female asthma patients in terms of health-related quality of life, asthma control, BMI, percentage of body fat, and comorbidities

Dietary patterns of adults with asthma treated at a referral center for asthma

Objectives: To assess the association between dietary patterns, nutritional status and asthma control in patients treated at a referral center for asthma in Porto Alegre, Brazil. Methods: This is a cross-sectional study with 198 adult asthma patients. Participants answered 24h food recall and questionnaire of the history of the disease, degree of control and severity, in addition to performing pulmonary and anthropometric assessments. We used exploratory factor analysis and extraction of the factors the method of analysis of main components to derive the dietary patterns. Results: The mean of body mass index was 29.6 ± 5.7 kg/m²; and 41.9% were classified as obese. Regarding the severity of the disease, 72.7% were classified as having severe persistent asthma. The degree of control, 59.6% of patients had uncontrolled asthma. Three dietary patterns were identified: "Sugars", "Healthy", "Fats and Alcohol." It was observed in this study, that the Fat and Alcohol pattern was significantly associated with male gender. However, no associations were observed between the other variables and dietary patterns. Conclusion: This study was the first to identify the dietary patterns in asthmatics in Brazil. Patterns found in the present study were “Sugars”, “Healthy” and “Fats and Alcohol”. However, not a significant association between the three standards and nutritional status and disease control

The small heat shock protein B8 (HSPB8) modulates proliferation and migration of breast cancer cells

open12noBreast cancer (BC) is one of the major causes of cancer death in women and is closely related to hormonal dysregulation. Estrogen receptor (ER)-positive BCs are generally treated with anti hormone therapy using antiestrogens or aromatase inhibitors. However, BC cells may become resistant to endocrine therapy, a process facilitated by autophagy, which may either promote or suppress tumor expansion. The autophagy facilitator HSPB8 has been found overexpressed in some BC. Here we found that HSPB8 is highly expressed and differentially modulated by natural or synthetic selective ER modulators (SERMs), in the triple-positive hormone-sensitive BC (MCF-7) cells, but not in triple-negative MDA-MB-231 BC cells. Specific SERMs induced MCF-7 cells proliferation in a HSPB8 dependent manner whereas, did not modify MDA-MB-231 cell growth. ER expression was unaffected in HSPB8-depleted MCF-7 cells. HSPB8 over-expression did not alter the distribution of MCF-7 cells in the various phases of the cell cycle. Conversely and intriguingly, HSPB8 downregulation resulted in an increased number of cells resting in the G0/G1 phase, thus possibly reducing the ability of the cells to pass through the restriction point. In addition, HSPB8 downregulation reduced the migratory ability of MCF-7 cells. None of these modifications were observed, when another small HSP (HSPB1), also expressed in MCF-7 cells, was downregulated. In conclusion, our data suggest that HSPB8 is involved in the mechanisms that regulate cell cycle and cell migration in MCF-7 cells.openPiccolella, Margherita; Crippa, Valeria; Cristofani, Riccardo; Rusmini, Paola; Galbiati, Mariarita; Elena Cicardi, Maria; Meroni, Marco; Ferri, Nicola; Morelli, Federica F; Carra, Serena; Messi, Elio; Poletti, AngeloPiccolella, Margherita; Crippa, Valeria; Cristofani, Riccardo; Rusmini, Paola; Galbiati, Mariarita; Elena Cicardi, Maria; Meroni, Marco; Ferri, Nicola; Morelli, Federica F; Carra, Serena; Messi, Elio; Poletti, Angel

Dietary patterns of adults with asthma treated at a referral center for asthma

Introduction: Consumption of foods with anti-inflammatory and antioxidant components could contribute to a better control of the asthma. The aim of this study was to assess the association between dietary patterns, nutritional status, and asthma control in patients treated at an asthma referral center in Porto Alegre, Brazil. Methods: This is a cross-sectional study with 198 adult asthma patients. Participants completed a 24-hour food recall and a questionnaire on disease history, degree of control, and severity, as well as pulmonary and anthropometric assessments. We used exploratory factor analysis and principal component analysis as an extraction method to derive the dietary patterns. Results: The mean body mass index was 29.6 (SD, 5.7) kg/m², and 41.9% were classified as obese. Regarding disease severity, 72.7% were classified as having severe persistent asthma, and concerning the degree of control, 59.6% of the patients had uncontrolled asthma. Three dietary patterns were identified: “Sugars”, “Healthy”, and “Fats and Alcohol”. It was observed that the Fats and Alcohol pattern was significantly associated with men. However, no associations were observed between the other variables and dietary patterns. Conclusion: This was the first study to identify the dietary patterns in asthmatics in Brazil. Patterns found in the present study were “Sugars”, “Healthy” and “Fats and Alcohol”. However, there was no significant association between the 3 patterns and nutritional status or disease control

Nuovi dati sugli edifici termali di Sabratha

The architecture of the six Roman baths in Sabratha developed in the second century during the reorganization of the urban space after the earthquake of the Flavian period. They are all well organized in the axial arrangement of the cold and hot baths, with frigidarium as the focus of the structure, served by apodyteria, environments with benches for visitors and latrinae, and also with appropriate paths and well-wishers (the mosaics in the so-called Terme del Teatro) or marble statues (in the latrine of the so-called Terme a mare). The spaces for the hot bath stand out for the sequence of the laconicum, the tepidarium and of the calidarium, independent and equipped with the praefurnia. In the Forum area the ‘Terme a mare’ imposed themselves for its original technical and structural insights aimed at obtaining a building area bigger than the tectonics of the soil could then ensure. The ‘Terme del Teatro’ on their turn spearheaded the experimentation with new analytical techniques aiming at the restitution of the original project

Oral Bacterial Microbiota in Digestive Cancer Patients: A Systematic Review

The relation between the gut microbiota and human health is increasingly recognized. Recently, some evidence suggested that dysbiosis of the oral microbiota may be involved in the development of digestive cancers. A systematic review was conducted according to the PRISMA guidelines to investigate the association between the oral microbiota and digestive cancers. Several databases including Medline, Scopus, and Embase were searched by three independent reviewers, without date restriction. Over a total of 1654 records initially identified, 28 studies (2 prospective cohort studies and 26 case-controls) were selected. They investigated oral microbiota composition in patients with esophageal squamous cell carcinoma (n = 5), gastric cancer (n = 5), colorectal cancer (n = 9), liver carcinoma (n = 2), and pancreatic cancer (n = 7). In most of the studies, oral microbiota composition was found to be different between digestive cancer patients and controls. Particularly, oral microbiota dysbiosis and specific bacteria, such as Fusobacterium nucleatum and Porphyromonas gingivalis, appeared to be associated with colorectal cancers. Current evidence suggests that differences exist in oral microbiota composition between patients with and without digestive cancers. Further studies are required to investigate and validate oral–gut microbial transmission patterns and their role in digestive cancer carcinogenesis

Bioproduction and characterization of sodium, potassium, and calcium lactobionates

Lactobionic acid and its salts are substances that have several applications in the pharmaceutical area. These products were obtained by bioconversion through the enzymatic complex glucose-fructose-oxidoreductase (GFOR)/gluconolactonase (GL) present in calcium alginate immobilized cells of Zymomonas mobilis. In the reactions catalyzed by this enzyme system, the medium pH must be controlled at slightly acid values. For this purpose, NaOH, KOH, or Ca(OH)2 were used, and as a result, the respective salts were formed. The kinetic study on the formation of sodium, potassium and calcium lactobionates was followed by the steps of purification and characterization aiming the potential use of these compounds in the pharmaceutical area. In the assays for the bioproduction of sodium, potassium or calcium lactobionates, yields of 74, 77 and 84% were obtained, respectively. In the salts purification step, purity levels of approximately 95% were achieved. The structural identities of the lactobionate salts were determined by high resolution mass spectrometry, in addition to the 13C and 1H NMR analysis. The characterization demonstrates the selectivity of the enzymatic reaction of GFOR/GL of Z. mobilis, in the production of lactobionic acid and its salts