De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control "always" matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.

Functionalized Mouth-Conformable Interfaces for pH Evaluation of the Oral Cavity.

Oral health monitoring is highly desired, especially for in home use, however, current methods are not sensitive enough and technically convoluted for this purpose. This paper presents incorporation of bioactive materials and colorimetric chemical sensors into routinely used oral appliances transforming them into bioresponsive, conformable interfaces. Specifically, endodontic paper points and dental floss can be functionalized to locally sense and monitor pH variations within the oral cavity via color changes. Moreover, edible colorimetric indicators are developed and used to make sensing, edible devices in the form factor of candies that can dynamically and visually respond to acidity changes in saliva. These interfaces would enable early detection of caries (e.g., using dental floss and paper points) providing low-cost point of care devices that respond in real-time by detecting pH variations in biological fluids thus bringing monitoring to home settings .

3D Imaging of PDL Collagen Fibers during Orthodontic Tooth Movement in Mandibular Murine Model.

Orthodontic tooth movement is a complex biological process of altered soft and hard tissue remodeling as a result of external forces. In order to understand these complex remodeling processes, it is critical to study the tooth and periodontal tissues within their 3D context and therefore minimize any sectioning and tissue artefacts. Mouse models are often utilized in developmental and structural biology, as well as in biomechanics due to their small size, high metabolic rate, genetics and ease of handling. In principle this also makes them excellent models for dental related studies. However, a major impediment is their small tooth size, the molars in particular. This paper is aimed at providing a step by step protocol for generating orthodontic tooth movement and two methods for 3D imaging of the periodontal ligament fibrous component of a mouse mandibular molar. The first method presented is based on a micro-CT setup enabling phase enhancement imaging of fresh collagen tissues. The second method is a bone clearing method using ethyl cinnamate that enables imaging through the bone without sectioning and preserves endogenous fluorescence. Combining this clearing method with reporter mice like Flk1-Cre;TdTomato provided a first of its kind opportunity to image the 3D vasculature in the PDL and alveolar bone.

In situ AFM-based nanoscale rheology reveals regional non-uniformity in viscoporoelastic mechanical behavior of the murine periodontal ligament.

The periodontal ligament (PDL) is a critical player in the maintenance of tooth health, acting as the primary stabilizer of tooth position. Recent studies have identified two unique regions within the PDL, the 'dense collar' region and the 'furcation' region, which exhibit distinct structural and compositional differences. However, specific functional differences between these regions have yet to be investigated. We adapted an AFM-based nanoscale rheology method to regionally assess mechanical properties and poroelasticity in the mouse PDL while minimizing the disruption of the 3-dimensional native boundary conditions, and then explored tissue mechanical function in four different regions within the dense collar as well as in the furcation region. We found significant differences between the collar and furcation regions, with the collar acting as a stabilizing ligamentous structure and the furcation acting as both a compressive cushion for vertical forces and a conduit for nutrient transport. While this finding supports our hypothesis, based on previous studies investigating structural and compositional differences, we also found surprising inhomogeneity within the collar region itself. This inhomogeneity supports previous findings of a tilting movement in the buccal direction of mandibular molar teeth and the structural adaptation to prevent lingual movement. Future work will aim to understand how different regions of the PDL change functionally during biological or mechanical perturbations, such as orthodontic tooth movement, development, or aging, with the ultimate goal of better understanding the mechanobiology of the PDL function in health and disease.

Advertisement of electronic cigarettes in Italy: characteristics of online videos and the most popular promotional messages.

Given the increasing popularity of electronic cigarettes (ECs) and a lack of regulation of EC advertising, this study aimed to analyse online videos promoting ECs to assess the main marketing messages that could influence consumers' perceptions of associated risks and benefits. A web search of EC advertising videos was performed on YouTube by using keywords related to EC promotion. An evaluation grid was used to analyse promotional messages contained in each video. The most frequent promotional messages were related to health benefits (67.7%) and to the possibility of quitting smoking (57.4%). Messages that could also be appealing to adolescents and young adults, such as those promoting the multiple flavors available and the technological improvement of ECs, were present in 41.2% and 42.7% of the videos respectively. ECs similar to traditional cigarettes in appearance were included in 52.9% of the videos. EC promotional videos address messages not only to smokers who want to quit or decrease tobacco consumption but also to nonsmokers, especially young people. The use of ECs similar to traditional cigarettes may be a gateway to tobacco cigarette use. Since EC use may represent an important public health concern, regulatory policies on EC advertising should be established.

Nonuniformity in ligaments is a structural strategy for optimizing functionality.

Ligaments serve as compliant connectors between hard tissues. In that role, they function under various load regimes and directions. The 3D structure of ligaments is considered to form as a uniform entity that changes due to function. The periodontal ligament (PDL) connects the tooth to the bone and sustains different types of loads in various directions. Using the PDL as a model, employing a fabricated motorized setup in a microCT, we demonstrate that the fibrous network structure within the PDL is not uniform, even before the tooth becomes functional. Utilizing morphological automated segmentation methods, directionality analysis, as well as second harmonic generation imaging, we find high correlation between blood vessel distribution and fiber density. We also show a structural feature in a form of a dense collar around the neck of the tooth as well as a preferred direction of the fibrous network. Finally, we show that the PDL develops as a nonuniform structure, with an architecture designed to sustain specific types of load in designated areas. Based on these findings, we propose that ligaments in general should be regarded as nonuniform entities, structured already at developmental stages for optimal functioning under variable load regimes.

Direct microCT imaging of non-mineralized connective tissues at high resolution.

The 3D imaging of soft tissues in their native state is challenging, especially when high resolution is required. An X-ray-based microCT is, to date, the best choice for high resolution 3D imaging of soft tissues. However, since X-ray attenuation of soft tissues is very low, contrasting enhancement using different staining materials is needed. The staining procedure, which also usually involves tissue fixation, causes unwanted and to some extent unknown tissue alterations. Here, we demonstrate that a method that enables 3D imaging of soft tissues without fixing and staining using an X-ray-based bench-top microCT can be applied to a variety of different tissues. With the sample mounted in a custom-made loading device inside a humidity chamber, we obtained soft tissue contrast and generated 3D images of fresh, soft tissues with a resolution of 1 micron voxel size. We identified three critical conditions which make it possible to image soft tissues: humidified environment, mechanical stabilization of the sample and phase enhancement. We demonstrate the capability of the technique using different specimens: an intervertebral disc, the non-mineralized growth plate, stingray tessellated radials (calcified cartilage) and the collagenous network of the periodontal ligament. Since the scanned specimen is fresh an interesting advantage of this technique is the ability to scan a specimen under load and track the changes of the different structures. This method offers a unique opportunity for obtaining valuable insights into 3D structure-function relationships of soft tissues.

Tooth periodontal ligament: Direct 3D microCT visualization of the collagen network and how the network changes when the tooth is loaded.

The periodontal ligament (PDL), a soft tissue connecting the tooth and the bone, is essential for tooth movement, bone remodeling and force dissipation. A collagenous network that connects the tooth root surface to the alveolar jaw bone is one of the major components of the PDL. The organization of the collagenous component and how it changes under load is still poorly understood. Here using a state-of-the-art custom-made loading apparatus and a humidified environment inside a microCT, we visualize the PDL collagenous network of a fresh rat molar in 3D at 1 µm voxel size without any fixation or contrasting agents. We demonstrate that the PDL collagen network is organized in sheets. The spaces between sheets vary thus creating dense and sparse networks. Upon vertical loading, the sheets in both networks are stretched into well aligned arrays. The sparse network is located mainly in areas which undergo compressive loading as the tooth moves towards the bone, whereas the dense network functions mostly in tension as the tooth moves further from the bone. This new visualization method can be used to study other non-mineralized or partially mineralized tissues, and in particular those that are subjected to mechanical loads. The method will also be valuable for characterizing diseased tissues, as well as better understanding the phenotypic expressions of genetic mutants.

Tooth-PDL-bone complex: response to compressive loads encountered during mastication - a review.

The components of the tooth-periodontal ligament (PDL)-alveolar bone complex act in a synergistic manner to dissipate the loads incurred during mastication. The complex incorporates a diverse array of structural features for this purpose. These include the non-mineralized and hence soft PDL that absorbs much of the initial loads. The internal structure of the tooth also includes soft interphases that essentially surround the dentine core. These interphases, although stiffer than the PDL, still are more compliant than the dentine core, and are thus key components that allow the tooth itself to deform and hence help dissipate the compressive loads. There is also direct evidence that even under moderate compressive loads, when the tooth moves in the alveolar bone socket, this movement is guided by specific locations where the tooth comes into contact with the bone surface. The combination of all these responses to load is that each tooth type appears to move and deform in a specific manner when loaded. Much, however, still remains to be learned about these three-dimensional responses to load and the factors that control them. Such an understanding will have major implications for dentistry, that include a better understanding of phenomena such as abfraction, the manner in which tooth implants function even in the absence of a PDL-like tissue and the implications to bone remodelling of the movements imposed during orthodontic interventions.

Histomorphometric analysis of newly formed bone after bilateral maxillary sinus augmentation using two different osteoconductive materials and internal collagen membrane.

Deproteinized bovine bone mineral (DBBM) and human freeze-dried bone allograft (FDBA) were compared in five patients undergoing bilateral maxillary sinus floor augmentation using DBBM on one side and FDBA on the contralateral side. After 9 months, core biopsy specimens were harvested. Mean newly formed bone values were 31.8% and 27.2% at FDBA and DBBM sites, respectively (P = .451); mean residual graft particle values were 21.5% and 24.2%, respectively (P = .619); and mean connective tissue values were 46.7% and 48.6%, respectively (P = .566). Within the limits of the present study, it is suggested that both graft materials are equally suitable for sinus augmentation.

Tooth movements are guided by specific contact areas between the tooth root and the jaw bone: A dynamic 3D microCT study of the rat molar.

Teeth sustain high loads over a lifetime and yet intact tooth failure is rare. The different structures of the tooth, jaw bone and the intervening soft periodontal ligament enable the tooth to endure repeated loading during mastication. Although mechanical and functional properties of the different components are thoroughly investigated, the manner in which the whole tooth functions under load is still enigmatic. A custom-made loading system inside a microCT scanner was used to directly visualize the root movements in relation to the jaw bone as the rat molar tooth was loaded. At low loads no contact was observed between the root surface and the bone, whereas at higher loads three specific contact areas between the root surface and the jaw bone were observed. These contact areas restrict tooth movement in the buccal-lingual direction, but enable the tooth to rock in a "seesaw" like manner in the distal-mesial direction. The contact areas appear to play a role in determining tooth motion and in turn define the manner in which the whole tooth moves when loaded. These observations are important for understanding basic structure-function relations of the tooth-PDL-bone system, and have direct implications for better understanding pathological and therapeutic processes in orthodontics, periodontics and jaw bone regeneration.

Patients' self-perception of tooth shade in relation to professionally objective evaluation.

OBJECTIVE: Self-assessment of teeth shade was compared with professional assessment. METHOD AND MATERIALS: Patients' anterior teeth shade evaluation was conducted first by the patient (n = 193) and then by the clinician using the Vita shade guide. RESULTS: In 18.7% of participants, self-assessment of teeth shade matched in hue and chroma to the clinician's evaluation. A positive correlation was found between participants' self-assessment of their shade and the clinician's assessment (P = .014; Pearson product moment correlation). Participants assessed their shade darker than the clinician (P < .001; chi-square test). Only 3.6% were highly satisfied with the shade of their teeth, and 83.4% were interested in a future bleaching procedure. Tooth shade was more accurately assessed by women (P = .02) and nonsmokers (P = .03; chi-square test). CONCLUSION: A patient's preference toward a lighter shade should be addressed during treatment planning to match the patient's expectations for esthetics and increase patient satisfaction of treatment outcome. Patients may prefer white and shiny rather than a natural appearance.

Inorganic fullerene-like tungsten disulfide nanocoating for friction reduction of nickel-titanium alloys.

AIMS: To fabricate a friction-reducing coating onto different nickel-titanium (NiTi) substrates using inorganic fullerene-like tungsten disulfide (IF-WS(2)) nanoparticles and to estimate in vitro friction reducing extent of the coating. MATERIALS & METHODS: Different NiTi substrates were coated with cobalt and IF-WS(2) nanoparticles film by the electrodeposition procedure. Coating composition analyses was made by scanning-electron microscopy, energy dispersive x-ray spectroscopy, x-ray powder diffractometry and x-ray photoelectron spectroscopy. Friction evaluation was carried out using standard tribological tests and an Instron system. RESULTS: Stable and well-adhered cobalt + IF-WS(2) coating of the NiTi substrates was obtained. Friction tests presented up to 66% reduction of the friction coefficient. CONCLUSION: NiTi alloy is widely used for many medical appliances; hence, this unique friction-reducing coating could be implemented to provide better manipulation and lower piercing rates.

The association of orthodontic treatment and fixed retainers with gingival health.

BACKGROUND: The use of postorthodontic fixed retainers made of wire and composite resin bonded to the lingual/palatal tooth aspect is a common practice that can affect gingival health. The purpose of this study was to evaluate the association of orthodontic treatment and fixed retainers with gingival health. METHODS: The study included 92 consecutive subjects who arrived for routine dental examination at a military dental clinic between May and August 2007. Plaque and gingival indices, gingival recession, probing depth, and bleeding on probing were measured at the anterior sextants. When a fixed retainer was present, the distance was measured between the retainer and incisal edge and to the cemento-enamel junction. Past orthodontic treatment and smoking habits were self-reported. Postorthodontic patients were sorted by the presence or absence of fixed retainers. RESULTS: The mean probing depth was 1.90 +/- 0.2 mm, and gingival recession was 0.06 +/- 0.02 mm; 20.8% of all sites exhibited bleeding on probing. Current smoking was reported by 20 (21.7%) patients. Labial gingival recession was significantly greater in treated (0.13 +/- 0.2 mm) patients compared to non-treated patients (0.05 +/- 0.2 mm; P = 0.03). Localized lingual gingival recession was significantly greater in teeth with fixed retainers (0.09 +/- 0.2 mm) compared to teeth with no fixed retainers (0.01 +/- 0.1 mm; P = 0.0002), as were plaque and gingival indices and bleeding on probing. Plaque on the lingual/palatal aspect showed a weak, positive correlation with lingual gingival recession (r = 0.16; P = 0.033). CONCLUSION: Orthodontic treatment and fixed retainers were associated with an increased incidence of gingival recession, increased plaque retention, and increased bleeding on probing; however, the magnitude of the difference in recession was of low clinical significance.

Dental and oral trauma during childhood and adolescence in Israel: occurrence, causes, and outcomes.

The occurrence and causes of oral and dental injuries in a young Israeli population during childhood and adolescence were evaluated, as well as participants' awareness of using protective devices, such as mouth guards, during sporting activities. The survey consisted of 427 young adults, aged 18-21 years. A questionnaire was distributed relating to past oral and dental injuries over their lifetime; type of sporting activity practiced, specifying time, place and cause of injury; and use and awareness of protective devices. Participants who reported to be injured were asked to report the type of their injury, treatment provided, and satisfaction with the results. The total number of dental and oral injuries was 133, affecting 31.1% of the participants, in which 72 (16.9%) suffered dental injuries, mostly because of falls (64%), followed by sporting activities (23.2%), street-fights (7.2%), and car accidents (5.6%). Injuries occurred at school in 36.5% of cases and at home in 23.8% of cases. The most frequently reported injury was laceration (47.3%) followed by tooth fracture (41.9%). Of the 427 participants, 239 (56%) were active in at least one type of sport. Only 22.6% were aware of protective devices, e.g. mouth guards, and only 2.8% actually used these devices. These results show the high risk of potential dental and oral injury during childhood and adolescence, a lack of knowledge regarding the benefits of mouth guards and their limited use. Increased awareness of protective measures and devices, and their actual use should be encouraged with public health education.

Patients' satisfaction with dental esthetics.

BACKGROUND: Esthetics has become an important issue in modern society, as it seems to define one's character. In the past, functional demands were the main consideration in dental treatment. Today, with the decrease in caries prevalence, the focus has shifted toward dental esthetics. The authors conducted a study to evaluate the factors influencing patients' satisfaction with their dental appearance and with the results of esthetic treatment. METHODS: The authors surveyed a population of 407 adults (mean age, 21 years). They distributed a questionnaire regarding satisfaction with current dental esthetics and previous esthetic treatments. RESULTS: Of the 407 subjects, 152 (37.3 percent) were dissatisfied with their dental appearance. Tooth color was the primary reason for dissatisfaction (133 [89.3 percent] of 149 subjects), followed by poor tooth alignment (36 [23.7 percent] of 152 subjects), although 110 (27 percent) of the 407 subjects had received orthodontic treatment. The authors found no correlation between patients' satisfaction with their dental appearance and having undergone any procedure to whiten their teeth. Nevertheless, 134 (88.2 percent) of the dissatisfied subjects reported that they would like to undergo this procedure. CONCLUSIONS: Tooth color was a major factor with regard to dental esthetics. Most subjects were interested in improving their appearance and whitening their teeth. CLINICAL IMPLICATIONS: When planning treatment, dentists should take into consideration esthetic objectives in addition to function, structure and biology. This requires the clinician to rely on several disciplines in dentistry to deliver the highest level of dental care, which should lead to a higher level of patient satisfaction.

Self-assessed dental status, oral behavior, DMF, and dental anxiety.

The purpose of this study was to evaluate the relation between self-assessed dental status, oral behavior, dental anxiety, and DMF scores. The study was conducted among young army personnel (eighteen to twenty-one years old) who arrived at a single military dental clinic for dental screening. A questionnaire was used to collect the data anonymously. The questionnaire included self-assessment of dental status and behavior, as well as the Dental Anxiety Scale (DAS). Dental caries status was evaluated using the World Health Organization (WHO) caries diagnostic criteria for decayed, missing, and filled teeth (DMFT). A total of 393 young adults were examined (98.3 percent response rate). Approximately one-third brushed their teeth once a day or not at all. Of the participants, 10.7 percent assessed their dental status as "Poor" and 46.3 percent as "Fair." Furthermore, 25.5 percent assessed their dental treatment needs as high. The average DAS score was 7.14. The average DMF score was 6.2. There was a correlation between self-reported tooth status, participants' assessment of their dental treatment needs, and DMF score (p<0.0001). Anxious participants assessed their dental treatment needs as higher (p=0.05). The dental practitioner could ask patients to assess their dental status prior to treatment or appointment. These findings will help the practitioner to accomplish more effective time and patient management.

[Clinical application of the biological variability data of the thyroid hormones]. / Aplicación clínica de los datos de variabilidad biológica de las hormonas tiroideas.

BACKGROUND: The selection of laboratory tests with greater effectiveness for identifying patients with thyroid disorders (sensitivity) from non affected subjects (specificity) is, at present, under discussion. The study of biological variation can contribute to point out the laboratory tests with greater effectiveness. METHODS: Total blood was collected daily for five consecutive days from 25 healthy volunteers, which maintaining their usual life style all over the period. RESULTS: The biological coefficients of variation--within and between--subject, the individuality indexes and the critical differences between consecutive results are estimated. The effect of pulsatility over the results obtained is also discussed. CONCLUSIONS: The most effective laboratory test for the diagnosis of thyroid disorders is TSH, with the precaution of doing a second analysis if the first result falls close to either the lower or higher reference range limits. The best laboratory tests for the monitoring of hypo- and hyperthyroidism are total T4 and free T4, in which a critical difference between consecutive results higher than 15% indicates a significant change in the patient status.

[Tubular handling of potassium in cystinosis]. / Manejo tubular del potasio en la cistinosis.

Seven patients with cystinosis (Ccr between 30 and 90 ml/m/1.73 m2), were studied attempting to delineate renal tubular handling of potassium. Ks, Ck/Ccr X 100, Aldou and UAldo V/Ks were determined in basal conditions; tubular handling of water and sodium, and clearance of potassium were studied during hypotonic saline diuresis. Results obtained in cystinosis were compared with normal values and with values found in renal insufficiencies in the same range of GFR. Studies performed indicate that in cystinosis Ks is lower and Ck/Ccr X 100 and UAldo V/Ks higher than in normal children. During hypotonic saline diuresis, patients with cystinosis presented higher fractional water, sodium and potassium clearances than control children with the same range of GFR.